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Effects of Formulation on Microbicide Potency and Mitigation of the Development of Bacterial Insusceptibility

机译：配方对杀菌力的影响和细菌敏感性的降低

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Risk assessments of the potential for microbicides to select for reduced bacterial susceptibility have been based largely on data generated through the exposure of bacteria to microbicides in aqueous solution. Since microbicides are normally formulated with multiple excipients, we have investigated the effect of formulation on antimicrobial activity and the induction of bacterial insusceptibility. We tested 8 species of bacteria (7 genera) before and after repeated exposure (14 passages), using a previously validated gradient plating system, for their susceptibilities to the microbicides benzalkonium chloride, benzisothiozolinone, chlorhexidine, didecyldimethyl ammonium chloride, DMDM-hydantoin, polyhexamethylene biguanide, thymol, and triclosan in aqueous solution (nonformulated) and in formulation with excipients often deployed in consumer products. Susceptibilities were also assessed following an additional 14 passages without microbicide to determine the stability of any susceptibility changes. MICs and minimum bactericidal concentrations (MBC) were on average 11-fold lower for formulated microbicides than for nonformulated microbicides. After exposure to the antimicrobial compounds, of 72 combinations of microbicide and bacterium there were 19 ≥4-fold (mean, 8-fold) increases in MIC for nonformulated and 8 ≥4-fold (mean, 2-fold) increases in MIC for formulated microbicides. Furthermore, there were 20 ≥4-fold increases in MBC (mean, 8-fold) for nonformulated and 10 ≥4-fold (mean, 2-fold) increases in MBC for formulated microbicides. Susceptibility decreases fully or partially reverted back to preexposure values for 49% of MICs and 72% of MBCs after further passage. In , formulated microbicides exhibited greater antibacterial potency than unformulated actives and susceptibility decreases after repeated exposure were lower in frequency and extent.
机译：杀菌剂选择降低细菌敏感性的潜力的风险评估主要基于通过细菌暴露于水溶液中的杀菌剂而产生的数据。由于杀微生物剂通常与多种赋形剂一起配制，因此我们研究了该制剂对抗菌活性和诱导细菌敏感性的影响。我们使用先前验证的梯度平板系统测试了反复暴露（14传）之前和之后的8种细菌（7个属）对杀菌剂对苯扎氯铵，苯并异硫唑啉酮，氯己定，二癸基二甲基氯化铵，DMDM-乙内酰脲，聚六亚甲基醚的敏感性。双胍，百里香酚和三氯生在水溶液中（非配方）以及与通常在消费品中使用的赋形剂一起配制而成。在没有杀微生物剂的情况下，经过另外14次传代后，还对药敏性进行了评估，以确定药敏性变化的稳定性。配制的杀菌剂的MIC和最低杀菌浓度（MBC）平均比未配制的杀菌剂低11倍。暴露于抗微生物化合物后，在72种杀菌剂和细菌的组合中，非配方产品的MIC增加19≥4倍（平均8倍），而非配方药物的MIC增加8≥4倍（平均2倍）。配制的杀菌剂。此外，未配制的杀微生物剂的MBC增加20≥4倍（平均8倍），MBC增长10≥4倍（平均2倍）。进一步通过后，49％的MIC和72％的MBC的磁化率完全或部分恢复为接触前值。在中，配制的杀菌剂比未配制的活性剂显示出更大的抗菌效力，并且在反复接触后，敏感性和敏感性降低的频率和程度均较低。

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