Pneumococcal infections in children after transplantation.

Bacterial infections in recipients of bone marrow and solid-organ transplants remain a major cause of morbidity and death. The cases of 42 children who had undergone transplantation and developed an infection with Streptococcus pneumoniae were retrospectively reviewed. Thirty-four patients had 1 episode of infection, whereas 7 had 2 episodes and 1 had 3 episodes of infection. Solid-organ recipients were more likely to have recurrent invasive disease (P<.02). A total of 31 (74%) of 42 patients were on immunosuppressive therapy, and 74% had been on antimicrobial therapy within 30 days before diagnosis of S. pneumoniae infection. Only 33% of eligible patients had received a pneumococcal vaccine. Twenty-six percent of isolates recovered were not susceptible to penicillin, and 18% were not susceptible to ceftriaxone. Two patients experienced infection-related deaths; one of these had a penicillin-nonsusceptible isolate. The antimicrobial susceptibilities and outcome of infections with S. pneumoniae in patients who have undergone transplantation are similar to those in the general pediatric population.

Linezolid for the treatment of community-acquired pneumonia in hospitalized children. Linezolid Pediatric Pneumonia Study Group.

OBJECTIVE: To determine the safety, tolerance, pharmacokinetics and efficacy of linezolid, a new oxazolidinone antibiotic in the treatment of community-acquired pneumonia in hospitalized children. DESIGN: A Phase II, open label multicenter study of intravenous linezolid followed by oral linezolid suspension, both at a dose of 10 mg/kg every 12 h. Efficacy was assessed at 7 to 14 days after the last dose of linezolid. PATIENTS: Children 12 months to 17 years old with community-acquired pneumonia admitted to the hospital of 14 participating centers. RESULTS: From July 21, 1998, through May 14, 1999, 79 children were enrolled and 78 received linezolid. Sixty-six children completed treatment and follow-up and were evaluable for clinical outcome. The median age of the evaluable patients was 3 years (range, 1 to 12 years); 47 were 2 to 6 years old. Pathogens were isolated from blood or pleural fluid cultures in 8 children: Streptococcus pneumoniae, 6 (2 penicillin-resistant); Group A Streptococcus, 1; methicillin-resistant Staphylococcus aureus, 1. Chest tubes were placed in 9 patients. The mean total duration of intravenous and oral administration was 12.2 +/- 6.2 days (range, 6 to 41 days). The mean peak and trough plasma concentrations of linezolid were 9.5 +/- 4.8 and 0.8 +/- 1.2 microg/ml, respectively. At the follow-up visit 7 to 14 days after the last dose of linezolid, 61 patients (92.4%) were considered cured including all the patients with proven pneumococcal pneumonia, one failed (methicillin-resistant Staphylococcus aureus) and 4 were considered indeterminate. The most common adverse effects in the intent to treat group were diarrhea (10.3%), neutropenia (6.4%) and elevation in alanine aminotransferase (6.4%). CONCLUSIONS: Linezolid was well-tolerated and could be considered an alternative to vancomycin for treating serious infections caused by antibiotic-resistant Gram-positive cocci in children pending results of additional studies.

Outcome of invasive infections outside the central nervous system caused by Streptococcus pneumoniae isolates nonsusceptible to ceftriazone in children treated with beta-lactam antibiotics.

