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

Shio Shin Jean, Li Wen Chang, Po Ren Hsueh

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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-relatedS. 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 byS. 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.

Original languageEnglish
Pages (from-to)388-393
Number of pages6
JournalJournal of Global Antimicrobial Resistance
Volume23
DOIs
Publication statusPublished - Dec 2020

Keywords

  • Clinical breakpoint
  • Community-acquired pneumonia
  • Epidemiological cut-off value
  • Nemonoxacin
  • Staphylococcus aureus
  • Streptococcus pneumoniae

ASJC Scopus subject areas

  • Microbiology
  • Immunology and Allergy
  • Immunology
  • Microbiology (medical)

Fingerprint Dive into the research topics of 'Tentative clinical breakpoints and epidemiological cut-off values of nemonoxacin for Streptococcus pneumoniae and Staphylococcus aureus isolates associated with community-acquired pneumonia'. Together they form a unique fingerprint.

Cite this