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Attributable burden in patients with carbapenem-nonsusceptible gram-negative respiratory infections.

ABSTRACT: OBJECTIVE:We aimed to describe the clinical and economic burden attributable to carbapenem-nonsusceptible (C-NS) respiratory infections. METHODS:This retrospective matched cohort study assessed clinical and economic outcomes of adult patients (aged ?18 years) who were admitted to one of 78 acute care hospitals in the United States with nonduplicate C-NS and carbapenem-susceptible (C-S) isolates from a respiratory source. A subset analysis of patients with principal diagnosis codes denoting bacterial pneumonia or other diagnoses was also conducted. Isolates were classified as community- or hospital-onset based on collection time. A generalized linear mixed model method was used to estimate the attributable burden for mortality, 30-day readmission, length of stay (LOS), cost, and net gain/loss (payment minus cost) using propensity score-matched C-NS versus C-S cohorts. RESULTS:For C-NS cases, mortality (25.7%), LOS (29.4 days), and costs ($81,574) were highest in the other principal diagnosis, hospital-onset subgroup; readmissions (19.4%) and net loss (-$9522) were greatest in the bacterial pneumonia, hospital-onset subgroup. Mortality and readmissions were not significantly higher for C-NS cases in any propensity score-matched subgroup. Significant C-NS-attributable burden was found for both other principal diagnosis subgroups for LOS (hospital-onset: 3.7 days, P = 0.006; community-onset: 1.5 days, P<0.001) and cost (hospital-onset: $12,777, P<0.01; community-onset: $2681, P<0.001). CONCLUSIONS:Increased LOS and cost burden were observed in propensity score-matched patients with C-NS compared with C-S respiratory infections; the C-NS-attributable burden was significant only for patients with other principal diagnoses.

SUBMITTER: Tabak YP

PROVIDER: S-EPMC7034906 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Attributable burden in patients with carbapenem-nonsusceptible gram-negative respiratory infections.

Tabak Ying P YP Sung Anita A Ye Gang G Vankeepuram Latha L Gupta Vikas V McCann Eilish E

PloS one 20200221 2

<h4>Objective</h4>We aimed to describe the clinical and economic burden attributable to carbapenem-nonsusceptible (C-NS) respiratory infections.<h4>Methods</h4>This retrospective matched cohort study assessed clinical and economic outcomes of adult patients (aged ≥18 years) who were admitted to one of 78 acute care hospitals in the United States with nonduplicate C-NS and carbapenem-susceptible (C-S) isolates from a respiratory source. A subset analysis of patients with principal diagnosis codes ...[more]

PMID: 32084236

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Project description:BACKGROUND:Rates of colonization and infection with carbapenem-resistant Gram-negative pathogens are on the rise, particularly in southeastern European countries, and this is increasingly true in Germany as well. The organisms in question include enterobacteriaceae such as Klebsiella pneumoniae and Escherichia coli and non-fermenting bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. As the carbapenems have been the gold standard to date for the systemic treatment of serious infections with Gram-negative bacteria, carbapenem resistance presents new and difficult challenges in therapeutic decision-making, particularly because of the high frequency of coresistance. METHODS:This review is based on pertinent publications retrieved by a selective search in PubMed and on other applicable literature. RESULTS:Multiresistant Gram-negative (MRGN) pathogens are classified in Germany according to their resistance to four different classes of antibiotics; fluoroquinolones, piperacillin, third-generation cephalosporins, and carbapenems. Quadruple MRGN pathogens are resistant to all four groups, triple MRGN pathogens to three of them. There are a number of therapeutic alternatives to carbapenems that can be applied with the aid of sensitive microbiological and/or molecular genetic testing. The following antibiotics are often the only ones that can be used to treat quadruple MRGN pathogens: colistin, aminoglycosides, tigecycline, fosfomycin, ceftazidime/avibactam, and ceftolozan/tazobactam. Carbapenems, too, may still be an option in certain situations. There is also evidence that combinations of antibiotics against which the pathogen is resistant individually can some- times be a valid treatment option; these include combinations of colistin with one or two carbapenems. CONCLUSION:The treatment of severe infection with carbapenem-resistant pathogens should be individualized and carried out in an interdisciplinary framework, in consideration of antibiotic pharmacokinetics and pharmacodynamics in each case. The treat- ment options are based on evidence from in vitro studies, retrospective studies, and case series, which must be interpreted with caution. Randomized clinical trials are needed to test each of the various combined approaches.

