Skip Navigation

The Epidemiology of Candidemia in Two United States Cities: Results of a Population-Based Active Surveillance

  1. Annie S. Kao1,a,
  2. Mary E. Brandt1,
  3. W. Ruth Pruitt1,
  4. Laura A. Conn2,
  5. Bradley A. Perkins1,
  6. David S. Stephens3,
  7. Wendy S. Baughman3,
  8. Arthur L. Reingold4,
  9. Gretchen A. Rothrock4,
  10. Michael A. Pfaller5,
  11. Robert W. Pinner2, and
  12. Rana A. Hajjeh1
  1. 1Division of Bacterial and Mycotic Diseases, Atlanta, Georgia
  2. 2Office of Surveillance, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
  3. 3Georgia Emerging Infections Program, Emory University and the Department of Veterans Affairs Medical Center, Atlanta, Georgia
  4. 4California Emerging Infections Program, University of California, Berkeley, California
  5. 5University of Iowa College of Medicine, Iowa City, Iowa
  1. Reprints or correspondence: Dr. Rana Hajjeh, Division of Bacterial and Mycotic Diseases, Mycotic Diseases Branch (Mailstop C09), Centers for Disease Control and Prevention, 1600 Clifton Road, Northeast, Atlanta, GA 30333 (rfh5{at}cdc.gov).

  • ↵Present affiliation: San Diego County Health and Human Services Agency, Division of AIDS and Community Epidemiology, San Diego, CA.

 
Next Section

Abstract

We conducted prospective, active population-based surveillance for candidemia (defined as any Candida species isolated from blood) in Atlanta and San Francisco (total population, 5.34 million) during 1992–1993. The average annual incidence of candidemia at both sites was 8 per 100,000 population. The highest incidence (75 per 100,000) occurred among infants ⩽1 year old. In 19% of patients, candidemia developed prior to or on the day of admission. Underlying medical conditions included cancer (26%), abdominal surgery (14%), diabetes mellitus (13%), and human immunodeficiency virus infection (10%). In 47% of cases, species of Candida other than Candida albicans were isolated, most commonly Candida parapsilosis, Candida glabrata, and Candida tropicalis. Antifungal susceptibility testing of 394 isolates revealed minimal levels of azole resistance among C. albicans, C. tropicalis, and C. parapsilosis. These data document the substantial burden of candidemia and its changing epidemiology. Continued surveillance will be important to monitor the epidemiology of candidemia and to detect emergence of resistance to azoles.

Bloodstream infections due to Candida species are becoming increasingly important causes of morbidity and mortality in hospitalized patients. Recent nosocomial surveillance data showed that Candida species were the fourth most common group of organisms recovered from the blood of hospitalized patients in the United States, and these organisms accounted for 8%–15% of all hospital-acquired bloodstream infections [1–3]. Over the last 2 decades, both the incidence of nosocomial candidemia and the proportion of bloodstream infections due to Candida species other than Candida albicans have increased [2, 4–6]. Recent studies have yielded important information about the epidemiology of candidemia but have usually consisted of retrospective reviews of medical records from individual hospitals or prospective surveillance in selected sentinel institutions, which may not be representative of all of the hospitals serving a community or population. In addition, these studies are subject to selection bias because they evaluated only hospitalized patients. Recent changes in health care delivery in the United States, with a shift toward shorter hospitalizations and an increased use of home health care, have led to a change in the spectrum of infections seen in the community.

We conducted active, population-based laboratory surveillance for candidemia in 2 areas of the United States to develop a better understanding of its public health burden and epidemiological features. In addition to providing accurate information on disease incidence and trends both in the population as a whole and in specific risk groups, this approach also captures reports of infections that occur outside the hospital and so avoids the bias that results from including only selected referral institutions. Furthermore, analysis of a population-based collection of isolates provides more precise and more representative estimates of species distribution and the incidence of antifungal drug resistance within the population surveyed. We report the results of this surveillance and discuss the implications of the changing epidemiology of candidemia.

Previous SectionNext Section

Methods

Surveillance for candidemia was conducted in conjunction with Emory University School of Medicine and the Department of Veterans Affairs Medical Center in Atlanta, and with the Western Consortium for Public Health in San Francisco as part of an active population-based laboratory surveillance for invasive bacterial and mycotic infections, which has been previously described [7]. For this study, the surveillance area consisted of the San Francisco Bay Area in California (Alameda, Contra Costa, and San Francisco counties; population 2,877,078) and the metropolitan Atlanta area (Fulton, DeKalb, Cobb, Gwinnett, Clayton, Douglas, Newton, and Rockdale counties; population 2,468,387). Surveillance was conducted prospectively for 24 months from 1 January 1992 to 31 December 1993. Reporting facilities consisted of all hospitals, as well as private and public reference laboratories in the surveillance areas, which included 28 small (<200 beds) non-teaching hospitals, 20 large (⩾200 beds) non-teaching hospitals, 31 small teaching hospitals, and 8 large teaching hospitals (a total of 77 participating laboratories).

