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Unusually High Incidences of Staphylococcus aureus Infection within Studies of Ventilator Associated Pneumonia Prevention Using Topical Antibiotics: Benchmarking the Evidence Base.

ABSTRACT: Selective digestive decontamination (SDD, topical antibiotic regimens applied to the respiratory tract) appears effective for preventing ventilator associated pneumonia (VAP) in intensive care unit (ICU) patients. However, potential contextual effects of SDD on Staphylococcus aureus infections in the ICU remain unclear. The S. aureus ventilator associated pneumonia (S. aureus VAP), VAP overall and S. aureus bacteremia incidences within component (control and intervention) groups within 27 SDD studies were benchmarked against 115 observational groups. Component groups from 66 studies of various interventions other than SDD provided additional points of reference. In 27 SDD study control groups, the mean S. aureus VAP incidence is 9.6% (95% CI; 6.9-13.2) versus a benchmark derived from 115 observational groups being 4.8% (95% CI; 4.2-5.6). In nine SDD study control groups the mean S. aureus bacteremia incidence is 3.8% (95% CI; 2.1-5.7) versus a benchmark derived from 10 observational groups being 2.1% (95% CI; 1.1-4.1). The incidences of S. aureus VAP and S. aureus bacteremia within the control groups of SDD studies are each higher than literature derived benchmarks. Paradoxically, within the SDD intervention groups, the incidences of both S. aureus VAP and VAP overall are more similar to the benchmarks.

SUBMITTER: Hurley JC

PROVIDER: S-EPMC5874616 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Unusually High Incidences of Staphylococcus aureus Infection within Studies of Ventilator Associated Pneumonia Prevention Using Topical Antibiotics: Benchmarking the Evidence Base.

Hurley James C JC

Microorganisms 20180104 1

Selective digestive decontamination (SDD, topical antibiotic regimens applied to the respiratory tract) appears effective for preventing ventilator associated pneumonia (VAP) in intensive care unit (ICU) patients. However, potential contextual effects of SDD on Staphylococcus aureus infections in the ICU remain unclear. The S. aureus ventilator associated pneumonia (S. aureus VAP), VAP overall and S. aureus bacteremia incidences within component (control and intervent ...[more]

PMID: 29300363

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Project description:IntroductionSelective digestive decontamination (SDD) appears to have a more compelling evidence base than non-antimicrobial methods for the prevention of ventilator associated pneumonia (VAP). However, the striking variability in ventilator associated pneumonia-incidence proportion (VAP-IP) among the SDD studies remains unexplained and a postulated contextual effect remains untested for.MethodsNine reviews were used to source 45 observational (benchmark) groups and 137 component (control and intervention) groups of studies of SDD and studies of three non-antimicrobial methods of VAP prevention. The logit VAP-IP data were summarized by meta-analysis using random effects methods and the associated heterogeneity (tau2) was measured. As group level predictors of logit VAP-IP, the mode of VAP diagnosis, proportion of trauma admissions, the proportion receiving prolonged ventilation and the intervention method under study were examined in meta-regression models containing the benchmark groups together with either the control (models 1 to 3) or intervention (models 4 to 6) groups of the prevention studies.ResultsThe VAP-IP benchmark derived here is 22.1% (95% confidence interval; 95% CI; 19.2 to 25.5; tau2 0.34) whereas the mean VAP-IP of control groups from studies of SDD and of non-antimicrobial methods, is 35.7 (29.7 to 41.8; tau2 0.63) versus 20.4 (17.2 to 24.0; tau2 0.41), respectively (P < 0.001). The disparity between the benchmark groups and the control groups of the SDD studies, which was most apparent for the highest quality studies, could not be explained in the meta-regression models after adjusting for various group level factors. The mean VAP-IP (95% CI) of intervention groups is 16.0 (12.6 to 20.3; tau2 0.59) and 17.1 (14.2 to 20.3; tau2 0.35) for SDD studies versus studies of non-antimicrobial methods, respectively.ConclusionsThe VAP-IP among the intervention groups within the SDD evidence base is less variable and more similar to the benchmark than among the control groups. These paradoxical observations cannot readily be explained. The interpretation of the SDD evidence base cannot proceed without further consideration of this contextual effect.

