Treatment of Infections Due to MDR Gram-Negative Bacteria

Abstract

The treatment of multidrug-resistant Gram-negative bacteria (MDR-GNB) infections in critically ill patients presents many challenges. Since an effective treatment should be administered as soon as possible, resistance to many antimicrobial classes almost invariably reduces the probability of adequate empirical coverage, with possible unfavorable consequences. In this light, readily available patient's medical history and updated information about the local microbiological epidemiology remain critical for defining the baseline risk of MDR-GNB infections and firmly guiding empirical treatment choices, with the aim of avoiding both undertreatment and overtreatment. Rapid diagnostics and efficient laboratory workflows are also of paramount importance both for anticipating diagnosis and for rapidly narrowing the antimicrobial spectrum, with de-escalation purposes and in line with antimicrobial stewardship principles. Carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa , and Acinetobacter baumannii are being reported with increasing frequencies worldwide, although with important variability across regions, hospitals and even single wards. In the past few years, new treatment options, such as ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, plazomicin, and eravacycline have become available, and others will become soon, which have provided some much-awaited resources for effectively counteracting severe infections due to these organisms. However, their optimal use should be guaranteed in the long term, for delaying as much as possible the emergence and diffusion of resistance to novel agents. Despite important progresses, pharmacokinetic/pharmacodynamic optimization of dosages and treatment duration in critically ill patients has still some areas of uncertainty requiring further study, that should take into account also resistance selection as a major endpoint. Treatment of severe MDR-GNB infections in critically ill patients in the near future will require an expert and complex clinical reasoning, of course taking into account the peculiar characteristics of the target population, but also the need for adequate empirical coverage and the more and more specific enzyme-level activity of novel antimicrobials with respect to the different resistance mechanisms of MDR-GNB.

In vitro activity of colistin against multidrug-resistant Acinetobacter baumannii isolates harboring blaOXA-23-like and blaOXA-24-like genes: A multicenter based study

“…In our results, all CRAB isolates were susceptible to colistin with a MIC value ≤2 mg/mL. Polymyxins are usually drug of choice to treat infections caused by MDR Gram-negative bacteria [12]. Previously two comparable reports were available from southern region [10,29], but our study was the first report from our region in the north of Iran.…”

“…Colistin (also known as polymyxin E) is a multicomponent polypeptide antibiotic and relatively old polymyxin that achieved its antimicrobial effect by acting directly on bacterial cell membrane. [11] Currently, colistin is a reliable option for treatment of infections caused by MDR Gram-negative bacteria [10,12].…”

Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales

“…In the absence of porin deficient mutations or efflux pumps, gram-negative resistance to pivotal antibiotics in our area is mainly mediated by the production of β-lactamases, such as class A (such as ESBL, KPC), class C (AmpC), and some class D enzymes (e.g., OXA 48) [22]. None of these affects ceftazidime-avibactam [23] and this context represents, in our opinion, the situation in which the drug could be used as an alternative to carbapenem for the treatment of MDR gram-negative pathogens [24].…”

Multi-Drug Resistant Acinetobacter: Detection of blaNDM-1 genotype and biofilm formation at a tertiary care hospital in Eastern Nepal

“…Acinetobacter appears to have a propensity to develop antibiotic resistance extremely rapidly, as a consequence of prolong antibiotic exposure. Hence, the increasing trends of Acinetobacter MDR strains were reported globally [27].…”