An incident case of candidemia was defined by the first isolation of any Candida species from a blood culture from a resident of one of the surveillance areas. For patients who had more than one episode of candidemia, the second episode was defined as incident if it occurred at least 2 months after the first. Surveillance staff received standardized reports of all bloodstream Candida isolates biweekly from laboratory contacts in each surveillance area. Laboratory records of all hospitals in the surveillance areas were audited every 6–12 months to estimate completeness of reporting and to detect additional cases. Cases found after audits were added to the analysis, so that this surveillance captured virtually 100% of candidemia cases reported in the surveillance areas. Medical records were reviewed to obtain data regarding demographics, underlying medical conditions, and outcome (defined as survival or death within 30 days after the incident candidemia episode). Data on premature births and neonatal complications were not part of the coded data collection instrument but were often reported in the “comments” field.

The number of days of hospitalization before onset of candidemia (patient-days) was calculated as the difference between the date of admission and the collection date of a blood sample that yielded positive results on culture. Patients whose blood yielded Candida organisms on culture either prior to or on the day of hospital admission were classified as having outpatient-acquired candidemia. Patients who developed candidemia ⩾1 day after hospitalization were classified as having inpatient-acquired candidemia. For neonates (aged ⩽30 days), the duration of hospitalization before illness was defined as the period between birth and collection of the first blood sample that yielded positive results on culture.

Statistical methods. Statistical analyses were done with Epi-Info version 6.02 [8]. δ2 tests were used to test for significant associations between defined variables.

Crude age-, sex-, and race-specific incidences were calculated for each surveillance area by using 1990 population data from the U.S. Bureau of the Census. For calculation of incidence among neonates, the population denominator of the 0- to 12-month age group was divided by 12. The estimated prevalence of human immunodeficiency virus (HIV) infection was available for the San Francisco area only (1.28%) and was obtained from the Department of Health Services, Office of AIDS (Sacramento, CA). The number of persons with cancer for 1992–1993 was available for California only and was provided by the Northern California Cancer Center (Union City, CA). Estimated numbers of persons with adult-diagnosed diabetes in each state were provided by the Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention (CDC, Atlanta, GA). County-specific vital statistics data were used to obtain denominator data for neonates. The annual rates of disease incidence for specific groups were calculated by dividing the number of candidemia patients with a given underlying medical condition by the total estimated population with the same underlying disease in our surveillance sites.

Microbiological methods. Detection and species determination of isolates were performed in the submitting laboratories according to their standard protocols. Personnel in participating laboratories were then asked to send all Candida isolates obtained from blood samples to CDC, where species confirmation was done by use of standard identification methods [9]. CDC-confirmed species identification was used when available. In cases in which isolates were not sent to CDC, species identification provided by the referring laboratory was used. Antifungal susceptibility testing was done at the University of Iowa by broth microdilution to determine minimum inhibitory concentrations (MICs) for flucytosine, fluconazole, and itraconazole, according to the guidelines of the National Committee for Clinical Laboratory Standards (NCCLS) [10]. The Etest method with RPMI 1640 agar medium was used for amphotericin B [11, 12].

Previous SectionNext Section

Results

A total of 837 incident cases of candidemia were identified in Atlanta and San Francisco between January 1992 and December 1993 (table 1). The average annual incidence of candidemia in the 2 sites was 8 cases per 100,000 population. There was no statistically significant difference in the average annual incidence between Atlanta (8.7 per 100,000) and San Francisco (7.1 per 100,000). The number of incident cases of candidemia due to any Candida species increased slightly from 1992 (406 cases) to 1993 (430 cases) but was not statistically significant (P = .4). The proportion of incident cases of candidemia due to a Candida species other than C. albicans increased by ∼7% (179 [44%] of 406 in 1992 vs. 218 [51%] of 430 in 1993; P = .06). Figure 1 summarizes the incidences of candidemia by race, sex and age group. The incidence of candidemia was highest among blacks (RR, 2.0; 95% CI, 1.7–2.3), among males (RR, 1.5; 95% CI, 1.3–1.7), and among persons ⩽1 year old (table 1). Incidence was twice as high among blacks of all age groups (figure 1) and 4× higher among black infants (0–12 months) than among white infants (165 vs. 41 per 100,000). No seasonal clustering of candidemia was detected at either site. Outcome information was available for 741 patients, of whom 240 (29%) died.

