Brian A. Lauer

Enterovirus infections in neonates

Twenty-seven ill neonates with enterovirus infections were studied to learn if enterovirus infection can be distinguished from neonatal sepsis. Enterovirus infection was associated with the summer-fall season (93%), recent maternal illness (59%), absence of other perinatal problems (81%), and findings of fever (93%), viral meningitis (62%), diarrhea (81%), and rash (41%). Four children developed thrombocytopenia and three necrotizing enterocolitis. Three children died, all with Coxsackie B virus infections that likely were acquired in utero. Although no single feature is pathognomonic, this constellation of epidemiologic and clinical findings, coupled with negative bacterial cultures, should suggest the possibility of neonatal enterovirus infection.

Pathogens associated with acute lower respiratory tract infection in young children.

To determine the agents associated with acute lower respiratory infection in young children, we studied 102 hospitalized children less than 5 years old using culture and serology for viruses and Chlamydia trachomatis, fluorescent anti-body testing for pertussis and respiratory syncytial virus, blood cultures and counterimmunoelectrophoresis of nasopharyngeal secretions and urine for pneumococcal and Haemophilus influenzae type b antigens. At least one agent was detected in 87 children and multiple agents were found in 33. Viruses were detected 80 times; respiratory syncytial virus was most common (61 cases) and was detected as often by fluorescent antibody testing as by culture. C. trachomatis was detected in 10 children; all were less than 4 months old and 9 had mixed infections. Bacteria were detected 32 times, were usually pneumococcus (23) or H. influenzae (5) and were detected more often by counterimmunoelectrophoresis than by blood culture. Compared with children yielding only C. trachomatis or viruses, those with bacteria were significantly more likely to have fever, a band count over 2000/mm3 and radiographic consolidation. In this study acute lower respiratory infection was associated commonly with viruses, often with multiple pathogens but not with C. trachomatis after 4 months of age.

Single-dose amoxicillin therapy with follow-up urine culture: Effective initial management for acute uncomplicated urinary tract infections

To learn whether a single dose of amoxicillin is safe, effective therapy for acute uncomplicated urinary tract infections, 388 symptomatic nonpregnant women were randomly grouped to receive oral amoxicillin, either as a single 3 g dose of 250 mg three times a day for two weeks. Patients had quantitative as well as dip-slide cultures of urine and tests for antibody-coated bacteria in urine. Follow-up urine cultures were obtained one week after completion of treatment. Results of antimicrobial susceptibility and antibody-coated bacterial tests did not alter the randomized therapy. Among 162 patients with bacteriologically confirmed infections, cure rates were 60.6 percent (43 of 71) for single-dose versus 73.6 percent (67 of 91) for two-week treatment (p = 0.07). Although more antibody-coated bacteria-negative patients (89.6 percent; 26 of 29) were cured overall, a substantial proportion of antibody-coated bacteria-positive patients were also cured by both single-dose (59.3 percent; 32 of 54) and 14-day therapy (64.6 percent; 42 of 65). There were fewer adverse effects in the single-dose treatment group. We conclude that a single 3 g dose of amoxicillin, with follow-up urine culture, provides safe and effective management for acute uncomplicated urinary tract infections in nonpregnant women.

Immunogenicity and safety of Haemophilus influenzae type b-tetanus protein conjugate vaccine alone or mixed with diphtheria-tetanus-pertussis vaccine in infants☆☆☆★

Haemophilus capsular polysaccharide-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) vaccines were administered in a single syringe (group 1) or separate syringes (group 2) to 284 infants at 2, 4, and 6 months of age. Group 1 infants had a slightly greater incidence of local reactions. Systemic reactions were similar. The geometric mean titers of polyribosylribitol phosphate (PRP) serum antibody concentrations after the third dose of PRP-T vaccine were 4.8 and 4.3 micrograms/ml for groups 1 and 2, respectively. Antibody responses to DTP antigens were also similar. The immunogenicity and safety of the PRP-T and DTP vaccines are equivalent when the vaccines are administered in separate syringes or the same syringe to infants.

Neisseria lactamica Meningitis

Neisseria lactamica was recovered from the blood and cerebrospinal fluid of a 7-month-old girl with acute purulent meningitis. The isolate was identified initially as N meningitidis. However, additional biochemical testing at the Center for Disease Control showed that the organism fermented lactose and produced beta-D-galactosidase, thereby confirming its identity as N lactamica.

