Chloramphenicol (with special reference to Hedgehogs, Elephants, Bears, Lagomorphs, Ferrets and Great Apes)

• Chloramphenicol: Fine white to greyish yellow white elongated plates/needle-like crystals. (B263); colourless crystals, intensely bitter taste. (B135.44.w44)

• Chloramphenicol palmitate: bland, mild tasting, fine white unctuous crystalline powder with a faint odour. (B263)

• Chloramphenicol sodium succinate: white to light yellow powder. (B263)

• 151°C. (W324)

• Chloramphenicol: poorly soluble (B135.44.w44);  about 2.5 mg/ml water at 25°C. (B263); slightly soluble. (W324)

• Chloramphenicol palmitate: insoluble in water. (B263)

• Chloramphenicol sodium succinate: highly soluble in water. (B135.44.w44, B263)

• Chloramphenicol: highly soluble in alcohol. (B135.44.w44, B263)

• Chloramphenicol palmitate: sparingly soluble in alcohol (B263)

• Chloramphenicol sodium succinate: freely soluble in alcohol. (B263)

• Lipid-soluble. (B201)

• Chloramphenicol: neutral. (B135.44.w44)

• Binds (reversibly) to the 50S ribosomal subunit of susceptible bacteria, blocking the action of peptidyl transferase and interfering with amino acid incorporation into peptides, preventing bacterial protein synthesis. (B135.44.w44,B263)
• Also bind to mitochondrial ribosomes of rapidly proliferating mammalian cells such as bone marrow, inhibiting mitochondrial protein synthesis. (B135.44.w44, B263)
• Irreversibly inhibits cytochrome P450 enzymes involved in barbiturate metabolism (B201)

• Chloramphenicol: capsules and tablets should be stored at room temperature (15-30°C) (B263)

• Chloramphenicol palmitate: oral suspension should be stored in tight containers at room temperature with protection from light and from freezing. (B263)

• Chloramphenicol sodium succinate: powder for injection should be stored preferably at 15-30°C, certainly below 40°C. Following reconstitution with sterile water, stable at room temperature for 30 days or frozen for six months. Discard if solution becomes cloudy. (B263)

• Saturated aqueous solution of chloramphenicol (0.25%) if protected from light maintains stability, at room temperature or refrigerated, for many months. (B135.44.w44)

Associated Techniques

• Usually bacteriostatic; may be bactericidal at higher concentrations or against very susceptible organisms such as Haemophilus influenzae, Neisseria meningitidis, some strains of Bacteroides. (B135.44.w44, B263)
• Wide spectrum of activity. (B263)
  • Active against many Gram-positive aerobic organisms including many streptococci and staphylococci (B201.1.w1, B263). Inhibitory at concentrations on 1.0-10 µg/ml. (B135.44.w44)
  • Active against some Gram-negative aerobic bacteria including Neisseria, Brucella, Salmonella, Shigella, Haemophilus spp. (B263) Inhibitory at concentrations of 0.2-0.5 µg/ml. (B263)
  • Active against Actinobacillus, Bordetella, Haemophilus, Pasteurella spp. (B201.1.w1)
  • Active against many anaerobic bacteria including Clostridium spp., Bacteroides (including Bacteroides fragilis), Fusobacterium, Veillonella. (B263)
  • Active against Nocardia, Chlamydia, Mycoplasma, Rickettsia. (B201.1.w1, B263)
    • Activity against Mycoplasma is unreliable. (B201.1.w1)

• Particularly for infections with anaerobic bacteria. (B263)

• Prohibited for use in food-producing animals. (B201.1.w1, B263)
• In dogs: not the best choice for lower urinary tract infections as only a small amount is excreted unchanged in the urine. (B263)
• Clinically ineffective against chlamydiae (Chlamydia spp.). (B135.44.w44)
• Increasing frequency of plasmid-mediated resistance in salmonellae (Salmonella spp.). (B135.44.w44)
• Plasmid-mediated resistance is due to production of chloramphenicol acetyltransferase; this bacterial enzyme inactivates chloramphenicol. (B135.44.w44)
• Activity against Mycoplasma and Proteus spp. is unreliable. (B201.1.w1)
• Inactive against Pseudomonas spp. (B201.1.w1)

• Usual serum therapeutic range five to 15 µg/ml.(B263)
• Chloramphenicol sodium succinate for injection: contains 2.3 mEq sodium per gram of chloramphenicol. (B263)
• Bitter tasting: crushed tablets or capsule contents may be rejected by animals. (B263)
• Occasional resistant mutant bacteria which are less permeable to chloramphenicol (two to four times more resistant than the main population) emerge only slowly in treated individuals. (B135.44.w44)

