Emergence of Rifampin-Resistant Strains of Staphylococcus aureus During Combination Therapy with Vancomycin and Rifampin: A Report of Two Cases

Simon, G. L.; Smith, Ronald H.; Sande, Merle A.

doi:10.1093/clinids/5.supplement_3.s507

Cited by 42 publications

(21 citation statements)

References 7 publications

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“…The addition of intrathecal or intraventricular doses of vancomycin remains a reasonable possibility for treating some unresponsive cases (3,10,28). The combination of vancomycin with rifampin might be a good therapeutic alternative (4,24), although the possibility of developing rifampin resistance during therapy might exist if very low levels of vancomycin are present in the CSF (27); however, this possibility would be of little concern if substantial improvement could be achieved through the addition of rifampin to vancomycin therapy. New studies will have to be carried out to discover the most appropriate therapy for adult meningitis due to pneumococci exhibiting both a high level of resistance to penicillin and resistance to chloramphenicol.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of vancomycin for therapy of adult pneumococcal meningitis

Viladrich

Gudiol

Liñares

et al. 1991

Antimicrob Agents Chemother

238

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The emergence of pneumococci resistant to penicillin and other agents prompted us to evaluate intravenous vancomycin for the therapy of pneumococcal meningitis, which has an overall mortality of 30%. Eleven consecutive adult patients with cerebrospinal fluid (CSF)-culture-proven pneumococcal meningitis and positive initial CSF Gram stain were given intravenous vancomycin (usual dosage, 7.5 mg/kg every 6 h for 10 days). The MBCs of vancomycin ranged from 0.25 to 0.5 micrograms/ml. Early adjunctive therapy with intravenous dexamethasone, mannitol, and sodium phenytoin was also instituted. After 48 h of therapy, all 11 patients showed a satisfactory clinical response, although the CSF culture remained positive in one case; median trough CSF and serum vancomycin levels were 2 and 5.1 micrograms/ml, respectively, and trough CSF bactericidal titers ranged from less than 1:2 to 1:16. On day 3, one patient died of acute heart failure. Four patients had clinical failure at on days 4 (two patients), 7 (one), and 8 (one) of therapy; they all immediately responded to a change in antibiotic therapy. The remaining six patients were cured after 10 days of vancomycin therapy. At this point, median peak CSF and serum vancomycin levels were 1.9 and 18.5 micrograms/ml, respectively. A transient alteration of renal function occurred in two patients, and persistent slight hypoacusia occurred in three patients. In summary, 11 adults with pneumococcal meningitis were treated with vancomycin and early adjunctive therapy including dexamethasone. All patients initially improved, and 10 were ultimately cured of the infection. However, four patients experienced a therapeutic failure, which led to a change in vancomycin therapy.

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Section: Resultsmentioning

confidence: 99%

Evaluation of vancomycin for therapy of adult pneumococcal meningitis

Viladrich

Gudiol

Liñares

et al. 1991

Antimicrob Agents Chemother

238

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“…Rapid development of resistance may occur by single step mutation, depending on the inoculum size (24). In vitro (14), animal model (16,17,29), and clinical failures (4,5,8,20,21) have been reported for treatment with rifampin. Therefore, rifampin combinations with vancomycin, teicoplanin, ciprofloxacin, and fleroxacin have been evaluated to prevent emergence of rifampin resistance.…”

Section: Discussionmentioning

confidence: 99%

In vivo verification of in vitro model of antibiotic treatment of device-related infection

Blaser

Vergères

Widmer

et al. 1995

Antimicrob Agents Chemother

112

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Device-related infections are difficult to treat with antibiotics alone. Standard susceptibility tests do not correlate with treatment success. Therefore, the utility of a pharmacokinetic in vitro model has been evaluated in comparison with the tissue-cage infection model in guinea pigs. The bactericidal activity of 28 treatment regimens has been studied by using three different test strains. In vitro efficacy was defined as reduction in the number of suspended or adherent bacteria, and in vivo efficacy was defined as reduction in the number of bacteria in tissue-cage fluid. Test results between the two models (in vivo and in vitro) correlated well, with correlation coefficients of 0.85 for in vivo efficacy versus in vitro efficacy against suspended bacteria and 0.72 for in vivo efficacy versus in vitro efficacy against adherent bacteria (P < 0.05) for Staphylococcus aureus, 0.96 and 0.82 (P < 0.05) for Staphylococcus epidermidis, and 0.89 and 0.97 for Escherichia coli, respectively. In contrast, standard susceptibility tests, ratios of MICs to trough or peak levels, ratios of the area under the curve to the MIC, or time above the MIC were not predictive for therapeutic outcome in either the in vitro or in vivo model. In both models, the bactericidal activity levels with combination regimens were significantly higher than those with single-drug regimens (P < 0.001). Furthermore, rifampin combinations with either vancomycin, teicoplanin, fleroxacin, or ciprofloxacin were significantly more bactericidal against adherent bacteria than netilmicin combinations with vancomycin or daptomycin (P < 0.01). Thus, in vivo verification of the pharmacokinetic in vitro model correlated well with the animal model. The in vitro model offers an alternative to the animal model in experiments that screen and assess antibiotic regimens against devicerelated infections.

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“…The reasons for considering rifampin combination therapy for native valve endocarditis (NVE) are (i) that it is highly active against S. aureus, (ii) that it has good tissue and vegetation penetration, and (iii) that oral therapy can be used to discharge intravenous drug users early from hospital (57,74,237). However, what has not been defined are the timing of the addition of rifampin to the other antibiotic in relation to bacteremia, the appropriate dose and interval of rifampin needed, how long therapy should be maintained once initiated, and patient adherence to therapy if being managed as an outpatient (57,74,163,227 Table 4).…”

Section: Staphylococcimentioning

confidence: 99%

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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Emergence of Rifampin-Resistant Strains of Staphylococcus aureus During Combination Therapy with Vancomycin and Rifampin: A Report of Two Cases

Cited by 42 publications

References 7 publications

Evaluation of vancomycin for therapy of adult pneumococcal meningitis

Evaluation of vancomycin for therapy of adult pneumococcal meningitis

In vivo verification of in vitro model of antibiotic treatment of device-related infection

Rifampin Combination Therapy for Nonmycobacterial Infections

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