cefotaxime and Meningitis--Pneumococcal

In France, conjugated pneumococcal vaccination has considerably modified the profile of pneumococcal meningitis by eliminating the most virulent strains resistant to beta-lactams. Over recent years, the nationwide pediatric meningitis network of the Pediatric Infectious Disease Group (GPIP) and the National Reference Centre of Pneumococci have not recorded any cases of meningitis due to pneumococcus resistant to third-generation cephalosporins (C3G), even though in 2021, strains with a less favorable profile appeared to emerge. These recent data justify renewal of the 2016 recommendations and limitation of vancomycin to the secondary phase of treatment of pneumococcal meningitis when the MIC of the isolated strain against injectable C3Gs is >0.5 mg/L. The only major change proposed by the GPIP in this 2023 update of its recommendations is discontinuation of the recommendation of a combination of ciprofloxacin and cefotaxime in Escherichia coli meningitis in newborns and young infants. The nationwide observatory of meningitis in children is a valuable tool because of its completeness and its continuity over the past 15 years. The maintenance of epidemiological surveillance will allow us to adapt new therapeutic regimens to the evolution of pneumococcal susceptibility profiles and to future serotype-specific changes. Community-acquired cerebral abscesses are rare diseases, of which the management requires a rigorous approach: high-quality imaging, bacteriological sampling prior to antibiotic therapy whenever possible, and antibiotic treatment including metronidazole in addition to cefotaxime. Multidisciplinary collaboration, including infectious disease and neurosurgical advice, is always called for.

Topics: Anti-Bacterial Agents; Cefotaxime; Child; Communicable Diseases; Humans; Infant; Infant, Newborn; Meningitis, Pneumococcal; Streptococcus pneumoniae

Streptococcus pneumoniae is a rarely recognized cause of neonatal sepsis and/or meningitis, but it is associated with substantial morbidity and mortality. Traditionally, S. pneumoniae is identified in the laboratory by demonstrating susceptibility to optochin. However, the emergence of optochin-resistant organisms makes definite identification difficult when only phenotypic tests are taken as markers. We present the case of a severe early-onset neonatal meningitis due to an atypical strain of S. pneumoniae. Laboratory methods utilized to certify this species diagnosis are discussed.

Topics: Anti-Bacterial Agents; Cefotaxime; Female; Humans; Infant, Newborn; Meningitis, Pneumococcal; Treatment Outcome

During the past decade antibiotic resistance among Streptococcus pneumoniae isolates has complicated the empiric approach to and treatment of pneumococcal meningitis. Standard empiric therapy for suspected bacterial meningitis for infants and children older than 1 month of age is the combination of cefotaxime or ceftriaxone and vancomycin. Treatment is modified after antimicrobial susceptibilities are available. The optimal treatment of pneumococcal meningitis caused by strains with a cefotaxime/ceftriaxone MIC >2 microg/ml is unknown, although the addition of rifampin to the initial combination is generally recommended. The role of newer agents including quinolones is under investigation. Dexamethasone remains the only adjunctive antiinflammatory therapy to consider. The empiric approach to the child with suspected bacterial meningitis who has received the pneumococcal conjugate vaccine currently remains unchanged.

Topics: Adult; Cefotaxime; Ceftriaxone; Dexamethasone; Drug Resistance; Drug Therapy, Combination; Humans; Infant; Meningitis, Pneumococcal; Streptococcus pneumoniae; Treatment Outcome; Vancomycin

A 39-year-old female, who had splenectomy for idiopathic thrombocytopenic purpura (ITP) in 1988, was admitted to our hospital with high fever, headache, and loss of consciousness on November 29,1997. Neck stiffness and Kernig's sign were present. Examination of cerebrospinal fluid showed pleocytosis up to 506 cells/mm3 with 89% of polymorphonuclear cells and elevated protein to 1,135 mg/dl, and absence of glucose, Streptococcus pneumoniae phagocytosis was detected in the fluid. We diagnosed her as having pneumococcal meningitis as overwhelming postsplenectomy infection (OPSI) syndrome. After administration of dexamethasone (8 mg/day), cefotaxime (4 g/day), and ampicillin (6 g/day), she survived without any complications. Splenectomized patients have been recognized as immunocompromized hosts, and carry high morbidity and mortality risk from fulminant bacterial infections. Therefore, emergency treatment is important to reduce high mortality in such infections. We present an adult case of OPSI syndrome which occurred as pneumococcal meningitis, and we would like to emphasize the importance of prompt use of corticosteroids and high dose of sensitive antibiotics before DIC may occur during the course of illness.

Topics: Adult; Ampicillin; Anti-Inflammatory Agents; Cefotaxime; Cephalosporins; Dexamethasone; Drug Therapy, Combination; Female; Humans; Immunocompromised Host; Meningitis, Pneumococcal; Penicillins; Postoperative Complications; Purpura, Thrombocytopenic, Idiopathic; Splenectomy; Treatment Outcome

Topics: Cefotaxime; Cephalosporins; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Female; Humans; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Middle Aged; Streptococcus pneumoniae

Topics: Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Humans; Infant; Meningitis, Pneumococcal; Rifampin; Streptococcus pneumoniae; Vancomycin

Recent reports have documented the increasing number of pneumococcal isolates that are relatively or completely resistant to penicillin and other antibiotics. This report documents a case in which third-generation cephalosporin failed in the treatment of pneumococcal meningitis and reviews the clinical and microbiological features of the seven similar cases reported to date. In all eight cases, the pneumococci were penicillin resistant. Taken together, these cases suggest that (1) children with intermediately penicillin-resistant pneumococcal meningitis (MIC, 0.1-1.0 micrograms/mL) who are treated with cefotaxime or ceftriaxone should be observed carefully for treatment failure and (2) children with highly penicillin-resistant pneumococcal meningitis (MIC, > or = 2.0 micrograms/mL) are best treated with vancomycin and rifampin until the MICs of cefotaxime and ceftriaxone for the pneumococcus are known.

Topics: Cefotaxime; Ceftriaxone; Drug Resistance, Microbial; Humans; Infant; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin Resistance; Rifampin; Streptococcus pneumoniae; Vancomycin

Topics: Age Factors; Aminoglycosides; Ampicillin; Anti-Bacterial Agents; Bacteria; Cefotaxime; Ceftriaxone; Cefuroxime; Cerebrospinal Fluid; Child, Preschool; Chloramphenicol; Humans; Infant; Infant, Newborn; Meningitis; Meningitis, Haemophilus; Meningitis, Listeria; Meningitis, Meningococcal; Meningitis, Pneumococcal; Prognosis; Spinal Puncture

Evidence from a recent randomized controlled trial suggests that dexamethasone as adjunct therapy in adult pneumococcal meningitis reduces mortality and neurological sequelae. However, adding dexamethasone has the potential to reduce penetration of vancomycin into the cerebrospinal fluid (CSF). We sought to determine concentrations of vancomycin in serum and CSF of patients with suspected or proven pneumococcal meningitis receiving dexamethasone to assess the penetration of vancomycin into the CSF during steroid therapy.. In an observational open multicenter study, adult patients admitted to the intensive care unit because of suspected pneumococcal meningitis received recommended treatment for pneumococcal meningitis, comprising intravenous cefotaxime (200 mg per kg of body weight per day), vancomycin (administered as continuous infusion of 60 mg per kg of body weight per day after a loading dose of 15 mg per kg of body weight), and adjunctive therapy with dexamethasone (10 mg every 6 h). Vancomycin levels in CSF were measured on day 2 or day 3 of therapy and were correlated with protein levels in CSF and vancomycin levels in serum (determined at the same time as levels in CSF).. Fourteen patients were included. Thirteen had proven pneumococcal meningitis; 1 patient, initially suspected of having pneumococcal meningitis, was finally determined to have meningitis due to Neisseria meningitidis. Mean levels of vancomycin in serum and CSF were 25.2 and 7.2 mg/L, respectively, and were positively correlated (r=0.6; P=.025). A positive correlation was also found between the ratio of vancomycin in CSF to vancomycin in serum and the level of protein in CSF (r=0.66; P=.01).. Appropriate concentrations of vancomycin in CSF may be obtained even when concomitant steroids are used. Dexamethasone can, therefore, be used without fear of impeding vancomycin penetration into the CSF of patients with pneumococcal meningitis, provided that vancomycin dosage is adequate. This study is registered at http://www.ClinicalTrials.gov/ (registration number NCT00162578).

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents; Cefotaxime; Dexamethasone; Female; Humans; Male; Meningitis, Meningococcal; Meningitis, Pneumococcal; Middle Aged; Vancomycin

Cefotaxime (CTX) and ceftriaxone (CRO) were compared for cerebrospinal fluid (CSF) penetration and antimicrobial efficacy in cases of bacterial meningitis in children. This was a comparative study of CRO (100mg/kg once daily) and CTX (50 mg/kg 6 hourly) in the treatment of children with bacterial meningitis. The aetiological agents included Streptococcus pneumoniae (SPn), Haemophilus influenzae type b (Hib) and Neisseria meningitidis (NMen). Minimum inhibitory concentrations (MICs) were measured. In 33 patients from whom a second CSF specimen was obtained, CSF was cultured and assayed for antibiotic concentration. Median MICs of CTX and CRO for SPn, Hib and NMen were 0.01 and 0.01 microg/mL, 0.004 and 0.002 microg/mL and 0.008 and 0.004 microg/mL, respectively. All 33 repeat lumbar puncture specimens were sterile. The lowest CSF level recorded (0.45 microg/mL for CTX) was 45 times the MIC (0.01 microg/mL). The highest levels (24-35 microg/mL for CRO) were up to 8750 times the MIC of the patient's causative organism. A wide range of CSF levels for both antibiotics was observed. Levels varied with post-dose interval and duration of illness. On the basis of these findings, clinicians should be reassured that repeat lumbar puncture is not recommended for the causative organisms in this study (i.e., for Hib, NMen and penicillin/cefotaxime/ceftriaxone fully-susceptible SPn).

