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Cycling empirical antibiotic therapy in hospitals: meta-analysis and models.

ABSTRACT: The rise of resistance together with the shortage of new broad-spectrum antibiotics underlines the urgency of optimizing the use of available drugs to minimize disease burden. Theoretical studies suggest that coordinating empirical usage of antibiotics in a hospital ward can contain the spread of resistance. However, theoretical and clinical studies came to different conclusions regarding the usefulness of rotating first-line therapy (cycling). Here, we performed a quantitative pathogen-specific meta-analysis of clinical studies comparing cycling to standard practice. We searched PubMed and Google Scholar and identified 46 clinical studies addressing the effect of cycling on nosocomial infections, of which 11 met our selection criteria. We employed a method for multivariate meta-analysis using incidence rates as endpoints and find that cycling reduced the incidence rate/1000 patient days of both total infections by 4.95 [9.43-0.48] and resistant infections by 7.2 [14.00-0.44]. This positive effect was observed in most pathogens despite a large variance between individual species. Our findings remain robust in uni- and multivariate metaregressions. We used theoretical models that reflect various infections and hospital settings to compare cycling to random assignment to different drugs (mixing). We make the realistic assumption that therapy is changed when first line treatment is ineffective, which we call "adjustable cycling/mixing". In concordance with earlier theoretical studies, we find that in strict regimens, cycling is detrimental. However, in adjustable regimens single resistance is suppressed and cycling is successful in most settings. Both a meta-regression and our theoretical model indicate that "adjustable cycling" is especially useful to suppress emergence of multiple resistance. While our model predicts that cycling periods of one month perform well, we expect that too long cycling periods are detrimental. Our results suggest that "adjustable cycling" suppresses multiple resistance and warrants further investigations that allow comparing various diseases and hospital settings.

SUBMITTER: Abel zur Wiesch P

PROVIDER: S-EPMC4072793 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Cycling empirical antibiotic therapy in hospitals: meta-analysis and models.

Abel zur Wiesch Pia P Kouyos Roger R Abel Sören S Viechtbauer Wolfgang W Bonhoeffer Sebastian S

PLoS pathogens 20140626 6

The rise of resistance together with the shortage of new broad-spectrum antibiotics underlines the urgency of optimizing the use of available drugs to minimize disease burden. Theoretical studies suggest that coordinating empirical usage of antibiotics in a hospital ward can contain the spread of resistance. However, theoretical and clinical studies came to different conclusions regarding the usefulness of rotating first-line therapy (cycling). Here, we performed a quantitative pathogen-specific ...[more]

PMID: 24968123

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Project description:BackgroundModification of empirical antimicrobials when warranted by culture results or clinical signs is recommended to control antimicrobial overuse and resistance. We aimed to assess the frequency with which patients were started on empirical antimicrobials, characteristics of the empirical regimen and the clinical characteristics of patients at the time of starting antimicrobials, patterns of changes to empirical therapy at different timepoints, and modifiable factors associated with changes to the initial empirical regimen in the first 5 days of therapy.MethodsWe did a chart review of adult inpatients receiving one or more antimicrobials in six US hospitals on 4 days during 2009 and 2010. Our primary outcome was the modification of antimicrobial regimen on or before the 5th day of empirical therapy, analysed as a three-category variable. Bivariate analyses were used to establish demographic and clinical variables associated with the outcome. Variables with p values below 0·1 were included in a multivariable generalised linear latent and mixed model with multinomial logit link to adjust for clustering within hospitals and accommodate a non-binary outcome variable.FindingsAcross the six study sites, 4119 (60%) of 6812 inpatients received antimicrobials. Of 1200 randomly selected patients with active antimicrobials, 730 (61%) met inclusion criteria. At the start of therapy, 220 (30%) patients were afebrile and had normal white blood cell counts. Appropriate cultures were collected from 432 (59%) patients, and 250 (58%) were negative. By the 5th day of therapy, 12·5% of empirical antimicrobials were escalated, 21·5% were narrowed or discontinued, and 66·4% were unchanged. Narrowing or discontinuation was more likely when cultures were collected at the start of therapy (adjusted OR 1·68, 95% CI 1·05-2·70) and no infection was noted on an initial radiological study (1·76, 1·11-2·79). Escalation was associated with multiple infection sites (2·54, 1·34-4·83) and a positive culture (1·99, 1·20-3·29).InterpretationBroad-spectrum empirical therapy is common, even when clinical signs of infection are absent. Fewer than one in three inpatients have their regimens narrowed within 5 days of starting empirical antimicrobials. Improved diagnostic methods and continued education are needed to guide discontinuation of antimicrobials.FundingUS Centers for Disease Control and Prevention, Division of Healthcare Quality Promotion; Robert Wood Johnson Foundation; US Department of Veterans Administration; US Department of Homeland Security.

