Tentative clinical breakpoints and epidemiological cut-off values of nemonoxacin for Streptococcus pneumoniae and Staphylococcus aureus isolates associated with community-acquired pneumonia. (December 2020)

• Record Type: Journal Article
• Authors: Jean, Shio-Shin; Chang, Li-Wen; Hsueh, Po-Ren
• Is Part Of: Journal of global antimicrobial resistance. Volume 23(2020)
• Page Start: 388
• Page End: 393
• Publication Date: 2020-12
• Subjects: Nemonoxacin -- Epidemiological cut-off value -- Clinical breakpoint -- Community-acquired pneumonia -- Staphylococcus aureus -- Streptococcus pneumoniae; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2020.10.017
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: Nemonoxacin is a novel non-fluorinated quinolone with oral and intravenous (IV) formulations. Excellent activity against community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae and Staphylococcus aureus . >92% of patients with S. pneumoniae or S. aureus CAP with nemonoxacin MICs ≤ 0.25 mg/L had good outcomes. Tentative ECOFF/MIC90 /MIC99 value of nemonoxacin was 0.06/0.125/1 mg/L for S. pneumoniae and 0.125/1/8 mg/L for S. aureus . Tentative S. pneumoniae / S. aureus CBPs of 0.5/0.25, 0.5/0.5 & 1/1 mg/L for oral 500 mg, IV 500 mg & IV 750 mg nemonoxacin. Abstract: Objectives: To determine the minimum inhibitory concentration (MIC) distribution, epidemiological cut-off (ECOFF) values and clinical breakpoints (CBPs) of nemonoxacin, a non-fluorinated quinolone, for community-acquired pneumonia (CAP)-related Streptococcus pneumoniae and Staphylococcus aureus . Methods: We pooled the susceptibility and clinical data of CAP patients enrolled in five clinical trials conducted in three countries from 2006 to 2017. Published pharmacokinetic (PK) profiles of oral (500 mg) and intravenous (IV) (500, 650 and 750 mg) nemonoxacin formulations and pharmacodynamic (PD) parameters of the two aforementioned CAP-related Gram-positive cocci (GPC) were used to determine plausible CBPs. Moreover, nemonoxacin MIC distributions of CAP-related S. pneumoniae ( n = 1800) and S. aureus ( n = 2000) isolates were obtained to evaluate ECOFF values using a visual estimation approach and ECOFFinder. Results: More than 92% of patients with CAP caused by S. pneumoniae or S. aureus with nemonoxacin MICs ≤ 0.25 mg/L presented positive clinical and microbiological outcomes. The ECOFF, MIC90 and MIC99 values of nemonoxacin were, respectively, 0.06, 0.125 and 1 mg/L for S. pneumoniae and 0.125, 1 and 8 mg/L for S. aureus . Based on differences in the PK profiles of oral and IV formulations, PD parameters of nemonoxacin for these CAP-GPC and clinical in vivo efficacy data, tentative CBPs of 0.5, 0.5 and 1 mg/L, respectively, were established for the 500 mg oral and 500 mg and 750 mg IV nemonoxacin formulations for S. pneumoniae, and 0.25, 0.5 and 1 mg/L for S. aureus . Conclusion: This study provides plausible nemonoxacin CBPs for two important CAP-GPC.