Impact of Tigecycline's MIC in the Outcome of Critically Ill Patients with Carbapenemase-Producing Klebsiella pneumoniae Bacteraemia Treated with Tigecycline Monotherapy-Validation of 2019's EUCAST Proposed Breakpoint Changes

Matthaios Papadimitriou-Olivgeris; Christina Bartzavali; Alexandra Nikolopoulou; Fevronia Kolonitsiou; Virginia Mplani; Iris Spiliopoulou; Myrto Christofidou; Fotini Fligou; Markos Marangos

doi:10.3390/antibiotics9110828

Impact of Tigecycline's MIC in the Outcome of Critically Ill Patients with Carbapenemase-Producing Klebsiella pneumoniae Bacteraemia Treated with Tigecycline Monotherapy-Validation of 2019's EUCAST Proposed Breakpoint Changes

Antibiotics (Basel). 2020 Nov 19;9(11):828. doi: 10.3390/antibiotics9110828.

Authors

Matthaios Papadimitriou-Olivgeris¹, Christina Bartzavali², Alexandra Nikolopoulou³, Fevronia Kolonitsiou², Virginia Mplani³, Iris Spiliopoulou², Myrto Christofidou², Fotini Fligou³, Markos Marangos¹

Affiliations

¹ Division of Infectious Diseases, School of Medicine, University of Patras, 265 04 Patras, Greece.
² Department of Microbiology, School of Medicine, University of Patras, 265 04 Patras, Greece.
³ Anesthesiology and Critical Care Medicine, School of Medicine, University of Patras, 265 04 Patras, Greece.

Abstract

Background: Tigecycline is a therapeutic option for carbapenemase-producing Klebsiella pneumoniae (CP-Kp). Our aim was to evaluate the impact of the tigecycline's minimum inhibitory concentration (MIC) in the outcome of patients with CP-Kp bacteraemia treated with tigecycline monotherapy.

Methods: Patients with monomicrobial bacteraemia due to CP-Kp that received appropriate targeted monotherapy or no appropriate treatment were included. Primary outcome was 30-day mortality. MICs of meropenem, tigecycline, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. PCR for bla_KPC, bla_VIM, bla_NDM, and bla_OXA genes was applied.

Results: Among 302 CP-Kp bacteraemias, 32 isolates (10.6%) showed MICs of tigecycline ≤ 0.5 mg/L, whereas 177 (58.6%) showed MICs that were 0.75-2 mg/L. Colistin and aminoglycoside susceptibility was observed in 43.0% and 23.8% of isolates, respectively. The majority of isolates carried bla_KPC (249; 82.5%), followed by bla_VIM (26; 8.6%), both bla_KPC and bla_VIM (16; 5.3%), and bla_NDM (11; 3.6%). Fifteen patients with tigecycline MIC ≤ 0.5 mg/L and 55 with MIC 0.75-2 mg/L were treated with tigecycline monotherapy; 30-day mortality was 20.0% and 50.9%, respectively (p = 0.042). Mortality of 150 patients that received other antimicrobials was 24.7%; among 82 patients that received no appropriate treatment, mortality was 39.0%. No difference in 30-day mortality was observed between patients that received tigecycline (MIC ≤ 0.5 mg/L) or other antimicrobials.

Conclusion: Tigecycline monotherapy was as efficacious as other antimicrobials in the treatment of bloodstream infections due to CP-Kp isolates with a tigecycline's MIC ≤ 0.5 mg/L.

Keywords: bloodstream infection; carbapenem-resistance; carbapenemase; ceftazidime/avibactam; colistin; mortality; tigecycline.