Risk factors for persistent candidemia infection in a neonatal intensive care unit and its effect on mortality and length of hospitalization.

OBJECTIVE: Candida infections cause substantial morbidity and mortality in neonates. Persistent candidemia has not been associated with increased risk of mortality compared with candidemia of shorter duration. This study sought to determine whether persistent candidemia was associated with increased length of hospitalization or mortality in neonates. STUDY DESIGN: A chart review was conducted of neonates with Candida bloodstream infections (n=37). Demographic, laboratory, pharmacy, nutrition and discharge data were abstracted. Contingency table analysis and logistic regression were used to analyze variables associated with persistent candidemia and mortality. The relationship between length of hospitalization and persistent candidemia was assessed with k-sample equality of medians test. RESULT: Nine patients (24%) had persistent candidemia. Increased time between blood culture draw and initial antifungal therapy was associated with increased incidence of persistent candidemia (P=0.03). Five patients (14%) died before hospital discharge; however, no deaths were attributed to persistent candidemia. Length of hospitalization was not increased with persistent candidemia. A decrease in the ratio of enteral feeding days to hyperalimentation days before collection of the first positive blood culture was significantly associated with an increase in all-cause mortality (P=0.03) and death attributed to candidemia (P=0.04). The risk of all-cause mortality decreased with a history of receiving any enteral feedings before the first positive blood culture (P=0.04), as did death attributed to candidemia (P=0.02). CONCLUSION: A duration of >1 day between the time of blood culture and the initial dose of systemic antifungal treatment places neonates at increased risk for developing persistent candidemia; however, this is not associated with increased mortality.

Failure of gamma-interferon to decrease mortality from group B streptococcal sepsis in neonatal rats.

Newborns possess an altered immune response to infection with impaired leukocyte chemotaxis and deficient production of gamma-interferon (IFN-gamma). IFN-gamma enhances neonatal leukocyte activation and movement. We proposed that IFN-gamma in conjunction with penicillin compared to penicillin therapy without IFN-gamma would increase survival from group B streptococcal sepsis in a neonatal rat model. Newborn rats were infected with 10(5) cfu of group B streptococci at 48-72 h of age and randomized to receive either serum albumin (controls), rat recombinant IFN-gamma, albumin and penicillin, or IFN-gamma and penicillin. Survival 120 h postinfection revealed: controls 5% (1/21); IFN-gamma 4% (1/24); penicillin 23% (5/22); and IFN-gamma plus penicillin 10% (2/21). Survival analysis with a lognormal parametric regression model revealed only the penicillin group to have improved survival compared to controls. Contrasting the penicillin group with the IFN-gamma plus penicillin group did not reveal a statistically significant difference by the Wald chi2 statistic (p = 0.25).

Prospective randomized double blind placebo-controlled evaluation of azithromycin for treatment of cat-scratch disease.

OBJECTIVE: To determine the efficacy of azithromycin in the treatment of patients with typical cat-scratch disease. DESIGN: Prospective, randomized, double blind, placebo-controlled clinical trial. SETTING: Large military medical center and its referring clinics. PATIENTS: Active duty military members and their dependents with laboratory-confirmed, clinically typical cat-scratch disease. INTERVENTION: Study participants assigned by randomization to treatment with oral azithromycin or placebo for 5 days. OUTCOME MEASURES: Lymph node volume was calculated using three dimensional ultrasonography at entry and at weekly intervals. The ultrasonographer was blinded to the treatment groups. Endpoint evaluations were predetermined as time in days to 80% resolution of the initial total lymph node volume. RESULTS: Demographic and clinical data showed that the azithromycin and placebo treatment groups were comparable at entry although the placebo group tended to be older. Eighty percent decrease of initial lymph node volume was documented in 7 of 14 azithromycin-treated patients compared with 1 of 15 placebo-treated controls during the first 30 days of observation (P = 0.026). After 30 days there was no significant difference in rate or degree of resolution between the two groups. CONCLUSIONS: Treatment of patients with typical cat-scratch disease with oral azithromycin for five days affords significant clinical benefit as measured by total decrease in lymph node volume within the first month of treatment.

A survey about management of febrile children without source by primary care physicians.

