Safety and prophylactic efficacy of low-dose rimantadine in adults during an influenza A epidemic.

A placebo-controlled, double-blind study to evaluate the safety and prophylactic efficacy of a low dose (100 mg) of rimantadine hydrochloride against naturally occurring influenza in adults was conducted at two sites. After the onset of the influenza season, volunteers (ages, 18 to 55 years) were assigned randomly to receive rimantadine or placebo daily. Subjects were monitored for adverse effects and evidence of influenza virus infection weekly for six weeks. Only 10 (8.7%) of 114 rimantadine recipients and 5 (4.4%) of 114 placebo control recipients reported one or more mild to moderate adverse symptoms, most of which were related to the gastrointestinal or central nervous system. Compared with placebo, low-dose rimantadine was highly effective in the prevention of influenza A virus infection (20 of 110 versus 7 of 112 participants; P less than 0.01) and influenza illness (7 of 110 versus 1 of 112 participants; P = 0.04). Influenza A/Leningrad/87-like (H3N2) virus was recovered from the nasopharynxes of only five placebo recipients. These findings indicate that low-dose rimantadine is well tolerated and highly effective for the prevention of influenza A illness in healthy adults.

Diagnostic studies of nosocomial diarrhea in children: assessing their use and value.

During a 17-month period (01/11/85-05/31/86) 225 cases of nosocomial diarrhea were identified in a children's hospital. Diarrhea was considered to be nosocomial if it began at least 72 hours after the patient's hospital admission or within 3 days after discharge. One or more routine diagnostic studies for identification of a pathogen were performed in 195 (87%) cases. The most commonly performed test was the bacterial stool culture. None of these samples yielded a bacterial pathogen. The only pathogens detected by routine laboratory studies were rotavirus (61/137 [45%] samples were positive for rotavirus by ELISA) and Clostridium difficile (9/54 [17%] positive for toxin). Of the patients whose tests were positive for rotavirus 56 were younger than 2 years of age, and all were identified in the winter and spring. When multiple stool samples were tested by the diagnostic laboratory, rotavirus was identified in an additional 14 patients whose initial stool samples were negative for rotavirus. All patients whose tests were positive for C. difficile toxin had received antibiotics within the previous 3 months. Ova/parasites were not detected in 53 of the tested stools. We also identified enteric adenovirus in six patients. Viruses were identified in 95 (42%) of the 225 cases of nosocomial gastroenteritis. Nosocomial diarrhea is common in a children's hospital. Rotavirus is the most commonly identified pathogen. Rotavirus testing is valuable in children with nosocomial diarrhea who are younger than 2 years of age, especially in the winter and spring. Multiple samples may be necessary to identify rotavirus. C. difficile toxin assay should be considered for patients who are receiving or who have received antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous recovery of bacterial and viral pathogens from cerebrospinal fluid.

Mixed bacterial infection in meningitis is well-documented, but there have been few previous reports of mixed viral-bacterial meningitis. A retrospective analysis of the bacterial and viral cerebrospinal fluid (CSF) cultures from a 1-year period in a 315-bed children's hospital revealed 5 patients with mixed viral-bacterial meningitis among 276 patients with viral and/or bacterial culture-positive meningitis. These 5 accounted for 2.8% of the patients with positive CSF viral cultures and 4.8% of those with positive CSF bacterial cultures. All of the viruses were identified as enteroviruses, and the bacteria were Group B Streptococcus, Group D Salmonella, Streptococcus pneumoniae, Haemophilus influenzae type b and Staphylococcus aureus. The ages of the patients ranged from 10 days to 22 years. The clinical course of each of the illnesses was typical of bacterial meningitis. This relatively high frequency of mixed viral-bacterial meningitis could affect the utility of rapid viral diagnostic tests for CSF viruses.

Polyacrylamide gel electrophoresis of RNA compared with polyclonal- and monoclonal-antibody-based enzyme immunoassays for rotavirus.

Polyacrylamide gel electrophoresis (PAGE) of rotaviral RNA, a sensitive and highly specific test for detecting rotavirus in stool, was compared with two commercially available enzyme immunoassays (EIAs), monoclonal (Pathfinder) and polyclonal (Rotazyme II). Stool samples from 204 children with nosocomial diarrhea were tested for rotavirus by both EIAs and by PAGE of RNA extracted from raw stools or 10% stool suspensions. Samples which tested positive by either EIA but were negative by PAGE were subjected to blocking EIA with rabbit or goat anti-SA11. Rotavirus was detected by PAGE and Pathfinder in 62 stools, but only 47 of these were positive by Rotazyme II. Blocking assays of EIA-positive, PAGE-negative samples suggested the presence of rotavirus in four additional stools. Sensitivity and specificity measured against PAGE and blocking assays were: Pathfinder, 0.985 and 0.934; and Rotazyme II, 0.731 and 0.927, respectively. False-positive rates were 0.134 for Pathfinder and 0.149 for Rotazyme II. The specificity and rate of false-positive results of Pathfinder were improved by using an adjusted optical density cutoff 4.36 times greater than that recommended by the manufacturer (specificity, 0.993; sensitivity, 0.985; false-positive rate, 0.015).

