rifampin and Meningitis--Pneumococcal

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

Topics: Anti-Bacterial Agents; Cephalosporins; Humans; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Penicillin Resistance; Rifampin; 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

Cefotaxime and ceftriaxone are currently the agents of first choice for empiric treatment of bacterial meningitis in children. Further studies are necessary to determine the optimal antibiotic therapy for meningitis caused by Streptococcus pneumoniae isolates relatively or fully resistant to penicillin. The Haemophilus influenzae type b capsular polysaccharide-protein conjugate vaccines undoubtedly will alter the relative importance of the three common meningeal pathogens in pediatrics and make additional studies of the adjunctive use of dexamethasone in the treatment of bacterial meningitis even more critical.

Topics: Anti-Bacterial Agents; Anti-Inflammatory Agents; Bacterial Capsules; Bacterial Vaccines; Dexamethasone; Haemophilus influenzae; Haemophilus Vaccines; Humans; Meningitis, Bacterial; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Pneumococcal Vaccines; Polysaccharides, Bacterial; Rifampin; Streptococcus pneumoniae

Topics: Ampicillin; Bacterial Infections; Brain Edema; Child, Preschool; Chloramphenicol; Cloxacillin; Gentamicins; Haemophilus influenzae; Humans; Infant; Infant, Newborn; Injections, Spinal; Meningitis; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Methicillin; Minocycline; Neisseria meningitidis; Penicillin G; Rifampin; Seizures; Shock; Streptococcus pneumoniae; Sulfonamides

There are reports of failure of extended-spectrum cephalosporin treatment in pneumococcal meningitis. On the basis of in vitro and animal experimental studies, the addition of vancomycin or rifampin to an extended-spectrum cephalosporin has been recommended for empiric treatment of these patients. Cerebrospinal fluid (CSF) was taken from 31 children with bacterial meningitis randomized to receive ceftriaxone alone (n = 11), ceftriaxone plus rifampin (n = 10), or ceftriaxone plus vancomycin (n = 10). The CSF from children receiving ceftriaxone alone was unable to kill intermediately ceftriaxone-resistant or fully resistant strains when the concentration of ceftriaxone in the CSF was less than 5 micrograms/ml. At higher concentrations bactericidal activity was present. We have shown that vancomycin penetrates reliably into the CSF of children with acute meningitis, which is in contrast to previous studies with adults. The addition of vancomycin or rifampin to ceftriaxone resulted in significantly enhanced CSF bactericidal activity compared with that of ceftriaxone alone against these resistant strains. Our data suggest that the addition of rifampin or vancomycin to ceftriaxone may be useful for the treatment of cephalosporin-resistant pneumococcal meningitis.

Topics: Acute Disease; Anti-Bacterial Agents; Ceftriaxone; Cephalosporin Resistance; Child, Preschool; Dexamethasone; Humans; Infant; Meningitis, Pneumococcal; Rifampin; Serum Bactericidal Test; Streptococcus pneumoniae; Vancomycin

Bacterial meningitis among critically ill adult patients remains associated with both high mortality and frequent, persistent disability. Vancomycin was added to treatment with a third-generation cephalosporin as recommended by French national guidelines. Because animal model studies had suggested interest in the use of rifampin for treatment of bacterial meningitis, and after the introduction of early corticosteroid therapy (in 2002), there was a trend toward increasing rifampin use for intensive care unit (ICU) patients. The aim of this article is to report on this practice.. Five ICUs participated in the study. Baseline characteristics and treatment data were retrospectively collected from charts of patients admitted with a diagnosis of acute bacterial meningitis during a 5-year period (2004-2008). The ICU mortality was the main outcome measure; Glasgow Outcome Scale and 3-month mortality were also assessed.. One hundred fifty-seven patients were included. Streptococcus pneumoniae and Neisseria meningitidis were the most prevalent causative microorganisms. The ICU mortality rate was 15%. High doses of a cephalosporin were the most prevalent initial antimicrobial treatment. The delay between admission and administration of the first antibiotic dose was correlated with ICU mortality. Rifampin was used with a cephalosporin for 32 patients (ranging from 8% of the cohort for 2004 to 30% in 2008). Administration of rifampin within the first 24 h of hospitalization could be associated with a lower ICU survival. Statistical association between such an early rifampin treatment and ICU mortality reached significance only for patients with pneumococcal meningitis (p=0.031) in univariate analysis, but not in the logistic model.. We report on the role of rifampin use for patients with community-acquired meningitis, and the results of this study suggest that this practice may be associated with lower mortality in the ICU. Nevertheless, the only independent predictors of ICU mortality were organ failure and pneumococcal infection. Further studies are required to confirm these results and to explain how rifampin use would reduce mortality.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Female; France; Glasgow Outcome Scale; Hospital Mortality; Humans; Intensive Care Units; Male; Meningitis, Bacterial; Meningitis, Meningococcal; Meningitis, Pneumococcal; Middle Aged; Neisseria meningitidis; Retrospective Studies; Rifampin; Treatment Outcome