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Female; Haemophilus influenzae type b; Humans; Infant; Infant, Newborn; Male; Meningitis, Bacterial; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal

Topics: Adolescent; Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Male; Meningitis, Pneumococcal; Prospective Studies; Treatment Outcome; Vancomycin

We treated nine patients (10 episodes) with meningitis caused by Streptococcus pneumoniae isolates with decreased susceptibilities to broad-spectrum cephalosporins with high doses of cefotaxime (300 mg/kg of body weight per day; maximum dose, 24 g/day). Early adjunctive therapy with dexamethasone was also administered. Cefotaxime MICs were 0.5 (three episodes), 1 (five episodes), and 2 (two episodes) micrograms/ml, and MBCs ranged from 1 to 4 micrograms/ml. Therapy was well tolerated, and all patients experienced prompt clinical improvement. One patient died 8 days after the end of therapy, the central nervous system infection had already been cured, and the remaining patients recovered without relapses.

Topics: Adult; Aged; Cefotaxime; Cephalosporin Resistance; Cephalosporins; Drug Administration Schedule; Female; Humans; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Middle Aged; Spain

In experimental models of meningitis and in children with meningitis, dexamethasone has been shown to reduce meningeal inflammation and to improve the outcome of disease.. We conducted a placebo-controlled, double-blind trial of dexamethasone therapy in 101 infants and children admitted to the National Children's Hospital, San José, Costa Rica, who had culture-proved bacterial meningitis or clinical signs of meningitis and findings characteristic of bacterial infection on examination of the cerebrospinal fluid. The patients were randomly assigned to receive either dexamethasone and cefotaxime (n = 52) or cefotaxime plus placebo (n = 49). Dexamethasone (0.15 mg per kilogram of body weight) was given 15 to 20 minutes before the first dose of cefotaxime and was continued every 6 hours thereafter for four days.. The demographic, clinical, and laboratory profiles were similar for the patients in the two treatment groups. By 12 hours after the beginning of therapy, the mean opening cerebrospinal pressure and the estimated cerebral perfusion pressure had improved significantly in the dexamethasone-treated children but worsened in the children treated only with cefotaxime (controls). At 12 hours meningeal inflammation and the concentrations of two cytokines (tumor necrosis factor alpha and platelet-activating factor) in the cerebrospinal fluid had decreased in the dexamethasone-treated children, whereas in the controls the inflammatory response in the cerebrospinal fluid had increased. At 24 hours the clinical condition and mean prognostic score were significantly better among those treated with dexamethasone than among the controls. At follow-up examination after a mean of 15 months, 7 of the surviving 51 dexamethasone-treated children (14 percent) and 18 of 48 surviving controls (38 percent) had one or more neurologic or audiologic sequelae (P = 0.007); the relative risk of sequelae for a child receiving placebo as compared with a child receiving dexamethasone was 3.8 (95 percent confidence interval, 1.3 to 11.5).. The results of this study, in which dexamethasone administration began before the initiation of cefotaxime therapy, provide additional evidence of a beneficial effect of dexamethasone therapy in infants and children with bacterial meningitis.

Topics: Adolescent; Bacterial Infections; Cefotaxime; Cerebrospinal Fluid Pressure; Child; Child, Preschool; Dexamethasone; Double-Blind Method; Female; Hearing Disorders; Humans; Infant; Male; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Nervous System Diseases; Tumor Necrosis Factor-alpha

In a multicentre study, 220 consecutive cases of bacterial meningitis in children older than 3 months were randomised to treatment with chloramphenicol, ampicillin (initially with chloramphenicol), cefotaxime, or ceftriaxone. The drugs were given in four equal daily doses for 7 days, except ceftriaxone which was given only once daily. 200 cases could be assessed; the causative organisms were Haemophilus influenzae type b (Hib) in 146; meningococci (Mnc) in 32; pneumococci (Pnc) in 13; and other or unknown in 9. In patients with Hib meningitis, sterilisation of the cerebrospinal fluid occurred most rapidly with ceftriaxone. Otherwise, in terms of overall clinical recovery, normalisation of laboratory indices, clinically significant adverse reactions, toxic effects, sequelae, and mortality rate, the treatment groups were very similar. However, there were 4 bacteriological failures, all in the chloramphenicol group. Also, the treatment was extended or changed in more cases in the chloramphenicol group than in the other groups. Chloramphenicol was thus inferior to the other three antimicrobials. Ampicillin is a good and cheap alternative, but there are difficulties with resistance. Easy administration tempts the use of ceftriaxone rather than cefotaxime but it causes diarrhoea. A 7-day course of ampicillin, cefotaxime, or ceftriaxone is sufficient in Hib, Mnc, or Pnc meningitis.

Topics: Adolescent; Ampicillin; Bacterial Infections; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Chloramphenicol; Female; Finland; Follow-Up Studies; Humans; Infant; Male; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Multicenter Studies as Topic; Random Allocation; Recurrence

Forty-five children (aged 1 day to 15 years) with bacterial meningitis were randomized to receive either traditional therapy (ampicillin and chloramphenicol or gentamicin, pending sensitivity) or ceftriaxone (100 mg/kg per day in two doses for a minimum of 10 days). The etiological agents involved were similar for the two groups and included Haemophilus influenzae type b, Neisseria meningitidis, Streptococcus pneumoniae, and group B streptococcus. Repeat spinal taps were carried out 24 to 48 h after admission. Organisms were seen on the Gram stain of one patient treated with ceftriaxone, but five patients in the traditional therapy group had organisms present on Gram stain of uncentrifuged spinal fluid or positive cultures of the spinal fluid (or both). Ceftriaxone entered the cerebrospinal fluid well, and the average cerebrospinal fluid bactericidal activity for ceftriaxone 1 h after a dose was at least 60 times greater than for ampicillin or chloramphenicol. In those patients who received treatment for a long enough period of time to permit evaluation, there was one death in each group, both due to S. pneumoniae. The length of fever and complications were similar for the patients in both groups. Ceftriaxone was well tolerated; diarrhea, seen in 5 of the 22 patients who received the drug, was the most commonly encountered adverse effect. It was mild, and in no case was it necessary to discontinue the drug. Ceftriaxone appears in this preliminary study to be a safe and acceptable single agent for the treatment of bacterial meningitis in children.

Topics: Adolescent; Ampicillin; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Chloramphenicol; Female; Gentamicins; Humans; Infant; Infant, Newborn; Male; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Random Allocation

Ceftriaxone is a new cephalosporin with a broad spectrum of antibacterial activity and unique serum and CSF pharmacokinetics. The drug was compared in a randomized fashion with ampicillin and chloramphenicol in the treatment of 19 children with Haemophilus influenzae type b meningitis. Ceftriaxone was also administered non-randomly to six other patients including three children with Gram-negative meningitis. Among the children with H. influenzae meningitis, no deaths were noted and the outcomes of the study and the control groups were similar. Ninety per cent of the isolates of H. influenzae were inhibited by 0.0625, 1 and 1 mg/l of ceftriaxone, ampicillin and chloramphenicol respectively. One child with pneumococcal meningitis and two children with meningococcal meningitis recovered rapidly and without incident during ceftriaxone therapy. Three children with Gram-negative meningitis caused by multiply-drug resistant organisms were bacteriologically cured within five days of the onset of therapy. Persistent pleocytosis and neurological disabilities were noted in two at the conclusion of therapy. Ceftriaxone, as a single agent, was comparable in efficacy with traditional antimicrobial therapy usually employed in childhood meningitis.

Topics: Adolescent; Ampicillin; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Chloramphenicol; Drug Therapy, Combination; Female; Humans; Infant; Male; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Random Allocation

78 patients with bacterial meningitis were evaluated in a prospective, randomised study comparing twice-daily ceftriaxone as single-drug therapy with ampicillin and chloramphenicol given every 6 h. The groups were comparable in age, sex, days of illness before admission, and bacterial colony counts in cerebrospinal fluid (CSF). The pathogens were Haemophilus influenzae type b (54 cases), streptococci (9 cases), meningococci (9 cases), and unknown (6 cases). In 40 CSF specimens obtained 4-12 h after initiation of therapy, cultures were negative in 57% of the ceftriaxone patients and in 42% of the others. The mean falls in the CSF bacterial colony counts were 4.7 and 5.0 log10 colony-forming units/ml, respectively. Mean bactericidal activity in CSF was significantly greater in the ceftriaxone than in the conventional treatment group at the beginning and end of therapy. There were no significant differences in clinical responses or in frequency of complications, except for mild diarrhoea, which occurred in 16 ceftriaxone patients and in 8 in the other group (p less than 0.05).

Topics: Adolescent; Ampicillin; Cefotaxime; Ceftriaxone; Cerebrospinal Fluid; Child; Child, Preschool; Chloramphenicol; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Infant; Male; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Prospective Studies; Random Allocation

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Cephalosporins; Humans; Meningitis; Meningitis, Bacterial; Meningitis, Pneumococcal; Microbial Sensitivity Tests

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Cephalosporins; Cohort Studies; Humans; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Mitomycin; Monobactams; Penicillin Resistance; Penicillins; Streptococcus pneumoniae

Pneumococcal meningitis is a devastating disease that requires adequate meningeal antibiotic penetration to limit the mortality. Despite a large usage in this indication, data about CSF concentration of cefotaxime during pneumococcal meningitis in adults are scarce. Therefore, we aimed to describe the CSF concentration obtained after high-dose cefotaxime administration in adult patients treated for Streptococcus pneumoniae meningitis.. In this multicentre, observational, retrospective study, cases of adult patients with S. pneumoniae meningitis hospitalized between January 2013 and October 2019 for whom cefotaxime concentration was measured in CSF were reviewed.. Cefotaxime concentration was analysed in 44 CSF samples collected among 31 patients. Median (IQR) age was 61 years (52-69). Dexamethasone was administered in 27 subjects. Median (IQR) cefotaxime daily dosage was 15 g (12-19), corresponding to 200 mg/kg (150-280). CSF samples were collected approximately 5 days after cefotaxime initiation. Median (IQR, range) cefotaxime CSF concentration was 10.3 mg/L (4.8-19.3, 1.2-43.4). Median (range) MIC for Streptococcus pneumoniae was 0.25 mg/L (0.008-1) (n = 22). The median (IQR, range) CSF/MIC ratio was 38 (12-146, 4-1844). Twenty-five CSF concentrations (81%) were above 10 times the MIC. Cefotaxime was discontinued in two patients for toxicity. In-hospital mortality rate was 29%.. Adult patients with pneumococcal meningitis treated with a high dose of cefotaxime (200 mg/kg/day) had elevated CSF concentrations with satisfying pharmacokinetics/pharmacodynamics parameters and tolerability profile. This study brings reassuring pharmacological data regarding the use of high-dose cefotaxime monotherapy for treating pneumococcal meningitis with susceptible strains to cefotaxime.

