Carbapenem-resistant Gram-negative pathogens in a German university medical center: Prevalence, clinical implications and the role of novel β-lactam/β-lactamase inhibitor combinations

• Published in: PloS one 2018-04, Vol.13 (4), p.e0195757-e0195757
• Main Authors: Katchanov, Juri, Asar, Lucia, Klupp, Eva-Maria, Both, Anna, Rothe, Camilla, König, Christina, Rohde, Holger, Kluge, Stefan, Maurer, Florian P
• Format: Article
• Language: English
• Subjects: Amides; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Bacteria; beta-Lactam Resistance; beta-Lactamase Inhibitors - pharmacology; beta-Lactamase Inhibitors - therapeutic use; Biology and Life Sciences; Carbapenemase; Carbapenems; Carbapenems - pharmacology; Ceftazidime; Cephalosporins; Chemotherapy; Colistin; Cross Infection; Drug resistance; Enterobacteriaceae; Female; Germany - epidemiology; Gram-negative bacteria; Gram-Negative Bacteria - classification; Gram-Negative Bacteria - drug effects; Gram-Negative Bacteria - genetics; Gram-Negative Bacterial Infections - drug therapy; Gram-Negative Bacterial Infections - epidemiology; Gram-Negative Bacterial Infections - microbiology; Gram-Negative Bacterial Infections - transmission; Health care; Health care facilities; Hospitals; Hospitals, University; Humans; Hygiene; Infections; Inhibitors; Intensive care; Male; Medicine; Medicine and Health Sciences; Microbial Sensitivity Tests; Microbiology; Multidrug resistance; Multidrug resistant organisms; Nosocomial infection; Patients; Prevalence; Pseudomonas aeruginosa; Retrospective Studies; Species; Tazobactam; Treatment Outcome; Virology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0195757

To determine the spectrum of infections with multidrug-resistant Gram-negative bacteria (MDR-GNB) and the clinical impact of the newly available betalactam/betalactamase inhibitor combinations ceftolozane/tazobactam and ceftazidime/avibactam in a German academic tertiary care center. Retrospective analysis. Between September 1, 2015 and August 31, 2016, 119 individual patients (0.22% of all hospital admissions) were colonized or infected with carbapenem-resistant MDR-GNB. The species distribution was Pseudomonas aeruginosa, n = 66; Enterobacteriaceae spp., n = 44; and Acinetobacter baumannii, n = 18. In 9 patients, carbapenem-resistant isolates belonging to more than one species were detected. Infection was diagnosed in 50 patients (total: 42.0%; nosocomial pneumonia: n = 23, 19.3%; bloodstream infection: n = 11, 9.2%). Antimicrobial treatment with broad-spectrum antibiotics prior to detection of a carbapenem-resistant isolate was documented in 105 patients (88.2%, prior administration of carbapenems: 62.2%). Nosocomial transmission was documented in 29 patients (24.4%). In 26 patients (21.8%), at least one carbapenem-susceptible, third-generation cephalosporin non-susceptible isolate was documented prior to detection of a carbapenem-resistant isolate belonging to the same species (median 38 days, IQR 23-78). 12 patients (10.1%) had documented previous contact to the healthcare system in a country with high burden of carbapenemase-producing strains. Genes encoding carbapenemases were detected in 60/102 patient isolates (58.8%; VIM-2, n = 25; OXA-48, n = 21; OXA-23-like, n = 10). Susceptibility to colistin was 94.3%. Ceftolozane/tazobactam and ceftazidime/avibactam were administered to 3 and 5 patients, respectively (in-hospital mortality: 66% and 100%). Development of drug-resistance under therapy was observed for both antimicrobials. i) The major predisposing factors for acquisition of carbapenem-resistant MDR-GNB were selective pressure due to preceding antimicrobial therapy and nosocomial transmission. ii) Colistin remains the backbone of antimicrobial chemotherapy for infections caused by carbapenem-resistant MDR-GNB. iii) Novel β-lactam/β-lactamase inhibitor combinations are of limited usefulness in our setting because of the high prevalence of Ambler class B carbapenemases and the emergence of nonsusceptibility under therapy.