Efficacy and safety of novel carbapenem-ß-lactamase inhibitor combinations: Results from phase II and III trials.

Objectives: The addition of novel ß-lactamase inhibitors to carbapenems restores the activity against multidrug-resistant Gram-negative bacteria. The aim of this study was to summarize the evidence on the efficacy and safety of novel carbapenem-ß-lactamase inhibitor combinations. Methods: We conducted a meta-analysis of clinical trials comparing novel carbapenem-ß-lactamase inhibitor combinations with comparators to assess the clinical and microbiological responses, mortality, and adverse events (AEs). Results: A total of 1,984 patients were included. The pooled risk ratios (RRs) of clinical cure, microbiological eradication, all-cause mortality, and 28-day mortality were 1.11 (95% CI: 0.98-1.26), 0.98 (95% CI: 0.82-1.16), 0.90 (95% CI: 0.49-0.94), and 0.68 (95% CI: 0.49-0.94) between the novel carbapenem-ß-lactamase inhibitor combinations and control groups. Sensitivity analysis revealed that the phase II trial of imipenem-cilastatin/relebactam (ICR) against complicated urinary tract infections could be the most important factor of heterogeneity for the microbiological response. The therapeutic effect of novel carbapenem-ß-lactamase inhibitor combinations was better in meropenem-vaborbactam (MEV), phase III trials, and number of patients less than 200. The RRs of AEs from any cause and serious adverse events (SAEs) for patients receiving novel carbapenem-ß-lactamase inhibitor combinations were 0.98 (95% CI: 0.93-1.04) and 1.01 (95% CI: 0.75-1.36), respectively. Conclusions: ICR and MEV were superior to comparators for clinical cure and survival rate in the treatment of complicated infections, and both were as tolerable as the comparators.

Comparative review of imipenem/cilastatin versus meropenem.

INTRODUCTION: Carbapenems are broad-spectrum antibacterial molecules. Imipenem-cilastatin and meropenem are the two main molecules used in French healthcare services. OBJECTIVE: We aimed to evaluate the relative strengths and weaknesses of these two molecules by considering their pharmacokinetic, pharmacodynamic, microbiological, and clinical properties. We demonstrated that imipenem-cilastatin and meropenem are not alike. METHOD: Review of the literature by querying the MEDLINE network. RESULTS: Imipenem-cilastatin is the first marketed molecule of the carbapenem class. It is more effective against Gram-positive cocci. Its stability does not allow for long infusions and its main adverse effect on the central nervous system limits its use. Meropenem is more effective against Gram-negative bacilli. Its stability and its milder adverse effects distinguish it from imipenem-cilastatin. CONCLUSION: Meropenem is preferred for daily use in healthcare services when carbapenems are to be used.

Reversible black tongue: A little known side effect of imipenem/cilastatin and evidence for novel mode of action.

WHAT IS KNOWN AND OBJECTIVE: Black tongue syndrome (BT) is a rare and self-limiting disorder which can result from physiological and metabolic condition and ingestion of toxic substances. Medications are the most common cause of BT. CASE SUMMARY: A 39-year-old male patient presented with BT after the initiation of imipenem/cilastatin. Within one week of cessation of these drugs, the patient's tongue returned to a normal colour. WHAT IS NEW AND CONCLUSION: This is the first case of BT induced by imipenem/cilastatin. Withdrawal of the combination is likely to reverse the condition.

Unusual Drug Fever Caused by Imipenem/Cilastatin and a Review of Literature.

INTRODUCTION: Drug fever is a febrile reaction caused by initiation of one drug or varieties of drugs and often disappears after cessation of the drug(s). Clinically, drug fever is frequently induced by antibiotics, anticonvulsants, and antineoplastics. There are few previous reports about drug fever caused by imipenem/cilastatin. CASE PRESENTATION: Here, we described a 66-year-old man undergoing the Ivor Lewis esophagectomy for esophageal carcinoma, who developed drug fever. The patient had a high temperature with shivering after administration of imipenem/cilastatin for 7 days. Furthermore, his temperature came down after discontinuing imipenem/cilastatin and receiving steroids. Body temperature increased rapidly 4 hours after intravenous readministration of imipenem/cilastatin and rapidly decreased to normal after discontinuing imipenem/cilastatin and administering steroids. CONCLUSION: Thorough history, blood tests, physical examination, and computed tomography (CT) did not reveal any evidence of fever. Drug fever caused by imipenem/cilastatin was considered. We also present a review of relevant literature and provide a point of reference for the clinical diagnosis and therapy of patients with drug fever.