Project description:BackgroundThe prevalence and effects of inappropriate empirical antibiotic therapy for bloodstream infections are unclear. We aimed to establish the population-level burden, predictors, and mortality risk of in-vitro susceptibility-discordant empirical antibiotic therapy among patients with bloodstream infections.MethodsOur retrospective cohort analysis of electronic health record data from 131 hospitals in the USA included patients with suspected-and subsequently confirmed-bloodstream infections who were treated empirically with systemic antibiotics between Jan 1, 2005, and Dec 31, 2014. We included all patients with monomicrobial bacteraemia caused by common bloodstream pathogens who received at least one systemic antibiotic either on the day blood cultures were drawn or the day after, and for whom susceptibility data were available. We calculated the prevalence of discordant empirical antibiotic therapy-which was defined as receiving antibiotics on the day blood culture samples were drawn to which the cultured isolate was not susceptible in vitro-overall and by hospital type by using regression tree analysis. We used generalised estimating equations to identify predictors of receiving discordant empirical antibiotic therapy, and used logistic regression to calculate adjusted odds ratios for the relationship between in-hospital mortality and discordant empirical antibiotic therapy.Findings21 608 patients with bloodstream infections received empirical antibiotic therapy on the day of first blood culture collection. Of these patients, 4165 (19%) received discordant empirical antibiotic therapy. Discordant empirical antibiotic therapy was independently associated with increased risk of mortality (adjusted odds ratio 1·46 [95% CI, 1·28-1·66]; p<0·0001), a relationship that was unaffected by the presence or absence of resistance or sepsis or septic shock. Infection with antibiotic-resistant species strongly predicted receiving discordant empirical therapy (adjusted odds ratio 9·09 [95% CI 7·68-10·76]; p<0·0001). Most incidences of discordant empirical antibiotic therapy and associated deaths occurred among patients with bloodstream infections caused by Staphylococcus aureus or Enterobacterales.InterpretationApproximately one in five patients with bloodstream infections in US hospitals received discordant empirical antibiotic therapy, receipt of which was closely associated with infection with antibiotic-resistant pathogens. Receiving discordant empirical antibiotic therapy was associated with increased odds of mortality overall, even in patients without sepsis. Early identification of bloodstream pathogens and resistance will probably improve population-level outcomes.FundingUS National Institutes of Health, US Centers for Disease Control and Prevention, and US Agency for Healthcare Research and Quality.

Project description:BackgroundAntibiotic-resistant bacteria, especially multidrug-resistant strains, play a key role in impeding critical patients from survival and recovery. The effectiveness of the empiric use of antibiotics in the circling manner in intensive care units (ICUs) has not been analyzed in detail and remains controversial. Therefore, this systematic review and meta-analysis were conducted to evaluate antibiotic-cycling effect on the incidence of antibiotic-resistant bacteria.MethodsWe searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science for studies focusing on whether a cycling strategy of empiric use of antibiotics could curb the prevalence of antibiotic-resistant bacteria in ICUs. The major outcomes were risk ratios (RRs) of antibiotic-resistant infections or colonization per 1,000 patient days before and after the implementation of antibiotic cycling. A random-effects model was adopted to estimate results in consideration of clinical heterogeneity among studies. The registration number of the meta-analysis is CRD42018094464.ResultsTwelve studies, involving 2,261 episodes of resistant infections or colonization and 160,129 patient days, were included in the final analysis. Based on the available evidence, the antibiotic-cycling strategy did not reduce the overall incidence of infections or colonization with resistant bacteria (RR = 0.823, 95% CI 0.655-1.035, p = .095). In subgroup analyses, the cycling strategy cut down the incidence of resistant bacteria more significantly than baseline period (p = .028) but showed no difference in comparison with mixing strategy (p = .758).Linking evidence to actionAlthough the cycling strategy performed better than relatively free usage of antibiotics in the baseline period on reducing resistant bacteria, the cycling strategy did not show advantage when compared with the mixing strategy in subgroup analyses. In addition, these viewpoints still need more evidence to confirm.

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Cycling empirical antibiotic therapy in hospitals: meta-analysis and models.

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Cycling empirical antibiotic therapy in hospitals: meta-analysis and models.

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