Catheter-associated urinary tract infections (CAUTIs) and non-CAUTI hospital-onset urinary tract infections: Relative burden, cost, outcomes and related hospital-onset bacteremia and fungemia infections.

OBJECTIVE: To describe the relative burden of catheter-associated urinary tract infections (CAUTIs) and non-CAUTI hospital-onset urinary tract infections (HOUTIs). METHODS: A retrospective observational study of patients from 43 acute-care hospitals was conducted. CAUTI cases were defined as those reported to the National Healthcare Safety Network. Non-CAUTI HOUTI was defined as a positive, non-contaminated, non-commensal culture collected on day 3 or later. All HOUTIs were required to have a new antimicrobial prescribed within 2 days of the first positive urine culture. Outcomes included secondary hospital-onset bacteremia and fungemia (HOB), total hospital costs, length of stay (LOS), readmission risk, and mortality. RESULTS: Of 549,433 admissions, 434 CAUTIs and 3,177 non-CAUTI HOUTIs were observed. The overall rate of HOB likely secondary to HOUTI was 3.7%. Total numbers of secondary HOB were higher in non-CAUTI HOUTIs compared to CAUTI (101 vs 34). HOB secondary to non-CAUTI HOUTI was more likely to originate outside the ICU compared to CAUTI (69.3% vs 44.1%). CAUTI was associated with adjusted incremental total hospital cost and LOS of $9,807 (P < .0001) and 3.01 days (P < .0001) while non-CAUTI HOUTI was associated with adjusted incremental total hospital cost and LOS of $6,874 (P < .0001) and 2.97 days (P < .0001). CONCLUSION: CAUTI and non-CAUTI HOUTI were associated with deleterious outcomes. Non-CAUTI HOUTI occurred more often and was associated with a higher facility aggregate volume of HOB than CAUTI. Patients at risk for UTIs in the hospital represent a vulnerable population who may benefit from surveillance and prevention efforts, particularly in the non-ICU setting.

Characteristics, costs, and outcomes associated with central-line-associated bloodstream infection and hospital-onset bacteremia and fungemia in US hospitals.

OBJECTIVES: To compare characteristics and outcomes associated with central-line-associated bloodstream infections (CLABSIs) and electronic health record-determined hospital-onset bacteremia and fungemia (HOB) cases in hospitalized US adults. METHODS: We conducted a retrospective observational study of patients in 41 acute-care hospitals. CLABSI cases were defined as those reported to the National Healthcare Safety Network (NHSN). HOB was defined as a positive blood culture with an eligible bloodstream organism collected during the hospital-onset period (ie, on or after day 4). We evaluated patient characteristics, other positive cultures (urine, respiratory, or skin and soft-tissue), and microorganisms in a cross-sectional analysis cohort. We explored adjusted patient outcomes [length of stay (LOS), hospital cost, and mortality] in a 1:5 case-matched cohort. RESULTS: The cross-sectional analysis included 403 patients with NHSN-reportable CLABSIs and 1,574 with non-CLABSI HOB. A positive non-bloodstream culture with the same microorganism as in the bloodstream was reported in 9.2% of CLABSI patients and 32.0% of non-CLABSI HOB patients, most commonly urine or respiratory cultures. Coagulase-negative staphylococci and Enterobacteriaceae were the most common microorganisms in CLABSI and non-CLABSI HOB cases, respectively. In case-matched analyses, CLABSIs and non-CLABSI HOB, separately or combined, were associated with significantly longer LOS [difference, 12.1-17.4 days depending on intensive care unit (ICU) status], higher costs (by $25,207-$55,001 per admission), and a >3.5-fold increased risk of mortality in patients with an ICU encounter. CONCLUSIONS: CLABSI and non-CLABSI HOB cases are associated with significant increases in morbidity, mortality, and cost. Our data may help inform prevention and management of bloodstream infections.

Sepsis: the LightCycler SeptiFast Test MGRADE®, SepsiTest™ and IRIDICA BAC BSI assay for rapidly identifying bloodstream bacteria and fungi - a systematic review and economic evaluation.