OBJECTIVE: To determine the outcome of children treated primarily with beta-lactam antibiotics for a systemic infection outside the central nervous system (CNS) caused by isolates of Streptococcus pneumoniae nonsusceptible to ceftriaxone (MIC > or = 1.0 microg/ml). DESIGN: Retrospective review of the medical records of children identified prospectively with invasive infections outside of the CNS caused by isolates of S. pneumoniae that were not susceptible to ceftriaxone between September, 1993, and August, 1999. A subset of this group treated primarily with beta-lactam antibiotics was analyzed for outcome. PATIENTS: Infants and children with pneumococcal infections cared for at eight children's hospitals. RESULTS: Among 2,100 patients with invasive infections outside the CNS caused by S. pneumoniae, 166 had isolates not susceptible to ceftriaxone. One hundred patients treated primarily with beta-lactam antibiotics were identified. From this group 71 and 14 children had bacteremia alone or with pneumonia, respectively, caused by strains with an MIC of 1.0 microg/ml. Bacteremia or pneumonia caused by isolates with a ceftriaxone MIC > or = 2.0 microg/ml occurred in 6 and 5 children, respectively. Three children with septic arthritis and 1 with cellulitis had infections caused by strains with an MIC to ceftriaxone of 1.0 microg/ml. Most were treated with parenteral ceftriaxone, cefotaxime or cefuroxime for one or more doses followed by an oral antibiotic. All but one child were successfully treated. The failure occurred in a child with severe combined immune deficiency and bacteremia (MIC = 1.0 microg/ml) who remained febrile after a single dose of ceftriaxone followed by 12 days of cefprozil. CONCLUSION: Ceftriaxone, cefotaxime or cefuroxime are adequate to treat invasive infections outside the CNS caused by pneumococcal isolates with MICs up to 2.0 microg/ml, a concentration currently considered resistant for these antibiotics by National Committee for Clinical Laboratory Standards breakpoints.

Pneumococcal facial cellulitis in children.

OBJECTIVE: To review the epidemiology and clinical course of facial cellulitis attributable to Streptococcus pneumoniae in children. DESIGN: Cases were reviewed retrospectively at 8 children's hospitals in the United States for the period of September 1993 through December 1998. RESULTS: We identified 52 cases of pneumococcal facial cellulitis (45 periorbital and 7 buccal). Ninety-two percent of patients were <36 months old. Most were previously healthy; among the 6 with underlying disease were the only 2 patients with bilateral facial cellulitis. Fever (temperature: >/=100.5 degrees F) and leukocytosis (white blood cell count: >15 000/mm(3)) were noted at presentation in 78% and 82%, respectively. Two of 15 patients who underwent lumbar puncture had cerebrospinal fluid with mild pleocytosis, which was culture-negative. All patients had blood cultures positive for S pneumoniae. Serotypes 14 and 6B accounted for 53% and 27% of isolates, respectively. Overall, 16% and 4% were nonsusceptible to penicillin and ceftriaxone, respectively. Such isolates did not seem to cause disease that was either more severe or more refractory to therapy than that attributable to penicillin-susceptible isolates. Overall, the patients did well; one third were treated as outpatients. CONCLUSIONS: Pneumococcal facial cellulitis occurs primarily in young children (<36 months of age) who are at risk for pneumococcal bacteremia. They present with fever and leukocytosis. Response to therapy is generally good in those with disease attributable to penicillin-susceptible or -nonsusceptible S pneumoniae. Ninety-six percent of the serotypes causing facial cellulitis in this series are included in the heptavalent-conjugated pneumococcal vaccine recently licensed in the United States.

Pneumococcal mastoiditis in children.

OBJECTIVE: To determine the impact of antibiotic resistance on the frequency, clinical features, and management/outcome of mastoiditis attributable to Streptococcus pneumoniae. DESIGN: Retrospective review of the medical records of children with mastoiditis caused by S pneumoniae from September 1993 through December 1998. PATIENTS: Infants and children with pneumococcal mastoiditis cared for at 8 children's hospitals in the United States. RESULTS: Thirty-four children with pneumococcal mastoiditis were identified. The median age of the children was 12 months (range: 2 months-12.5 years); 28 (82%) were

Pneumococcal conjugate vaccines - implications for community antibiotic prescribing.

Infections caused by Streptococcus pneumoniae are a major cause of morbidity and mortality in the pediatric population worldwide. Development of increasing resistance to multiple classes of antibiotics is making treatment of infections caused by this organism much more difficult. In order to prevent disease, a 23-valent pneumococal polysaccharide vaccine is available. However, this vaccine is poorly immunogenic in infants and young children. The development and licensing of pneumococcal conjugate vaccines that are safe and effective in the pediatric population is an important step in our ability to decrease the prevalence of pneumococcal disease seen.