Cerebritis y abscesos cerebrales por Streptococcus pneumoniae en un recien nacido.

Topics: Anti-Bacterial Agents; Anticonvulsants; Bacteremia; Brain Abscess; Bronchiolitis; Cardiotonic Agents; Cerebral Hemorrhage; Drug Therapy, Combination; Fatal Outcome; Humans; Immunocompromised Host; Infant, Newborn; Magnetic Resonance Imaging; Male; Meningitis, Pneumococcal; Pneumococcal Infections; Respiratory Syncytial Virus Infections; Rifampin; Spleen; Streptococcus pneumoniae; Vancomycin

Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model. Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (P < 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (P < 0.01) less apoptosis, and significantly (P < 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (P < 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Brain Damage, Chronic; Ceftriaxone; Chemokines; Cytokines; Daptomycin; Drug Administration Schedule; Drug Therapy, Combination; Hearing Loss; Inflammation; Meningitis, Pneumococcal; Random Allocation; Rats; Rats, Wistar; Rifampin

A case of Streptococcus pneumoniae meningitis in a possibly immune-compromised child with a ventriculoatrial shunt is described. The infection was successfully eradicated by treatment with intravenous ceftriaxone and rifampicin, without removal of the shunt.

Topics: Anti-Bacterial Agents; Ceftriaxone; Cerebrospinal Fluid Shunts; Drug Therapy, Combination; Female; Humans; Infant; Meningitis, Pneumococcal; Pneumonia, Pneumococcal; Prosthesis-Related Infections; Rifampin

Meropenem is a broad-spectrum carbapenem antibiotic that is highly active against the pathogens causing meningitis. The aims of this study was to determine the efficacies of meropenem alone and combined with rifampin against two Streptococcus pneumoniae strains with different susceptibility to beta-lactams using the guinea pig meningitis model and compare them with the standard ceftriaxone plus vancomycin therapy. All treatments except rifampin were bactericidal from 6 h. The addition of rifampin did not improve the activity of meropenem alone. Our results provide good evidence of the efficacy of meropenem in the treatment of penicillin- and cephalosporin-susceptible and -resistant pneumococcal meningitis similar to that of ceftriaxone plus vancomycin, suggesting that meropenem might be a good option in the management of this infection.

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Colony Count, Microbial; Disease Models, Animal; Drug Therapy, Combination; Female; Guinea Pigs; Humans; Meningitis, Pneumococcal; Meropenem; Microbial Viability; Rifampin; Streptococcus pneumoniae; Thienamycins; Time Factors; Treatment Outcome; Vancomycin

In bacterial meningitis, severe systemic and local inflammation causes long-term impairment and death of affected patients. The current antibiotic therapy relies on cell wall-active beta-lactam antibiotics, which rapidly sterilize the cerebrospinal fluid (CSF). However, beta-lactams inhibit cell wall synthesis, induce bacteriolysis, and thereby evoke a sudden release of high amounts of toxic and proinflammatory bacterial products. Because tissue damage in bacterial meningitis is the result of bacterial toxins and the inflammatory host response, any reduction of free bacterial compounds promises to prevent neuronal damage.. In vitro experiments and randomized prospective animal study.. University research laboratories.. Streptococcus pneumoniae broth cultures and New Zealand White rabbits.. We evaluated a concept to improve bacterial meningitis therapy in which a short-term pretreatment with the protein synthesis-inhibiting antibiotic rifampicin precedes the standard antibiotic therapy with ceftriaxone. First, logarithmically growing pneumococcal cultures were subdivided and exposed to different antibiotics. Then, rabbits suffering from pneumococcal meningitis were randomized to receive rifampicin pretreatment or ceftriaxone alone.. In pneumococcal cultures, quantitative immunoblotting and real-time polymerase chain reaction revealed a reduced release of pneumolysin and bacterial DNA by rifampicin pretreatment for 30 minutes in comparison with ceftriaxone treatment alone. In vivo, a 1-hour rifampicin pretreatment reduced the release of bacterial products and attenuated the inflammatory host response, as demonstrated by decreased CSF levels of prostaglandin E2 and total protein and increased glucose CSF/plasma ratios. Rifampicin pretreatment reduced infection-associated neuronal apoptotic cell loss compared with ceftriaxone-treated controls.. A short-term pretreatment with rifampicin reduced the beta-lactam-induced release of deleterious bacterial products, attenuated inflammation, and thereby decreased neuronal cell loss in experimental bacterial meningitis. This concept has the potential to reduce inflammation-associated neuronal injury in bacterial meningitis and should be evaluated in a clinical trial.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Ceftriaxone; Cell Culture Techniques; Disease Models, Animal; Drug Administration Schedule; Drug Therapy, Combination; Meningitis, Pneumococcal; Neurons; Rabbits; Rifampin

