"New" antimicrobials in veterinary medicine (Proceedings)

Unasyn (Ampicillin / sulbactam)

Unasyn 1.5 g vial (Generic ~$4.50) is commercially available containing ampicillin 1 g and sulbactam 0.5 g. Sulbactam is a beta lactamase inhibitor, therefore many people think of this drug as "injectable Clavamox." Unasyn is a broad spectrum antimicrobial with activity against Gram (+), Gram (-), anaerobes, Enterococcus spp, Leptospirosis spp. In comparison, to generic Unasyn ampicillin 1 g vial costs ~$4.75.

Dosing

30 – 40 mg/kg IV/SC/IM q 6-12 hours

Results in an ampicillin dose of 20-27 mg/kg

Cefpodoxime (Simplicef)

Cefpodoxime is a 3rd generation oral cephalosporin, however it does not penetrate BBB, prostate, or aqueous humor. It is not active against Pseudomonas aeruginosa. The wholesale cost of cefpodoxime is ~ $2 / 200 mg tab therefore a 20 kg dog administered cefpodoxime for 10 d would cost $10-20 (wholesale). Cefpodoxime has similar efficacy as cephalexin for Staph infections (i.e. pyoderma) with increased activity against E coli.

Dosing

5-10 mg/kg PO q 24 h

Cefocevin (Convenia)

Cefovecin is a veterinary specific 3rd generation cephalosporin that is primarily eliminated by renal mechanisms. Potential uses for cefovecin include: Bacteroides, E Coli, Staph, Strep, Pasteurella. However Pseudomonas, Bordetella, Enterococcus, and Clostridium are typically resistant. Cefovecin has a Long half-life due to high protein binding and slow clearance which is similar between IV and SC admin. Cefovecin is not a depot formula. It is labeled for SC admin only. Cefovecin has persistent drug concentrations, but the persistant low concentrations raises the concern of increased resistance.

Dosing

8 mg/kg q 7-14 days

Labeled for dogs and cats

Azithromycin

Azithromycin is an azalide antimicrobial. In general it can be thought of as being similar to the macrolides (i.e. erythromycin), but with increased antimicrobial activity except against Enterococcus spp. Azithromycin has less vomiting than erythromycin and penetrates lungs and tissues well. Adverse effects can include: nausea, vomiting, diarrhea. The spectrum includes Gram (+), Mycoplasma, Chlamydia, Borellia, Bordetella, and Bartonella. Azithromycin is not cost prohibitive: tablets, 250 mg, cost ~$1-2 per tablet and the suspension 40 mg/mL, 30 mL bottle, costs ~$20.

Dosing

The ideal dosing has not been established for dogs and cats

The current recommended dosages are:

Dogs: 3-10 mg/kg q 24 h x 3-7 days

Cats: 5 – 10 mg/kg q 24 h x 7 days than q 48 h

Ciprofloxacin

Ciprofloxacin is most commonly used as an alternative to enrofloxacin or other veterinary approved antimicrobials in companion animals. Extralabel use of ciprofloxacin in food animal species is strictly prohibited by AMDUCA. Ciprofloxacin has a very poor oral bioavailability in horses and is therefore ineffective for the oral treatment of systemic infections. The oral bioavailability of ciprofloxacin in cats is 33% compared to near 100% for enrofloxacin. Similarly, in dogs oral enrofloxacin is near 100% bioavailable, with ciprofloxacin being less bioavailable, but no studies have determined the actual oral bioavailability. Extralabel drug use of a human approved drug in companion (not food producing) animals such as dogs and cats is considered appropriate, even for economic reasons.

Ciprofloxacin and enrofloxacin have significantly different pharmacokinetic properties. Fluoroquinolone efficacy is best related to the area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio (AUC:MIC) with optimal dosages achieving a ratio of 125 or greater. Resistance to fluoroquinolones is minimized by achieving a maximum plasma concentration (CMAX) to MIC ratio of 8 or greater.

Ciprofloxacin administered 15 mg/kg PO q 12 hours results in an AUC of ~ 24 hr*mcg/mL per day. Therefore this dose would be optimal for bacteria with an MIC of 0.2 mcg/mL or less. The CMAX after 15 mg/kg of ciprofloxacin is ~ 2.0 mcg/mL which would decrease the potential resistance in bacteria with an MIC of 0.25 mcg/mL or less.

Enrofloxacin administered 5 mg/kg PO results in an enrofloxacin AUC of 4.5 hr*mcg/mL and a ciprofloxacin AUC 2.7 hr*mcg/mL for a total of 7.2 hr*mcg/mL sufficient for bacteria with an MIC of 0.06 mcg/mL or less. The CMAX of enrofloxacin is 1.2 mcg/mL and ciprofloxacin is 0.4 mcg/mL for a total of ~1.6 mcg/mL sufficient to delay resistance in bacteria with an MIC of 0.2 mcg/mL or less.

Fluoroquinolones typically are active against Staphylococcus spp. and gram negative aerobic bacteria (E coli, Klebsiella spp). Enrofloxacin, marbofloxacin, and ciprofloxacin have poor activity against anaerobic bacteria and Streptococcus spp. Therefore fluoroquinolones lack coverage in >1 quadrant in the typical 4 quadrant scheme of classifying bacteria. Enrofloxacin, ciprofloxacin, marbofloxacin et al are poor choices for abscesses, oral infections, and dental prophylaxis among other uses.

In general, the susceptibility of bacteria to enrofloxacin and ciprofloxacin are similar. The exception is Pseudomonas for which ciprofloxacin may be several times more active than enrofloxacin.

Fluoroquinolones tend to be well tolerated in most animals. Adverse effects can include gastrointestinal such as nausea, anorexia, vomiting and diarrhea. Retinal degeneration in cats has been reported with many fluoroquinolones, primarily with high doses or when administered to cats with renal disease. Although no reports documenting retinal degeneration from ciprofloxacin are available, it has not been extensively studied. All fluoroquinolones can cause articular cartilage damage in juvenile, growing animals. Recent reports documenting weakening of ligaments and tendons in humans are available which may or may not be applicable to veterinary patients. Animals with decreased renal function have decreased elimination of both ciprofloxacin and enrofloxacin, therefore the risk of toxicity and adverse effects are markedly increased. Signs of fluoroquinolones toxicity can include: dysphoria, seizures, coma, stupor, and blindness. Due to their CNS stimulatory effects, fluoroquinolones should be avoided in animals prone to seizures as they may elicit or exacerbate seizures. Fluoroquinolone decrease the metabolism of theophylline / aminophylline, therefore concurrent administration can result in theophylline toxicity manifested as tremors, seizures, tachycardia, and excitement.

Disclaimer: The information is accurate to the best of the author's knowledge. However recommendations change as new data become available and errors are possible. The author recommends double checking the accuracy of all information including dosages.