Categories
Veterinary Medicine

Bacterial endocarditis

Bacterial endocarditis is an acute or, more commonly, a subacute condition characterized by the formation of septic vegetative thrombi on the valves and / or mural endocardium. Thrombus formation most frequently involves the mitral or aortic valves and the highest incidence occurs in large breed, male dogs older than four years of age. The German shepherd breed appears predisposed. The pathogens most frequently isolated include Streptococcus sp,, Staphylococcus aurecus, Escherichia coli, Pseudomonas aeruginosa, Corynebacterium sp., Aerobacter acrogenes and Erysipelothrix rhusiopathiae.

Pathogenesis

Numerous predisposing factors have been implicated in the pathogenesis of valvular bacterial endocarditis. First, the valve must be damaged, for example by the turbulent blood flow associated with a congenital cardiac defect. Bacterial endocarditis involving the aortic valve has been reported in association with subaortic stenosis. The stenosis leads to ‘jetting’ of blood through the aortic valve which damages the valve leaflets and may eventually result in a degree of aortic regurgitation. Secondly, transient bacteraemiec episodes are presumably necessary to infect the sterile thrombi which form initially. The source of infection in many cases is speculative; infections involving the gastrointestinal tract, skin, lung, urogenital tract, oral cavity, bone and subcutaneous abscesses have been implicated in the pathogenesis as have other factors such as indwelling intravenous catheters, previous surgery and immunosuppressive drug therapy. The vegetations which form on the valves are friable and tend to form emboli. The lesions also alter valve structure and function and may result in mitral and / or aortic regurgitation which may lead ultimately to signs of congestive heart failure.

Clinical signs

The clinical manifestations of bacterial endocarditis reflect (1) altered valve function, (2) bacteraemia, (3) the dissemination of septic emboli with subsequent infarction and localization of infection in joints, kidneys, muscle, myocardium, lungs and central nervous system (CNS) tissue, and (4) the host immune response which may result in immune complex deposition in synovial membranes and glomeruli.

The clinical signs vary depending on which organs are involved. Typically the animal may present with rather non-specific signs (for example anorexia, lethargy, weight loss) in association with a fever. The pyrexie episodes are often intermittent and may last for several days before appearing to resolve spontaneously. Bacterial endocarditis should be considered as a differential diagnosis in an animal which presents with a history of recurrent pyrexia in the absence of more specific localizing signs.

Cardiac signs

A heart murmur may be present although this may develop late in the course of the disease. The murmur may be systolic if the mitral valve is involved or diastolic if due to aortic insufficiency. Embolization of the coronary blood supply leading to myocardial infarction or myocarditis may result in dysrhythmias (particularly ventricular dysrhythmias) or atrioventricular block. Some eases may develop cardiomcgaly and signs of left-sided congestive heart failure.

Extracardiac signs

Extracardiac signs include lethargy, anorexia, pyrexia due to transient, bacteraemic thxomboembolic episodes, lameness, muscle stiffness, petechial or ecchymotic haemorrhages due to thrombocytopenia, dyspnoea and seizures. Direct extension of the infection to one or more joints may result in a septic polyarthritis or prolonged antigenic stimulation may lead to immune complex deposition in the synovial membranes and the development of a non-septic (non-erosive) immune-mediated polyarthropathy.

Many of the clinical signs associated with bacterial endocarditis mimic those of systemic lupus erythematosus or the immune-mediated polyarthropathics since not only may the joints be involved but some animals test positive for anti-red cell, antiplatelet or antinuclcar antibodies.

Diagnosis of Bacterial endocarditis

Ante-mortem diagnosis is often difficult particularly if a cardiac murmur is not present.

Full haematolopical examination and complete biochemical screen.

A mild to moderate non-regenerative anaemia, neutrophilia with or without a left shift, and monocytosis may be evident. The anaemia may be attributed to the chronic inflammatory response; in a few cases there may be an immune-mediated component. Systemic thromboembolism may result in impaired renal function and / or liver damage or dysfunction. Increased alkaline phosphatase (ALP) activity, hypoglycaemia and hypoalbuminaemia are common findings in bacteraemic dogs.

Urine analysis and bacteriology

Urinary tract infections, including those originating in the prostate gland, are a potential source of blood-borne infection. Bacteraemia is often associated with bacteriuria hence a urine sample, preferably one obtained by cystocentesis, should be submitted for routine analysis and bacteriological culture / sensitivity.

Radiographic findings

Thoracic radiographs are often uninformative. Signs of congestive heart failure with left atrial and left ventricular enlargement and possibly pulmonary oedema may be evident in some dogs during the terminal stages of the disease.

Echocardiography

Echocardiography is the most useful and reliable technique for confirming a diagnosis of bacterial endocarditis ante-mortem. Moderate-sized vegetations can be visualized on the heart valves or mural endocardium.

Blood cultures

Bacteraemia in dogs with endocarditis is usually continuous. The timing of the blood cultures is less important and culturing blood during febrile episodes does not increase the frequency of positive results in dogs with endocarditis. Bacterial isolation rates between 50 and 80% have been reported. A negative blood culture does not preclude a diagnosis of bacterial endocarditis and repeated negative results have been reported in confirmed cases. In order to maximize the chances of obtaining a positive culture 2-3 blood samples should be collected, preferably at least one hour apart, over a 24 h period. Each blood sample should be collected from a different vein (jugular or cephalic) using standard aseptic technique. To minimize the risk of contamination a fresh needle should be attached to the syringe before the blood is transferred to the appropriate culture medium. Each sample should be submitted for aerobic and anaerobic culture. If possible, antibiotics should be discontinued at least 2 days beforehand since they may delay bacterial growth.

Synovial aspirates

Multiple joint taps should be obtained from animals with suspected joint involvement, that is those showing signs of shifting lameness. Synovial fluid should be submitted in EDTA for protein concentration and cytology, and in a sterile plain glass tube bacteriology.

Immunological screening tests

Some cases of bacterial endocarditis test positive for anti-red cell, anriplatelct and antinuclear anti-bodies making differentiation from SLH difficult.

Treatment of Bacterial endocarditis

The prognosis for subacute bacterial endocarditis is guarded. Bactericidal antibiotics should be administered for a minimum of 4-6 weeks (parenterally for the first two weeks and thereafter by the oral route) at doses well above the minimum inhibitory concentration. The choice of antibiotic ideally should be based on the blood culture results. Pending these results or in cases where the results are negative but bacterial endocarditis is either suspected or has been diagnosed, a combination of broad spectrum antibiotics should be given. A standard protocol is as follows.

Ampicillin (20-40 mg kg-1 body weight TID) and gentamycin (2 mg kg-1 body weight TID) in combination should be given intravenously for at least the first 5-10 days.

Thereafter, ampillin or cephalexin (20 mg kg-1 bodyweight) can be given orally for a further 2-4 weeks. Additional treatment for congestive heart failure should be given as appropriate.

Categories
Drugs

Amoxicillin / Clavulanate Potassium, Amoxicillin / Clavulanic Acid (Clavamox, Augmentin)

Potentiated Aminopenicillin

Highlights Of Prescribing Information

Bactericidal aminopenicillin with beta-lactamase inhibitor that expands its spectrum. Not effective against Pseudomonas or Enterobacter

Most likely adverse effects are GI related, but hypersensitivity & other adverse effects rarely occur

What Is Amoxicillin / Clavulanate Potassium, Amoxicillin / Clavulanic Acid Used For?

Amoxicillin/potassium clavulanate tablets and oral suspension products are approved for use in dogs and cats for the treatment of urinary tract, skin and soft tissue infections caused by susceptible organisms. It is also indicated for canine periodontal disease due to susceptible strains of bacteria.

Pharmacology / Actions

For information on the pharmacology/actions of amoxicillin, refer that monograph.

Clavulanic acid has only weak antibacterial activity when used alone and presently it is only available in fixed-dose combinations with either amoxicillin (oral) or ticarcillin (parenteral). Clavulanic acid acts by competitively and irreversibly binding to beta-lactamases, including types II, III, IV, and V, and penicillinases produced by Staphylococcus. Staphylococci that are resistant to penicillinase-resistant penicillins (e.g., oxacillin) are considered resistant to amoxicillin/potassium clavulanate, although susceptibility testing may indicate otherwise. Amoxicillin/potassium clavulanate is usually ineffective against type I cephalosporinases. These plasmid-mediated cephalosporinases are often produced by members of the family Enterobacteriaceae, particularly Pseudomonas aeruginosa. When combined with amoxicillin, there is little if any synergistic activity against organisms already susceptible to amoxicillin, but amoxicillin-resistant strains (due to beta-lactamase inactivation) may be covered.

When performing Kirby-Bauer susceptibility testing, the Augmenting (human-product trade name) disk is often used. Because the amoxicillinxlavulanic acid ratio of 2:1 in the susceptibility tests may not correspond to in vivo drug levels, susceptibility testing may not always accurately predict efficacy for this combination.

Pharmacokinetics

The pharmacokinetics of amoxicillin are presented in that drug’s monograph. There is no evidence to suggest that the addition of clavulanic acid significantly alters amoxicillin pharmacokinetics. Clavulanate potassium is relatively stable in the presence of gastric acid and is readily absorbed. In dogs, the absorption half-life is reportedly 0.39 hours with peak levels occurring about 1 hour after dosing. Specific bioavailability data for dogs or cats was not located.

Clavulanic acid has an apparent volume of distribution of 0.32 L/kg in dogs and is distributed (with amoxicillin) into the lungs, pleural fluid and peritoneal fluid. Low concentrations of both drugs are found in the saliva, sputum and CSF (uninflamed meninges). Higher concentrations in the CSF are expected when meninges are inflamed, but it is questionable whether therapeutic levels are attainable. Clavulanic acid is 13% bound to proteins in dog serum. The drug readily crosses the placenta but is not believed to be teratogenic. Clavulanic acid and amoxicillin are both found in milk in low concentrations.

Clavulanic acid is apparently extensively metabolized in the dog (and rat) primarily to l-amino-4-hydroxybutan-2-one. It is not known if this compound possesses any beta-lactamase inhibiting activity. The drug is also excreted unchanged in the urine via glomerular filtration. In dogs, 34-52% of a dose is excreted in the urine as unchanged drug and metabolites, 25-27% eliminated in the feces, and 16-33% into respired air. Urine levels of active drug are considered high, but may be only l/5th of those of amoxicillin.

Before you take Amoxicillin / Clavulanate Potassium, Amoxicillin / Clavulanic Acid

Contraindications / Precautions / Warnings

Penicillins are contraindicated in patients with a history of hyper-sensitivity to them. Because there maybe cross-reactivity, use penicillins cautiously in patients who are documented hypersensitive to other beta-lactam antibiotics (e.g., cephalosporins, cefamycins, carbapenems).

Do not administer systemic antibiotics orally in patients with septicemia, shock, or other grave illnesses as absorption of the medication from the GI tract may be significantly delayed or diminished.

Do not administer penicillins, cephalosporins, or macrolides to rabbits, guinea pigs, chinchillas, hamsters, etc. or serious enteritis and clostridial enterotoxemia may occur.

Adverse Effects

Adverse effects with the penicillins are usually not serious and have a relatively low frequency of occurrence.

Hypersensitivity reactions unrelated to dose can occur with these agents and can manifest as rashes, fever, eosinophilia, neutropenia, agranulocytosis, thrombocytopenia, leukopenia, anemias, lymphadenopathy, or full-blown anaphylaxis.

When given orally, penicillins may cause GI effects (anorexia, vomiting, diarrhea). Because the penicillins may alter gut flora, antibiotic-associated diarrhea can occur and allow the proliferation of resistant bacteria in the colon (superinfections).

Neurotoxicity (e.g., ataxia in dogs) has been associated with very high doses or very prolonged use. Although the penicillins are not considered hepatotoxic, elevated liver enzymes have been reported. Other effects reported in dogs include tachypnea, dyspnea, edema and tachycardia.

Reproductive / Nursing Safety

In humans, the FDA categorizes this drug as category B for use during pregnancy (Animal studies have not yet demonstrated risk to the fetus, hut there are no adequate studies in pregnant women; or animal studies have shown an adverse effect, hut adequate studies in pregnant women have not demonstrated a risk to the fetus in the first trimester of pregnancy, and there is no evidence of risk in later trimesters.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (Papich 1989), this drug is categorized as in class: A (Prohahly safe. Although specific studies may not have proved the safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women.)

Overdosage / Acute Toxicity

Acute oral penicillin overdoses are unlikely to cause significant problems other than GI distress, but other effects are possible (see Adverse Effects). In humans, very high dosages of parenteral penicillins, especially in patients with renal disease, have induced CNS effects.

