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.

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.

Acute otitis media caused by Streptococcus pneumoniae in children's hospitals between 1994 and 1997.

OBJECTIVE: To determine patterns of resistance for isolates of Streptococcus pneumoniae recovered from middle ear fluids of children from eight children's hospitals between September, 1994, and August, 1997. METHODS: Data were extracted retrospectively from the medical records of eight children's hospitals. A standardized data form was completed for each episode of pneumococcal infection. Systemic isolates (blood and pleural, synovial and spinal fluids) of S. pneumoniae were collected during the same period. All isolates of S. pneumoniae from each center were sent to a central laboratory. Susceptibility to penicillin and ceftriaxone was determined by microbroth dilution. Organisms were considered nonsusceptible to penicillin if the minimum inhibitory concentration was > or = 0.1 microg/ml and nonsusceptible to ceftriaxone if the minimum inhibitory concentration was > or = 1.0 microg/ml. RESULTS: S. pneumoniae was recovered from the middle ear fluids of 707 children from all centers during the study period. Thirty-nine (5.5%) were infections recorded at 4 centers which evaluated middle ear fluid only sporadically and were not included in this analysis. The remaining 668 infections reported by the 4 remaining participating hospitals reflect the experience of 608 children. There were 54% boys; 440 (73%) were Caucasian, 111 (18%) were African-American, 38 (6%) were Hispanic and for 19 (3%) the race was not recorded. The children ranged in age from 16 days to 13.8 years with a mean (+/-sD) of 26.0 (+/- 26.1) months. Children who received antibiotics in the 30 days before the middle ear isolate was recovered were more likely to harbor a resistant strain of S. pneumoniae than children who had not recently received an antibiotic (P < 0.001). Isolates recovered from children with spontaneous otorrhea were more likely to be susceptible to penicillin than isolates recovered during myringotomy, with or without the insertion of tympanostomy tubes (P < 0.01). There was wide variation in the susceptibility of middle ear isolates to penicillin and ceftriaxone according to geographic location; however, in every locale the middle ear isolates were less likely to be susceptible to penicillin and ceftriaxone than systemic isolates of S. pneumoniae. CONCLUSION: The prevalence of penicillin-resistant and cephalosporin-resistant S. pneumoniae in middle ear isolates derived from children cared for at four different children's hospitals was quite variable. In some locations the prevalence of resistance is still increasing, whereas in other areas the rate of resistance was at a plateau during the period of surveillance. The prevalence of isolates of S. pneumoniae susceptible to penicillin and ceftriaxone was always less common among middle ear isolates than among systemic isolates. Previous antibiotic use remains the most predictive factor for the recovery of isolates resistant to penicillin and ceftriaxone.

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

Efficacy and safety of ampicillin/sulbactam and cefuroxime in the treatment of serious skin and skin structure infections in pediatric patients. UNASYN Pediatric Study Group.

BACKGROUND: Pediatric skin and skin structure infections are often polymicrobial and require empiric therapy effective against pathogens that may be resistant to many antimicrobial agents. The present study tested the efficacy and safety of a parenteral beta-lactam/beta-lactamase inhibitor combination, ampicillin/sulbactam, and a beta-lactamase-stable cephalosporin, cefuroxime, in serious pediatric skin and skin structure infections requiring hospitalization and parenteral antimicrobial therapy. METHODS: This was a multicenter, randomized, prospective, comparative open label trial that enrolled patients 3 months through 11 years of age. Patients received 150 to 300 mg/kg/day ampicillin/sulbactam in equally divided intravenous doses every 6 h. Cefuroxime was given in a dosage of 50 to 100 mg/kg/day either intravenously or intramuscularly in equally divided doses every 6 or 8 h. Maximum treatment was not to exceed 14 days. Patients could receive subsequent oral antimicrobial treatment at the investigator's discretion. RESULTS: At final evaluation for clinical efficacy, 78.0% (n = 46) of the 59 evaluable patients who received ampicillin/sulbactam were cured and 22.0% (n = 13) were improved. The respective values for the 39 evaluable patients treated with cefuroxime were 76.9% (n = 30) and 23.1% (n = 9). At the end of treatment all pathogens were eradicated from 93.2% (n = 55) of 59 patients treated with ampicillin/sulbactam and from 100% of 39 who received cefuroxime. There were no significant differences between treatments in clinical or bacteriologic efficacy. Both ampicillin/sulbactam and cefuroxime were well-tolerated. CONCLUSION: Both ampicillin/sulbactam and cefuroxime provide safe and effective parenteral antibiotic therapy in pediatric patients with serious skin and skin structure infections.

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.

Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis.