Biliary flora and antimicrobial concentrations after Kasai's operation***

In 1976, a prospective study of children following hepatic portoenterostomy was initiated to determine (1) the efficacy of hepatic antimicrobial excretion, (2) the relationship of antimicrobial levels in bile to bilirubin clearance, and (3) the effect of antimicrobials in bile on the growth of bacteria within the bilioenteric conduit. Fifty simultaneous blood-bile peak-trough antimicrobial levels were assayed in 10 patients. Cephalosporin, aminoglycoside, and trimethoprim-sulfamethoxazole levels were determined 20, 19, and 4 times, respectively. Simultaneous quantitative bile cultures and bilirubin clearance measurements also were obtained. Adequate mean antimicrobial concentrations in serum were achieved. Detectable antimicrobial concentrations in bile were found in 100% of the patients receiving trimethoprim-sulfamethoxazole, 65% of those receiving cephalosporins, and 10% receiving aminoglycosides. Mean bile levels for each antimicrobial were always less than simultaneous serum levels. The mean bile to serum ratios of trimethoprim-sulfamethoxazole, cephalosporins, and aminoglycosides were 0.90, 0.32, and 0.01, respectively. There was no correlation between bilirubin clearance and antimicrobial levels in bile. The presence of antimicrobials in bile did not alter the frequency, type, or concentration of bacterial growth within the bilioenteric conduit. Antimicrobial activity in bile after hepatic portoenterostomy is characterized by: (1) moderate concentrations of trimethoprim-sulfamethoxazole and cephalosporins and low levels of aminoglycosides, (2) the independence of bilirubin clearance and antimicrobial bile concentrations, and (3) the inability to eliminate bacterial growth within the bilioenteric conduit with the achieved biliary antimicrobial levels.

Syringe preparation technique and minor adverse reactions to diphtheria-tetanus-pertussis immunization.

Minor local reactions and subcutaneous abscesses following diphtheria, tetanus and pertussis immunization have been attributed to vaccine left in the subcutaneous needle path from vaccine coating the needle. Various syringe preparation techniques have therefore been advocated to prevent reactions. To evaluate these recommendations we compared rates of minor reactions in 200 children randomly assigned to one of three groups that differed only in the handling of the filled syringe: in Group 1 the needle was changed before injection; in Group 2 the needle was wiped with sterile gauze before injection; in Group 3 the same needle was used to draw up and to inject the dose and was not wiped. Overall 27% of children had febrile (greater than 38 degrees C) reactions, 62% became fussy and 79% had a local reaction. Rates of reactions were nearly identical in the three groups, except that children in group 2 receiving their second dose or more of diphtheria-tetanus toxoid-pertussis vaccine were more likely to become febrile at greater than 38 degrees C (32%) or fussy (78%) (P less than 0.05 and P less than 0.02, respectively). We conclude that changing needles does not reduce the rate of minor local and systemic reactions. Wiping needles may increase the rate of reactions.

ORAL RIBAVIRIN THERAPY OF SUBACUTE SCLEROSING PANENCEPHALITIS (SSPE)

SSPE is a persistent fatal measles virus infection of the central nervous system. Because ribavirin is active in vitro against measles and reportedly efficacious in naturally occurring measles, we treated 2 patients with SSPE with oral ribavirin. The patients were an 11 year old girl and an 18 year old boy ill for 2 and 8 years, respectively. The dose was 10 mg/kg tid for 3 days, then bid daily for 6 and 14 weeks, respectively. Serum and cerebrospinal fluid (CSF) ribavirin concentrations (courtesy of J. Connor, Univ. of Calif. San Diego) and measles antibody titers (Courtesy of V. Berardi, Mass. State Dept. of Health) were measured serially. Clinical response was evaluated by neurological examination and EEG, and toxicity was monitored by blood count, electrolytes, urinalysis, liver and renal function tests. Ribavirin Concentration (uM) Patient #1 (Patient #2 pending)Neurological examination and EEGs were essentially unchanged during therapy. There was no decrease in antibody titers. Ribavirin was well tolerated except for mild hemolytic anemia in patient #1. CSF ribavirin levels were 75% of serum at 7 days, and remained above 66% for 6 weeks. Future therapeutic trials should consider prolonged treatment or higher doses of oral ribavirin early in the course of SSPE.