Figure 1
View larger version:
Figure 1

Incidence of candidemia cases, by race and age, selected US counties, California and Georgia, 1992–1993. Age- and race-specific rates were calculated by use of 1992 population data from US Bureau of Census.

Table 1
View larger version:
Table 1

Numbers and rates of incident candidemia cases by race, sex, and age in selected US counties, 1992–1993.

Species distribution.C. albicans was present in 52% of cases and was the most common species recovered, regardless of a patient's underlying clinical condition. Candida parapsilosis was recovered from 21% of isolates, followed by Candida glabrata (12%), Candida tropicalis (10%), Candida krusei (4%), Candida guilliermondii (2%), Candida lusitaniae (0.6%), and 0.1% (1 isolate each) for Candida famata, Candida lambica, Candida kefyr, and Candida sonorensis. No cases of Candida dubliniensis were identified within the isolates analyzed at CDC on the basis of biochemical criteria [13].

Species confirmation of 394 isolates from 375 patients (45% of reported cases) was performed at CDC. The misidentification rate (submitting laboratory identification vs. CDC identification) was 8%. The most commonly misidentified species was C. parapsilosis. Fifteen C. parapsilosis isolates were misidentified as any of 6 different species, most commonly as C. albicans (8 isolates). Conversely, 8 isolates of 4 different species were submitted to CDC as C. parapsilosis. Misidentifications were not linked to any particular submitting laboratory.

Underlying medical conditions.Table 2 summarizes the distribution of underlying medical conditions within this population of patients with candidemia. At least one underlying medical condition was identified in 753 cases of candidemia (90%). Cancer was the most common underlying condition (215 cases; 25.6% of total), and one-fourth of these cancers were hematologic. The average annual incidence of candidemia in cancer patients in California (the only site where denominator data were available) was 71 per 100,000 population, almost 10 times the rate of disease in the San Francisco surveillance area. Among adults (⩾18 years old) with diabetes who lived in the surveillance areas, the average annual incidence of candidemia was 28 per 100,000 population.

Table 2
View larger version:
Table 2

Underlying medical conditions among all patients with candidemia (n = 837).

HIV infection or AIDS was present in 82 cases (10% of total). In the San Francisco area, the estimated incidence of disease among HIV-infected persons was 72 per 100,000 population. Among all HIV-infected persons with candidemia, iv drug use was reported for 12% and cancer for 20%. C. albicans was identified in 50% of candidemias in the HIV-infected group, C. glabrata in 18%, C. parapsilosis in 12%, and C. krusei in 7%.

C. tropicalis infection was most often seen in persons with cancer (46% of cases of candidemia due to C. tropicalis) and diabetes mellitus (24% of cases due to C. tropicalis). Candidemia due to C. guilliermondii was more common in patients who had had cardiothoracic or abdominal surgery in the 2 months before fungal diagnosis (30% of the 11 cases due to C. guilliermondii). Of 15 patients infected with C. krusei, 6 (40%) were HIV-positive and 5 (33%) had cancer.

Candidemia in neonates. Of the 837 cases of candidemia, 60 (7.2%) occurred in neonates, for a rate of 466 per 100,000 neonates. The incidence of candidemia in neonates increased 2-fold between 1992 and 1993. The majority of neonates with candidemia were black (55%), and the average annual incidence of candidemia was approximately 4× higher among black than white neonates (960 vs. 238 per 100,000). Eighty-three percent of neonates had been in the hospital for >72 hours at the time of candidemia, with a median hospitalization of 20 days (range, 4–40 days). Thirty-five percent of neonates (21 of 60) were reported as having been born prematurely (23–28 weeks' gestation), and 10 (16%) died. Reported neonatal complications included low birth weight, short-gut syndrome, and respiratory failures. C. albicans was isolated in 53% of neonatal candidemias and C. parapsilosis in 45%.