BACKGROUND: Sepsis can lead to multiple organ failure and death. Timely and appropriate treatment can reduce in-hospital mortality and morbidity. OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of three tests [LightCycler SeptiFast Test MGRADE(®) (Roche Diagnostics, Risch-Rotkreuz, Switzerland); SepsiTest(TM) (Molzym Molecular Diagnostics, Bremen, Germany); and the IRIDICA BAC BSI assay (Abbott Diagnostics, Lake Forest, IL, USA)] for the rapid identification of bloodstream bacteria and fungi in patients with suspected sepsis compared with standard practice (blood culture with or without matrix-absorbed laser desorption/ionisation time-of-flight mass spectrometry). DATA SOURCES: Thirteen electronic databases (including MEDLINE, EMBASE and The Cochrane Library) were searched from January 2006 to May 2015 and supplemented by hand-searching relevant articles. REVIEW METHODS: A systematic review and meta-analysis of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. A decision tree was used to estimate the costs and quality-adjusted life-years (QALYs) associated with each test; all other parameters were estimated from published sources. The model was populated with evidence from the systematic review or individual studies, if this was considered more appropriate (base case 1). In a secondary analysis, estimates (based on experience and opinion) from seven clinicians regarding the benefits of earlier test results were sought (base case 2). A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Scenario analyses were used to assess uncertainty. RESULTS: For the review of diagnostic test accuracy, 62 studies of varying methodological quality were included. A meta-analysis of 54 studies comparing SeptiFast with blood culture found that SeptiFast had an estimated summary specificity of 0.86 [95% credible interval (CrI) 0.84 to 0.89] and sensitivity of 0.65 (95% CrI 0.60 to 0.71). Four studies comparing SepsiTest with blood culture found that SepsiTest had an estimated summary specificity of 0.86 (95% CrI 0.78 to 0.92) and sensitivity of 0.48 (95% CrI 0.21 to 0.74), and four studies comparing IRIDICA with blood culture found that IRIDICA had an estimated summary specificity of 0.84 (95% CrI 0.71 to 0.92) and sensitivity of 0.81 (95% CrI 0.69 to 0.90). Owing to the deficiencies in study quality for all interventions, diagnostic accuracy data should be treated with caution. No randomised clinical trial evidence was identified that indicated that any of the tests significantly improved key patient outcomes, such as mortality or duration in an intensive care unit or hospital. Base case 1 estimated that none of the three tests provided a benefit to patients compared with standard practice and thus all tests were dominated. In contrast, in base case 2 it was estimated that all cost per QALY-gained values were below £20,000; the IRIDICA BAC BSI assay had the highest estimated incremental net benefit, but results from base case 2 should be treated with caution as these are not evidence based. LIMITATIONS: Robust data to accurately assess the clinical effectiveness and cost-effectiveness of the interventions are currently unavailable. CONCLUSIONS: The clinical effectiveness and cost-effectiveness of the interventions cannot be reliably determined with the current evidence base. Appropriate studies, which allow information from the tests to be implemented in clinical practice, are required. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015016724. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A practice-based observational study on the use of micafungin in Surgical Critical Care Units.

INTRODUCTION: Echinocandins are first-line therapy in critically ill patients with invasive Candida infection (ICI). This study describes our experience with micafungin at Surgical Critical Care Units (SCCUs). METHODS: A multicenter, observational, retrospective study was performed (12 SCCUs) by reviewing all adult patients receiving 100 mg/24h micafungin for ≥72h during ad-mission (April 2011-July 2013). Patients were divided by ICI category (possible, probable + proven), 24h-SOFA (<7, ≥7) and outcome. RESULTS: 72 patients were included (29 possible, 13 probable, 30 proven ICI). Forty patients (55.6%) presented SOFA ≥7. Up to 78.0% patients were admitted after urgent surgery (64.3% with SOFA <7 vs. 90.3% with SOFA ≥7, p=0.016), and 84.7% presented septic shock. In 66.7% the site of infection was intraabdominal. Forty-nine isolates were recovered (51.0% C. albicans). Treatment was empirical (59.7%), microbiologically directed (19.4%), rescue therapy (15.3%), or anticipated therapy and prophylaxis (2.8% each). Empirical treatment was more frequent (p<0.001) in possible versus probable + proven ICI (86.2% vs. 41.9%). Treatment (median) was longer (p=0.002) in probable + proven versus possible ICI (13.0 vs. 8.0 days). Favorable response was 86.1%, without differences by group. Age, blood Candida isolation, rescue therapy, final MELD value and %MELD variation were significantly higher in patients with non-favorable response. In the multivariate analysis (R2=0.246, p<0.001) non-favorable response was associated with positive %MELD variations (OR=15.445, 95%CI= 2.529-94.308, p=0.003) and blood Candida isolation (OR=11.409, 95%CI=1.843-70.634, p=0.009). CONCLUSION: High favorable response was obtained, with blood Candida isolation associated with non-favorable response, in this series with high percentage of patients with intraabdominal ICI, septic shock and microbiological criteria for ICI.

Infections occurring in adult patients receiving mechanical circulatory support: the two-year experience of an Italian National Referral Tertiary Care Center.

OBJECTIVE: Infection during mechanical circulatory support is a frequent adverse complication. We analyzed infections occurring in this population in a national tertiary care center, and assessed the differences existing between the setting of extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VADs). DESIGN, SETTING, AND PARTICIPANTS: An observational study was made of patients treated with ECMO or VAD in the San Raffaele Scientific Institute (Italy) between 2009 and 2011. INTERVENTIONS: None. RESULTS: Thirty-nine percent of the 46 patients with ECMO and 69% of the 15 patients with VAD developed infection. We observed a mortality rate of 36.1% during mechanical circulatory support and of 55.7% during the global hospitalization period. Although Gram-negative infections were predominant overall, patients with ECMO were more prone to develop Candida infection (29%), and patients with VAD tended to suffer Staphylococcus infection (18%). Patients with infection had longer ECMO support (p=0.03), VAD support (p=0.01), stay in the intensive care unit (p=0.002), and hospital admission (p=0.03) than patients without infection. Infection (regression coefficient=3.99, 95% CI 0.93-7.05, p=0.02), body mass index (regression coefficient=0.46, 95% CI 0.09-0.83, p=0.02), fungal infection (regression coefficient=4.96, 95% CI 1.42-8.44, p=0.009) and obesity (regression coefficient=10.47, 95% CI 1.77-19.17, p=0.02) were predictors of the duration of ECMO support. Stepwise logistic regression analysis showed the SOFA score at the time of implant (OR=12.33, 95% CI 1.15-132.36, p=0.04) and VAD (OR=1.27, 95% CI 1.04-1.56, p=0.02) to be associated with infection. CONCLUSIONS: Infection is a major challenge during ECMO and VAD support. Each mechanical circulatory support configuration is associated with specific pathogens; fungal infections play a major role.

[Costs associated with nosocomial bacteraemias in a University Hospital]. / Costes asociados a las bacteriemias nosocomiales en un hospital universitario.

OBJECTIVE: To describe the increase in costs due to patients who had any episode of nosocomial bacteraemia (NB) in a University Hospital, compared to the costs of patients with the same illness who did not. METHODS: Descriptive and retrospective study. POPULATION: all hospitalisation episodes between January 2005 and December 2007. We compared the patients who suffered some episode of NB, with the patients who did not. Dependent variable: cost of the hospitalisation episode. Main explanatory variable: presence of nosocomial bacteraemia. A generalized linear model was adjusted, with Gamma distribution and link logarithm function, given the distribution of the costs. RESULTS: There were 640 hospital episodes with NB and 28,459 with no NB. The average incremental cost for the hospitalisations with NB was 14,735.5€, adjusted for the disease. The impact on the costs for the hospital due to patients with NB was 9,430,713€. The most frequent source of infection was the catheter (35.5%), with an average increase in cost of 18,078€. In the multivariable model, the cost of patients with NB and involving a Gram(+) microorganism was 2.1 times more than that of patients without bacteraemia (95% CI; 1.96-2.23), if the microorganism was Gram(-) it was 1.8 times more (95% CI; 1.70-1.93), and for a fungus it was 2.4 time more (95% CI; 1.95-2.89). CONCLUSIONS: This analysis shows the significant impact in the financial costs due to NB, and gives a measure of the cost-benefit of investing in resources to prevent them. Knowing the source cause of the bacteraemia allows priority to be given to these areas and to promote the necessary actions designed to prevent them.

Genetic diversity among Korean Candida albicans bloodstream isolates: assessment by multilocus sequence typing and restriction endonuclease analysis of genomic DNA by use of BssHII.

Multilocus sequence typing (MLST) has been successfully applied to the epidemiology of Candida albicans isolates not only within the hospital setting but also in multiple locations nationwide. We performed MLST to investigate the genetic relatedness among bloodstream infection (BSI) isolates of C. albicans recovered from 10 Korean hospitals over a 12-month period. The 156 isolates yielded 112 unique diploid sequence types (DSTs). While 95 DSTs were each derived from a single isolate, 17 DSTs were shared by 61 isolates (39.1%). Interestingly, 111 (71.1%) isolates clustered within previously known clades, and 29 (18.6%) clustered within a new clade that includes strains of Asian origin previously typed as singletons. This MLST study was complemented by restriction endonuclease analysis of genomic DNA using BssHII (REAG-B) in order to evaluate whether strains with identical DSTs and originating from the same hospital corresponded to nosocomial clusters. Importantly, only those isolates with a strong epidemiological relationship showed ≥95% identical REAG-B types. Our results indicate that REAG-B typing can be complementary to MLST but should be limited to the investigation of isolates of identical DSTs and when interhuman transmission is suspected.

Anidulafungin for the treatment of invasive candidiasis.

Candidaemia/invasive candidiasis (C/IC) is the most frequently occurring invasive fungal infection worldwide, with a particularly strong impact and high incidence in the intensive-care unit, where there is a need for new treatment options and strategies. The echinocandin anidulafungin has broad in vitro activity against a wide range of Candida species, along with favourable pharmacokinetics that allow administration in hepatic and renal impairment and with any comedication without the need for dose adjustments. The efficacy and safety of anidulafungin for the treatment of C/IC were demonstrated in a number of clinical studies and by some limited data from clinical practice. In a randomized comparative trial for the treatment of C/IC in adults, 76% of patients receiving anidulafungin and 60% of those given fluconazole were treated successfully (95% CI for difference: 4-27; p 0.01). Post hoc analyses suggest that anidulafungin is significantly more effective than standard-dose fluconazole for the treatment of candidaemia in critically ill patients. Anidulafungin is generally well tolerated, with commonly reported side effects including headache, hypokalaemia, gastrointestinal symptoms, abnormal liver function test results, and rash. In pharmaco-economic analyses, anidulafungin compared favourably with fluconazole (in terms of overall costs and hospital resource use) as well as with other echinocandins. Echinocandins, including anidulafungin, are now generally recommended as first-line therapy in moderately to severely ill patients, those with prior azole exposure, and patients with C/IC caused by Candida glabrata or Candida krusei.

Cost-effectiveness of micafungin as an alternative to fluconazole empiric treatment of suspected ICU-acquired candidemia among patients with sepsis: a model simulation.