Project description:BackgroundHospitalized patients with COVID-19 admitted to the intensive care unit (ICU) and requiring mechanical ventilation are at risk of ventilator-associated bacterial infections secondary to SARS-CoV-2 infection. Our study aimed to investigate clinical features of Staphylococcus aureus ventilator-associated pneumonia (SA-VAP) and, if bronchoalveolar lavage samples were available, lung bacterial community features in ICU patients with or without COVID-19.MethodsWe prospectively included hospitalized patients with COVID-19 across two medical ICUs of the Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy), who developed SA-VAP between 20 March 2020 and 30 October 2020 (thereafter referred to as cases). After 1:2 matching based on the simplified acute physiology score II (SAPS II) and the sequential organ failure assessment (SOFA) score, cases were compared with SA-VAP patients without COVID-19 (controls). Clinical, microbiological, and lung microbiota data were analyzed.ResultsWe studied two groups of patients (40 COVID-19 and 80 non-COVID-19). COVID-19 patients had a higher rate of late-onset (87.5% versus 63.8%; p = 0.01), methicillin-resistant (65.0% vs 27.5%; p < 0.01) or bacteremic (47.5% vs 6.3%; p < 0.01) infections compared with non-COVID-19 patients. No statistically significant differences between the patient groups were observed in ICU mortality (p = 0.12), clinical cure (p = 0.20) and microbiological eradication (p = 0.31). On multivariable logistic regression analysis, SAPS II and initial inappropriate antimicrobial therapy were independently associated with ICU mortality. Then, lung microbiota characterization in 10 COVID-19 and 16 non-COVID-19 patients revealed that the overall microbial community composition was significantly different between the patient groups (unweighted UniFrac distance, R2 0.15349; p < 0.01). Species diversity was lower in COVID-19 than in non COVID-19 patients (94.4 ± 44.9 vs 152.5 ± 41.8; p < 0.01). Interestingly, we found that S. aureus (log2 fold change, 29.5), Streptococcus anginosus subspecies anginosus (log2 fold change, 24.9), and Olsenella (log2 fold change, 25.7) were significantly enriched in the COVID-19 group compared to the non-COVID-19 group of SA-VAP patients.ConclusionsIn our study population, COVID-19 seemed to significantly affect microbiological and clinical features of SA-VAP as well as to be associated with a peculiar lung microbiota composition.

Project description:BACKGROUND:Aerosolized antibiotics have been proposed as a novel and promising treatment option for the treatment of ventilator-associated pneumonia (VAP). However, the optimum aerosolized antibiotics for VAP remain uncertain. METHODS:We included studies from two systematic reviews and searched PubMed, EMBASE, and Cochrane databases for other studies. Eligible studies included randomized controlled trials and observational studies. Extracted data were analyzed by pairwise and network meta-analysis. RESULTS:Eight observational and eight randomized studies were identified for this analysis. By pairwise meta-analysis using intravenous antibiotics as the reference, patients treated with aerosolized antibiotics were associated with significantly higher rates of clinical recovery (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.09-1.34; P?=?0.001) and microbiological eradication (RR 1.42, 95% CI 1.22-1.650; P?<?0.0001). There were no significant differences in the risks of mortality (RR 0.88, 95% CI 0.74-1.04; P?=?0.127) or nephrotoxicity (RR 1.00, 95% CI 0.72-1.39; P?=?0.995). Using network meta-analysis, clinical recovery benefits were seen only with aerosolized tobramycin and colistin (especially tobramycin), and microbiological eradication benefits were seen only with colistin. Aerosolized tobramycin was also associated with significantly lower mortality when compared with aerosolized amikacin and colistin and intravenous antibiotics. The assessment of rank probabilities indicated aerosolized tobramycin presented the greatest likelihood of having benefits for clinical recovery and mortality, and aerosolized colistin presented the best benefits for microbiological eradication. CONCLUSIONS:Aerosolized antibiotics appear to be a useful treatment for VAP with respect to clinical recovery and microbiological eradication, and do not increase mortality or nephrotoxicity risks. Our network meta-analysis in patients with VAP suggests that clinical recovery benefits are associated with aerosolized tobramycin and colistin (especially tobramycin), microbiological eradication with aerosolized colistin, and survival with aerosolized tobramycin, mostly based on observational studies. Due to the low levels of evidence, definitive recommendations cannot be made before additional, large randomized studies are carried out.

Dataset Information

Unusually High Incidences of Staphylococcus aureus Infection within Studies of Ventilator Associated Pneumonia Prevention Using Topical Antibiotics: Benchmarking the Evidence Base.

Publications

Unusually High Incidences of Staphylococcus aureus Infection within Studies of Ventilator Associated Pneumonia Prevention Using Topical Antibiotics: Benchmarking the Evidence Base.

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