Dataset Information

Carbapenem-resistant gram-negative bacteria in Germany: incidence and distribution among specific infections and mortality: an epidemiological analysis using real-world data.

ABSTRACT:

Purpose

Infections with carbapenem-resistant gram-negative bacteria (in Germany classified as 4MRGN) are a growing threat in clinical care. This study was undertaken to understand the overall burden of 4MRGN infections in Germany in the context of a Health Technology Appraisal (HTA) for Ceftazidime/Avibactam (CAZ/AVI). Besides, the incidences mortality was an endpoint of interest.

Methods

To assess infections with carbapenem-resistant gram-negative bacteria and related mortality, three different data sources have been used. From the German statistics office (DESTATIS) data have been retrieved to obtain the overall frequency these pathogens. Via two other databases, the German analysis database (DADB) and a Benchmarking of > 200 hospitals in a representative sample (BM-DB), the distribution of the infections and the mortality have been analyzed.

Results

DESTATIS data showed a total of 11,863 carbapenem-resistant gram-negative bacteria codings, of which 10,348 represent infections and 1515 carriers. The most frequent infections were complicated urinary tract infections (cUTI) (n = 2,337), followed by pneumonia (n = 1006) and intra-abdominal infections (n = 730). A considerable amount of patients had multiple infections in one hospital episode (n = 1258). In-hospital mortality was 18.6% in DADB and 14.3% in the BM-DB population, respectively. In cases with additional bloodstream infections, DADB mortality was correspondingly higher at 33.0%. DADB data showed an incremental mortality increase of 5.7% after 30 days and 10.0% after 90 days resulting in a cumulative 90 day mortality of 34.3%.

Conclusions

Infections with carbapenem-resistant gram-negative bacteria are still rare (6.8-12.4 per 100,000) but show a significant increase in mortality compared to infections with more sensitive pathogens. Using different data sources allowed obtaining a realistic picture.

SUBMITTER: Wilke MH

PROVIDER: S-EPMC9705437 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Publications

Carbapenem-resistant gram-negative bacteria in Germany: incidence and distribution among specific infections and mortality: an epidemiological analysis using real-world data.

Wilke Michael H MH Preisendörfer Birgit B Seiffert Anna A Kleppisch Maria M Schweizer Caroline C Rauchensteiner Stephan S

Infection 20220531 6

<h4>Purpose</h4>Infections with carbapenem-resistant gram-negative bacteria (in Germany classified as 4MRGN) are a growing threat in clinical care. This study was undertaken to understand the overall burden of 4MRGN infections in Germany in the context of a Health Technology Appraisal (HTA) for Ceftazidime/Avibactam (CAZ/AVI). Besides, the incidences mortality was an endpoint of interest.<h4>Methods</h4>To assess infections with carbapenem-resistant gram-negative bacteria and related mortality, ...[more]

PMID: 35639286

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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: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:Our objective was to describe the prescribing practices, clinical characteristics, and outcomes of patients treated with ceftolozane-tazobactam (C/T) for multidrug-resistant (MDR) Gram-negative infections. This was a multicenter, retrospective, cohort study at eight U.S. medical centers (2015 to 2019). Inclusion criteria were age ≥18 years and receipt of C/T (≥72 hours) for suspected or confirmed MDR Gram-negative infection. The primary efficacy outcome, evaluated among patients with MDR Pseudomonas aeruginosa infections, was composite clinical failure, namely, 30-day all-cause mortality, 30-day recurrence, and/or failure to resolve or improve infection signs or symptoms after C/T treatment. In total, 259 patients were included, and P. aeruginosa was isolated in 236 (91.1%). The MDR and extremely drug-resistant phenotypes were detected in 95.8% and 37.7% of P. aeruginosa isolates, respectively. The most common infection source was the respiratory tract (62.9%). High-dose C/T was used in 71.2% of patients with a respiratory tract infection (RTI) overall but in only 39.6% of patients with an RTI who required C/T renal dose adjustment. In the primary efficacy population (n = 226), clinical failure and 30-day mortality occurred in 85 (37.6%) and 39 (17.3%) patients, respectively. New C/T MDR P. aeruginosa resistance was detected in 3 of 31 patients (9.7%) with follow-up cultures. Hospital-acquired infection and Acute Physiological and Chronic Health Evaluation II (APACHE II) score were independently associated with clinical failure (adjusted odds ratio [aOR], 2.472 and 95% confidence interval [CI], 1.322 to 4.625; and aOR, 1.068 and 95% CI, 1.031 to 1.106, respectively). Twenty-five (9.7%) patients experienced ≥1 adverse effect (9 acute kidney injury, 13 Clostridioides difficile infection, 1 hepatotoxicity, 2 encephalopathy, and 2 gastrointestinal intolerance). C/T addresses an unmet medical need in patients with MDR Gram-negative infections.

Dataset Information

Carbapenem-resistant gram-negative bacteria in Germany: incidence and distribution among specific infections and mortality: an epidemiological analysis using real-world data.

Purpose

Methods

Results

Conclusions

Publications

Carbapenem-resistant gram-negative bacteria in Germany: incidence and distribution among specific infections and mortality: an epidemiological analysis using real-world data.

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