Group-specific antibody levels surrounding invasive pneumococcal illness in children infected with human immunodeficiency virus.

Pneumococcal antibody levels surrounding systemic pneumococcal illness (SPI) were measured in children infected with human immunodeficiency virus (HIV). Archived serum samples were collected from 28 HIV-infected children who had 34 cases of SPI, caused by pneumococcal groups 4, 6, 9, 14, 19, and 23. Serum samples collected within 23 weeks before and 13 weeks after the SPI were assayed by ELISA for antipneumococcal polysaccharide (PnPs) IgG antibody to 6 representative pneumococcal serotypes. There was a wide range (0. 16-30.80 microg/mL) of pre-SPI anti-PnPs antibody levels to the presumed infecting serotypes, with a geometric mean level of 0.83 microg/mL (n=34). Seventy-six percent of the antibody values were <2.0 microg/mL, and 95% were <5.0 microg/mL. Homologous seroresponses (>/=4-fold rise in anti-PnPs antibody) were detected in only 4 (27%) of 15 paired serum samples. Heterologous, noninfecting group seroresponses were detected frequently (72%) in the paired serum samples from these 4 homologous group seroresponders.

Clinical characteristics and outcome of children with pneumonia attributable to penicillin-susceptible and penicillin-nonsusceptible Streptococcus pneumoniae.

OBJECTIVE: To compare the clinical characteristics, treatment, and outcome of pediatric patients with pneumonia attributable to isolates of Streptococcus pneumoniae that were either susceptible or nonsusceptible to penicillin. DESIGN: Multicenter, retrospective study. SETTING: Eight children's hospitals in the United States. PARTICIPANTS: Two hundred fifty-four children with pneumococcal pneumonia identified from patients enrolled in the United States Pediatric Multicenter Pneumococcal Surveillance Study during the 3-year period from September 1, 1993 to August 31, 1996. OUTCOME MEASURES: Demographic and clinical variables including necessity for and duration of hospitalization, frequency of chest tube placement, antimicrobial therapy, susceptibility of isolates, and clinical outcome. RESULTS: There were 257 episodes of pneumococcal pneumonia that occurred in 254 patients. Of the 257 isolates, 22 (9%) were intermediate and 14 (6%) were resistant to penicillin; 7 (3%) were intermediate to ceftriaxone and 5 (2%) were resistant to ceftriaxone. There were no differences noted in the clinical presentation of the patients with susceptible versus nonsusceptible isolates. Twenty-nine percent of the patients had a pleural effusion. The 189 (74%) hospitalized patients were more likely to have an underlying illness, multiple lung lobe involvement, and the presence of a pleural effusion than nonhospitalized patients. Fifty-two of 72 hospitalized patients with pleural effusions had a chest tube placed, and 27 subsequently underwent a decortication drainage procedure. Eighty percent of the patients treated as outpatients and 48% of the inpatients received a parenteral second or third generation cephalosporin followed by a course of an oral antimicrobial agent. Two hundred forty-eight of the patients (97.6%) had a good response to therapy. Six patients died; however, only 1 of the deaths was related to the pneumococcal infection. CONCLUSION: The clinical presentation and outcome of therapy did not differ significantly between patients with penicillin-susceptible versus those with nonsusceptible isolates of S pneumoniae. Hospitalized patients were more likely to have underlying illnesses, multiple lobe involvement, and the presence of pleural effusions than patients who did not require hospitalization. In otherwise normal patients with pneumonia attributable to penicillin-resistant pneumococcal isolates, therapy with standard beta-lactam agents is effective.

Pediatric pneumococcal bone and joint infections. The Pediatric Multicenter Pneumococcal Surveillance Study Group (PMPSSG).

