回复 21# 蓝鱼o_0
在论坛说说，引起大家的关注是好的，但我认为，如果准备发表在杂志上，而且是可信度比较高的杂志，建议除了引用国内的研究证据以外，还应搜索一下国外的研究证据，进行比较全面的、有根有据的描述，让各个层面的人员心里有底，避免造成不必要的恐慌。
从美国《Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008》来看，滥用消毒剂会不会诱导对消毒剂不敏感的微生物？对消毒剂不敏感的微生物会不会对抗菌药物也降低敏感性？以及二者是否存在交叉耐受？这些问题更多的是一种学术层面上的探讨和研究，就目前的证据来看，这些问题并不影响我们日常抗菌药物的规范使用，以及我们日常的环境消毒方案。当然据我所知，有些消毒剂的厂家把他们的消毒剂对多重耐药菌的杀灭效果作为一个卖点，对于专业人员来说，我相信大家都有自己的判断能力。
Susceptibility of Antibiotic-Resistant Bacteria to Disinfectants
As with antibiotics, reduced susceptibility (or acquired “resistance”) of bacteria to disinfectants can arise by either chromosomal gene mutation or acquisition of genetic material in the form of plasmids or transposons 338, 341-343, 344 , 345, 346. When changes occur in bacterial susceptibility that renders an antibiotic ineffective against an infection previously treatable by that antibiotic, the bacteria are referred to as “resistant.” In contrast, reduced susceptibility to disinfectants does not correlate with failure of the disinfectant because concentrations used in disinfection still greatly exceed the cidal level. Thus, the word "resistance" when applied to these changes is incorrect, and the preferred term is “reduced susceptibility” or “increased tolerance”344, 347. No data are available that show that antibiotic-resistant bacteria are less sensitive to the liquid chemical germicides than antibiotic-sensitive bacteria at currently used germicide contact conditions and concentrations.
MRSA and vancomycin-resistant Enterococcus (VRE) are important health-care–associated agents. Some antiseptics and disinfectants have been known for years to be, because of MICs, somewhat less inhibitory to S. aureus strains that contain a plasmid-carrying gene encoding resistance to the antibiotic gentamicin 344. For example, gentamicin resistance has been shown to also encode reduced susceptibility to propamidine, quaternary ammonium compounds, and ethidium bromide 348, and MRSA strains have been found to be less susceptible than methicillin-sensitive S. aureus (MSSA) strains to chlorhexidine, propamidine, and the quaternary ammonium compound cetrimide 349. In other studies, MRSA and MSSA strains have been equally sensitive to phenols and chlorhexidine, but MRSA strains were slightly more tolerant to quaternary ammonium compounds 350. Two gene families (qacCD [now referred to as smr] and qacAB) are involved in providing protection against agents that are components of disinfectant formulations such as quaternary ammonium compounds. Staphylococci have been proposed to evade destruction because the protein specified by the qacA determinant is a cytoplasmic-membrane–associated protein involved in an efflux system that actively reduces intracellular accumulation of toxicants, such as quaternary ammonium compounds, to intracellular targets 351.
Other studies demonstrated that plasmid-mediated formaldehyde tolerance is transferable from Serratia marcescens to E. coli 352 and plasmid-mediated quaternary ammonium tolerance is transferable from S. aureus to E. coli.353. Tolerance to mercury and silver also is plasmid borne 341, 343-346.
Because the concentrations of disinfectants used in practice are much higher than the MICs observed, even for the more tolerant strains, the clinical relevance of these observations is questionable. Several studies have found antibiotic-resistant hospital strains of common healthcare-associated pathogens (i.e., Enterococcus, P. aeruginosa, Klebsiella pneumoniae, E. coli, S. aureus, and S. epidermidis) to be equally susceptible to disinfectants as antibiotic-sensitive strains 53, 354-356. The susceptibility of glycopeptide-intermediate S. aureus was similar to vancomycin-susceptible, MRSA 357. On the basis of these data, routine disinfection and housekeeping protocols do not need to be altered because of antibiotic resistance provided the disinfection method is effective 358, 359. A study that evaluated the efficacy of selected cleaning methods (e.g., QUAT-sprayed cloth, and QUAT-immersed cloth) for eliminating VRE found that currently used disinfection processes most likely are highly effective in eliminating VRE. However, surface disinfection must involve contact with all contaminated surfaces 358. A new method using an invisible flurorescent marker to objectively evaluate the thoroughness of cleaning activities in patient rooms might lead to improvement in cleaning of all objects and surfaces but needs further evaluation 360.
Lastly, does the use of antiseptics or disinfectants facilitate the development of disinfectant-tolerant organisms? Evidence and reviews indicate enhanced tolerance to disinfectants can be developed in response to disinfectant exposure 334, 335, 346, 347, 361. However, the level of tolerance is not important in clinical terms because it is low and unlikely to compromise the effectiveness of disinfectants of which much higher concentrations are used 347, 362.
The issue of whether low-level tolerance to germicides selects for antibiotic-resistant strains is unsettled but might depend on the mechanism by which tolerance is attained. For example, changes in the permeability barrier or efflux mechanisms might affect susceptibility to both antibiotics and germicides, but specific changes to a target site might not. Some researchers have suggested that use of disinfectants or antiseptics (e.g., triclosan) could facilitate development of antibiotic-resistant microorganisms 334, 335, 363. Although evidence in laboratory studies indicates low-level resistance to triclosan, the concentrations of triclosan in these studies were low (generally <1 μg/mL) and dissimilar from the higher levels used in antimicrobial products (2,000–20,000 μg/mL) 364, 365. Thus, researchers can create laboratory-derived mutants that demonstrate reduced susceptibility to antiseptics or disinfectants. In some experiments, such bacteria have demonstrated reduced susceptibility to certain antibiotics 335. There is no evidence that using antiseptics or disinfectants selects for antibiotic-resistant organisms in nature or that such mutants survive in nature366. ). In addition, the action of antibiotics and the action of disinfectants differ fundamentally. Antibiotics are selectively toxic and generally have a single target site in bacteria, thereby inhibiting a specific biosynthetic process. Germicides generally are considered nonspecific antimicrobials because of a multiplicity of toxic-effect mechanisms or target sites and are broader spectrum in the types of microorganisms against which they are effective 344, 347.
The rotational use of disinfectants in some environments (e.g., pharmacy production units) has been recommended and practiced in an attempt to prevent development of resistant microbes 367, 368. There have been only rare case reports that appropriately used disinfectants have resulted in a clinical problem arising from the selection or development of nonsusceptible microorganisms. |
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