Outpatient-acquired versus inpatient-acquired candidemia. Of the 837 cases, 772 (92%) were in hospitalized patients. Table 3 describes the characteristics of 155 patients (20.2% of the 767 hospitalized patients for whom admission dates were available) who had positive blood cultures either prior to (21 patients, 2.7% of hospitalized group) or on the day of hospital admission (134 patients, 17.4% of hospitalized group). The demographic and clinical characteristics of these patients were very similar to those of the rest of the study population, with cancer (25% of cases), diabetes (14%), and HIV infection (12%) the most commonly reported underlying diseases (table 3). Species other than C. albicans were found to be significantly associated with outpatient-acquired candidemia (P < .05). In particular, half of candidemias acquired outside the hospital were caused by 3 non–C. albicans species: C. parapsilosis (26% of outpatients), C. glabrata (16%), and C. tropicalis (7%).

Table 3
View larger version:
Table 3

Characteristics of patients with candidemia from whom culture of blood yielded positive results prior to or on day of admission (outpatients) and those with positive cultures ⩾1 day after admission (inpatients).

Of the 772 hospitalized patients, 551 (71%; 66% of total cases) had been in the hospital for at least 3 days when candidemia developed. For this group, the median duration of hospitalization before diagnosis of candidemia was 15 days (range, 1–221 days).

Antifungal susceptibility testing. Amphotericin B, flucytosine, fluconazole, and itraconazole MICs are shown in table 4. Susceptibility testing was done on 394 isolates from 375 patients (45% of reported cases). The data are reported as the concentrations of each antifungal agent necessary to inhibit 50% (MIC50) and 90% (MIC90) of isolates. Some of these results have been reported elsewhere [14].

Table 4
View larger version:
Table 4

In vitro susceptibilities of Candida isolates obtained from blood to amphotericin B, flucytosine, fluconazole, and itraconazole.

Only 2 isolates of C. albicans, both collected from the same patient on the same day, were resistant to fluconazole (MIC, ⩾64 μg/mL); one of these isolates was also resistant to itraconazole (MIC, ⩾1 μg/mL). C. tropicalis and C. parapsilosis were also generally susceptible to these azole drugs (table 4). One isolate of C. tropicalis was resistant to both fluconazole (MIC, 256 μg/mL) and itraconazole (MIC, 16 μg/mL), whereas one isolate was resistant to itraconazole only (MIC, 1 μg/mL). One isolate of C. parapsilosis was resistant to itraconazole (MIC, 2 μg/mL) but displayed dose-dependent susceptibility (MIC, 32 μg/mL) to fluconazole. A higher proportion of C. glabrata and C. krusei isolates were resistant to the triazoles (table 4), as has been previously noted [15]. Itraconazole was more active against C. krusei (MIC90, 0.5 μg/mL) than against C. glabrata (MIC90, 4.0 μg/mL). No differences between the 2 geographic areas were seen in the distributions of MIC values.

Previous SectionNext Section

Discussion

This report emphasizes the substantial public health burden of candidemia. In addition to being associated with high mortality, candidemia occurred at an annual incidence of 8 per 100,000 population, a rate higher than that of various serious invasive bacterial or fungal infections, such as invasive meningococcal disease (1 per 100,000 population [16]), invasive group B streptococcal disease (6.4 per 100,000 population [17]), or cryptococcosis (up to 6.7 per 100,000 population [18]). This study highlights the importance of candidemia among persons not hospitalized and persons infected with HIV, in addition to the well-known high-risk groups, such as patients with cancer. Furthermore, it emphasizes the seriousness and magnitude of candidemia in neonates and confirms previous reports of the increasing proportion of non–C. albicans species as agents of candidemia.

Nearly half these cases of bloodstream infections due to Candida species were caused by non–C. albicans species. The emergence of non–C. albicans species, particularly C. krusei and C. glabrata, as agents of candidemia has been attributed to the increasing use of azole drugs and the resulting selection of species less susceptible to these agents [19, 20]. This study provides a historical perspective of the patterns of resistance among Candida species in the early 1990s. Overall, the in vitro susceptibility results for amphotericin B, flucytosine, and fluconazole for this group of isolates were consistent with other studies of isolates of Candida obtained from blood [21–23]. In this study, we document amphotericin B MICs ranging from 0.016 to 6 μg/mL, with 7% of isolates demonstrating potential resistance at concentrations of ⩾2.0 μg/mL. Only 6% of isolates in this study were resistant to flucytosine (MIC, ⩾32 μg/mL) [10]. Notably, a pattern of decreased susceptibility (relative to other species of Candida) to both amphotericin B (MIC90, 6.0 μg/mL) and flucytosine (MIC90, 32 μg/mL) was noted for C. krusei (table 4): 70% of C. krusei isolates were inhibited by amphotericin B at ⩾2 μg/mL and 80% were inhibited by flucytosine at ⩾32 μg/mL. The decreased susceptibility of C. krusei to both amphotericin B and flucytosine, although not widely appreciated, was consistent with previous reports for this organism [15, 21, 22, 24]. The clinical significance of these in vitro data is unclear at present; Goldman et al. [25] found that response rates of C. krusei infection were significantly better among patients who received amphotericin B in doses of >1 mg/kg of body weight per day than among patients who had received lower doses. Taken together, these data suggest that C. krusei may merit consideration as a multiply-resistant fungal pathogen [24].