OBJECTIVE: To describe the clinical and microbiological characteristics of infants and children with bone and joint infections caused by penicillin-susceptible and penicillin-nonsusceptible strains of Streptococcus pneumoniae. DESIGN: Multicenter, prospective patient accrual; retrospective chart review of identified patients. SETTING: Eight children's hospitals in the United States. PARTICIPANTS: Forty-two children with bone and/or joint infections prospectively enrolled in the United States Pediatric Multicenter Pneumococcal Surveillance Study from September 1, 1993 to August 31, 1996. OUTCOME MEASURES: Data were collected on multiple variables, including age, gender, race, days of symptoms before and during hospitalization, antibiotic and surgical therapy, laboratory and imaging studies. RESULTS: Of the 42 children enrolled (21 bone, 21 joint infections), 14 had isolates that were not susceptible to penicillin. Eight of 16 (50%) strains isolated from children who received antibiotics within 4 weeks before hospitalization were not susceptible to penicillin, compared with 4 of 15 (27%) strains isolated from children without previous antibiotic exposure. Clinical response to therapy was similar between children infected by penicillin-susceptible strains compared with those infected by penicillin-nonsusceptible strains, including duration of hospitalization (9.1 days vs 11.2 days), days of intravenous antibiotic therapy (25.3 days vs 24.6 days), days of fever (3.6 days vs 3.1 days), and sequelae (14% vs 7%). The most commonly prescribed single agents for parenteral therapy in definitive treatment were ceftriaxone (36%), penicillin (15%), and clindamycin (15%). Oral therapy followed parenteral therapy in 56% of children. The mean (+/- standard deviation) duration of total antibiotic therapy in children with osteomyelitis was 57.5 +/- 48.6 days (range, 23-196 days) and 29.2 +/- 11.8 days (range, 12-67 days) for arthritis. Late sequelae (long-term destructive changes of the bone or joint) were documented in 5 (12%) children, 4 with osteomyelitis, and 1 with arthritis. Sequelae occurred in 30% of children with long bone osteomyelitis associated with infection in the adjacent joint. The age of children with sequelae was younger than those without sequelae (6.4 months vs 18.6 months). CONCLUSIONS: The demographic characteristics and anatomic sites of infection in our patients were similar to previously published series collected from single institutions before the emergence of significant antibiotic resistance in S pneumoniae. Our analysis suggests that children infected by penicillin-nonsusceptible strains have a similar clinical response to therapy when compared with children infected by penicillin-susceptible strains.

Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use.

OBJECTIVES: To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone. DESIGN AND PATIENTS: Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight children's hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review. OUTCOME: Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone. RESULTS: Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 microgram/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (>/=8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone. CONCLUSIONS: Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. (ABSTRACT TRUNCATED)

Three-year multicenter surveillance of systemic pneumococcal infections in children.

OBJECTIVE: To track antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from children with systemic infections and determine outcome of treatment. DESIGN: A 3-year (September 1993 through August 1996) prospective surveillance study of all invasive pneumococcal infections in children. PATIENTS: Infants and children cared for at eight children's hospitals in the United States with culture-proven systemic pneumococcal infection. RESULTS: One thousand two hundred ninety-one episodes of systemic pneumococcal infection were identified in 1255 children. An underlying illness was present in the children for 27% of the episodes. The proportion of isolates that were nonsusceptible to penicillin or ceftriaxone increased annually and nearly doubled throughout the 3-year period; for the last year the percentages of isolates nonsusceptible to penicillin and ceftriaxone were 21% and 9.3%, respectively. There was no difference in mortality between patients with penicillin-susceptible or nonsusceptible isolates. Only 1 of 742 patients with bacteremia had a repeat blood culture that was positive > 1 day after therapy was started. All 24 normal children with bacteremia attributable to isolates resistant to penicillin had resolution of their infection; the most common treatment regimen was a single dose of ceftriaxone followed by an oral antibiotic. CONCLUSIONS: The percentage of pneumococcal isolates nonsusceptible to penicillin and ceftriaxone increased yearly among strains recovered from children with systemic infection. Because empiric antibiotic therapy already has changed for suspected pneumococcal infections, antibiotic resistance has not been associated with increased mortality. Careful monitoring of antibiotic susceptibility and outcome of therapy is necessary to continually reassess current recommendations for treatment.

