- Chloramphenicol is a broad-spectrum, bacteriostatic anti-microbial agent that acts through the inhibition of protein synthesis via the 70S ribosome and its 50S ribosomal subunit.
- Due to high lipophilicity, it has good penetration into protected sites (eg, brain, aqueous humor, prostate).1
- Although adverse effects limit use of chloramphenicol as a first-choice treatment, methicillin-resistant Staphylococcus pseudintermedius is often susceptible.2
Adverse Effects & Risk Factors
- Common adverse effects in dogs include GI upset (eg, vomiting, diarrhea, anorexia, drooling, gagging), lethargy, restlessness, increased hepatocellular enzymes, and generalized trembling or shaking.2
- Anemia and other bone marrow suppression can occur secondary to mitochondrial damage at high doses or extended durations.
- Dogs can experience effects at doses of 225 mg/kg for 14 days or 50 mg/kg for 50 days.2,3
- Cats are at higher risk than dogs because of deficiencies in effective glucuronidation enzymes that can lead to prolonged plasma, tissue, and, subsequently, mitochondrial concentrations.3
- Peripheral neuropathy that manifests as pelvic limb weakness in larger dogs (>55 lb [25 kg]) has been reported.2
- Signs resolved after the drug was discontinued.
- Risk factors include a history of hepatic disease, neoplastic disease, polypharmacy, and exposure durations over 10 days.
- Baseline and midtreatment CBC and serum chemistry profiles are recommended in patients with any of these factors.1,2,4
- Humans are susceptible to developing anemia (dose-dependent and idiosyncratic aplastic forms) from inhibition of mitochondrial protein synthesis via the 70S ribosome.
- Owners should be advised to handle the drug carefully and use appropriate protective equipment (eg, gloves, eye protection, facial shields) when needed.1,2
- Efficacy is decreased when chloramphenicol is used with bactericidal drugs such as fluoroquinolones or other inhibitors of the 50S ribosomal subunit (eg, macrolides).1
- Chloramphenicol specifically inhibits canine CYP2B11 and thus increases the half-life of methadone, barbiturates (eg, phenobarbital), digoxin, propofol, and primidone in dogs.5-7
- Because of highly variable changes in drug pharmacokinetics, therapeutic drug monitoring of chronic medications (eg, phenobarbital) is recommended midway through and after treatment with chloramphenicol.
- Patients should be monitored for such adverse effects as sedation, polyuria, and polydipsia during treatment.7
- Chloramphenicol is metabolized by both phase I and phase II enzymes in the liver.
- Hepatic dysfunction can increase plasma concentrations and half-life, which can lead to an increased risk for adverse effects.
- Conversely, induction of P450 enzymes from concurrent administration of medications such as phenobarbital can decrease plasma concentrations and half-life, which can lead to a decrease in overall efficacy.1,5
- Selective pressure changes to normal flora can lead to resistance in fecal enterococci and a nosocomial source for multidrug-resistant bacteria with zoonotic potential.8
- Cohabitation with dogs and cats has been associated with zoonotic transfer of multidrug-resistance (mdr) genes between enterococci.8
- Resistance to chloramphenicol is associated with resistance to other antimicrobial agents.8
- Risk factors for fecal resistance include coprophagia and previous exposure to fluoroquinolone antimicrobial agents.8
- Alternative administration routes (eg, regional limb perfusion) may lower systemic exposure and decrease gut microbiome changes and should be considered when possible.9
Legal Considerations for Use
- The Animal Medicinal Drug Use Clarification Act of 1994 specifically prohibits extra-label use of chloramphenicol in food animals.10
- Because of the increased popularity of pot-bellied pigs as pets, veterinarians must recognize that all porcine species are considered under federal law as food animals.
- This federal law also applies to meat rabbits and backyard chickens, which occasionally may be presented to small animal practices.10
- Dowling PM. Chloramphenicol, thiamphenicol, and florfenicol. In: Giguère S, Prescott JF, Baggot JD, Walker RD, Dowling PM, eds. Antimicrobial Therapy in Veterinary Medicine. 4th ed. Ames, IA: Blackwell Publishing; 2006:241-248.
- Short J, Zabel S, Cook C, Schmeitzel L. Adverse events associated with chloramphenicol use in dogs: a retrospective study (2007-2013). Vet Rec. 2014;175(21):537.
- Papich MG, Riviere JE. Chloramphenicol and derivatives, macrolides, lincosamides, and miscellaneous antimicrobials. In: Riviere JE, Papich MG, eds. Veterinary Pharmacology and Therapeutics. 9th ed. Ames, IA: Wiley-Blackwell; 2009:945-982.
- Li CH, Cheng YW, Liao PL, Yang YT, Kang JJ. Chloramphenicol causes mitochondrial stress, decreases ATP biosynthesis, induces matrix metalloproteinase-13 expression, and solid-tumor cell invasion. Toxicol Sci. 2010;116(1):140-150.
- KuKanich B, KuKanich K. Chloramphenicol significantly affects the pharmacokinetics of oral methadone in Greyhound dogs. Vet Anaesth Analg. 2015;42(6):597-607.
- Ciaccio PJ, Duignan DB, Halpert JR. Selective inactivation by chloramphenicol of the major phenobarbital-inducible isozyme of dog liver cytochrome P-450. Drug Metab Dispos. 1987;15(6):852-856.
- Houston DM, Cochrane SM, Conlon P. Phenobarbital toxicity in dogs concurrently treated with chloramphenicol. Can Vet J. 1989;30(7):598.
- Leite-Martins L, Mahú MI, Costa AL, et al. Prevalence of antimicrobial resistance in faecal enterococci from vet-visiting pets and assessment of risk factors. Vet Rec. 2015;176(26):674.
- Kelmer G, Tatz AJ, Famini S, Bdolah-Abram T, Soback S, Britzi M. Evaluation of regional limb perfusion with chloramphenicol using the saphenous or cephalic vein in standing horses. J Vet Pharmacol Ther. 2015;38(1):35-40.
- Animal Medicinal Drug Use Clarification Act of 1994, 21 USC §530 (1994). U.S. Government Publishing Office. Accessed at https://www.ecfr.gov/cgi-bin/text-idx?SID=054808d261de27898e02fb175b7c9ff9&node=21:188.8.131.52.16&rgn=div5#21:184.108.40.206.220.127.116.11. Updated October 1, 2017. Accessed October 4, 2017.
Material from Clinician’s Brief may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.