Project description:IntroductionInfections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) are a significant cause of mortality and represent a serious challenge to health systems. The early identification of mortality predictors could guide appropriate treatment and follow-up. We aimed to identify the factors associated with 90-day all-cause mortality in patients with CR-GNB infections.MethodsWe conducted a cohort study from 1 January 2019 to 30 April 2022. The primary outcome was death from any cause during the first 90 days after the date of the first CR-GNB-positive culture. Secondary outcomes included infection relapse, invasive mechanical ventilation during follow-up, need for additional source control, acute kidney injury, Clostridioides difficile infection, and all-cause hospital admission after initial discharge. Bivariate and multivariate Cox-proportional hazards models were constructed to identify the factors independently associated with 90-day all-cause mortality.ResultsA total of 225 patients with CR-GNB infections were included. Death occurred in 76 (34%) cases. The most-reported comorbidities were immunosuppression (43%), arterial hypertension (35%), and COVID-19 (25%). The median length of stay in survivors was 18 days (IQR 10-34). Mechanical ventilation and ICU admission after diagnosis occurred in 8% and 11% of cases, respectively. Both infection relapse and rehospitalisation occurred in 18% of cases. C. difficile infection was diagnosed in 4% of cases. Acute kidney injury was documented in 22% of patients. Mechanical ventilation after diagnosis, ICU admission after diagnosis, and acute kidney injury in the first ten days of appropriate treatment were more frequently reported among non-survivors. In the multivariate analysis, age (HR 1.19 (95%CI 1.00-1.83)), immunosuppression (HR 1.84 (95%CI 1.06-3.18)), and septic shock at diagnosis (HR 2.40 (95% 1.41-4.08)) had an independent association with death during the first 90 days after the CR-GNB infection diagnosis. Receiving antibiogram-guided appropriate treatment was independently associated with a lower risk of death (HR 0.25 (95%CI 0.14-0.46)).ConclusionsThe presence of advanced age, immunosuppression, septic shock at diagnosis, and inappropriate treatment are associated with higher 90-day all-cause mortality in hospitalised patients with infections due to CR-GNB. Recognition of the risk factors for adverse outcomes could further assist in patient care and the design of interventional studies that address the severe and widespread problem that is carbapenem resistance.

Project description:Abstract Background Escherichia coli and Klebsiella pneumoniae with a piperacillin-tazobactam–nonsusceptible/ceftriaxone-susceptible (TZP-NS/CRO-S) phenotype have been increasingly identified, with limited available literature evaluating treatment strategies. Methods This was a retrospective study of noncritically ill adults hospitalized between 2013 and 2021 and treated at least 48 hours for TZP-NS/CRO-S E coli or K pneumoniae infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy. Results Of 1062 patients screened, 200 were included (CG, n = 51; CSG, n = 149). Baseline characteristics, including Charlson Comorbidity Index (CCI; median [interquartile range], 6 [3–9] vs 6 [4–9]; P = .704), were similar between groups, except for more immunocompromised CG patients (29% vs 11%, P = .001). The most common infection sources were urinary (31% vs 57%, P = .002) and bloodstream (18% vs 17%, P = .887). Eighty-eight percent of the CG received meropenem, while 58% of the CSG received ceftriaxone as targeted therapy. There was no statistical difference in the primary endpoint between overall groups (27% vs 17%, P = .123), nor when stratified by infection source. More patients in the CSG switched to oral therapy (15 [29%] vs 100 [67%], P < .001). In multivariate analysis, CCI was an independent predictor of the primary outcome (odds ratio [OR], 1.199 [95% confidence interval, 1.074–1.340]; P = .001), while treatment with carbapenem-sparing therapy was not. Conclusions Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort. Piperacillin-tazobactam–nonsusceptible/ceftriaxone-susceptible Enterobacterales have been increasingly identified in the New York metropolitan area. In noncritically ill patients with uncomplicated infections of this phenotype, carbapenem-sparing agents, including third-generation cephalosporins, may be considered.

Dataset Information

Attributable burden in patients with carbapenem-nonsusceptible gram-negative respiratory infections.

Publications

Attributable burden in patients with carbapenem-nonsusceptible gram-negative respiratory infections.

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