Topics: Animals; Anti-Bacterial Agents; Ceftriaxone; Drug Administration Schedule; Drug Therapy, Combination; Humans; Meningitis, Pneumococcal; Rabbits; Rifampin

The aim of the study was to assess the in vitro and in vivo efficacy of ceftriaxone, vancomycin and rifampicin alone and combined against Streptococcus pneumoniae ATCC 51916 (MIC of ceftriaxone: 32 mg/L).. In vitro killing curves were performed with clinically achievable CSF antibiotic concentrations. In the rabbit model of pneumococcal meningitis, we studied the efficacy of and effects on inflammation of treatment with ceftriaxone 100 mg/kg/day, vancomycin 30 mg/kg/day and rifampicin 15 mg/kg/day, alone and combined, over a 26 h period.. Time-kill curves showed that vancomycin was bactericidal, and ceftriaxone and rifampicin produced a bacteriostatic effect. An additive effect was observed when combinations of ceftriaxone plus vancomycin were studied at subinhibitory concentrations. Emergence of resistance to rifampicin was detected both when rifampicin was studied alone and when combined with ceftriaxone or vancomycin. In the rabbit meningitis model, ceftriaxone was bacteriostatic, whereas rifampicin and vancomycin were bactericidal at 24 h. Although not synergistic, the combinations of ceftriaxone plus vancomycin or rifampicin, and vancomycin plus rifampicin, improved the efficacy of any antibiotic tested alone--all combinations were bactericidal from 6 h--and significantly decreased inflammatory parameters in CSF compared with control and ceftriaxone groups.. Ceftriaxone plus vancomycin, and vancomycin plus rifampicin appeared to be effective in the therapy of experimental pneumococcal meningitis caused by highly cephalosporin-resistant strains such as ATCC 51916. Our results provide an experimental basis for using these combinations as empirical therapy for pneumococcal meningitis, regardless of the degree of cephalosporin resistance of the causative strain.

Topics: Animals; Ceftriaxone; Cephalosporin Resistance; Cerebrospinal Fluid; Colony Count, Microbial; Disease Models, Animal; Drug Combinations; Drug Interactions; Drug Resistance, Bacterial; Female; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Rabbits; Rifampin; Streptococcus pneumoniae; Vancomycin

To evaluate the therapeutic efficacy of ceftriaxone + vancomycin + rifampicin (CVR) in the treatment of pneumococcal meningitis caused by a multidrug-resistant strain, single-drug regimens (ceftriaxone 100 mg/kg, rifampicin 15 mg/kg, or vancomycin 20 mg/kg), double-drug regimens (ceftriaxone + vancomycin [CV] and ceftriaxone + rifampicin [CR]) and a triple-drug combination (CVR) with or without dexamethasone were compared in a rabbit meningitis model. Meningitis was induced by a highly penicillin-resistant (MIC 2 mg/l) and ceftriaxone-resistant (MIC 4 mg/l) pneumococcal strain. Final therapeutic efficacy was evaluated by the bacterial concentration at 24 h, and the bacterial killing rate was also evaluated. All combination regimens were superior to ceftriaxone or vancomycin single-drug regimens with regard to sterilisation of CSF and bacterial killing rate. Rifampicin was as effective as combination regimens. Regardless of dexamethasone, therapeutic efficacy of CVR and CR were superior to that of CV. CVR showed comparable therapeutic efficacy to CR. Data suggested that CVR would not have additional therapeutic benefit over CR during the initial 24 h of treatment.

