Dexamethasone treatment for bacterial meningitis in children and adults

Four hundred twenty-nine patients with bacterial meningitis were assigned on a nonselective alternating basis into one of two therapeutic regimens. Patients in Group I received dexamethasone in addition to standard antibacterial chemotherapy of ampicillin and chloramphenicol whereas those in Group II received antibacterial chemotherapy alone. Dexamethasone was given intramuscularly (8 mg to children younger than 12 years and 12 mg to adults every 12 hours for 3 days). Both treatment groups were comparable with regard to age, sex, duration of symptoms and state of consciousness at the time of hospitalization. A significant reduction in the case fatality rate (P less than 0.01) was observed in patients with pneumococcal meningitis receiving dexamethasone; only 7 of 52 patients died compared with 22 of 54 patients not receiving dexamethasone. A reduction in the overall neurologic sequelae (hearing impairment and paresis) was observed in patients receiving dexamethasone. This reduction was significant only in patients with Streptococcus pneumoniae meningitis; none of the 45 surviving patients receiving steroids had hearing loss whereas 4 of 32 patients not receiving dexamethasone had severe hearing loss (P less than 0.05). No significant difference was observed between the two groups with regard to time for patients to become afebrile or to regain consciousness or in the mean admission and 24- to 36-hour cerebrospinal fluid leukocyte count, glucose or protein content.     

Intensive short course chemotherapy for tuberculous meningitis.

This nonrandomized, open clinical investigation of tuberculous meningitis evaluated 53 children with Stage I (n = 8), Stage II (n = 29) and Stage III (n = 16) disease. The overall mortality was 20.8% (11 of 53) with a rate of sequelae of 35.7% (15 of 42) in survivors reflecting the advanced stages of children at diagnosis. Various combinations of standard antituberculous drugs including isoniazid, rifampin, pyrazinamide, streptomycin and ethambutol were given. Three treatment durations used during various time periods were evaluated: 12, 9 and 6 months with only the 6-month regimen receiving pyrazinamide (PZA). This prospective evaluation demonstrated that: (1) severe disease at presentation is highly associated with early mortality (P less than 0.05), regardless of drug regimen; and (2) intensive short course chemotherapy (6 months) with PZA, regardless of stage of disease at presentation, is more efficacious than longer course therapy (9 or 12 months) without PZA in preventing total negative outcomes and sequelae (P less than 0.05). This study demonstrates that a 6-month regimen containing PZA can be used in treating children with tuberculous meningitis.     

Randomized trial of four vs. seven days of ceftriaxone treatment for bacterial meningitis in children with rapid initial recovery

BACKGROUND: Seven days or more of antimicrobial treatment is the standard for bacterial meningitis, although third generation cephalosporins are usually able to sterilize cerebrospinal fluid within 24 h. The limited experience from shorter regimens in children is encouraging, and we hypothesized that in rapidly recovering patients older than 3 months of age it would pose no risk for adverse outcome. METHODS: Strict clinical and laboratory criteria were used to define rapid initial recovery, in which case ceftriaxone therapy was either stopped after 4 days (4 injections) in children born on even dates (N = 53) or continued for 7 days in patients born on odd dates (N = 47). Outcomes were compared on Day 7 of hospitalization and at 1 to 3 months after discharge. RESULTS: On Day 7 no differences (P > 0.05 for each criteria) were observed between the 4-day and the 7-day groups regarding fever, clinical signs or serum C-reactive protein concentration. At the follow-up visit 1 to 3 months after discharge the 4-day group had fewer sequelae than the 7-day group (0% vs. 5% neurologic sequelae, P = 0.39 and 3% vs. 9% hearing loss, P = 0.49, respectively). One child in the 4-day group who had fully recovered was subsequently readmitted 53 days after the first hospitalization with recurrent Haemophilus influenzae meningitis. CONCLUSIONS: Four days of ceftriaxone therapy proved to be a safe alternative in patients with rapid initial recovery from bacterial meningitis. A 4-day course of treatment is particularly beneficial for countries with limited resources.     