How to use Amoxicillin / Clavulanate Potassium, Amoxicillin / Clavulanic Acid

Note: All doses are for combined quantities of both drugs (unless noted otherwise).

Amoxicillin / Clavulanate Potassium, Amoxicillin / Clavulanic Acid dosage for dogs:

For susceptible infections:

a) 13.75 mg/kg PO twice daily; do not exceed 30 days of therapy (Package insert; Clavamox — Pfizer)

b) For susceptible UTI’s: 12.5 mg/kg PO q12h for 5-7 days For susceptible skin, soft tissue infections: 12.5 mg/kg PO q12h for 5-7 days (may need to extend to 21 days; do not exceed past 30 days). Much higher doses have been recommended for resistant skin infections.

For susceptible deep pyodermas: 12.5 mg/kg PO q12h for 14-120 days

For systemic bacteremia: 22 mg/kg PO q8 – 12h for 7 days

Note: Duration of treatments are general guidelines; generally treat for at least 2 days after all signs of infection are gone. ()

c) For Gram-positive infections: 10 mg/kg PO twice daily

For Gram-negative infections: 20 mg/kg PO three times daily ()

d) For non-superficial pyoderma: 10-25 mg/kg PO twice daily for 3- 6 weeks. Maximum dose is 650 mg twice daily. Increase to three times daily if no response in 1 week. If no response by the 2nd week, discontinue. ()

e) For recurrent pyoderma: 13.75-22 mg/kg PO q8-12h ()

Amoxicillin / Clavulanate Potassium, Amoxicillin / Clavulanic Acid dosage for cats:

For susceptible infections:

a) 62.5 mg PO twice daily; do not exceed 30 days of therapy (Package insert; Clavamox — Pfizer)

b) For Gram-positive infections: 10 mg/kg PO twice daily;

For Gram-negative infections: 20 mg/kg PO three times daily ()

c) For susceptible UTI’s: 62.5 mg/cat (total dose) PO q12h for 10-30 days;

For susceptible skin, soft tissue infections: 62.5 mg/cat (total dose) or 10-20 mg/kg PO q12hfor 5-7 days;

For susceptible sepsis, pneumonia: 10-20 mg/kg PO q8h for 7-10 days Note: Duration of treatment are general guidelines, generally treat for at least 2 days after all signs of infection are gone. ()

Amoxicillin / Clavulanate Potassium, Amoxicillin / Clavulanic Acid dosage for ferrets:

For susceptible infections:

a) 10-20 mg/kg PO 2-3 times daily ()

Amoxicillin / Clavulanate Potassium, Amoxicillin / Clavulanic Acid dosage for birds:

For susceptible infections:

a) 50-100 mg/kg PO q6-8h ()

b) Ratites: 10-15 mg/kg PO twice daily ()

Client Information

■ The oral suspension should preferably be refrigerated, but refrigeration is not absolutely necessary; any unused oral suspension should be discarded after 10 days

■ Amoxicillin/clavulanate may be administered orally without regard to feeding status

■ If the animal develops gastrointestinal symptoms (e.g., vomiting, anorexia), giving with food may be of benefit

Monitoring

■ Because penicillins usually have minimal toxicity associated with their use, monitoring for efficacy is usually all that is required unless toxic signs or symptoms develop. Serum levels and therapeutic drug monitoring are not routinely performed with these agents.

Chemistry / Synonyms

A beta-lactamase inhibitor, clavulanate potassium occurs as an off-white, crystalline powder that has a pKa of 2.7 (as the acid) and is very soluble in water and slightly soluble in alcohol at room temperatures. Although available in commercially available preparations as the potassium salt, potency is expressed in terms of clavulanic acid. Amoxicillin may also be known as: amoxycillin, p-hydroxyampicillin, or BRL 2333; many trade names are available. Clavulanate potassium may also be known as: clavulanic acid, BRL-14151K, or kalii clavulanas.

Storage / Stability / Compatibility

Clavulanate products should be stored at temperatures less than 24°C (75°F) in tight containers. Potassium clavulanate is reportedly very susceptible to moisture and should be protected from excessive humidity.

After reconstitution, oral suspensions are stable for 10 days when refrigerated. Unused portions should be discarded after that time. If kept at room temperature, suspensions are reportedly stable for 48 hours. The veterinary oral suspension should be reconstituted by adding 14 mL of water and shaking vigorously; refrigerate and discard any unused portion after 10 days.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Oral Tablets (4:1 ratio):

62.5 mg: Amoxicillin 50 mg/12.5 mg clavulanic acid (as the potassium salt)

125 mg: Amoxicillin 100 mg/25 mg clavulanic acid (as the potassium salt)

250 mg: Amoxicillin 200 mg/50 mg clavulanic acid (as the potassium salt)

375 mg: Amoxicillin 300 mg/75 mg clavulanic acid (as the potassium salt); Clavamox Tablets (Pfizer); (Rx). Approved for use in dogs and cats.

Powder for Oral Suspension:

Amoxicillin 50 mg/12.5 mg clavulanic acid (as the potassium salt) per mL in 15 mL dropper bottles; Clavamox Drops (Pfizer); (Rx). Approved for use in dogs and cats.

Human-Labeled Products:

Note: Human-labeled amoxicillin/clavulanate products have varying ratios of amoxicillin:clavulanate ranging from 2:1 to 7:1.

Amoxicillin (as trihydrate)/Clavulanic Acid (as potassium salt) Tablets: Amoxicillin 250 mg/125 mg clavulanic acid; Amoxicillin 500 mg/125 mg clavulanic acid; Amoxicillin 875 mg/125 mg clavulanic acid; Augmenting (GlaxoSmithKline); generic (Rx)

Chewable Tablets: Amoxicillin 125 mg/31.25 mg clavulanic acid; Amoxicillin 200 mg/28.5 mg clavulanic acid; 250 mg/62.5 mg clavulanic acid & 400 mg/57 mg clavulanic acid; Augmenting (GlaxoSmithKline); generic; (Rx)

Powder for Oral Suspension — Amoxicillin/Clavulanic Acid (as potassium salt) after reconstitution: Amoxicillin 125 mg/31.25 mg clavulanic acid per 5 mL in 75 mL, 100 mL & 150 mL; Amoxicillin 200 mg/28.5 mg clavulanic acid per 5 mL in 50 mL, 75 mL &100 mL; Amoxicillin 250 mg/62.5 mg clavulanic acid per 5 mL in 75 mL, 100 mL & 150 mL; Amoxicillin 400 mg/57 mg clavulanic acid per 5 mL in 50 mL, 75 mL & 100 mL; 600 mg/42.9 mg clavulanic acid per 5 mL in 75 mL, 100 mL, 125 mL & 200 mL; Augmenting & Augmentin ES-600 (GlaxoSmithKline); Amoclan (West-ward); generic; (Rx)

Categories
Drugs

Amoxicillin (Amoxil, Amoxi-Tabs)

Aminopenicillin

Highlights Of Prescribing Information

Bactericidal aminopenicillin with same spectrum as ampicillin (ineffective against bacteria that produce beta-lactamase)

Most likely adverse effects are GI-related, but hypersensitivity & other adverse effects rarely occur

Available in oral & parenteral dosage forms in USA

What Is Amoxicillin Used For?

The aminopenicillins have been used for a wide range of infections in various species. FDA-approved indications/species, as well as non-approved uses, are listed in the Dosages section below.

Pharmacology / Actions

Like other penicillins, amoxicillin is a time-dependent, bactericidal (usually) agent that acts by inhibiting cell wall synthesis. Although there may be some slight differences in activity against certain organisms, amoxicillin generally shares the same spectrum of activity and uses as ampicillin. Because it is better absorbed orally (in non-ruminants), higher serum levels maybe attained than with ampicillin.

Penicillins are usually bactericidal against susceptible bacteria and act by inhibiting mucopeptide synthesis in the cell wall resulting in a defective barrier and an osmotically unstable spheroplast. The exact mechanism for this effect has not been definitively determined, but beta-lactam antibiotics have been shown to bind to several enzymes (carboxypeptidases, transpeptidases, endopeptidases) within the bacterial cytoplasmic membrane that are involved with cell wall synthesis. The different affinities that various beta-lactam antibiotics have for these enzymes (also known as penicillin-binding proteins; PBPs) help explain the differences in spectrums of activity the drugs have that are not explained by the influence of beta-lactamases. Like other beta-lactam antibiotics, penicillins are generally considered more effective against actively growing bacteria.

The aminopenicillins, also called the “broad-spectrum” or ampicillin penicillins, have increased activity against many strains of gram-negative aerobes not covered by either the natural penicillins or penicillinase-resistant penicillins, including some strains of E. coli, Klebsiella, and Haemophilus. Like the natural penicillins, they are susceptible to inactivation by beta-lactamase-producing bacteria (e.g., Staph aureus). Although not as active as the natural penicillins, they do have activity against many anaerobic bacteria, including Clostridial organisms. Organisms that are generally not susceptible include Pseudomonas aeruginosa, Serratia, Indole-positive Proteus {Proteus mirahilis is susceptible), Enterobacter, Citrobacter, and Acinetobacter. The aminopenicillins also are inactive against Rickettsia, mycobacteria, fungi, Mycoplasma, and viruses.

In order to reduce the inactivation of penicillins by beta-lactamases, potassium clavulanate and sulbactam have been developed to inactivate these enzymes and thus extend the spectrum of those penicillins. When used with a penicillin, these combinations are often effective against many beta-lactamase-producing strains of otherwise resistant E. coli, Pasturella spp., Staphylococcus spp., Klebsiella, and Proteus. Type I beta-lactamases that are often associated with E. coli, Enterobacter, and Pseudomonas are not generally inhibited by clavulanic acid.

Pharmacokinetics

Amoxicillin trihydrate is relatively stable in the presence of gastric acid. After oral administration, it is about 74-92% absorbed in humans and monogastric animals. Food will decrease the rate, but not the extent of oral absorption and many clinicians suggest giving the drug with food, particularly if there is concomitant associated GI distress. Amoxicillin serum levels will generally be 1.5-3 times greater than those of ampicillin after equivalent oral doses.

After absorption, the volume of distribution for amoxicillin is approximately 0.3 L/kg in humans and 0.2 L/kg in dogs. The drug is widely distributed to many tissues, including liver, lungs, prostate (human), muscle, bile, and ascitic, pleural and synovial fluids. Amoxicillin will cross into the CSF when meninges are inflamed in concentrations that may range from 10-60% of those found in serum. Very low levels of the drug are found in the aqueous humor, and low levels found in tears, sweat and saliva. Amoxicillin crosses the placenta, but it is thought to be relatively safe to use during pregnancy. It is approximately 17-20% bound to human plasma proteins, primarily albumin. Protein binding in dogs is approximately 13%. Milk levels of amoxicillin are considered low.

Amoxicillin is eliminated primarily through renal mechanisms, principally by tubular secretion, but some of the drug is metabolized by hydrolysis to penicilloic acids (inactive) and then excreted in the urine. Elimination half-lives of amoxicillin have been reported as 45-90 minutes in dogs and cats, and 90 minutes in cattle. Clearance is reportedly 1.9 mL/kg/min in dogs.

Before you take Amoxicillin

Contraindications / Precautions / Warnings

Penicillins are contraindicated in patients with a history of hyper-sensitivity to them. Because there may be cross-reactivity, use penicillins cautiously in patients who are documented hypersensitive to other beta-lactam antibiotics (e.g., cephalosporins, cefamycins, carbapenems).

Do not administer penicillins, cephalosporins, or macrolides to rabbits, guinea pigs, chinchillas, hamsters, etc. or serious enteritis and clostridial enterotoxemia may occur.

Do not administer systemic antibiotics orally in patients with septicemia, shock, or other grave illnesses as absorption of the medication from the GI tract may be significantly delayed or diminished. Parenteral (preferably IV) routes should be used for these cases.

Adverse Effects

Adverse effects with the penicillins are usually not serious and have a relatively low frequency of occurrence.

Hypersensitivity reactions unrelated to dose can occur with these agents and can manifest as rashes, fever, eosinophilia, neutropenia, agranulocytosis, thrombocytopenia, leukopenia, anemias, lymphadenopathy, or full-blown anaphylaxis.

When given orally, penicillins may cause GI effects (anorexia, vomiting, diarrhea). Because the penicillins may alter gut flora, antibiotic-associated diarrhea can occur and allow the proliferation of resistant bacteria in the colon (superinfections).