The low levels of azole resistance in vitro observed for C. tropicalis and C. parapsilosis suggest that the emergence of non–C. albicans species may be mediated by one or more confounding risk factors in addition to selection for species not susceptible to azole drugs. The establishment of NCCLS-standardized methods for yeast susceptibility testing has improved our knowledge about susceptibility patterns among Candida species. However, data correlating MIC results with clinical outcome in candidemia are still limited [26], so that the application of in vitro results to clinical management remains difficult. Studies to understand this correlation better will be necessary, as will continuing surveillance to monitor fungal resistance patterns.

The observation that nearly one-fifth of bloodstream infections due to Candida species developed in persons before or on the day of hospital admission underscores how changing patterns of health care delivery in the United States are resulting in increasing numbers of nonhospitalized persons who are at risk for candidemia. The demographic and clinical characteristics of these patients were similar to those of patients who developed candidemia while hospitalized, which suggests that they have similar risk factors. Half of the outpatient candidemias were caused by 3 non–C. albicans species, the most common of which, C. parapsilosis, has been associated with intravascular catheters and parenteral alimentation [27–29]. Further studies, particularly studies evaluating outpatient therapies and invasive procedures, could help clarify the occurrence of disease caused by particular Candida species. Many candidemias in the outpatient population would not have been detected through routine surveillance for nosocomial diseases, a fact that highlights one advantage of population-based surveillance.

The high incidence of bloodstream infections due to Candida among infants is consistent with previous studies, in which risk factors identified for candidemia in neonates included low birth weight [30, 31], the use of intravascular catheters [32, 33], complications associated with prematurity, and fungal colonization following vaginal deliveries [34]. The discrepancy between rates of infection in black and white infants may be partly due to the elevated incidence of prematurity and low birth weight among black infants [35, 36]. In this study, 31% of neonates ⩽7 days old with candidemia were diagnosed within 2 days of birth, which suggests possible intrapartum transmission. This study also found that, unlike other non–C. albicans species, C. parapsilosis was recovered in 45% of cases candidemia in neonates. Although C. parapsilosis has been increasingly associated with neonatal sepsis [6, 31], its prevalence among neonates is not well understood, and nosocomial transmission in intensive care nurseries has been suggested [6]. Further risk factor and molecular subtyping studies are needed to analyze the epidemiological features of neonatal candidemia and to develop approaches to prevention.

HIV infection was reported as the underlying illness in 10% of all patients with candidemia. Although this finding may be a reflection of the high HIV prevalence in the 2 study areas, candidemia has not been widely recognized as a serious problem in HIV-infected persons. Disseminated candidiasis, including fungemia, has been described among HIV-infected children [37] but rarely in adults. A recent French study described 13 episodes of candidemia in patients with late-stage AIDS over a 5-year period but did not report the proportion of AIDS patients who developed this complication [38]. Risk factors for candidemia in these persons, in particular iv antibiotics, hyperalimentation, and long-term indwelling venous catheters, may be similar to those in other immunocompromised persons. However, in this study, a large proportion of HIV-infected persons with candidemia were not hospitalized at the time of diagnosis, which again suggests the need for a better understanding of risk factors for candidemia in immunocompromised outpatients.

Although a number of risk factors for candidemia have been identified, consensus on appropriate prevention measures has not been achieved to date. Suggested measures for management of central or peripheral iv catheters are still controversial [39–42]. Strategies such as decreasing the number of antibiotics prescribed and instituting triazole chemoprophylaxis for high-risk groups [43] have been suggested but have not been widely implemented. A panel of experts gathered to review management and prevention of severe Candida infections developed consensus on some prevention measures (e.g., the use of antifungal agents for chemoprophylaxis) [44], but the data available to formulate these recommendations were limited and often controversial. The effectiveness of prevention measures for candidemia, as well as the cost-effectiveness and potential complications of such measures, require further evaluation. In particular, the role of azole chemoprophylaxis in development of drug resistance in C. albicans and in emergence of less-susceptible fungal pathogens needs to be examined. Continued surveillance of candidemia will be important to track trends of this serious infection and to document changes in its epidemiological features.

