Antibiotic therapy of fulminant E. coli K1 sepsis in infant rabbits

A model of overwhelming E. coli K1 sepsis and early meningitis was developed in infant rabbits and used to compare clinical and bacteriologic efficacy of ampicillin, moxalactam, cephalothin and chloramphenicol. Intraperitoneal injection of 10(7) E. coli K1 into 1- or 2-wk-old rabbits produced a rapidly progressive infection which, if left untreated, produced bacteremia in 100% of animals, meningitis in 78%, and mortality in 100%. Therapy was initiated 4 h after ip infection at which time mean bacterial concentration (log10 CFU/ml) ranged from 4.4-4.8 in the blood and from 1.8-2.3 in the cerebral spinal fluid (CSF). Pre-treatment frequency of bacteremia (100%) and meningitis (17-23%) was similar for all experimental groups. Antibiotic concentrations in blood and CSF 2 h after a dose exceeded the E. coli minimum inhibitory concentration with the exception of CSF cephalothin, which was undetectable. Moxalactam, ampicillin, and chloramphenicol significantly reduced the incidence of bacteremia and meningitis relative to cephalothin or saline controls (P less than 0.02). Mortality rates among the former three groups were high (64-82%) but significantly less than in saline or cephalothin-treated rabbits (100%). In this neonatal model of fulminant sepsis with early meningitis, moxalactam provided no therapeutic advantage over ampicillin or chloramphenicol.     

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.     

Effect of ampicillin and chloramphenicol against Haemophilus influenzae.

Synergy, determined by isobolograms constructed from the minimal inhibitory concentrations of combinations of ampicillin and chloramphenicol, was observed against six of 13 ampicillin-susceptible Haemophilus influenzae type b isolates and against five of eight ampicillin-resistant strains by using a small inoculum of 10(4) colony forming units (CFU) per milliliter. Synergy occurred against nine of 13 ampicillin-susceptible and against two of eight ampicillin-resistant strains using a large inoculum of 10(7) CFU/ml. When synergy was not observed, additive effects occurred against the remainder of isolates. Additive effects were also observed against single strains of chloramphenicol-resistant, nontypeable H. influenzae and H. parainfluenzae. No antagonism was observed. These data indicate that ampicillin and chloramphenicol may be synergistic against a significant number of H. influenzae strains depending on inoculum size, but the effect is unpredictable for a given isolate. These data support the recommendation that ampicillin and chloramphenicol both be used as initial therapy for patients with suspected bacterial meningitis.     

Ampicillin-chloramphenicol-resistant Haemophilus influenzae: plasmid-mediated resistance in bacterial meningitis

A 4-month-old infant with congenital heart disease and sepsis and arthritis, and subsequently meningitis, caused by an antibiotic-resistant strain of Haemophilus influenzae type b, failed to respond to sequential therapy with ampicillin and trimethoprim/sulfamethoxazole. Following treatment with ceftizoxime, the infant was well for 42 days, until he returned to the hospital and died. A total of 10 Haemophilus influenzae type b isolates, all outer membrane protein subtype 51, was isolated from the pretreatment blood and synovium, cerebrospinal fluid and subdural fluids, and the petrous pyramids at autopsy. Pretreatment isolates had no detectable plasmid DNA, chloramphenicol acetyltransferase or beta-lactamase; the minimal inhibitory concentration for ampicillin (AM) and chloramphenicol (CM) was 0.2 and 0.8 microgram/ml, respectively. However, all cerebrospinal fluid isolates had a 42-44 mD plasmid and produced chloramphenicol acetyltransferase and beta-lactamase; the minimal inhibitory concentration of these isolates to AM and CM were 12.5 and 25 micrograms/ml, respectively, and were also resistant to tetracycline and sulfonamide. Resistance to AM and CM was cotransferred by filter-mating conjugation at a frequency of one to two transconjugants per 10(5) to an Rd haemophilus recipient. Posttreatment isolates from the petrous pyramids also were resistant to AM and CM and produced chloramphenicol acetyltransferase and beta-lactamase activity, but had no plasmid DNA. These findings and data from genetic studies suggested that plasmid-bearing antibiotic-resistant Haemophilus influenzae type b was selected from a heterogenous population, and that the AM/CM resistance transposons were incorporated into the bacterial chromosome.     