High doses or very prolonged use have been associated with neurotoxicity (e.g., ataxia in dogs). Although the penicillins are not considered hepatotoxic, elevated liver enzymes have been reported. Other effects reported in dogs include tachypnea, dyspnea, edema and tachycardia.

Reproductive / Nursing Safety

Penicillins have been shown to cross the placenta; safe use during pregnancy has not been firmly established, but neither have there been any documented teratogenic problems associated with these drugs. However, use only when the potential benefits outweigh the risks. In humans, the FDA categorizes this drug as category B for use during pregnancy () In a separate system evaluating the safety of drugs in canine and feline pregnancy (), this drug is categorized as in class: A (Probably safe. Although specific studies may not have proved the safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women.)

Overdosage / Acute Toxicity

Acute oral penicillin overdoses are unlikely to cause significant problems other than GI distress but other effects are possible (see Adverse Effects). In humans, very high dosages of parenteral penicillins, especially in patients with renal disease, have induced CNS effects.

How to use Amoxicillin

Amoxicillin dosage for dogs:

For susceptible infections:

a) For Gram-positive infections: 10 mg/kg PO, IM, SC twice daily for at least 2 days after symptoms subside.

For Gram-negative infections: 20 mg/kg PO three times daily or IM, SC twice daily for at least 2 days after symptoms subside ()

b) For susceptible UTI’s: 10-20 mg/kg PO q12h for 5-7 days. For susceptible systemic infections (bacteremia/sepsis): 22-30 mg/kg IV, IM, SC q8h for 7 days.

For susceptible orthopedic infections: 22-30 mg/kg IV, IM, SC, or PO q6-8h for 7-10 days. ()

c) For Lyme disease: 22 mg/kg PO q12h for 21-28 days ()

Amoxicillin dosage for cats:

For susceptible infections:

a) For Gram-positive infections: 10 mg/kg PO, IM, SC twice daily for at least 2 days after symptoms subside.

For Gram-negative infections: 20 mg/kg PO three times daily or IM, SC twice daily for at least 2 days after symptoms subside ()

b) For susceptible UTI’s and soft tissue infections: 50 mg (total dose per cat) or 11-22 mg/kg PO once daily for 5-7 days. For sepsis: 10-20 mg/kg IV, SC, or PO q12h for as long as necessary. Note: Duration of treatment are general guidelines, generally treat for at least 2 days after all signs of infection are gone. ()

c) C. perfringens, bacterial overgrowth (GI): 22 mg/kg PO once daily for 5 days ()

d) C. perfringens enterotoxicosis: 11-22 mg/kg PO two to three times daily for 7 days ()

e) For treating H. pylori infections using triple therapy: amoxi-cillin 20 mg/kg PO twice daily for 14 days; metronidazole 10-15 mg/kg PO twice daily; clarithromycin 7.5 mg/kg PO twice daily ()

Amoxicillin dosage for ferrets:

For eliminating Helicobacter gastritis infections:

a) Using triple therapy: Metronidazole 22 mg/kg, amoxicillin 22 mg/kg and bismuth subsalicylate (original Pepto-Bismol) 17.6 mg/kg PO. Give each 3 times daily for 3-4 weeks. ()

b) Using triple therapy: Metronidazole 20 mg/kg PO q12h, amoxicillin 20 mg/kg PO q12h and bismuth subsalicylate 17.5 mg/kg PO q8h. Give 21 days. Sucralfate (25 mg/kg PO q8h) and famotidine (0.5 mg/kg PO once daily) are also used. Fluids and assisted feeding should be continued while the primary cause of disease is investigated. ()

For susceptible infections:

a) 10-35 mg/kg PO or SC twice daily ()

Amoxicillin dosage for rabbits, rodents, and small mammals:

Note: See warning above in Contraindications a) Hedgehogs: 15 mg/kg IM or PO q12h ()

Amoxicillin dosage for cattle:

For susceptible infections:

a) 6-10 mg/kg SC or IM q24h (Withdrawal time = 30 days) ()

b) For respiratory infections: 11 mg/kg IM or SC q12h ()

c) Calves: Amoxicillin trihydrate: 7 mg/kg PO q8-12h ()

Amoxicillin dosage for horses:

For susceptible infections:

a) For respiratory infections: 20-30 mg/kg PO q6h ()

b) Foals: Amoxicillin Sodium: 15-30 mg/kg IV or IM q6-8h; amoxicillin trihydrate suspension: 25-40 mg/kg PO q8h; amoxicillin/clavulanate 15-25 mg/kg IV q6-8h ()

Amoxicillin dosage for birds:

For susceptible infections:

a) For most species: 150-175 mg/kg PO once to twice daily (using 50 mg/mL suspension) ()

b) 100 mg/kg q8h PO ()

c) 100 mg/kg q8h, IM, SC, PO ()

d) Ratites: 15-22 mg/kg PO twice daily; in drinking water: 250 mg/gallon for 3-5 days ()

Amoxicillin dosage for reptiles:

For susceptible infections:

a) For all species: 22 mg/kg PO ql2 -24h; not very useful unless used in combination with aminoglycosides ()

Client Information

■ The oral suspension should preferably be refrigerated, but refrigeration is not absolutely necessary; any unused oral suspension should be discarded after 14 days

■ Amoxicillin may be administered orally without regard to feeding status

■ If the animal develops gastrointestinal symptoms (e.g., vomiting, anorexia), giving with food may be of benefit

Chemistry / Synonyms

An aminopenicillin, amoxicillin is commercially available as the trihydrate. It occurs as a practically odorless, white, crystalline powder that is sparingly soluble in water. Amoxicillin differs structurally from ampicillin only by having an additional hydroxyl group on the phenyl ring.

Amoxicillin may also be known as: amoxycillin, p-hydroxyampicillin, or BRL 2333; many trade names are available.

Storage / Stability / Compatibility

Amoxicillin capsules, tablets, and powder for oral suspension should be stored at room temperature (15-30°C) in tight containers. After reconstitution, the oral suspension should preferably be refrigerated (refrigeration not absolutely necessary) and any unused product discarded after 14 days.

Dosage Forms / Regulatory Status/Withdrawal Times

Veterinary-Labeled Products:

Amoxicillin Oral Tablets: 50 mg, 100 mg, 150 mg, 200 mg, & 400 mg; Amoxi-Tabs (Pfizer); (Rx). Approved for use in dogs and cats.

Amoxicillin Powder for Oral Suspension 50 mg/mL (after reconstitution) in 15 mL or 30 mL bottles; Amoxi-Drop (Pfizer); (Rx). Approved for use in dogs and cats.

Amoxicillin Intramammary Infusion 62.5 mg/syringe in 10 mL syringes; Amoxi-Mast (Schering-Plough); (Rx). Approved for use in lactating dairy cattle. Slaughter withdrawal (when administered as labeled) = 12 days; Milk withdrawal (when administered as labeled) = 60 hours.

Human-Labeled Products:

Amoxicillin Tablets (chewable) (as trihydrate): 125 mg, 200 mg, 250 mg, & 400 mg; Amoxf/(GlaxoSmithKline); generic; (Rx)

Amoxicillin Tablets (as trihydrate): 500 mg & 875 mg; Amoxil (GlaxoSmithKline); generic; (Rx)

Amoxicillin Capsules (as trihydrate): 250 mg, & 500 mg; Amoxil (GlaxoSmithKline); generic; (Rx)

Amoxicillin (as trihydrate) Powder for Oral Suspension: 50 mg/mL (in 15 and 30 mL bottles), 125 mg/5 mL in 80 mL & 150 mL; 200 mg/5 mL in 50 mL, 75 mL & 100 mL; 250 mg/5 mL in 80 mL, 100 mL & 150 mL; 400 mg/5 mL in 50 mL, 75 mL & 100 mL; Amoxil & Amoxil Pediatric Drops (GlaxoSmithKline); (Apothecon), Trimox (Sandoz); generic; (Rx)

AmoxiciUin Tablets for Oral Suspension: 200 mg & 400 mg; Disper-Mox (Ranbaxy); (Rx)

Categories
Drugs

Amikacin Sulfate (Amikin, Amiglyde-V)

Aminoglycoside Antibiotic

Highlights Of Prescribing Information

Parenteral aminoglycoside antibiotic that has good activity against a variety of bacteria, predominantly gram-negative aerobic bacilli

Adverse Effects: Nephrotoxicity, ototoxicity, neuromuscu-lar blockade

Cats may be more sensitive to toxic effects

Risk factors for toxicity: Preexisting renal disease, age (both neonatal & geriatric), fever, sepsis & dehydration

Now usually dosed once daily when used systemically

What Is Amikacin Sulfate Used For?

While parenteral use is only approved in dogs, amikacin is used clinically to treat serious gram-negative infections in most species. It is often used in settings where gentamicin-resistant bacteria are a clinical problem. The inherent toxicity of the aminoglycosides limit their systemic use to serious infections when there is either a documented lack of susceptibility to other, less toxic antibiotics or when the clinical situation dictates immediate treatment of a presumed gram-negative infection before culture and susceptibility results are reported.

Amikacin is also approved for intrauterine infusion in mares. It is used with intra-articular injection in foals to treat gram-negative septic arthritis.

Pharmacology/Actions

Amikacin, like the other aminoglycoside antibiotics, act on susceptible bacteria presumably by irreversibly binding to the 30S ribosomal subunit thereby inhibiting protein synthesis. It is considered a bactericidal concentration-dependent antibiotic.

Amikacin’s spectrum of activity includes: coverage against many aerobic gram-negative and some aerobic gram-positive bacteria, including most species of E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Enterobacter, Serratia, and Shigella, Mycoplasma, and Staphylococcus. Several strains of Pseudomonas aeruginosa, Proteus, and Serratia that are resistant to gentamicin will still be killed by amikacin.

Antimicrobial activity of the aminoglycosides is enhanced in an alkaline environment.

The aminoglycoside antibiotics are inactive against fungi, viruses and most anaerobic bacteria.

Pharmacokinetics

Amikacin, like the other aminoglycosides is not appreciably absorbed after oral or intrauterine administration, but is absorbed from topical administration (not from skin or the urinary bladder) when used in irrigations during surgical procedures. Patients receiving oral aminoglycosides with hemorrhagic or necrotic enteritises may absorb appreciable quantities of the drug. After IM administration to dogs and cats, peak levels occur from ½1 hour later. Subcutaneous injection results in slightly delayed peak levels and with more variability than after IM injection. Bio availability from extravascular injection (IM or SC) is greater than 90%.

After absorption, aminoglycosides are distributed primarily in the extracellular fluid. They are found in ascitic, pleural, pericardial, peritoneal, synovial and abscess fluids; high levels are found in sputum, bronchial secretions and bile. Aminoglycosides are minimally protein bound (<20%, streptomycin 35%) to plasma proteins. Aminoglycosides do not readily cross the blood-brain barrier nor penetrate ocular tissue. CSF levels are unpredictable and range from 0-50% of those found in the serum. Therapeutic levels are found in bone, heart, gallbladder and lung tissues after parenteral dosing. Aminoglycosides tend to accumulate in certain tissues such as the inner ear and kidneys, which may help explain their toxicity. Volumes of distribution have been reported to be 0.15-0.3 L/kg in adult cats and dogs, and 0.26-0.58 L/kg in horses. Volumes of distribution may be significantly larger in neonates and juvenile animals due to their higher extracellular fluid fractions. Aminoglycosides cross the placenta; fetal concentrations range from 15-50% of those found in maternal serum.

Elimination of aminoglycosides after parenteral administration occurs almost entirely by glomerular filtration. The approximate elimination half-lives for amikacin have been reported to be 5 hours in foals, 1.14-2.3 hours in adult horses, 2.2-2.7 hours in calves, 1-3 hours in cows, 1.5 hours in sheep, and 0.5-2 hours in dogs and cats. Patients with decreased renal function can have significantly prolonged half-lives. In humans with normal renal function, elimination rates can be highly variable with the aminoglycoside antibiotics.

Before you take Amikacin Sulfate

Contraindications / Precautions / Warnings

Aminoglycosides are contraindicated in patients who are hypersensitive to them. Because these drugs are often the only effective agents in severe gram-negative infections, there are no other absolute contraindications to their use. However, they should be used with extreme caution in patients with preexisting renal disease with concomitant monitoring and dosage interval adjustments made. Other risk factors for the development of toxicity include age (both neonatal and geriatric patients), fever, sepsis and dehydration.

Because aminoglycosides can cause irreversible ototoxicity, they should be used with caution in “working” dogs (e.g., “seeing-eye,” herding, dogs for the hearing impaired, etc.).

