Colonization with antibiotic-resistant Streptococcus pneumoniae in children with sickle cell disease.

OBJECTIVE: Because of susceptibility to severe pneumococcal infection, children with sickle cell disease (SCD) routinely receive penicillin prophylaxis. Increasing rates of penicillin resistance have been reported throughout the world. Our objective was to assess the prevalence of nasopharyngeal colonization with Streptococcus pneumoniae and to assess the antimicrobial susceptibility of the organisms in children with SCD. STUDY DESIGN: Nasopharyngeal cultures for S. pneumoniae were obtained from all children with SCD attending clinics in a statewide university-based network. Background colonization rates were determined in children attending day care centers in some of the same locations. All recovered S. pneumoniae organisms were tested for susceptibility to penicillin, and all resistant strains were examined for susceptibility to other antibiotics. RESULTS: Overall nasopharyngeal pneumococcal colonization rates among children with SCD were 12%. Colonization was associated with age less than 2 years (p <0.001) and day care attendance for more than 20 hr/wk (p = 0.00005). More than half of these strains (62%) were resistant to penicillin, 33% having intermediate resistance (minimal inhibitory concentration 0.06 to 1 microgram/ml) and 29%, high level resistance (minimal inhibitory concentration > or = 2.0 microgram/ml). Penicillin resistance was associated with penicillin prophylaxis (p <0.01). Many of these organisms were also resistant to other classes of antibiotics. CONCLUSIONS: Although penicillin prophylaxis and pneumococcal vaccine for patients with SCD have reduced overall nasopharyngeal colonization and disease caused by S. pneumoniae (p <0.001), a higher percentage of colonizing strains are now resistant both to penicillin and to other antimicrobial agents (p <0.01). Newer strategies for preventing disease and early management of suspected pneumococcal infection in these children must be developed.

Usefulness of scanning procedures for diagnosis of fever of unknown origin in children.

During a 5-year study period, 109 patients were referred to a large children's hospital for evaluation of prolonged fever of unknown origin, defined as temperature greater than or equal to 38 degrees C (100.4 degrees F) for 3 weeks or longer and negative findings on initial examination. A two-phase protocol of outpatient followed by inpatient diagnostic studies was instituted for most patients. Confirmed diagnoses were achieved in just 36 of these children (33%) in the following disease categories: infectious, 24 (22%); autoimmune, 7 (6%); and neoplastic, 2 (2%). Scanning or special procedures and the number with positive results (in parentheses) were as follows: abdominal ultrasonography, 43 (8); abdominal computed tomography, 14 (3); indium scan 11 (5); gallium scanning, 4 (1), upper gastrointestinal tract series, 13 (2); technetium bone scanning 15 (2); bone marrow examination, 16 (1); and cranial computed tomography, 7 (0). These studies rarely led to an unsuspected diagnosis. It appears most appropriate in evaluating fever of unknown origin in children to obtain only basic laboratory studies such as a complete blood cell count, urinalysis and culture, chest radiograph, tuberculin skin test, and, in the older child, an antinuclear antibody titer. When these test results are negative, almost all children can be observed clinically for progression of illness or a focus that might then direct specific diagnostic procedures.

Significance of opacification of the maxillary and ethmoid sinuses in infants.

To evaluate the incidence and significance of radiographic sinus opacification in infants, we performed computed tomography (CT) of the maxillary and ethmoid sinuses in conjunction with routine cranial CT in 100 infants from birth to 12 months of age. CT was performed for indications other than sinusitis. Prospective concurrent clinical history was obtained and physical examination of the upper respiratory tract was performed. Of 100 infants, 16 had hypoplasia of the maxillary sinuses; 81% (13/16) of these were less than 2 months of age. The antra showed progressive increase in size during the first year of life. Of the 100 infants, 70 had CT sinus opacification, including 67% of those without historical or physical evidence of upper respiratory tract infection. There was a positive correlation of CT findings between the maxillary and ethmoid sinuses in 80% of the infants older than 2 months of age but in only 49% of the younger infants. Radiographic sinus opacification in infants is of uncertain significance and is not diagnostic of upper respiratory tract infection, much less of sinusitis.

Intrauterine herpes simplex virus infections.

Neonatal herpes simplex virus (HSV) infection is usually acquired at birth, although a few infants have had findings suggestive of intrauterine infection. We describe 13 babies who had clinical manifestations of intrauterine HSV infection, including skin lesions and scars at birth (12), chorioretinitis (eight), microcephaly (seven), hydranencephaly (five), and microphthalmia (two). All infants had combinations of these defects. Infection was proved by viral isolation in each case; all isolates were HSV-2. Two infants died during the first week of life; 10 of the surviving infants had severe neurologic sequelae, and one infant was blind. Four mothers experienced an apparent primary genital HSV infection, and one had recurrent infection, at varying times during gestation. The remaining women denied a history of symptoms of genital HSV infection. These findings indicate that intrauterine HSV infection can occur as a consequence of either primary or recurrent maternal infection and has severe consequences for the fetus.

A prospective randomized comparison of cefotaxime vs ampicillin and chloramphenicol for bacterial meningitis in children.

Fifty children with bacterial meningitis were prospectively randomized to receive cefotaxime (50 mg/kg/dose every 6 hours) or ampicillin and chloramphenicol in standard doses. Twenty-three patients received cefotaxime and 27 received standard therapy. Bacterial isolates included: Haemophilus influenzae (29), Streptococcus pneumoniae (eight), Neisseria meningitidis (eight), group B streptococci (three), and Salmonella enteritidis (two). Ten (34%) of the H. influenzae isolates were resistant to ampicillin, nine on the basis of beta-lactamase production. All strains were susceptible to cefotaxime. Clinical cure rates for the cefotaxime (100%) and standard therapy (96%) groups were similar; survival without detectable sequelae was similar, at 78% and 77%, respectively. The duration of therapy, 11.1 +/- 2.4 days (range 10 to 21 days) vs 11.9 +/- 3.9 days (range 10 to 21 days), and days to defervescence, 4.7 +/- 2.6 days (range 1 to 14 days) vs 5.6 +/- 2.9 days (range 2 to 17 days), were similar in the cefotaxime and standard therapy groups, respectively. No adverse drug reactions or side effects were noted in either group. Cefotaxime was found to be as safe and effective as standard therapy for the treatment of bacterial meningitis in children.

Specific inhibitory factors of cellular immunity in children with subacute sclerosing panencephalitis.

Employing a 51Cr release cytotoxicity microassay, and using both measles-and SSPE-infected target cells, four patients with documented SSPE were evaluated for specific cellular and humoral immunity. Mononuclear leukocytes from SSPE patients and control subjects exhibited comparable cytotoxicity. Serum and CSF from these SSPE patients inhibited the cellular response to SSPE-infected cells but not to measles-infected cells. Moreover, fresh whole serum alone from control donors produced significant 51Cr release from both cell lines, whereas SSPE whole serum was effective only against measles-infected cells. CSF from an additional ten patients with SSPE was examined for inhibitory activity: seven of these completely blocked and one partially blocked cell-mediated cytotoxicity to SSPE-infected cells. Preliminary characterization of the serum inhibitory factor suggested that it is IgM or antigen-antibody complexes. These data also suggest antigenic differences between the SSPE and measles viruses.