Antibiotic Susceptibility of 629 Bacterial Blood and CSF Isolates from Swedish Infants and the Therapeutic Implications

Tullus, K., Olsson-Liljequist, B., Lundström, G. and Burman, L. G. (Department of Paediatrics, St. Göran's Children's Hospital and Department of Bacteriology, the National Bacteriological Laboratory, Stockholm, Sweden). Antibiotic susceptibility of 629 bacterial blood and CSF isolates from Swedish infants and the therapeutic implications. Acta Paediatr Scand 80: 205, 1991.
Blood and CSF isolates ( n =629) from Swedish infants up to one year of age were tested in vitro against 13 antimicrobial agents in order to update the guidelines for empiric therapy of septicaemia and meningitis. Ampicillin plus gentamicin provided inadequate empiric therapy for meningitis, due to the poor CSF penetration of the aminoglycoside and the frequent occurrence of bacterial resistance to ampicillin. Ceftazidime and cefuroxime were moderately active, particularly against isolates from small infants. Cefotaxime today seemed to provide the best empiric therapy of septicaemia and meningitis in infants. Because of the occurrence of Listeria and enterococcal infections, ampicillin should initially be added and other combinations are also advisable for the occasional cases of Enterobacter, Citrobacter, Serratia , and Pseudomonas infections. For coagulase-negative staphylococci only vancomycin offered a broad activity (100% at achievable serum levels).     

Pneumococcal meningitis in the newborn period in a prevaccination era: a 10-year experience at a tertiary intensive care unit

There are few data with respect to pneumococcal meningitis in neonates. Epidemiological aspects, clinical features and outcomes in newborn infants diagnosed with pneumococcal meningitis were evaluated in this study. Nineteen newborn infants in a neonatal intensive care unit diagnosed with culture-proven community-acquired bacterial meningitis between January 1999 and December 2008 were reviewed, and of them, eight patients were diagnosed as pneumococcal meningitis. Overall, among 10,186 hospitalized newborn infants, 132 community-acquired sepsis/meningitis cases (1.3%) were suspected, and blood cultures were performed in all, while cerebrospinal fluid (CSF) cultures could be performed in 124 cases. Rate of blood culture positivity was 45%. Nineteen (15.3%) of 124 were diagnosed as culture-proven community-acquired bacterial meningitis, which was confirmed by CSF growth. Eight (42.1%) of 19 had pneumococcal meningitis. In pneumococcal cases, abundant Gram-positive diplococci were seen on CSF smear and Streptococcus pneumoniae was isolated from CSF cultures. All isolates were susceptible to penicillin and third-generation cephalosporins. Irritability (n: 7), poor sucking (n: 7) and fever (n: 6) were the principal findings on the initial physical examination. Of all patients with pneumococcal meningitis, four were initially given cefotaxime plus amikacin treatment, and the remaining four were initially given cefotaxime plus ampicillin plus vancomycin. Antibiotic treatment in two patients was revised during their clinical course. Additionally, in three patients, vancomycin and ampicillin was discontinued on the third day when antibiogram of CSF cultures revealed penicillin sensitivity. Overall, mortality in pneumococcal meningitis was 50%. In the surviving patients, two had epilepsy, one sensorineural hearing loss, and two mental-motor retardation. Pneumococcal meningitis was the leading cause of community-acquired neonatal meningitis in our patients. Immunization against pneumococcal disease in developing countries would be beneficial for public health and for newborn infants.     

Antibiotic Susceptibility of Type b Haemophilus influenzae and Streptococcus pneumoniae, and Antibiotic Concentration in Cerebrospinal Fluid

Antibiotic susceptibilities of 38 type b Haemophilus influenzae and 28 Streptococcus pneumoniae strains isolated from cerebrospinal fluid, blood and other specimens between 1973 and 1988 were studied. Minimal inhibitory concentrations (MICs) of ampicillin against 10 β-lactamase positive and 28 negative H. influenzae isolates were 32–64 and 0.25 μg/ml, respectively. The MIC of chloramphenicol against one of the β-lactamase positive H. influenzae strains was 8 but MICs against the rest of the organisms were 0.5–1 μg/ml. MICs of cefotaxime, ceftriaxone and cefuroxime against all H. influenzae strains were 0.016, 0.008 and 0.5 μg/ml, respectively. No S. pneumoniae isolates were resistant to penicillin G and MICs of this drug were 0.016–0.032 μg/ml. MICs of cefotaxime, ceftriaxone and cefuroxime against all S. pneumoniae strains were 0.016–0.032, 0.016–0.032 and 0.032–0.063 μg/ml, respectively. MICs of chloramphenicol against 15, 4 and 9 of S. pneumoniae isolates were 2, 8 and 16 μg/ml, respectively. Antibiotic concentrations in the cerebrospinal fluid of patients with bacterial meningitis after intravenous administration of ampicillin (50–70 mg/kgx4/day), penicillin G (31–63 mg/kgx4/day), cefotaxime (50 mg/kgx4/day) and chloramphenicol (25 mg/kgx4/day) were 4.70±1.83 (n=11), 0.57±0.32 (n=7), 4.97±2.60 (n=9) and 8.52±3.54 μg/ml (n=3), respectively. The initial choice of antibiotics in older children with bacterial meningitis is a combination of ampicillin (75 mg/kgx4/day) and cefotaxime (50 mg/kgx4/day) to cover ampicillin-resistant H. influenzae, S. pneumoniae , and Listeria monocytogenes in Japan. These antibiotics should be changed according to the causative organisms and their antibiotic susceptibilities.     