Topics: Animals; Ceftriaxone; Colony Count, Microbial; Dexamethasone; Drug Evaluation, Preclinical; Drug Therapy, Combination; Meningitis, Pneumococcal; Rabbits; Rifampin; Streptococcus pneumoniae; Vancomycin

Rifampin (RIF) releases smaller quantities of lipoteichoic acids (LTAs) from Streptococcus pneumoniae than ceftriaxone (CRO). Due to the rapid development of resistance, RIF cannot be used as a single agent for therapy of bacterial meningitis. For this reason, we compared the effect of treatment with RIF followed by treatment with CRO (RIF-CRO) or the effect of treatment with clindamycin (CLI) followed by treatment with CRO (CLI-CRO) to that of CRO alone on the concentrations of LTAs and teichoic acids in vitro. The effects of RIF-CRO on LTA concentrations in cerebrospinal fluid (CSF) and on neuronal injury were investigated in a rabbit model of S. pneumoniae meningitis. In vitro, bacterial titers were effectively reduced by CRO, RIF-CRO, and CLI-CRO when each drug was used at 10 micro g/ml. The levels of release of LTAs after the initiation of therapy were lower in RIF-CRO- and CLI-CRO-treated cultures than in cultures treated with CRO alone (P < 0.05 from 3 to 12 h after initiation of treatment). Similarly, in rabbits, the increase in the amount of LTAs in CSF was lower in RIF-CRO-treated animals than in CRO-treated animals (P = 0.02). The density of dentate apoptotic granular cells was lower after RIF-CRO therapy than after CRO therapy (medians, 58.4 and 145.6/mm(2), respectively; 25th quartiles, 36.3 and 81.7/mm(2), respectively; 75th quartiles, 100.7 and 152.3/mm(2), respectively; P = 0.03). Therefore, initiation of therapy with a protein synthesis-inhibiting antibacterial and continuation of therapy with a combination that includes a beta-lactam may be a strategy to decrease neuronal injury in bacterial meningitis.

Topics: Animals; Ceftriaxone; Drug Therapy, Combination; Lipopolysaccharides; Meningitis, Pneumococcal; Neurons; Rabbits; Rifampin; Teichoic Acids

The increasing incidence of ciprofloxacin resistance in Streptococcus pneumoniae may limit the efficacy of the new quinolones in difficult-to-treat infections such as meningitis. The aim of the present study was to determine the efficacy of clinafloxacin alone and in combination with teicoplanin and rifampin in the therapy of ciprofloxacin-susceptible and ciprofloxacin-resistant pneumococcal meningitis in rabbits. When used against a penicillin-resistant ciprofloxacin-susceptible strain (Clinafloxacin MIC 0.12 microg/ml), clinafloxacin at a dose of 20 mg/kg per day b.i.d. decreased bacterial concentration by -5.10 log cfu/ml at 24 hr. Combinations did not improve activity. The same clinafloxacin schedule against a penicillin- and ciprofloxacin-resistant strain (Clinafloxacin MIC 0.5 microg/ml) was totally ineffective. Our data suggest that a moderate decrease in quinolone susceptibility, as indicated by the detection of any degree of ciprofloxacin resistance, may render these antibiotics unsuitable for the management of pneumococcal meningitis.

Topics: Animals; Cerebrospinal Fluid; Ciprofloxacin; Disease Models, Animal; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fluoroquinolones; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Rabbits; Rifampin; Streptococcus pneumoniae; Teicoplanin; Treatment Outcome