Previous SectionNext Section

Acknowledgments

We thank personnel in the CDC Fungal Reference Laboratory for their contributions to this study; Associations of Schools of Public Health Fellowship Program; Gwendolyn Smith for contributing to laboratory data management; and gratefully acknowledge the many participants in the CDC Fungal Active Surveillance, who collected isolates for this study.

Previous SectionNext Section

Footnotes

  • Financial support: Associations of Schools of Public Health (Public Health System Fellowship Program SD-15/15-CID96-001 to A.S.K.).

  • Received January 28, 1999.
  • Revision received June 17, 1999.
Previous Section
 

References

  1. ↵
    1. Wenzel RP,
    2. Pfaller MA
    . Candida species: emerging hospital bloodstream pathogens. Infect Control Hosp Epidemiol 1991;12:523-4.
    MedlineWeb of Science
  2. ↵
    1. Fridkin SK,
    2. Jarvis WR
    . Epidemiology of nosocomial fungal infections. Clin Microbiol Rev 1996;9:499-511.
    Abstract/FREE Full Text
  3. ↵
    1. Beck-Sague CM,
    2. Jarvis W
    . National Nosocomial Infections Surveillance System. Secular trends in the epidemiology of nosocomial fungal infections in the United States, 1980–1990. J Infect Dis 1993;167:1247-51.
    Abstract/FREE Full Text
  4. ↵
    1. Pfaller MA
    . Nosocomial candidiasis: emerging species, reservoirs, and modes of transmission. Clin Infect Dis 1996;(22(suppl)):S89-94.
    1. Pittet D,
    2. Wenzel RP
    . Nosocomial bloodstream infections. Arch Intern Med 1995;155:1177-84.
    Abstract/FREE Full Text
  6. ↵
    1. Pfaller MA,
    2. Messer SA,
    3. Houston A,
    4. et al
    . National epidemiology of mycoses survey: a multicenter study of strain variation and antifungal susceptibility among isolates of Candida species. Diagn Microbiol Infect Dis 1998;31:289-96.
    CrossRefMedlineWeb of Science
  7. ↵
    1. Rees JR,
    2. Pinner RW,
    3. Hajjeh RA,
    4. Brandt ME,
    5. Reingold AL
    . The epidemiologic features of invasive mycotic infections in the San Francisco Bay Area 1992–93: results of population-based active surveillance. Clin Infect Dis 1998;27:1138-47.
    Abstract/FREE Full Text
  8. ↵
    Epi Info manual, version 6. Atlanta GA: Centers for Disease Control and Prevention; 1995.
  9. ↵
    1. Murray RP,
    2. Baron EJ,
    3. Pfaller MA,
    4. Tenover FC,
    5. Yolken RH
    1. Warren NG,
    2. Hazen KC
    . Candida, Cryptococcus, and other yeasts of medical importance. In: Murray RP, Baron EJ, Pfaller MA, Tenover FC, Yolken RH, editors. Manual of clinical microbiology. 6th ed. Washington, DC: American Society for Microbiology; 1995. p. 723-37.
  10. ↵
    Wayne, PA: National Committee for Clinical Laboratory Standards; 1997. National Committee for Clinical Laboratory Standards. Reference method for broth dilution antifungal susceptibility testing of yeast: approved standard. NCCLS document M27-A.
  11. ↵
    1. Wanger A,
    2. Mills K,
    3. Nelson PW,
    4. Rex JH
    . Comparison of E-test and National Committee for Clinical Laboratory Standards broth macrodilution method for antifungal susceptibility testing: enhanced ability to detect amphotericin B-resistant Candida isolates. Antimicrob Agents Chemother 1995;39:2520-2.
    Abstract/FREE Full Text
  12. ↵
    1. Pfaller MA,
    2. Messer SA,
    3. Bolmstrom A
    . Evaluation of E test for determining in vitro susceptibility of yeast isolates to amphotericin B. Diagn Microbiol Infect Dis 1998;32:223-7.
    CrossRefMedlineWeb of Science
  13. ↵
    1. Sullivan D,
    2. Coleman D
    . Candida dubliniensis: characteristics and identification. J Clin Microbiol 1998;36:329-34.
    FREE Full Text
  14. ↵
    1. Pfaller MA,
    2. Messer SA,
    3. Hollis RJ,
    4. et al
    . Trends in species distribution and susceptibility to fluconazole among blood stream isolates of Candida species in the United States. Diagn Microbiol Infect Dis 1999;33:217-22.