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)     

Paradoxical intracranial tuberculoma requiring surgical treatment

Paradoxical enlargement of intracranial tuberculomas or development of new ones during adequate antituberculous chemotherapy is an uncommon event. Treatment of such cases is controversial. Steroid therapy is usually advocated without change in the antituberculous drug program. However, in some patients whose lesions fail medical treatment, or who have superficially located large lesions, surgical therapy may be required. A 15-year-old girl with pulmonary miliary tuberculosis, tuberculous meningitis and multiple intracranial tuberculomas is presented. While her pulmonary lesions and intracranial tuberculomas except one were healed with chemotherapy, one tuberculoma increased in size 1 month after starting chemotherapy. She was followed with dexamethasone treatment in addition to antituberculous therapy for 2 months. Then, the lesion was removed because it had increased in size in spite of appropriate chemotherapy.     

Outcome of penicillin-nonsusceptible Streptococcus pneumoniae meningitis: a nested case-control study

BACKGROUND: There are few data comparing the clinical features, management and outcome of penicillin-nonsusceptible (PNSP) meningitis patients with penicillin-susceptible (PSSP) meningitis patients. METHODS: We performed a retrospective, nested case-control study comparing cases with PNSP meningitis with controls with PSSP meningitis obtained from the Immunization Monitoring Program, Active (IMPACT) cross-Canada surveillance study of invasive infections. RESULTS: There were 30 PNSP meningitis cases (10.1% of total) and 45 PSSP meningitis controls from 6 centers obtained from 297 meningitis cases in the IMPACT database from 1991 through 1999. Vancomycin was used for empiric therapy in no cases and controls in 1991 to 1993 and in all cases in 1999. A third generation cephalosporin was used in 93.3% of confirmed PNSP cases, and 70.0% also received vancomycin and/or rifampin. Penicillin was used in 66.7% of confirmed PSSP cases. PNSP cases were more likely than PSSP controls to have a second lumbar puncture (odds ratio, 4.1; P= 0.01). PNSP cases were treated with intravenous antibiotics for an average of 15.6 days compared with 12.3 days for controls ( P= 0.04). Among PNSP cases, those patients who did not receive empiric vancomycin were treated with intravenous antibiotics for an average of 18.5 days compared with 12.0 days for those who did receive empiric vancomycin ( P= 0.04). The overall mortality was 5.3%, and 36.6% of survivors had >or=1 neurologic sequelae, including 19.7% with hearing loss. In multivariate statistical models, PNSP was not a risk factor for intensive care unit admission or neurologic sequelae. CONCLUSIONS: Management of suspected bacterial meningitis and confirmed meningitis in Canadian children changed in the past decade. Treatment of PNSP meningitis is significantly different from that for PSSP meningitis. These changes have occurred in response to the emergence of PNSP in Canada. Neurologic sequelae remain common after meningitis, but there are no differences between PNSP cases and PSSP cases.     

Prediction of neurologic sequelae in childhood tuberculous meningitis: a review of 20 cases and proposal of a novel scoring system

BACKGROUND: Despite effective antituberculous medications, the mortality and morbidity remain high in children with tuberculous meningitis (TBM). The traditional clinical staging for TBM developed by Lincoln et al in 1960 has been widely used to predict long term neurologic sequelae (NS). In the current era of critical care medicine and corticosteroid therapy, a new scoring system is needed to predict NS more accurately in children with TBM. METHODS: We reviewed all available cases of TBM in San Diego, CA, during 1991-2001 retrospectively, and we developed a novel scoring system to predict NS in children with TBM. We assessed a tuberculous meningitis acute neurologic (TBAN) score at day 0 and on day 3 of hospitalization, to compare children who subsequently developed severe NS with those who did not. RESULTS: Among 20 children with TBM, 7 children developed severe NS and 1 child died during hospitalization. The TBAN score was higher on day 0 in those with severe NS (5.5 versus 2.0, P = 0.09), and the difference became statistically significant by day 3 of hospitalization (5.5 versus 0.0, P = 0.02). Sensitivity and specificity of the TBAN score (> or =4) on day 0 (75 and 92%) and day 3 (88 and 100%) to predict severe NS were superior to the traditional clinical staging system on day 0 (63 and 58%). CONCLUSIONS: The TBAN score is an objective marker for predicting severe NS in children with TBM.     

