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      Declining Incidence of Candidemia and the Shifting Epidemiology of Candida Resistance in Two US Metropolitan Areas, 2008–2013: Results from Population-Based Surveillance

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          Abstract

          Background

          Recent reports have demonstrated a decline in bacterial bloodstream infections (BSIs) following adherence to central line insertion practices; however, declines have been less evident for BSIs due to Candida species.

          Methods

          We conducted active, population-based laboratory surveillance for candidemia in metropolitan Atlanta, GA and Baltimore, MD over a 5-year period. We calculated annual candidemia incidence and antifungal drug resistance rates.

          Results

          We identified 3,848 candidemia cases from 2008–2013. Compared with 2008, candidemia incidence per 100,000 person-years decreased significantly by 2013 in both locations (GA: 14.1 to 9.5, p<0.001; MD: 30.9 to 14.4, p<0.001). A total of 3,255 cases (85%) had a central venous catheter (CVC) in place within 2 days before the BSI culture date. In both locations, the number of CVC-associated cases declined (GA: 473 to 294; MD: 384 to 151). Candida albicans (CA, 36%) and Candida glabrata (CG, 27%) were the most common species recovered. In both locations, the proportion of cases with fluconazole resistance decreased (GA: 8.0% to 7.1%, −10%; MD: 6.6% to 4.9%, −25%), while the proportion of cases with an isolate resistant to an echinocandin increased (GA: 1.2% to 2.9%, +147%; MD: 2.0% to 3.5%, +77%). Most (74%) echinocandin-resistant isolates were CG; 17 (<1%) isolates were resistant to both drug categories (multidrug resistant [MDR], 16/17 were CG). The proportion of CG cases with MDR Candida increased from 1.8% to 2.6%.

          Conclusions

          We observed a significant decline in the incidence of candidemia over a five-year period, and increases in echinocandin-resistant and MDR Candida. Efforts to strengthen infection control practices may be preventing candidemia among high-risk patients. Further surveillance for resistant Candida is warranted.

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          Most cited references15

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          Changes in incidence and antifungal drug resistance in candidemia: results from population-based laboratory surveillance in Atlanta and Baltimore, 2008-2011.

          Candidemia is common and associated with high morbidity and mortality; changes in population-based incidence rates have not been reported. We conducted active, population-based surveillance in metropolitan Atlanta, Georgia, and Baltimore City/County, Maryland (combined population 5.2 million), during 2008-2011. We calculated candidemia incidence and antifungal drug resistance compared with prior surveillance (Atlanta, 1992-1993; Baltimore, 1998-2000). We identified 2675 cases of candidemia with 2329 isolates during 3 years of surveillance. Mean annual crude incidence per 100 000 person-years was 13.3 in Atlanta and 26.2 in Baltimore. Rates were highest among adults aged ≥65 years (Atlanta, 59.1; Baltimore, 72.4) and infants (aged <1 year; Atlanta, 34.3; Baltimore, 46.2). In both locations compared with prior surveillance, adjusted incidence significantly declined for infants of both black and white race (Atlanta: black risk ratio [RR], 0.26 [95% confidence interval {CI}, .17-.38]; white RR: 0.19 [95% CI, .12-.29]; Baltimore: black RR, 0.38 [95% CI, .22-.64]; white RR: 0.51 [95% CI: .29-.90]). Prevalence of fluconazole resistance (7%) was unchanged compared with prior surveillance; 32 (1%) isolates were echinocandin-resistant, and 9 (8 Candida glabrata) were multidrug resistant to both fluconazole and an echinocandin. We describe marked shifts in candidemia epidemiology over the past 2 decades. Adults aged ≥65 years replaced infants as the highest incidence group; adjusted incidence has declined significantly in infants. Use of antifungal prophylaxis, improvements in infection control, or changes in catheter insertion practices may be contributing to these declines. Further surveillance for antifungal resistance and efforts to determine effective prevention strategies are needed.
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            Species identification and antifungal susceptibility testing of Candida bloodstream isolates from population-based surveillance studies in two U.S. cities from 2008 to 2011.