Topics: Adult; Aged; Anti-Bacterial Agents; Cefotaxime; Humans; Meningitis, Pneumococcal; Middle Aged; Retrospective Studies; Streptococcus pneumoniae

Although the pneumococcal conjugate vaccine (PCV) has decreased the incidence of invasive pneumococcal disease (IPD) in children, cases of IPD caused by non-PCV serotypes have been increasing. Here, we report two cases of bacterial meningitis caused by meropenem-resistant Streptococcus pneumoniae; in both the cases, 13-valent PCV (PCV13) had been administered. The isolated S. pneumoniae strains were non-PCV13 serotype 35B and resistant to penicillin G, cefotaxime, and meropenem. In addition, multilocus sequence typing (MLST) revealed the sequence type (ST) to be 558. In case 1, a 6-month-old girl recovered without sequelae after antibiotic therapy comprising cefotaxime and vancomycin, whereas in case 2, a 9-month-old boy was treated with an empirical treatment comprising ceftriaxone and vancomycin administration. However, maintaining the blood concentration of vancomycin within the effective range was difficult, due to which the antibiotics were changed to panipenem/betamipron. During the treatment, he presented with seizures, which were effectively controlled with antiepileptic drugs. The rate of incidence of penicillin-susceptible IPD has been substantially increasing after the introduction of PCV. However, an upsurge in IPD cases due to multidrug-resistant (MDR) serotype 35B has been reported in countries where PCV13 was introduced before introducing in Japan. Moreover, an increase in the proportion of MDR serotype 35B and decrease in the susceptibility to broad-spectrum antimicrobials, including meropenem, have been reported. Hence, the number of meningitis cases caused by MDR serotype 35B/ST558 may increase in the future.

Topics: Anti-Bacterial Agents; beta-Alanine; Cefotaxime; Drug Resistance, Multiple, Bacterial; Female; Humans; Infant; Male; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Multilocus Sequence Typing; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae; Thienamycins; Treatment Outcome

To evaluate the impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children.. Children younger than 15years of age attending 27 hospitals in the Region of Madrid with confirmed pneumococcal meningitis were identified in a prospective surveillance study, from 2007 to 2015. Clinical data, neurological sequelae, pneumococcal vaccination status, serotyping and antibiotic susceptibility were recorded.. One hundred and four cases of pneumococcal meningitis were identified, 63 during the period of routine 7-valent pneumococcal conjugate vaccine immunisation (May 2007-April 2010) and 41 during the period of 13-valent pneumococcal conjugate vaccine immunisation (May 2010-April 2015). When both periods were compared, a 62% (95% CI: 45-75%) decrease in the incidence of pneumococcal meningitis was observed, from 2.19 cases per 100,000 inhabitants in the PCV7 period to 0.81 per 100,000 inhabitants in the PCV13 period (p=0.0001), mainly due to an 83% (95% CI: 30-96%) reduction in cases caused by serotype 19A. Isolates not susceptible to cefotaxime (MIC>0.5μg/L) decreased from 27% to 8%, (p=0.02). Mean patient ages rose from 28.7months to 38.5months (p<0.05). Case fatality rate across both periods was 5%. An unfavourable outcome (death or neurological sequelae) occurred in 27% of patients, while the rate was similar in both periods. There was no increase in meningitis caused by pneumococcal serotypes not included in 13-valent pneumococcal conjugate vaccine throughout the years of the study.. Immunisation with 13-valent pneumococcal conjugate vaccine has reduced the rate of pneumococcal meningitis in children less than 15years, with a near-elimination of cefotaxime-resistant isolates, but morbidity has remained unchanged. A shift of pneumococcal meningitis towards slightly higher age groups was also observed.

Topics: Adolescent; Age Factors; Anti-Bacterial Agents; Cefotaxime; Child; Child, Preschool; Female; Heptavalent Pneumococcal Conjugate Vaccine; Humans; Immunologic Surveillance; Incidence; Infant; Male; Meningitis, Pneumococcal; Pneumococcal Infections; Pneumococcal Vaccines; Prospective Studies; Serogroup; Serotyping; Spain; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate

Topics: Anti-Bacterial Agents; Cefotaxime; Coinfection; Disease Outbreaks; Disease Susceptibility; Drug Therapy, Combination; Enterovirus Infections; Female; Humans; Infant; Magnetic Resonance Imaging; Meningitis, Pneumococcal; Meningitis, Viral; Seasons; Vancomycin

Topics: Amoxicillin; Anti-Bacterial Agents; Cefotaxime; Child; Drug Resistance, Multiple, Bacterial; France; Humans; Meningitis, Pneumococcal; Pneumococcal Vaccines; Societies, Medical; Vaccines, Conjugate

To determine the common aetiolog of acute bacterial meningitis in children and their antibiotic susceptibility pattern.. A retrospective study with a review of cerebrospinal fluid culture reports of paediatric patients aged 0-15 years, suspected of acute meningitis in the Medical Microbiology Department of Aminu Kano Teaching Hospital, Kano, Nigeria from October 2006 to October 2009 from October 2006 to October 2009.. A positive culture bacterial isolation rate of 3.3% (n=50/1500) with prevalence of Streptococcus pneumoniae (24%), Neisseria meningitidis (22%), Escherichia coli (16%), Haemophilus influenzae (14%), Group B streptococci (8%) and Enterococci (8%) which were susceptible to ceftriaxone (96%), cefotaxime (95%) and ciprofloxacin (93%) across the bacterial isolates. Neonates were 55% (n=6.8/12.4) most at risk.. Neonates are the most at risk of acute bacterial meningitis. In the absence of antibiotic susceptibility report, ceftriaxone should be considered as a first choice reliable antibiotic for empirical treatment of meningitis in children, in this environment.

Topics: Adolescent; Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Cerebrospinal Fluid; Child; Child, Preschool; Ciprofloxacin; Enterococcus; Escherichia coli; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Meningitis, Bacterial; Meningitis, Escherichia coli; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Nigeria; Retrospective Studies; Streptococcus agalactiae; Tertiary Care Centers

To review the epidemiology and clinical course of invasive pneumococcal diseases of infants younger than 60 days.. All Streptococcus pneumoniae strains isolated from blood and cerebrospinal fluid cultures of infants below the age of 60 days during the years 1999-2009 were included in this study. Demographic, clinical, and laboratory data were collected from medical records.. In all, 24 cases of pneumococcal invasive infections were identified. The primary diagnoses were bacteremia without a focus (n = 13), meningitis (n = 6), bacteremia with otitis media (n = 3), and joint infection with bacteremia (n = 2). Only one of the serotypes found is included in the heptavalent pneumococcal conjugated vaccine (PCV7).. Streptococcus pneumoniae should be considered and treated empirically in infants with suspected invasive bacterial disease during the first 60 days of life. Routine vaccination with PCV7 in not expected to substantially reduce the incidence of invasive pneumococcal disease in Israeli infants of this age as a result of herd immunity.

Topics: Anti-Bacterial Agents; Bacteremia; Cefotaxime; Female; Humans; Infant; Infant, Newborn; Israel; Male; Meningitis, Pneumococcal; Penicillins; Pneumococcal Infections; Treatment Outcome

A total of 8172 isolates from invasive pneumococcal disease was collected from 1992 to 2006 in Germany. From these, 88 were from children < or = 60 days of age, where the leading serotypes were 7F (14.8%), 1 and 14 (13.6% each), 3 (8.0%), and 9V (6.8%). The serotype distribution found in this study suggests that pneumococcal infections are transferred to them both by older siblings and adults. The theoretical serotype coverages for the pneumococcal vaccines were 36.8% (7-valent), 67.8% (10-valent), 80.5% (13-valent) and 89.7% (23-valent). Since the serotype distribution among children < or = 60 days differs considerably from those vaccinated against pneumococci (6 or 8 weeks up to 5 years), our data suggest, that future epidemiological surveys might profit from a separate presentation of serotype and coverage data from children < or = 60 days to increase the accuracy especially of coverage data among children. Penicillin G resistance was observed in 3.1% of meningitis cases. In the non-meningitis group no penicillin G nonsusceptible strains were detected. Concerning cefotaxime, 3.1% of isolates from meningitis cases were resistant, while in the non-meningitis group all isolates were susceptible. Among the non-meningitis cases no nonsusceptibility to amoxicillin was found. Further resistance rates were 14.9% for macrolides, and 4.6% for clindamycin.

