title: Treating complicated carbapenem-resistant enterobacteriaceae infections with ceftazidime/avibactam: a retrospective study with molecular strain characterisation.
abstract: Ceftazidime/avibactam (CAZ/AVI) is the first antimicrobial agent with activity against carbapenem-resistant Enterobacteriaceae (CRE) approved by the US Food and Drug Administration (FDA). Notably, human clinical outcome data for this indication are limited. Therefore, a retrospective study was performed to evaluate the clinical outcomes and bacterial genomic characteristics of patients hospitalised at a tertiary medical centre with CRE infections treated for the first time with CAZ/AVI. From a total of 44 patients with CRE infections, 6 patients were treated with CAZ/AVI. The duration of CAZ/AVI treatment ranged from 7 days to 28 days. Five patients achieved clinical cure, however two relapsed with the same carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strain within 3 weeks of completion of CAZ/AVI treatment. In addition, one patient with CR-Kp pneumonia experienced clinical failure despite having a documented CAZ/AVI-susceptible CR-Kp strain [minimum inhibitory concentration (MIC) = 2 mg/L]. Consequently, the overall rate of unsuccessful outcome in this small cohort of patients was 50%. All strains carried KPC-3, OXA-9 and different TEM and SHV β-lactamases, but none carried the intrinsically avibactam-resistant class B metallo-β-lactamases. No obvious differences in antibiotic resistance genes were observed. This study provides an early glimpse of the clinical outcomes of patients with CR-Kp infections treated with CAZ/AVI. Findings of clinical failure and relapse in patients with no prior exposure to CAZ/AVI and with documented susceptibility to CAZ/AVI highlight the urgent need for well-designed clinical studies evaluating the effectiveness of CAZ/AVI in the treatment of CRE infections.
authors.affiliation: Department of Medicine, Infectious Diseases Division, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 900, Chicago, IL 60611, USA. Electronic address: fiorella.krapp@northwestern.edu.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Krapp
authors.affiliation: Department of Medicine, Infectious Diseases Division, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 900, Chicago, IL 60611, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Grant
authors.affiliation: Department of Medicine, Infectious Diseases Division, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 900, Chicago, IL 60611, USA.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Sutton
authors.affiliation: Department of Medicine, Infectious Diseases Division, Northwestern University Feinberg School of Medicine, 645 N. Michigan Avenue, Suite 900, Chicago, IL 60611, USA.
authors.forename: Egon A
authors.initials: EA
authors.lastname: Ozer
authors.affiliation: Northwestern Memorial Hospital, Department of Pharmacy, Chicago, IL, USA; Rosalind Franklin University of Medicine and Science, College of Pharmacy, Department of Pharmacy Practice, North Chicago, IL, USA.
authors.forename: Viktorija O
authors.initials: VO
authors.lastname: Barr
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D053961:Azabicyclo Compounds / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics; D000073182:Carbapenem-Resistant Enterobacteriaceae / Q000145:classification* / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D002442:Ceftazidime / Q000627:therapeutic use*; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D014481:United States; D065093:beta-Lactamase Inhibitors / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D001426:Bacterial Proteins; D004338:Drug Combinations; C000595613:avibactam, ceftazidime drug combination; D065093:beta-Lactamase Inhibitors; D002442:Ceftazidime
keywords: Carbapenem-resistant Enterobacteriaceae; Ceftazidime/avibactam; Klebsiella pneumoniae; Multidrug resistance; β-Lactamase inhibitor