BACKGROUND: The management of young children with fever without source is controversial, and differences between physician specialties have been noted previously. The emergence of penicillin-resistant Streptococcus pneumoniae, the sharp decline in invasive Haemophilus influenzae infections in immunized populations and publication of practice guidelines have potentially altered physician practices. OBJECTIVE: To determine the present practice preferences of pediatricians, family medicine physicians (FP) and emergency medicine physicians (EP). METHODS: We mailed a checklist survey to 1600 randomly selected pediatricians, family medicine practitioners (FP) and emergency medicine physicians (EP) in the United States and replicated the methodology of a 1991/1992 survey. Physicians were asked about their evaluation and management of children of various ages (3 weeks, 7 weeks, 4 months and 16 months) with fever without source. RESULTS: Most primary care physicians would admit the 3- and 7-week-old infants. For the 4-month-old infant 59% of EP, 45% of pediatricians and 28% of FP would give empiric antibiotic(s) as an outpatient (P=0.005 for FP compared with pediatricians and P=0.02 for EP compared with pediatricians). The majority of physicians would manage the 16-month-old child as an outpatient without antibiotic therapy. Ceftriaxone was the preferred antibiotic for outpatient empiric therapy. There was a 3-fold increase (28% vs. 9%) for pediatricians in the use of empiric outpatient antibiotics for the 7-week-old infant in the present survey compared with the 1991/1992 survey. CONCLUSIONS: Physicians in the United States generally agree in their management of the young febrile infant, but with increasing patient age there is considerable variation. FP were the least aggressive in their evaluation and EP were the most aggressive.

Chemiluminescent and flow cytometric analysis of gamma interferon preincubation on neonatal and adult rat polymorphonuclear leukocytes.

Gamma interferon (IFN-gamma) has multiple immunomodulating effects and has been postulated as a possible immunopotentiating agent for the prevention or treatment of neonatal infections. This report describes the effect of rat recombinant IFN-gamma on the oxidative burst activity and CD11b expression of neonatal and adult rat polymorphonuclear leukocytes (PMNL). Oxidative burst activity was assessed by chemiluminescence and dihydrorhodamine flow cytometry. Neonatal PMNL exhibited significantly less oxidative burst activity than did adult PMNL. IFN-gamma mildly enhanced the chemiluminescence response of PMNL from both the rat pups and adults, but this effect was not statistically significant when analyzed by a multivariate model of repeated-measures analysis of variance for both chemiluminescence and dihydrorhodamine flow cytometry. CD11b expression was also not significantly enhanced by IFN-gamma.

Antimicrobial treatment of occult bacteremia: a multicenter cooperative study.

This prospective multicenter study was conducted to define more clearly clinical and laboratory criteria that predict a strong probability of occult bacteremia and to evaluate the effect of empiric broad spectrum antimicrobial treatment of these children. Children 3 to 36 months old with fever > or = 40 degrees C (104 degrees F) or, > or = 39.5 degrees C (103 degrees F) with white blood cells (WBC) > or = 15 x 10(9)/liter, and no focus of infection had blood cultures obtained and were randomized to treatment with oral amoxicillin/potassium clavulanate or intramuscular ceftriaxone. Sixty of 519 (11.6%) study patients had positive blood cultures: Streptococcus pneumoniae, 51; Haemophilus influenzae b, 6; Neisseria meningitidis, 2; and Group B Streptococcus, 1. Subgroups of high risk were identified as fever > or = 39.5 degrees C and WBC > or = 15 x 10(9)/liter, 55 of 331 or 16.6% positive with increasing incidence of positive culture with increasing increments of degrees of leukocytosis to WBC > or = 30 x 10(9)/liter where 9 of 21 or 42.9% were positive. Subgroups of significantly lower risk were identified as fever > or = 39.5 degrees C and WBC < 15 x 10(9)/liter, 5 of 182 or 2.7% positive and those with WBC < 10 x 10(9)/liter, 0 of 99 or 0.0% positive. Children with positive cultures who received ceftriaxone were nearly all afebrile after 24 hours whereas a significant number who received amoxicillin/potassium clavulanate remained febrile. In the 459 culture-negative children more amoxicillin/potassium clavulanate-treated children developed diarrhea and had less improvement in clinical scores after 24 hours than ceftriaxone-treated children.(ABSTRACT TRUNCATED AT 250 WORDS)

Measles revaccination response in a school-age population.

