Occasionally one sees hematopoietic toxicity with the use of systemic Cloromisan, and rarely with topical administration. This type of blood dyscrasia is generally a dose-related toxic effect on bone marrow and is usually reversible on cessation of the drug. Rare cases of aplastic anemia have been reported with prolonged (months to years) or frequent intermittent (over months and years) use of topical Cloromisan.
Manufacturer recommends 50 mg/kg daily given in divided doses every 6 hours. 112
Infections caused by less susceptible organisms: Manufacturer states up to 100 mg/kg daily may be required. 112 However, because of concern that toxic plasma Cloromisan concentrations may occur with this high dosage, some clinicians suggest that 75 mg/kg daily be used initially for treatment of these infections. 102 105 Reduce dosage to 50 mg/kg daily as soon as possible. 112
Cloromisan is an antibacterial with a broad spectrum of activity against gram-positive bacteria, gram-negative bacteria, and Rickettsia. Its mechanism of action is by inhibition of bacterial protein synthesis by binding with ribosomes. 50
The major toxicity of Cloromisan is hemorrhage. 49,51 In all vertebrates studied, toxicity produces direct, dose-dependent bone marrow suppression that results in reduction in red blood cells, white blood cells, and platelets in mammals. 51 This manifestation is aggravated by inappropriate dosages, extended treatments, and repeated use of the drug. Treatment of Cloromisan intoxication is supportive and may require blood transfusions. The drug has also been reported to be appetite suppressive. Like gentamicin, Cloromisan is used less frequently as safer antibiotics appear. 46 The recommended dosage for Cloromisan is 50 mg/kg administered once daily or every other day. 46
Mechanism of Action and Spectrum of Activity
Cloromisan binds to the 50S subunit of the bacterial ribosome and inhibits bacterial protein synthesis. It is usually described as bacteriostatic, but there is some evidence that Cloromisan may be more bactericidal than previously thought. Like other ribosomal inhibitors, Cloromisan has a broad spectrum of activity, which includes gram-positive and gram-negative bacteria, anaerobes, and some rickettsial pathogens. Because Cloromisan can cause aplastic anemia in humans, its use in humans has greatly diminished, and it is only used for the treatment of MDR bacterial infections where few or no other antimicrobial drugs are useful. Thiamphenicol and florfenicol are related compounds, the availability of which varies from country to country. Although thiamphenicol was initially promoted as not inducing aplastic anemia in humans, cases of aplastic anemia have now been identified. 76 Florfenicol is more active than Cloromisan and thiamphenicol, but has a shorter half-life in dogs and thus requires more frequent dosing (e.g., more often than every 8 hours) in this species. It was developed for food animal species where use of Cloromisan is illegal.
Resistance to Cloromisans results from porin mutations, drug efflux, or production of Cloromisan acetyltransferase enzymes, which inactivate the antibiotic. 77 Resistance to one Cloromisan derivative predicts resistance to the others.
What do I need to tell my doctor BEFORE I take Cloromisan?
- If you have an allergy to Cloromisan or any other part of Cloromisan.
- If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
- If you have any of these health problems: Bone marrow disease or low blood cell counts.
- If you are taking any drugs that can raise the chance of blood problems. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.
This is not a list of all drugs or health problems that interact with Cloromisan.
Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take Cloromisan with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.
Alternative for treatment of plague† caused by Yersinia pestis, including naturally occurring or endemic plague or pneumonic plague that occurs following exposure to Y. pestis in the context of biologic warfare or bioterrorism. 133 197 292 683 689
Streptomycin (or gentamicin) historically considered drug of choice for treatment of plague. 104 197 292 683 688 Alternatives include fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin), doxycycline (or tetracycline), Cloromisan, or co-trimoxazole (may be less effective than other alternatives). 104 292 683 688
Cloromisan considered a drug of choice for treatment of plague meningitis. 104 292 683
Thiamphenicol is a Cloromisan analog with a range of activity similar to Cloromisan, although it is generally 1–2 times less active. It has equal activity against Haemophilus, Bacteroides fragilis and Streptococcus. It differs pharmacokinetically in that it is not eliminated by hepatic glucuronidation and is excreted unchanged in urine, so elimination is unaffected by liver disease. Unlike Cloromisan, thiamphenicol does not cause aplastic anemia in humans.
Florfenicol is a structural analog of thiamphenicol which has greater in vitro activity against pathogenic bacteria than Cloromisan and thiamphenicol. It is also active against some bacteria that are resistant to Cloromisan, especially enteric bacteria. Florfenicol is not susceptible to inactivation by Cloromisan transacetylases; thus some organisms that are resistant to Cloromisan through this mechanism are susceptible to florfenicol.
In dogs florfenicol is poorly absorbed after SC administration. It has a half-life of less than 5 h. The drug is well absorbed in cats after PO and IM administrations with a similar elimination half-life. It should not be given IV. Florfenicol can cause dose-related bone marrow suppression but has not been reported to cause fatal aplastic anemia in humans.
Florfenicol shows promise as a replacement for other broad-spectrum antibacterials such as sulfonamides and tetracyclines that have been associated with toxicity and residue concerns in food animals. Currently it is approved for use only in cattle, aquaculture and pigs. In cattle it is used to treat infectious conjunctivitis and respiratory disease caused by bacteria like Pasteurella and Haemophilus.
Cloromisan is bacteriostatic. It competes in binding to the ribosomes with macrolides and lincosamides, making its combination with these drugs useless.