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Objectives: The aim of this prospective phase II, randomized, investigator-blinded study (NCT00690378) was to compare the efficacy and safety of ceftazidime-avibactam and imipenem-cilastatin in hospitalized adults with serious complicated urinary tract infection (cUTI) due to Gram-negative pathogens., Patients and Methods: Patients aged between 18 and 90 years with cUTI were enrolled and stratified by infection type (acute pyelonephritis or other cUTI) and randomized 1:1 to receive intravenous ceftazidime 500 mg plus avibactam 125 mg every 8 hours or imipenem-cilastatin 500 mg every 6 hours. Patients meeting pre-specified improvement criteria after 4 days could be switched to oral ciprofloxacin. Patients were treated for a total of 7-14 days. The primary efficacy objective was a favorable microbiological response at the test-of-cure (TOC) visit 5-9 days post-therapy in microbiologically evaluable (ME) patients., Results: Overall, 135 patients received study therapy (safety population); 62 were included in the ME population (ceftazidime-avibactam, n = 27; imipenem-cilastatin, n = 35). The predominant uropathogen was Escherichia coli. Favorable microbiological response was achieved in 70.4% of ME patients receiving ceftazidime-avibactam and 71.4% receiving imipenem-cilastatin at the TOC visit (observed difference -1.1% [95% CI: -27.2%, 25.0%]). Among ME patients with ceftazidime-resistant uropathogens, response was observed in 6/7 (85.7%) receiving ceftazidime-avibactam. Adverse events were observed in 67.6% and 76.1% of patients receiving ceftazidime-avibactam and imipenem-cilastatin, respectively. Limitations of the study include the small number of patients in the ME population., Conclusion: The results suggest that the efficacy and safety of ceftazidime-avibactam may be similar to that of imipenem-cilastatin.

Antibiotic-induced severe neutropenia and less frequently agranulocytosis has been reported. In most of these cases a relatively normal myelopoiesis is found. We report on the first case of agranulocytosis with histological evidence of pure white cell aplasia associated with imipenem-cilastatin treatment.

Proconvulsive tendency of imipenem/cilastatin is one of its well-known side effects. Most studies report incidence rates ranging from 1.5 to 3%. There is no study on the incidence rate among children with systemic malignancies. Eighty-two patients with various malignancies who received imipenem/cilastatin 143 times for neutropenic fever between March 1994 and October 1999 in Department of Pediatric Oncology, Gazi University, were identified. Three of these patients had convulsions attributed to imipenem/cilastatin; 3.6% of the patients had seizure, or 2% of imipenem/cilastatin administrations was followed by a seizure attack.

118 patients with complicated intra-abdominal infections participated in an open randomized comparative multicenter trial in order to compare the clinical and microbiological efficacy and safety of biapenem with imipenem/cilastatin (Tienam). 31 men and 27 women (mean age 52.3 years) were enrolled in the biapenem group, and 43 men and 17 women (mean age 52.3 years) in the imipenem/cilastatin group. The patients received either biapenem 500 mg every 8 h or imipenem/cilastatin 500 mg/500 mg every 6 h by intravenous infusion for up to 13 days (mean 6.5 days). 28/43 evaluable patients (65.1%) receiving biapenem and 27/40 evaluable patients (67.5%) in the imipenem/cilastatin group were clinically cured. The microbiological response was satisfactory in 28/43 evaluable patients (65.1%) receiving biapenem and in 27/40 evaluable patients (67.5%) receiving imipenem/cilastatin. No significant differences in clinical or microbiological efficacy between the two treatment groups were found. The present study shows that biapenem may be useful in the treatment of intra-abdominal infections.

515 patients with intra-abdominal infection participated in an open randomized comparative multicenter trial in order to compare the efficacy, safety, and tolerance of imipenem/cilastatin with cefuroxime/metronidazole. 258 patients (mean age 56 years) received imipenem/cilastatin 1.5-2.0 g/day, and 257 patients (mean age 54 years) received cefuroxime 3.0-4.5 g/day plus metronidazole 1.0-1.5 g/day for at least 3 days. 130/161 evaluable patients (80.8%) receiving imipenem/cilastatin and 124/145 evaluable patients (85.5%) receiving cefuroxime/metronidazole were clinically cured. The microbiological response was favorable in 86.9% in the imipenem/cilastatin group and in 90.8% in the cefuroxime/metronidazole group. The two treatment groups were similar with respect to median time to defervescence which was 4 days. The median duration of treatment was 6 days and the median time to discharge from hospital was 9 days in both groups. Drug-related adverse reactions were observed in 14 patients receiving iminpenem/cilastatin and in 8 patients receiving cefuroxime/metronidazole. 19 patients in the imipenen/cilastatin group and 12 patients in the cefuroxime/metronidazole group died. No correlation was found between the deaths and the study drugs. The present study shows that intra-abdominal infections can be treated successfully with imipenem/cilastatin as well as with cefuroxime/metronidazole.