STUDY OBJECTIVE: Tobramycin is commonly used to treat respiratory tract infections in patients with cystic fibrosis. We designed a study to determine the pharmacokinetics and safety of once-daily dosing of tobramycin in this population. DESIGN: Multiple blood samples were collected from each patient, and serum concentrations of tobramycin were determined by a fluorescence polarization immunoassay. Blood urea nitrogen and serum creatinine levels were measured every 2 to 3 days, and audiometric evaluations were performed at the start and end of therapy. MEASUREMENTS AND RESULTS: Eighteen patients (mean age, 24.6 years) received tobramycin at doses of 7 to 15 mg/kg/d as a single-dose infusion over 20 min. The maximum serum concentration of tobramycin ranged from 40.1 to 64.6 mg/L. A mean dose of 11.9+/-1.9 mg/kg was needed to obtain a theoretical mean peak serum concentration of 42.4+/-4.5 mg/L. The mean total body clearance, apparent volume of distribution, and elimination half-life was 1.7+/-0.4 mL/min/kg, 0.27+/-0.06 L/kg, and 1.8+/-0.3 h, respectively. The period of time that the serum concentration exceeded eight times the theoretical minimum inhibitory concentration of 1 mg/L ranged from 2.1 to 4.4 h, which was nearly five times longer compared with the use of divided daily doses in the same patients during previous hospitalizations. No nephrotoxicity, ototoxicity, or adverse effects occurred in any patient. CONCLUSION: Based on our data, tobramycin may be used safely in once-daily doses to treat exacerbations of respiratory tract infections in patients with cystic fibrosis.

Pharmacokinetics of cefpirome in pediatric patients.

Cefpirome is a new investigational cephalosporin. We designed a study to determine the pharmacokinetics and tolerance of cefpirome in pediatric patients. A single dose of cefpirome was administered intravenously over 15 min to 18 patients (age 0.5 to 18 years). The doses were 10 mg/kg of body weight for five patients, 25 mg/kg of body weight for seven patients, and 50 mg/kg of body weight for six patients. Blood samples were collected at 0, 0.25, 0.5, 1, 3, 5, and 8 h after the dose, and cefpirome was measured by a high-performance liquid chromatography method. The maximum concentration in serum ranged from about 53.6 to 454 micrograms/ml after doses of 10 to 50 mg/kg. The total body clearance, apparent volume of distribution, and elimination half-life were 2.15 +/- 0.70 ml/min/kg, 0.32 +/- 0.32 liter/kg, and 1.8 +/- 1.3 h, respectively. No significant adverse effects were attributed to cefpirome. These data may be useful in conducting efficacy and safety studies of cefpirome in pediatric patients.

Pharmacokinetics and cerebrospinal fluid concentrations of cefixime in infants and young children.

Limited data are available about cefixime pharmacokinetics and cerebrospinal fluid (CSF) penetration in infants and young children. Ten patients with bacterial meningitis and 8 undergoing CSF shunt placement, aged 2-22 months (mean 9.5 +/- 6.5 months), were given a single dose of cefixime suspension, 8 mg/kg, before undergoing a routine lumbar puncture. Patients were fasted for 2 h before and 2 h after drug administration. Blood samples were collected just before drug administration (0 h) and at 1, 2, 3, 4, 6, 8 h; CSF was obtained at 1-8.8 h after drug administration. Cefixime was measured by a high-performance liquid chromatographic method. The peak serum concentration of cefixime ranged from 0.85 to 6.2 (mean 3.1) micrograms/ml and occurred at 2-8 h (mean 4.5). The area under the serum concentration-time curve ranged from 5.3 to 28.4 micrograms h/ml, and the elimination half-life ranged from 2.6 to 5.6 h. CSF concentrations ranged from 0.02 to 0.57 micrograms/ml. The mean CSF concentration of cefixime was 0.22 micrograms/ml in patients with meningitis and 0.10 microgram/ml in those undergoing shunt placement (p < 0.02). The mean CSF concentration/serum concentration ratio was 11.7 in patients with meningitis compared with 5.4 in those undergoing shunt procedures (p < 0.02). These data indicate that cefixime can be considered as an alternative to other antimicrobials for infants and children with respiratory and urinary tract infections, since the observed peak serum concentration exceeded the minimum inhibitory concentrations of the common pathogens by severalfold.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxic shock syndrome occurring in children with abrasive injuries beneath casts.

Staphylococcal toxic shock syndrome has been reported in a number of nonmenstrual settings, including orthopedic patients with postoperative staphylococcal wound infections. We describe two cases of toxic shock syndrome in children with focal cutaneous staphylococcal infections occurring beneath casts placed for limb immobilization. These cases illustrate a new and potentially hidden site of staphylococcal infection leading to toxic shock syndrome.