            Between 2008 and 2011, population-based candidemia surveillance was conducted in Atlanta, GA, and Baltimore, MD. Surveillance had been previously performed in Atlanta in 1992 to 1993 and in Baltimore in 1998 to 2000, making this the first population-based candidemia surveillance conducted over multiple time points in the United States. From 2,675 identified cases of candidemia in the current surveillance, 2,329 Candida isolates were collected. Candida albicans no longer comprised the majority of isolates but remained the most frequently isolated species (38%), followed by Candida glabrata (29%), Candida parapsilosis (17%), and Candida tropicalis (10%). The species distribution has changed over time; in both Atlanta and Baltimore the proportion of C. albicans isolates decreased, and the proportion of C. glabrata isolates increased, while the proportion of C. parapsilosis isolates increased in Baltimore only. There were 98 multispecies episodes, with C. albicans and C. glabrata the most frequently encountered combination. The new species-specific CLSI Candida MIC breakpoints were applied to these data. With the exception of C. glabrata (11.9% resistant), resistance to fluconazole was very low (2.3% of isolates for C. albicans, 6.2% for C. tropicalis, and 4.1% for C. parapsilosis). There was no change in the proportion of fluconazole resistance between surveillance periods. Overall echinocandin resistance was low (1% of isolates) but was higher for C. glabrata isolates, ranging from 2.1% isolates resistant to caspofungin in Baltimore to 3.1% isolates resistant to anidulafungin in Atlanta. Given the increase at both sites and the higher echinocandin resistance, C. glabrata should be closely monitored in future surveillance.
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              The long-term effect of premier pay for performance on patient outcomes.

              Pay for performance has become a central strategy in the drive to improve health care. We assessed the long-term effect of the Medicare Premier Hospital Quality Incentive Demonstration (HQID) on patient outcomes. We used Medicare data to compare outcomes between the 252 hospitals participating in the Premier HQID and 3363 control hospitals participating in public reporting alone. We examined 30-day mortality among more than 6 million patients who had acute myocardial infarction, congestive heart failure, or pneumonia or who underwent coronary-artery bypass grafting (CABG) between 2003 and 2009. At baseline, the composite 30-day mortality was similar for Premier and non-Premier hospitals (12.33% and 12.40%, respectively; difference, -0.07 percentage points; 95% confidence interval [CI], -0.40 to 0.26). The rates of decline in mortality per quarter at the two types of hospitals were also similar (0.04% and 0.04%, respectively; difference, -0.01 percentage points; 95% CI, -0.02 to 0.01), and mortality remained similar after 6 years under the pay-for-performance system (11.82% for Premier hospitals and 11.74% for non-Premier hospitals; difference, 0.08 percentage points; 95% CI, -0.30 to 0.46). We found that the effects of pay for performance on mortality did not differ significantly among conditions for which outcomes were explicitly linked to incentives (acute myocardial infarction and CABG) and among conditions not linked to incentives (congestive heart failure and pneumonia) (P=0.36 for interaction). Among hospitals that were poor performers at baseline, mortality was similar in the two groups of hospitals at the start of the study (15.12% and 14.73%; difference, 0.39 percentage points; 95% CI, -0.36 to 1.15), with similar rates of improvement per quarter (0.10% and 0.07%; difference, -0.03 percentage points; 95% CI, -0.08 to 0.02) and similar mortality rates at the end of the study (13.37% and 13.21%; difference, 0.15 percentage points; 95% CI, -0.70 to 1.01). We found no evidence that the largest hospital-based pay-for-performance program led to a decrease in 30-day mortality. Expectations of improved outcomes for programs modeled after Premier HQID should therefore remain modest.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                30 March 2015
                2015
                : 10
                : 3
                : e0120452
                Affiliations
                [1 ]Mycotic Diseases Branch, Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America
                [2 ]Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America
                [3 ]Georgia Emerging Infections Program, Atlanta Veterans Affairs Medical Center and Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America
                V.P.Chest Institute, INDIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AAC LHH MMF RH BS TMC SRL BJP. Performed the experiments: AAC LHH MMF RH BS TMC SRL BJP. Analyzed the data: AAC SRL BJP. Contributed reagents/materials/analysis tools: AAC LHH MMF RH BS TMC SRL BJP. Wrote the paper: AAC LHH MMF SRL BJP.

                Article
                PONE-D-14-43454
                10.1371/journal.pone.0120452
                4378850
                25822249
                09d28c3e-27f9-44a2-a5cf-66bb6074b83d

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

                History
                : 14 October 2014
                : 22 January 2015
                Page count
                Figures: 5, Tables: 2, Pages: 12
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
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