New treatment options for multiresistant gram negatives
- PMID: 32068644
- DOI: 10.1097/QCO.0000000000000627
New treatment options for multiresistant gram negatives
Abstract
Purpose of review: Multidrug-resistant (MDR) Gram-negative bacteria infections are listed among the top public health threats of the current era. As a result, there has been an increase in efforts to develop new therapeutic agents against MDR Gram-negatives. The purpose of this review is to summarize the clinical and preclinical findings associated with recently approved drugs and the drugs in clinical development against ESBL and carbapenemase-producing Enterobacterales, carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii infections.
Recent findings: There are a number of ESBL active agents in late stage clinical development that can help spare carbapenems. Likewise, recently approved β-lactam/β-lactamase inhibitor combinations allow a change in the treatment of KPC and OXA-48 producers and carbapenem-resistant P. aeruginosa from colistin to new, safer agents. Treatment of Meta-beta-lactamase (MBL) producers remains an unmet need - apart from cefiderocol, most agents with MBL activity are still in clinical development. Among the few agents with carbapenem-resistant A. baumannii activity, durlobactam/sulbactam in phase III clinical trials provides hope.
Summary: Armamentarium against MDR Gram-negatives has expanded with the dominance of agents active against ESBL and KPC producers. There is a need to prioritize MBL producers and carbapenem-resistant A. baumannii, as well as the need for clinical trials to test the new agents against serious infections.
References
-
- Hampton T. Report reveals scope of US antibiotic resistance threat. JAMA 2013; 310:1661–1663.
-
- Gupta V, Ye G, Olesky M, et al. National prevalence estimates for resistant Enterobacteriaceae and Acinetobacter species in hospitalized patients in the United States. Int J Infect Dis 2019; 85:203–211.
-
- Harris PNA, Tambyah PA, Lye DC, et al. MERINO Trial Investigators and the Australasian Society for Infectious Disease Clinical Research Network (ASID-CRN). Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone Resistance: A Randomized Clinical Trial. JAMA 2018; 320:984–994.
-
- Hayden MK, Won SY. Carbapenem-sparing therapy for extended-spectrum beta-lactamase-producing E coli and Klebsiella pneumoniae bloodstream infection: the search continues. JAMA 2018; 320:979–981.
-
- Shortridge D, Pfaller MA, Castanheira M, Flamm RK. Antimicrobial activity of ceftolozane-tazobactam tested against enterobacteriaceae and Pseudomonas aeruginosa with various resistance patterns isolated in U.S. Hospitals (2013–2016) as Part of the surveillance program: program to assess ceftolozane-tazobactam susceptibility. Microb Drug Resist 2018; 24:563–577.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous
