Andre N. Sofair

Incidence of Bloodstream Infections Due to Candida Species and In Vitro Susceptibilities of Isolates Collected from 1998 to 2000 in a Population-Based Active Surveillance Program

ABSTRACT To determine the incidence of Candida bloodstream infections (BSI) and antifungal drug resistance, population-based active laboratory surveillance was conducted from October 1998 through September 2000 in two areas of the United States (Baltimore, Md., and the state of Connecticut; combined population, 4.7 million). A total of 1,143 cases were detected, for an average adjusted annual incidence of 10 per 100,000 population or 1.5 per 10,000 hospital days. In 28% of patients, Candida BSI developed prior to or on the day of admission; only 36% of patients were in an intensive care unit at the time of diagnosis. No fewer than 78% of patients had a central catheter in place at the time of diagnosis, and 50% had undergone surgery within the previous 3 months. Candida albicans comprised 45% of the isolates, followed by C. glabrata (24%), C. parapsilosis (13%), and C. tropicalis (12%). Only 1.2% of C. albicans isolates were resistant to fluconazole (MIC, ≥64 μg/ml), compared to 7% of C. glabrata isolates and 6% of C. tropicalis isolates. Only 0.9% of C. albicans isolates were resistant to itraconazole (MIC, ≥1 μg/ml), compared to 19.5% of C. glabrata isolates and 6% of C. tropicalis isolates. Only 4.3% of C. albicans isolates were resistant to flucytosine (MIC, ≥32 μg/ml), compared to <1% of C. parapsilosis and C. tropicalis isolates and no C. glabrata isolates. As determined by E-test, the MICs of amphotericin B were ≥0.38 μg/ml for 10% of Candida isolates, ≥1 μg/ml for 1.7% of isolates, and ≥2 μg/ml for 0.4% of isolates. Our findings highlight changes in the epidemiology of Candida BSI in the 1990s and provide a basis upon which to conduct further studies of selected high-risk subpopulations.

Excess mortality, hospital stay, and cost due to candidemia: a case-control study using data from population-based candidemia surveillance.

OBJECTIVE To determine the mortality, hospital stay, and total hospital charges and cost of hospitalization attributable to candidemia by comparing patients with candidemia with control-patients who have otherwise similar illnesses. Prior studies lack broad patient and hospital representation or cost-related information that accurately reflects current medical practices. DESIGN Our case-control study included case-patients with candidemia and their cost-related data, ascertained from laboratory-based candidemia surveillance conducted among all residents of Connecticut and Baltimore and Baltimore County, Maryland, during 1998 to 2000. Control-patients were matched on age, hospital type, admission year, discharge diagnoses, and duration of hospitalization prior to candidemia onset. RESULTS We identified 214 and 529 sets of matched case-patients and control-patients from the two locations, respectively. Mortality attributable to candidemia ranged between 19% and 24%. On multivariable analysis, candidemia was associated with mortality (OR, 5.3 for Connecticut and 8.5 for Baltimore and Baltimore County; P < .05), whereas receiving adequate treatment was protective (OR, 0.5 and 0.4 for the two locations, respectively; P < .05). Candidemia itself did not increase the total hospital charges and cost of hospitalization; when treatment status was accounted for, having received adequate treatment for candidemia significantly increased the total hospital charges and cost of hospitalization (

Comparison of Visual and Spectrophotometric Methods of Broth Microdilution MIC End Point Determination and Evaluation of a Sterol Quantitation Method for In Vitro Susceptibility Testing of Fluconazole and Itraconazole against Trailing and Nontrailing Candida Isolates

6,000 to

Excess costs of hospital care associated with neonatal candidemia

29,000 and

Epidemiology of Community-Onset Candidemia in Connecticut and Maryland

3,000 to

Surveillance for Unexplained Deaths and Critical Illnesses Due to Possibly Infectious Causes, United States, 1995-1998

22,000, respectively) and the length of stay (3 to 13 days). CONCLUSION Our findings underscore the burden of candidemia, particularly regarding the risk of death, length of hospitalization, and cost associated with treatment.