Aminoglycosides should be used with caution in patients with neuromuscular disorders (e.g., myasthenia gravis) due to their neuromuscular blocking activity.

Because aminoglycosides are eliminated primarily through renal mechanisms, they should be used cautiously, preferably with serum monitoring and dosage adjustment in neonatal or geriatric animals.

Aminoglycosides are generally considered contraindicated in rabbits/hares as they adversely affect the GI flora balance in these animals.

Adverse Effects

The aminoglycosides are infamous for their nephrotoxic and ototox-ic effects. The nephrotoxic (tubular necrosis) mechanisms of these drugs are not completely understood, but are probably related to interference with phospholipid metabolism in the lysosomes of proximal renal tubular cells, resulting in leakage of proteolytic enzymes into the cytoplasm. Nephrotoxicity is usually manifested by: increases in BUN, creatinine, nonprotein nitrogen in the serum, and decreases in urine specific gravity and creatinine clearance. Proteinuria and cells or casts may be seen in the urine. Nephrotoxicity is usually reversible once the drug is discontinued. While gentamicin may be more nephrotoxic than the other aminoglycosides, the incidences of nephrotoxicity with all of these agents require equal caution and monitoring.

Ototoxicity (8th cranial nerve toxicity) of the aminoglycosides can manifest by either auditory and/or vestibular clinical signs and may be irreversible. Vestibular clinical signs are more frequent with streptomycin, gentamicin, or tobramycin. Auditory clinical signs are more frequent with amikacin, neomycin, or kanamycin, but either form can occur with any of these drugs. Cats are apparently very sensitive to the vestibular effects of the aminoglycosides.

The aminoglycosides can also cause neuromuscular blockade, facial edema, pain/inflammation at injection site, peripheral neuropathy and hypersensitivity reactions. Rarely, GI clinical signs, hematologic and hepatic effects have been reported.

Reproductive / Nursing Safety

Aminoglycosides can cross the placenta and while rare, may cause 8th cranial nerve toxicity or nephrotoxicity in fetuses. Because the drug should only be used in serious infections, the benefits of therapy may exceed the potential risks. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should he used cautiously as a last resort when the benefit of therapy clearly outweighs the risks.)

Aminoglycosides are excreted in milk. While potentially, amikacin ingested with milk could alter GI flora and cause diarrhea, amikacin in milk is unlikely to be of significant concern after the first few days of life (colostrum period).

Overdosage / Acute Toxicity

Should an inadvertent overdosage be administered, three treatments have been recommended. Hemodialysis is very effective in reducing serum levels of the drug but is not a viable option for most veterinary patients. Peritoneal dialysis also will reduce serum levels but is much less efficacious. Complexation of drug with either carbenicillin or ticarcillin (12-20 g/day in humans) is reportedly nearly as effective as hemodialysis. Since amikacin is less affected by this effect than either tobramycin or gentamicin, it is assumed that reduction in serum levels will also be minimized using this procedure.

How to use Amikacin Sulfate

Note: Most infectious disease clinicians now agree that aminoglycosides should be dosed once a day in most patients (mammals). This dosing regimen yields higher peak levels with resultant greater bacterial kill, and as aminoglycosides exhibit a “post-antibiotic effect”, surviving susceptible bacteria generally do not replicate as rapidly even when antibiotic concentrations are below MIC. Periods where levels are low may also decrease the “adaptive resistance” (bacteria take up less drug in the presence of continuous exposure) that can occur. Once daily dosing may decrease the toxicity of aminoglycosides as lower urinary concentrations may mean less uptake into renal tubular cells. However, patients who are neutropenic (or otherwise immunosuppressed) may benefit from more frequent dosing (q8h). Patients with significantly diminished renal function who must receive aminoglycosides may need to be dosed at longer intervals than once daily. Clinical drug monitoring is strongly suggested for these patients.

Amikacin Sulfate dosage for dogs:

For susceptible infections:

a) Sepsis: 20 mg/kg once daily IV ()

b) 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). ()

c) 15-30 mg/kg IV, IM or SC once daily (q24h) ()

Amikacin Sulfate dosage for cats:

For susceptible infections:

a) Sepsis: 20 mg/kg once daily IV ()

b) 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). ()

c) 10-15 mg/kg IV, IM or SC once daily (q24h) ()

Amikacin Sulfate dosage for ferrets:

For susceptible infections:

a) 8-16 mg/kg IM or IV once daily ()

b) 8-16 mg/kg/day SC, IM, IV divided q8-24h ()

Amikacin Sulfate dosage for rabbits, rodents, and small mammals:

a) Rabbits: 8-16 mg/kg daily dose (may divide into q8h-q24h) SC, IM or IV Increased efficacy and decreased toxicity if given once daily. If given IV, dilute into 4 mL/kg of saline and give over 20 minutes. ()

b) Rabbits: 5-10 mg/kg SC, IM, IV divided q8-24h Guinea pigs: 10-15 mg/kg SC, IM, IV divided q8-24h Chinchillas: 10-15 mg/kg SC, IM, IV divided q8-24h Hamster, rats, mice: 10 mg/kg SC, IM q12h Prairie Dogs: 5 mg/kg SC, IM q12h ()

c) Chinchillas: 2-5 mg/kg SC, IM q8- 12h ()

Amikacin Sulfate dosage for cattle:

For susceptible infections:

a) 10 mg/kg IM q8h or 25 mg/kg q12h ()

b) 22 mg/kg/day IM divided three times daily ()

Amikacin Sulfate dosage for horses:

For susceptible infections:

a) 21 mg/kg IV or IM once daily (q24h) ()

b) In neonatal foals: 21 mg/kg IV once daily ()

c) In neonatal foals: Initial dose of 25 mg/kg IV once daily; strongly recommend to individualize dosage based upon therapeutic drug monitoring. ()

d) Adults: 10 mg/kg IM or IV once daily (q24h)

Foals (<30 days old): 20-25 mg/kg IV or IM once daily (q24h).

For uterine infusion:

a) 2 grams mixed with 200 mL sterile normal saline (0.9% sodium chloride for injection) and aseptically infused into uterus daily for 3 consecutive days (Package insert; Amiglyde-V — Fort Dodge)

b) 1-2 grams IU ()

For intra-articular injection as adjunctive treatment of septic arthritis in foals:

a) If a single joint is involved, inject 250 mg daily or 500 mg every other day; frequency is dependent upon how often joint lavage is performed. Use cautiously in multiple joints as toxicity may result (particularly if systemic therapy is also given). ()

For regional intravenous limb perfusion (RILP) administration in standing horses:

a) Usual dosages range from 500 mg-2 grams; dosage must be greater than 250 mg when a cephalic vein is used for perfusion and careful placement of tourniquets must be performed. ()

Amikacin Sulfate dosage for birds:

For susceptible infections:

a) For sunken eyes/sinusitis in macaws caused by susceptible bacteria: 40 mg/kg IM once or twice daily. Must also flush sinuses with saline mixed with appropriate antibiotic (10-30 mL per nostril). May require 2 weeks of treatment. ()

b) 15 mg/kg IM or SC q12h ()

c) For gram-negative infections resistant to gentamicin: Dilute commercial solution and administer 15-20 mg/kg (0.015 mg/g) IM once a day or twice a day ()

d) Ratites: 7.6-11 mg/kg IM twice daily; air cell: 10-25 mg/egg; egg dip: 2000 mg/gallon of distilled water pH of 6 ()

Amikacin Sulfate dosage for reptiles:

For susceptible infections:

a) For snakes: 5 mg/kg IM (forebody) loading dose, then 2.5 mg/kg q72h for 7-9 treatments. Commonly used in respiratory infections. Use a lower dose for Python curtus. ()

b) Study done in gopher snakes: 5 mg/kg IM loading dose, then 2.5 mg/kg q72h. House snakes at high end of their preferred optimum ambient temperature. ()

c) For bacterial shell diseases in turtles: 10 mg/kg daily in water turtles, every other day in land turtles and tortoises for 7-10 days. Used commonly with a beta-lactam antibiotic. Recommended to begin therapy with 20 mL/kg fluid injection. Maintain hydration and monitor uric acid levels when possible. ()

d) For Crocodilians: 2.25 mg/kg IM q 72-96h ()

e) For gram-negative respiratory disease: 3.5 mg/kg IM, SC or via lung catheter every 3-10 days for 30 days. ()

Amikacin Sulfate dosage for fish:

For susceptible infections:

a) 5 mg/kg IM loading dose, then 2.5 mg/kg every 72 hours for 5 treatments. ()

Monitoring

■ Efficacy (cultures, clinical signs, WBC’s and clinical signs associated with infection). Therapeutic drug monitoring is highly recommended when using this drug systemically. Attempt to draw samples at 1,2, and 4 hours post dose. Peak level should be at least 40 mcg/mL and the 4-hour sample less than 10 mcg/mL.

■ Adverse effect monitoring is essential. Pre-therapy renal function tests and urinalysis (repeated during therapy) are recommended. Casts in the urine are often the initial sign of impending nephrotoxicity.

■ Gross monitoring of vestibular or auditory toxicity is recommended.

Client Information

■ With appropriate training, owners may give subcutaneous injections at home, but routine monitoring of therapy for efficacy and toxicity must still be done

■ Clients should also understand that the potential exists for severe toxicity (nephrotoxicity, ototoxicity) developing from this medication

■ Use in food producing animals is controversial as drug residues may persist for long periods

Chemistry / Synonyms

A semi-synthetic aminoglycoside derived from kanamycin, amikacin occurs as a white, crystalline powder that is sparingly soluble in water. The sulfate salt is formed during the manufacturing process. 1.3 grams of amikacin sulfate is equivalent to 1 gram of amikacin. Amikacin may also be expressed in terms of units. 50,600 Units are equal to 50.9 mg of base. The commercial injection is a clear to straw-colored solution and the pH is adjusted to 3.5-5.5 with sulfuric acid.

Amikacin sulfate may also be known as: amikacin sulphate, amikacini sulfas, or BB-K8; many trade names are available.

Storage / Stability/Compatibility

Amikacin sulfate for injection should be stored at room temperature (15 – 30°C); freezing or temperatures above 40°C should be avoided. Solutions may become very pale yellow with time but this does not indicate a loss of potency.

Amikacin is stable for at least 2 years at room temperature. Autoclaving commercially available solutions at 15 pounds of pressure at 120°C for 60 minutes did not result in any loss of potency.

Note: When given intravenously, amikacin should be diluted into suitable IV diluent etc. normal saline, D5W or LRS) and administered over at least 30 minutes.

Amikacin sulfate is reportedly compatible and stable in all commonly used intravenous solutions and with the following drugs: amobarbital sodium, ascorbic acid injection, bleomycin sulfate, calcium chloride/gluconate, cefoxitin sodium, chloramphenicol sodium succinate, chlorpheniramine maleate, cimetidine HCl, clindamycin phosphate, colistimethate sodium, dimenhydrinate, diphenhydramine HCl, epinephrine HCl, ergonovine maleate, hyaluronidase, hydrocortisone sodium phosphate/succinate, lincomycin HCl, metaraminol bitartrate, metronidazole (with or without sodium bicarbonate), norepinephrine bitartrate, pentobarbital sodium, phenobarbital sodium, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine HCL, secobarbital sodium, sodium bicarbonate, succinylcholine chloride, vancomycin HCL and verapamil HCL.

The following drugs or solutions are reportedly incompatible or only compatible in specific situations with amikacin: aminophylline, amphotericin B, ampicillin sodium, carbenicillin disodium, cefazolin sodium, cephalothin sodium, cephapirin sodium, chlorothiazide sodium, dexamethasone sodium phosphate, erythromycin gluceptate, heparin sodium, methicillin sodium, nitrofurantoin sodium, oxacillin sodium, oxytetracycline HCL, penicillin G potassium, phenytoin sodium, potassium chloride (in dextran 6% in sodium chloride 0.9%; stable with potassium chloride in “standard” solutions), tetracycline HCL, thiopental sodium, vitamin B-complex with C and warfarin sodium. Compatibility is dependent upon factors such as pH, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information.

In vitro inactivation of aminoglycoside antibiotics by beta-lac-tam antibiotics is well documented. While amikacin is less susceptible to this effect, it is usually recommended to avoid mixing these compounds together in the same syringe or IV bag unless administration occurs promptly. See also the information in the Amikacin Sulfate Interaction and Amikacin Sulfate/Lab Interaction sections.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Amikacin Sulfate Injection: 50 mg (of amikacin base) per mL in 50 mL vials; Amiglyde-V (Fort Dodge), AmijectD (Butler), Amikacin K-9 (RXV), Amikacin C (Phoenix), Amtech Amimax C (IVX), Caniglide (Vedco); generic (VetTek); (Rx); Approved for use in dogs.

