At the threshold: Defining clinically meaningful resistance thresholds for antibiotic choice in community-acquired pneumonia

被引:37
作者
Daneman, Nick [2 ]
Low, Donald E. [3 ,5 ]
McGeer, Alison [3 ,4 ]
Green, Karen A. [4 ]
Fisman, David N. [1 ,5 ]
机构
[1] Hosp Sick Children, Res Inst, Toronto, ON M5G 1E6, Canada
[2] Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada
[3] Mt Sinai Hosp, Dept Microbiol, Toronto, ON M5G 1X5, Canada
[4] Mt Sinai Hosp, Dept Infect Control, Toronto, ON M5G 1X5, Canada
[5] Ontario Cent Publ Hlth Lab, Toronto, ON, Canada
关键词
D O I
10.1086/529440
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Community-acquired pneumonia caused by Streptococcus pneumoniae is a major source of morbidity and mortality. Macrolide antibiotics are recommended as empirical first-line therapy for patients with community-acquired pneumonia. Guidelines suggest a 25% rate of high-level macrolide resistance in the community as the threshold beyond which macrolides should not be used. We evaluated the implications of this threshold for clinical failure rates. Methods. We developed a theoretical model linking the prevalence of macrolide resistance to patient outcomes, based on the epidemiological concept of risk difference. We estimated the risk of clinical failure as a function of the likelihood and impact of discordant therapy and of the probability of clinical failure even in the presence of optimal therapy. The model was parameterized on the basis of the best available data derived from the published medical literature, and clinical failures were valued monetarily using an expected net benefit approach. Results. Under the proposed 25% resistance threshold, the risk difference for such therapy would be 1.2% (95% credible interval, 0.5%-3.1%) for death, 1.6% (95% credible interval, 0.5%-3.2%) for bacteremia, and 3.3% (95% credible interval, 1.1%-5.7%) for prolonged clinical course; excess risks of death were valued at >$10,000 per empirical treatment of community-acquired pneumonia and were further elevated in high-risk populations. Excluding low-level resistance resulted in a 4-fold underestimation of projected risks. Conclusion. A 25% resistance threshold that fails to consider low-level resistance will result in high excess rates of morbidity and mortality because of discordant therapy. Whether projected failure rates are classified as unacceptable is an important health policy question, because risk of clinical failure needs to be weighed against other considerations.
引用
收藏
页码:1131 / 1138
页数:8
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