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.     

Bacterial meningitis in India: An IJP survey

Conclusions It can be concluded that bacterial meningitis is an important cause of childhood morbidity and mortality. Isolation of causative pathogenes is poor in our country. A routine gram staining of CSF and use of rapid diagnostic kits with better culture facilities would be helpful in improving the outcome. In first 3 months of life, therapy should include one of the 3rd generation cephalosporins with an aminoglycoside. For meningitis in age groups between 3 months to 12 years, chloramphenicol and ampicillin should be the first line empirical therapy. If gram-ve organisms are suspected or isolated, one of the 3rd generation cephalosporins with or without an aminoglycoside is good alternative. The treatment can be stopped in uncomplicated case after 7–10 days (5 days of afebride period) in meningitis caused by meningococcus, pneumococcus andH. infuenzae. For BM caused by gram-ve bacilli treatment for 21 days is recommended. There is no need to perform CSF examination at the conclusion of therapy in cases of bacterial meningitis beyond neonatal period. There is a need to further evaluate therapeutic regimens like chloramphenicol alone, ceftriaxone home therapy, especially for rural areas etc. to decrease the cost of hospitalisation in referral hospitals.     

Cefotaxime monotherapy in bacterial meningitis in childhood

Bacterial meningitis in 20 children was treated with cefotaxime. 17 children received this antibiotic throughout the disease as monotherapy, three were changed to Penicillin G (2) or ampicillin (1), after sensitivity of the pathogen was known, although cefotaxime had been effective. All bacterial isolates were highly susceptible to cefotaxime. All CSF cultures were sterile at second tap, performed 24 to 48 hrs after therapy was started. Cefotaxime and desacetyl-cefotaxime concentrations in CSF, measured by HPLC in 9 patients were in the range of 4 to 34 (average 17.6) mg/l and 2.1 to 82 (average: 15.1) mg/l, representing a CSF-serum ratio of 8 to 74% (average 45.6%) for cefotaxime and 25 to 151% (average: 73.7%) for desacetyl-cefotaxime. Clinical outcome was favourable in 17 patients. There were one death and late neurological deficits in three. Cefotaxime monotherapy is recommended instead of standard therapy with chloramphenicol and/or ampicillin because of superior antibacterial activity, lower toxicity and lesser side-effects for primary meningitis in children caused by N. meningitides, S. pneumoniae, or H. influenzae type b.     

Haemophilus influenzae meningitis. A comparison between chloramphenicol and ampicillin therapy with special reference to impaired hearing.

131 patients suffering from meningitis due to Haemophilus influenzae or parainfluenzae were re-examined after 1-15 years, using hospital records, questionnaires, and audiological examination, especially to compare chloramphenicol and ampicillin therapy. Mortality was 3.8%. Subdural effusions occurred in 14.5% of cases uni- or bilaterally. There was deafness in 2.3%, and moderate hearing loss in 8.4%. Convulsions appeared later in 6.9%. The final outcome was good in 60%. The most important factors in prognosis seemed to be the severity of the symptoms and the condition of the patient on admission to hospital. No clear difference was seen between the results of chloramphenicol and ampicillin therapy, but total loss of vestibular function was found in 3 cases in the ampicillin group, and in none in the chloramphenicol group. In mortality and deafness, the differences in outcome were similar, although not statistically significant. As these observations show, the therapy used in Haemophilus influenzae meningitis needs re-evaluation.     

