cilastatin--imipenem-drug-combination and Meningitis--Bacterial

The tolerability of the 2 most frequently used carbapenems, imipenem/cilastatin and meropenem, is reviewed. Both of these drugs, but especially imipenem, are potentially neurotoxic and may cause seizures if overdosed relative to renal function and/or bodyweight. The therapeutic margin is considerably narrower with imipenem/cilastatin which cannot be given at doses required for treatment of bacterial meningitis. Meropenem on the other hand, is considerably less prone to cause seizures and its tolerability and efficacy are well documented in 3 relatively large, controlled studies in adults and children with meningitis. They showed that meropenem was as effective and well tolerated as cefotaxime or ceftriaxone. Another potential advantage of meropenem over imipenem/cilastatin is that it can be given intravenously at a high rate without increased risk of nausea or vomiting. An obvious reason for using a carbapenem instead of a cephalosporin for empirical treatment of life-threatening infections is that both imipenem/cilastatin and meropenem have a broader spectrum of activity. They are also more resistant to hydrolysis by the most common beta-lactamases, including the class I cephalosporinase frequently produced by Enterobacter spp. and Pseudomonas spp. and the extended spectrum enzymes, now commonly found in Escherichia coli and Klebsiella spp.

Topics: Adult; Cephalosporins; Child; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Tolerance; Humans; Imipenem; Meningitis, Bacterial; Meropenem; Risk Assessment; Seizures; Thienamycins

A 40-year-old male with no history of underlying disease was admitted to Hokusho Central Hospital on May 25, 1991, complaining of high fever and headache. Physical examination on admission revealed a temperature of 38.5 degrees C, a pulse rate of 84 beat/min (relative bradycardia) and no abnormal findings for the chest or abdomen. Slight neck stiffness without Kernig's sign was observed at neurological examination. Laboratory data were: ESR 11 mm/lh, WBC 12000/mm3, C-reactive protein positive. Lumbar puncture showed an initial pressure of 230 mmH2O; CSF revealed a cell count of 2633/3 mm3 with mononuclear pleocytosis, total protein of 76 mg/dl and sugar of 54 mg/dl (CSF:blood glucose ratio 0.47). We initially suspected tuberculous or cryptococcal meningitis, but Campylobacter fetus subsp. fetus (C. fetus) was isolated from the CSF and venous blood on the 27th hospital day. IPM/CS 1 g/day, MINO 200 mg/day and FOM 4 g/day were intravenously administered. This antibiotic therapy was very effective: the patient was soon afebrile, and gradually all signs and symptoms were resolved. C. fetus was sensitive to IMP/CS, MINO, KM, GM, EM, OFLX, CP. The patient was discharged with no complication. He has eaten raw beef frequently before admission, but stool culture for C. fetus was negative.

Topics: Adult; Campylobacter fetus; Campylobacter Infections; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Fosfomycin; Humans; Imipenem; Male; Meningitis, Bacterial; Minocycline