Beware of broad-spectrum generalizations: ceftazidime-avibactam compared to meropenem for the treatment of gram-negative pneumonia

Efficacy and safety of cefiderocol or best available therapy for the treatment of serious infections caused by carbapenem-resistant Gram-negative bacteria (CREDIBLE-CR): a randomised, open-label, multicentre, pathogen-focused, descriptive, phase 3 trial

“…Patients who are at highest risk of being infected by resistant pathogens are often excluded from these trials. 22 By permitting the use of best available therapy as a comparator in an open-label study design in different geographical locations, this study could directly assess the efficacy and safety of cefiderocol in patients with evidence of carbapenem-resistant Gram-negative infections caused by any Gram-negative pathogen, including Acinetobacter spp. 18 Thus, patients were enrolled irrespective of infection type, comorbidities, pathogen species, or carbapenem resistance mechanism, resulting in a heterogeneous patient population.…”

New cephalosporins for the treatment of pneumonia in internal medicine wards

“…All-cause fatality rates seemed to be 8% and 7% in the C/A and meropenem groups, respectively (25). This registration study has also placed some dubiousness about safety in the C/A group compared to meropenem, with reported higher rates of serious adverse reactions (19% vs. 13%) and adverse events leading to study drug discontinuation (4% vs. 2.7%) (132)(133)(134).…”

“…IV over 2 h) plus meropenem placebo or meropenem 1 g (q8h IV over 30 minutes) plus C/A placebo for 7 to 14 days (25). Additionally, from randomization, openlabel aminoglycosides, and linezolid or vancomycin were permitted while awaiting culture results for 24 to 72 h (25,(132)(133)(134). The primary endpoint in this study was clinical cure at the TOC visit with additional secondary endpoints, including all-cause 28-day mortality (25).…”

“…Data from the REPROVE study (25,132) have defined C/A as a valid alternative to carbapenems in carbapenemresistant Enterobacteriaceae (CRE) nosocomial respiratory infections. Despite that, should be considered that patients in the clinical practice who are receiving C/ A, might be frail, with several comorbidities (133,134). De novo resistance and development of resistance during C/A therapy, are reported in literature (123)(124)(125)(126).…”

Current trends in the treatment of pneumonia due to multidrug-resistant Gram-negative bacteria

“…Ceftazidime/avibactam was shown to be non-inferior to meropenem in a recent large randomized controlled trial of non-CRE pneumonia 33 . Meropenem itself has been used as a comparator agent in many pneumonia studies, and vaborbactam achieves high epithelial lining fluid concentrations 34 . In contrast, in the absence of confirmatory data, plazomicin should not be considered a first-line choice for monotherapy of CRE pneumonia.…”