INTRODUCTION: Recent epidemiologic literature indicates that candidal species resistant to azoles are becoming more prevalent in the face of increasing incidence of hospitalizations with candidemia. Echinocandins, a new class of antifungal agents, are effective against resistant candidal species. As delaying appropriate antifungal coverage leads to increased mortality, we evaluated the cost-effectiveness of 100 mg daily empiric micafungin (MIC) vs. 400 mg daily fluconazole (FLU) for suspected intensive care unit-acquired candidemia (ICU-AC) among septic patients. METHODS: We designed a decision model with inputs from the literature in a hypothetical 1000-patient cohort with suspected ICU-AC treated empirically with either MIC or FLU or no treatment accompanied by a watchful waiting strategy. We examined the differences in the number of survivors, acquisition costs of antifungals, and lifetime costs among survivors in the cohort under each scenario, and calculated cost per quality adjusted life year (QALY). We conducted Monte Carlo simulations and sensitivity analyses to determine the stability of our estimates. RESULTS: In the base case analysis, assuming ICU-AC attributable mortality of 0.40 and a 52% relative risk reduction in mortality with appropriate timely therapy, compared with FLU (total deaths 31), treatment with MIC (total deaths 27) would result in four fewer deaths at an incremental cost/death averted of $61,446. Similarly, in reference case, incremental cost-effectiveness of MIC over FLU was $34,734 (95% confidence interval $26,312 to $49,209) per QALY. The estimates were most sensitive to the QALY adjustment factor and the risk of candidemia among septic patients. CONCLUSIONS: Given the increasing likelihood of azole resistance among candidal isolates, empiric treatment of ICU-AC with 100 mg daily MIC is a cost-effective alternative to FLU.

Epidemiology, management, and risk factors for death of invasive Candida infections in critical care: a multicenter, prospective, observational study in France (2005-2006).

OBJECTIVE: To describe the evolving epidemiology, management, and risk factors for death of invasive Candida infections in intensive care units (ICUs). DESIGN: Prospective, observational, national, multicenter study. SETTING: One hundred eighty ICUs in France. PATIENTS: Between October 2005 and May 2006, 300 adult patients with proven invasive Candida infection who received systemic antifungal therapy were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred seven patients (39.5%) with isolated candidemia, 87 (32.1%) with invasive candidiasis without documented candidemia, and 77 (28.4%) with invasive candidiasis and candidemia were eligible. In 37% of the cases, candidemia occurred within the first 5 days after ICU admission. C. albicans accounted for 57.0% of the isolates, followed by C. glabrata (16.7%), C. parapsilosis (7.5%), C. krusei (5.2%), and C. tropicalis (4.9%). In 17.1% of the isolates, the causative Candida was less susceptible or resistant to fluconazole. Fluconazole was the empirical treatment most commonly introduced (65.7%), followed by caspofungin (18.1%), voriconazole (5.5%), and amphotericin B (3.7%). After identification of the causative species and susceptibility testing results, treatment was modified in 86 patients (31.7%). The case fatality ratio in ICU was 45.9% and did not differ significantly according to the type of episode. Multivariate analysis showed that factors independently associated with death in ICU were type 1 diabetes mellitus (odds ratio [OR] 4.51; 95% confidence interval [CI] 1.72-11.79; p = 0.002), immunosuppression (OR 2.63; 95% CI 1.35-5.11; p = 0.0045), mechanical ventilation (OR 2.54; 95% CI 1.33-4.82; p = 0.0045), and body temperature >38.2 degrees C (reference, 36.5-38.2 degrees C; OR 0.36; 95% CI 0.17-0.77; p = 0.008). CONCLUSIONS: More than two thirds of patients with invasive candidiasis in ICU present with candidemia. Non-albicans Candida species reach almost half of the Candida isolates. Reduced susceptibility to fluconazole is observed in 17.1% of Candida isolates. Mortality of invasive candidiasis in ICU remains high.

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part I. Epidemiology and diagnosis.

BACKGROUND: Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting, particularly in the intensive care unit (ICU). OBJECTIVES AND METHODS: To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and a European expert panel discussion. RESULTS AND CONCLUSIONS: Candida albicans remains the most frequently isolated fungal species followed by C. glabrata. The diagnosis of invasive candidiasis involves both clinical and laboratory parameters, but neither of these are specific. One of the main features in diagnosis is the evaluation of risk factor for infection which will identify patients in need of pre-emptive or empiric treatment. Clinical scores were built from those risk factors. Among laboratory diagnosis, a positive blood culture from a normally sterile site provides positive evidence. Surrogate markers have also been proposed like 1,3 beta-D: glucan level, mannans, or PCR testing. Invasive candidiasis and candidemia is a growing concern in the ICU, apart from cases with positive blood cultures or fluid/tissue biopsy, diagnosis is neither sensitive nor specific. The diagnosis remains difficult and is usually based on the evaluation of risk factors.