Topics: Age Factors; Amoxicillin; Anti-Bacterial Agents; Cefotaxime; Drug Resistance, Bacterial; Female; Germany; Humans; Infant; Infant, Newborn; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin G; Pneumococcal Infections; Pneumococcal Vaccines; Serotyping; Streptococcus pneumoniae; Vaccines, Conjugate

To present a patient who developed bilateral endogenous endophthalmitis secondary to Streptococcus pneumoniae meningitis.. A 44-year-old man who was unconscious because of bacterial meningitis was referred to us for conjunctival hyperemia and decreased pupillary light reflexes. Ophthalmoscopy revealed inflammation in the anterior chamber and vitreous opacities in both eyes. He was diagnosed as having endogenous endophthalmitis associated with the meningitis. Ceftazidime and vancomycin hydrochloride were injected intravitreally and subconjunctivally repeatedly in both eyes.. Vision improved to 20/200 in the left eye 1 month later, but the right eye became hypotonic and blind. Vision deteriorated to light perception in the left eye due to a retinal detachment with proliferative vitreoretinopathy, and vitreous surgery successfully reattached the retina. Vision recovered to 20/80, and the retina has remained attached for 1 year.. We recommend that endogenous endophthalmitis be suspected in cases of meningitis, and if present, intravitreal and subconjunctival antibiotics should be promptly given to preserve vision.

Topics: Adult; Ampicillin; Anti-Bacterial Agents; Bacteremia; Cefotaxime; Ceftazidime; Cerebrospinal Fluid; Drug Therapy, Combination; Endophthalmitis; Eye Infections, Bacterial; Functional Laterality; Humans; Male; Meningitis, Pneumococcal; Retinal Detachment; Scleral Buckling; Streptococcus pneumoniae; Vancomycin; Visual Acuity; Vitrectomy; Vitreoretinopathy, Proliferative

We report on a 35-year-old man who developed pneumococcal meningitis while receiving antiviral therapy with interferon (consensus interferon, CIFN) and ribavirin for chronic hepatitis C. Antibiotic therapy was started four days after the onset of symptoms. Unfortunately, the patient developed a persisting right-sided cochlear hearing impairment. Antiviral therapy led to sustained viral response of hepatitis C. At the age of 14 years he had experienced a hemorrhagic shock after a traffic accident, received multiple blood transfusions and undergone a splenectomy. He had not received vaccination against Streptococcus pneumoniae. This case report reminds us that splenectomized patients without previous pneumococcal vaccination should receive such vaccination before immunomodulatory treatment.

Topics: Adult; Antiviral Agents; Bacterial Proteins; Cefotaxime; Dose-Response Relationship, Drug; Drug Therapy, Combination; Follow-Up Studies; Hearing Loss, Unilateral; Hepatitis C, Chronic; Humans; Infusions, Intravenous; Interferon Type I; Interferon-alpha; Male; Meningitis, Pneumococcal; Opportunistic Infections; Penicillin G; Pneumococcal Vaccines; Randomized Controlled Trials as Topic; Recombinant Proteins; Ribavirin; Risk Factors; Splenectomy

Daptomycin monotherapy was superior to ceftriaxone monotherapy and was highly efficacious in experimental pneumococcal meningitis, sterilizing the cerebrospinal fluid (CSF) of three of three rabbits after 4 to 6 h. With daptomycin therapy only a negligible release of [(3)H]choline as marker of cell wall lysis was detectable in the CSF, peaking around 250 cpm/min after 4 h, compared to a peak of around 2,400 cpm/min after 4 to 6 h for the ceftriaxone-treated rabbits.

Topics: Animals; Anti-Bacterial Agents; Bacteriolysis; Ceftriaxone; Cell Wall; Cerebrospinal Fluid; Choline; Daptomycin; Disease Models, Animal; Humans; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin Resistance; Rabbits; Streptococcus pneumoniae; Treatment Outcome; Tritium

Few adverse effects have been reported with adjunctive dexamethasone treatment in pneumococcal meningitis. Nevertheless, we report a case of cerebral vasculitis. A 49-year-old man was admitted for fever and altered mental status. Lumbar puncture revealed a high inflammatory response and Streptococcus pneumoniae was identified by culture. Antibacterial therapy and adjunctive dexamethasone treatment were initiated as recommended. The immediate outcome was favorable but due to the onset of focal cerebral abnormalities, a CT scan was performed on the ninth day showing cerebral vasculitis. The patient died on the thirteenth day despite antibacterial therapy and resuscitation. In our case, a secondary neurological worsening appeared when adjunctive dexamethasone treatment was stopped suggesting a rebound effect. Observation of similar cases may lead to modifying adjunctive dexamethasone treatment protocol in bacterial meningitis.

Topics: Amoxicillin; Anti-Inflammatory Agents; Arthritis, Infectious; Brain Edema; Cefotaxime; Chemotherapy, Adjuvant; Coma; Dexamethasone; Drug Therapy, Combination; Emergencies; Encephalocele; Fatal Outcome; Fever; Humans; Knee Joint; Male; Meningitis, Pneumococcal; Middle Aged; Substance Withdrawal Syndrome; Vancomycin; Vasculitis, Central Nervous System

Culture-negative bacterial meningitis with secondary complications remains a significant challenge. Optimal treatment requires identification of the infecting organism. While the gold standard for diagnosis remains cerebrospinal fluid culturing, a significant number of cultures remain negative despite clinical evidence of meningitis. This patient illustrates the usefulness of polymerase chain reaction technology in identifying a specific organism, in an otherwise culture-negative bacterial meningitis with spinal cord abscess.

Topics: Anti-Bacterial Agents; Brain; Cefotaxime; Child; DNA, Bacterial; DNA, Ribosomal; Drug Therapy, Combination; Epidural Abscess; False Negative Reactions; Female; Humans; Magnetic Resonance Imaging; Meningitis, Pneumococcal; Polymerase Chain Reaction; Spinal Cord; Streptococcus pneumoniae; Vancomycin

To determine the probability of meropenem (Merrem, AstraZeneca Pharmaceuticals L.P., Wilmington, DE, USA) and cefotaxime (Claforan, Aventis Pharmaceuticals Inc., Bridgewater, NJ, USA) achieving bactericidal exposures in the cerebrospinal fluid against Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae.. A 5,000-patient Monte Carlo simulation in a population of 10-year-old children with meningitis was conducted. Pediatric pharmacokinetic data were derived from the literature. Pathogen minimum inhibitory concentrations (MICs) were obtained from common bacteria that had caused meningitis collected during pediatric clinical trials. Time above the MIC exposures in the cerebrospinal fluid was calculated. Bactericidal exposure or probability of target attainment was defined as 40% and 50% time above the MIC for meropenem and cefotaxime, respectively. High cumulative fractions of responses were defined as >90% probability of target attainment against the populations of bacteria.. Meropenem was calculated to achieve 94.7%, 94.3%, and 96.1% cumulative fractions of response against S. pneumoniae, H. influenzae, and N. meningitidis, respectively. Cefotaxime only achieved a high likelihood of bactericidal attainment against N. meningitidis (91.6%). Against S. pneumoniae and H. influenzae, cefotaxime was only calculated to achieve 84.3% and 84.8% cumulative fractions of response, respectively.. In a simulated population of 10-year-old children, meropenem had a high likelihood of attaining bactericidal exposures in the cerebrospinal fluid. Cefotaxime had a >90% cumulative fraction of response against only N. meningitidis. Therefore, at the doses simulated, meropenem may be a more appropriate empiric choice for the treatment of bacterial meningitis in pediatric patients presumed to be caused by these pathogens until culture and susceptibility data are available.

Topics: Anti-Bacterial Agents; Body Weight; Cefotaxime; Child; Computer Simulation; Dose-Response Relationship, Drug; Humans; Meningitis, Bacterial; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Meropenem; Monte Carlo Method; Thienamycins

Experts recommend that children with suspected pneumococcal meningitis should empirically receive combination therapy with vancomycin plus either ceftriaxone or cefotaxime. The relationship between timing of the first dose of vancomycin relative to other antibiotics and outcome in these children, however, has not been addressed.. Medical records of children with pneumococcal meningitis at a single institution from 1991-2001 were retrospectively reviewed. Vancomycin start time was defined as the number of hours from initiation of cefotaxime or ceftriaxone therapy until the administration of vancomycin therapy. Outcome variables were death, sensorineural hearing loss, and other neurologic deficits at discharge. Associations between independent variables and outcome variables were assessed in univariate and multiple logistic regression analyses.. Of 114 subjects, 109 received empiric vancomycin therapy in combination with cefotaxime or ceftriaxone. Ten subjects (9%) died, whereas 37 (55%) of 67 survivors who underwent audiometry had documented hearing loss, and 14 (13%) of 104 survivors were discharged with other neurologic deficits. Subjects with hearing loss had a significantly shorter median vancomycin start time than did those with normal hearing (<1 vs 4 hours). Vancomycin start time was not significantly associated with death or other neurologic deficits in univariate or multivariate analyses. Multiple logistic regression revealed that hearing loss was independently associated with vancomycin start time <2 hours, blood leukocyte count <15000/microL, and cerebrospinal fluid glucose concentration <30 mg/dL.. Early empiric vancomycin therapy was not clinically beneficial in children with pneumococcal meningitis but was associated with a substantially increased risk of hearing loss. It may be prudent to consider delaying the first dose of vancomycin therapy until > or =2 hours after the first dose of parenteral cephalosporin in children beginning therapy for suspected or confirmed pneumococcal meningitis.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Drug Therapy, Combination; Female; Hearing Loss, Sensorineural; Humans; Infant; Male; Meningitis, Pneumococcal; Survival Rate; Vancomycin

Over the last decade Streptococcus pneumoniae has emerged as the most common bacterial pathogen for meningitis in all age groups, beyond the neonatal period.. To determine the epidemiological and clinical characteristics; and risk factors for mortality of pneumoccocal meningitis in children in a developing transitional country.. A retrospective study that included patients<15 years of age admitted at the Instituto de Medicina Tropical of Paraguay, from January 1990 until December 2003 with the diagnosis of bacterial meningitis caused by S. pneumoniae. Clinical and laboratory data were collected and analysed in order to identify risk factors associated with morbidity and mortality outcomes of this infection.. Seventy-two patients (between the ages of 35 days and 14 years) were identified. Forty-two per cent of patients had seizures prior to or at the time of admission, 36% were admitted in a comatose state, and 19% with shock. Mortality was 33% (24/72), and 18% of the survivors (11/60) developed severe sequelae. Upon admission, the following variables were strongly correlated with mortality: age<12 months (P=0.007), the presence of seizures (P=0.0001) or development of seizures 48 h after admission (P=0.01), a cerebrospinal fluid (CSF) glucose level of <10 mg/dl (P=0.01), CSF albumin>200 mg/dl (P=0.0003), an absolute blood neutrophil count<2000/mm3 (P=0.006) and a haemoglobin value of <9 g/dl (P=0.0001).. This study confirms the high morbidity and mortality associated with S. pneumoniae meningitis in Paraguay. Certain clinical parameters and laboratory findings in blood and CSF at the time of admission could be used as predictors for mortality or severe sequelae among survivors.