Streptococcus pneumoniae, a common pathogen in pediatric infections, has become resistant to penicillin and make these infections difficult to treat. Rifampin and chloramphenicol have been recommended as alternative therapies, since they are less costly and more accessible to communities with limited resources. However, their use may be restricted by the differing levels of resistance found in target populations. The objective was to determine minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) for chloramphenicol and rifampin in strains of S. pneumoniae. These strains were newly isolated from children under age 5 that had demonstrated systemic infections and meningitis. A subgroup of 107 isolates of S. pneumoniae was selected from 324 strains isolated during a period of 2 years (1994-1996). Among these isolates, 60 were penicillin-resistant and 47 were susceptible; 53 isolates were from children with meningitis. MIC and MBC for chloramphenicol and rifampicin were obtained by standard methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS). S. pneumoniae ATCC strain 49619 served as the control. An isolate was considered susceptible to chloramphenicol when MIC = 4 microg/ml and resistant when MIC = 8 microg/ml. A strain was considered susceptible to rifampin when MIC = 1 microg/ml and resistant when MIC = 4 microg/ml. MBC was determined by recording the lower concentration of the antibiotic that inhibited 99.9% of the initial inoculum. Chloramphenicol resistance was found in 21% of the 107 isolates. In the group susceptible to penicillin, 11% were resistant to chloramphenicol and in the group resistant to penicillin 28% was resistant to chloramphenicol as well. MBC was found > 4 microg/ml in 28% of the isolates susceptible to penicillin and in 60% of the resistant isolates. No isolates were found resistant to rifampin. However, 2 penicillin resistant isolates showed CBM > 1 microg/ml to rifampin, and one with CIM = 1 microg/ml had a MBC to rifampicin of 16 microg/ml. Meningitis isolates showed higher CIM and CBM than the group of total isolates. These data suggest that chloramphenicol is not recommended for invasive infections caused by S. pneumoniae in Colombia. Rifampin is a more effective therapy in combination with other antibiotics for treatment of this kind of infections. Further studies are necessary to clarify the significance of low levels of MBC to rifampin found in some strains, sin

Topics: Anti-Bacterial Agents; Child, Preschool; Chloramphenicol; Colombia; Humans; Infant; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Pneumococcal Infections; Rifampin; Streptococcus pneumoniae

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

Topics: Adolescent; Age Distribution; Canada; Case-Control Studies; Cephalosporins; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Incidence; Infant; Logistic Models; Male; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Multivariate Analysis; Penicillin Resistance; Reference Values; Retrospective Studies; Rifampin; Risk Assessment; Sex Distribution; Streptococcus pneumoniae; Treatment Outcome; Vancomycin

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

The object of the study was to assess the efficacy of rifampicin and the combination of rifampicin plus vancomycin in a rabbit model of experimental penicillin-resistant pneumococcal meningitis. We also studied the effect of concomitant dexamethasone on the CSF antibiotic levels and inflammatory parameters. The rabbit model of pneumococcal meningitis was used. Groups of eight rabbits were inoculated with 106 cfu/mL of a cephalosporin-resistant pneumococcal strain (MIC of cefotaxime/ceftriaxone 2 mg/L). Eighteen hours later they were treated with rifampicin 15 mg/kg/day, vancomycin 30 mg/kg/day or both plus minus dexamethasone (0.25 mg/kg/day) for 48 h. Serial CSF samples were withdrawn to carry out bacterial counts, antibiotic concentration and inflammatory parameters. Rifampicin and vancomycin promoted a reduction of >3 log cfu/mL at 6 and 24 h, and cfu were below the level of detection at 48 h. Combination therapy with vancomycin plus rifampicin was not synergic but it had similar efficacy to either antibiotic alone and it was able to reduce bacterial concentration below the level of detection at 48 h. Concomitant use of dexamethasone decreased vancomycin levels when it was used alone (P< 0.05), but not when it was used in combination with rifampicin. Rifampicin alone at 15 mg/kg/day produced a rapid bactericidal effect in this model of penicillin-resistant pneumococcal meningitis. The combination of vancomycin and rifampicin, although not synergic, proved to be equally effective. Using this combination in the clinical setting may allow rifampicin administration without emergence of resistance, and possibly concomitant dexamethasone administration without significant interference with CSF vancomycin levels.

Topics: Animals; Brain Edema; Cerebrospinal Fluid; Colony Count, Microbial; Dexamethasone; Disease Models, Animal; Drug Therapy, Combination; Female; Meningitis, Pneumococcal; Penicillin Resistance; Rabbits; Rifampin; Streptococcus pneumoniae; Time Factors; Vancomycin

