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临床革兰氏阴性和革兰氏阳性细菌菌株对磷霉素的敏感性评估及其在感染治疗中的意义。

Assessment of the Susceptibility of Clinical Gram-Negative and Gram-Positive Bacterial Strains to Fosfomycin and Significance of This Antibiotic in Infection Treatment.

作者信息

Kowalska-Krochmal Beata, Mączyńska Beata, Rurańska-Smutnicka Danuta, Secewicz Anna, Krochmal Grzegorz, Bartelak Małgorzata, Górzyńska Aleksandra, Laufer Klaudyna, Woronowicz Krystyna, Łubniewska Joanna, Łappo Jolanta, Czwartos Magdalena, Dudek-Wicher Ruth

机构信息

Department of Pharmaceutical Microbiology and Parasitology, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland.

Department of Laboratory Diagnostics, Jan Mikulicz-Radecki University Teaching Hospital, Borowska 213, 50-556 Wrocław, Poland.

出版信息

Pathogens. 2022 Nov 30;11(12):1441. doi: 10.3390/pathogens11121441.

Abstract

Multidrug resistance of bacteria has prompted intensive development work on new medicines, but also the search for effective options among the oldest antibiotics. Although intravenous fosfomycin (IVFOS) seems to be an interesting proposal, the recommended agar dilution method for susceptibility determination poses a major problem in routine diagnostic testing. As a consequence, there is a lack of comprehensive data on the frequency of isolation of susceptible or resistant strains. This fact triggered the disposition of EUCAST concerning the revision of IVFOS breakpoints (BPs), including withdrawal of BPs for (excluding ) and coagulase-negative staphylococci. Therefore, the aim of this study was to assess the activity of fosfomycin against numerous clinical strains using recommended methods. : A total of 997 bacterial strains were tested from the following genera: , spp., spp., spp., and spp., for which there are currently no BPs. The strains were isolated from various clinical materials from patients hospitalized in five hospitals. During the investigation, the recommended agar dilution method was used. Susceptibility to other antibiotics and resistance mechanisms were determined using an automatic method (Phoenix) the disk diffusion method, and E-tests. MIC values of fosfomycin were estimated for all strains and for susceptible and multidrug-resistant (MDR) strains individually. : Except for and , 83% of the strains were susceptible to IVFOS, including the largest percentage of and . spp. turned out to be the least susceptible strains (66%). The highest proportion of susceptibility to fosfomycin was found among strains that were sensitive to other antibiotics (80.9%), and the lowest was found among Gram-negative carbapenemase-producing bacteria (55.6%) and ESBL+ bacteria (61.6%). The MIC evaluation revealed the lowest MIC and MIC values for (0.5 mg/L and 1 mg/L, respectively) and (4 mg/L and 32 mg/L, respectively). The highest values of MIC were found for spp. (256 mg/L), while the highest values of MIC were found for spp. and spp. (256 mg/L and 512 mg/L, respectively). : IVFOS appears to be suitable for the treatment of many infections, including the empirical treatment of polymicrobial infections and those caused by MDR strains, since the sensitivity of the studied strains to this antibiotic in different groups ranged from 66% to as much as 99%. Sensitivity to fosfomycin was also demonstrated by 60% of carbapenem-resistant strains; therefore, IVFOS is one of the few therapeutic options that can be effective against the most resistant Gram-negative rods. In light of the general consultation posted by EUCAST, obtaining data such as IVFOS MIC value distributions may be vital for the decision of implementing fosfomycin into breakpoint tables.

摘要

细菌的多重耐药性促使人们大力研发新型药物,同时也促使人们在最古老的抗生素中寻找有效的选择。尽管静脉注射磷霉素(IVFOS)似乎是一个有趣的提议,但推荐的用于药敏测定的琼脂稀释法在常规诊断测试中带来了一个重大问题。因此,缺乏关于敏感或耐药菌株分离频率的全面数据。这一事实引发了欧洲抗菌药物敏感性试验委员会(EUCAST)对IVFOS折点(BPs)进行修订的决定,包括撤销针对[具体菌种](不包括[具体菌种])和凝固酶阴性葡萄球菌的BPs。因此,本研究的目的是使用推荐方法评估磷霉素对众多临床菌株的活性。:共对来自以下菌属的997株细菌进行了测试:[具体菌属1]、[具体菌属2]菌、[具体菌属3]菌、[具体菌属4]菌和[具体菌属5]菌,目前尚无针对这些菌属的BPs。这些菌株是从五家医院住院患者的各种临床材料中分离出来的。在调查过程中,使用了推荐的琼脂稀释法。使用自动方法(Phoenix)、纸片扩散法和E试验测定对其他抗生素的敏感性和耐药机制。分别估计了所有菌株以及敏感和多重耐药(MDR)菌株的磷霉素MIC值。:除了[具体菌种1]和[具体菌种2]外,83%的菌株对IVFOS敏感,其中[具体菌种3]和[具体菌种4]的比例最高。[具体菌属5]菌被证明是最不敏感的菌株(66%)。对其他抗生素敏感的菌株中对磷霉素敏感性比例最高(80.9%),而在产碳青霉烯酶的革兰氏阴性菌(55.6%)和产超广谱β-内酰胺酶(ESBL+)细菌(61.6%)中比例最低。MIC评估显示[具体菌种6]的MIC和MIC值最低(分别为0.5 mg/L和1 mg/L)以及[具体菌种7](分别为4 mg/L和32 mg/L)。[具体菌属8]菌的MIC值最高(256 mg/L),而[具体菌属9]菌和[具体菌属10]菌的MIC值最高(分别为256 mg/L和512 mg/L)。:IVFOS似乎适用于治疗许多感染,包括对多种微生物感染和由MDR菌株引起的感染进行经验性治疗,因为所研究的不同组菌株对这种抗生素的敏感性范围从66%到高达99%。60%的耐碳青霉烯菌株也对磷霉素敏感;因此,IVFOS是少数几种可能对最耐药的革兰氏阴性杆菌有效的治疗选择之一。鉴于EUCAST发布的总体咨询意见,获取诸如IVFOS MIC值分布等数据对于将磷霉素纳入折点表的决策可能至关重要。

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