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环丙沙星在汗液中的排泄及多重耐药表皮葡萄球菌

Excretion of ciprofloxacin in sweat and multiresistant Staphylococcus epidermidis.

作者信息

Høiby N, Jarløv J O, Kemp M, Tvede M, Bangsborg J M, Kjerulf A, Pers C, Hansen H

机构信息

Department of Clinical Microbiology, Rigshospitalet, University of Copenhagen, Denmark.

出版信息

Lancet. 1997 Jan 18;349(9046):167-9. doi: 10.1016/S0140-6736(96)09229-X.

Abstract

BACKGROUND

Staphylococcus epidermidis develops resistance to ciprofloxacin rapidly. That this antibiotic is excreted in apocrine and eccrine sweat of healthy individuals might be the reason for the development of such resistance. We assessed whether S epidermidis isolated from the axilla and nasal flora of healthy people could develop resistance to ciprofloxacin after a 1-week course of this antibiotic.

METHODS

The concentration of ciprofloxacin in sweat was measured in seven volunteers after oral administration of 750 mg ciprofloxacin twice daily for 7 days, and the development of resistance in S epidermidis from axilla and nostrils was monitored during and 2 months after the treatment. Genotyping of S epidermidis was done by restriction fragment length polymorphism.

FINDINGS

The mean concentration of ciprofloxacin in sweat increased during the 7 days of treatment-from 2.2 micrograms/mL 2.5 h after the first tablet to 2.5 micrograms/mL after the fifth tablet, and 5.5 micrograms/mL after the 13th tablet. All persons harboured susceptible S epidermidis (minimal inhibitory concentration [MIC] 0.25 microgram/mL) in axilla and nostrils before treatment. Four resistant strains were detected, two intermediate-level (MIC 4-12 micrograms/mL) and two high-level (MIC > 32 micrograms/mL). Three of these strains were found in all the participants, and a ciprofloxacin-sensitive variant of one of the high-level resistant strains was also found before the start of the treatment. The high-level resistant strains were also resistant to methicillin, erythromycin, gentamicin, sulphonamide, and trimethoprim. A mean of 2.7 days after the start of the treatment, development of ciprofloxacin resistance was detected in S epidermidis from the axilla of all persons, compared with 11 days for the appearance of resistant S epidermidis in nostrils. The resistant strains persisted for an average of 37 and 39 days in axilla and nostrils, respectively, after the end of the treatment.

INTERPRETATION

The rapid development of resistance to ciprofloxacin due to excretion of this drug into the sweat might be involved in the development of multiresistant S epidermidis and possibly other skin bacteria in hospitals and in communities with high use of ciprofloxacin or related drugs.

摘要

背景

表皮葡萄球菌对环丙沙星的耐药性发展迅速。这种抗生素在健康个体的顶泌汗腺和小汗腺汗液中排泄,可能是产生这种耐药性的原因。我们评估了从健康人的腋窝和鼻腔菌群分离出的表皮葡萄球菌在接受为期1周的环丙沙星治疗后是否会对其产生耐药性。

方法

7名志愿者每日口服750mg环丙沙星,分两次服用,共7天,测定服药后汗液中环丙沙星的浓度,并在治疗期间及治疗后2个月监测腋窝和鼻孔处表皮葡萄球菌耐药性的发展情况。采用限制性片段长度多态性方法对表皮葡萄球菌进行基因分型。

结果

治疗7天期间,汗液中环丙沙星的平均浓度升高——从服用第一片药后2.5小时的2.2μg/mL升至服用第五片药后的2.5μg/mL,以及服用第13片药后的5.5μg/mL。治疗前,所有受试者腋窝和鼻孔处的表皮葡萄球菌均为敏感菌(最低抑菌浓度[MIC]为0.25μg/mL)。检测到4株耐药菌株,其中2株为中度耐药(MIC为4 - 12μg/mL),2株为高度耐药(MIC> 32μg/mL)。所有受试者中均发现了其中3株耐药菌株,并且在治疗开始前还发现了1株高度耐药菌株的环丙沙星敏感变体。高度耐药菌株对甲氧西林、红霉素、庆大霉素、磺胺类药物和甲氧苄啶也耐药。治疗开始后平均2.7天,所有受试者腋窝处的表皮葡萄球菌检测到环丙沙星耐药性,而鼻孔处出现耐药表皮葡萄球菌的时间为11天。治疗结束后,耐药菌株在腋窝和鼻孔处分别平均持续存在37天和39天。

解读

环丙沙星排泄至汗液中导致的对该药耐药性的快速发展,可能与医院及环丙沙星或相关药物高使用社区中多重耐药表皮葡萄球菌以及可能的其他皮肤细菌的产生有关。

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