• Rapid and complete absorption; peak serum levels about 30 minutes after oral administration. (B135.44.w44, 263)
  • In humans: daily oral dose of 2g results in blood chloramphenicol levels of 8µg/ml. (B135.44.w44)
• In cats: lower peak serum level when chloramphenicol palmitate oral suspension is given to fasted individuals. (B263)
• Chloramphenicol sodium succinate: rapid and good absorption following intramuscular or subcutaneous administration; does not need to be administered only intravenously. (B263)
• Hydrolysis of chloramphenicol palmitate and chloramphenicol sodium succinate to chloramphenicol occurs in the liver. (B263)

• Wide distribution throughout the body. (B135.44.w44, B201.1.w1, B263)
• Readily crosses cell membranes. (B135.44.w44, B201.1.w1)
• Highest levels in liver and kidneys. (B263)
• Therapeutic levels are reached in most tissues and fluids, including: aqueous humour and vitreous humour of the eye, synovial fluid. (B201.1.w1, B263)
• In cerebrospinal fluid (CSF), levels are up to 50% of serum levels, and higher if the meninges are inflamed (N.B. four to six hours lag time to reach peak CSF levels). (B263)
  • Brain levels may reach serum levels. (B135.44.w44)
• In the prostate levels reach about 50% of serum levels. (B263)
• Crosses the placenta. (B263)
• Enters milk; in humans reaches 50% of plasma levels. (B263)

Volume of distribution:

• Dog: 1.8 L/kg. (B263)
• Cat: 2.4 L/kg. (B263)
• Horse: 1.41 L/kg. (B263)

• About 30-60% plasma protein bound. (B263); about 30% plasma protein bound. (B135.44.w44)

• Primarily hepatic, metabolised by glucuronidative mechanisms. (B263)
  • Conjugation with glucuronic acid. (B135.44.w44, B201)
• Also inactivated by reduction to inactive aryl amines.(B135.44.w44)
• About five to 15% excreted unchanged in urine. (B263); about 10% of active chloramphenicol and most of the inactive products are excreted in urine. (B135.44.w44)
• Small amounts of active drug are excreted in bile or faeces. (B135.44.w44)
• In cats: 25% or more excreted unchanged in urine, due to low ability to glucuronidate drugs. (B263)

• Dog: 1-1.5 hours. (B263)
• Pony/foal less than one hour. (B263)
• Cat: 4-8 hours. (B263)
• Pigeon: 26 minutes. (B263)
• Bald eagle: nearly five hours. (B263)
• Peafowl: nearly five hours. (B263)

• May inhibit hepatic metabolism of various drugs including chlorpropamide, cyclophosphamide, pentobarbital, phenobarbitone, phenytoin, primidone, tolbutamide, warfarin. (B135.44.w44, B263)
  • Metabolism of barbiturates may be affected for up to three weeks by a single 50mg/kg dose of chloramphenicol in dogs.(B201)
  • Shown to increase pentobarbital anaesthesia duration in dogs by 120%, in cats by 200%.(B263)
  • Phenobarbital may decrease chloramphenicol plasma concentrations.(B263)
  • Anorexia and CNS depression may occur in dogs with concurrent primidone administration, (B263)
• May decrease haematological response to iron salts and to Vitamin B₁₂. (B263)
• Serum half life may be increased slightly by concurrent administration of Penicillin. (B263)
• May antagonise the bactericidal activity of penicillins or aminoglycoside antibiotics, although this has not been demonstrated in vivo. (B263)
• Serum levels may be decreased by concomitant administration of rifampin.(B263)
• Potential antagonism of other antibacterial agents which act by binding to the 50S ribosomal subunit (e.g. erythromycin, clindamycin, lincomycin, tylosin); chloramphenicol may also antagonise the action of these other antibiotics. However the clinical significance of such potential interactions has not been determined.(B263)
• Response to vaccinations may be decreased as chloramphenicol may suppress antibody production if given prior to an antigenic stimulus.(B263)

Chloramphenicol sodium succinate: 

