Increased Usage of Antiseptics Is Associated with Reduced Susceptibility in Clinical Isolates of Staphylococcus aureus
Increased Usage of Antiseptics Is Associated with Reduced Susceptibility in Clinical Isolates of Staphylococcus aureus
复制标题
DOI：
10.1128/mbio.00894-18
复制
发表时间：
2018-05-01
期刊：
影响因子：
6.4
通讯作者：
Webber, Mark
中科院分区：
文献类型：
--
作者：
Hardy, Katherine;Sunnucks, Katie;Webber, Mark
医院获得性感染是发病率和死亡率的主要原因，预防感染的制度在感染控制中至关重要。这些措施包括对携带甲氧西林耐药金黄色葡萄球菌(MRSA)的脆弱患者使用包括洗必泰和辛替尼定在内的防腐剂进行非殖民化。然而，人们对杀生剂抗药性的可能发展提出了关切。在这项研究中，我们组装了一组金黄色葡萄球菌分离物，包括在洗必泰和辛替尼定开发之前收集的分离物和分离物，这些分离物来自英国一家主要医院信托基金，期间非殖民化制度发生了变化。我们观察到，在洗必泰高使用期分离株的MIC和最低杀菌浓度(MBC)显著增加。在将辛替尼定引入TRUST后，迅速出现了奥替尼定MIC和MBC增加的菌株。两种杀菌剂之间没有明显的交叉耐药性。采用可变数目串联重复序列分析、qac基因聚合酶链式反应和全基因组测序相结合的方法对分离株进行分型，并研究其可能的耐药机制。没有单一菌株的扩增与杀生剂耐受性下降有关，杀菌剂敏感性与QAC外排泵基因的携带无关。然而，先前与洗必泰出口相关的NorA或Norb外排泵内的突变被发现，这表明这可能是杀生剂耐受的一个重要机制。我们提出的证据表明，面对患者的杀生挑战，分离株正在进化，非殖民化制度的变化反映在分离株易感性的变化上。医院内的重要感染仍然是死亡和疾病的主要原因。我们对抗这一问题的一种方法是将高危患者从携带可导致MRSA等疾病的细菌中分离出来。这是用包括洗必泰和辛替尼定在内的防腐剂完成的。然而，人们担心细菌可能会对这些防腐剂产生抗药性。在这项研究中，我们观察了MRSA的分离株，发现防腐剂的使用与分离株中耐药性的增加之间存在相关性。我们还认为，这些耐受性更强的分离株对防腐剂产生抗药性的机制是改变输出这些药物的输送泵。这些信息表明，我们需要更密切地研究防腐剂对临床重要细菌的影响。
Hospital-acquired infection is a major cause of morbidity and mortality, and regimes to prevent infection are crucial in infection control. These include the decolonization of vulnerable patients with methicillin-resistant Staphylococcus aureus (MRSA) carriage using antiseptics, including chlorhexidine and octenidine. Concern has been raised, however, regarding the possible development of biocide resistance. In this study, we assembled a panel of S. aureus isolates, including isolates collected before the development of chlorhexidine and octenidine and isolates, from a major hospital trust in the United Kingdom during a period when the decolonization regimes were altered. We observed significant increases in the MIC and minimum bactericidal concentration (MBC) of chlorhexidine in isolates from periods of high usage of chlorhexidine. Isolates with increased MICs and MBCs of octenidine rapidly emerged after octenidine was introduced in the trust. There was no apparent cross-resistance between the two biocidal agents. A combination of variable-number tandem repeat (VNTR) analysis, PCR for qac genes, and whole-genome sequencing was used to type isolates and examine possible mechanisms of resistance. There was no expansion of a single strain associated with decreased biocide tolerance, and biocide susceptibility did not correlate with carriage of qac efflux pump genes. Mutations within the NorA or NorB efflux pumps, previously associated with chlorhexidine export, were identified, however, suggesting that this may be an important mechanism of biocide tolerance. We present evidence that isolates are evolving in the face of biocide challenge in patients and that changes in decolonization regimes are reflected in changes in susceptibility of isolates.IMPORTANCE Infection in hospitals remains a major cause of death and disease. One way in which we combat this is by decolonizing at-risk patients from carriage of bacteria which can cause disease such as MRSA. This is done with antiseptics, including chlorhexidine and octenidine. There is concern, however, that bacteria may be able to become resistant to these antiseptics. In this study, we looked at isolates of MRSA and found that there was a correlation between the use of antiseptics and increased resistance in the isolates. We also suggest that the mechanism by which these more tolerant isolates may become resistant to antiseptics is that of changing a transport pump that exports these agents. This information suggests that we need to study the impact of antiseptics on clinically important bacteria more closely.