Due to the dramatic upsurge in the incidence of measles, the American Academy of Pediatrics and the Immunization Practices Advisory Committee of the Centers for Disease Control revised their measles immunization policies in 1989 to include a routine two-dose schedule. The objectives of this study were the following: (1) determine the prevalence of immunologically measles-susceptible subjects in a previously vaccinated, school-age, military dependent population; and (2) assess risk factors to identify immunologically measles-susceptible subjects. Serum was collected just prior to measles revaccination and again 2 weeks later. Measles-specific IgG and IgM titers were determined by enzyme-linked immunosorbent assay. Immunologically measles-susceptible subjects constituted 9.8% of the population. The interval since previous measles vaccination was significantly related to pre- and postrevaccination IgG titers in a repeated-measures analysis of variance model. The magnitude of increase in IgG titer following revaccination and analysis of trend for proportions of measles-susceptible subjects were significantly related to the age of initial vaccination. This study supports continued measles revaccination; in addition, revaccination appears to be of greater value at 11 to 12 years of age than at 4 to 6 years of age.

Impetigo. Current etiology and comparison of penicillin, erythromycin, and cephalexin therapies.

We attempted to determine the causative bacterial pathogens of impetigo in children in our area, to compare the effectiveness of three frequently used oral antimicrobial treatment regimens, and to correlate the antimicrobial sensitivity of the bacterial isolates with clinical responses to treatment. Seventy-three children with impetigo were randomly assigned to receive penicillin V potassium or cephalexin monohydrate, both administered in dosages of 40 to 50 mg/kg per day, or erythromycin estolate administered in a dosage of 30 to 40 mg/kg per day. All drugs were given in three divided doses for 10 days. Treatment failure was defined as persistence of lesions 8 to 10 days after initiation of drug therapy as determined by examiners blinded to the treatment therapies. Forty-five (62%) cultures showed Staphylococcus aureus only, 14 (19%) showed S aureus and group A beta-hemolytic streptococci, six (8%) showed group A beta-hemolytic streptococci only, and eight (11%) showed no growth or other organisms. Treatment failure occurred in six (24%) of 25 patients treated with penicillin V, one (4%) of 25 patients treated with erythromycin estolate, and no patients treated with cephalexin. We conclude that S aureus is the most common cause of impetigo in children in our study population, that cephalexin is the most effective treatment, that erythromycin estolate is nearly equally effective and may be preferred on a cost-effectiveness basis, and that penicillin V is inadequate for treatment of this infection.

Penicillin tolerance and erythromycin resistance of group A beta-hemolytic streptococci in Hawaii and the Philippines.

Penicillin remains the drug of choice for the treatment of streptococcal pharyngitis, with erythromycin as an alternative drug for individuals who cannot take penicillin. Two areas of concern in the management of streptococcal pharyngitis are (1) the prevalence of penicillin-tolerant group A beta-hemolytic streptococci reported in recent studies and (2) the high prevalence of erythromycin resistance in some geographic areas. We tested 305 isolates of group A beta-hemolytic streptococci from Hawaii and the Philippines for penicillin minimum inhibitory concentrations and minimum bactericidal concentrations and erythromycin minimum inhibitory concentrations. There was no evidence of penicillin resistance or tolerance. The prevalence of erythromycin-resistant and moderately susceptible isolates was 3.6% and 2.3%, respectively. There was a trend toward greater erythromycin resistance levels among Hawaiian isolates, but this was not statistically significant.

Nontyphoidal Salmonella enteric infections and bacteremia.

Antimicrobial treatment of nontyphoidal Salmonella gastroenteritis is usually advocated for infants younger than 3 months of age based on published data showing that infants in this age group are more prone to have bacteremia and develop extraintestinal focal infections. A review of nontyphoidal Salmonella isolates from our institution from January, 1981, through March, 1988, was undertaken to assess the role of age and specific serovar on the incidence of bacteremia. Two hundred twenty isolates were identified: one cerebrospinal fluid, 14 blood and 205 stool. The mean age of patients with bacteremia was 182 months, not significantly different from the mean age of 142 months for patients with stool isolates. Salmonella weltevreden was the most frequent isolate accounting for 23% of all isolates and all isolates of this organism were from stool cultures. Patients with S. weltevreden infections had mean and median ages of 50 and 2.5 months and were younger than patients with stool isolates from other serovars who had mean and median ages of 174 and 38 months. Infants younger than 3 or 6 months of age with positive stool cultures in whom blood cultures were obtained did not demonstrate a higher incidence of bacteremia than did older patients. We conclude that the incidence of bacteremia in patients with nontyphoidal Salmonella gastroenteritis is highly related to the invasiveness of the infecting specific Salmonella serovar.