Topics: Acute Disease; Adolescent; Age Distribution; Anti-Bacterial Agents; Cefotaxime; Child; Child, Preschool; Coma; Female; Humans; Infant; Male; Meningitis, Pneumococcal; Paraguay; Penicillins; Retrospective Studies; Risk Factors; Seizures; Streptococcus pneumoniae; Treatment Outcome

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Cefotaxime; Dexamethasone; Drug Resistance, Bacterial; Humans; Meningitis, Haemophilus; Meningitis, Pneumococcal; Metalloproteins; Neisseria meningitidis; Spain; Streptococcus pneumoniae; Vaccines, Conjugate

Topics: Anti-Bacterial Agents; beta-Lactam Resistance; Cefotaxime; Central America; Humans; Infant; Male; Meningitis, Pneumococcal; Streptococcus pneumoniae; Vancomycin

Topics: Adult; Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Humans; Meningitis, Pneumococcal; Penicillin Resistance; Pneumococcal Infections; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Cefotaxime, given in two doses (each 100 mg/kg of body weight), produced a good bactericidal activity (-0.47 Deltalog(10) CFU/ml. h) which was comparable to that of levofloxacin (-0.49 Deltalog(10) CFU/ml. h) against a penicillin-resistant pneumococcal strain WB4 in experimental meningitis. Cefotaxime combined with levofloxacin acted synergistically (-1.04 Deltalog(10) CFU/ml. h). Synergy between cefotaxime and levofloxacin was also demonstrated in vitro in time killing assays and with the checkerboard method for two penicillin-resistant strains (WB4 and KR4). Using in vitro cycling experiments, the addition of cefotaxime in sub-MIC concentrations (one-eighth of the MIC) drastically reduced levofloxacin-induced resistance in the same two strains (64-fold increase of the MIC of levofloxacin after 12 cycles versus 2-fold increase of the MIC of levofloxacin combined with cefotaxime). Mutations detected in the genes encoding topoisomerase IV (parC and parE) and gyrase (gyrA and gyrB) confirmed the levofloxacin-induced resistance in both strains. Addition of cefotaxime in low doses was able to suppress levofloxacin-induced resistance.

Topics: Animals; Anti-Infective Agents; Cefotaxime; Cephalosporins; DNA, Bacterial; Drug Resistance, Bacterial; Drug Synergism; Levofloxacin; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Mutation; Ofloxacin; Penicillin Resistance; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Streptococcus pneumoniae

The incidence of infection with penicillin-non-susceptible Streptococcus pneumoniae is increasing rapidly worldwide. Spain and France are highly affected, whereas the level of penicillin resistance in Germany, Italy, The Netherlands and Scandinavia is low. We report a lethal episode of meningitis due to penicillin- and cefotaxime-intermediate S. pneumoniae in a 7-year-old, allogene bone marrow transplanted German boy, 5 weeks after a holiday in Spain. Three days prior to the infection the patient showed good performance status. He was in complete remission without signs of graft-versus-host disease (GVHD). He died on day 341 post bone marrow transplant (BMT), 2 days after the onset of meningitis. Penicillin-non-susceptible S. pneumoniae should be regarded as a potential infectious agent even in countries with a low prevalence of resistance.

Topics: Bone Marrow Transplantation; Cefotaxime; Cephalosporin Resistance; Child; Disease Progression; Drug Resistance, Multiple, Bacterial; Fatal Outcome; Germany; Humans; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin Resistance; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Assessment; Streptococcus pneumoniae

In 1999, in Rhône-Alpes region, in a survey of resistance to antibiotics of Streptococcus pneumoniae, 35 cases of meningitis were observed. A retrospectic questionnary was sent to each participant. MICs to Penicillin, Amoxicillin and Cefotaxime were determined with ATB-PNEUMO gallery or E-test and by disk diffusion for the other antibiotics. The results were interpreted according to the recommendations of the CA-SFM. Mean age was 38.1 years (range : 1 month -78 years) and sex-ratio 2/5. Eight patients had previously received antibiotics, 22 patients had risk factors and 23 were transferred in intensive care unit. The patients received C3G + glycopeptide in 15 of 16 children and in 13/19 adults according to the consensus recommendations. Diagnostic was made on the direct examination of CSF in 83%, and blood cultures was positive in 74.3% of cases. The percentage of PRP was 48.6% with 17.1% of intermediate-amoxicilline and 14.3% intermediate-cefotaxime strains. Resistance to trimethoprim-sulfamethoxazole was 45.7%, to chloramphenicol 30% and to fosfomycin 6.9%. All the strains were susceptible to rifampicin and vancomycin. Among the 17 PRP strains, 7 were belonging to serotype 6 (6 in children). The clinical outcome was fatal in 7 male cases (20%), without risk factors in 3 children and 6 of 7 strains were susceptible to penicillin. Six patients (17%) had auditive and/or neurologic sequellaes. This study shows that nearly 50% of strains isolated in meningitis, in Rhône-Alpes region, were not susceptible to penicillin, and confirms the frequency of sequellaes while the mortality is not related with the resistance of strains to the antibiotics.

Topics: Adolescent; Adult; Aged; Amoxicillin; Cefotaxime; Child; Child, Preschool; Chloramphenicol; Drug Resistance, Microbial; Female; Fosfomycin; France; Humans; Infant; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Middle Aged; Penicillins; Retrospective Studies; Rifampin; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

We have undertaken this retrospective study to determine factors associated with in-hospital mortality and morbidity in 80 adult patients with severe Streptococcus pneumoniae meningitis. Clinical characteristics at admission of patients infected with susceptible (n = 54) and nonsusceptible (n = 17) strains to penicillin G were similar: age: 51 +/- 19 versus 58 +/- 15 yr (p = 0.16); Simplified Acute Severity Score (SAPS II): 39 +/- 14 versus 41 +/- 11 (p = 0.68); and Glasgow Coma Score: 8 +/- 3 versus 9.5 +/- 3 (p = 0.21), respectively. In-hospital mortality was 25% (20/80), with one death among the 17 patients (6%) infected with a nonsusceptible strain (p = 0.03). High-dose dexamethasone was used in 22 cases. By multivariate analysis, three factors were independently associated with death: platelet count < 100 G/L (adjusted odds ratio [aOR] = 32.7; 95% CI = 3.2 to 332.5; p = 0.0032), arterial pH > 7.47 (aOR = 33.1; 95% CI = 3.4 to 319.7; p = 0.0025), and mechanical ventilation (aOR = 48.8; 95% CI = 2.6 to 901.5; p = 0.009). When adjusting for the identified prognostic factors, corticosteroids significantly reduced the risk of death (aOR = 0.069; 95% CI = 0.005 to 0.9; p = 0.048). Only SAPS II was predictive of adverse outcome (death or neurologic deficit). We conclude that in intubated patients with S. pneumoniae meningitis, hyperventilation should be used with caution. Nonsusceptibility to penicillin G is not associated with a worse outcome. High-dose corticosteroids may be beneficial in the most severely ill patients.

Topics: Adolescent; Adult; Cefotaxime; Dexamethasone; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Meningitis, Pneumococcal; Middle Aged; Opportunistic Infections; Penicillin Resistance; Penicillins; Prognosis; Survival Rate; Treatment Outcome

Conventional diagnostic methods for bacterial meningitis are frequently not rapid or sensitive enough to guide initial antimicrobial therapy. Streptococcus pneumoniae is the most frequent and severe cause of community-acquired bacterial meningitis and treatment is complicated by the increasing prevalence of antimicrobial resistance to third-generation cephalosporins. We used a new rapid antigen test in the cerebrospinal fluid and urine of patients with suspected bacterial meningitis, and found it to be highly sensitive and specific for the detection of pneumococci. This test might help guide initial therapy for bacterial meningitis according to the local rates of pneumococcal antimicrobial resistance.

