Johannesburg, South Africa
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PubMed | University Hospital of Tuebingen, Hospital Universitario La Paz, Universitatsklinikum Cologne, Hospitales Universitarios Virgen Macarena y Virgen del Rocio and 26 more.
Type: Journal Article | Journal: The Journal of antimicrobial chemotherapy | Year: 2016

Data about the efficacy of ertapenem for the treatment of bloodstream infections (BSI) due to ESBL-producing Enterobacteriaceae (ESBL-E) are limited. We compared the clinical efficacy of ertapenem and other carbapenems in monomicrobial BSI due to ESBL-E.A multinational retrospective cohort study (INCREMENT project) was performed (ClinicalTrials.gov identifier: NCT01764490). Patients given monotherapy with ertapenem or other carbapenems were compared. Empirical and targeted therapies were analysed. Propensity scores were used to control for confounding; sensitivity analyses were performed in subgroups. The outcome variables were cure/improvement rate at day 14 and all-cause 30 day mortality.The empirical therapy cohort (ETC) and the targeted therapy cohort (TTC) included 195 and 509 patients, respectively. Cure/improvement rates were 90.6% with ertapenem and 75.5% with other carbapenems (P=0.06) in the ETC and 89.8% and 82.6% (P=0.02) in the TTC, respectively; 30 day mortality rates were 3.1% and 23.3% (P=0.01) in the ETC and 9.3% and 17.1% (P=0.01) in the TTC, respectively. Adjusted ORs (95% CI) for cure/improvement with empirical and targeted ertapenem were 1.87 (0.24-20.08; P=0.58) and 1.04 (0.44-2.50; P=0.92), respectively. For the propensity-matched cohorts it was 1.18 (0.43-3.29; P=0.74). Regarding 30 day mortality, the adjusted HR (95% CI) for targeted ertapenem was 0.93 (0.43-2.03; P=0.86) and for the propensity-matched cohorts it was 1.05 (0.46-2.44; P=0.90). Sensitivity analyses were consistent except for patients with severe sepsis/septic shock, which showed a non-significant trend favouring other carbapenems.Ertapenem appears as effective as other carbapenems for empirical and targeted therapy of BSI due to ESBL-E, but further studies are needed for patients with severe sepsis/septic shock.


PubMed | University Hospital of Tuebingen, Hospital Universitario La Paz, Universitatsklinikum Cologne, Hospitales Universitarios Virgen Macarena y Virgen del Rocio and 27 more.
Type: Journal Article | Journal: Antimicrobial agents and chemotherapy | Year: 2016

The spread of extended-spectrum--lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is leading to increased carbapenem consumption. Alternatives to carbapenems need to be investigated. We investigated whether -lactam/-lactamase inhibitor (BLBLI) combinations are as effective as carbapenems in the treatment of bloodstream infections (BSI) due to ESBL-E. A multinational, retrospective cohort study was performed. Patients with monomicrobial BSI due to ESBL-E were studied; specific criteria were applied for inclusion of patients in the empirical-therapy (ET) cohort (ETC; 365 patients), targeted-therapy (TT) cohort (TTC; 601 patients), and global cohort (GC; 627 patients). The main outcome variables were cure/improvement rate at day 14 and all-cause 30-day mortality. Multivariate analysis, propensity scores (PS), and sensitivity analyses were used to control for confounding. The cure/improvement rates with BLBLIs and carbapenems were 80.0% and 78.9% in the ETC and 90.2% and 85.5% in the TTC, respectively. The 30-day mortality rates were 17.6% and 20% in the ETC and 9.8% and 13.9% in the TTC, respectively. The adjusted odds ratio (OR) (95% confidence interval [CI]) values for cure/improvement rate with ET with BLBLIs were 1.37 (0.69 to 2.76); for TT, they were 1.61 (0.58 to 4.86). Regarding 30-day mortality, the adjusted OR (95% CI) values were 0.55 (0.25 to 1.18) for ET and 0.59 (0.19 to 1.71) for TT. The results were consistent in all subgroups studied, in a stratified analysis according to quartiles of PS, in PS-matched cases, and in the GC. BLBLIs, if active in vitro, appear to be as effective as carbapenems for ET and TT of BSI due to ESLB-E regardless of the source and specific species. These data may help to avoid the overuse of carbapenems. (This study has been registered at ClinicalTrials.gov under registration no. NCT01764490.).