Bacterial compounds induce the production of reactive oxygen species (ROS) in meningitis. Rifampin releases smaller quantities of proinflammatory compounds from Streptococcus pneumoniae than do beta-lactam antibiotics. Therefore, rabbits infected intracisternally with S. pneumoniae were treated intravenously either with rifampin 5 mg/kg/h or ceftriaxone 10 mg/kg/h (n=9 each). Before initiation of antibiotic treatment, a strong positive correlation between ROS production of cerebrospinal fluid (CSF) phagocyte populations and bacterial CSF titers was observed (granulocytes: rs=.90, P<.0001; monocytes: rs=.81, P<.0001). CSF leukocytes from rifampin-treated rabbits produced less ROS (monocytes at 2 h after initiation of treatment: P=.045; at 5 h: P=.014; granulocytes at 5 h: P=.036) than did leukocytes from animals receiving ceftriaxone. The CSF malondialdehyde concentrations and the density of apoptotic neurons in the dentate gyrus were lower in rifampin- than in ceftriaxone-treated animals (P=.002 and.005). The use of rifampin to reduce the release of ROS and to decrease secondary brain injury appears promising.

Topics: Animals; Anti-Bacterial Agents; Apoptosis; Ceftriaxone; Cerebrospinal Fluid; Hippocampus; Meningitis, Pneumococcal; N-Formylmethionine Leucyl-Phenylalanine; Neurons; Phagocytes; Rabbits; Reactive Oxygen Species; Rifampin

Topics: Acute Kidney Injury; Adult; Amoxicillin; Anti-Bacterial Agents; Antibiotics, Antitubercular; Female; Guidelines as Topic; Humans; Meningitis, Pneumococcal; Penicillins; Rifampin; Time Factors; Vancomycin

Compared with beta-lactam antibiotics, rifampin releases smaller quantities of proinflammatory cell wall products from Streptococcus pneumoniae in vitro. Mice infected intracerebrally with S. pneumoniae were treated subcutaneously with 2-mg doses of rifampin or ceftriaxone (n=43 each) every 12 h for 3 days and then observed for another 3 days. Rifampin reduced overall mortality from 49% to 26% (P=.04). Kaplan-Meyer analysis revealed a substantial reduction of mortality during the first 24 h in mice receiving rifampin (difference in survival time: P=.007). Eight h after receiving a single 2-mg dose of rifampin or ceftriaxone, rifampin-treated mice had lower serum and cerebrospinal fluid concentrations of lipoteichoic and teichoic acids than did ceftriaxone-treated mice (median serum level: <0.5 vs. 27.0 ng/mL, P=.02; median cerebrospinal fluid level of pooled specimens: 97.5 vs. 206.0 ng/mL). Thus, the use of rifampin appears promising for reducing the release of proinflammatory bacterial components and decreasing early mortality in bacterial meningitis.

Topics: Animals; Ceftriaxone; Inflammation Mediators; Meningitis, Pneumococcal; Mice; Mice, Inbred C57BL; Probability; Rifampin

The fluoroquinolone trovafloxacin was bactericidal (0.47 +/- 0.23 delta log10 CFU/ml x h after 10 mg/kg of body weight and 0.78 +/- 0.15 delta log10 CFU/ml x h after 30 mg/kg) in the treatment of experimental meningitis caused by a highly penicillin-resistant (MIC and minimum bactericidal concentration = 4 and 4 microg/ml) strain of Streptococcus pneumoniae. Combinations with ampicillin and rifampin were indifferent compared to single drugs.

Topics: Ampicillin; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Fluoroquinolones; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Naphthyridines; Penicillin Resistance; Rabbits; Rifampin; Streptococcus pneumoniae

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

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

Rifampin at a maximally effective dose was less active than ceftriaxone (both drugs at 10 mg/kg of body weight.h) in a rabbit model of pneumococcal meningitis (delta log10 CFU/ml.h, -0.40 +/- 0.13 versus -0.77 +/- 0.18; P < 0.01). The bactericidal activity of rifampin decreased at concentrations in cerebrospinal fluid greater than those that are clinically achievable, and use of rifampin in combination with ofloxacin had no synergistic or additive effect.