Amikacin Sulfate Intrauterine Solution: 250 mg (of amikacin base) per mL in 48 mL vials; Amifuse E (Butler), Amiglyde-V (Fort Dodge), Amikacin E (Phoenix), Amikacin E (RXV), Amtech Amimax E (IVX), Equi-phar Equiglide (Vedco); (Rx); Approved for use in horses not intended for food.

WARNING: Amikacin is not approved for use in cattle or other food-producing animals in the USA. Amikacin Sulfate residues may persist for long periods, particularly in renal tissue. For guidance with determining use and withdrawal times, contact FARAD (see Phone Numbers & Websites in the appendix for contact information).

Human-Labeled Products:

Amikacin Injection: 50 mg/mL and 250 mg/mL in 2 mL and 4 mL vials and 2 mL syringes; Amikin (Apothecon); generic; (Rx)

Categories
Diseases

Infective Endocarditis

Infective endocarditis (IE) is a life-threatening disorder that results from microorganisms that colonize the cardiac endocardium, which commonly causes destruction of valves or other structures within the heart. Bacteremia is by far the most common etiology, with the mitral and aortic valve most frequently affected. Vegetation may cause thromboembolism or metastatic infections, which involve multiple body organs and produce a large variety of clinical signs which makes diagnosis difficult. The incidence of infective endocarditis in necropsied dogs has been reported to range from 0.06% to 6.6%. Evaluation of clinical data from university animal hospitals points to infective endocarditis as a comparably rare condition with incidences ranging from 0.04% to 0.13%. Medium to large breed, mainly purebred, middle-aged male dogs are reported to be predisposed. The incidence in cats, based on clinical experience, is considered to be 7 to 10 times lower than in dogs. Animals with congenital heart disease have a low incidence of infective endocarditis”, but associations have been reported with subaortic stenosis and occasionally with PDA. infective endocarditis has not been found to have any association with chronic mitral valve insufficiency in dogs.

Infective Endocarditis: Pathology

Vegetation associated with by infective endocarditis mainly affects the left heart with the highest incidence involving the mitral valve. Involvement of the right heart or mural endocardium is uncommon. Pathologic findings vary and depend on the virulence of the infecting organism, the duration of infection, and the immunologic response. Intracardiac vegetation consists of different layers of fibrin, platelets, bacteria, red and white cells, and is often covered by an intact endothelium. Bacteria may continue to grow despite antibiotic therapy owing to the location deep within the vegetation and a slow metabolic rate. Necrosis and destruction of the valve stroma or chordae tendineae proceed rapidly in peracute or acute infective endocarditis, which causes valvular insufficiency and cardiac failure.

Infective Endocarditis: Etiology and Pathogenesis

Transient or persistent bacteremia is a prerequisite for the development of infective endocarditis. A large number of bacteria have been associated with bacteremia (see section on Blood Culture below) and some are known to cause infective endocarditis. Most bacteria require predisposing factors to cause infective endocarditis, such as depression of the immunosystem or endothelial damage, sometimes with depositions of platelet-fibrin complexes, to adhere to the valve and create infective endocarditis. The origin of the bacteremia may be active infection localized somewhere within the body. A proportion of cases with infective endocarditis has no clinically detectable source of infection. Possible routes for bacteria to reach and infect the endocardium are by direct contact with the surface endothelium via the bloodstream or from capillaries within the valve (vasculitis).

The consequences of infective endocarditis depend on several factors: virulence of the infective agent; site of infection; degree of valvular destruction; influence of vegetation on valvular function; production of exo- or endotoxins; interaction with the immunosystem with the formation of immunocomplexes; and development of thromboembolism and metastatic infections. Gram-negative bacteremia results often in a peracute or acute clinical manifestation, whereas gram-positive bacteremia typically results in a subacute or chronic condition. The vegetation may cause valvular insufficiency or obstruction. The destruction of valvular tissue is caused by the action of bacteria or the cellular response from the immunologic system. Deposition of immunocomplexes in different organs may cause glomerulonephritis, myositis, or polyarthritis. Septic embolization that produces clinical signs is uncommon but 84% of affected dogs had evidence of systemic embolization at necropsy and glomerulonephritis was reported in 16% of 44 dogs with infective endocarditis.

Infective Endocarditis: Case History and Clinical Signs

The diagnosis of infective endocarditis can easily be overlooked because the case history and clinical signs are not specific and there may be an absence of predisposing factors to raise the suspicion of infective endocarditis. Clinical signs are variable and occur in different combinations. Commonly reported signs include lethargy, weakness, fever (sometimes recurrent), anorexia, weight loss, GI disturbances, and lameness. Stiffness and pain originating from joints or muscles may be caused by immunomediated responses and abdominal pain may be caused by secondary renal or splenic infarction, septic embolization, or abscess formation. If the condition leads to severe valvular damage, especially of the aortic valve, signs of cardiac failure and syncope from arrhythmias may occur. Predisposing factors that in combination with the clinical signs above, should raise the suspicion of infective endocarditis are immunosuppressive drug therapy, such as cortico-steroids; aortic stenosis; recent surgery, especially in conjunction with trauma to mucosal surfaces in the oral or genital tract and infections in these body regions, especially prostatitis; indwelling catheters, infected wounds, abscesses, or pyoderma.

Physical Examination

Most clinical signs lack specificity for infective endocarditis. However, fever, heart murmur (particularly if newly developed), and lameness are considered classical signs. Fever is reported to occur in 80% to 90% in dogs with infective endocarditis. Absence of fever is reported to be more common in cases with aortic valve involvement but may also be attributed to treatment with antibiotics or corticosteroids.

Since aortic insufficiency is otherwise uncommon in dogs, the finding of a diastolic murmur and bounding peripheral pulse should raise the suspicion of infective endocarditis of the aortic valve. Systolic murmurs may be caused by destruction of the mitral valve, which results in mitral regurgitation or vegetations that obstruct the aortic outflow tract, which leads to stenosis. These murmurs are, in contrast to diastolic murmurs, poor indicators of infective endocarditis since they frequendy occur in dogs with other conditions, such as chronic mitral valve insufficiency and aortic stenosis. It should be noted that 26% of dogs with infective endocarditis are reported to lack audible murmurs. Lameness is also an inconsistent finding in infective endocarditis with an incidence of 34% in one study. A range of other physical findings may be present, depending on which organs are affected by circulating immunocomplexes or septic embolization. Possible findings are pain reactions from muscles or abdomen (spleen, intestines, or kidneys), cold extremities, cyanosis, and skin necrosis from severe embolization and a variety of neurologic disturbances if the central nervous system is affected.

Blood Culture

Positive blood cultures are crucial evidence of infective endocarditis. The theory that bacteremia from infective endocarditis is intermittent has changed in recent years to the opinion that, if existent, it is continuous. Thus negative or intermittent positive cultures are unusual when collection and handling of samples is conducted properly. The time for sampling is probably not critical, but a constant finding through repeat samplings is valuable to exclude sample contamination. The technique for obtaining samples aseptically and anaerobically is important and described in detail below. In cases of positive blood culture, it is important to evaluate if the microorganism is consistent with the diagnosis of infective endocarditis.

Microorganisms known to cause infective endocarditis in dogs are, in order of reported incidence, Stapkylococcus aureus, E. coli, betahemolytic streptococci, Pseudotnonas aeroginosa, Corynebacterium spp., Erysipelothrix rhusiopathiae (tonsillarium), and Bartonella irinsonii. B. vinsonii and related proteobacteria has recently been recognized as a potential cause for endocarditis in dogs. They have been found in dogs with cardiac arrhythmias, endocarditis, or myocarditis. Bartonella spp. are also a potential cause for infective endocarditis in cats. Furthermore, Bartonella spp. have been reported to occasionally cause infective endocarditis in immunocompromised (but also immunocompetent) humans, with the cat serving as the major reservoir (cat scratch disease). The recommended antibiotic therapy when the resistance is unknown is erythro-mycin or doxycycline. Immediate antibiotic therapy of humans after significant dog or cat bites may furthermore be motivated as commensals, such as Capnocytophaga canimorsus, in the saliva of dogs and cats have been reported to occasionally cause septicemia with a mortality as high as 30%. Negative blood cultures are fairly common and may be due to antibiotic therapy, chronic situations with “incapsulated” infections, noninfective infective endocarditis (only platelets and fibrin in vegetation), or failure to grow organisms from samples. Some bacteria may grow slowly and samples should not be regarded as definitely negative until they have been incubated for 10 days. More common is a rapid growth of microorganisms with 90% of cultures positive within 72 hours of incubation.

Obtaining Blood Cultures

The referral laboratory should be contacted concerning the preferred type of preprepared vials before obtaining a sample; special additives are available if the patient has been on antibiotics. Pediatric vials are useful because less blood is required but volumes in the range of 20 to 30 mL increase the chance for growth. To avoid contamination, strictly aseptic sampling should be observed which includes thorough shaving and disinfection of the sampling site and strict use of sterile gloves. Three samples with adequately filled vials from different puncture sites should be collected. If samples are collected with a syringe, suction should cease before withdrawal of the needle from the patient to avoid contamination with skin bacteria and a new sterile needle should be used for the transfer of blood into the bottles. The bottles should be prewarmed to 37° C and, after sampling, incubated at the same temperature. Sampling through indwelling catheters should be avoided but may be used as a second choice. The former recommendation to draw samples over 24-hour periods has changed, since multiple simultaneously drawn samples in humans have been shown to be equally sensitive.

Electrocardiographic Findings

Arrhythmia is reported to occur in 50% to 75% of dogs with infective endocarditis.sn.86 Ventricular premature beats and tachyarrhythmias are the most commonly encountered arrhythmias, but they are usually not life threatening. Deviation in the ST-segment suggests myocardial hypoxia and may indicate coronary artery embolism or ischemia from heart failure. Evidence of chamber enlargement may occur in chronic infective endocarditis. All the mentioned ECG abnormalities are, however, nonspecific.

Radiogrophic Findings

Radiography often does not add any information specific for infective endocarditis. In cases of chronic infective endocarditis with aortic or mitral insufficiency, left-sided cardiac enlargement may be detected. Calcified deposits on the valve leaflets are occasionally observed in chronic cases.

Echocardiographic Findings

Echocardiography has significantly improved the possibility of diagnosis and monitoring of animals with infective endocarditis. Valvular vegetations may be detected using two-dimensional echocardiography, although minor lesions may be difficult to distinguish from myxomatous lesions. M-mode can be used to measure secondary changes in cardiac size and to detect abnormal mitral valve motion such as fluttering from aortic regurgitation. Mitral or aortic regurgitation may be detected using continous or color-flow Doppler echocardiography.

Other Laboratory Findings

Mild anemia is found in 50% to 60% of cases with infective endocarditis. The anemia is similar to those from other infections, usually being normocytic and normochromic. Leukocytosis is found in about 80% of dogs with infective endocarditis, usually due to neutrophilia and monocy-tosis (left shift). Other findings that may be encountered include elevated blood urea nitrogen (BUN) due to embolization, metastatic infection, heart failure, or immune-mediated disease.

Urine analysis may reveal pyuria, bacteriuria, or proteinuria. Elevated serum alkaline phosphatase may be found, probably caused by circulating endotoxins and reduced hepatic function, which may cause hypoalbuminemia. The serum glucose concentration may be decreased and serologic tests for immuno-mediated disease, such as Coombs test, may be positive.

Diagnosis of Infective Endocarditis

Since the clinical signs of infective endocarditis are often a result of complications, rather than reflecting the intracardiac infection, the diagnosis may easily be overlooked. Major criteria for infective endocarditis are positive blood cultures with typical microorganisms for infective endocarditis from two separate samples plus evidence of cardiac involvement. The localization and severity of cardiac lesions is confirmed by echocardiographic visualization of vegetations. In the absence of positive cultures, a tentative diagnosis of infective endocarditis can be made if there is clinical and laboratory evidence of systemic infection, such as fever and leukocytosis plus cardiac involvement and possibly signs of embolization.

Management of Infective Endocarditis

The goal of therapy is to eradicate the infective microorganism and to treat all secondary complications. A successful outcome of the therapy is based on early diagnosis and immediate and aggressive treatment. Only bactericidal antibiotics capable of penetrating fibrin should be considered. The antibiotic concentration in serum and deep within vegetations should exceed the organisms minimal inhibitory concentration (MIC), but preferably also the minimum bactericidal concentration (MBC), continuously or throughout most of the interval between doses. Treatment should continue for at least 6 weeks to eradicate dormant microorganisms.

