Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance

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.

Section: Introductionmentioning

confidence: 99%

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

Papadimitriou-Olivgeris

Bartzavali

Nikolopoulou

et al. 2020

“…In addition to original research studies, the Special Issue includes two comprehensive reviews of the management of Gram-negative bacterial infections. Bassetti and colleagues summarize various beta-lactam resistance mechanisms and discuss antimicrobial treatment options for BSI due to Gram-negative bacteria with DTR [ 29 ]. The authors objectively review novel antimicrobial agents, examine the activity of these agent for various antimicrobial resistance mechanisms, and provide insight into the role of these agents in clinical practice [ 29 ].…”

mentioning

confidence: 99%

“…Bassetti and colleagues summarize various beta-lactam resistance mechanisms and discuss antimicrobial treatment options for BSI due to Gram-negative bacteria with DTR [ 29 ]. The authors objectively review novel antimicrobial agents, examine the activity of these agent for various antimicrobial resistance mechanisms, and provide insight into the role of these agents in clinical practice [ 29 ]. Since the respiratory tract is one of the most common sources of Gram-negative bacteria with DTR, Martin-Loeches summarizes current concepts in the management of community-acquired and ventilator-associated pneumonia in intensive care units [ 30 ].…”

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confidence: 99%

Gram-Negative Bloodstream Infection: Implications of Antimicrobial Resistance on Clinical Outcomes and Therapy

Al-Hasan

2020

“…Newer antimicrobials might offer an important adjunction in our already limited armamentarium, since they have shown high rates of in vitro susceptibility in isolates resistant to many currently used antimicrobials. The majority of newer antimicrobials are beta-lactam/beta-lactamase inhibitor combinations with variable activity against different types of carbapenemase genes, a novel cephalosporin (cefiderocol), a novel aminoglycoside (plazomicin), and a novel tetracycline (eravacycline) [ 20 ]. Two studies from Greece showed that 100% and 94.3% of K. pneumoniae isolates were susceptible to cefiderocol and plazomicin, respectively [ 21 , 22 ].…”

Section: Discussionmentioning

confidence: 99%

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

Papadimitriou-Olivgeris

Bartzavali

Georgakopoulou

et al. 2021

Background: The increased frequency of bacteraemias caused by pandrug-resistant Klebsiella pneumoniae (PDR-Kp) has significant implications. The aim of the present study was to identify predictors associated with mortality of PDR-Kp bacteraemias. Methods: Patients with monomicrobial bacteraemia due to PDR-Kp were included. K. pneumoniae was considered PDR if it showed resistance to all available groups of antibiotics. Primary outcome was 30-day mortality. Minimum inhibitory concentrations (MICs) of meropenem, tigecycline, fosfomycin, and ceftazidime/avibactam were determined by Etest, whereas for colistin, the broth microdilution method was applied. blaKPC, blaVIM, blaNDM, and blaOXA genes were detected by PCR. Results: Among 115 PDR-Kp bacteraemias, the majority of infections were primary bacteraemias (53; 46.1%), followed by catheter-related (35; 30.4%). All isolates were resistant to tested antimicrobials. blaKPC was the most prevalent carbapenemase gene (98 isolates; 85.2%). Thirty-day mortality was 39.1%; among 51 patients with septic shock, 30-day mortality was 54.9%. Multivariate analysis identified the development of septic shock, Charlson comorbidity index, and bacteraemia other than primary or catheter-related as independent predictors of mortality, while a combination of at least three antimicrobials was identified as an independent predictor of survival. Conclusions: Mortality of PDR-Kp bloodstream infections was high. Administration of at least three antimicrobials might be beneficial for infections in critically ill patients caused by such pathogens.