HAEMOPHILUS INFLUENZAE MENINGITIS A Comparison between Chloramphenicol and Ampicillin Therapy with Special Reference to Impaired Hearing

ABSTRACT. 131 patients suffering from meningitis due to Haemophilus influenzae or parainfluenzae were re-examined after 1–15 years, using hospital records, questionnaires, and audiological examination, especially to compare chloramphenicol and ampicillin therapy. Mortality was 3.8%. Subdural effusions occurred in 14.5% of cases uni- or bilaterally. There was deafness in 2.3%, and moderate hearing loss in 8.4%. Convulsions appeared later in 6.9%. The final otucome was good in 60%. The most important factors in prognosis seemed to be the severity of the symptoms and the condition of the patient on admission to hospital. No clear difference was seen between the results of chloramphenicol and ampicillin therapy, but total loss of vestibular function was found in 3 cases in the ampicillin group, and in none in the chloramphenicol group. In mortality and deafness, the differences in outcome were similar, although not statistically significant. As these observations show, the therapy used in Haemophilus influenzae meningitis needs re-evaluation.     

Direct detection of the multidrug resistance genome of Haemophilus influenzae in cerebrospinal fluid of children: implications for treatment of meningitis

BACKGROUND: Multidrug resistance (MDR), specifically to ampicillin and chloramphenicol, has complicated the treatment of Haemophilus influenzae type b (Hib) meningitis. This is worsened by use of prior antibiotics, which limits identification of the causative agent by culture and increases reliance on antigen detection. OBJECTIVE: We aimed to develop a PCR assay for detecting the family of Haemophilus integrating and conjugative elements (ICEs) represented by ICEHin1056 among antibiotic resistant Hib, and then apply this directly to CSF to diagnose Hib meningitis and predict organism susceptibility, irrespective of culture results. STUDY DESIGN: Primers specific for orf 51 of ICEHin1056 were designed and multiplexed with Bex primers, specific for H. influenzae, and tested on culture positive and negative cases. RESULTS: Of 73 Hib isolates, orf 51 PCR amplicons, predicting the presence of ICEs, were found in all 33 MDR isolates while only in 1 of 33 sensitive strains. The remaining 7 ampicillin susceptible, chloramphenicol and tetracycline resistant strains did not produce a PCR product to orf 51. PCR amplification from CSF specimens of these culture positive cases produced identical results with 100% and 97% positive and negative predictive values, respectively. Multiplex PCR to detect Bex and orf 51 identified another 16 MDR Hib cases among 81 culture-negative CSF samples. CONCLUSIONS: Direct PCR for orf 51 in CSF identified resistance pattern of 51% more Hib strains than culture alone (110 versus 73). The ability to detect MDR, in culture negative Hib meningitis cases has significant implications for better directing antibiotic treatment of meningitis cases and thus for preventing disability and death.     

Thiamphenicol in treatment of Haemophilus influenzae meningitis.

17 infants and children with pyogenic meningitis (14 Haemophilus influenzae, 2 Diplococcus pneumoniae, 1 Neisseria meningitidis) were treated with thiamphenicol, 100 mg/kg body weight/day in 4 doses i.v., as single drug. In the H. influenzae group 10 patients were cured, 4 had relapses of meningitis, 3 with documented subdural effusions. This group is compared with 14 children matched for age, initial leucocyte and CSF cell count treated with ampicillin: all of these were cured, 1 had a subdural effusion. Thiamphenicol concentrations were determined in the serum and CSF 2 h after administration. The mean serum levels were between 10-12 mcg/ml, the mean CSF levels varied from 5.4 mcg/ml at the beginning to 1-1.9 mcg/ml at the end of meningitis. The MIC of H. influenzae was 0.6-12 mcg/ml. A significant, acute, and dose related bone marrow toxicity of thiamphenicol could be documented, but was always rapidly fully reversible. We conclude that thiamphenicol cannot replace chloramphenicol in the treatment of pyogenic meningitis as single systemic antibiotic. Special indications for thiamphenicol in this disease are discussed.     

Invasive Haemophilus influenzae type B diseases in Bangladesh, with increased resistance to antibiotics

