Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada.
Clinical Microbiology, Diagnostic Services, Shared Health Manitoba, Winnipeg, Canada.
J Antimicrob Chemother. 2022 Oct 28;77(11):3035-3038. doi: 10.1093/jac/dkac275.
Multiple susceptible breakpoints are published to interpret fosfomycin MICs: ≤64 mg/L for Escherichia coli and Enterococcus faecalis grown from urine (CLSI M100); ≤32 mg/L for Enterobacterales and staphylococci when parenteral fosfomycin is prescribed (EUCAST); and ≤8 mg/L for uncomplicated urinary tract infection with E. coli when oral fosfomycin is used (EUCAST). Clinical laboratories are frequently requested to test fosfomycin against antimicrobial-resistant urinary isolates not included in standard documents.
The in vitro activity of fosfomycin was determined using the CLSI agar dilution method for a 2007-20 collection of clinically significant Gram-negative (3656 Enterobacterales; 140 Pseudomonas aeruginosa) and Gram-positive (346 E. faecalis; 94 Staphylococcus aureus) urinary isolates from the CANWARD surveillance study. Comparator agents were tested using CLSI broth microdilution.
Using the CLSI MIC breakpoint (≤64 mg/L), 99.2% of E. coli (n = 2871; MIC90, 4 mg/L), including 96.7% of ESBL-positive isolates, were fosfomycin susceptible. Similarly, 95.8% of E. coli, including 95.2% of ESBL-positive isolates, were fosfomycin susceptible at ≤8 mg/L (EUCAST oral susceptible MIC breakpoint). All other species of Enterobacterales (except Citrobacter freundii) and P. aeruginosa had higher fosfomycin MICs (MIC90s, 64 to >512 mg/L) than E. coli. Using published breakpoints, 88.4% of E. faecalis (MIC ≤64 mg/L) and 97.9% of S. aureus (MIC ≤32 mg/L) isolates were fosfomycin susceptible.
Fosfomycin demonstrated in vitro activity against frequently encountered Gram-positive and Gram-negative urinary pathogens; however, the extrapolation of current CLSI and EUCAST MIC breakpoints to pathogens not specified by standard methods requires further study and is currently not recommended.
有多个易感断点被公布用于解释磷霉素 MIC 值：CLSI M100 规定，对来自尿液的大肠埃希菌和粪肠球菌，MIC 值≤64mg/L；当给予肠杆菌科和葡萄球菌注射用磷霉素时，EUCAST 规定 MIC 值≤32mg/L；当使用口服磷霉素治疗大肠埃希菌引起的单纯性尿路感染时，EUCAST 规定 MIC 值≤8mg/L。临床实验室经常被要求检测不在标准文件中的抗微生物耐药性的尿分离株对抗磷霉素的活性。
使用 CLSI 琼脂稀释法对来自 CANWARD 监测研究的 2007-20 年收集的临床显著的革兰氏阴性（3656 株肠杆菌科；140 株铜绿假单胞菌）和革兰氏阳性（346 株粪肠球菌；94 株金黄色葡萄球菌）尿分离株进行了磷霉素的体外活性检测。使用 CLSI 肉汤微量稀释法检测比较剂。
使用 CLSI MIC 断点（≤64mg/L），99.2%（n=2871）的大肠埃希菌，包括 96.7%的 ESBL 阳性分离株，对磷霉素敏感。同样，在 ≤8mg/L（EUCAST 口服敏感 MIC 断点）时，95.8%的大肠埃希菌，包括 95.2%的 ESBL 阳性分离株，对磷霉素敏感。其他肠杆菌科（除弗劳地柠檬酸杆菌外）和铜绿假单胞菌的所有其他种的磷霉素 MIC 值（MIC90，64 至 >512mg/L）均高于大肠埃希菌。使用公布的断点，88.4%的粪肠球菌（MIC≤64mg/L）和 97.9%的金黄色葡萄球菌（MIC≤32mg/L）分离株对磷霉素敏感。
磷霉素对常见的革兰氏阳性和革兰氏阴性尿病原体具有体外活性；然而，将当前 CLSI 和 EUCAST MIC 断点外推至标准方法未指定的病原体需要进一步研究，目前不建议这样做。