Complementary and alternative medicine use in chronic liver disease patients.

ABSTRACT Visual determination of MIC end points for azole antifungal agents can be complicated by the trailing growth phenomenon. To determine the incidence of trailing growth, we performed testing of in vitro susceptibility to fluconazole and itraconazole using the National Committee for Clinical Laboratory Standards broth microdilution M27-A reference procedure and 944 bloodstream isolates of seven Candida spp., obtained through active population-based surveillance between 1998 and 2000. Of 429 C. albicans isolates, 78 (18.2%) showed trailing growth at 48 h in tests with fluconazole, and 70 (16.3%) showed trailing in tests with itraconazole. Of 118 C. tropicalis isolates, 70 (59.3%) showed trailing growth in tests with fluconazole, and 35 (29.7%) showed trailing in tests with itraconazole. Trailing growth was not observed with any of the other five Candida spp. tested (C. dubliniensis, C. glabrata, C. krusei, C. lusitaniae, and C. parapsilosis). To confirm whether or not isolates that showed trailing growth in fluconazole and/or itraconazole were resistant in vitro to these agents, all isolates that showed trailing growth were retested by the sterol quantitation method, which measures cellular ergosterol content rather than growth inhibition after exposure to azoles. By this method, none of the trailing isolates was resistant in vitro to fluconazole or itraconazole. For both agents, a 24-h visual end point or a spectrophotometric end point of 50% reduction in growth relative to the growth control after 24 or 48 h of incubation correlated most closely with the result of sterol quantitation. Our results indicate that MIC results determined by either of these end point rules may be more predictive of in vivo outcome for isolates that give unclear visual end points at 48 h due to trailing growth.

Measurement of serum D-arabinitol/creatinine ratios for initial diagnosis and for predicting outcome in an unselected, population-based sample of patients with Candida fungemia.

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

Stability of Allelic Frequencies and Distributions of Candida albicans Microsatellite Loci from U.S. Population-Based Surveillance Isolates

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.

The Epidemiology and Clinical Characteristics of Patients With Newly Diagnosed Alcohol-related Liver Disease: Results From Population-based Surveillance

BACKGROUND Almost one-third of patients with bloodstream infections with Candida species (candidemia) have onset of disease that occurs outside of the hospital or < or = 2 days after hospital admission (i.e., community-onset candidemia). We compared the characteristics of patients who developed candidemia by the timing of onset of infection. METHODS Incident episodes of candidemia were identified through active, population-based surveillance in Connecticut and in Baltimore and Baltimore County, Maryland, during 1 October 1998-30 September 2000. The molecular subtypes of a sample of 45 Candida parapsilosis isolates were evaluated using Southern blots hybridized with the complex probe Cp3-13. RESULTS Overall, 356 (31%) of the 1143 incident episodes of candidemia were classified as community-onset disease (occurring < or = 2 days after hospital admission), and 132 (37%) were caused by Candida albicans, 89 (25%) were caused by Candida glabrata, 57 (16%) were caused by C. parapsilosis, and 53 (15%) were caused by Candida tropicalis. Community-onset disease was less likely to be associated with concurrent immunosuppressive therapy, recent surgery, or use of a central venous catheter, compared with inpatient disease. Among patients with community-onset disease, the median time from blood culture to initiation of antifungal treatment was 2.7 days, the 30-day case-fatality rate was 26%, and 262 patients (75%) had been hospitalized at least once in the previous 3 months. Although there were few differences between patients with very recent hospitalization (in the previous 1 month), less recent hospitalization (previous 1-3 months), and no documented past hospitalization, C. parapsilosis was more frequently associated with community-onset disease as hospitalization became more distant. C. parapsilosis strains tended to be unique to the patient, with little similarity found between strain types, on the basis of epidemiologic classification of patients. CONCLUSION We report that community-onset candidemia is common and occurs in patients with extensive contact with the health care system. Disease caused by C. parapsilosis tends to involve unique strains.