Evaluation of antimicrobial regimens for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis

Friedland, Ian R.; Paris, Maria; Ehrett, Stuart; Hickey, Sheila; Olsen, Kurt; McCracken, George H.

doi:10.1128/aac.37.8.1630

Cited by 222 publications

(132 citation statements)

References 18 publications

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“…This is in good agreement with the results of a recent study with the same model that used two penicillin-and cephalosporin-resistant pneumococci. In that study, rifampin showed moderate bactericidal activity compared with the bactericidal activity of vancomycin or a new quinolone (9). In an earlier study in the rabbit model of Listeria monocytogenes meningitis, rifampin was also significantly less effective than ampicillin or penicillin (18).…”

mentioning

confidence: 96%

Rifampin for therapy of experimental pneumococcal meningitis in rabbits

Nau

Kaye

Sachdeva

et al. 1994

Antimicrob Agents Chemother

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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 (Aloglo 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.Pneumococci resistant to multiple antibiotics are an increasing challenge (13). At present, more than 10% of the pneumococci isolated in Spain, South Africa, Mexico, Poland, and Kenya are not susceptible to penicillin G (11). Penicillin resistance can substantially complicate the therapy of pneumococcal meningitis. In a study from Spain, 15 of 66 Streptococcus pneumoniae strains isolated from patients with meningitis were only moderately susceptible or resistant to penicillin G, and 7 of these strains were also resistant to chloramphenicol (22). Furthermore, resistance to penicillin is regularly associated with reduced susceptibilities to other ,B-lactams, and failures of cefotaxime and ceftriaxone for the treatment of meningitis caused by penicillin-resistant S. pneumoniae have been observed (1,2,8). Rifampin has been used successfully as an adjunct in the treatment of central nervous system infections caused by S. pneumoniae and staphylococci (15, 17). This prompted us to evaluate rifampin, which has low MICs for most strains of penicillin-resistant S. pneumoniae (11,22), in a rabbit model of experimental pneumococcal meningitis (3). We also examined whether increased bactericidal activity could be achieved by the combination of rifampin-ofloxacin. Rifampin-quinolone combinations have been used to treat other infections (6), and ofloxacin is one of the more active clinically available quinolones against pneumococci on the basis of the ratio of its MIC to achievable levels in serum. Ceftriaxone was used as the comparison drug in the studies.In vitro studies. All studies were performed with a penicillin-susceptible S. pneumoniae type 3 strain (MIC and MBC of penicillin G, 0.03 ,ug/ml) originally isolated from a patient with meningitis (20). MICs and MBCs were determined by a standard broth dilution method by using Todd-Hewitt broth (THB; Difco Laboratories, Detroit, Mich.) and an inoculum of 105 CFU/ml. The MIC was defined as the lowest concentration of an antibiotic that inhibited visible growth after 24 h of incubation at 37°C in room air with 5% CO2. The MBC was defined as the lowest antibiotic concentration that reduced the initial inoculum by >99.9%. The MIC and MBCs for the experimental strain of S. pneumoniae were, respectively, 0.008 and 0.06 ,ug/ml for rifampin, 0.5 and 1 ,ug/ml for ofloxacin, and

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mentioning

confidence: 96%

Rifampin for therapy of experimental pneumococcal meningitis in rabbits

Nau

Kaye

Sachdeva

et al. 1994

Antimicrob Agents Chemother

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“…In an experimental model of meningitis, the combination of vancomycin and ceftriaxone was shown to be synergistic, while vancomycin plus rifampin, and ceftriaxone plus rifampin were indifferent (showed no synergy) when given in combination against penicillin-and cephalosporin-resistant pneumococcus (21,22). Furthermore, when the combination of vancomycin plus ceftriaxone or rifampin plus ceftriaxone was used, there was significantly enhanced CSF bactericidal activity compared with the use of ceftriaxone alone against the resistant strains in these children (23).…”

