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Risk Factors for Mortality among Patients with Pseudomonas aeruginosa Bloodstream Infections: What Is the Influence of XDR Phenotype on Outcomes?

ABSTRACT: This study aimed to assess the impact of extensively drug-resistant (XDR) phenotype on mortality in Pseudomonas aeruginosa bacteremia. A retrospective cohort study was performed in a tertiary hospital from January 2000 to December 2018. All consecutive prospectively recorded P. aeruginosa bacteremia in adult patients were assessed. In this study, 382 patients were included, of which 122 (31.9%) due to XDR P. aeruginosa. Independent factors associated with 14-day mortality were as follows: high-risk source of bacteremia (hazard ratio (HR) 3.07, 95% confidence interval (CI), 1.73-5.46), septic shock (HR 1.75, 95% CI, 1.12-2.75), and higher Pitt scores (one-point increments; HR 1.25, 95% CI, 1.12-1.38). Otherwise, the appropriateness of definitive antibiotic therapy was a protective factor (HR 0.39, 95% CI, 0.24-0.62). The same variables were also associated with 30-day mortality. XDR phenotype was not associated with 14- or 30-day mortality. In a subanalysis considering only high-risk source cases, combined antimicrobial therapy was independently associated with 14-day favorable outcome (HR 0.56, 95% CI, 0.33-0.93). In conclusion, XDR phenotype was not associated with poor prognosis in patients with P. aeruginosa bacteremia in our cohort. However, source of infection, clinical severity, and inappropriate definitive antibiotic therapy were risk factors for mortality. Combined antimicrobial therapy should be considered for high-risk sources.

SUBMITTER: Montero MM

PROVIDER: S-EPMC7074151 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Risk Factors for Mortality among Patients with Pseudomonas aeruginosa Bloodstream Infections: What Is the Influence of XDR Phenotype on Outcomes?

Montero María Milagro MM López Montesinos Inmaculada I Knobel Hernando H Molas Ema E Sorlí Luisa L Siverio-Parés Ana A Prim Nuria N Segura Concepción C Duran-Jordà Xavier X Grau Santiago S Horcajada Juan Pablo JP

Journal of clinical medicine 20200214 2

This study aimed to assess the impact of extensively drug-resistant (XDR) phenotype on mortality in Pseudomonas aeruginosa bacteremia. A retrospective cohort study was performed in a tertiary hospital from January 2000 to December 2018. All consecutive prospectively recorded P. aeruginosa bacteremia in adult patients were assessed. In this study, 382 patients were included, of which 122 (31.9%) due to XDR P. aeruginosa. Independent factors associated with 14-day mortality we ...[more]

PMID: 32074947

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Project description:Gram-negative bloodstream infections (GNBSI) are confirmed by the presence of gram-negative bacteria in the bloodstream and pose a significant healthcare issue as they increase the risk of sepsis and mortality. In England, the aim is to reduce GNBSI cases and further deterioration through enhanced population surveillance of patients with a laboratory-confirmed GNBSI to inform on healthcare policies. The objective of this study was to evaluate the factors associated with in-hospital mortality in patients with a laboratory-confirmed Escherichia coli, Klebsiella or Pseudomonas aeruginosa GNBSIs, with data obtained from the enhanced data capture for the surveillance of GNBSIs. All patients with a laboratory-confirmed GNBSI at a single centre, admitted between April 2017 and March 2019, were included in this retrospective observational study. Demographic and recent exposure to healthcare risk factors were collected and assessed for the association with in-hospital mortality. In 1113 patients with laboratory-confirmed GNBSIs, the in-hospital mortality rate was 13%. Multivariable analysis confirmed that patients with respiratory (OR = 3.73, 95%CI = 2.05-6.76), gastrointestinal (2.61; 1.22-5.58) or skin (3.61; 1.24-10.54) infection primary focus had a greater risk of in-hospital mortality, compared to upper urinary tract infections. Increased risk of in-hospital mortality was also observed in patients with hospital-onset GNBSIs (OR = 1.87; 1.17-2.97) compared with community-onset healthcare acquired GNBSIs, or who were on dialysis at the time of the GNBSI (3.28; 1.01-10.14), as well as in patients who had recently been discharged from hospital (1.55; 1.01-2.38), or had a vascular device recently manipulated (2.41; 1.01-5.74). Results confirm that the data obtained from the enhanced data capture for GNBSIs in England can predict in-hospital mortality in patients with a GNBSI. Several factors associated with an increased risk of in-hospital mortality have been identified. Results should be reported back to clinicians in order to identify patients at a greater risk of dying in-hospital who may benefit from further monitoring.

Project description:ObjectiveBacteremia caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) has high mortality, threatening the healthcare quality worldwide. Analysis is required to update the epidemiological data of CRPA bloodstream infections (BSI) and evaluate the prevalent strains in China. Moreover, it is necessary to clarify the risk factors associated with the development and mortality of CRPA bacteremia.MethodsThis is a 9-year multicenter retrospective study, enrolling 137 patients with CRPA BSI and 137 carbapenem-susceptible P. aeruginosa (CSPA) BSI during January 2012 and December 2020. Antimicrobials susceptibility between the two groups were compared. Risk factors of CRPA BSI were identified by binary logistic regression for development and cox regression for mortality. The Kaplan-Meier method was used to compare time to mortality. CRPA and difficult-to-treat resistant P. aeruginosa (DTRPA) detection rate was analyzed year-by-year in ZYH.ResultsA total of 7,384 P. aeruginosa clinical samples were cultured in ZYH during 9 years, and notable increase of CRPA and DTRPA detection rate in P. aeruginosa BSI was identified (from 17 to 60%; from 2.1 to 25%). Multivariate analysis revealed that prior ICU hospitalization, immunosuppressive therapy and exposure to carbapenems were independent risk factors for development of CRPA BSI. The 30-day crude mortality of 137 CRPA BSI was 39%. A total of 46 DTRPA were identified, and the 30-day mortality for patients infected by DTRPA was 50%. The 30-day crude mortality of CRPA BSI was independently associated with multiple organ failure and higher Pitt bacteremia score, whereas receipt appropriate therapy improved prognosis.ConclusionA significant increase in the detection rate of CRPA and DTRPA in P. aeruginosa BSI was identified. Strict policies for carbapenems usage, cautious decisions regarding the usage of immunosuppressive agent and standard care for patients with prior ICU hospitalization are necessary for CRPA BSI management.