Excess costs of hospital care associated with neonatal candidemia.

BACKGROUND: Nosocomial bloodstream infections are associated with increased hospital costs in adult and pediatric patients. Candida is an increasingly important nosocomial pathogen within intensive care nurseries. The purpose of this study was to determine the attributable cost of candidemia in neonates. METHODS: This case-control study included all neonates with candidemia receiving care in hospitals in Connecticut and in Baltimore County and the city of Baltimore, MD. We identified 47 cases and 130 control patients. Multivariable linear regression was used to control for state, birth weight and mortality to determine the effect of candidemia on length of stay, cost per day and total hospital costs. RESULTS: Candidemia was associated with a $28,000 increase in total hospital costs in multivariable analysis. This increase in total cost was the result of both an increase in costs per day and length of hospital stay. Other cost-increasing variables included in the analysis were: state of origin (Connecticut), survival and decreasing birth weight. CONCLUSIONS: This represents the first study of the adjusted costs of candidemia in neonates. In addition to high mortality, candidemia was associated with increased hospital costs. This cost analysis could be helpful in determining the financial benefits of preventing candidemia in high risk neonates.

Healthcare-associated bloodstream infection: A distinct entity? Insights from a large U.S. database.

OBJECTIVE: To gain a better understanding of the epidemiology, microbiology, and outcomes of early-onset, culture-positive, community-acquired, healthcare-associated, and hospital-acquired bloodstream infections. DESIGN: We analyzed a large U.S. database (Cardinal Health, MediQual, formerly MedisGroups) to identify patients with bacterial or fungal bloodstream isolates from 2002 to 2003. SETTING: The data set included administrative and clinical variables (physiologic, laboratory, culture, and other clinical) from 59 hospitals. Bloodstream infections were identified in those hospitals collecting clinical and culture data for at least the first 5 days of admission. PATIENTS: Patients with bloodstream infection within 2 days of admission were classified as having community-acquired bloodstream infection. Those with a prior hospitalization within 30 days, transfer from another facility, ongoing chemotherapy, or long-term hemodialysis were classified as having healthcare-associated bloodstream infection. Bloodstream infections that developed after day 2 of admission were classified as hospital-acquired bloodstream infection. A total of 6,697 patients were identified as having bloodstream infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Healthcare-associated bloodstream infection accounted for more than half (55.3%) of all bloodstream infections. Nearly two thirds (62.3%) of hospitalized patients with bloodstream infection suffered from either hospital-acquired bloodstream infection or healthcare-associated bloodstream infection and had higher morbidity and mortality rates than those with community-acquired bloodstream infection. Of all bloodstream infection pathogens, fungal organisms were associated with the highest crude mortality, longest length of stay in hospital, and greatest total charges. Of all bacterial bloodstream infections, methicillin-resistant Staphylococcus aureus was associated with the highest crude mortality rate (22.5%), the longest mean length of stay (11.1 +/- 10.7 days), and the highest median total charges ($36,109). After we controlled for confounding factors, methicillin-resistant S. aureus was associated with the highest independent mortality risk (odds ratio 2.70; confidence interval 2.03-3.58). S. aureus was the most commonly encountered pathogen in all types of early-onset bacteremia. CONCLUSIONS: Healthcare-associated bloodstream infection constitutes a distinct entity of bloodstream infection with its unique epidemiology, microbiology, and outcomes. Methicillin-resistant Staphylococcus aureus carries the highest relative mortality risk among all pathogens.

Candidaemia and antifungal therapy in a French University Hospital: rough trends over a decade and possible links.