Topics: Adult; Cefotaxime; Female; Humans; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillins; Polysaccharides, Bacterial; Predictive Value of Tests

Despite the lack of evidence defining a time interval during which cerebrospinal fluid (CSF) culture yield will not be affected by previous antibiotic therapy, recent publications cite a "minimum window" of 2 to 3 hours for recovery of bacterial pathogens after parenteral antibiotic administration. We conducted a retrospective review of children with bacterial meningitis to describe the rate at which parenteral antibiotic pretreatment sterilizes CSF cultures.. The medical records of pediatric patients who were discharged from a tertiary children's hospital during a 5-year period with the final diagnosis of bacterial meningitis or suspected bacterial meningitis were reviewed. The decay in yield of CSF cultures over time was evaluated in patients with lumbar punctures (LP) delayed until after initiation of parenteral antibiotics and in patients with serial LPs before and after initiation of parenteral antibiotics.. The pathogens that infected the 128 study patients were Streptococcus pneumoniae (49), Neisseria meningitidis (37), group B Streptococcus (21), Haemophilus influenzae (8), other organisms (11), and undetermined (3). Thirty-nine patients (30%) had first LPs after initiation of parenteral antibiotics, and 55 (43%) had serial LPs before and after initiation of parenteral antibiotics. After >/=50 mg/kg of a third-generation cephalosporin, 3 of 9 LPs in meningococcal meningitis were sterile within 1 hour, occurring as early as 15 minutes, and all were sterile by 2 hours. With pneumococcal disease, the first negative CSF culture occurred at 4.3 hours, with 5 of 7 cultures negative from 4 to 10 hours after initiation of parenteral antibiotics. Reduced susceptibility to beta-lactam antibiotics occurred in 11 of 46 pneumococcal isolates. Group B streptococcal cultures were positive through the first 8 hours after parenteral antibiotics. Blood cultures were positive in 74% of cases without pretreatment and in 57% to 68% of cases with negative CSF cultures.. The temptation to initiate antimicrobial therapy may override the principle of obtaining adequate pretreatment culture material. The present study demonstrates that CSF sterilization may occur more rapidly after initiation of parenteral antibiotics than previously suggested, with complete sterilization of meningococcus within 2 hours and the beginning of sterilization of pneumococcus by 4 hours into therapy. Lack of adequate culture material may result in inability to tailor therapy to antimicrobial susceptibility or in unnecessarily prolonged treatment if the clinical presentation and laboratory data cannot exclude the possibility of bacterial meningitis.

Topics: Adolescent; Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Confidence Intervals; Female; Humans; Infant; Infant, Newborn; Male; Meningitis, Bacterial; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Patient Selection; Spinal Puncture; Time Factors

Topics: Cefotaxime; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Infant; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Severity of Illness Index; Spinal Puncture; Streptococcus pneumoniae; Thienamycins; Treatment Failure; Vancomycin

Limited data are available on clinical outcomes of meningitis due to cefotaxime-nonsusceptible Streptococcus pneumoniae. We analyzed data from 109 cases of pneumococcal meningitis in Atlanta, Baltimore, and San Antonio, which were identified through population-based active surveillance from November 1994 to April 1996. Pneumococcal isolates from 9% of the cases were resistant to cefotaxime, and isolates from 11% had intermediate susceptibility. Children were more likely to have cephalosporin-nonsusceptible pneumococcal meningitis, but mortality was significantly higher among adults aged 18-64 years. Vancomycin was given upon admission to 29% of patients, and within 48 h of admission to 52%. Nonsusceptibility to cefotaxime was not associated with the following outcomes: increased mortality, prolonged length of hospital or intensive care unit (ICU) stay, requirement of intubation or oxygen, ICU care, discharge to another medical or long-term-care facility, or neurological deficit. Empirical use of vancomycin, current prevalence of drug-resistant S. pneumoniae, and degree of nonsusceptibility to cefotaxime may have influenced these findings.

Topics: Adolescent; Adult; Age Distribution; Aged; Anti-Bacterial Agents; Cefotaxime; Cephalosporin Resistance; Cephalosporins; Child; Child, Preschool; Female; Humans; Incidence; Infant; Infant, Newborn; Male; Meningitis, Pneumococcal; Middle Aged; Population Surveillance; Risk Factors; Streptococcus pneumoniae; Vancomycin

Topics: Adolescent; Cefotaxime; Ceftriaxone; Cephalosporin Resistance; Cephalosporins; Cerebrospinal Fluid; Child; Child, Preschool; Female; Humans; Infant; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Retrospective Studies; Streptococcus pneumoniae; Treatment Outcome

Twenty-two non-neutropenic adult patients with Streptococcus pneumoniae meningitis received granulocyte-colony stimulating factor (G-CSF) (300-450 Ig/day subcutaneously for 6 days) in addition to cefotaxime plus dexamethasone (9-12 g/day for 10 days and 16 mg/day for 3 days iv, respectively). Patients recovered without evident sequelae in all cases but one (with bilateral hearing deficit). No adverse event was recorded. Improvement of inflammation indices in the cerebrospinal fluid was rapid. The most rapid improvement was seen in glucose concentration, which returned to normal ranges within 24-48 h of treatment. In this study G-CSF administration appeared to be safe and effective; further controlled clinical trials are justified.

Topics: Adult; Aged; Anti-Inflammatory Agents; Cefotaxime; Cephalosporins; Chemotherapy, Adjuvant; Dexamethasone; Drug Therapy, Combination; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Meningitis, Pneumococcal; Middle Aged; Pilot Projects; Recombinant Proteins; Streptococcus pneumoniae

Topics: Adolescent; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Drug Resistance, Multiple; Humans; India; Infant; Meningitis, Pneumococcal; Penicillin Resistance

Topics: Cefotaxime; Cephalosporins; Drug Resistance, Microbial; Female; Humans; Meningitis, Pneumococcal; Middle Aged

Topics: Cefotaxime; Cephalosporin Resistance; Humans; Infant; Male; Meningitis, Pneumococcal; Penicillin Resistance; Streptococcus pneumoniae

An extended-spectrum cephalosporin has been considered appropriate therapy for non-meningeal infections caused by drug-resistant Streptococcus pneumoniae. We report a toddler who had breakthrough bacteremia and meningitis develop because of drug-resistant pneumococcus while receiving treatment with cefotaxime and cefuroxime for pneumonia.

Topics: Bacteremia; Cefotaxime; Cefuroxime; Cephalosporin Resistance; Cephalosporins; Drug Resistance, Multiple; Humans; Infant; Infusions, Intravenous; Male; Meningitis, Pneumococcal; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Topics: Administration, Oral; Anti-Bacterial Agents; Cefotaxime; Ceftazidime; Cephalosporins; Community-Acquired Infections; Costs and Cost Analysis; Cross Infection; Drug Resistance, Microbial; Drug Resistance, Multiple; Enterococcus; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Humans; Macrolides; Meningitis, Bacterial; Meningitis, Meningococcal; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Neutropenia; Pneumococcal Infections; Pneumonia, Bacterial; Systemic Inflammatory Response Syndrome; Urinary Tract Infections

Topics: Adult; Bacteremia; Cefotaxime; Cerebral Infarction; Cerebrospinal Fluid; Epilepsies, Partial; Female; Humans; Immunocompetence; Meningitis, Haemophilus; Meningitis, Pneumococcal; Recurrence; Rifampin

Topics: Anti-Bacterial Agents; Cefotaxime; Cephalosporin Resistance; Cephalosporins; Drug Therapy, Combination; Humans; Infant; Male; Meningitis, Pneumococcal; Streptococcus pneumoniae; Vancomycin

Penicillin-resistant Streptococcus pneumoniae (PRP) is of worldwide concern. Treatment failures and fatalities of meningitis caused by PRP have been reported in other locations but not yet in Israel. We describe an 11-month-old infant with meningitis caused by PRP who failed to respond to initial treatment with cefotaxime. Vancomycin treatment caused a prompt cure. The minimal inhibitory concentrations of the isolate to penicillin, cefuroxime and cefotaxime were 1.0, 4.0 and 1.0 micrograms/ml, respectively. New guidelines for the treatment of meningitis in Israel are suggested.

Topics: Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Humans; Infant; Israel; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin Resistance; Streptococcus pneumoniae; Vancomycin

Topics: Anemia, Sickle Cell; Bacteremia; Cefotaxime; Cephalosporin Resistance; Child; Drug Therapy, Combination; Humans; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae; Vancomycin

In June 1993, the National Committee for Clinical Laboratory Standards (NCCLS) recommended stringent new interpretive guidelines for antibiotics indicated for Streptococcus pneumoniae meningitis. To assess the predictive values of the recommended breakpoints, retrospective data were collected from patients who had S. pneumoniae infections and were treated with cefotaxime monotherapy. Susceptibilities based on the NCCLS interpretative categories were compared with clinical and bacteriologic outcomes. In 76 evaluable patients, the most common infections were bacteremia-septicemia (n = 49), meningitis (n = 37), and lower respiratory tract infection (n = 14). Under the NCCLS breakpoints proposed in 1993, 55 isolates would have been classed as susceptible to cefotaxime (MIC, < or = 0.25 microgram/ml), 18 would have been classed as intermediate (MIC, 0.5 to 1.0 microgram/ml), and 2 would have been classed as resistant (MIC, > or = 2 micrograms/ml). Of 75 cefotaxime-treated patients for whom cefotaxime MICs were recorded, 73 were clinically cured or improved (37 of 37 with meningitis and 36 of 38 with other infections). One case of bacteremia and one case of bone-and-joint infection were scored as therapeutic failures because initial monotherapy had to be modified because of an adverse drug reaction. Excluding these patients, there were 18 patients infected with S. pneumoniae that would have been classed as not fully susceptible (i.e., MICs > or = 0.5 microgram/ml); all of these patients were cured or improved. The results of this analysis demonstrate that successful treatment with cefotaxime did not correlate well with the guidelines for the susceptibility of pneumococcal isolates to either penicillin or cefotaxime established by the 1993 NCCLS breakpoint recommendations. Because of this study and other similar findings, the NCCLS adopted more clinically relevant guidelines in 1994.

Topics: Aged; Bacteremia; Cefotaxime; Cephalosporin Resistance; Cephalosporins; Female; Humans; Infant; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Practice Guidelines as Topic; Streptococcus pneumoniae

Topics: Cefotaxime; Cephalosporins; Drug Resistance, Microbial; Female; Humans; Infant; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Streptococcus pneumoniae

Topics: Aged; Cefotaxime; Cephalosporins; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Male; Meningitis, Pneumococcal; Penicillin Resistance; Streptococcus pneumoniae

Topics: Cefotaxime; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Humans; Meningitis, Pneumococcal; Staphylococcus

Two infants, aged 8.5 and 11 months, were admitted for meningitis caused by Streptococcus pneumoniae. Failure of cefotaxime led to the identification of highly penicillin-G-resistant strains. Minimum inhibitory concentrations (MICs) for penicillin were > 2 micrograms/ml, and cefotaxime MICs were 2 micrograms/ml. Both patients rapidly responded to a combination of i.v. imipenem and rifampicin. It is now mandatory to test in-vitro susceptibilities of Streptococcus pneumoniae to penicillin G and other beta-lactam agents when meningitis is diagnosed in infants.

