At the Threshold: Defining Clinically Meaningful Resistance Thresholds for Antibiotic Choice in Community‐Acquired Pneumonia

Abstract

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.

Human Antimicrobial Peptide LL-37 Induces MefE/Mel-Mediated Macrolide Resistance in Streptococcus pneumoniae

“…Their finding would be consistent with low-level in vitro MICs, as observed for mega-containing isolates, that increase upon in vivo induction of a resistance determinant, resulting in MICs that exceed the threshold established by existing guidelines (MICs Ն 16 g/ml) (25) beyond which macrolides should no longer be used. Taken together, induction of MefE/Mel by LL-37 provides an intriguing, possible explanation for the observed macrolide treatment failures in disease caused by low-level-resistant pneumococci (3,5,6,13,14,16,22,23).…”

“…MefE/Mel-mediated MICs for erythromycin range from 1 to 32 g/ml and increase by 4-fold upon macrolide induction, on average (37). The clinical implications of low-level macrolide resistance (1 to 8 g/ml) are controversial (3,14,17,26). Recent studies provide evidence that infection with low-level macrolide-resistant pneumococci constitutes a risk factor for treatment failure (5,4,13,22,23).…”

Treatment of community-acquired pneumonia

“…9,10 The findings by Vardakas and colleagues support the current recommendations of the Infectious Diseases Society of America and the American Thoracic Society 3 for the treatment of community-acquired pneumonia. These guidelines recommend a macrolide antibiotic or doxycycline for patients who were previously healthy and who have not used antimicrobial drugs within the previous 3 months.…”

Early discharge and outpatient treatment of patients admitted for acute pulmonary embolism

“…However, we disagree that markers of myocardial injury and RVD should be performed prior to clinical scores. In fact, there is increasing evidence that the Pulmonary Embolism Severity Index (PESI) and Simplified PESI (sPESI) identify low-risk patients who might benefit from outpatient therapy of their disease without the need for echocardiography or troponin tests [2,3]. S.N.C.…”