Nosocomial rotaviral diarrhea: pattern of spread on wards in a children's hospital.

Nosocomial gastroenteritis in a 315-bed hospital for children was examined prospectively from January 11 through May 31, 1985. There were 85 cases of nosocomial diarrhea during the study period, and these were identified on each of the 13 hospital wards. Rotavirus was identified in 40% of cases. Incidence of nosocomial rotavirus was highest on wards where most children were less than 2 years of age, except for the infectious diseases (isolation) ward (0.24 versus 2.30 cases per 100 admissions, p = 1.70 x 10(-4), Fisher exact test). The lower incidence on the infectious diseases ward occurred despite the greater potential for exposure to rotavirus, since 70% of children admitted with community-acquired rotavirus diarrhea were placed on the infectious diseases ward. Better infection control, especially hand washing, aided by the structure of the infectious diseases ward, may have been responsible for this difference.

Adenovirus infections and respiratory illnesses in children in group day care.

Adenovirus infections and respiratory illnesses among 123 children attending a research day care center were analyzed from data collected prospectively from 1967 through 1981. During the 15-year study period, 298 adenovirus isolates were recovered from respiratory secretions of the study children, and five different serotypes were identified, with types 1, 2, and 5 accounting for 92% of the typed isolates. Annual incidence of each serotype varied greatly, with types 2 and 5 predominating before 1975 and type 1 thereafter. Exposure to adenovirus in the day care center correlated with acquisition of infection. Through two years of age, children were exposed to 3.4 +/- 0.9 (mean +/- SD) different serotypes and became infected by 2.1 +/- 0.8 different types. Most infections occurred before the child's second birthday, and incidence was highest from six to 12 months of age (1.4 primary infections/child-year). Mild and febrile illness accompanied 75% of primary isolations. Otitis media occurred in 37% of illnesses over all ages and in greater than 50% of illnesses among infants.

Cefuroxime therapy for bacteremic soft-tissue infections in children.

Although it is used extensively in Europe, there is a limited amount of published data concerning pediatric clinical experience with cefuroxime in the United States. Thirty-six children, ranging from 3.5 to 57 months of age, received intravenous cefuroxime (75 mg/kg/day in three divided doses) for soft-tissue infections of the face or epiglottis. Infections treated included preseptal (19 patients) and buccal (13 patients) cellulitis and epiglottitis (four patients). Blood cultures were positive in 22 patients, yielding Haemophilus influenzae type b in 17 (four were beta-lactamase-positive), Streptococcus pneumoniae in four; and beta-lactamase-positive, nontypable H influenzae in one. An additional five patients with buccal cellulitis had negative blood cultures but H influenzae type b antigenuria. A satisfactory clinical response was noted in all patients, and repeated blood cultures performed in initially bacteremic patients were sterile. Cefuroxime therapy was well tolerated, and abnormal laboratory results were infrequent, except for absolute granulocytopenia (granulocytes, less than 1,500/cu mm), which occurred in six patients but could not be ascribed to a drug effect because of the uncontrolled design of our study. Treatment with cefuroxime appears to be a safe and effective therapy for pediatric soft-tissue infections due to H influenzae and S pneumoniae.

A new animal model for human respiratory tract disease due to adenovirus.

Cotton rats (Sigmodon hispidus) were tested as a model for human respiratory tract infection due to adenovirus. After intranasal instillation of 10(6.1) 50% tissue culture infectious doses (TCID50) of adenovirus type 5 into one-month-old cotton rats, groups were killed at intervals for nasal and lung titration of virus and lung histopathology. In lung, eclipse occurred at 8 hr followed by peak viral titer (10(7.5) TCID50/g of lung) on day 5. Titers fell to 10(3.2) TCID50/g by day 10 and persisted at that level through the remainder of the study (day 28) despite appearance of serum neutralizing antibody after day 6. Interstitial pneumonia paralleled viral growth, and peribronchial mononuclear infiltration followed one to two days later. Titers in nasal mucosa peaked on day 3 but were undetectable beyond day 21. Pulmonary histopathology and viral replicative patterns paralleled findings in natural human disease.

Effect of penicillin prophylaxis on nasopharyngeal colonization with Streptococcus pneumoniae in children with sickle cell anemia.

Polyvalent pneumococcal vaccine and oral penicillin prophylaxis are frequently used in patients with functional or anatomic asplenia to protect them from fulminant Streptococcus pneumoniae sepsis. We studied nasopharyngeal colonization with pneumococci in 34 patients with sickle cell anemia (aged 6 months to 5 years) receiving penicillin prophylaxis and in 63 age- and race-matched comparison patients. Patients with sickle cell anemia had fewer positive initial pneumococcal nasopharyngeal cultures than did the comparison group (14.5% vs 34.4%, P = 0.03) and significantly lower carriage rates during the respiratory illness season of November to March (8.7% vs 40.5%, P = 0.005). Penicillin prophylaxis did not result in emergence of penicillin-resistant pneumococci or in an increased carriage rate of Haemophilus influenzae type b. Our data suggest a mechanism of action for penicillin prophylaxis and provide some evidence for the relative safety of this regimen.