Chloramphenicol

Chloramphenicol

Jennifer L. Buur, DVM, PhD, DACVCP, Western University of Health Sciences

November 2017|Peer Reviewed

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Chloramphenicol

Overview

  • 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 

Drug Interactions

  • 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

Antimicrobial Stewardship

  • 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

References and Author Information

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