Section: Dual Therapy With Vancomycin and Third-generation Cephalospomentioning

confidence: 97%

“…Furthermore, when the combination of vancomycin plus ceftriaxone or rifampin plus ceftriaxone was used, there was significantly enhanced CSF bactericidal activity compared with the use of ceftriaxone alone against the resistant strains in these children (23). Thus, even though there is no obvious synergy between various antibiotics in vitro (21,22), combinations of antibiotics appear to improve bactericidal effects in vivo (23). Experts recommend a dosage of cefotaxime for empirical use of 300 mg/kg/day (derived from experience in children who failed therapy with a cefotaxime dosage of 200 mg/kg/day) (1).…”

Section: Dual Therapy With Vancomycin and Third-generation Cephalospomentioning

confidence: 99%

Therapy of suspected bacterial meningitis in Canadian children six weeks of age and older

2001

Paediatrics &Amp; Child Health

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“…Reduced susceptibility to penicillin and third-generation cephalosporins of Streptococcus pneumoniae is a growing problem in China although resistance rates vary considerably between countries [2]. Some experts advise that when Streptococcus pneumoniae has been identified and susceptibility testing is pending or not available, empiric treatment should include vancomycin or rifampicin, although there is uncertainty regarding the benefit of adding vancomycin or rifampicin to a third-generation cephalosporin in Streptococcus pneumoniae meningitis patients [39][40][41]. Erythromycin, tetracycline, clindamycin, penicillin and trimethoprim/sulfamethoxazole were the least effective antibiotics against Streptococcus pneumoniae.…”

Section: Discussionmentioning

confidence: 99%

The microbiology and clinical characteristics of bacterial and fungal meningitis in a Chinese hospital

Chen¹,

Hu²,

Liu³

2017

Arch Med Sci Civil Dis

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A b s t r a c t Introduction:The aim was to investigate the distribution, antibiotic resistance, initial clinical and laboratory characteristics of pathogens isolated from the cerebrospinal fluid samples (CSF). Material and methods: The CSF were subjected for identification. The minimum inhibitory concentrations (MICs) of antimicrobial agents were tested. The initial clinical and laboratory characteristics were collected. Results: The rate of positive yield of pathogen meningitis in our study was 8.16% . Among the 1994 non-repetitive pathogens, Gram-positive pathogen was the most common (71.71%), followed by Gram-negative pathogen (20.36%), fungal (6.62%) and Mycobacterium tuberculosis (1.30%). Coagulase-negative staphylococci (CNS) was the most common Gram-positive pathogen and Acinetobacter baumannii (Ab) was the most common Gram-negative pathogen. As to fungal pathogen, Cryptococcus neoformans (CN) was the most common. The main CNS showed higher antimicrobial resistant rate for Penicillin G, oxacillin, clindamycin and erythromycin. Acinetobacter baumannii resistant to the most tested antibiotics and only showed considerable rate of resistance to cefoperazone/sulbactam, tigecycline and amikacin. All CN were susceptible to 5-fluorocytosine and only 3.6% CN were resistance to fluconazole. Long days of hospital stay, fever and meningeal irritation signs were common symptoms in the bacterial and fungal meningitis. Head injury, disturbance of consciousness, the pupil size of both eyes was not equal, pupillary reaction to light was slow or absent were more common in the Ab meningitis. The CSF protein concentration and white blood cells count as well as glucose concentration can be used in guiding initial treatment and further microbiological investigation. Conclusions: The main pathogens showed higher antimicrobial resistant rate and the selection of empiric antibiotics should take into consideration local epidemiology, antibiotic resistance patterns and the suspected causative microorganism.

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Evaluation of antimicrobial regimens for treatment of experimental penicillin- and cephalosporin-resistant pneumococcal meningitis

Cited by 222 publications

References 18 publications

Rifampin for therapy of experimental pneumococcal meningitis in rabbits

Rifampin for therapy of experimental pneumococcal meningitis in rabbits

Therapy of suspected bacterial meningitis in Canadian children six weeks of age and older

The microbiology and clinical characteristics of bacterial and fungal meningitis in a Chinese hospital

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