Combination therapy for extensively-drug resistant gram-negative bacteria

Abstract

The ongoing crisis and emergence of extensively-drug resistant (XDR) gram-negative pathogens in the nosocomial setting is worrisome. The limited armamentarium in combination with the increasing resistance rates of last resort antibiotics has led clinicians to re-exploit existing antibiotic classes. Areas covered: Current state of evidence concerning the administration of monotherapy versus combination therapy for the treatment of XDR gram-negative microorganism as well as salvage treatment are presented. Herein, the current knowledge concerning in vitro studies, animal models and clinical studies are discussed in detail. Expert commentary: The efficacy of combination therapy in carbapenemase-producing K. pneumoniae is associated with reduced mortality in patients with septic shock and rapidly fatal underlying diseases. There is moderate evidence in support of the use of monotherapy for treating carbapenemase-producing Acinetobacter baumannii infections, however for septic shock patients, cancer patients and infections with an isolate with MIC in the upper limit of susceptibility combination therapy could be recommended. There are currently minimal and of low quality clinical evidence suggesting that combination treatment has no therapeutic advantage over monotherapy for XDR Pseudomonas aeruginosa infections. The in vivo validity of novel compounds and necessity for combination therapy is to be evaluated in future studies particularly for XDR infections.

<p>Extensively drug-resistant Gram-negative bacterial bloodstream infection in hematological disease</p>

“…Twenty-seven patients diagnosed with XDR-GNB BSI were retrospective reviewed in this study between January 1, 2013, and December 31, 2017 in Department of Hematology, the First Affiliated Hospital of USTC (University of Science and Technology of China). XDR-GNB was defined as resistant to almost all classes of antibiotics except one or two classes of antibiotics (mainly polymyxin and tigecycline) 3–5. The BacT/ALERT 3D automated blood culture system (BioMérieux, Lyon, France) was used to process all blood samples.…”

“…Definitions of XDR-GNB, BSI, neutropenia, and GVHD were defined according to previously published criteria 3–8. Patient-, disease-, and treatment-related variables were measured using chi-squared test (categorical variables) or Mann–Whitney U test (continuous variables).…”

Synergistic Antibacterial Activity of Combined Antimicrobials and the Clinical Outcome of Patients With Carbapenemase-Producing Acinetobacter baumannii Infection

“…Several new antimicrobial agents, including aztreonam/avibactam, cefiderocol, and eravacycline, might be promising therapeutic options in treating CRAB infections (Leone et al, 2019). Currently, the treatment options for CRAB infections are limited, including colistin, tigecycline, sulbactam, and aminoglycosides (Karaiskos et al, 2017). Therefore, knowing which of the existing antimicrobials to select in controlling CRAB infections is a huge challenge for clinicians.…”

“…Therefore, knowing which of the existing antimicrobials to select in controlling CRAB infections is a huge challenge for clinicians. Observational studies have shown no difference in statistics between monotherapy and combination therapy in mortality and clinical efficacy in patients with CRAB infections (Karaiskos et al, 2017). There are also no convincing studies that recommend the combination of carbapenems, colistin, or sulbactam (Karaiskos et al, 2017).…”

In vivo Activity of Silver Nanoparticles Against Pseudomonas aeruginosa Infection in Galleria mellonella

“…Colistin is a last-resort antibiotic used in P. aeruginosa therapy, but it displays nephro and neurotoxicity. Furthermore, strains of P. aeruginosa resistant to colistin have already been reported (Hill et al, 2014;Karaiskos et al, 2017). Hence, there is an urgent need for the screening and development of new antimicrobial drugs effective against P. aeruginosa.…”