Management of Cases with Tentative Diagnosis of infective endocarditis

A blood culture (see section above) and an antibiotic sensitivity profile should be obtained. While results from cultures and sensitivity tests are awaited, intravenous treatment with a high dosage of bactericidal antibiotic IV, such as cephalosporins (second generation), should be initiated. Alternatives to cephalosporins are combinations of ampicillin or amoxicillin for gram-positive organisms and gentamicin or amikacin for gram-negative organisms. An alternative to gentamicin and amikacin, which are potentially toxic and only recommended to be used for at most one week, is enrofloxacin for suspected gram-negative infective endocarditis. Enrofloxacin is bactericidal and may penetrate myocardium and heart valves and is also indicated for treating Bartonella infections. Choice of antibiotic should preferably depend on the suspected source of infection and the estimated resistance pattern for the primary infection. Practitioners should try to identify the source of infection and treat it as aggressively as possible, such as use of surgical drainage or debridement. Possible secondary problems should be identified, such as heart or renal failure that need therapy or may impair the prognosis.

For dogs with heart failure from aortic regurgitation, hydralazine titered to an adequate reduction of arterial blood pressure is effective and should be considered as a part of medical therapy. When results are available from blood cultures, appropriate antibiotics are selected and aggressive IV treatment continued for 5 to 10 days while renal function is monitored. If results from cultures are negative, the decision to continue antibiotic therapy should be based on clinical improvement. Depending on the early outcome of therapy, subcutaneous administration may substitute a 5 to 10 days IV treatment, and later be superseded by oral preparations. The duration of therapy should be at least 6 weeks on the effective antibiotic. Frequent clinical examinations, blood screening, and urine analyses should be performed during that period.

Prognosis of Infective Endocarditis

Factors that indicate a poor prognosis include late diagnosis and late start of therapy; vegetations on valves (especially the aortic); gram-negative infections, heart or renal failure that do not respond to therapy; septic embolization or metastatic infection; elevation of serum alkaline phosphatase and hypoalbuminemia (70% mortality is reported if this is found in cases with infective endocarditis); concurrent treatment with corticosteroids, regardless if antibiotics are given simultaneously; treatment with bacteriostatic antibiotics or premature termination of antibiotic therapy. Factors that indicate a more favorable prognosis include only mitral valve involvement (47% of dogs are reported to survive); gram-positive infections, origin of infection being the skin, abscesses, cellulitis, or wound infections.

Prevention of Infective Endocarditis

Prophylactic antibiotics may be indicated 1 to 2 hours before and 12 to 24 hours after diagnostic or surgical procedures when turbulent blood flow is suspected to have damaged the endocardium, such as aortic stenosis, patent ductus arteriosus (PDA), or ventral septal defect (VSD). In these cases, early treatment of all manifest infections is important to avoid bacteremia and reduce the risk for infective endocarditis, and caution should be observed when bleeding or infection is anticipated or evident in the oral, urogenital, intestinal, or respiratory tract. Amoxicillin may be the first choice, but other antibiotics, such as clindamycin or cephalosporins, may also be considered depending on the organ system involved and site of infection.

Categories
Drugs

Acetylcysteine (N-acetylcysteine, Mucomyst, NAC)

Antidote; Mucolytic

Highlights Of Prescribing Information

Used primarily as a treatment for acetaminophen or phenol toxicity & for its mucolytic effect; used anecdotally for treating degenerative myelopathy

Also used as a topical ophthalmic ()

Has caused hypersensitivity & bronchospasm when used in pulmonary tree

Administer via gastric- or duodenal tube for acetaminophen poisoning in animals

What Is Acetylcysteine Used For?

Acetylcysteine is used in veterinary medicine as both a mucolytic agent in the pulmonary tree and as a treatment for acetaminophen or phenol toxicity in small animals. It has been used anecdotally with aminocaproic acid to treat degenerative myelopathy in dogs.

In horses with strangles, acetylcysteine instilled into the gutteral pouch has been used to help break up chondroids and avoid the need for surgical removal. Acetylcysteine enemas have been used in neonatal foals to break up meconium refractory to repeated enemas.

Before you take Acetylcysteine

Contraindications / Precautions / Warnings

Acetylcysteine is contraindicated (for pulmonary indications) in animals hypersensitive to it. There are no contraindications for its use as an antidote.

Because acetylcysteine may cause bronchospasm in some patients when used in the pulmonary system, animals with bronchospastic diseases should be monitored carefully when using this agent.

Adverse Effects

When given orally for acetaminophen toxicity, acetylcysteine can cause GI effects (nausea, vomiting) and rarely, urticaria. Because the taste of the solution is very bad, use of taste masking agents {e.g., colas, juices) have been used. Since oral dosing of these drugs may be very difficult in animals, gastric or duodenal tubes may be necessary.

Rare adverse effects reported when acetylcysteine is administered into the pulmonary tract, include: hypersensitivity, chest tightness, bronchoconstriction, and bronchial or tracheal irritation.

Overdosage / Acute Toxicity

The LD50 of acetylcysteine in dogs is 1 g/kg (PO) and 700 mg/kg (IV). It is believed that acetylcysteine is quite safe (with the exception of the adverse effects listed above) in most overdose situations.

How to use Acetylcysteine

Acetylcysteine dosage for dogs:

For acetaminophen toxicity:

a) A 2-3 hour wait between activated charcoal and PO administration of acetylcysteine (NAC) is necessary. Give NAC as an initial oral loading dose of 140 mg/kg (dilute to 5% in dextrose or sterile water), followed by 70 mg/kg PO four times daily (q6h) for 7 treatments. With ingestion of massive quantities, some authors suggest using a 280 mg/kg loading dose and continuing treatment for 12-17 doses. May also be given IV after diluting to 5% and given via slow IV over 15-20 minutes. Additional therapy may include IV fluids, blood or Oxyglobin, ascorbic acid and SAMe. ()

b) 150 mg/kg PO or IV initially, then 50 mg/kg q4h for 17 additional doses ()

c) Loading dose of 140 mg/kg PO, then 70 mg/kg PO every 6 hours for 7 treatments ()

For phenol toxicity:

a) 140 mg/kg PO or IV initially, then 50 mg/kg q4h for 3 days. May be partially effective to reduce hepatic and renal injury. Resultant methemoglobinemia should be treated with ascorbic acid or methylene blue. ()

For respiratory use:

a) 50 mL/hr for 30-60 minutes every 12 hours by nebulization ()

For degenerative myelopathy:

a) 25 mg/kg PO q8h for 2 weeks, then q8h every other day. The 20% solution should be diluted to 5% with chicken broth or suitable diluent. Used in conjunction with aminocaproic acid (500 mg per dog PO q8h indefinitely). Other treatments may include prednisone (0.25-0.5 mg/kg PO daily for 10 days then every other day), Vitamin C (1000 mg PO q12h) and Vitamin E (1000 Int. Units PO q12h). Note: No treatment has been shown to be effective in published trials. ()

Acetylcysteine dosage for cats:

For acetaminophen toxicity:

a) A 2-3 hour wait between activated charcoal and PO administration of acetylcysteine (NAC) is necessary. Give NAC as an initial oral loading dose of 140 mg/kg (dilute to 5% in dextrose or sterile water), followed by 70 mg/kg PO four times daily (q6h) for 7 treatments. With ingestion of massive quantities, some authors suggest using a 280 mg/kg loading dose and continuing treatment for 12-17 doses. May also be given IV after diluting to 5% and given via slow IV over 15-20 minutes. Additional therapy may include IV fluids, blood or Oxyglobin9, ascorbic acid and SAMe. ()

b) 150 mg/kg PO or IV initially, then 50 mg/kg q4h for 17 additional doses ()

For phenol toxicity:

a) 140 mg/kg PO or IV initially, then 50 mg/kg q4h for 3 days. May be partially effective to reduce hepatic and renal injury. Resultant methemoglobinemia should be treated with ascorbic acid or methylene blue. ()

For respiratory use:

a) 50 mL/hr for 30-60 minutes every 12 hours by nebulization ()

For adjunctive treatment of hepatic lipidosis (see also Carnitine):

a) Identify underlying cause of anorexia and provide a protein replete feline diet, give acetylcysteine (NAC) at 140 mg/kg IV over 20 minutes, then 70 mg/kg IV q12h; dilute 10% NAC with saline 1:4 and administer IV using a 0.25 micron filter; correct hypokalemia and hypophosphatemia, beware of electrolyte changes with re-feeding phenomenon ()

Acetylcysteine dosage for horses:

To help break up chondroids in the gutteral pouch:

a) Instill 20% solution ()

In neonatal foals to break up meconium refractory to repeated enemas:

a) 8 grams in 20 g sodium bicarbonate in 200 mL water (pH of 7.6), give as enema as needed to effect ()

b) With foal in lateral recumbency, insert a 30 french foley catheter with a 30 cc bulb for a retention enema. Using gravity flow, infuse slowly 100-200 mL of 4% acetylcysteine solution and retain for 30-45 minutes. IV fluids and pain medication should be considered. Monitor for possible bladder distention. ()

Monitoring

When used for acetaminophen poisoning:

■ Hepatic enzymes (particularly in dogs)

■ Acetaminophen level, if available (particularly in dogs)

■ Hemogram, with methemoglobin value (particularly in cats)

■ Serum electrolytes, hydration status

Client Information

■ This agent should be used in a clinically supervised setting only

Chemistry / Synonyms

The N-acetyl derivative of L-cysteine, acetylcysteine occurs as a white, crystalline powder with a slight acetic odor. It is freely soluble in water or alcohol.

Acetylcysteine may also be known as: N-acetylcysteine or N-acetyl-L-cysteine, NAC, 5052 acetylcysteinum, NSC-111180, Acetadote, Mucomyst or ACC.

Storage / Stability/Compatibility

When unopened, vials of sodium acetylcysteine should be stored at room temperature (15-30°C). After opening, vials should be kept refrigerated and used within 96 hours. The product labeled for IV use states to use within 24 hours.

Acetylcysteine is incompatible with oxidizing agents; solutions can become discolored and liberate hydrogen sulfide when exposed to rubber, copper, iron, and during autoclaving. It does not react to aluminum, stainless steel, glass or plastic. If the solution becomes light purple in color, potency is not appreciably affected, but it is best to use non-reactive materials when giving the drug via nebulization. Acetylcysteine solutions are incompatible with amphotericin B, ampicillin sodium, erythromycin lactobionate, tetracycline, oxytetracycline, iodized oil, hydrogen peroxide and trypsin.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

Human-Labeled Products:

Acetylcysteine injection: 20% (200 mg/mL), (0.5 mg/mL EDTA in 30 mL single-dose vials, preservative free; Acetadote (Cumberland); (Rx)

Acetylcysteine Solution: 10% & 20% (as sodium) in 4 mL, 10 mL, 30 mL & 100 mL (20% only) vials; Mucomyst (Apothecon); (Rx) Note: If using this product for dilution and then intravenous dosing, it is preferable to use a 0.2 micron in-line filter.

Categories
Horses

Treatment of RFM

Although many mares with RFM do not become clinically ill, early prophylactic intervention is widely practiced because the complications associated with RFM may be severe and potentially life threatening. Many farm managers and horse owners with a veterinary client-patient relationship may be instructed to begin intramuscular (IM) injections of oxytocin 2 to 4 hours postpartum if the fetal membranes have not been passed. The membranes should be tied up above the hocks to prevent soiling and tearing. Tying a weight (e.g., a brick) to the membranes is not recommended because it may predispose the mare to development of a uterine horn intussusception. Injections of oxytocin should be given every hour for at least 6 treatments. The half-life of oxytocin in the mare is brief (12 min).

The initial starting dose of oxytocin should be on the low side (10-20IU/500 kg) because sensitivity to oxytocin varies widely. The dose of oxytocin can then be tailored to each individual mare. A positive response will result in passage of uterine fluid from the vagina. Mares should be monitored following injection because any obvious cramping will begin within 10 minutes of IM injection. If a 10- to 20-IU oxytocin treatment does not result in an outward manifestation of discomfort by the mare, such as sweating and restlessness, then the dose can be increased in 10- to 20-IU increments until an effect is noticed. The dose should only be high enough to elicit mild colic signs. Mares with uterine inertia because of dystocia may be initially very resistant to the effect of oxytocin and may become more sensitive in the subsequent hours. If cramping and rolling result then the dose should be reduced. Some mares become inattentive mothers during the time when they are distracted by RFM or uncomfortable from the oxytocin-induced cramping. Thus the foal should be kept in a safe place when the mare is in pain. Nursing should be encouraged to stimulate the natural release of oxytocin associated with milk letdown.