Dexamethasone and bacterial meningitis in Pakistan

The objective of this study was to assess, in a developing country setting, the effect of dexamethasone therapy on bacterial meningitis outcomes. A prospective double blind placebo controlled trial was conducted in 89 children aged from 2 months to 12 years suffering from bacterial meningitis. Neurological, developmental, and hearing assessments were conducted at one, four, and 12 months after discharge. Forty eight patients received dexamethasone and 41 placebo. Initial antimicrobial drugs used were ampicillin and chloramphenicol. For all patients at the time of admission the mean duration of illness was 5.7 days; 47% had had seizures and 56% had impaired consciousness. Seventeen of 89 (19%) patients died. The mortality for the dexamethasone group was 25% as compared with 12% in the group receiving placebo. Presentation to the hospital after four days of symptoms and with impaired conscious state were independent predictors of death. Of the dexamethasone group survivors, 26.5% had neurological sequelae and 42.3% had hearing impairment, whereas in the placebo group it was 24% and 30% respectively. Altered state of consciousness was a predictor of neurological sequelae. The presence of neurological sequelae and high cerebrospinal fluid protein independently predicted hearing loss. No beneficial effect of dexamethasone was observed on morbidity or mortality of this group of patients with bacterial meningitis. Dexamethasone is therefore not useful in developing countries as adjunctive treatment in patients seriously ill with bacterial meningitis, who present late for treatment and have been partially treated.     

Comparative efficacy of ceftriaxone and cefuroxime for treatment of bacterial meningitis

To assess the comparative efficacy of cefuroxime and ceftriaxone for the treatment of bacterial meningitis, we reviewed the records from four prospective efficacy trials conducted at our institution. One hundred seventy-four infants and children received ceftriaxone and 159 received cefuroxime. The clinical characteristics of the two groups were comparable at admission. After 24 hours of therapy, routine cerebrospinal fluid cultures for all patients treated with ceftriaxone were sterile, whereas 9% of cerebrospinal fluid cultures were positive in cefuroxime-treated patients (p less than 0.001). More cefuroxime-treated patients had abnormal physical examinations at the time of discharge than did ceftriaxone-treated patients (39/159 vs 25/174, p = 0.02). At 6-week and 1-year follow-up examinations, there was no longer a statistically significant difference in the incidence of neurologic abnormalities between the two therapy groups, but the incidence of hearing impairment in one or both ears was higher in the cefuroxime (18%) than in the ceftriaxone (11%) treatment group. Both regimens are efficacious for the treatment of bacterial meningitis, but some patients may not respond as satisfactorily to cefuroxime as to ceftriaxone.     

Correlation of interleukin-1 beta and cachectin concentrations in cerebrospinal fluid and outcome from bacterial meningitis

Because interleukin-1 beta (IL-1 beta) and cachectin (tumor necrosis factor) are thought to mediate the body's response to microbial invasion, we measured IL-1 beta and tumor necrosis factor concentrations in paired cerebrospinal fluid (CSF) samples (on admission to the hospital, CSF1; 18 to 30 hours later, CSF2) from 106 infants and children with bacterial meningitis. In CSF1, IL-1 beta was detected in 95% of samples; the mean (+/- 1 SD) concentration was 944 +/- 1293 pg/ml. Patients with CSF1 IL-1 beta concentrations greater than or equal to 500 pg/ml were more likely to have neurologic sequelae (p = 0.001). Tumor necrosis factor was present in 75% of CSF1 samples; the mean concentration was 787 +/- 3358 pg/ml. In CSF2 the mean IL-1 beta concentration was 135 +/- 343 pg/ml, and IL-1 beta concentrations correlated significantly with CSF2 leukocyte count, with glucose, lactate, protein, and tumor necrosis factor concentrations, and with neurologic sequelae. Tumor necrosis factor was detected in CSF2 specimens of 53 of 106 patients, with a mean concentration of 21 +/- 65 pg/ml. Of the 106 patients, 47 received dexamethasone therapy at the time of diagnosis. These patients had significantly lower concentrations of IL-1 beta and higher glucose and lower lactate concentrations in CSF2, and they had a significantly shorter duration of fever compared with the values in patients not treated with steroids (p less than or equal to 0.002). Our data suggest a possible role of IL-1 beta and tumor necrosis factor as mediators of meningeal inflammation in patients with bacterial meningitis, and might explain, in part, the beneficial effect of dexamethasone as adjunctive treatment in this disease.     

Dexamethasone in bacterial meningitis: To use or not to use?