Topics: Anti-Bacterial Agents; Cefotaxime; Cephalosporins; Drug Therapy, Combination; Humans; Imipenem; Infant; Male; Meningitis, Pneumococcal; Penicillin Resistance; Rifampin; Streptococcus pneumoniae; Thienamycins

Topics: Anemia, Sickle Cell; Cefotaxime; Cephalosporins; Drug Therapy, Combination; Female; Humans; Infant; Meningitis, Pneumococcal; Penicillin Resistance; Vancomycin

Topics: Base Sequence; Cefotaxime; Cephalosporins; Cross Infection; DNA Primers; DNA, Bacterial; Drug Therapy, Combination; Female; Gentamicins; Humans; Infant; Meningitis, Pneumococcal; Molecular Sequence Data; Penicillin Resistance; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Streptococcus pneumoniae; Treatment Failure; Vancomycin

Topics: Cefotaxime; Fosfomycin; Meningitis, Pneumococcal

Topics: Anemia, Sickle Cell; Bacteremia; Cefotaxime; Cephalosporins; Child; Drug Resistance, Microbial; Drug Resistance, Multiple; Drug Therapy, Combination; Humans; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Pneumococcal Infections; Streptococcus pneumoniae; Vancomycin

Due to a worldwide increasing number of cephalosporin resistant Streptococcus (S) pneumoniae strains, it appears necessary to modify the current treatment of pneumococcal meningitis. The authors recommend an initial antimicrobial regimen associating cefotaxime or ceftriaxone to vancomycin in any case of bacterial meningitis in which S pneumoniae appears to be involved (Gram positive cocci on direct examination of the CSF and/or presence of soluble bacterial antigen). There is also a need for a reappraisal of the duration of the treatment which, in any case, should not be shorter than 10 days. In the case of meningitis due to a penicillin resistant S pneumoniae, lumbar puncture must be repeated until sterilisation of the CSF.

Topics: Cefotaxime; Ceftriaxone; Drug Therapy, Combination; Humans; Infant; Meningitis, Pneumococcal; Vancomycin

Topics: Cefotaxime; Humans; Male; Meningitis, Pneumococcal; Middle Aged; Penicillin Resistance; Vancomycin

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.

Topics: Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Drug Resistance, Microbial; Humans; Infant; Leukocyte Count; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin Resistance; Retrospective Studies; Streptococcus pneumoniae; Treatment Outcome

Topics: Cefotaxime; Humans; Infant; Male; Meningitis, Pneumococcal; Penicillin Resistance

Topics: Anti-Bacterial Agents; Cefotaxime; Drug Resistance, Microbial; Female; Humans; Meningitis, Pneumococcal; Middle Aged; Streptococcus pneumoniae

A case of pneumococcal meningitis in an infant with a ventriculo-peritoneal shunt is reported. There was initial failure of treatment with penicillin and cefotaxime in full dosage. Eradication of infection without shunt removal was eventually achieved by adding rifampicin to the antibiotic regime.

Topics: Cefotaxime; Cerebrospinal Fluid Shunts; Female; Humans; Infant; Meningitis, Pneumococcal; Penicillin G; Peritoneal Cavity; Rifampin

We report a case of invasive disease caused by penicillin resistant Streptococcus pneumoniae. The prevalence of penicillin and multiple drug resistant pneumococcal strains is increasing worldwide. We must assume that the incidence of clinically significant illness caused by these agents will also increase. Based on this assumption, we make suggestions as to how clinicians should alter their therapeutic approach to pneumococcal illness.

Topics: Ampicillin Resistance; Cefotaxime; Humans; Infant; Male; Meningitis, Pneumococcal

Topics: Ampicillin; Ampicillin Resistance; Cefotaxime; Drug Resistance, Microbial; Humans; Imipenem; Infant; Male; Meningitis, Pneumococcal; Streptococcus pneumoniae

Topics: Ampicillin; Ampicillin Resistance; Cefotaxime; Child, Preschool; Drug Resistance, Microbial; Humans; Male; Meningitis, Pneumococcal; Streptococcus pneumoniae; Vancomycin

Topics: Adult; Aged; Cefotaxime; Female; Humans; Male; Meningitis, Pneumococcal; Middle Aged; Penicillin G; Penicillin Resistance; Pneumococcal Infections; Pneumonia, Pneumococcal; Streptococcus pneumoniae

Of 66 episodes of pneumococcal meningitis seen in Bellvitge Hospital, Barcelona, Spain (January 1981 to June 1987), 15 (23 percent) were due to penicillin-resistant pneumococci [minimal inhibitory concentrations (MICs) of 0.1 to 4 micrograms/ml]. Fifty percent of these strains were also resistant to chloramphenicol. Most were sporadic community-acquired cases. Clinical characteristics were similar in both penicillin-resistant and penicillin-sensitive cases. Those cases with MICs of greater than 1 microgram/ml did not show a response to penicillin therapy. Of nine patients treated with cefotaxime (200 to 350 mg/kg per day) with penicillin G MICs of 0.1 to 4 micrograms/ml and cefotaxime MICs of less than or equal to 0.03 to 1 microgram/ml, seven recovered, one experienced a relapse after 14 days of therapy and the infection was cured with intravenous vancomycin, and one patient died with sterile cerebrospinal fluid. Thus, adults with meningitis due to penicillin-resistant pneumococci may be adequately treated with high doses (around 300 mg/kg per day) of intravenous cefotaxime if MICs of penicillin G are less than or equal to 4 micrograms/ml. Cases with higher resistance may require another antibiotic such as vancomycin.

Topics: Adult; Anti-Bacterial Agents; Cefotaxime; Female; Humans; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin G; Penicillin Resistance; Streptococcus pneumoniae

The authors carried out this work with the purpose both of verifying the present importance of penicillin G for the treatment of pneumococcal meningitis and of comparing it with the clinical effectiveness of other medicines presently available for the same purpose. They have studied 27 patients with clinical and laboratory diagnosis of pneumococcal meningitis and which were admitted in the "Serviço de Infecto-Contagiosos" of Santa Maria Hospital, Lisbon, for the period from 1.1.81 until 31.05.86. Of these patients 18 were males and 9 females, ranging from 8 to 80 years old. All of them were treated exclusively with penicillin G, the medium dose being 400,000 IU/kg per day and for a medium period of 15 days. The final results accounted for: 23 patients healed (85.2%), 2 decreased (7.4%) and the remaining 2 (7.4%) with neurological sequels by the time of discharge from the hospital. These, in our opinion, are values for the minimum equivalent to those in other series of the same pathology and under treatment by the different medicines presently available in alternative. Bearing in mind these results and considering it is more expensive to use these new antibiotics, the authors think they may state that penicillin G keeps ahead for the treatment of pneumococcal meningitis, except for cases of hypersensitivity to this medicine or penicillin-resistance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cefotaxime; Ceftazidime; Ceftriaxone; Child; Costs and Cost Analysis; Female; Humans; Male; Meningitis, Pneumococcal; Middle Aged; Penicillin G

Topics: Aminoglycosides; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Cephalosporins; Child; Child, Preschool; Drug Therapy, Combination; Humans; Infant; Infant, Newborn; Meningitis; Meningitis, Haemophilus; Meningitis, Listeria; Meningitis, Meningococcal; Meningitis, Pneumococcal

Information on 62 bacteriologically confirmed cases of bacterial meningitis treated with cefotaxime in this country was obtained retrospectively from infectious disease consultants. This series of cases differed markedly from the world cumulative case data thus far presented. One of the two most common organisms treated was the pneumococcus (allergy to penicillin or misdiagnosis of the Gram stain results were the major reasons given). The other organism was Klebsiella. Unanticipated bacteriologic successes were noted in two cases of staphylococcal meningitis secondary to parameningeal foci. The bacteriologic cure rate and survival rate were about 85 percent. Failure of monotherapy was seen in one case of Pseudomonas meningitis, as well as in three of five cases of Enterobacter meningitis. In addition, two cases of Escherichia coli meningitis in which moxalactam therapy inexplicably failed were cured with cefotaxime. Close analysis of killing kinetics appeared to explain the Enterobacter and E. coli failures. Thus, overall not all gram-negative species and not all isolates of any particular species that cause meningitis can be successfully treated by cephalosporins. Data obtained during the investigative trials do not appear to be entirely predicative of what occurred during the free clinical use of an antibiotic. Post-investigatory follow-up and surveillance of all newly introduced therapeutic agents are needed.

Topics: Adult; Aged; Bacterial Infections; Cefotaxime; Escherichia coli; Escherichia coli Infections; Humans; Infant, Newborn; Klebsiella Infections; Male; Meningitis; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Middle Aged; Moxalactam

Cefmenoxime, a new semisynthetic cephalosporin, was evaluated in vitro and in vivo in comparison with penicillin G against a type III group B streptococcal strain. In vitro, the minimal inhibitory and minimal bactericidal concentrations of the two drugs were very close (less than or equal to 2 dilutions). In-vivo studies using experimental bacteraemia and meningitis in newborn rats revealed that despite similar drug levels, cefmenoxime had significantly greater bactericidal titres in blood at 6-7 h after administration and bacterial clearance from blood was significantly faster with cefmenoxime than with penicillin G at the end of one day of treatment. In addition, all animals with cefmenoxime therapy had bactericidal titres in cerebrospinal fluid greater than or equal to 1:8 at 1-2 h after administration, whereas most (67%) animals receiving penicillin G had titres less than 1:8. However, overall efficacy of cefmenoxime was similar to that of penicillin G. These findings suggest that cefmenoxime may be an effective alternative against group B streptococcal infection.