If the mare fails to respond to six oxytocin injections or if she is clinically ill, a thorough veterinary examination is indicated. One option is to start an intravenous (IV) drip of oxytocin at 0.1 IU/ml of saline (i.e., 100 IU oxytocin per 1 L saline). The IV flow rate should be set so that the mare has visible signs of contractions every S to 10 minutes. The oxytocin drip treatment protocol will, in effect, revert the mare back into labor for about 1 hour.

The technique described by Burns and colleagues () works best when the membranes are fresh. Some clinicians perform the procedure prophylacti-cally after a dystocia to reduce the likelihood of membrane retention. The clinician should wear waterproof clothing and a sterile surgical glove over a clean rectal sleeve. The perineum of the mare and external portion of the membranes are washed thoroughly. The opening at the cervical star, which leads into the allantoic cavity, is identified. A clean large-bore stomach tube is introduced, and the membranes are gathered around the tube. In addition, 4 L or more of a warm 1% povidone iodine solution is pumped or gravity fed into the chorioallantois until the fluid overflows. The tube is withdrawn as the RFM are tied shut with umbilical tape. Oxytocin may then be administered so that the uterus contracts against the distended membranes. This technique distends the endometrial crypts and often permits release of the microcotyledons. If the procedure is unsuccessful then it may be repeated several hours later. However, the retained membranes soon become autolytic and tend to tear as soon as distention starts.

If partial retention of the membranes is diagnosed, or if the membranes are badly torn, the uterus may be distended with 1% povidone iodine solution as described previously. The fluid distention and uterine contractions may help loosen the membranes. If the piece of membrane can be reached, it may be gently teased off the en-dometrium and removed. However, if the membrane tag is firmly adhered then continued traction is contraindicated. Once or twice daily flushing and the process of au-tolysis will eventually loosen the membranes. This procedure also may be carefully performed in mares that retain the membranes after a cesarean section. However, it is important to use a lower volume of infusate so that the uterine closure and fibrin seal are not disrupted.

Toxemic mares that are clinically ill and are passing a fetid uterine discharge may require systemic support with IV fluids, frequent IV treatments with oxytocin, and twice daily high-volume uterine lavage. Gentle manual removal of the fetid membranes may be necessary in these mares. Back and forth uterine lavage is performed with a clean stomach tube, bilge, or stomach pump. A dilute (1%) povidone iodine solution or sterile fluids are used to remove bacteria and inflammatory debris from the uterus. The clinician should hold the end of the tube cupped in the hand within the uterine cavity to prevent the tube from forcefully sucking against the wall when the fluid is being siphoned back. During the first few lavage procedures, persistence and patience in obtaining a clean return from the uterus is often rewarded with rapid clinical improvement and uterine involution. Lavage should be repeated once or twice daily until all debris is removed, the lavage is clear, and the uterus is well involuted.

Prophylactic administration of antibiotic and antiinflammatory medication is often prescribed early in the course of RFM in an attempt to prevent complications. Common antimicrobial choices are trimethoprim sulfa (30 mg/kg, q24h PO), or procaine penicillin G (22,000 IU/kg ql2h IM) for a minimum of 3 to 5 days. If the mare is systemically ill then broad-spectrum medications such as penicillin-aminoglycoside combinations are recommended. The formulations or derivatives of penicillin include the following: procaine penicillin (22,000 IU/kg ql2h IM), sodium and potassium penicillin (22,000 IU/kg q6h IV), ampicillin (50 mg/kg q8h IV), or ticarcillin (44 mg/kg q8h IM) for resistant cases. Aminoglycosides such as gentamicin (6 mg/kg q24h IM or IV) or amikacin (6.6 mg/kg ql2h IV or IM) are used for mixed and gram-negative infections or resistant cases. Appropriate antibiotic use is confirmed by uterine culture and sensitivity results.

The mostly commonly used antiinflammatory medication for endotoxemic mares is flunixin meglumine, 1.1 mg/kg IV. In milder cases, flunixin meglumine (0.25-0.5 mg/kg q8h IV), ketoprofen (2 mg/kg ql2h IV), vedaprofen (2 mg/kg ql2h PO), or phenylbutazone (4 mg/kg IV or PO) are used. Hyperimmune plasma is administered if it is available.

Laminitis in mares with RFM is a serious complication. Lateral radiographs of the distal phalanx will help establish the degree of rotation, and the prognosis. Symptomatic care such as hosing the hooves with cold water, or application of foam pads or special shoes to the hooves can provide extra support and promote comfort. Phenylbutazone at 2 g every 24 hours by mouth is sometimes used prophylactically.

Mares with lactation failure should be treated with domperidone at 1.1 mg/kg orally every 12 hours to encourage lactation.

Categories
Horses

Endometrial Culture and Antimicrobial Therapy

Sampling of the surface of the endometrium for pathogenic microflora is an important part of the breeding soundness evaluation of the mare. Additionally, most breeding sheds and stallion owners require broodmares to have a negative uterine culture before natural mating. Breeds that allow artificial insemination may be less restrictive with this requirement. Other indications for endometrial culture include recent dystocia or retained fetal membranes, detection of intrauterine fluid by ultrasonography, or previously diagnosed endometritis.

Sampling Technique

Antimicrobial Therapy

It is imperative that any anatomic defects — such as poor perineal conformation, rectovaginal fistulas, perineal lacerations, and vesicovaginal reflux — be surgically corrected. Without doing so, endometritis will recur despite appropriate antimicrobial therapy. A list of agents used for intrauterine antimicrobial therapy in the mare is given in Table Antimicrobial Therapy for Intrauterine Use in the Mare. In most mares, a volume of 50 to 100 ml will give adequate dispersion over the entire endometrial surface. Mares whose uteri are enlarged may require volumes greater than 100 ml to achieve uniform distribution throughout both horns and the body of the uterus. Treatment once daily for 4 to 6 days during estrus is usually adequate for most cases of endometritis. It is often beneficial to precede antimicrobial infusion with uterine lavage, thereby mechanically removing organic debris, which can interfere with the efficacy of most antibiotics. Postpartum mares — or those with an especially enlarged uterus that lacks tone — benefit temporarily from lavage with warm saline before infusion with antimicrobial agents. Oxytocin is an effective tool to enhance uterine clearance of the mare. It is advisable to wait several hours after using any intrauterine antimicrobial agents before administering oxytocin; otherwise, uterine contractions will prematurely expel the antimicrobial agent. In such cases, combining uterine lavage and oxytocin with systemic antimicrobial therapy may prove more efficacious and cost-effective.

Table Antimicrobial Therapy for Intrauterine Use in the Mare*

Antimicrobial Dose Comments
amikacin sulfate 2g Gram-negative organisms; buffer with equal volume 7.5% bicarbonate
ampicillin 1-3 g  
ceftiofur ig Broad spectrum (Streptococcus zooepidemicus)
gentamicin 1-2 g Cram-negative organ-
sulfate   isms; buffer with equal volume 7.5% bicarbonate
kanamycin sulfate 1-2 g Escherichia coli; toxic to spermatozoa
penicillin 5 million units S. zooepidemicus
polymixin B 1 million units Pseudomonas spp.
ticarcillin fig Broad spectrum
ticarcillin/ clavulanic acid 6 g/200 mg Broad spectrum
nystatin 500,000 units Antimycotic; must use sterile water (precipitates in saline)
clotrimazole 500 mg Antimycotic; suspension or cream; q24-48h for 1 -2 weeks
vinegar 2% Antimycotic; 20 ml wine vinegar in 1 L of saline; used as a lavage fluid

*Parts of this table from Asbury AC, Lyle SK: Infectious causes of infertility.

The use of systemic antimicrobial therapy is becoming an increasingly popular route for treating mares with endometritis, especially in mares prone to postmating endometritis during the postovulatory period, in mares whose biopsy shows evidence of inflammation deep in the stratum spongiosum, and in mares that receive embryos by transcervical transfer. Trimethoprim/sulfa combinations (30 mg/kg q24h or divided ql2h PO) and ceftiofur (4 mg/kg IM q24h) are broad-spectrum antibiotics that should be safe for the early embryo. Enrofloxacin (7.5 mg/kg q24h PO) also has broad-spectrum activity but would not be recommended for use in pregnant or potentially pregnant mares. The bioavailability of the tablet form of enrofloxacin appears to be superior to that of the injectable preparation.

Uterine infections due to fungal or yeast infections are difficult to treat and often follow chronic bacterial endometritis with extensive intrauterine antibiotic use. Clotrimazole and uterine lavage with dilute vinegar solutions are anecdotally the most effective treatments but can require more than one course of therapy. Dilute povidone-iodine lavage solutions (0.05%) have also been suggested. Vaginal speculum examinations are important to monitor cervical inflammation. Some mares are extremely sensitive to even dilute iodine solutions, in which case severe cervicitis, vaginitis, and intraluminal uterine adhesions can result. Occasionally spontaneous recovery from fungal endometritis is seen. In most cases these infections tend to be extremely difficult to resolve; the owner should be given a guarded prognosis for fertility.

Categories
Veterinary Medicine

Canine Parvovirus

1. What are the common clinical signs in dogs with canine parvovirus (CPV)?

• Lethargy

• Vomiting

• Inappetence

• Fever

• Acute-onset diarrhea

• Profound neutropenia (white blood cells < 1000/mm3)

Puppies between the ages of 6 weeks to 6 months are most commonly affected. In a Canadian study, sexually intact dogs had a 4-fold greater risk than spayed or neutered dogs, and the months of July, August, and September had a 3-fold increase in cases of canine parvovirus.

2. What systems other than the GI tract are involved with canine parvovirus?

In a study of dogs with the GI form of canine parvovirus, arrhythmia was diagnosed in 21 of 148 cases, including supraventricular arrhythmias and conduction disturbances. Some dogs developed significant enlargement of the cardiac silhouette and other radiographic cardiac abnormalities. CPV can replicate in bone marrow, heart, and endothelial cells; replication in endothelial cells of the brain produces neurologic disease.

3. What other infectious diseases may be mistaken for canine parvovirus infection?

Infection with Salmonella sp., Campylobacter sp., or Escherichia coli may mimic canine parvovirus symptoms and also cause the shift in white blood cells. CPV infection also may be confused with hemorrhagic gastroenteritis (HGE), although HGE is seen most commonly in smaller breeds and usually resolves in 24 hours. Coronavirus often presents with GI signs, but neutropenia tends to resolve more rapidly than with canine parvovirus infection. Clinical signs of infection with coronavirus are usually seen only in dogs also infected with parvovirus.

4. What is the primary mode of transmission of canine parvovirus?

The number of viral particles in the feces is quite high; the fecal-oral route is the most likely means of transmission. No studies of vomitus have been done, but it probably contains viral particles.

5. How does canine parvovirus infect the intestines?

Viral replication occurs in the oropharynx during the first 2 days of infection, spreading to other organ systems via the blood. By the third to fifth day a marked viremia develops. The virus reaches the intestinal mucosa from the blood rather than from the intestinal lumen. Clinical signs are seen 4-5 days after exposure, and the incubation period ranges from 3-8 days, with shedding of the virus on day 3.

6. Where does canine parvovirus replicate in the body?

The virus replicates in rapidly dividing cells, which include lymph nodes, spleen, bone marrow, and intestines. In the intestines, viral replication kills the germinal epithelium of the intestinal crypts, leading to epithelial loss, shortening of the intestinal villi, vomiting, and diarrhea. Lymphoid necrosis and destruction of myeloproliferative cells result in lymphopenia and, in severe cases, panleukopenia. Only about one-third of canine parvovirus cases have defined neutropenia or lymphopenia.

7. How has the clinical presentation of CPV infection changed since the 1970s?

There are several strains of canine parvovirus, including the original strain, CPV-1; the minute virus; and the most severe strain, CPV-2 (with subtypes 2a and 2b). CPV-2b is now the most common strain in the United States. CPV-1, which dominated in the 1970s, caused a milder disease associated with fever and a larger window for treatment. CPV-2b causes a more explosive acute syndrome that affects young dogs 6-12 weeks of age, making the window between the first signs of GI upset and treatment much narrower and more critical. There have been no major changes in presentation in the past 6 years; lethargy, listlessness, and bloody diarrhea are the most common presenting signs. Other diseases associated with or mistaken for canine parvovirus are canine distemper virus, coccidial or giardial infection, hookworms, roundworms, or a combination of these.