Anti-CD11b monoclonal antibody in an infant rat model of Haemophilus influenzae type b sepsis and meningitis.

Five-day-old infant rats were injected intraperitoneally (i.p.) with anti-CD11b monoclonal antibody (1 B6) at a dose of 2 mg/kg or phosphate-buffered saline (PBS) either 1 h before or 3 or 24 h after inoculation with 10(5) cfu Haemophilus influenzae type b (Hib). When administered 1 h before infection, 23% of the 1B6- versus 17% of the PBS-treated rats and 87% of the 1B6- versus 83% of the PBS-treated animals died at 24 and 48 h, respectively. There was a similar mortality for 1B6 or PBS treatment at 3 h after infection. Thirteen of 15 (87%) 1B6 animals versus 16/17 (94%) PBS animals had positive CSF cultures at 48 h. No differences in mortality were observed in separate experiments where animals received 1B6 or PBS 3 or 24 h after infection with Hib and were treated with a single ampicillin dose (100 mg/kg) 24 h after infection. The median CSF white blood cell count/mm3 was 5627 and 4860 for the animals with meningitis receiving 1B6 and PBS, respectively, although the 1B6-treated animals had a lower percentage of polymorphonuclear cells in the CSF (P = 0.05). Histologic examination of the meninges, choroid plexus and cochlea showed a slight decrease in the numbers of inflammatory cells in animals treated with 1B6. 1B6 did not change the incidence of meningitis and only slightly decreased the degree of inflammation within the central nervous system, although animals treated with 1B6 have an altered CSF leucocyte response with the presence of more mononuclear cells as opposed to polymorphonuclear cells in their CSF. 1B6 may play a role in inhibiting neutrophil emigration to sites of inflammation within the central nervous system but is not beneficial in decreasing mortality in an infant rat model of H. influenzae type b sepsis and meningitis.

Presumed central nervous system Whipple's disease in a child: case report.

Whipple's disease is a rare, chronic, multisystem illness that is pathologically characterized by the accumulation of macrophages in the involved tissue that have a positive periodic acid-Schiff reaction. It is typically seen in middle-aged white men, and only four cases involving persons younger than 15 years of age have been reported. CNS Whipple's disease without intestinal manifestations is rare; only six cases have been reported in the literature, all involving adults. We report the case of a young boy with clinical, laboratory, radiographic, and pathological signs and symptoms consistent with CNS Whipple's disease who responded to therapy with trimethoprimsulfamethoxazole.

Hematogenous bacterial meningitis in an intercellular adhesion molecule-1-deficient infant mouse model.

Mice genetically deficient in the gene encoding for intercellular adhesion molecule-1 (ICAM-1) production were compared with wild-type mice after injection with Haemophilus influenzae type b (Hib) or Streptococcus pneumoniae. The incidence of Hib bacteremia was greater in the ICAM-1-deficient mice than wild-type mice (P = .007), but mortality was greater for wild-type mice at 24 h (P = .03). In contrast, the incidence of S. pneumoniae bacteremia was equivalent but mortality was greater in ICAM-1-deficient mice at 24 h (P = .0003). More ICAM-1-deficient mice had cerebrospinal fluid cultures (CSF) positive for Hib (P = .04), whereas all animals at sacrifice had CSF cultures positive for S. pneumoniae. CSF white blood cell counts and histology of the meninges and cochlea were no different between groups for either organism. ICAM-1 deficiency may be protective early in Hib infection but has a detrimental effect in S. pneumoniae infection.

Pediatric lung abscess: clinical management and outcome.

