Fluconazole for prophylaxis against candidal rectal colonization in the very low birth weight infant.

BACKGROUND: Candidal infections are an important cause of morbidity and mortality in the very low birth weight (VLBW) infant. Current intervention focuses on treatment once candidal septicemia is either suspected or diagnosed. Studies have suggested that colonization with candidal species is an important risk factor for subsequent infection. OBJECTIVE: To determine whether prophylactic fluconazole for the first 28 days of life results in a decreased incidence of candidal colonization in the VLBW infant. RESEARCH DESIGN: Prospective, randomized, controlled, intention-to-treat design comparing prophylaxis with fluconazole versus placebo for the first 28 days of life. SETTING: A tertiary level intensive care nursery in a major teaching hospital in Charleston, South Carolina. PATIENTS: One hundred three infants with a birth weight of <1500 g, either inborn or outborn, who were admitted to the intensive care nursery between January 1998 and February 1999. METHODS: Infants were enrolled within 72 hours of life with rectal cultures performed on the day of randomization (DOR), as well as day of life (DOL) 7, 14, and 28. Those infants with a birth weight of <1250 g had additional cultures on DOL 35, 49, and 56. Cultures were plated on selective media for isolation of candidal organisms. Infants were randomized to receive either fluconazole (6 mg/kg) or placebo on the DOR. Subsequent doses were given every 72 hours until DOL 7 and then every 24 hours until DOL 28. Medication was given either intravenously or by feeding tube once the infant had been gavage feeding for a 48-hour period without feeding intolerance. Aspartate aminotransferase and alanine aminotransferase levels were obtained on DOR and DOL 7, 14, and 28 to assess for fluconazole toxicity. The minimal inhibitory concentration to fluconazole was determined for all positive cultures to assess the development of resistance. RESULTS: The infants who received fluconazole (n = 53) and placebo (n = 50) had no statistical difference in the major risk factors known to increase the chances of candidal septicemia in the VLBW infant. Rectal colonization by candidal species was detected in 8 of the 53 fluconazole-treated patients (15.1%) and in 23 of the 50 infants treated with placebo (46%). Fluconazole significantly reduced rectal colonization from DOL 14 through DOL 56 in all infants with a birth weight of <1250 g, and from DOL 14 through DOL 56 in all infants with a birth weight of 1250 to 1500 g. Alanine aminotransferase levels were higher in the fluconazole versus the placebo-treated group on DOL 14 (18.1 IU/L vs 15 IU/L), but no clinically significant abnormalities were observed. Candida albicans was the most common species isolated. There was no increase in species of Candida noted for their intrinsic resistance to fluconazole, and there was no statistically significant difference in the minimal inhibitory concentrations to fluconazole for all C albicans isolates in either group at any period. CONCLUSION: Prophylactic administration of fluconazole to the VLBW infant for the first 28 days of life is safe and results in a decreased risk of rectal colonization by candidal species. Larger studies to determine the effect of prophylaxis on candidal septicemia and development of resistance in such a selective high-risk group are warranted before initiation of routine prophylaxis.fluconazole, very low birth weight infant, prophylaxis, candidal sepsis, sensitivities to fluconazole.

Flavobacterium meningosepticum sepsis in an infant with a diarrheal prodrome.

A full term, previously normal 2 1/2-month-old black boy was transferred to our hospital from an outlying facility on hospital day 5 for failure to thrive. Three weeks before transfer, the infant was hospitalized for a diarrheal illness with fever. The baby received 3 days of ceftriaxone empirically and was discharged home after the sepsis evaluation was negative. Mild diarrhea and steady weight loss continued and the baby was readmitted. Blood culture done on admission grew Flavobacterium meningosepticum, an organism previously described as an uncommon cause of sepsis in neonates and immunocompromised individuals. As it is water-borne, it has been associated with infection via contaminated water. This organism is usually resistant to antibiotics commonly used for empiric treatment. To our knowledge, this is the first reported case of Flavobacterium bacteremia associated with a prodromal and concurrent diarrheal illness.

Evidence for person-to-person transmission of Candida lusitaniae in a neonatal intensive-care unit.

Candida lusitaniae is an increasingly important nosocomial bloodstream pathogen. Epidemiological investigation and molecular typing techniques identified three neonates infected with identical strains of C lusitaniae that were distinguished readily from epidemiologically unrelated strains from other locations in the hospital. The results of this study provide evidence for nosocomial transmission of C lusitaniae in a neonatal intensive-care unit and suggest that these infants are at increased risk for infection with this agent.

Resistance of gluconeogenic and glycogenic pathways in obese-hyperglycemic mice.

The genetically obese-hyperglycemic mouse, C57 BL/6J-ob, exhibits hyperglycemia and hyperinsulinemia. We have investigated the in vivo hepatic response to a glucose load in female obese mice and their lean littermates. Within 15 min after the administration of glucose (1.5 g/kg) to fasted lean mice, gluconeogenesis from [14C]alanine markedly decreased, endogenous hepatic levels of alanine and other gluconeogenic precursors increased, and glycogen synthetase was activated by virtue of an increase in the precent of synthetase I. These changes persisted up to 60 min and then returned to fasting values. In contrast, obese mice did not produce any of the above changes when given a similar glucose load. Failure to activate glycogen synthetase occurred despite the presence of synthetase D phosphatase activity. In lean mice [14C]glucose synthesis from [14C]glycerol exceeded that from [14C]alanine and was not suppressed by glucose administration, indicating the site of control of gluconeogenesis to be below the triose phosphate step. Insulin resistance in obese mice may involve the liver, as well as peripheral tissues studied by others.