Dataset Information

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species.

ABSTRACT: OBJECTIVES:There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. METHODS:This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. RESULTS:A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis. CONCLUSIONS:These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

SUBMITTER: Derrick C

PROVIDER: S-EPMC7277875 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to <i>Enterobacter</i>, <i>Serratia</i>, and <i>Citrobacter</i> Species.

Derrick Caroline C Bookstaver P Brandon PB Lu Zhiqiang K ZK Bland Christopher M CM King S Travis ST Stover Kayla R KR Rumley Kathey K MacVane Shawn H SH Swindler Jenna J Kincaid Scott S Branan Trisha T Cluck David D Britt Benjamin B Pillinger Kelly E KE Jones Bruce M BM Fleming Virginia V DiMondi V Paul VP Estrada Sandy S Crane Brad B Odle Brian B Al-Hasan Majdi N MN Justo Julie Ann JA

Antibiotics (Basel, Switzerland) 20200514 5

<h4>Objectives</h4>There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species.<h4>Methods</h4>This multicenter, retrospective cohort study evaluated adult hospitalized patie ...[more]

PMID: 32423104

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Project description:Background: There have been no reports in Bulgaria about quinolone resistance determinants among Enterobacter spp. Aims: To investigate plasmid and chromosomal quinolone resistance rates among 175 third-generation cephalosporin resistant Enterobacter spp. isolates (167 Enterobacter cloacae complex and eight Enterobacter aerogenes isolates) collected at a university hospital in Varna, Bulgaria, as well as to reveal their association with ESBL/AmpC production and a carriage of specific plasmid replicon types. Methods: PCR, isoelectric focusing, replicon typing, sequencing, and epidemiology typing were carried out. Results: A high level of combined third-generation cephalosporin and quinolone resistant Enterobacter spp. was found - 79.4%. The ESBL production rate was 87%, consisting mainly of CTX-M-15 among E. cloacae complex (in 76%) and CTX-M-3 among E. aerogenes (in 88%). Plasmid mediated quinolone resistance (PMQR) determinants were identified in 57% of the isolates. The most commonly detected PMQR determinants were qnrB (90%), consisting mainly of qnrB1 (in 61%), and qnrB9 (in 27%) of the isolates. Both alleles were transferred with CTX-M-15 genes; transconjugants showed HI2 replicons (for qnrB1 positive transconjugants) and were non-typeable (for qnrB9). One Enterobacter spp. isolate produced qnrB4. QnrA1, qnrS1, and aac(6')-Ib-cr were detected in single isolates only. QnrC, qnrD, qepA, and oqxAB genes were not found. QnrB was associated with CTX-M-15 production, and qnrS1 was linked to CTX-M-3. Alterations in 83 and 87 positions of gyrB in quinolone-resistance determining regions, and 80 position of parC were detected in high level quinolone resistant isolates. Among all the Enterobacter spp. isolates tested, one predominant clone A was identified (53%). Conclusion: Our data showed the necessity of more prudent use of quinolones and third-generation cephalosporins, because of the risk of promoting dissemination, and selection of multiple resistance determinants (ESBL, PMQR) among Enterobacter spp. isolates in Bulgaria.

Project description:Introduction: Antimicrobial resistance is a global public health concern, but the problems are context specific, with each county or setting facing differing challenges. In Africa, third-generation cephalosporin resistant Enterobacterales (3GCR-E) are of particular concern, given the widespread reliance on ceftriaxone for treatment of severe infection in this setting. In Malawi, despite the rising prevalence of 3GCR-E, the health impact of these infections has not been described. This study is designed to estimate attributable mortality, morbidity and economic cost of 3GC-R bloodstream infection (BSI) in a large, urban hospital. Methods: This study will investigate the burden of antimicrobial resistance by recruiting a a prospective longitudinal cohort of patients who have bloodstream infection with 3GCR-E, at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients whose blood culture is positive for either 3GC-S or 3GC-R Enterobacterales will be enrolled and provide clinical and healthcare economic data. Patients will be followed throughout their hospital stay and to 6-months post discharge. Mortality, direct and indirect costs and other health outcomes will be compared between patients with 3GC-R and comparable 3GC-sensitive BSI. Based on our observation that some patients with clinical suspicion of sepsis and 3GC-R BSI are surviving without an effective antibiotic, we review each patient prospectively and classify what role the isolated bacteria is playing in the patient's clinical presentation. These classifications will then be incorporated into our analysis. Ethics and dissemination: The study protocol has been approved by the Malawi College of Medicine Research Ethics Committee and by the Liverpool School of Tropical Medicine Research Ethics committee. Written informed consent will be obtained from study participants or their parents/guardians. Results will be submitted to international peer-reviewed journals, presented at international conferences and shared with participating communities and collaborators.

Project description:Data which accurately enumerate the economic costs of antimicrobial resistance (AMR) in low- and middle- income countries are essential. This study aimed to quantify the impact of third-generation cephalosporin resistant (3GC-R) bloodstream infection (BSI) on economic and health related quality of life outcomes for adult patients in Blantyre, Malawi. Participants were recruited from a prospective, longitudinal cohort study of hospitalised patients with bloodstream infection caused by Enterobacterales at Queen Elizabeth Central Hospital (QECH). Primary costing studies were used to estimate the direct medical costs associated with the inpatient stay. Recruited participants were asked about direct non-medical and indirect costs associated with their admission and their health-related quality of life was measured using the EuroQol EQ-5D questionnaire. Multiple imputation was undertaken to account for missing data. Costs were adjusted to 2019 US Dollars. Cost and microbiology surveillance data from QECH, Blantyre was used to model the annual cost of, and quality-adjusted life years lost to, 3GC-R and 3GC-Susceptible BSI from 1998 to 2030 in Malawi. The mean health provider cost per participant with 3GC-R BSI was US$110.27 (95%CR; 22.60-197.95), higher than for those with 3GC-S infection. Patients with resistant BSI incurred an additional indirect cost of US$155.48 (95%CR; -67.80, 378.78) and an additional direct non-medical cost of US$20.98 (95%CR; -36.47, 78.42). Health related quality of life outcomes were poor for all participants, but participants with resistant infections had an EQ-5D utility score that was 0.167 (95% CR: -0.035, 0.300) lower than those with sensitive infections. Population level burden estimates suggest that in 2016, 3GC-R accounted for 84% of annual societal costs from admission with bloodstream infection and 82% of QALYs lost. 3GC-R bloodstream infection was associated with higher health provider and patient level costs than 3GC-S infection, as well as poorer HRQoL outcomes. We demonstrate a substantial current and future economic burden to society as a result of 3GC-R E. coli and Klebsiella spp. BSI, data urgently needed by policy makers to provide impetus for implementing strategies to reduce AMR.

Dataset Information

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to Enterobacter, Serratia, and Citrobacter Species.

Publications

Multicenter, Observational Cohort Study Evaluating Third-Generation Cephalosporin Therapy for Bloodstream Infections Secondary to <i>Enterobacter</i>, <i>Serratia</i>, and <i>Citrobacter</i> Species.

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