Varicella in the neonatal ICU due to the Varicella vaccine Oka strain.

BACKGROUND: Varicella vaccination of non-immune post-partum women is recommended to reduce the risk of chickenpox in mothers and their infants. Though rare, transmission of the varicella vaccine strain vOka can occur from recent vaccinees to non-immune contacts who usually develop mild chickenpox. METHODS/RESULTS: Here we describe an infant hospitalized in the neonatal ICU with vaccine-strain varicella due to transmission from their mother who received the varicella vaccine post-partum. We describe the infection prevention and control strategies implemented to prevent further transmission. CONCLUSION: Vaccine-strain varicella transmission from mother to infant is a rare event and its occurrence in the neonatal ICU setting can be challenging. Anticipatory guidance for mothers vaccinated in the postpartum period and support of parents of an infected infant are recommended.

Use of antibiotics in paediatric long-term care facilities.

BACKGROUND: Adult long-term care (LTC) facilities have high rates of antibiotic use, raising concerns about antimicrobial resistance. Few studies have examined antibiotic use in paediatric LTC facilities. AIM: To describe antibiotic use in three paediatric LTC facilities and to describe the factors associated with use. METHODS: A retrospective cohort study was conducted from September 2012 to December 2015 in three paediatric LTC facilities. Medical records were reviewed for demographics, healthcare-associated infections (HAIs), antimicrobial use and diagnostic testing. Logistic regression was used to identify predictors for antibiotic use. The association between susceptibility testing results and appropriate antibiotic coverage was determined using Chi-squared test. FINDINGS: Fifty-eight percent (413/717) of residents had at least one HAI, and 79% (325/413) of these residents were treated with at least one antibiotic course, totalling 2.75 antibiotic courses per 1000 resident-days. Length of enrolment greater than one year, having a neurological disorder, having a tracheostomy, and being hospitalized at least once during the study period were significantly associated with receiving antibiotics when controlling for facility (all P < 0.001). Diagnostic testing was performed for 40% of antibiotic-treated HAIs. Eighty-six percent of antibiotic courses for identified bacterial pathogens (201/233) provided appropriate coverage. Access to susceptibility testing was not associated with appropriate antibiotic choice (P = 0.26). CONCLUSION: Use of antibiotics in paediatric LTC facilities is widespread. There is further need to assess antibiotic use in paediatric LTC facilities. Evaluation of the adverse outcomes associated with inappropriate antibiotic use, including the prevalence of resistant organisms in paediatric LTC facilities, is critical.

Surgical site infections in a longitudinal cohort of neonatal intensive care unit patients.

OBJECTIVE: To estimate the incidence and identify risk factors for surgical site infections (SSIs) among infants in the neonatal intensive care unit (NICU). STUDY DESIGN: A prospective cohort study of infants undergoing surgical procedures from May 2009 to April 2012 in three NICUs was performed. SSI was identified if documented by an attending neonatologist and treated with intravenous antibiotics. Independent risk factors were identified using logistic regression, adjusting for NICU. RESULT: A total of 902 infants underwent 1346 procedures and experienced 60 SSIs (incidence: 4.46/100 surgeries). Risk factors for SSIs included younger chronological age (odds ratio (OR) 1.03 per day decrease, 95% confidence interval (CI) 1.01, 1.04), lower gestational age (OR 1.09 per week decrease, CI 1.02, 1.18), male sex (OR 1.17, CI 1.04, 1.34) and use of central venous catheter (OR 4.40, CI 1.19, 9.62). Only 43% had surgical site cultures obtained and Staphylococcus aureus was most commonly isolated. CONCLUSION: SSIs complicated 4.46% of procedures performed in the NICU. Although few modifiable risk factors for SSIs were identified, future efforts should focus on evaluating the impact of current prevention strategies on the incidence of neonatal SSI.

Developing clinical decision support within a commercial electronic health record system to improve antimicrobial prescribing in the neonatal ICU.

