Waheed N. Khan

An outbreak of Hemophilus influenzae type b meningitis in an enclosed hospital population

Five cases of HITB maningitis occurred within six months in an enclosed population of 28 to 32 chronically ill children. Studies of nasopharyngeal carriage and serum HITB anticapsular antibodies were started after the third case occurred. Two patients had low (less than 0.04 and 0.05mug/ml) antibodies and were not carriers when studied prior to onset of their disease. The carriage rate was approximately 20% among the children. Carriage was usually prolonged, and acquisition was not prevented by high antibody levels. Attempts to arrest this outbreak with type b polysaccharide immunization and ampicillin therapy are discussed in the context of HITB meningitis as a contagious disease.

Immunoglobulin M determinations in neonates and infants as an adjunct to the diagnosis of infection

Immunoglobulin gamma-M levels and C-reactive protein were studied in 613 neonates and infants. A high correlation between high IgM levels and infection was found. However, C-reactive protein was not found to be of value as a parameter of infection. Cord blood did not contain C-reactive protein, while IgM levels among healthy newborns were normal. Both typical and atypical sudden death cases yielded high IgM levels, but the results were inconclusive because of the small number of cases tested. Determination of IgM levels by a simple radial diffusion method is recommended, provided specific reference standard sera is used with commercially prepared immunoglobulin plates.

Persistent Purulent Otitis Media

Of 429 children with acute otitis media who returned for follow-up evalu ation, 49 (11%) were unresponsive to a 10- to 14-day course of ampicillin, amoxicillin, or erythromycin/sulfisoxazole. Patients with persistent purulent otitis media were noted to have immobile, bulging, yellow or grey, abscessed tympanic membranes at the follow-up visit. A myringotomy was performed on 45 children. Cultures of middle-ear exudate yielded ampicillin-resistant Haemophilus influenzae in 14 (31%), ampicillin-susceptible pathogens ( H. in fiuenzae or Streptococcus pneumoniae) in 23 (51%), and no growth in 8 (18%).

Ceftazidime in the treatment of meningitis in infants and children over one month of age

Ceftazidime, a new beta-lactamase-resistant cephalosporin, was compared with a combination of ampicillin and chloramphenicol for the treatment of meningitis in 100 infants and children aged one month to 15 years. In this open, randomized trial conducted in the Dominican Republic, 61 patients received 50 mg/kg of ceftazidime intravenously every eight hours; 39 received ampicillin plus chloramphenicol in conventional dosages. Seventy-eight of the patients had discernible isolates in samples from cerebrospinal fluid, six had a positive diagnostic Directogen result, and the remainder either had miscellaneous pathogens evident in samples of cerebrospinal fluid, bacteriologic growth in cultures of blood samples only, or no bacteriologic growth in cultures of either cerebrospinal fluid or blood. Among patients with discernible etiologic agents in samples of cerebrospinal fluid, 11 of 57 (19 percent) ceftazidime-treated patients died, and five of 27 (19 percent) patients treated with the combination died. Mortality by pathogen was as follows for patients who received ceftazidime or ampicillin plus chloramphenicol, respectively: Hemophilus influenzae, two of 27 (7 percent) and one of 15 (6 percent); Streptococcus pneumoniae, six of 12 (50 percent) and two of five (40 percent); Neisseria meningitidis, none of 11 (0 percent) and one of six (17 percent); and Salmonella, neither of two (0 percent) and one of one (100 percent). Overall mortality in the ceftazidime group was 20 percent versus 21 percent in the combination group. No significant toxicities were noted in the patients treated with ceftazidime.

Aztreonam in the Treatment of Gram-Negative Meningitis and Other Gram-Negative Infections

Ninety patients (41 males, 49 females) with a diagnosis of meningitis, urinary tract infection (UTI), gastroenteritis or other miscellaneous gram-negative infections were enrolled. Their ages ranged from 7 days to 10 years, with a mean age of 4 months. 58 (63%) patients had an etiology confirmed by either positive culture (52; 89%) or latex agglutination (6; 10%). 41 of these patients had meningitis diagnosed by positive CSE culture (38) or by positive CSF latex agglutination (3); 27/41 patients also had positive blood cultures. Aztreonam MIC100 for 27 isolates of Haemophilus influenzae, all ampicillin-sensitive, was 0.19 micrograms/ml; 4 Salmonella sp., 1 Neisseria meningitidis and 1 Serratia marcescens isolates were inhibited by 0.19 micrograms/ml, and the MIC100 for 2 Klebsiella pneumoniae, 1 Proteus vulgaris and 2 Pseudomonas aeruginosa isolates were 0.045 and 0.19, 0.022 and 12.5 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics of Efavirenz 400 mg Once Daily During Pregnancy and Post-Partum

Background A clinical trial showed that efavirenz 400 mg once daily (EFV400) is as effective as the standard adult dose. World Health Organization recommends EFV400 as an alternative first-line agent, but data are lacking in the third trimester of pregnancy (TT). We investigated the pharmacokinetics, efficacy, and CYP2B6 pharmacogenetics in HIV-infected women (WLWH) on EFV400 during TT and post-partum (PP). Methods An open-label 2-center study (United Kingdom, Uganda) was conducted in WLWH receiving antiretroviral regimens containing efavirenz 600 mg, who had their efavirenz dose reduced to EFV400. Weekly therapeutic drug monitoring (TDM), steady-state pharmacokinetic profiles (TT and PP), safety, virological efficacy, and CYP2B6 polymorphisms at positions 516 (C > T) and 938 (T > C) were evaluated. Results Twenty-five WLWH of African origin were enrolled. All had viral loads <50 copies/mL at baseline, which were maintained throughout the study. No infant was HIV infected. No WLWH were withdrawn due to low EFV400 TDM results. Geometric mean ratios (TT/PP; 90% confidence interval) for EFV400 maximum observed plasma concentration, area under the curve, and plasma concentration measured 24 hours after the observed dose were 0.97 (.85-1.10), 0.87 (.76-.99), and 0.77 (.65-.91), respectively. Five of 25 WLWH were slow metabolizers. Conclusions Although EFV400 pharmacokinetic parameters were slightly lower for TT compared with PP values, efavirenz concentrations exceeded cutoff levels established by the study and those measured in antiretroviral-naive patients receiving EFV400 in ENCORE1. All subjects maintained a viral load <50 copies/mL, suggesting that EFV400 can be used in pregnant WLWH.