دورية أكاديمية

Activity of Delafloxacin and Levofloxacin against Stenotrophomonas maltophilia at Simulated Plasma and Intrapulmonary pH Values.

التفاصيل البيبلوغرافية
العنوان: Activity of Delafloxacin and Levofloxacin against Stenotrophomonas maltophilia at Simulated Plasma and Intrapulmonary pH Values.
المؤلفون: Vialichka A; College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA., Biagi M; College of Pharmacy, University of Illinois Chicago, Rockford, Illinois, USA., Meyer K; College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA., Wu T; College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA., Shajee A; College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA., Tan X; College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA., Wenzler E; College of Pharmacy, University of Illinois Chicago, Chicago, Illinois, USA.
المصدر: Microbiology spectrum [Microbiol Spectr] 2022 Aug 31; Vol. 10 (4), pp. e0270521. Date of Electronic Publication: 2022 Jul 11.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: ASM Press Country of Publication: United States NLM ID: 101634614 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2165-0497 (Electronic) Linking ISSN: 21650497 NLM ISO Abbreviation: Microbiol Spectr Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : ASM Press, 2013-
مواضيع طبية MeSH: Gram-Negative Bacterial Infections* , Stenotrophomonas maltophilia*, Anti-Bacterial Agents/pharmacology ; Fluoroquinolones/pharmacology ; Humans ; Hydrogen-Ion Concentration ; Levofloxacin/pharmacology ; Microbial Sensitivity Tests
مستخلص: Fluoroquinolones have become a popular treatment option for Stenotrophomonas maltophilia infections. Although levofloxacin is most commonly used, delafloxacin demonstrates comparable in vitro activity when evaluated under standard susceptibility testing conditions at neutral pH. At acidic pH, the activity of the anionic delafloxacin is improved, while the activity of the zwitterionic levofloxacin is reduced. Because the human respiratory tract has a pH of ~6.6 and is the most common site of S. maltophilia infection, it is vital to understand the activity of these agents in this environment. Therefore, levofloxacin and delafloxacin were tested against clinical S. maltophilia isolates via broth microdilution testing ( n  = 37) and time-kill analysis ( n  = 5) in neutral cation-adjusted Mueller-Hinton broth (CAMHB) (pH 7.3) and acidic CAMHB (aCAMHB) (pH 6.5). In CAMHB, MIC 50 values were similar between levofloxacin and delafloxacin (8 mg/L versus 8 mg/L). In aCAMHB, levofloxacin MICs did not change, while delafloxacin MICs decreased by a median of 4 log 2 dilutions (MIC 50 values of 8 mg/L versus 0.25 mg/L). In time-kill analyses, levofloxacin and delafloxacin at the maximum drug concentration for the free drug ( fC max ) were bactericidal against 3 and 2 isolates in CAMHB, respectively. In aCAMHB, levofloxacin was not bactericidal against any isolate, while delafloxacin was bactericidal against the same 2 isolates. Relative to CAMHB, levofloxacin activity was reduced by 2.5 log 10 CFU/mL in aCAMHB, whereas delafloxacin activity was increased 2.7 log 10 CFU/mL. Although the bactericidal activity of levofloxacin against S. maltophilia was attenuated in an acidic environment in this study, the increased potency of delafloxacin at pH 6.5 did not translate into improved bactericidal activity in time-kill analyses, compared to pH 7.3. IMPORTANCE Stenotrophomonas maltophilia most often infects the lungs, where the physiologic environment is naturally slightly acidic (pH ~6.6), compared to most parts of the body (such as the bloodstream), which have neutral pH values (~7.4). Pneumonia due to S. maltophilia is often treated with the antibiotic levofloxacin, despite the activity of levofloxacin being known to be impaired at acidic pH. Unfortunately, currently available methods for susceptibility testing of levofloxacin against S. maltophilia are performed at a neutral pH and therefore may not accurately represent the activity of levofloxacin at the site of infection in the lungs. A similar but newer antibiotic in the same class as levofloxacin, namely, delafloxacin, is not affected by being in an acidic environment and may actually work better at lower pH values. Therefore, the purpose of this study was to investigate whether one drug might be better than the other in this setting by testing each agent's ability to kill S. maltophilia at pH 7.3 and pH 6.5. These findings could then be used to design confirmatory studies that may ultimately impact which drug is given to patients with lung infections due to S. maltophilia.
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فهرسة مساهمة: Keywords: Stenotrophomonas maltophilia; acidic environment; delafloxacin; epithelial lining fluid; fluoroquinolone; levofloxacin; pH; pharmacodynamics; pneumonia; susceptibility testing; time-kill assay
المشرفين على المادة: 0 (Anti-Bacterial Agents)
0 (Fluoroquinolones)
6315412YVF (delafloxacin)
6GNT3Y5LMF (Levofloxacin)
تواريخ الأحداث: Date Created: 20220721 Date Completed: 20220908 Latest Revision: 20231020
رمز التحديث: 20231020
مُعرف محوري في PubMed: PMC9431699
DOI: 10.1128/spectrum.02705-21
PMID: 35862943
قاعدة البيانات: MEDLINE
الوصف
تدمد:2165-0497
DOI:10.1128/spectrum.02705-21