OBJECTIVE: To develop and implement a clinical decision support (CDS) tool to improve antibiotic prescribing in neonatal intensive care units (NICUs) and to evaluate user acceptance of the CDS tool. METHODS: Following sociotechnical analysis of NICU prescribing processes, a CDS tool for empiric and targeted antimicrobial therapy for healthcare-associated infections (HAIs) was developed and incorporated into a commercial electronic health record (EHR) in two NICUs. User logs were reviewed and NICU prescribers were surveyed for their perceptions of the CDS tool. RESULTS: The CDS tool aggregated selected laboratory results, including culture results, to make treatment recommendations for common clinical scenarios. From July 2010 to May 2012, 1,303 CDS activations for 452 patients occurred representing 22% of patients prescribed antibiotics during this period. While NICU clinicians viewed two culture results per tool activation, prescribing recommendations were viewed during only 15% of activations. Most (63%) survey respondents were aware of the CDS tool, but fewer (37%) used it during their most recent NICU rotation. Respondents considered the most useful features to be summarized culture results (43%) and antibiotic recommendations (48%). DISCUSSION: During the study period, the CDS tool functionality was hindered by EHR upgrades, implementation of a new laboratory information system, and changes to antimicrobial testing methodologies. Loss of functionality may have reduced viewing antibiotic recommendations. In contrast, viewing culture results was frequently performed, likely because this feature was perceived as useful and functionality was preserved. CONCLUSION: To improve CDS tool visibility and usefulness, we recommend early user and information technology team involvement which would facilitate use and mitigate implementation challenges.

Antimicrobial susceptibility and molecular typing of MRSA in cystic fibrosis.

OBJECTIVES: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients in the United States is approximately 25%. Little is known about the relative proportion of hospital- versus community-associated strains or the antimicrobial susceptibility of MRSA in different CF centers. We hypothesized that the majority of MRSA isolates obtained from children with CF are those endemic in the hospital and that those associated with community acquisition (SCCmec IV) would be more resistant than typically seen in non-CF MRSA isolates. METHODS: We studied MRSA strains from seven pediatric CF centers to determine the clonal distribution based on DNA sequencing of the staphylococcal protein A gene (spa typing), the type of staphylococcal chromosomal cassette mec (SCCmec), and the proportion of strains with Panton-Valentine leukocidin (PVL). Antimicrobial susceptibility to systemic and topical antibiotics was compared between different MRSA types. RESULTS: We analyzed 277 MRSA isolates from unique patients (mean age 11.15 ± 4.77 years, 55% male). Seventy % of isolates were SCCmec II PVL negative and the remainder SCCmec IV. Overall 17% MRSA strains were PVL positive (all SCCmec IV). Spa typing of 118 isolates showed most of the SCCmec II strains being t002, while SCCmec IV PVL positive isolates were t008, and SCCmec IV PVL negative isolates represented a variety of spa-types. The proportions of SCCmec II strains and spa-types were similar among centers. Overall rates of resistance to trimethoprim-sulfamethoxazole (4%), tetracycline (7%), tigecycline (0.4%), linezolid (0.4%) as well as fosfomycin (0.4%), fusidic acid (3%), and mupirocin (1%) were low. No strains were resistant to vancomycin. SCCmec II strains had higher rates of resistance to ciprofloxacin and clindamycin (P < 0.001) than SCCmec IV strains. CONCLUSIONS: In this U.S. study, most MRSA isolates in the pediatric CF population were SCCmec II PVL negative. Rates of resistance were low, including to older and orally available antibiotics such as trimethoprim-sulfamethoxazole.

Phase II studies of nebulised Arikace in CF patients with Pseudomonas aeruginosa infection.

RATIONALE: Arikace is a liposomal amikacin preparation for aerosol delivery with potent Pseudomonas aeruginosa killing and prolonged lung deposition. OBJECTIVES: To examine the safety and efficacy of 28 days of once-daily Arikace in cystic fibrosis (CF) patients chronically infected with P aeruginosa. METHODS: 105 subjects were evaluated in double-blind, placebo-controlled studies. Subjects were randomised to once-daily Arikace (70, 140, 280 and 560 mg; n=7, 5, 21 and 36 subjects) or placebo (n=36) for 28 days. Primary outcomes included safety and tolerability. Secondary outcomes included lung function (forced expiratory volume at one second (FEV1)), P aeruginosa density in sputum, and the Cystic Fibrosis Quality of Life Questionnaire-Revised (CFQ-R). RESULTS: The adverse event profile was similar among Arikace and placebo subjects. The relative change in FEV1 was higher in the 560 mg dose group at day 28 (p=0.033) and at day 56 (28 days post-treatment, 0.093L±0.203 vs -0.032L±0.119; p=0.003) versus placebo. Sputum P aeruginosa density decreased >1 log in the 560 mg group versus placebo (days 14, 28 and 35; p=0.021). The Respiratory Domain of the CFQ-R increased by the Minimal Clinically Important Difference (MCID) in 67% of Arikace subjects (560 mg) versus 36% of placebo (p=0.006), and correlated with FEV1 improvements at days 14, 28 and 42 (p<0.05). An open-label extension (560 mg Arikace) for 28 days followed by 56 days off over six cycles confirmed durable improvements in lung function and sputum P aeruginosa density (n=49). CONCLUSIONS: Once-daily Arikace demonstrated acute tolerability, safety, biologic activity and efficacy in patients with CF with P aeruginosa infection.

The epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in a neonatal intensive care unit, 2000-2007.

OBJECTIVE: To assess the epidemiology of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) infections in a neonatal intensive care unit (NICU). STUDY DESIGN: A retrospective chart review was conducted from 2000-2007; demographic and clinical characteristics of infected infants and crude mortality were assessed. RESULTS: During the study period, there were 123 infections caused by MSSA and 49 infections caused by MRSA. Although the types of infections caused by MSSA and MRSA were similar, infants with MRSA infections were younger at clinical presentation than infants with MSSA infections (P=0.03). The overall rate of S. aureus infections was approximately 15-30 per 1000 patient-admissions. The rate of bacteremia and skin and soft tissue infections remained stable over time. Among extremely low birth weight infants (birth weight <1000 g), 4.8 and 1.8% developed an infection caused by MSSA or MRSA, respectively. Infections occurred in a bimodal distribution of birth weight; 53% of infections occurred in extremely low birth weight infants and 27% occurred among term infants birth weight >or=2500 g, many of whom underwent surgical procedures. CONCLUSIONS: MSSA and MRSA remain significant pathogens in the NICU, particularly for extremely premature infants and term infants undergoing surgery. Further work should investigate infection control strategies that effectively target the highest risk groups and determine if vertical transmission of MRSA is responsible for the younger age at presentation of infection.

Development of a statewide collaborative to decrease NICU central line-associated bloodstream infections.

OBJECTIVE: To characterize hospital-acquired bloodstream infection rates among New York State's 19 regional referral NICUs (at regional perinatal centers; RPCs) and develop strategies to promote best practices to reduce central line-associated bloodstream infections (CLABSIs). STUDY DESIGN: During 2006 and 2007, RPC NICUs reported bloodstream infections, patient-days and central line-days to the Department of Health, and shared their results. Aiming to improve, participants created a central line-care bundle based on visiting a potentially best performing NICU and reviewing the literature. RESULT: All 19 RPCs participated in this quality initiative, contributing 218,096 patient-days and 56,911 central line-days of observation. Individual RPC nosocomial sepsis infection (NI) rates ranged from 1.0 to 5.8 NIs per 1000 patient-days (2006), and CLABSI rates ranged from 2.6 to 15.1 CLABSIs per 1000 central line-days (2007). A six-fold rate variation among RPC NICUs was observed. Participants unanimously approved a level-1 evidence-based central line-care bundle. CONCLUSION: Individual RPC rates and consequent morbidity and resource use attributable to these infections were substantial and varied greatly. No center was without infections. It is hoped that the cooperation and accountability exhibited by the RPCs will result in a major network for characterizing performance and improving outcomes.

Nosocomial transmission of Mycobacterium tuberculosis in a children's hospital.

An infant was admitted for evaluation of respiratory distress and tracheomalacia. After several weeks of hospitalization, both the infant and her mother were diagnosed with culture-positive pulmonary tuberculosis (TB). Sixteen pediatric patients and 293 health care workers were evaluated for exposure to Mycobacterium tuberculosis. Tuberculin skin test conversions occurred in 6.7% of patients and 1.9% of pediatric health care workers. While nosocomial transmission of TB is relatively rare in children's hospitals, this report highlights the differences between TB control efforts in pediatric vs. adult facilities, including the importance of screening the adult visitors of children admitted with suspected TB.

Risk factors for Candida species colonization of neonatal intensive care unit patients.