PubMed | Hospital Universitario La Paz, Universitatsklinikum Cologne, Hospitales Universitarios Virgen Macarena y Virgen del Rocio, National Taiwan University Hospital and 24 more.
Type: | Journal: The Journal of antimicrobial chemotherapy | Year: 2017

Bloodstream infections (BSIs) due to ESBL-producing Enterobacteriaceae (ESBL-E) are frequent yet outcome prediction rules for clinical use have not been developed. The objective was to define and validate a predictive risk score for 30day mortality.A multinational retrospective cohort study including consecutive episodes of BSI due to ESBL-E was performed; cases were randomly assigned to a derivation cohort (DC) or a validation cohort (VC). The main outcome variable was all-cause 30day mortality. A predictive score was developed using logistic regression coefficients for the DC, then tested in the VC.The DC and VC included 622 and 328 episodes, respectively. The final multivariate logistic regression model for mortality in the DC included age >50 years (OR=2.63; 95% CI: 1.18-5.85; 3 points), infection due to Klebsiella spp. (OR=2.08; 95% CI: 1.21-3.58; 2 points), source other than urinary tract (OR=3.6; 95% CI: 2.02-6.44; 3 points), fatal underlying disease (OR=3.91; 95% CI: 2.24-6.80; 4 points), Pitt score >3 (OR=3.04; 95CI: 1.69-5.47; 3 points), severe sepsis or septic shock at presentation (OR=4.8; 95% CI: 2.72-8.46; 4 points) and inappropriate early targeted therapy (OR=2.47; 95% CI: 1.58-4.63; 2 points). The score showed an area under the receiver operating curve (AUROC) of 0.85 in the DC and 0.82 in the VC. Mortality rates for patients with scores of<11 and 11 were 5.6% and 45.9%, respectively, in the DC, and 5.4% and 34.8% in the VC.We developed and validated an easy-to-collect predictive scoring model for all-cause 30day mortality useful for identifying patients at high and low risk of mortality.


Lowman W.,Wits Donald Gordon Medical Center | Lowman W.,University of Witwatersrand
South African Medical Journal | Year: 2016

Background. Hospital-acquired infections (HAIs) are a significant although unquantified burden in South Africa. Lack of adequate surveillance compounds this problem. Objective. To report on the establishment and outcomes of a unit-specific surveillance system for hospital-acquired infections, based on international standards, in a private academic hospital. Methods. Active unit-specific surveillance of device-associated infections (DAIs) was introduced over a 2-year period. The surveillance system was based on the US National Healthcare Safety Network (NHSN) utilising standardised definitions. Analysis of DAI rates and device utilisation was done according to Centers for Disease Control and Prevention methods. Comparative analysis using study-derived annualised data and existing NHSN data was done. Results. Surveillance results of DAI rates showed significant reductions in intensive care unit-related ventilator-associated pneumonia (42%) and central line-associated bloodstream infections (100%) over a 3-year period. Substantial variations in DAI rates and utilization ratios between wards highlight the importance of unit-specific surveillance. Conclusions. Active surveillance requires a significant investment in resources and is a sustained operational challenge, although equally significant benefits are derived from a better understanding of HAIs with more targeted interventions and efficient use of resources. A robust surveillance system is an essential component of any healthcare infection prevention and control programme and is a prerequisite to contextualising the HAI burden of hospitals. © 2016, South African Medical Association. All rights reserved.

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