Permanent neurologic disabilities are seen in up to a quarter of survivors of bacterial meningitis despite major improvements in therapy. Experimental studies have demonstrated that most of the pathology in meningitis is mediated by inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin-1 (IL-1), which are produced by host cells in response to bacterial invasion of the meninges. Dexamethasone has been used in a number of clinical trials to moderate the host response and to improve neurologic outcome of meningitis. Results of six randomized, placebo controlled trials are summarized in this review. Dexamethasone treatment did not lower mortality. Only a moderate, but not a significant reduction in the neurologic and audiologic sequelae was seen in dexamethasone recipients whenHaemophilus influenzae type b (Hib) was the causative agent of meningitis. Following routine use of Hib vaccine, meningitis caused by this agent has virtually disappeared in the USA. Hence, findings from these trials may no longer be applicable in countries with high rates of immunization against Hib. Presently, there is little or no evidence showing a benefit of dexamethasone therapy in meningitis caused byS. pneumoniae orN. meningitidis. Global emergence of penicillin and cephalosporin resistantS. pneumoniae has raised new concerns about the use of dexamethasone in pneumococcal meningitis. Since dexamethasone significantly decreases the penetration and concentration of vancomycin and ceftriaxone in the CSF and delays CSF sterilization, adjunctive dexamethasone therapy may increase the risk of treatment failure in meningitis caused by antibiotic resistant pneumococci. An antibiotic combination should be used in the treatment of meningitis caused by antibiotic resistant pneumococci, particularly if dexamethasone is also being administered concurrently.     

Lack of effectiveness of dexamethasone in neonatal bacterial meningitis

A clinical trial was conducted to determine whether dexamethasone as adjunctive therapy alters the outcome of bacterial meningitis in neonates. Fifty-two full-term neonates with bacterial meningitis were enrolled in a prospective study. Infants were alternately assigned to receive either dexamethasone or not. Twenty-seven received dexamethasone in addition to standard antibiotic treatment and 25 received antibiotics alone. Dexamethasone therapy was started 10–15 min before the first dose of antibiotics in a dose of 0.15 mg/kg per 6 h for 4 days. Baseline characteristics, clinical and laboratory features in the two groups were virtually similar. Both groups showed a similar clinical response and similar frequency of mortality and sequelae. Six (22%) babies in the treatment group died compared to 7 (28%) in the control group (P = 0.87). At follow up examinations up to the age of 2 years, 6 (30%) of dexamethasone recipients and 7 (39%) of the control group had mild or moderate/severe neurological sequelae. Audiological sequelae were seen in two neonates in the dexamethasone group compared to one in the control group. Conclusion Adjunctive dexamethasone therapy does not improve the outcome of neonatal bacterial meningitis. Received: 22 December 1997 / Accepted: 14 March 1998     

Long-term sequelae of group B streptococcal meningitis in infants

The long-term outcome and admission features predictive of outcome were determined for 61 patients with group B streptococcal meningitis treated between 1974 and 1979. Infection was rapidly fatal in 13 patients (21%). Among the 48 survivors, 38 (79%) 3 years of age or older were available for comprehensive evaluation. Excluding five who had died before age 3 years, the mean age at evaluation was 6.0 years (range 3.3 to 9.0 years). Among survivors, 11 (29%) had severe neurologic sequelae, eight (21%) had mild to moderate deficits, and 19 (50%) were functioning normally. Analysis of predictive features revealed a significant risk of death or severe impairment among infants who at hospital admission were comatose or semicomatose, had decreased perfusion, total peripheral WBC less than 5,000/mm3, absolute neutrophil count less than 1000/mm3, and CSF protein greater than 300 mg/dl (P less than or equal to 0.05). These data indicate that, although mortality from group B streptococcal meningitis has declined, approximately half of the survivors of acute infection have some degree of morbidity when evaluated at ages permitting the detection of language delay and borderline or mild mental retardation.     