BACKGROUND: Candida spp. are increasingly important pathogens in neonatal intensive care units (NICU). Prior colonization is a major risk factor for candidemia, but few studies have focused on risk factors for colonization, particularly in NICU patients. METHODS: A prospective, multicenter cohort study was performed in six NICUs to determine risk factors for Candida colonization. Infant gastrointestinal tracts were cultured on admission and weekly until NICU discharge and health care worker hands were cultured monthly for Candida spp. RESULTS: The prevalence of Candida spp. colonization was 23% (486 of 2157 infants); 299 (14%), 151 (7%) and 74 (3%) were colonized with Candida albicans, Candida parapsilosis and other Candida spp., respectively. Multiple logistic regression analysis adjusting for length of stay, birth weight < or = 1000 g and gestational age < 32 weeks revealed that use of third generation cephalosporins was associated with either C. albicans (155 incident cases) or C. parapsilosis (104 incident cases) colonization. Use of central venous catheters or intravenous lipids were risk factors for C. albicans, whereas delivery by cesarean section was protective. Use of H2 blockers was an independent risk factor for C. parapsilosis. Of 2989 cultures from health care workers' hands, 150 (5%) were positive for C. albicans and 575 (19%) for C. parapsilosis, but carriage rates did not correlate with NICU site-specific rates for infant colonization. CONCLUSIONS: We speculate that NICU patients acquire Candida spp., particularly C. parapsilosis, from the hands of health care workers. H2 blockers, third generation cephalosporins and delayed enteral feedings alter gastrointestinal tract ecology, thereby facilitating colonization.

Plesiomonas shigelloides sepsis and splenic abscess in an adolescent with sickle-cell disease.

Plesiomonas shigelloides is a rare cause of self-limiting gastroenteritis. We report a case of extraintestinal P. shigelloides infection in an adolescent with sickle-cell disease who presented with bacteremia complicated by a splenic abscess. Despite the high mortality rate reported in extraintestinal P. shigelloides infection, the patient survived after drainage of the abscess and treatment with antibiotics.

Identification and antimicrobial susceptibility of Alcaligenes xylosoxidans isolated from patients with cystic fibrosis.

In the past decade, potential pathogens, including Alcaligenes species, have been increasingly recovered from cystic fibrosis (CF) patients. Accurate identification of multiply antibiotic-resistant gram-negative bacilli is critical to understanding the epidemiology and clinical implications of emerging pathogens in CF. We examined the frequency of correct identification of Alcaligenes spp. by microbiology laboratories affiliated with American CF patient care centers. Selective media, an exotoxin A probe for Pseudomonas aeruginosa, and a commercial identification assay, API 20 NE, were used for identification. The activity of antimicrobial agents against these clinical isolates was determined. A total of 106 strains from 78 patients from 49 CF centers in 22 states were studied. Most (89%) were correctly identified by the referring laboratories as Alcaligenes xylosoxidans. However, 12 (11%) strains were misidentified; these were found to be P. aeruginosa (n = 10), Stenotrophomonas maltophilia (n = 1), and Burkholderia cepacia (n = 1). Minocycline, imipenem, meropenem, piperacillin, and piperacillin-tazobactam were the most active since 51, 59, 51, 50, and 55% of strains, respectively, were inhibited. High concentrations of colistin (100 and 200 microg/ml) inhibited 92% of strains. Chloramphenicol paired with minocycline and ciprofloxacin paired with either imipenem or meropenem were the most active combinations and inhibited 40 and 32%, respectively, of strains. Selective media and biochemical identification proved to be useful strategies for distinguishing A. xylosoxidans from other CF pathogens. Standards for processing CF specimens should be developed, and the optimal method for antimicrobial susceptibility testing of A. xylosoxidans should be determined.

Prevalence of infectious diseases among internationally adopted children.

OBJECTIVE: Internationally adopted children are at increased risk of infections acquired in their country of origin. Ongoing surveillance of this unique population is needed to detect changing epidemiology and provide appropriate care. METHODS: We performed a retrospective cohort study of 504 children adopted from abroad and evaluated from 1997 to 1998 to determine the prevalence of and factors associated with various infectious diseases. RESULTS: The mean age of the study participants at medical evaluation was 1.6 years; 71% were girls, and they were adopted from 16 countries, including China (48%), Russia (31%), Southeast Asia (8%), Eastern Europe (8%), and Latin America (5%). Overall, 75 (19%) of 404 children tested had tuberculin skin tests >/=10 mm, but all had normal chest radiographs. BCG vaccination (odds ratio [OR]: 7.37; 95% confidence interval [CI]: 3.29, 17.16) and being Russian born (OR: 2.90; 95% CI: 1.68, 5.00) were risk factors for latent tuberculosis infection. Fourteen (2.8%) children had detectable hepatitis B surface antigen, but no child had active hepatitis C, human immunodeficiency virus, or syphilis. Giardia lamblia antigen was detected in 87 (19%) of 461 tested children, and such children were older (mean: 22 months vs 15.5 months) and more likely to have been born in Eastern Europe (OR: 2.82; 95% CI: 1.70, 4.68). CONCLUSIONS: We demonstrated increased rates of latent tuberculosis infection and G lamblia infection than previously reported. Thus, ongoing surveillance of internationally adopted children, international trends in infectious diseases, and appropriate screening will ensure the long-term health of adopted children as well as their families.