Topics: Animals; Cefmenoxime; Cefotaxime; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin G; Rats; Sepsis; Streptococcal Infections; Streptococcus agalactiae

Four new cephalosporins, cefotaxime, cefpimizole (U 63196E), BMY 28142, and HR 810 were evaluated in experimental pneumococcal meningitis. Cefotaxime penetrated only moderately into the cerebrospinal fluid of rabbits with meningitis, whereas cefpimizole, BMY 28142, and HR 810 all exhibited unusually good penetration. The bactericidal activity in infected cerebrospinal fluid was comparable for the four drugs.

Topics: Animals; Cefepime; Cefotaxime; Cefpirome; Cephalosporins; Meningitis, Pneumococcal; Rabbits; Streptococcus pneumoniae

The pharmacokinetics and bacteriological efficacies of penicillin G, ceftriaxone, vancomycin, and imipenem were determined in rabbits with experimental meningitis caused by Streptococcus pneumoniae strains with different penicillin susceptibilities. Drug dosages were adjusted to attain peak concentrations in serum that were similar to those observed in infants and children. In animals infected with a penicillin-susceptible (MBC, 0.008 micrograms/ml) pneumococcus, penicillin G and ceftriaxone reduced the number of organisms in cerebrospinal fluid (CSF) by greater than or equal to 4.14 log10 CFU/ml after single doses and after 9-h continuous infusions. A single large dose (50 mg/kg) of penicillin G was comparatively ineffective (-2.15 log10 CFU/ml) against a relatively penicillin-resistant (MBC, 0.5 micrograms/ml) strain, whereas ceftriaxone therapy resulted in a 3.66- and 4.77-log10 CFU/ml reduction after single doses and 9-h continuous infusions, respectively. In animals in which meningitis was caused by a penicillin-resistant (MBC, 8.0 micrograms/ml) pneumococcus, a single dose of penicillin (50 or 150 mg/kg) or of ceftriaxone failed to lower the number of organisms in CSF. Vancomycin and imipenem reduced the counts in CSF by at least 2.19 and 4.10 log10 CFU/ml after single doses and 9-h infusions, respectively. In all experiments, a bactericidal titer of greater than or equal to 1:8 in CSF was necessary to achieve a maximal bacteriological effect.

Topics: Animals; Anti-Bacterial Agents; Cefotaxime; Ceftriaxone; Kinetics; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin G; Penicillin Resistance; Penicillins; Rabbits; Streptococcus pneumoniae; Vancomycin

Topics: Adult; Anti-Bacterial Agents; Cefotaxime; Humans; Male; Meningitis, Pneumococcal; Penicillin G; Penicillin Resistance; Streptococcus pneumoniae

Forty-six consecutive patients with pneumococcal meningitis were treated with cefotaxime (CTX). Ages ranged from 1-79 years: 29 adults, six adolescents, six children and five infants. Underlying diseases were found in 38 patients (82.6%). Twenty-six patients (56.5%) were admitted in coma. All isolates were sensitive to CTX, with MICs for 12 strains ranging from 0.01 to 0.08 mg/l. CTX was used as single-drug therapy for 12 to 27 days-mean 15 days. The daily dose of CTX was 200 mg/kg, in four or six equal intravenous doses. CTX penetration into the CSF was studied in four patients. 40 patients (87.0%) were cured. The mortality rate was 13.0%. All dead patients had been admitted in coma. The mortality rate in comatose patients was 23.1%. CSF sterilization was obtained within 72 h after starting treatment, mostly (90.7%) in the first 48 h. No serious side-effects were observed. The study proves that CTX is a safe and very successful therapy for pneumococcal meningitis.

Topics: Adolescent; Adult; Aged; Cefotaxime; Child; Child, Preschool; Female; Humans; Infant; Male; Meningitis, Pneumococcal; Middle Aged

In order to define the characteristics of the antibacterial activity of beta-lactam antibiotics in the treatment of bacterial meningitis, the relationship between cerebrospinal fluid (CSF) drug concentrations and the rate of bacterial killing was investigated for penicillin G and four new cephalosporins in an animal model of meningitis due to Streptococcus pneumoniae. All five drugs showed a significant correlation between increasing drug concentrations in CSF and increasing bactericidal rates. Minimal activity was observed in CSF at drug concentrations of approximately the broth minimal bactericidal concentration (MBC). Maximal activity occurred with CSF concentrations 10-30 times higher. In vitro tests did not reproduce the unique correlation of increasing drug concentrations and killing activity found in vivo. When evaluating new beta-lactam antibiotics for the treatment of bacterial meningitis, it is reasonable to establish a minimum standard of CSF drug concentrations of greater than or equal to 30 times the MBC against the infecting organism.

Topics: Animals; Anti-Bacterial Agents; Cefmenoxime; Cefotaxime; Ceftriaxone; Meningitis, Pneumococcal; Moxalactam; Penicillin G; Rabbits; Streptococcus pneumoniae

The pharmacokinetics of ceftriaxone were studied in five infants (7 to 15 months old) and five young children (24 to 70 months old). Both groups received a single 50-mg/kg dose in an intravenous infusion over 5 min. No major pharmacokinetic differences were observed between the two populations. The total (bound plus unbound) plasma concentration-versus-time data could be described in each case by a biexponential equation. Changes in renal clearance indicated time- and dose- dependent pharmacokinetic behavior. The fraction excreted unchanged in the urine (fu) and the biological half-life (t 1/2 (beta)) were, however, dose independent. The average values were 47% for fu (0 to 12 h) and 6.5 for T 1/2 (beta). Weight-corrected total systemic clearance was C1TS = 0.71 ml/min per kg; volume of distribution was VD (beta) = 394 mg/kg. The data support intravenous administration of 50 mg of ceftriaxone per kg of body weight every 12 h in assessing its activity against Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis in postneonatal-stage pediatric patients.

Topics: Cefotaxime; Ceftriaxone; Child, Preschool; Female; Half-Life; Humans; Infant; Infusions, Parenteral; Kinetics; Male; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Protein Binding; Serum Albumin

The pharmacokinetics and bacteriological efficacy of cefoperazone, cefuroxime, ceftriaxone, and moxalactam were evaluated in the experimental rabbit meningitis model of Haemophilus influenzae type b or Streptococcus pneumoniae infection. The cerebrospinal fluid penetration of these beta-lactam antibiotics was from 3 to 14% and was greater in Haemophilus-infected that in pneumococcus-infected animals. With the exception of moxalactam, the antibacterial activity in cerebrospinal fluid and change in concentration of bacteria during therapy with the test drugs were comparable to those of penicillin G in pneumococcal infection. In animals infected with H. influenzae, cefoperazone, moxalactam, and ceftriaxone were as effective as chloramphenicol in reducing the bacterial counts in cerebrospinal fluid. Moxalactam and ceftriaxone produced the largest cerebrospinal fluid bactericidal titers against this beta-lactamase-producing strain of Haemophilus. On the basis of these data, it was concluded that ceftriaxone and cefoperazone were effective against both pathogens in this meningitis model, whereas moxalactam was effective against only Haemophilus, and cefuroxime was effective against only S. pneumoniae.

Topics: Animals; Cefoperazone; Cefotaxime; Ceftriaxone; Cefuroxime; Cephalosporins; Cephamycins; Dose-Response Relationship, Drug; Infusions, Parenteral; Kinetics; Male; Meningitis, Haemophilus; Meningitis, Pneumococcal; Moxalactam; Rabbits; Streptococcus pneumoniae

Ceftriaxone is a wide-spectrum-third generation cephalosporin characterized by outstandingly high efficacy as well as pharmokinetic properties making it suitable for administration in a single daily injection. Ceftriaxone has been found to be useful for treatment of the very severe infectious pathology in countries where hygiene and medical superstructures are still rudimentary. Eighteen of 20 patients with purulent meningitis (13 to Neisseria meningitidis A, 3 to Streptoc. pneumoniae, 1 to Listeria and 3 aseptic) recovered (there being 2 deaths at the 36th hour) after a mean 6 days of hospitalization. Despite the very delicate patient condition, recovery was seen in all 11 cases of very grave bronchopneumopathy, generally due to Streptoc, pneumonia. A dose of 2 g/day in 1 or 2 IV injections is sufficient in the adult, 0.50 g in a single dose being injected to infants weighing less than 10 kg, Meningitis required 4 to 7 days treatment (9 days in a case of Listeria) while the treatment period was longer for respiratory infections. Seven patients had been refractory to treatment with beta-lactamines and/or aminosides, and no adverse drug reactions were noted.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Bronchopneumonia; Cefotaxime; Ceftriaxone; Child; Child, Preschool; Female; Hospitals, University; Humans; Infant; Injections; Male; Meningitis; Meningitis, Meningococcal; Meningitis, Pneumococcal; Middle Aged; Niger

Single-dose pharmacokinetics of ceftriaxone were determined in 19 patients with proven bacterial meningitis. The dosage was 50 mg of ceftriaxone per kg. The plasma concentration time curve declined in a biexponential manner. The mean peak plasma concentration was 207 micrograms/ml, and the elimination half-life was 4 h. In 12 patients, multiple-dose pharmacokinetics were determined after a loading dose of 75 mg of ceftriaxone per kg, followed by 50-mg/kg doses every 8 h in 5 patients or every 12 h in 7 patients. The mean peak plasma concentration was 230 micrograms/ml after the first dose and 263 micrograms/ml after the last dose. Of 12 patients, 5 had trough values that were larger after multiple doses than after a single dose. Mean penetration of ceftriaxone into cerebrospinal fluid was 3.1%. The median cerebrospinal fluid bactericidal titer against the patients pathogens was greater than 1:1,024 and less than 1:2,048. The drug was well tolerated without adverse effects.

Topics: Bacteria; Cefotaxime; Ceftriaxone; Child, Preschool; Female; Humans; Infant; Kinetics; Male; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Microbial Sensitivity Tests