Three-hundred and twelve episodes of fever in 234 neutropenic patients with haematological malignancies were treated empirically with either imipenem or a combination of piperacillin and gentamicin. There were no significant differences in the percentages of patients responding to therapy at either 72 h (59% and 56% of assessable episodes in the imipenem and combination groups respectively) or at the end of treatment (55% and 53% of assessable episodes in the imipenem and combination groups respectively). Patients in the piperacillin plus gentamicin group experienced significantly more renal tubular damage whereas those who received imipenem suffered more nausea or vomiting. We conclude that imipenem monotherapy represents an acceptable alternative to piperacillin plus gentamicin as empirical therapy of the febrile neutropenic patient.

One hundred and twenty-two patients with uncomplicated urinary tract infections were treated with either 400 mg bd norfloxacin or 160/800 mg bd cotrimoxazole for 7 days. Follow-up examinations showed norfloxacin to be equally effective as cotrimoxazole in the eradication of bacteriuria and symptoms. Norfloxacin caused fewer and less severe side effects.

Six patients, aged between 68 and 83 years, with glomerular filtration rates (GFR) between 31 and 80 ml/min received imipenem/cilastatin as treatment for acute lower respiratory tract infection. A combination of 500 mg of both agents was administered, 6-hourly, intravenously over 30 min. After a minimum of four doses, blood specimens were obtained for assay of imipenem and cilastatin concentrations by HPLC. Pharmacokinetic parameters were calculated from the results. The mean half life was 1.6 h for imipenem and 2.1 h for cilastatin, values similar to those reported for patients with moderate renal impairment. Elimination constant, clearance and AUC significantly correlated with GFR but not with age. No accumulation was observed.

There are many clinical studies comparing antibiotic treatments, but the majority are too small to have sufficient power to be reasonably certain of detecting statistically a moderate treatment effect. For example, few of the 19 studies published on imipenem-cilastatin for empirically treating febrile neutropenic patients were able to show any significant treatment effect in either direction when compared with alternative regimens. We therefore undertook a meta-analysis of these studies and made 21 pairwise comparisons of a control regimen with imipenem-cilastatin. Eleven comparisons were made between imipenem-cilastatin and a beta-lactam-aminoglycoside combination, and a further 10 between the carbapenem and a beta-lactam regimen either alone or combined with a glycopeptide or other beta-lactam antibiotic. These two data sets were analysed separately. Imipenem-cilastatin demonstrated a beneficial treatment effect over that achieved by aminoglycoside containing control regimens, yielding a typical odds ratio (OR) of 0.77 (95% CI 0.61 to 0.98). A beneficial treatment effect for the carbapenem regimen was also shown against regimens that did not include an aminoglycoside, with the typical OR being 0.67 (95% CI 0.54 to 0.84). Although there was clinical heterogeneity between studies, the treatment effect itself was relatively homogenous. These results show meta-analysis to be a useful aid for interpreting the data from clinical studies that are intrinsically too small to provide conclusive results.

The results of clinical trials in which norfloxacin was used for 7 days compared with amoxycillin or cotrimoxazole, or for 3 days compared with citrated nalidixic acid, are presented. Additionally, the results of a concurrent open study of 3 days of norfloxacin in the management of simple urinary tract infections are discussed. Resistance to norfloxacin was only encountered in 0.2% of pathogens isolated. Norfloxacin was as effective in eradicating bacteriuria as amoxycillin, cotrimoxazole or citrated nalidixic acid. The response to 3 days of norfloxacin was similar to that seen after 7 days therapy with this compound, or to 7 days of cotrimoxazole. The incidence of adverse experiences to norfloxacin in 758 patients was below 10%.