Cathelicidin peptides inhibit multiply antibiotic-resistant pathogens from patients with cystic fibrosis.

Endogenous peptide antibiotics are under investigation as inhaled therapeutic agents for cystic fibrosis (CF) lung disease. The bactericidal activities of five cathelicidin peptides (LL37 [human], CAP18 [rabbit], mCRAMP [mouse], rCRAMP [rat], and SMAP29 [sheep]), three novel alpha-helical peptides derived from SMAP29 and termed ovispirins (OV-1, OV-2, and OV-3), and two derivatives of CAP18 were tested by broth microdilution assays. Their MICs were determined for multiply antibiotic-resistant Pseudomonas aeruginosa (n = 24), Burkholderia cepacia (n = 5), Achromobacter xylosoxidans (n = 5), and Stenotrophomonas maltophilia (n = 5) strains isolated from CF patients. SMAP29 was most active and inhibited mucoid and nonmucoid P. aeruginosa strains (MIC, 0.06 to 8 microg/ml). OV-1, OV-2, and OV-3 were nearly as active (MIC, 0.03 to 16 microg/ml), but CAP18 (MIC, 1.0 to 32 microg/ml), CAP18-18 (MIC, 1.0 to >32 microg/ml), and CAP18-22 (MIC, 0.5 to 32 microg/ml) had variable activities. LL37, mCRAMP, and rCRAMP were least active against the clinical isolates studied (MIC, 1.0 to >32 microg/ml). Peptides had modest activities against S. maltophilia and A. xylosoxidans (MIC range, 1.0 to > 32 microg/ml), but none inhibited B. cepacia. However, CF sputum inhibited the activity of SMAP29 substantially. The effects of peptides on bacterial cell membranes and eukaryotic cells were examined by scanning electron microscopy and by measuring transepithelial cell resistance, respectively. SMAP29 caused the appearance of bacterial membrane blebs within 1 min, killed P. aeruginosa within 1 h, and caused a dose-dependent, reversible decrease in transepithelial resistance within 5 h. The tested cathelicidin-derived peptides represent a novel class of antimicrobial agents and warrant further development as prophylactic or therapeutic agents for CF lung disease.

Observational study of the use of infection control interventions for Mycobacterium tuberculosis in pediatric facilities.

INTRODUCTION: Hospital transmission of Mycobacterium tuberculosis (TB) is a problem in US facilities where adults are treated. However, specific guidelines for facilities in which pediatric patients are cared for have never been defined, nor has any study attempted to assess pediatric health care worker (HCW) compliance with TB infection control (IC) guidelines. METHODS: An observational study was performed in two pediatric inpatient hospitals from May, 1996, to December, 1997. A trained observer tallied persons (i.e. professional HCWs, ancillary HCWs and non-HCWs) entering and leaving occupied TB isolation rooms and recorded adherence with IC practices (e.g. proper use of respirators, prompt door closures, door signage). RESULTS: Thirty children with confirmed or suspected TB were admitted during the study period and observed for a total of 242 h during which 656 visits by professional (n = 391) and ancillary (n = 131) HCWs and by family members (n = 134) were recorded. During 30% of visits doors remained open an average of 10 min, and during 20% of visits no respiratory protection was worn. In all, visitors wore the correct respiratory protection appropriately only 55% of the time. HCWs were more likely to wear respiratory protection when caring for children with a positive acid-fast bacillus smear than family members, but professional staff were no more likely than ancillary staff to do so. CONCLUSIONS: This is the first study to quantify compliance with IC practices for TB in pediatric hospitals. The majority of visitors entering TB isolation rooms occupied by children with confirmed or suspected TB complied with IC guidelines, but discrepancies were seen. Rather than relying on TB IC guidelines designed for adult facilities, guidelines specific for pediatric facilities that consider the local epidemiology of TB should be developed.