Antibiotic treatment of children with unsuspected meningococcal disease

BACKGROUND: Data from an earlier study suggest that patients with unsuspected meningococcal disease (UMD) cannot be differentiated easily from febrile children with viral syndromes on the basis of physical examinations or peripheral blood counts. Some children with meningococcal disease therefore are treated inadvertently as outpatients. OBJECTIVE: To determine whether antibiotic therapy administered at the outpatient visit prevents complications, permanent sequelae, or death in children with UMD. METHODS: We reviewed the medical records of patients younger than 20 years with invasive meningococcal disease at 7 pediatric referral centers from January 1, 1981, through December 31, 1996. Patients were considered to have UMD if they underwent evaluation and discharge as outpatients and if blood and/or cerebrospinal fluid cultures obtained at evaluation yielded Neisseria meningitidis. We compared the frequency of development of complications (meningitis, sepsis, and pericarditis), permanent sequelae (limb amputation, skin grafting, and persistent neurologic disability) or death between patients who did and did not receive antibiotics at the outpatient visits. RESULTS: Of 58 children with UMD, 19 (33%) received antibiotics and 39 (67%) did not. Complications occurred significantly less frequently in the antibiotic-treated group (7/19 [37%] vs 27/39 [69%]; odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08-0.81; P = .03). There was no significant difference in death or permanent sequelae between groups (0/19 vs 3/39 [8%]; OR, 0; 95% CI, 0-2.61; P=.54). There was insufficient power, however, to exclude the possibility of a clinically meaningful difference between the groups with regard to these latter outcomes. CONCLUSIONS: Antibiotic administration to young patients with UMD at the time of the outpatient visit is associated with a reduction in complications from this disease. Although the routine use of antibiotics in febrile outpatients younger than 20 years cannot be advocated, empirical treatment should be considered in the setting of higher probability of meningococcal disease.     

Countercurrent immunoelectrophoresis in the evaluation of infants with group B streptococcal disease

Admission specimens of CSF, serum, and urine from 67 patients with proved group B streptococcal (GBS) bacteremia and/or meningitis were evaluated by countercurrent immunoelectrophoresis (CIE). Group B and type-specific antigens were detected in 81% of CSF, 63% of serum, and 96% of concentrated urine specimens by CIE. Each of 26 infants with meningitis from whom all three body fluids were available and ten with bacteremia from whom both serum and urine were collected at admission had GBS antigens detected by CIE in at least one specimen. No false positive reactions were observed. Among patients with type III, GBS meningeal infection, fatal outcome or neurologic sequelae were significantly correlated with concentration of type III antigen in admission CSF and duration of antigenuria when compared to normal survivors (P = less than .05, Mann-Whitney U tests). CIE appears to be a useful diagnostic and prognostic tool for infants with GBS infection if admission specimens from more than one source are examined and appropriately high-titered antisera are employed for testing.     

Moxalactam therapy of Haemophilus influenzae type b meningitis in children

Thirty-four children with Haemophilus influenzae type b meningitis were given prospectively either moxalactam (200 mg/kg/day) or ampicillin (400 mg/kg/day) plus chloramphenicol (75 mg/kg/day). One patient in each group died. The mean duration of fever, clinical response, sequential cerebrospinal fluid findings, and incidence of neurologic sequelae were similar between groups. Moxalactam cerebrospinal fluid bioactivity was significantly greater than that of ampicillin or chloramphenicol throughout therapy. Neutropenia, liver enzyme abnormalities, and diarrhea were not significantly different. In eight of 11 patients given moxalactam (versus one of 14 controls) there was complete elimination of gram-negative aerobic flora in the stools by day 10 (P = 0.002); however, none acquired Clostridium difficile. Moxalactam in effective therapy for H. influenzae type b meningitis.     

Predicting asparaginase-associated pancreatitis

BACKGROUND: Pancreatitis is a well-known, but little-understood complication of asparaginase. There is no predictor of who will develop asparaginase-associated pancreatitis (AAP). To better define this population, we present a retrospective analysis regarding AAP and provide a review of the relevant literature. METHODS: We systematically reviewed medical records of 254 asparaginase recipients during a 5-year period. Pancreatitis was defined and graded according to CTCAE v3.0. RESULTS: Pancreatitis was diagnosed in 48 (19%) patients. Thirty-three (13%) patients were identified as having AAP. Twelve cases occurred after Escherichia coli asparaginase and 20 followed PEG-asparaginase. Pancreatitis was independent of the individual or cumulative asparaginase dose. The interval to pancreatitis diagnosis was longer for PEG-asparaginase than E. coli asparaginase (P = 0.02). AAP was seen more frequently in patients receiving prednisone (P = 0.02) and daunomycin (P = 0.006) while less frequent with dexamethasone (P = 0.04). Other chemotherapy agents appeared to have no association with AAP. As observed by others, those with pancreatitis were older (P = 0.001), but the significance of this remains uncertain. CONCLUSIONS: This study emphasizes our inability to predict who will develop pancreatic toxicity from asparaginase and suggests that those at risk might have an unidentified genetic predisposition.     

Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation

A randomized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia. A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone (n = 12) or saline placebo (n = 11). Dexamethasone (0.5 mg/kg per day) was given in tapering doses for 7 days followed by hydrocortisone (8 mg/kg per day) which was progressively reduced for a total of 17 days of therapy. Infants who received dexamethasone required less oxygen on days 8 and 17 (P less than .05) and were more likely to extubate 8 days after therapy than infants in the control group (respectively 8/12 vs 3/11 infants, P less than .05; P = .12 after Yates correction). The use of dexamethasone significantly shortened median duration of mechanical ventilation (4 vs 22 days, P less than .05) but had no effect on length of oxygen therapy, hospitalization, home oxygen therapy, occurrence and severity of retinopathy of prematurity, rate of growth, and mortality. No significant complications resulted from dexamethasone therapy. Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract (23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group, P less than .05). Dexamethasone administration resulted in short-term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia.     

Pneumococcal meningitis in children: relationship of antibiotic resistance to clinical characteristics and outcomes.

BACKGROUND: The relationship of antibiotic susceptibility to clinical outcome in children with pneumococcal meningitis is uncertain. Previous studies have been limited by inclusion of relatively few patients infected with nonsusceptible pneumococci and inconsistent use of empiric vancomycin. METHODS: Medical records of 86 children with culture-confirmed pneumococcal meningitis at a single institution from October, 1991, to October, 1999, were retrospectively reviewed, and differences in presentation and outcome based on antibiotic susceptibility of pneumococcal isolates were assessed. RESULTS: Of 86 isolates 34 were nonsusceptible to penicillin (12 resistant). Of 60 isolates for which cefotaxime susceptibility data were available, 17 were nonsusceptible (12 resistant). Antibiotic susceptibility was not significantly associated with death, intensive care unit admission, mechanical ventilation, focal neurologic deficits, seizures, secondary fever, abnormal neuroimaging studies or hospital days. Children with penicillin-resistant isolates had significantly higher median blood leukocyte counts (24,100/microliter vs. 15,700/microliter, P = 0.03) and lower median CSF protein concentrations (85 mg/dl vs. 219 mg/dl, P = 0.04), were more likely to have a CSF glucose concentration of > or = 50 mg/dl (7 of 11 vs. 15 of 68, P = 0.009) and had lower rates of sensorineural hearing loss (1 of 8 vs. 25 of 40, P = 0.02) than children with isolates that were not resistant to penicillin. Children with cefotaxime-nonsusceptible isolates had an increased median duration of primary fever compared with those with nonsusceptible strains (6 days vs. 3.5 days, P = 0.02). CONCLUSIONS: In children with pneumococcal meningitis, penicillin resistance was associated with a reduced risk of hearing loss, while cefotaxime resistance was associated with a longer duration of fever. Other outcome measures were not significantly influenced by the antibiotic susceptibility of pneumococcal isolates.     

Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin.

BACKGROUND: Trovafloxacin is a new fluoroquinolone that exhibits good penetration into the central nervous system and excellent antimicrobial activity against common meningeal pathogens, including beta-lactam-resistant pneumococci. PURPOSE AND DESIGN: A multicenter, randomized clinical trial was conducted in children with bacterial meningitis to compare the safety and efficacy of trovafloxacin with that of ceftriaxone with or without vancomycin therapy. RESULTS: A total of 311 patients, ages 3 months to 12 years, were enrolled, of whom 203 were fully evaluable, 108 treated with trovafloxacin and 95 with the conventional regimen. Both groups were comparable with regard to baseline characteristics: age; cerebrospinal fluid findings; use of dexamethasone; history of seizures; and etiologic agents. No significant differences between trovafloxacin and the comparator, respectively, were detected in any of the following outcome measures: clinical success at 5 to 7 weeks after treatment (79% vs. 81%); deaths (2% vs. 3%); seizures after enrollment (22% vs. 21%); and severe sequelae (14% vs. 14%). Only 4 of 284 children developed joint abnormalities up to 6 months after treatment, 1 (0.9%) child received trovafloxacin and 3 (3.1%) received the comparator regimen. None of the evaluable patients experienced significant abnormalities of liver function during treatment. One nonevaluable patient who received trovafloxacin for 5 days and ceftriaxone for 11 days was readmitted to the hospital with hepatitis of unknown etiology 1 day after discharge. The episode resolved with liver function tests returning to normal within 2 months. CONCLUSIONS: We conclude that trovafloxacin is an effective antibiotic for treatment of pediatric bacterial meningitis. These favorable results support further evaluation of fluoroquinolone therapy for children with meningitis or other serious bacterial infections.