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对第三代头孢菌素耐药的革兰氏阴性杆菌:β-内酰胺酶特性及对Sch 34343的敏感性

Gram-negative bacilli resistant to third-generation cephalosporins: beta-lactamase characterization and susceptibility to Sch 34343.

作者信息

Medeiros A A, Hare R, Papa E, Adam C, Miller G H

出版信息

J Antimicrob Chemother. 1985 Jun;15 Suppl C:119-32. doi: 10.1093/jac/15.suppl_c.119.

DOI:10.1093/jac/15.suppl_c.119
PMID:3875602
Abstract

We studied 192 recent clinical isolates, comprising six species of Gram-negative bacilli resistant either to cefotaxime or latamoxef (Moxalactam), from several hospitals. All isolates were resistant to several other third-generation cephalosporins or a monobactam. Two to five types of chromosomal beta-lactamases, as defined by isoelectric focusing, were readily identified in each species. Isolates of Citrobacter, Enterobacter and Serratia produced higher levels of chromosomal beta-lactamase than corresponding cefotaxime-susceptible strains. In addition, 20 of 57 produced one or two plasmid-determined beta-lactamases, TEM-1, OXA-2, or a novel enzyme, OHIO-1. The penem and carbapenem antibiotics, Sch 34343 and imipenem, were more active than cefotaxime, ceftazidime, ceftriaxone, latamoxef and aztreonam against isolates of Acinetobacter, Citrobacter, Ent. aerogenes, Ent. cloacae and Morganella, whereas imipenem, ceftazidime, and aztreonam were more active against Serratia isolates. The addition of plasmid-determined beta-lactamase increased resistance to piperacillin, cefoperazone and cefamandole but not to cefotaxime, ceftazidime, ceftriaxone, latamoxef, aztreonam, Sch 34343, or imipenem. Of 24 strains susceptible to aminoglycosides, none produced a plasmid-determined beta-lactamase, whereas 20 were found among the 33 strains resistant to aminoglycosides. Resistance of clinical isolates to newer beta-lactams appears to be due primarily to a high level of chromosomal cephalosporinase present without inducing agents. The plasmid-determined beta-lactamases, TEM-1 and OHIO-1, contributed little to resistance to most of the newer beta-lactams but were strongly associated with aminoglycoside resistance in these selected isolates. The greater in-vitro efficacy of the penem and carbapenem antibiotics, Sch 34343 and imipenem, against most of these isolates makes them promising candidates as first line agents against these pathogens.

摘要

我们研究了来自几家医院的192株近期临床分离菌,这些分离菌包括六种对头孢噻肟或拉氧头孢(羟羧氧酰胺菌素)耐药的革兰氏阴性杆菌。所有分离菌对其他几种第三代头孢菌素或单环β-内酰胺类抗生素均耐药。通过等电聚焦法确定,在每个菌种中均可轻易鉴定出两到五种染色体β-内酰胺酶。柠檬酸杆菌、肠杆菌和沙雷氏菌的分离菌产生的染色体β-内酰胺酶水平高于相应的对头孢噻肟敏感的菌株。此外,57株分离菌中有20株产生了一种或两种由质粒决定的β-内酰胺酶,即TEM-1、OXA-2或一种新型酶OHIO-1。青霉烯类和碳青霉烯类抗生素Sch 34343和亚胺培南,对不动杆菌属、柠檬酸杆菌属、产气肠杆菌、阴沟肠杆菌和摩根氏菌属的分离菌比头孢噻肟、头孢他啶、头孢曲松、拉氧头孢和氨曲南更具活性,而亚胺培南、头孢他啶和氨曲南对沙雷氏菌属分离菌更具活性。由质粒决定的β-内酰胺酶的存在增加了对哌拉西林、头孢哌酮和头孢孟多的耐药性,但对头孢噻肟、头孢他啶、头孢曲松、拉氧头孢、氨曲南、Sch 34343或亚胺培南没有影响。在24株对氨基糖苷类敏感的菌株中,没有一株产生由质粒决定的β-内酰胺酶,而在33株对氨基糖苷类耐药的菌株中发现了20株。临床分离菌对新型β-内酰胺类抗生素的耐药性似乎主要是由于在没有诱导剂的情况下存在高水平的染色体头孢菌素酶。由质粒决定的β-内酰胺酶TEM-1和OHIO-1对大多数新型β-内酰胺类抗生素的耐药性贡献不大,但在这些选定的分离菌中与氨基糖苷类耐药性密切相关。青霉烯类和碳青霉烯类抗生素Sch 34343和亚胺培南对大多数这些分离菌具有更高的体外疗效,这使得它们有望成为针对这些病原体的一线药物。

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引用本文的文献

1
Molecular genetic analysis of cephalosporinase production and its role in beta-lactam resistance in clinical isolates of Enterobacter cloacae.阴沟肠杆菌临床分离株中头孢菌素酶产生的分子遗传学分析及其在β-内酰胺耐药中的作用
Antimicrob Agents Chemother. 1987 Feb;31(2):295-9. doi: 10.1128/AAC.31.2.295.
2
Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam combined with ampicillin and broad-spectrum penicillins against defined beta-lactamase-producing aerobic gram-negative bacilli.β-内酰胺酶抑制剂YTR 830、克拉维酸和舒巴坦与氨苄西林及广谱青霉素联合应用对特定产β-内酰胺酶需氧革兰氏阴性杆菌的比较活性
Antimicrob Agents Chemother. 1986 Jun;29(6):980-5. doi: 10.1128/AAC.29.6.980.
3
Molecular epidemiology of OHIO-1 beta-lactamase.
俄亥俄-1型β-内酰胺酶的分子流行病学
Antimicrob Agents Chemother. 1987 Dec;31(12):2007-9. doi: 10.1128/AAC.31.12.2007.