Τόμος 3 (1985) – Τεύχος 1 – Άρθρο 2 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 3 (1985) – Issue 1 – Article 2 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

PHARMAKON-PRESS

^{Τμήμα Επιστημονικής Πληροφόρησης}

2: 263-271 (1985)

PHARMAKON-Press: Epitheorese Klin. Farmakol. Farmakokinet.

2: 263-271 (1985)

Chloramphenicol

Chloramphenicol, isolated from Streptomyces νenezuelae, was the first broad spectrum antibiotic. It is bactericidal a­gainst most Haemophilus influenzae and Stre­ptococcus pneumoniae and bacteriostatic a­gainst most other aerobic and anaerobic ba­cteria, as well as Chlamydia, Mycoplasma and Rickettsia. Its antimicrobial activity is related to binding to the 50s subunit of the 70s bacte­rial ribosome. Chloramphenicol is more bioa­vailable by the oral than by parenteral admini­stration. Orally administered chloramphenicol palmitate is hydrolysed mainly in the small intestine (more than 90% of the dose) by pan­creatic lipase to active chloramphenicol base, which is then absorbed. After i.v. administra­tion of inactive chloramphenicol succinate, the hydrolysis takes place in the liver, kidneys and lungs with a variable rate. The drug is rapidly distributed in various body compartments, in­cluding brain and cerebrospinal fluid (CSF); the CSF/blood ratio is 35 to 65%. Chlorampheni­col is eliminated mainly by glucuronidation in the liver (85 to 90%) and excretion in the urine as glucuronide, free drug or as succinate. To ensure efficacy and avoid toxicity maximum serum concentrations of 10 to 20 μg/ml and minimum concentrations of 5 to 10 μg/ml are desirable; a dose of 75 mg/kg/day is now generally recommended, with specific adjust­ments for newborns. Adverse effects associat­ed with the use of chloramphenicol are: com­mon: reversible bone marrow suppression (do­se and time dependent), grey baby syndrome (dose-dependent in neonates; rarely, therea­fter), optic neuritis (3 to 5% of children with cystic fibrosis); uncommon: rash, fever, anaphy­laxis, hair loss, delayed wound healing, haemo­lysis in patients with G6PD deficiency; pseudo-membranous colitis, hepatitis, villous atrophy of intestinal mucosa, encephalopathy, peripheral neuropathy; rare: non-reversible aplastic anae­mia – idiosyncratic reaction (incidence approx. 1:40,000), acidosis. Until 1984 different bacte­ria resistant to chloramphenicol have been reported worldwide: Salmonella spp. (typhoidal and non-typhoidal strains), H. influenzae type b strains, Staph. aureus, Staph. epidermidis, S. pneumoniae. Chloramphenicol resistance is u­sually due to bacterial acquisition of an R­ plasmid encoded for acetyl-transferase; this en­zyme acetylates hydroxy groups in chloramphe­nicol side-chain, thus inactivating the drug. In the 1980s chloramphenicol is considered as a first-line drug for invasive bacterial infections in infancy and early childhood where Η. influenzae is likely pathogen, for rickettsial infe­ctions in children under 8 years of age, for the initial therapy of brain abscess, and in selected intraocular infections.

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