Daniel K. Benjamin

Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document.

OBJECTIVES: Our objectives were to identify factors associated with the duration of the first antibiotic course initiated in the first 3 postnatal days and to assess associations between the duration of the initial antibiotic course and subsequent necrotizing enterocolitis or death in extremely low birth weight infants with sterile initial postnatal culture results. METHODS: We conducted a retrospective cohort analysis of extremely low birth weight infants admitted to tertiary centers in 1998-2001. We defined initial empirical antibiotic treatment duration as continuous days of antibiotic therapy started in the first 3 postnatal days with sterile culture results. We used descriptive statistics to characterize center practice, bivariate analyses to identify factors associated with prolonged empirical antibiotic therapy (> or =5 days), and multivariate analyses to evaluate associations between therapy duration, prolonged empirical therapy, and subsequent necrotizing enterocolitis or death. RESULTS: Of 5693 extremely low birth weight infants admitted to 19 centers, 4039 (71%) survived >5 days, received initial empirical antibiotic treatment, and had sterile initial culture results through the first 3 postnatal days. The median therapy duration was 5 days (range: 1-36 days); 2147 infants (53%) received prolonged empirical therapy (center range: 27%-85%). Infants who received prolonged therapy were less mature, had lower Apgar scores, and were more likely to be black. In multivariate analyses adjusted for these factors and center, prolonged therapy was associated with increased odds of necrotizing enterocolitis or death and of death. Each empirical treatment day was associated with increased odds of death, necrotizing enterocolitis, and the composite measure of necrotizing enterocolitis or death. CONCLUSION: Prolonged initial empirical antibiotic therapy may be associated with increased risk of necrotizing enterocolitis or death and should be used with caution.

Infections caused by antibiotic-resistant bacteria, especially the "ESKAPE" pathogens, continue to increase in frequency and cause significant morbidity and mortality. New antimicrobial agents are greatly needed to treat infections caused by gram-negative bacilli (GNB) resistant to currently available agents. The Infectious Diseases Society of America (IDSA) continues to propose legislative, regulatory, and funding solutions to this continuing crisis. The current report updates the status of development and approval of systemic antibiotics in the United States as of early 2013. Only 2 new antibiotics have been approved since IDSA's 2009 pipeline status report, and the number of new antibiotics annually approved for marketing in the United States continues to decline. We identified 7 drugs in clinical development for treatment of infections caused by resistant GNB. None of these agents was included in our 2009 list of antibacterial compounds in phase 2 or later development, but unfortunately none addresses the entire spectrum of clinically relevant GNB resistance. Our survey demonstrates some progress in development of new antibacterial drugs that target infections caused by resistant GNB, but progress remains alarmingly elusive. IDSA stresses our conviction that the antibiotic pipeline problem can be solved by the collaboration of global leaders to develop creative incentives that will stimulate new antibacterial research and development. Our aim is the creation of a sustainable global antibacterial drug research and development enterprise with the power in the short term to develop 10 new, safe, and efficacious systemically administered antibiotics by 2020 as called for in IDSA's "10 × '20 Initiative."

BACKGROUND: Neonatal candidiasis is associated with substantial morbidity and mortality rates. Neurodevelopmental follow-up data for a large multicenter cohort have not been reported. METHODS: Data were collected prospectively for neonates born at <1000 g at National Institute of Child Health and Human Development-sponsored Neonatal Research Network sites between September 1, 1998, and December 31, 2001. Uniform follow-up evaluations, including assessments of mental and motor development with the Bayley Scales of Infant Development II, were completed for all survivors at corrected ages of 18 to 22 months. We evaluated risk factors for the development of neonatal candidiasis, responses to antifungal therapy, and the association between candidiasis and subsequent morbidity and death. RESULTS: The cohort consisted of 4579 infants; 320 of 4579 (7%) developed candidiasis; 307 of 320 had Candida isolated from blood, 27 of 320 had Candida isolated from cerebrospinal fluid, and 13 (48%) of 27 of those with meningitis had negative blood cultures. In multivariate analysis of risk factors on day of life 3, birth weight, cephalosporins, gender, and lack of enteral feeding were associated with development of candidiasis. After diagnosis, most neonates had multiple positive cultures despite antifungal therapy, and 10% of neonates had candidemia for > or =14 days. Death or neurodevelopmental impairment (NDI) was observed for 73% of extremely low birth weight infants who developed candidiasis. Death and NDI rates were greater for infants who had delayed removal or replacement of central catheters (>1 day after initiation of antifungal therapy), compared with infants whose catheters were removed or replaced promptly. CONCLUSIONS: Blood cultures were negative for approximately one half of the infants with Candida meningitis. Persistent candidiasis was common. Delayed catheter removal was associated with increased death and NDI rates.