Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia*

Jung, Young Ju; Koh, Younsuck; Hong, Sang Bum; Chung, Joo Won; Choi, Sang Ho; Kim, Nam Joong; Kim, Seung Up; Choi, Ik Su; Han, Song Yi; Kim, Won Dong; Yun, Sung Cheol; Lim, Chae Man

doi:10.1097/ccm.0b013e3181b9ecea

Cited by 70 publications

(49 citation statements)

References 33 publications

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“…The final response rate observed, about 68.6%, was comparable to the rates seen in clinical trials with hospitalised adults with MRSA infections [10,17,19,21]. However, we found that our high vancomycin MIC group had an early clinical response rate of 35.3%, despite a final clinical response rate at the end of therapy of 64.7%.…”

Section: Discussionsupporting

confidence: 80%

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Relationship between the MIC of vancomycin and clinical outcome in patients with MRSA nosocomial pneumonia

et al. 2011

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Section: Discussionsupporting

confidence: 80%

“…Patients infected with MRSA isolates with vancomycin MICs [1 lg/mL may respond better to combination therapies or linezolid [16][17][18][19][20][21].…”

Section: Discussionmentioning

confidence: 99%

Relationship between the MIC of vancomycin and clinical outcome in patients with MRSA nosocomial pneumonia

et al. 2011

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“…In particular, our model offers an explanation for why the strategy suggested for some antibiotic treatments of pairing a broadly penetrating drug (e.g., rifampicin) with a narrowly penetrating one (e.g., vancomycin) to increase total drug coverage (51) might fail frequently due to the rapid evolution of resistance against the drug with higher penetration (51)(52)(53). It also offers an alternative explanation of why certain drugs are more vulnerable to resistance.…”

Section: Discussionmentioning

confidence: 97%

Imperfect drug penetration leads to spatial monotherapy and rapid evolution of multidrug resistance

Moreno-Gámez

Hill

Rosenbloom

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

138

149

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Infections with rapidly evolving pathogens are often treated using combinations of drugs with different mechanisms of action. One of the major goal of combination therapy is to reduce the risk of drug resistance emerging during a patient’s treatment. Although this strategy generally has significant benefits over monotherapy, it may also select for multidrug-resistant strains, particularly during long-term treatment for chronic infections. Infections with these strains present an important clinical and public health problem. Complicating this issue, for many antimicrobial treatment regimes, individual drugs have imperfect penetration throughout the body, so there may be regions where only one drug reaches an effective concentration. Here we propose that mismatched drug coverage can greatly speed up the evolution of multidrug resistance by allowing mutations to accumulate in a stepwise fashion. We develop a mathematical model of within-host pathogen evolution under spatially heterogeneous drug coverage and demonstrate that even very small single-drug compartments lead to dramatically higher resistance risk. We find that it is often better to use drug combinations with matched penetration profiles, although there may be a trade-off between preventing eventual treatment failure due to resistance in this way and temporarily reducing pathogen levels systemically. Our results show that drugs with the most extensive distribution are likely to be the most vulnerable to resistance. We conclude that optimal combination treatments should be designed to prevent this spatial effective monotherapy. These results are widely applicable to diverse microbial infections including viruses, bacteria, and parasites.

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“…A recent study of 93 patients in South Korea demonstrated that vancomycin plus rifampicin was more effective in the treatment of MRSA nosocomial pneumonia than vancomycin alone [26]. Further clinical data are required to assess whether such therapy has clinical utility.…”

Section: Vancomycinmentioning

confidence: 99%

Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options

Welte

Pletz

2010

International Journal of Antimicrobial Agents

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Effect of vancomycin plus rifampicin in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia*

Abstract: Vancomycin plus rifampicin seems to be more effective than vancomycin alone in the treatment of nosocomial methicillin-resistant Staphylococcus aureus pneumonia.

Cited by 70 publications

References 33 publications

Relationship between the MIC of vancomycin and clinical outcome in patients with MRSA nosocomial pneumonia

Relationship between the MIC of vancomycin and clinical outcome in patients with MRSA nosocomial pneumonia

Imperfect drug penetration leads to spatial monotherapy and rapid evolution of multidrug resistance

Antimicrobial treatment of nosocomial meticillin-resistant Staphylococcus aureus (MRSA) pneumonia: current and future options

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