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Project description:BackgroundInfections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) are related to higher mortality. The objective of this study was to explore clinical outcomes of CRPA bacteremia, identify risk factors and also, compare the efficacy of traditional and novel antibiotic regimens.MethodsThis retrospective study was conducted at a blood diseases hospital in China. The study included hematological patients who were diagnosed with CRPA bacteremia between January 2014 and August 2022. The primary endpoint was all-cause mortality at day 30. Secondary endpoints included 7-day and 30-day clinical cure. Multivariable Cox regression analysis was employed to identify mortality-related risk factors.Results100 patients infected with CRPA bacteremia were included and 29 patients accepted allogenic-hematopoietic stem cell transplantation. 24 received ceftazidime-avibactam (CAZ-AVI)-based therapy and 76 received other traditional antibiotics. 30-day mortality was 21.0%. Multivariable cox regression analysis showed neutropenia >7 days after bloodstream infections (BSI) (P=0.030, HR: 4.068, 95%CI: 1.146~14.434), higher Pitt bacteremia score (P<0.001, HR:1.824, 95%CI: 1.322~2.517), higher Charlson comorbidity index (P=0.01, HR: 1.613, 95%CI: 1.124~2.315) and bacteremia due to multidrug-resistant Pseudomonas aeruginosa (MDR-PA) (P=0.024, HR:3.086, 95%CI: 1.163~8.197) were identified as independent risk factors of 30-day mortality. After controlling for confounders, an additional multivariable cox regression analysis revealed definitive regimens containing CAZ-AVI were associated with lower mortality in CRPA bacteremia (P=0.016, HR: 0.150, 95%CI: 0.032~0.702), as well as in MDR-PA bacteremia (P=0.019, HR: 0.119, 95%CI: 0.020~0.709).ConclusionsFor patients with hematological diseases and CRPA bacteremia, 30-day mortality rate was 21.0% (21/100). Neutropenia >7 days after BSI, higher Pitt bacteremia score, higher Charlson comorbidity index and bacteremia due to MDR-PA increased 30-day mortality. CAZ-AVI-based regimens were effective alternatives for bacteremia due to CRPA or MDR-PA.

Project description:Pseudomonas aeruginosa frequently becomes resistant to aminoglycosides by the acquisition of aminoglycoside modifying enzyme (AME) genes and the occurrence of mutations in the mexZ, fusA1, parRS, and armZ genes. We examined resistance to aminoglycosides in a collection of 227 P. aeruginosa bloodstream isolates collected over 2 decades from a single United States academic medical institution. Resistance rates of tobramycin and amikacin were relatively stable over this time, while the resistance rates of gentamicin were somewhat more variable. For comparison, we examined resistance rates to piperacillin-tazobactam, cefepime, meropenem, ciprofloxacin, and colistin. Resistance rates to the first four antibiotics were also stable, although uniformly higher for ciprofloxacin. Colistin resistance rates were initially quite low, rose substantially, and then began to decrease at the end of the study. Clinically relevant AME genes were identified in 14% of isolates, and mutations predicted to cause resistance were relatively common in the mexZ and armZ genes. In a regression analysis, resistance to gentamicin was associated with the presence of at least one gentamicin-active AME gene and significant mutations in mexZ, parS, and fusA1. Resistance to tobramycin was associated with the presence of at least one tobramycin-active AME gene. An extensively drug-resistant strain, PS1871, was examined further and found to contain five AME genes, most of which were within clusters of antibiotic resistance genes embedded in transposable elements. These findings demonstrate the relative contributions of aminoglycoside resistance determinants to P. aeruginosa susceptibilities at a United States medical center. IMPORTANCE Pseudomonas aeruginosa is frequently resistant to multiple antibiotics, including aminoglycosides. The rates of resistance to aminoglycosides in bloodstream isolates collected over 2 decades at a United States hospital remained constant, suggesting that antibiotic stewardship programs may be effective in countering an increase in resistance. Mutations in the mexZ, fusA1, parR, pasS, and armZ genes were more common than acquisition of genes encoding aminoglycoside modifying enzymes. The whole-genome sequence of an extensively drug resistant isolate indicates that resistance mechanisms can accumulate in a single strain. Together, these results suggest that aminoglycoside resistance in P. aeruginosa remains problematic and confirm known resistance mechanisms that can be targeted for the development of novel therapeutics.

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Risk Factors for Mortality among Patients with Pseudomonas aeruginosa Bloodstream Infections: What Is the Influence of XDR Phenotype on Outcomes?

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Risk Factors for Mortality among Patients with <i>Pseudomonas aeruginosa</i> Bloodstream Infections: What Is the Influence of XDR Phenotype on Outcomes?

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