• Reported compatible with: "all commonly used intravenous fluids, amikacin sulfate, aminophylline, ampicillin sodium (in syringe for 1 hr.), ascorbic acid, calcium chloride/gluconate, cephalothin sodium, cephapirin sodium, colistimethate sodium, corticotropin, cyanocobalamin, dimenhydrinate, dopamine HCl, ephedrine sulfate, heparin sodium, hydrocortisone sodium succinate, hydroxyzine HCl, kanamycin sulfate, lidocaine HCl, magnesium sulfate, metaraminol bitartrate, methicillin sodium, methyldopate HCl, methylprednisolone sodium succinate, metronidazole w/ or w/o sodium bicarbonate, nafcillin sodium, oxacillin sodium, oxytocin, penicillin G potassium/sodium, pentobarbital sodium, phenylephrine HCl w/ or w/o sodium bicarbonate, phytonadione, thiopental sodium, verapamil HCl, and vitamin B-complex with C." (B263)
• Reported incompatible with (or conflicting data): "chlorpromazine HCl, glycopyrrolate, metoclopramide HCl, oxytetracycline HCl, polymyxin B sulfate, prochlorperazine edislyate/methsylate, promethazine HCl, tetracycline HCl, and vancomycin HCl." (B263)
• Compatibility is affected by factors including pH, concentration, temperature and diluents used. (B263)

• Chloramphenicol sodium succinate: May be given by the intravenous, intramuscular or subcutaneous routes. (B263)

Use of Drugs (Medication):

• Before administration of any pharmaceutical product the manufacturer's datasheet must be consulted regarding operator safety, relevant withdrawal times etc.
• Many drugs are not registered for use in particular species and additional care should be taken in their use, with proper regard for possible toxic effects. 
• Consideration should be given to relevant legislation regarding the use of drugs.
• In the UK, guidelines regarding the use of drugs are set out in the Royal College of Veterinary Surgeons' Guide to Professional Conduct 2000: (See: LCofC1 - RCVS Guide to Professional Conduct 2000 - Choice of Medicinal Products).

Erinaceus europaeus - West European Hedgehog:

• 30 mg/kg intramuscularly every 12 hours. Broad spectrum; for acute salmonellosis (Salmonellosis). (B22.27.w3, B267)
• 50 mg/kg orally twice daily. Broad spectrum; for acute salmonellosis. (B22.27.w3, B267)
• Chloramphenicol sodium succinate 20 mg/kg intramuscularly or subcutaneously twice daily or 40 mg/kg oral once daily. (D93)
• Ocular: ophthalmic ointment, 5-6 times daily topically. (D93)

• 50 mg/kg orally, subcutaneously or intramuscularly, every twelve hours. (B267)
• 30 mg/kg every 12 hours or 50 mg/kg oral every 12 hours. Bacteriostatic, useful against Salmonellae. (J204.59.w1)

"Hedgehog" (species not distinguished between Atelerix albiventris - Four-toed hedgehog or Erinaceus europaeus - West European Hedgehog):

• 50 mg/kg orally, every 12 hours. (B150.w1)
• 30-50 mg/kg subcutaneously, intramuscularly, intravenously or intraosseously, every 12 hours. (B150.w1)

Ocular: topical administration for treatment of eye infections (N.B. not effective against Chlamydia spp. infection). (B135.44.w44)

Lagomorphs - Oryctolagus cuniculus domesticus - Domestic rabbit:

• 50 mg/kg orally once daily. (B373.Guide.w41)
• 15 mg/kg intramuscularly twice daily. (B373.Guide.w41)
• 50 mg/kg orally every 12 - 24 hours. (B546)
• 25 mg/kg orally every 8 - 12 hours. (B548.w8)
• 30 mg/kg orally every 12 hours. (B548.w8)
• 30 mg/kg subcutaneously, intramuscularly or intravenously every 8 -12 hours. (B548.w8)
• 50 mg/kg orally, subcutaneously, intramuscularly or intravenously every eight hours. (B548.w8)
• 1.3 mg per mL of drinking water. (B548.w8)
  • Note: "Partially effective at 0.5 mg/kg in clinical trial for Pasteurellosis in Lagomorphs." (B548.w8)
• Chloramphenicol palmitate 50 mg/kg orally every 12 to 24 hours for 5 - 7 days. (B601.15.w15)
  • Not for use in food animals. (B601.15.w15)
• Chloramphenicol succinate 50 mg/kg subcutaneously every 12 hours. (B601.15.w15)
• 30 - 50 mg/kg orally every 12 hours. (B602.41.w41)
• 30 mg/kg intramuscularly daily. Broad-spectrum bacteriostatic agent. Note: there are restrictions on the use of chloramphenicol, particularly since rabbits are a species used as food animals. (B603.5.w5)
• Topically, ophthalmological. (B601.15.w15)

In Elephants:

Loxodonta africana - African Elephant

• Daily flushing of an infected tusk tract with 2-5 g of chloromycetin sodium succinate (chosen based on culture and sensitivity) was used in the treatment of a six-year-old Loxodonta africana - African Elephant. (J4.189.w4)