BACKGROUND: Evidence for an increased prevalence of candidaemia and for high associated mortality in the 1990s led to a number of different recommendations concerning the management of at risk patients as well as an increase in the availability and prescription of new antifungal agents. The aim of this study was to parallel in our hospital candidemia incidence with the nature of prescribed antifungal drugs between 1993 and 2003. METHODS: During this 10-year period we reviewed all cases of candidemia, and collected all the data about annual consumption of prescribed antifungal drugs. RESULTS: Our centralised clinical mycology laboratory isolates and identifies all yeasts grown from blood cultures obtained from a 3300 bed teaching hospital. Between 1993 and 2003, 430 blood yeast isolates were identified. Examination of the trends in isolation revealed a clear decrease in number of yeast isolates recovered between 1995-2000, whereas the number of positive blood cultures in 2003 rose to 1993 levels. The relative prevalence of Candida albicans and C. glabrata was similar in 1993 and 2003 in contrast to the period 1995-2000 where an increased prevalence of C. glabrata was observed. When these quantitative and qualitative data were compared to the amount and type of antifungal agents prescribed during the same period (annual mean defined daily dose: 2662741; annual mean cost: 615,629 euros) a single correlation was found between the decrease in number of yeast isolates, the increased prevalence of C. glabrata and the high level of prescription of fluconazole at prophylactic doses between 1995-2000. CONCLUSION: Between 1993 and 2000, the number of cases of candidemia halved, with an increase of C. glabrata prevalence. These findings were probably linked to the use of Fluconazole prophylaxis. Although it is not possible to make any recommendations from this data the information is nevertheless interesting and may have considerable implications with the introduction of new antifungal drugs.

The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis.

BACKGROUND: Candida species are the fourth most common cause of bloodstream infection and are the leading cause of invasive fungal infection among hospitalized patients in the United States. However, the frequency and outcomes attributable to the infection are uncertain. This retrospective study set out to estimate the incidence of candidemia in hospitalized adults and children in the United States and to determine attributable mortality, length of hospital stay, and hospital charges related to candidemia. METHODS: We used the Nationwide Inpatient Sample 2000 for adult patients and the Kids' Inpatient Database 2000 for pediatric patients. We matched candidemia-exposed and candidemia-unexposed patients by the propensity scores for the probability of candidemia exposure, which were derived from patient characteristics. Attributable outcomes were calculated as the differences in estimates of outcomes between propensity score-matched patients with and without candidemia. RESULTS: In the United States in 2000, candidemia was diagnosed in an estimated 1118 hospital admissions of pediatric patients and 8949 hospital admissions of adult patients, yielding a frequency of 43 cases per 100,000 pediatric admissions (95% confidence interval [CI], 35-52 cases per 100,000 pediatric admissions) and 30 cases per 100,000 adult admissions (95% CI, 26-34 cases per 100,000 adult admissions). In pediatric patients, candidemia was associated with a 10.0% increase in mortality (95% CI, 6.2%-13.8%), a mean 21.1-day increase in length of stay (95% CI, 14.4-27.8 days), and a mean increase in total per-patient hospital charges of 92,266 dollars (95% CI, 65,058 dollars-119,474 dollars). In adult patients, candidemia was associated with a 14.5% increase in mortality (95% CI, 12.1%-16.9%), a mean 10.1-day increase in length of stay (95% CI, 8.9-11.3 days), and a mean increase in hospital charges of 39,331 dollars (95% CI, 33,604 dollars-45,602 dollars). CONCLUSION: The impact of candidemia on excess mortality, increased length of stay, and the burden of cost of hospitalization underscores the need for improved means of prevention and treatment of candidemia in adults and children.

Secular trends of candidemia in a large tertiary-care hospital from 1988 to 2000: emergence of Candida parapsilosis.

