Pharmacokinetics of oral zidovudine administered during labour: a preliminary study.

OBJECTIVES: The aim of this study was to determine whether oral zidovudine (ZDV) given during labour would provide a similar systemic exposure to the established intravenous regimen used to prevent mother-to-child transmission in HIV-infected pregnant women. METHODS: ZDV pharmacokinetic parameters following oral administration during labour were determined in 10 HIV-infected pregnant women in active labour. All subjects were converted to intravenous ZDV prior to delivery. RESULTS: In cohort 1 (n=6), subjects received 300 mg oral ZDV every 3 h for three doses. Oral therapy was well tolerated but plasma ZDV concentrations were substantially lower than previously reported with continuous intravenous therapy. Based on the pharmacokinetic results from cohort 1, women in cohort 2 (n=4) received an initial 600 mg dose followed by two 400 mg doses every 3 h. ZDV area under the curve and concentrations in cohort 2 increased approximately in proportion to the increase in dose but varied 6-7-fold. In both cohorts, ZDV pharmacokinetic parameters suggested erratic absorption. CONCLUSIONS: While ZDV exposure improved with the increased dosing regimen, our sample size was small and larger studies are needed to establish whether oral ZDV administration during labour can consistently provide equivalent exposure to intravenous administration.

Pharmacokinetics of dapsone administered daily and weekly in human immunodeficiency virus-infected children.

Although dapsone is a commonly used alternative agent for prophylaxis against Pneumocystis carinii pneumonia in children intolerant to trimethoprim-sulfamethoxazole, there are few data that describe dapsone pharmacokinetics in children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0. 3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/kg weekly resulted in peak concentrations equivalent to those reached in adults receiving 100-mg tablets daily. For the entire population, the median half-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0.0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 liters/kg). The median dapsone oral clearance was significantly increased in those infants less than 2 years of age compared to the oral clearance in those over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and that the concentrations in the sera of children receiving 2 mg/kg daily or 4 mg/kg weekly are equivalent to those seen in adults receiving standard dapsone dosing. Dapsone oral clearance appears to be increased in children under 2 years of age.

Mycobacterium fortuitum infection of ventriculoperitoneal shunt.

Mycobacterium fortuitum is one of the rapidly growing mycobacteria found in soil, dust, and water. It can be isolated as a normal colonizing organism, but as a pathogen this organism causes mainly skin and soft tissue infection preceded by trauma. A wide variety of infections can occur in individuals with predisposing conditions. Central nervous system infection with M fortuitum is rare, and meningitis occurs after surgery or trauma. We believe that ventriculoperitoneal (VP) shunt infection with this organism has not been reported in the literature. Practitioners should be aware of this rare entity and should suspect it in the presence of cerebrospinal fluid pleocytosis with sterile culture, and after trauma, surgery, or manipulation of the VP shunt hardware. Mycobacterium fortuitum is resistant to most first-line and second-line antituberculous drugs, and treatment should include surgical debridement in addition to prolonged antimicrobial therapy.

Usefulness of acute phase reactants in the diagnosis of acute infections in HIV-infected children.

BACKGROUND: Children infected with the human immunodeficiency virus (HIV) often have hypergammaglobulinemia, causing elevation of the erythrocyte sedimentation rate (ESR). This study was done to determine whether C-reactive protein (CRP) is a better indicator of acute infection than ESR in HIV-infected children. METHODS: Erythrocyte sedimentation rate, CRP, and immunoglobulin G (IgG) levels were measured in sick and otherwise healthy HIV-infected children. McNemar's test was used to compare ESR and CRP. RESULTS: In 22 of the 26 cases (85%), the IgG level was elevated, and in all cases ESR was elevated. In 20 of these 22 (91%), both ESR and CRP were elevated. Of the 18 controls, 17 (94%) had elevated IgG, 14 of 17 (82%) had elevated ESR, and 1 (7%) had elevated CRP. The sensitivity for ESR and CRP was 96% and 92%, respectively, and the specificity for ESR and CRP was 17% and 94%, respectively. CONCLUSIONS: Since CRP is more specific than ESR in predicting acute infection in HIV-infected children, it should be used in the evaluation of acute infection in this population.

Polymerase chain reaction testing for early detection of HIV infection in children.

Diagnosis of vertically acquired human immunodeficiency virus (HIV) infection is often difficult because of transplacentally acquired maternal antibodies. The polymerase chain reaction (PCR) test is commercially available and has high sensitivity and specificity. To evaluate the usefulness of PCR testing in the early diagnosis of perinatally acquired HIV infection, we reviewed records of 122 children having follow-up in the Northeast Florida Pediatric AIDS Program. Seventy-two children were excluded for various reasons. Of the remaining 50 children, 37 had PCR testing. In 5 children, the initial PCR test was done at > 18 months of age. Results of PCR testing were positive in 8 of 13 (62%) at birth, 12 of 18 (67%) by 1 month of age, 18 of 23 (78%) by 2 months of age, and 20 of 24 (83%) by 3 months of age. In 24 of 27 (85%), results were positive by the time the children reached 4 months of age. Our data suggest that the PCR test is a useful tool for early diagnosis of vertically transmitted HIV infection.

Visceral leishmaniasis in Pakistani children.