Pulmonary abscess is an infrequent but significant problem in children. We retrospectively reviewed the charts of 45 children with documented lung abscesses admitted and treated at Texas Children's Hospital, Houston, over the 11-year period from January, 1982, to December, 1993, and report their presenting symptoms, bacteriology, clinical management and outcome.

Infectious disease of public health significance among children and adolescents in Texas.

In the past decade, many infectious diseases in children that were perceived to have been almost eliminated have returned with a vengeance in Texas. Across the state, vaccination rates are exceptionally low, and outbreaks of measles, mumps, and pertussis have been identified. Tuberculosis cases in children increased 77%, and cases of congenital syphilis increased 578% between 1987 and 1991. The new epidemic of HIV infection has placed additional strain on an already overburdened, inadequate public health system in Texas. This article identifies some of the major infections of public health significance among the children of Texas. A common theme for most of these problems is that they are preventable diseases that are not being prevented. Many children in Texas will suffer now and in the future if these public health problems remain ignored.

Molecular epidemiology of coagulase-negative Staphylococcus blood isolates from neonates with persistent bacteremia and children with central venous catheter infections.

Multilocus enzyme electrophoresis was used to genetically characterize sequential isolates of coagulase-negative staphylococci (CONS) from 3 neonates with persistent bacteremia and organisms cultured from several sites in 23 children with presumed catheter-related sepsis (CRS). For 2 of 3 neonates and 21 (91%) of 23 of the patients with presumed CRS, the same CONS clone was isolated from multiple consecutive blood cultures (mean, 7.3 isolates; range, 3-19). For the 23 children with presumed CRS, 7 (30%) had catheter hub (CH) and 7 (30%) had catheter exist site (CES) cultures positive for CONS; cultures from 3 of these patients (from both CH and CES) grew CONS. Genetic analysis of isolates recovered from the CH and peripheral and central venous catheter blood cultures of all 7 patients revealed clonal identity of the strain grown from all sites. In contrast, only 4 (57%) of 7 of the CONS isolates from the CES were the same clone as that isolated from the blood. These data suggest that repetitive isolation of CONS during the course of CRS is due to ongoing bacteremia, not culture contamination with distinct CONS isolates. The results also are consistent with the hypothesis that the CH is a more likely site of initial colonization by CONS than the exist site in patients with CRS.

Antibiotic therapy and acute outcome of meningitis due to Streptococcus pneumoniae considered intermediately susceptible to broad-spectrum cephalosporins.

Children with meningitis due to Streptococcus pneumoniae isolates that are relatively or fully resistant to penicillin and have decreased susceptibility to broad-spectrum cephalosporins (MIC, > or = 2.0 micrograms/ml) who have failed treatment with broad-spectrum cephalosporins have been reported. The National Committee for Clinical Laboratory Standards has newly revised guidelines indicating that S. pneumoniae isolates associated with meningitis for which the MICs are > or = 0.5 micrograms/ml should be considered resistant to broad-spectrum cephalosporins. This recommendation is not clearly based on data related to clinical outcome and may be too conservative. We present data on five children who had S. pneumoniae meningitis due to isolates that were relatively or fully resistant to penicillin (MIC range, 0.125 to 4.0 micrograms/ml) and had cefotaxime or ceftriaxone MICs of 0.50 to 2.0 micrograms/ml. Their clinical courses and outcomes were comparable to those of five children with S. pneumoniae meningitis due to strains that were relatively or fully resistant to penicillin and were inhibited by cefotaxime at concentrations of < or = 0.25 micrograms/ml, as well as to those of 25 patients with S. pneumoniae meningitis due to penicillin-susceptible isolates identified during the same period. Children with meningitis due to S. pneumoniae with cefotaxime or ceftriaxone MICs of < or = 1.0 micrograms/ml may be adequately treated with these antibiotics. Further clinical data are required before solid recommendations can be made regarding cephalosporin breakpoints for S. pneumoniae.