8. When and how does one diagnose canine parvovirus?

CPV is most easily diagnosed with a fecal enzyme-linked immunosorbent assay (ELIS A). If the test is negative but canine parvovirus is still suspected, isolate the animal and run the test again in 48 hours. The virus is not usually shed until day 3, and conscientious clients may bring the animal to the hospital at the first sign of illness. The period during which canine parvovirus is shed in the feces is brief, and the virus is not usually detectable until day 10-12 after infection. Usually the acute phase of illness has passed by this time. Modified live canine parvovirus vaccines shed in the feces may give a false-positive ELISA result 4-10 days after vaccination.

One also may use a combination of ELISA, complete blood count, and radiographs to diagnose canine parvovirus. Radiographs may help to rule out the possibility of an intestinal foreign body, and detection of generalized ileus with fluid-filled loops of intestines supports the diagnosis of canine parvovirus. Be sure to have enough antigen in the fecal sample when running the ELISA; watery stools may dilute the antigen and give a false-negative result.

Conclusive proof of canine parvovirus infection is made with electron microscope identification of the virus.

9. What are the recommendations for inpatient care of dogs with CPV?

1. Aggressive fluid therapy. Correct dehydration and provide intravenous maintenance fluid volumes of a balanced crystalloid solution. Make every attempt to replace continuing losses (vomitus and diarrhea) with equal volumes of crystalloid fluids. The easiest method is simply to estimate the volume lost and double your estimate. Continuing losses need to be replaced at the time that they occur. Use Normosol with at least 20 mEq/L of potassium chloride supplementation. Monitor glucose level. If necessary, add 2.5-5% dextrose to intravenous fluids. A 5% dextrose solution creates an osmotic diuresis, but it also allows assessment of progress in dealing with a septic case (glucose increases when the animal receives 5% dextrose if the sepsis is resolving). Low levels of magnesium chloride may be added to fluids to help correct unresponsive hypokalemia.

2. Antibiotic therapy. Broad-spectrum parenteral antibiotics are recommended because of disruption of the mucosal barrier and potential sepsis. Bacteremia is identified in 25% of dogs infected with parvovirus. A combination of ampicillin and gentamicin is recommended. Most veterinarians use only a first-generation cephalosporin in dogs without neutropenia or fever and reserve ampicillin and gentamicin or amikacin for dogs with signs of sepsis. One should be cautious about using an aminoglycoside because of renal toxicity.

3. Endotoxin-neutralizing products. Endotoxin-neutralizing products may be administered along with antibiotic therapy. The rationale for their use is based on the large population of gram-negative bacteria; by killing the bacteria, antibiotic therapy may shower the body with en-dotoxin, thus exacerbating the canine parvovirus condition. Studies have shown that endotoxin-neutralizing products decrease the incidence of septic shock. They may be diluted (4 ml/kg) with an equal volume of saline and administered intravenously over 30-60 minutes. Dogs who have recovered from parvovirus infections can be a good source for serum. Serum should be collected within 4 months of infection.

4. Antiemetics. Metoclopramide is the drug of choice. Phenothiazine derivatives should be used with caution and only after adequate volume replacement is initiated to avoid severe hypotension. Antiemetics are especially useful when continued vomiting makes it difficult to maintain hydration or electrolyte balance.

5. Motility modifiers. The use of motility modifiers is controversial. Anticholinergic anti-diarrheal medications may suppress segmental contractions and actually hasten transit time. Narcotic analgesics and synthetic opiates are better choices but should be reserved for severe or prolonged cases because slowing the flow through the intestine may increase toxin absorption.

6. Nothing per os (NPO). Begin a slow return to water 24 hours after the animal stops vomiting, and slowly progress to gruel made from a bland diet.

10. What is granulocyte colony-stimulating factor (GCSF)? What role does it have in treating dogs with CPV?

Granulocyte colony-stimulating factor selectively stimulates release of granulocytes form the bone marrow. Preliminary studies have shown that it reduces morbidity and mortality due to canine parvovirus. Unfortunately, it is available only as a human drug and is expensive, but when the positive benefits are considered, its use may be justified.

11. Does interferon benefit a dog with parvovirus infection?

Interferon given parenterally has been shown to be beneficial. The suggested dosage of human recombinant interferon is 1.3 million units/m2 subcutaneously 3 times/week.

12. How is a dog with canine parvovirus monitored?

Monitor respiration and central venous pressure (CVP) to prevent overhydration. With osmotic diarrhea the animal loses protein. If abdominal or extremity swelling is observed or if the total solids drop by 50% from admission values or go below 2.0 gm/dl, the animal should be supplemented with either 6% hetastarch or plasma to maintain colloid oncotic pressures. Blood glucose should be monitored at least 4 times/day on the first two days. Glucose level may drop precipitously and suddenly. Most importantly, weigh the dog at least twice each day. If adequate crystalloid replacement is provided, body weight does not decrease from initial values. Ideally body weight should increase at a rate comparable to the degree of dehydration originally assessed. Dogs that can hold down water for 12 hours may be offered a gruel made from bland foods. Most dogs force-fed by hand will vomit. This response may be physical or psychological (association of food with vomiting). Nasogastric tubes seem to help this problem. Metoclopramide speeds gastric emptying, acts as an antiemetic, and decreases gastric distention when added to the liquid diet. Dogs that are not vomiting should be offered food even if the diarrhea has not totally stopped. A low-fat, high-fiber diet is a good choice to stimulate intestinal motility.

13. How do you know when to send a dog home?

The dog should stay in the hospital for 12 hours after it has ingested solid food with no vomiting. Clients should report immediately any vomiting in the next 7 days or refusal to eat for 24 hours. A high-fiber diet is recommended for reducing diarrhea. A recheck appointment in 1 week with a stool sample helps the clinician to assess progress.

14. What recommendations do you offer to clients who have had a CPV-infected animal in their household and now want a new pet?

Prevention involves a proper vaccination regimen, limited exposure to other animals (especially in puppies less than 12 weeks of age), cleaning contaminated areas with bleach (allowing prolonged contact time), and vacuuming all surfaces with which the previous pet came into contact (rugs, carpet, walls, furniture). Newer higher-titer vaccines (some of which may be started as early as 4 weeks) are helpful. Generally, one should wait at least 1 month before bringing the new pet into the home. It is doubtful that the environment (especially outdoors) will ever be completely free of the virus. Canine parvovirus is a hardy and ubiquitous organism.

15. How long can a dog with CPV be expected to retain immunity?

A dog that has recovered from canine parvovirus can maintain life-long immunity.

16. What is the recommended vaccination schedule for dogs? Is it the same for every breed?

Some breeds are more susceptible to canine parvovirus than others. Rottweilers, American pitbull terriers, Doberman pinschers, and German shepherds are the most susceptible, whereas toy poodles and Cocker spaniels are less susceptible. The new higher-titer vaccines have a higher antigen level and a more virulent vaccine strain that can overcome maternal antibodies, unlike the older lower-titer vaccines. These vaccines narrow the window of infection, especially for susceptible breeds. The vaccination protocol for the new high-titer vaccines is 6, 9, and 12 weeks. Susceptible breeds should be vaccinated only with the high-titer canine parvovirus vaccine and then with a combination vaccine at 6-8, 12, and 16 weeks. For less susceptible breeds, the combination vaccines at 6-8, 12, and 16 weeks should be adequate. Some parvovirus vaccines are approved for use as early as 4 weeks of age.

17. How do you manage a sick puppy when the client is unwilling to pursue hospital treatment for CPV?

Canine parvovirus can be treated on an outpatient basis. A combination of dietary restriction, subcutaneous fluids, and, in some cases, GI medications may be used with a follow-up appointment in 1-3 days. Outpatient recommendations include the following:

• Small, frequent amounts of fluid

• Bland food

• Oral antibiotics

• Strong recommendation to have the pet reexamined and admitted for therapy if vomiting returns or anorexia persists

Nine of ten clients bring the dog back for inpatient care shortly after taking it home. Before treating an outpatient, remember that mildly depressed dogs may have a rectal temperature of 106° F and a blood glucose of 30 mg/dl in 12 hours or less.

18. Should a dog with suspected CPV be hospitalized and placed in isolation?

Undoubtedly hospitalization provides the best chance for survival. Isolation is more controversial. In most veterinary hospitals, isolation means that the animal is housed in a section of the hospital that is not staffed at all times. The adage “out of sight, out of mind” has led to the demise of many CPV-infected dogs. Experience with housing dogs with canine parvovirus in the critical care unit at the Veterinary Teaching Hospital of Colorado State University has shown that nosocomial infections can be avoided with a common-sense approach to patient management. The animal is placed in the least traveled area and has its own cleaning supplies; gowns and gloves are worn each time the animal is handled; and the animal’s cage is kept as clean as humanly possible. These procedures are no different from those in an isolation area. By being housed in an area where constant attention can be given, the animal receives adequate fluid replacement therapy and is monitored for changes, which occur rapidly.

19. How is nutrition provided for vomiting dogs?

Tough question! Dogs that have not eaten for 3-5 days are probably in a negative nitrogen balance, and certainly intestinal villi have undergone atrophy if not already destroyed by the canine parvovirus. The sooner patients begin receiving oral nutrition, the more rapidly they will recover. In addition, micronutrient therapy for the intestinal mucosa is required for maintenance of the mucosal barrier. Without this barrier, sepsis and bacteremia are more likely. Unfortunately, the only means to provide micronutrients is the oral route.

Glucose therapy does not provide nutritional support. It is best to think of dextrose as simply a source of water. One liter of 5% dextrose solution contains a mere 170 kcal. Increasing dextrose concentrations beyond 5% usually results in glycosuria and osmotic diuresis.

Patients that have not eaten for several days are primed for fat metabolism; thus, Intralipid (20%) may be added to fluids. It should be administered through a central IV catheter and requires strict aseptic management, which may be difficult if the patient is in an isolation area of the hospital.

For dogs that retain water without vomiting, glutamine may be added directly to the water bowl. Often placing electrolyte solutions in the water bowl is a good way to start the animal drinking. Placing dextrose in these fluids or even using commercial solutions such as Ensure-Plus in the bowl helps to provide intestinal nutrients.

20. Should parvovirus antibody levels be measured to check the immune status of the puppy?

Although antibodies to parvovirus can be measured, a negative titer does not necessarily mean that the dog is susceptible to canine parvovirus. Repeated revaccination of antibody-negative dogs usually does not result in significant titers.

Categories
Veterinary Medicine

Canine Hemorrhagic Gastroenteritis

1. What is canine hemorrhagic gastroenteritis (HGE)?

Canine hemorrhagic gastroenteritis is a syndrome characterized by the acute onset of profuse vomiting and bloody diarrhea with significant hemoconcentration.

2. What is the cause3 of hemorrhagic gastroenteritis?

The cause is unknown. Although the term hemorrhagic gastroenteritis implies an inflammatory condition, the disease is more likely due to altered intestinal mucosal permeability and perhaps mucosal hypersecretion. Cultures of GI contents from HGE-affected dogs have yielded large numbers of Clostridium perfringens, leading to speculation that this organism or its exotoxins are the cause.

3. Which dogs are most likely to be affected with HGE?

Toy and miniature breeds seem particularly prone to HE (hemorrhagic gastroenteritis), especially toy and miniature poodles and schnauzers, but the syndrome may affect any breed.

4. What are the clinical signs of hemorrhagic gastroenteritis?

• Acute onset of vomiting

• Profuse, bloody, fetid diarrhea

• Severe depression

• Shock

5. How is the diagnosis of HGE made?

• Extreme hemoconcentration (packed cell volume > 50-60%)

• Bloody, fetid diarrhea

• No leukopenia

• Fecal cytology with increased numbers of clostridial organisms

6. Describe the treatment for hemorrhagic gastroenteritis.

• Intensive fluid therapy until the packed cell volume is in the normal range and then continued intravenous crystalloid fluids (Normosol-R + potassium chloride) until vomiting is controlled.

• Antibiotics to control C. perfringens (ampicillin or amoxicillin)

• Restriction of food and water

• Antiemetic drugs (metoclopramide)

7. What is the prognosis of hemorrhagic gastroenteritis?

• Early, aggressive fluid therapy consistently results in significant improvement within 24 hours.

• If vomiting and diarrhea are not resolved in 48 hours, a search for other causes mimicking hemorrhagic gastroenteritis should be conducted (parvovirus, coronavirus, GI foreign bodies, intussusception, intestinal volvulus, clostridial enteritis, lymphocytic-plasmocytic enteritis).