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

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 blaKPC, blaVIM, blaNDM, and blaOXA 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 blaKPC (249; 82.5%), followed by blaVIM (26; 8.6%), both blaKPC and blaVIM (16; 5.3%), and blaNDM (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.

Clinical Efficacy, Antibiotic Resistance Genes, Virulence Factors and Outcome of Hospital-Acquired Pneumonia Induced by Klebsiella pneumoniae Carbapenemase 2-Producing with Tigecycline Treatment in the ICU

“…The 30-day mortality rate of the latter was higher than that of the former. 27 It was inconsistent with our findings. This may be due to the study being mainly monotherapy with tigecycline.…”

Clinical and Molecular Characteristics of Patients with Bloodstream Infections Caused by KPC and NDM Co-Producing Carbapenem-Resistant Klebsiella pneumoniae

“…Based on previous studies, the effectiveness of using tigecycline was comparable to other antimicrobial drugs in treating BSIs caused by CRKP with a MIC of 0.5 mg/L or below. 40 Nevertheless, only four isolates (1.7%) showed MICs of tigecycline ≤ 0.5 mg/L in our study. Moreover, tigecycline is not suggested for the treatment of CRE BSIs.…”

Mortality of Pandrug-Resistant Klebsiella pneumoniae Bloodstream Infections in Critically Ill Patients: A Retrospective Cohort of 115 Episodes

“…During the ten-year study period (2010–2019), PDR-Kp represented 27.9% of all K. pneumoniae bacteraemias ( Supplementary Figure ). This high percentage of PDR isolates could be attributed to the antibiotic selective pressure in an area with endemic carbapenemase-producing K. pneumoniae infections [ 5 ], lack of newer antimicrobials, and the revision by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) of tigecycline’s breakpoints rendering most isolates that previously were considered susceptible or intermediate as being resistant to tigecycline [ 11 ]. The mortality in our cohort was high (39.1%), especially in patients with septic shock (54.9%), and it was higher than previously reported [ 6 , 7 , 8 , 9 , 10 ].…”