Pandrug-resistant Gram-negative bacteria: a systematic review of current epidemiology, prognosis and treatment options

Abstract

Background The literature on the epidemiology, mortality and treatment of pandrug-resistant (PDR) Gram-negative bacteria (GNB) is scarce, scattered and controversial. Objectives To consolidate the relevant literature and identify treatment options for PDR GNB infections. Methods A systematic search in MEDLINE, Scopus and clinical trial registries was conducted. Studies reporting PDR clinical isolates were eligible for review if susceptibility testing for all major antimicrobials had been performed. Characteristics and findings of retrieved studies were qualitatively synthesized. Results Of 81 studies reviewed, 47 (58%) were published in the last 5 years. The reports reflected a worldwide dissemination of PDR GNB in 25 countries in 5 continents. Of 526 PDR isolates reported, Pseudomonas aeruginosa (n=175), Acinetobacter baumannii (n=172) and Klebsiella pneumoniae (n=125) were most common. PDR GNB were typically isolated in ICUs, but several studies demonstrated wider outbreak potential, including dissemination to long-term care facilities and international spread. All-cause mortality was high (range 20%–71%), but appeared to be substantially reduced in studies reporting treatment regimens active in vitro. No controlled trial has been performed to date, but several case reports and series noted successful use of various regimens, predominantly synergistic combinations, and in selected patients increased exposure regimens and newer antibiotics. Conclusions PDR GNB are increasingly being reported worldwide and are associated with high mortality. Several treatment regimens have been successfully used, of which synergistic combinations appear to be most promising and often the only available option. More pharmacokinetic/pharmacodynamic and outcome studies are needed to guide the use of synergistic combinations.

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

“…The increasing incidence of infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB), such as Pseudomonas aeruginosa, Acinetobacter baumannii, or members of the order Enterobacterales, has dramatically hindered the selection of an appropriate antimicrobial therapy, leading to an increase in morbidity and mortality in patients with such infections [1][2][3][4].…”

A novel colistin adjuvant identified by virtual screening for ArnT inhibitors

“…Its high intrinsic antibiotic resistance, mostly due to low outer membrane permeability and active drug efflux, makes infections by this pathogen challenging to treat. 6 , 7 The evolution of resistance in this pathogen is particularly problematic in CF patients, whose ability to resolve bacterial infection is impaired by defective host defences. 8–10 Chronic lung infections in these patients require continuous therapeutic treatments that generally select for antibiotic-resistant clones.…”

Treatment options for K. pneumoniae, P. aeruginosa and A. baumannii co-resistant to carbapenems, aminoglycosides, polymyxins and tigecycline: an approach based on the mechanisms of resistance to carbapenems

“…For the management of carbapenem-resistant Gram-negative bacteria (GNB), clinicians often resort to combination therapy based on polymyxins (including colistin or polymyxin B), aminoglycosides and tigecycline [ 1 , 2 ]. However, in a recent systematic review of the literature, we found that GNB with simultaneous resistance to carbapenems, aminoglycosides, polymyxins and tigecycline (CAPT-resistant), are increasingly being reported worldwide [ 3 ]. The CAPT-resistance phenotype is predominantly encountered in Acinetobacter baumannii , Klebsiella pneumoniae and Pseudomonas aeruginosa.…”

“…The CAPT-resistance phenotype is predominantly encountered in Acinetobacter baumannii , Klebsiella pneumoniae and Pseudomonas aeruginosa. It typically affects severely ill patients and patients in intensive care units, but the potential for hospital-wide dissemination or between health-care facilities has been well documented [ 3 ].…”