OBJECTIVE: To analyze the secular trends of candidemia in a large tertiary-care hospital to determine the overall incidence, as well as the incidence by ward and by species, and to detect the occurrence of outbreaks. DESIGN: Retrospective descriptive analysis. Secular trends were calculated using the Mantel-Haenszel test. SETTING: A large tertiary-care referral center in Spain with a pediatric intensive care unit (ICU) to which more than 500 children with congenital cardiac disease are admitted annually. PATIENTS: All patients with candidemia occurring from 1988 to 2000 were included. Cases were identified from laboratory records of blood cultures. RESULTS: There were 331 episodes of candidemia. The overall incidence of nosocomial candidemia was 0.6 episode per 1,000 admissions and remained stable throughout the study period (P = .925). The species most frequently isolated was Candida albicans, but the incidence of C. parapsilosis candidemia increased (P = .035). In the pediatric ICU, the incidence of C. parapsilosis was 5.6 episodes per 1,000 admissions and it was the predominant species. Outbreaks occurred occasionally in the pediatric ICU, suggesting nosocomial transmission. CONCLUSIONS: During this 13-year period, the incidence of candidemia remained stable in this hospital, but C. parapsilosis increased in frequency. Occasional outbreaks of candidemia suggested nosocomial transmission of Candida species.

Assessment of preemptive treatment to prevent severe candidiasis in critically ill surgical patients.

OBJECTIVE: To assess the efficacy of a preemptive antifungal therapy in preventing proven candidiasis in critically ill surgical patients. DESIGN: Before/after intervention study, with 2-yr prospective and 2-yr historical control cohorts. SETTING: Surgical intensive care unit (SICU) in a university-affiliated hospital. PATIENTS: Nine hundred and thirty-three patients, 478 in the prospective group and 455 in the control group, with SICU stay > or =5 days. INTERVENTIONS: During the prospective period, systematic mycological screening was performed on all patients admitted to the SICU, immediately at admittance and then weekly until discharge. A corrected colonization index was used to assess intensity of Candida mucosal colonization. Patients with corrected colonization index > or =0.4 received early preemptive antifungal therapy (fluconazole intravenously: loading dose 800 mg, then 400 mg/day for 2 wks). MEASUREMENTS AND MAIN RESULTS: End points of this study were the frequency of proven candidiasis, especially SICU-acquired candidiasis. During the retrospective period, 32 patients of 455 (7%) presented with proven candidiasis: 22 (4.8%) were imported and 10 (2.2%) were SICU-acquired cases. During the prospective period, 96 patients with corrected colonization index > or =0.4 of 478 received preemptive antifungal treatment and only 18 cases (3.8%) of proven candidiasis were diagnosed; all were imported infections. Candida infections occurred more frequently in the control cohort (7% vs. 3.8%; p = .03). Incidence of SICU-acquired proven candidiasis significantly decreased from 2.2% to 0% (p < .001, Fisher test). Incidence of proven imported candidiasis remained unchanged (4.8% vs. 3.8%; p = .42). No emergence of azole-resistant Candida species (especially Candida glabrata, Candida krusei) was noted during the prospective period. CONCLUSIONS: Targeted preemptive strategy may efficiently prevent acquisition of proven candidiasis in SICU patients. Further studies are being performed to assess cost-effectiveness of this strategy and its impact on selection of azole-resistant Candida strains on a long-term basis.

Clinical manifestations and molecular epidemiology of late recurrent candidemia, and implications for management.

The aim of this study was to define the epidemiology and clinical manifestations of late recurrent candidemia. For this purpose, late recurrent candidemia was defined as an episode of candidemia occurring at least 1 month after the apparent complete resolution of an infectious episode caused by the same Candida sp. A total of five patients with recurrent candidemia were investigated. For all patients, isolates from the initial and recurrent episodes of candidemia were available for in vitro susceptibility testing and genetic characterization by DNA-based techniques. The results revealed the following salient features: prolonged duration between the initial and recurrent episodes (range, 1-8 months); recurrence of candidemia despite anti-fungal therapy; importance of retained intravascular catheters, neutropenia, and corticosteroids as factors predisposing to recurrence; high morbidity and mortality; no emergence of antifungal drug resistance between the initial and recurrent episodes; and relapse of infection due to the original infecting strain, rather than reinfection with a new strain. These findings raise several issues about the management and follow-up of patients with candidemia, which require assessment in future studies.