Induction of leukaemia in chloramphenicol-treated toads.

Chloramphenicol has been associated with the development of aplastic anaemia. As it is still widely used in Egypt, we studied its effect on 100 Egyptian toads (Bufo regularis) given a dose of chloramphenicol of 5 mg/40 g body weight for 12 weeks. We found it induced numerous, severe ultrastructural changes in almost all types of leukocytes. These changes were similar to those induced by the chemical carcinogen 7,12-dimethylbenz(a)anthracene in 100 toads used as the carcinogen control group, and similar to those in leukocytes reported in humans with leukaemia. We recommend regulations be applied on the use of this antibiotic in countries where it is still widely used.

Experimental chloramphenicol intoxication in neonatal calves: intravenous administration.

Chloramphenicol was administered intravenously for eight to 17 days to five newborn calves at a daily dosage of 100 mg kg-1. Haemodynamic, haematological, blood chemistry, serum enzyme, urinalysis and clinical responses were evaluated. High levels of serum chloramphenicol were observed throughout the study although a marked increase in elimination rate was seen with increasing age. The most severe adverse effects were severe hypotension following rapid intravenous administration and severe gastrointestinal dysfunction with diarrhoea accompanying prolonged high dosage. There appeared to have been a haematological effect in one calf, but it was of minor significance compared with the other effects.

Chloramphenicol-induced bone marrow injury: possible role of bacterial metabolites of chloramphenicol.

To explore the potential role of some bacterial metabolites of chloramphenicol (CAP) in CAP-induced hematotoxicity, we examined their cytotoxic effects on bone marrow cells in vitro using a number of cytotoxicity parameters. Among the metabolites tested, dehydro-CAP (DHCAP) and p-nitrophenyl-2-amino-3 hydroxypropanone-HCI (NPAP) were more toxic than CAP. DHCAP was at least as toxic as nitroso-CAP. At concentrations of less than or equal to 10(-4) mol/L, DHCAP caused total irreversible inhibition of myeloid colony (CFU-GM) growth and 80% inhibition of DNA synthesis in human bone marrow. Incubation of human bone marrow cells with 10(-4) mol/L nitroso-CAP or DHCAP for 24 hours resulted in 75% and 65% cell death respectively. Although DHCAP was 10- to 20-fold more cytotoxic than CAP, it was only one third as effective in inhibiting mitochondrial protein synthesis, indicating that DHCAP exerts its toxic effect by alternate mechanisms. The cytotoxicity of DHCAP and its relative stability, compared to the unstable nitroso CAP, suggest that this bacterial metabolite of CAP, and possibly others, may play a significant role in CAP-induced hematotoxicity.

Resin hemoperfusion for chloramphenicol intoxication.

A case report of a three kilogram, four month infant who received excessive doses of chloramphenicol for the treatment of bacterial meningitis is presented. The child was treated with resin hemoperfusion (XAD-4) to reduce her serum chloramphenicol concentration. Her treatment was complicated by hypocalcemia and thrombocytopenia. During hemoperfusion a mean clearance of chloramphenicol of 27.4 ml/min was achieved. This represents a significant improvement over normal body clearance (4.7 ml/min/kg) in pediatric patients. We conclude that using hemoperfusion is an effective modality which may be used as an adjunct to supportive therapy when there is a need to increase the body clearance of chloramphenicol.

Chloramphenicol toxicity in neonates: its incidence and prevention.

The incidence of dose related chloramphenicol toxicity was determined in 64 neonates from 12 hospitals. Ten of the 64 exhibited symptoms attributed clinically to chloramphenicol toxicity. Nine received the dose prescribed and one an overdose. Symptoms of the grey baby syndrome were observed in five of the 10 babies; four babies suffered reversible haematological reactions; and one baby was described as very grey. Peak serum chloramphenicol concentrations in these 10 babies ranged from 28 to 180 mg/l and trough concentrations from 19 to 47 mg/l. Serum chloramphenicol concentrations above the therapeutic range (15-25 mg/l) were observed in a further 27 neonates (two had received a 10-fold overdose), none of whom showed signs of toxicity. Serious toxicity was associated with either prescription of dosages greater than that recommended or overdosage of chloramphenicol. High concentrations in young neonates may be avoided by prescribing and giving the recommended dose and then careful monitoring; concentrations should be maintained between 15 and 25 mg/l. No babies with concentrations within this range showed clinical signs of toxicity.

Treatment of an infant with severe chloramphenicol intoxication using charcoal-column hemoperfusion.

A 3,200 gm 12-day-old male infant with complex urologic problems underwent charcoal hemoperfusion for severe accidental chloramphenicol intoxication. Immediately prior to CH, with a serum chloramphenicol level of 98 micrograms/ml, the child was in profound shock, ashen-gray, hypothermic, and acidotic. Chloramphenicol levels indicated virtually complete removal of this drug by the CH column. Three hours of CH treatment resulted in a reduction of the chloramphenicol level to 13.5 micrograms/ml and complete reversal of the described clinical syndrome. No serious complications of CH were encountered. We conclude that chloramphenicol poisoning is treatable by CH and that this therapeutic modality may be safely carried out in infants and small children.