In Bears (Ursidae - Bears (Family)):

• 20-50 mg/ kg orally every eight hours has been used for the treatment of Bacterial Gastroenteritis in Bears. (B64.26.w5)
• 250 mg parenterally three times daily for six days in the treatment of Leptospirosis. (B16.9.w9, P1.1975.w1)
• Topical application to the skin at 10 g/gallon weekly, for treatment and continuing control of Dermatophilosis in Bears. (P1.1977.w1)

• In general: "Domestic dog drugs and dosages are used to treat bears." (B336.51.w51)

In Dogs:

• 50 mg/kg orally or by slow intravenous injection, 1-2 times daily. (B373.1.w1)

In Ferrets - Mustela putorius furo - Ferret:

• Chloramphenicol palmitate liquid 50 mg/kg orally twice daily. "Drug of choice but now restricted use (children)." (B626.App.w22)
• Chloramphenicol succinate 30 - 50 mg/kg intramuscularly or subcutaneously twice daily. "Can be given orally but with sugar solution as it is bitter."(B626.App.w22)
• 30 - 50 mg/kg intramuscularly or subcutaneously every 12 hours. (B631.21.w21)
• 25 - 50 mg/kg orally every 12 hours. (B602.41.w41)
• 50 mg/kg orally (chloramphenicol palmitate) or subcutaneously or intramuscularly (chloramphenicol succinate) twice daily. (J213.3.w1)

Great Apes

• Adult Pan troglodytes - Chimpanzee: Chloramphenicol succinate 20 mg/kg intramuscularly twice daily, or 50 mg/kg subcutaneously three times daily. (W768.Jun2012.w1)
• 45 mg/kg in the treatment of Shigellosis. (P6.2.w10)
• Primates 25-50 mg/kg intramusclarly or orally, twice to four times daily. Excellent broad-spectrum; this may be the antibiotic of choice in gorillas. (D425.3.15.w3o)

• In cats: close monitoring is indicated if prolonged high-dose therapy is required. (B263)
• Serum monitoring may be required if chloramphenicol is administered with other drugs with which it may interact (see: Drug Interactions above)

• Prohibited  for use in food-producing animals by the USA FDA. (B263)

• Contraindicated in individuals hypersensitive to chloramphenicol. (B263)
• Extreme caution is suggested if used at all in individuals with pre-existing haematological abnormalities, particularly pre-existing non-regenerative anaemia. (B263)
• Not for use in patients with hepatic failure unless no other effective antibiotics are available. (B263)
• Use with caution in individuals with hepatic impairment or renal impairment as the drug may accumulate; monitoring of blood levels and dosing adjustment (decrease) may be required in such individuals (B263)
• Use with caution in neonates, particularly young kittens. (B263)
• Use with caution in nursing bitches/queens, particularly in the first week after parturition, since the drug is excreted in milk. (B263)
• Use with extreme caution, if at all, concurrently with other drugs causing myelosuppression (such as cyclophosphamide). (B263)
• Use with extreme caution, if at all, in cats with renal failure. (B263)
• Vaccinations should be postponed if possible in individuals receiving chloramphenicol (see above: Drug Interactions).

• Dose-related reversible bone marrow suppression.
  • Early signs of bone marrow toxicity may include vacuolation of early cells in the myeloid and erythroid series, lymphocytopaenia, neutropaenia. (B263)
  • Development of aplastic anaemia (as reported in humans) does not appear to be a significant problem in veterinary patients. (B263)
• Anorexia, vomiting, diarrhoea and depression may be noted. (B263)
• High incidence of adverse effects noted in cats given 50 mg/kg twice daily for two to three weeks. (B263)
• In cats may accumulate (due to limited metabolism) resulting in reversible bone-marrow suppression. (B201.1.w1)

• Before the use of any pharmaceutical product the label instructions for the product should be consulted regarding operator safety/warnings.
• Handle with care: increased risk of fatal aplastic anaemia following human exposure to chloramphenicol. (B135.44.w44, B263)
  • Do not inhale powder.(B263)
  • Wash hands after handling tablets.(B263)
  • Wear gloves, avoid drug-skin contact. (B201.1.w1)

• Potentially serious bone marrow toxicity.(B263)
  • The gut should be emptied using standard protocols. (B263)

• Dose-related reversible bone marrow suppression may be seen, particularly with long term therapy. (B263)

• Not shown safe for use during pregnancy. May decrease protein synthesis (particularly in the bone marrow) in the fetus.(B263)

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