Visceral leishmaniasis is endemic in Pakistan. No studies of visceral leishmaniasis in childhood have been reported from Pakistan. We prospectively studied clinical and laboratory features in 58 Pakistani children with visceral leishmaniasis. Mean age of the children was 2.9 years. Fever, pallor, and abdominal distention were the most common clinical manifestations, and hematologic abnormalities were the most common laboratory findings. All children recovered after antimicrobial therapy. Pakistani children with visceral leishmaniasis tended to be younger than affected children from Africa and were less likely to have lymphadenopathy.

Multidrug-resistant Salmonella typhi in Pakistani children: clinical features and treatment.

Multidrug-resistant Salmonella typhi has become a major public health problem. In this study, typhoid fever was diagnosed by isolation of Salmonella typhi from blood or by a positive Widal's reaction in 170 Pakistani children. There were 111 boys (65%) and 59 girls (35%). The average age was 6.2 years; 4 (2%) were less than 1 year old, 78 (46%) were 1 to 5 years old, and 88 (52%) were more than 5 years old. All patients were pretreated with antibiotics. Salmonella typhi was detected by culture in 109 cases (64%), by Widal's test in 84 (49%), and by both in 23 (14%). All 79 isolates that were multidrug resistant were sensitive to ofloxacin, cefotaxime, and ceftriaxone. Clinical features of infections due to resistant S typhi did not differentiate these from other cases of typhoid. Fifty-five infections (70%) due to resistant S typhi were treated with ofloxacin and 24 (30%) with ceftriaxone. Sixteen patients had complications, and all recovered.

Epidemiology of nontyphoidal salmonellae at a tertiary care center in northeast Florida.

Nontyphoidal salmonellae (NTS) are often isolated from stool specimens of individuals having evaluation of gastroenteritis. The significance of isolation of NTS in a stool specimen from previously healthy individuals with gastroenteritis is not clear. The purpose of this study was to determine which serotypes were being isolated most frequently and whether some serotypes were responsible for the majority of infections. A 6-year review yielded 433 stool isolates of NTS. Only 12 isolates were from specimens other than stool. Thirty-five different strains were isolated over the last 6-year period. The most common isolates were S javiana, 126 (29%); S newport, 85 (20%); S typhimurium, 47 (11%); S muenchen, 28 (7%); and S heidelberg, 21 (6%). These five strains were isolated in each of the 6 years of the review and were responsible for 313 (72%) isolates. The most common isolate for each year was S javiana, a strain that has not previously been reported as the predominant human isolate in invasive diseases or in outbreaks. In fact, S javiana is not even among the 10 most common NTS isolates reported to the Centers for Disease Control and Prevention nationally.

Changing epidemiology of childhood meningitis.

The changing epidemiology of meningitis at Wolfson Children's Hospital in Jacksonville between 1985 and 1994 was reviewed to determine the impact of Haemophilus influenzae type b vaccination. The cases were also straified by age. A significant decrease in the cases of Haemophilus influenzae type b meningitis was found between 1991 and 1994. This was most likely due to the introduction of conjugate Haemophilus influenzae type b vaccine for young infants.

Cost-effectiveness of Haemophilus influenzae type b conjugate vaccine program in Florida.

Introduction of Haemophilus influenzae type b (Hib) vaccine has significantly decreased this disease's incidence in childhood. The cost-effectiveness and economic impact of the Hib immunization program in Florida were investigated and three periods compared: I = 1984-1988; II = 1989-1990; and III = 1991-1992. The cost per year of Hib disease in Period I was $27.48 million while that in Periods II and III was $15.95 million and $.88 million respectively. The total savings in millions were: Periods I and II = $11.53; Periods II and III = $11.07; and Periods I and III = $22.6. The greatest saving was realized between Periods I and III because of the initiation of immunization with the Hib vaccine starting at two months of age during Period III. Hib immunization is cost-effective and significant savings would more than pay for the cost of the program.

Latex particle agglutination tests on the cerebrospinal fluid. A reappraisal.

Rapid diagnostic tests are often used to identify microbial etiology of infection early. Latex particle agglutination (LPA) tests on the cerebrospinal fluid (CSF) are frequently used for purpose of rapid diagnosis. We evaluated their usefulness in management of patients with suspected meningitis. We also evaluated the cost effectiveness of LPAs during an 11-month period; 1,540 CSF specimens were tested for H. influenzae type b, Group B streptococcal (GBS), N. meningitidis and S. pneumoniae using LPAs. Only 27 were positive. LPAs were useful in management of only the neonates with GBS infection. On the whole, LPAs were very expensive and not cost-effective.

Haemophilus influenzae type B invasive disease in urban and rural children: immunization patterns and prevalence of disease.

To examine the impact of the introduction of Haemophilus influenzae type b (Hib) conjugate vaccine, we reviewed the incidence of Hib invasive disease in the state of Florida from 1984 to 1992. We analyzed the incidence of disease in two populations of children, one residing in an urban area and the other in a rural area. This study was designed to compare incidence rates prior to and following the introduction of Hib vaccine for children. Our data show a > 80% decrease in the incidence of Hib invasive disease in the state of Florida and a similar decrease in both the urban and rural populations examined. Analysis of the data revealed that the majority of children contracting Haemophilus influenzae type b invasive disease in both populations were either not immunized or were only partially immunized.