OBJECTIVE: To determine the prevalence, age-group distribution, serotype, and antibiotic susceptibility patterns of invasive Haemophilus influenzae type b (Hib) isolates in Bangladeshi children because data regarding Hib diseases in developing countries are scarce, which has led to delay of the introduction of Hib vaccine in these countries. METHODS: Children diagnosed with meningitis (n = 1412) and pneumonia (n = 2434) were enrolled in this surveillance study for Hib invasive diseases. Cerebrospinal fluid (CSF) and blood specimens, and the subsequent isolates, were processed using standard procedures. RESULTS: During 1993 to 2003, 455 H influenzae strains were isolated from patients with meningitis (n = 425) and pneumonia (n = 30), and an additional 68 Hib meningitis cases were detected by latex agglutination (LA) testing. Overall, 35% of pyogenic meningitis cases were a result of H influenzae, 97.1% of which were Hib. Most (91.4%) cases occurred during the first year of life. Resistance to ampicillin, chloramphenicol, and cotrimoxazole was 32.5%, 21.5%, and 49.2%, respectively. There was a trend toward increasing resistance for all three drugs. Resistance to ampicillin and chloramphenicol was almost universally coexistent and was associated with increased sequelae compared with the patients infected with susceptible strains (31% [23/75] vs 11% [21/183]; P <.001). CONCLUSION: Hib is the most predominant cause of meningitis in young Bangladeshi children. Resistance to ampicillin and chloramphenicol and the high cost of third-generation cephalosporin highlight the importance of disease prevention through vaccination against Hib.     

Bacterial meningitis--an update.

This report emphasizes new clinical information about bacterial meningitis in infants and children. Important elements of diagnosis include examination for the presence of shock and increased intracranial pressure. In such cases, initial treatment should focus on appropriate fluid therapy, administration of oxygen, reduction of intracranial pressure and use of corticosteroids. Currently, antibiotics of choice include ampicillin plus either cefotaxime or ceftriaxone in young infants, and one of these cephalosporins in older patients (beyond 3 months of age). Shorter durations of therapy (5 to 7 days for meningococcus, 7 days for haemophilus and 7-10 days for pneumococcus) are now commonly employed. In many centers, dexamethasone is started before the first dose of antibiotic and continued for 4 days to reduce neurologic and audiologic sequelae. Future trends will include studies of endotoxin neutralizers and non-steroidal anti-inflammatory drugs to reduce further tissue injury in meningitis. Prevention of meningitis is the ultimate goal. Since Haemophilus influenzae vaccination can now begin at 2 months, this approach may bring important results soon.     

Hearing impairment following therapy of Haemophilus influenzae meningitis.

From 97 children with bacteriologically confirmed Haemophilus influenzae meningitis, 39 were treated with chloramphenicol (before 1970) and 58 with ampicillin (since 1970). In 1977 all patients were followed up with history, clinical examination, and audiometry. Sensorineural hearing defect was found in 5 chloramphenicol patients and in 10 ampicillin patients. Of the 82 patients for whom treatment was begun within 48 h of onset of symptoms, only two showed hearing deficit, while 13 of the 15 patients in whom treatment was begun later suffered from hearing impairment. It appears that it is not the antibiotic, but the delay between onset of symptoms and start of therapy, that is decisive for the occurrence of inner ear impairment.     

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.     

Initial Chemotherapy for Purulent Meningitis in Children

The combination of ampicillin with either gentamicin or chloramphenicol, which is currently the initial chemotherapy for purulent meningitis, has lost its effectiveness in recent years because of an increase in the incidence of ampicillin-resistant strains. This has made it necessary to search for a suitable substitute therapy. Twenty-two new β-lactam agents were compared with penicillin G and ampicillin in terms of their antibacterial activity in relation to the principal causative microbes of meningitis and their ability to transfer into the cerebrospinal fluid (CSF) of rabbits with experimental staphylococcal meningitis. In addition, a survey was conducted of the therapeutic efficacy achieved by these drugs in cases seen by the authors and in other domestic and overseas cases. Finally, an investigation was made as to whether or not the transfer of the drug into the CSF was suppressed when it was administered simultaneously with ampicillin. From the results, it was surmised that in future the most appropriate initial chemotherapy for purulent meningitis will be a combination of cefotaxime, or perhaps ceftriaxone, plus ampicillin.     

Multiply resistant Haemophilus influenzae type b causing meningitis: comparative clinical and laboratory study

Thirty-five patients with meningitis caused by Haemophilus influenzae type b were admitted to our hospital from January 1981 to December 1984; 60% of the strains were resistant to ampicillin, 65.7% to chloramphenicol, and 57% to both antibiotics. No significant differences in age, sex, previous treatment, clinical symptoms, outcome, and mortality were found between the 20 patients whose strains were resistant to both ampicillin and chloramphenicol and the other 15 patients whose strains were susceptible to ampicillin, chloramphenicol, or both. Alternative therapeutic agents were a combination of carbenicillin and gentamicin and new cephalosporins. At present, cefotaxime is our treatment of choice for meningitis caused by H. influenzae type b.