Evaluation of ceftriaxone, vancomycin and rifampicin alone and combined in an experimental model of meningitis caused by highly cephalosporin-resistant Streptococcus pneumoniae ATCC 51916

Ribes, Sandra; Taberner, Ferran; Domènech, A.; Cabellos, Carmen; Tubau, Fé; Liñares, Josefina; Viladrich, Pedro F.; Gudiol, Francesc

doi:10.1093/jac/dki323

Cited by 20 publications

(10 citation statements)

References 9 publications

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“…This is in agreement with the in vivo study by Ribes et al [26], where rifampicin achieved excellent bactericidal effects in CSF at concentrations of ≥ 3.7 × MIC, whereas in broth, only bacteriostatic effects were observed. The in vivo reduction of -4.25 Δlog 10 CFU/ml observed with S. pneumoniae at the mentioned concentration range of approximately 3-13 times the MIC at 24 h was similar to the in vitro reduction of -3 to -4 Δlog 10 CFU/ml in CSF at 24 h with S. aureus at rifampicin concentrations ranging from 2 to 8 times the MIC [13] .…”

Section: Comparison In Vitro Vs In Vivo and Conclusionsupporting

confidence: 93%

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Understanding the Activity of Antibiotics in Cerebrospinal Fluid in vitro

Matzneller

Burian²,

Zeitlinger³

et al. 2016

Pharmacology

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Background: In vitro studies suggest that antimicrobial activity of antibiotics meant to treat central nervous system infections such as meningitis or ventriculitis may be altered by cerebrospinal fluid (CSF). This could explain the reason behind the often observed discrepancies between the activity of antibiotics determined in artificial growth media in vitro, and their sometimes reduced clinical efficacy in CSF in vivo. If conducted in CSF, in vitro microbiological investigations might predict the ability of antibiotic drugs to treat CSF infections better than experiments in artificial growth media. In addition, they are less expensive, critical and time consuming than animal studies, and might potentially be appreciated in drug development as a rapid and cost-effective means to gain valuable information on drugs meant to treat infections residing in CSF. Summary: Data from microbiological in vitro experiments performed in CSF were compiled for fosfomycin, rifampicin, cefepime, cefotaxime, ceftriaxone, ciprofloxacin, gentamicin and vancomycin. Where possible, correlations between in vitro data and evidence from in vivo studies were established. Key Messages: As discussed in the text, no clear correlations between in vitro studies in CSF and clinical outcomes could be identified. Methodological recommendations derived from the collected studies are summarized in order to optimize future research on the topic.

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Section: Comparison In Vitro Vs In Vivo and Conclusionsupporting

confidence: 93%

“…In vivo Ribes et al [26] jections at a dosage of 15 mg/kg and performed a concomitant static in vitro time-kill study in an unspecified medium. For unclear reasons, different time points (6 h in vitro and 24 h in vivo) were used for the quantification of antibacterial effects, perturbing the comparability of the data.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Understanding the Activity of Antibiotics in Cerebrospinal Fluid in vitro

Matzneller

Burian²,

Zeitlinger³

et al. 2016

Pharmacology

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“…Rifampin combination therapy has been used for S. pneumoniae infections, especially meningitis caused by penicillin-resistant strains (penicillin-resistant S. pneumoniae [PRSP]) (56,211,236).…”

Section: Other Diseasesmentioning

confidence: 99%

“…The in vitro data for the vancomycin-rifampin combination therapy for treatment of S. pneumoniae infection using time-kill studies again showed indifference, similarly to S. aureus (94). Despite data suggesting that rifampin has poor penetration into the brain, animal studies have had mixed results (56,179,211,236). Using a rabbit model, Nau et al found that rifampin was significantly less active against S. pneumoniae in the CSF than ceftriaxone, with paradoxically less efficacy at higher doses of rifampin (179).…”

Section: Other Diseasesmentioning

confidence: 99%

“…Cormican et al showed in an in vivo study that cephalosporin monotherapy was effective and that the addition of rifampin decreased the bactericidal activity of cefotaxime (56). However, 2 separate in vivo studies of experimental PRSP meningitis comparing ceftriaxone to combination therapy with rifampin found that rifampin combination therapy was highly effective (211,236). The addition of rifampin to meropenem did not improve the clearance of PRSP in a guinea pig model (88).…”

Section: Other Diseasesmentioning

confidence: 99%

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Rifampin Combination Therapy for Nonmycobacterial Infections

2010

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SUMMARY The increasing emergence of antimicrobial-resistant organisms, especially methicillin-resistant Staphylococcus aureus (MRSA), has resulted in the increased use of rifampin combination therapy. The data supporting rifampin combination therapy in nonmycobacterial infections are limited by a lack of significantly controlled clinical studies. Therefore, its current use is based upon in vitro or in vivo data or retrospective case series, all with major limitations. A prominent observation from this review is that rifampin combination therapy appears to have improved treatment outcomes in cases in which there is a low organism burden, such as biofilm infections, but is less effective when effective surgery to obtain source control is not performed. The clinical data support rifampin combination therapy for the treatment of prosthetic joint infections due to methicillin-sensitive S. aureus (MSSA) after extensive debridement and for the treatment of prosthetic heart valve infections due to coagulase-negative staphylococci. Importantly, rifampin-vancomycin combination therapy has not shown any benefit over vancomycin monotherapy against MRSA infections either clinically or experimentally. Rifampin combination therapy with daptomycin, fusidic acid, and linezolid needs further exploration for these severe MRSA infections. Lastly, an assessment of the risk-benefits is needed before the addition of rifampin to other antimicrobials is considered to avoid drug interactions or other drug toxicities.

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Evaluation of meropenem alone and combined with rifampin in the guinea pig model of pneumococcal meningitis

Force

Taberner

Cabellos

et al. 2009

Eur J Clin Microbiol Infect Dis

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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.

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Evaluation of ceftriaxone, vancomycin and rifampicin alone and combined in an experimental model of meningitis caused by highly cephalosporin-resistant Streptococcus pneumoniae ATCC 51916

Cited by 20 publications

References 9 publications

Understanding the Activity of Antibiotics in Cerebrospinal Fluid in vitro

Understanding the Activity of Antibiotics in Cerebrospinal Fluid in vitro

Rifampin Combination Therapy for Nonmycobacterial Infections

Evaluation of meropenem alone and combined with rifampin in the guinea pig model of pneumococcal meningitis

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