Persistence of immunity to varicella-zoster virus after vaccination of healthcare workers.

OBJECTIVE: Varicella-zoster virus (VZV) vaccine is recommended to protect susceptible healthcare workers (HCWs) from serious disease and to prevent nosocomial spread of VZV. We evaluated clinical outcomes and serological responses in HCWs after immunization with live attenuated VZV vaccine. DESIGN: Vaccinees were immunized from 1979 to 1998 during VZV vaccine trials, as well as after licensure, and followed prospectively for 1 month to 20.6 (mean 4.6) years after vaccination. Sera were tested by fluorescent antibody to membrane antigen (FAMA), latex agglutination (LA), and enzyme-linked immunoassay (EIA) to detect VZV-specific antibodies. STUDY PARTICIPANTS: The median age of the 120 HCWs was 26 years; 51 (42%) were males. INTERVENTIONS: Ninety eight (82%) of these study subjects received vaccine prepared by Merck and 22 (18%) by SmithKline Beecham; 25, 81, and 14 vaccinees received one dose, two doses, and three doses, respectively. RESULTS: The crude attack rate was 10%; 12 of 120 HCWs developed chickenpox 6 months to 8.4 years after vaccination. The attack rates following household and hospital exposures were 18% (4/22) and 8% (6/72), respectively. All resulting illness was mild to moderate (mean 40 vesicles). Seroconversion after vaccination was documented by FAMA in 96% of HCWs, although 31% lost detectable antibodies. Compared with FAMA, LA and EIA were 82% and 74% sensitive and 94% and 89% specific, respectively. CONCLUSIONS: The VZV vaccine effectively protected HCWs from varicella, particularly from serious disease. Currently available serological tests are not optimal, and improved assays are needed.

Nosocomial rotavirus in a pediatric hospital.

We describe a nosocomial rotavirus outbreak among pediatric cardiology patients and the impact of a prospective, laboratory-based surveillance program for rotavirus in our university-affiliated, quartenary-care pediatric hospital in New York City. Improved compliance with infection control and case-finding among patients and healthcare workers halted the outbreak.

Comparison of two commercial systems (Vitek and MicroScan-WalkAway) for antimicrobial susceptibility testing of Pseudomonas aeruginosa isolates from cystic fibrosis patients.

Antimicrobial susceptibility testing of cystic fibrosis (CF) isolates of Pseudomonas aeruginosa is difficult because the organisms are often mucoid and slow-growing. This study of 498 CF strains examined the correlation of results derived from two commonly used commercial systems (Vitek, MicroScan-WalkAway) with a reference method for 10 antimicrobials. Correlation to reference results was unacceptably low for all agents and both commercial systems had a high rate of very major (false-susceptible) errors. Although mucoid strains produced a 4.8% greater intermethod error, it was not markedly different than non-mucoid strains for the Vitek System. Overall, these tested commercial systems performed poorly for CF isolates in contrast to earlier reported, high correlations with the reference methods (broth microdilution frozen panels and agar dilution) of the National Committee for Clinical Laboratory Standards, the standardized disk diffusion test, and the Etest (AB BIODISK, Solna, Sweden).

Risk factors for candidal bloodstream infections in surgical intensive care unit patients: the NEMIS prospective multicenter study. The National Epidemiology of Mycosis Survey.

To assess risk factors for development of candidal blood stream infections (CBSIs), a prospective cohort study was performed at 6 sites that involved all patients admitted to the surgical intensive care unit (SICU) for >48 h over a 2-year period. Among 4276 such patients, 42 CBSIs occurred (9.82 CBSIs per 1000 admissions). The overall incidence was 0.98 CBSIs per 1000 patient days and 1.42 per 1000 SICU days with a central venous catheter in place. In multivariate analysis, factors independently associated with increased risk of CBSI included prior surgery (relative risk [RR], 7.3), acute renal failure (RR, 4.2), receipt of parenteral nutrition (RR, 3.6), and, for patients who had undergone surgery, presence of a triple lumen catheter (RR, 5.4). Receipt of an antifungal agent was associated with decreased risk (RR, 0.3). Prospective clinical studies are needed to identify which antifungal agents are most protective and which high-risk patients will benefit from antifungal prophylaxis.