    CrossRefMedlineWeb of Science
  15. ↵
    1. Pfaller MA,
    2. Jones RN,
    3. Messer SA,
    4. Edmond MB,
    5. Wenzel RP
    . SCOPE Participant Group. National Surveillance of nosocomial blood stream infection due to species of Candida other than Candida albicans: frequency of occurrence and antifungal susceptibility in the SCOPE Program. Diagn Microbiol Infect Dis 1998;30:121-9.
    CrossRefMedlineWeb of Science
  16. ↵
    Centers for Disease Control and Prevention. Laboratory-based surveillance for meningococcal disease in selected areas-United States, 1989–91. MMWR Morb Mortal Wkly Rep 1993;42:21-30.
    Medline
  17. ↵
    Centers for Disease Control and Prevention. Group B streptococcal disease in the United States, 1990: report from a multistate active surveillance system. MMWR Morb Mortal Wkly Rep 1992;41(SS-46):25-32.
  18. ↵
    1. Hajjeh RA,
    2. Conn LA,
    3. Stephens DS,
    4. et al
    . Cryptococcosis: population-based multistate active surveillance and risk factors in human immunodeficiency virus-infected persons. J Infect Dis 1999;179:449-54.
    Abstract/FREE Full Text
  19. ↵
    1. Abi-Said D,
    2. Anaissie E,
    3. Uzun O,
    4. Raad I,
    5. Pinzcowski H,
    6. Vartivarian S
    . The epidemiology of hematogenous candidiasis caused by different Candida species. Clin Infect Dis 1997;24:1122-8.
    Abstract/FREE Full Text
  20. ↵
    1. White MH
    . The contribution of fluconazole to the changing epidemiology of invasive candidal infections. Clin Infect Dis 1997;24:1129-30.
    FREE Full Text
  21. ↵
    1. Pfaller MA,
    2. Barry AL
    . In vitro susceptibilities of clinical yeast isolates to three antifungal agents determined by the microdilution test. Mycopathologia 1995;130:3-9.
    CrossRefMedlineWeb of Science
  22. ↵
    1. Rex JH,
    2. Pfaller MA,
    3. Barry AL,
    4. Nelson PW,
    5. Webb CD
    . Antifungal susceptibility testing of isolates from a randomized multicenter trial of fluconazole versus amphotericin B as treatment of non-neutropenic patients with candidemia. Antimicrob Agents Chemother 1995;39:40-4.
    Abstract/FREE Full Text
  23. ↵
    1. Nguyen MH,
    2. Clancy CJ,
    3. Yu VL,
    4. et al
    . Do in vitro susceptibility data predict the microbiologic response to amphotericin B? Results of a prospective study of patients with Candida fungemia. J Infect Dis 1998;177:425-30.
    Abstract/FREE Full Text
  24. ↵
    1. Berrouane YF,
    2. Hollis RJ,
    3. Pfaller MA
    . Strain variation among and antifungal susceptibilities of isolates of Candida krusei. J Clin Microbiol 1996;34:1856-8.
    Abstract/FREE Full Text
  25. ↵
    1. Goldman M,
    2. Pottage JC,
    3. Weaver DC
    . Candida krusei fungemia: report of four cases and review of the literature. Medicine (Baltimore) 1993;72:143-50.
    Medline
  26. ↵
    1. Rex JH,
    2. Pfaller MA,
    3. Galgiani JN,
    4. et al
    . Development of interpretive breakpoints for antifungal susceptibility testing: conceptual framework and analysis of in vitro-in vivo correlation data for fluconazole, itraconazole, and candida infections. Clin Infect Dis 1997;24:235-47.
    Abstract/FREE Full Text
  27. ↵
    1. Weems JJ Jr,
    2. Chamberland ME,
    3. Ward J,
    4. Willy M,
    5. Padhye AA,
    6. Solomon SL
    . Candida parapsilosis fungemia associated with parenteral nutrition and contaminated blood pressure transducers. J Clin Microbiol 1987;25:1029-32.
    Abstract/FREE Full Text
    1. Solomon SL,
    2. Khabbaz RF,
    3. Parker RH,
    4. et al
    . An outbreak of Candida parapsilosis bloodstream infections in patients receiving parenteral nutrition. J Infect Dis 1984;149:98-102.
    Abstract/FREE Full Text
  29. ↵
    1. Weems JJ Jr
    . Candida parapsilosis: epidemiology, pathogenicity, clinical manifestations, and antimicrobial susceptibility. Clin Infect Dis 1992;14:756-66.