Topics: Animals; Ceftriaxone; Drug Synergism; Meningitis, Pneumococcal; Microbial Sensitivity Tests; Rabbits; Rifampin; Serum Bactericidal Test; Streptococcus pneumoniae

Treatment of pneumococcal meningitis has become problematic because of the emergence of penicillin- and cephalosporin-resistant strains and because of the concern that dexamethasone therapy might reduce penetration of antibiotics into the cerebrospinal fluid (CSF). We addressed these issues with our rabbit meningitis model by studying two pneumococcal isolates that were resistant to penicillin and ceftriaxone and susceptible to vancomycin and rifampin. Ceftriaxone, vancomycin, and rifampin were given alone or in combination, with or without coadministration of dexamethasone. Treatment was started 12 to 14 h after intracisternal inoculation of approximately 10(4) CFU of one of the organisms. Rifampin concentrations in serum and CSF were similar, regardless of whether dexamethasone was given, whereas those of ceftriaxone were somewhat lower at each time point in animals given dexamethasone. The penetration of vancomycin into CSF was consistently and substantially reduced with dexamethasone treatment, which resulted in a delay in CSF sterilization not observed in non-dexamethasone-treated animals. When rifampin was used with ceftriaxone for treatment of meningitis caused by the more resistant strain, bacteriologic cure occurred promptly, with or without dexamethasone therapy. In areas with high rates of occurrence of resistant pneumococcal strains, we believe initial empiric therapy of bacterial meningitis should include two antibiotics: ceftriaxone and either rifampin or vancomycin. When dexamethasone is used, the combination of ceftriaxone and rifampin is preferred for therapy.

Topics: Animals; Ceftriaxone; Cerebrospinal Fluid; Cyclosporine; Dexamethasone; Drug Resistance, Microbial; Drug Therapy, Combination; Male; Meningitis, Pneumococcal; Penicillins; Rabbits; Rifampin; Vancomycin

The most appropriate therapy for meningitis caused by Streptococcus pneumoniae strains resistant to the extended-spectrum cephalosporins is unknown. We evaluated ceftriaxone, vancomycin, and rifampin alone and in different combinations and meropenem, cefpirome, and clinafloxacin alone in the rabbit meningitis model. Meningitis was induced in rabbits by intracisternal inoculation of one of two pneumococcal strains isolated from infants with meningitis (ceftriaxone MICs, 4 and 1 microgram/ml, respectively). Two doses, 5 h apart, of each antibiotic were given intravenously (except that ceftriaxone was given as one dose). Cerebrospinal fluid bacterial concentrations were measured at 0, 5, 10, and 24 h after therapy was started. Clinafloxacin was the most active single agent against both strains. Against the more resistant strain, ceftriaxone or meropenem alone was ineffective. The combination of vancomycin and ceftriaxone was synergistic, suggesting that this combination might be effective for initial empiric therapy of pneumococcal meningitis until results of susceptibility studies are available.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Cefpirome; Ceftriaxone; Cephalosporins; Disease Models, Animal; Drug Resistance, Microbial; Drug Synergism; Drug Therapy, Combination; Fluoroquinolones; Male; Meningitis, Pneumococcal; Meropenem; Microbial Sensitivity Tests; Penicillin Resistance; Quinolones; Rabbits; Rifampin; Thienamycins; Vancomycin

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

Two toddlers who attended the same day-care center were hospitalized hours apart with sepsis and meningitis due to a multiply resistant Streptococcus pneumoniae. We determined the prevalence of multiply resistant S pneumoniae respiratory carriage and disease in infants, toddlers, and staff in the day-care center and in household contacts. The nasopharynges of 82 (96%) of 85 day-care center children, 26 (90%) of 29 day-care center staff, and 28 (90%) of 31 family members were cultured. Streptococcus pneumoniae grew from 29 (35%) of the 82 cultured day-care center children. Ten (34%) of the S pneumoniae isolates were resistant to sulfamethoxazole-trimethoprim, oxacillin, and tetracycline and were relatively resistant to penicillin (minimum inhibitory concentration, 0.5 mg/L). All were serotype 14 and had the same antibiotic resistance pattern. Treatment of 97% of the day-care center children and staff with rifampin (10 mg/kg twice daily for 2 days) resulted in 70% reduction in positive nasopharyngeal cultures for S pneumoniae. No additional disease due to multiply resistant S pneumoniae was identified in the day-care center during a 9-month follow-up period. This report documents that an outbreak of multiply resistant invasive S pneumoniae occurred in a day-care center setting; that nasopharyngeal colonization of exposed children was common; and that rifampin treatment of 2 days only partially eradicated the organism from colonized individuals.

Topics: Administration, Oral; Carrier State; Child Day Care Centers; Disease Outbreaks; Drug Resistance, Microbial; Humans; Infant; Meningitis, Pneumococcal; Nasopharynx; Prevalence; Rifampin; Sepsis; Streptococcal Infections; Texas