    Abstract/FREE Full Text
  30. ↵
    1. Faix RG
    . Systemic Candida infections in infants in intensive care nurseries: high incidence of central nervous system involvements. J Pediatr 1984;105:616-22.
    CrossRefMedlineWeb of Science
  31. ↵
    1. El-Mohandes AE,
    2. Johnson-Robbins L,
    3. Keiser JF,
    4. Simmens SJ,
    5. Aure MV
    . Incidence of Candida parapsilosis colonization in intensive care nursery population and its association with invasive fungal disease. Pediatr Infect Dis J 1994;13:520-4.
    MedlineWeb of Science
  32. ↵
    1. Baley JE,
    2. Kleigman RM,
    3. Fanaroff AA
    . Disseminated fungal infection in very low-birthweight infants: clinical manifestations and epidemiology. Pediatrics 1984;73:153-7.
    Abstract/FREE Full Text
  33. ↵
    1. Curry CR,
    2. Quie PG
    . Fungal septicemia in patients receiving parenteral hyperalimentation. N Engl J Med 1971;285:1221-5.
    MedlineWeb of Science
  34. ↵
    1. Reef SE,
    2. Lasker BA,
    3. Butcher DS,
    4. et al
    . Nonperinatal nosocomial transmission of Candida albicans in a neonatal intensive care unit: prospective study. J Clin Microbiol 1998;36:1255-9.
    Abstract/FREE Full Text
  35. ↵
    1. Foster HW Jr,
    2. Thomas DJ,
    3. Semenya KA,
    4. Thomas J
    . Low birthweight in African Americans: does intergenerational well-being improve outcome? J Natl Med Assoc 1993;85:516-20.
    Medline
  36. ↵
    1. Parker JD,
    2. Schoendorf KC,
    3. Kiely JL
    . Associations between measures of socioeconomic status and low birth weight, small for gestational age, and premature delivery in the United States. Ann Epidemiol 1994;4:271-8.
    Medline
  37. ↵
    1. Walsh TJ,
    2. Gonzales CE,
    3. Roilides E,
    4. et al
    . Fungemia in children infected with the human immunodeficiency virus: new epidemiologic pattern, pathogens, and improved outcome with antifungal therapy. Clin Infect Dis 1995;20:900-6.
    Abstract/FREE Full Text
  38. ↵
    1. Launay O,
    2. Lortholary O,
    3. Bouges-Michel C,
    4. Jarrousse B,
    5. Bentata M,
    6. Guillevin L
    . Candidemia: a nosocomial complication in adults with late-stage AIDS. Clin Infect Dis 1998;26:1134-41.
    Abstract/FREE Full Text
  39. ↵
    1. Dato VM,
    2. Dajani AS
    . Candidemia in children with central venous catheters: role of catheter removal and amphotericin B therapy. Pediatr Infect Dis J 1990;9:309-14.
    MedlineWeb of Science
    1. Eppes SC,
    2. Troutman JL,
    3. Gutman LT
    . Outcome of treatment of candidemia in children whose central catheters were removed or retained. Pediatr Infect Dis J 1989;8:99-104.
    CrossRefMedlineWeb of Science
    1. Lecciones JA,
    2. Lee JW,
    3. Navarro EE,
    4. et al
    . Vascular catheter-associated fungemia in patients with cancer: analysis of 155 episodes. Clin Infect Dis 1992;14:875-83.
    Abstract/FREE Full Text
  42. ↵
    1. Groeger JS,
    2. Luca AB,
    3. Thaler HT,
    4. et al
    . Infectious morbidity associated with long-term use of venous access devices in patients with cancer. Ann Intern Med 1993;119:1168-74.
    Abstract/FREE Full Text
  43. ↵
    1. Wingard JR,
    2. Vaughan WP,
    3. Braine HG,
    4. Merz WG,
    5. Saral R
    . Prevention of fungal sepsis in patients with prolonged neutropenia: a randomized, double-blind, placebo-controlled trial of intravenous miconazole. Am J Med 1987;83:1103-10.
    CrossRefMedlineWeb of Science
  44. ↵
    1. Edwards JE
    . International conference for the development of a consensus on the management and prevention of severe candidal infections. Clin Infect Dis 1997;25:43-59.
    Abstract/FREE Full Text
| Table of Contents

This Article

  1. Clin Infect Dis. (1999) 29 (5): 1164-1170. doi: 10.1086/313450
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most