Ronald N. Jones, Qing Li, Bruce Kohut, Douglas J. Biedenbach，Jan Bell, John D. Turnidge
三抗生素软膏（TAO）含有新霉素，多黏菌素B ，杆菌肽，20世纪50年代在美国(USA)作为处方药被推出，自70年代以来便作为非处方药(OTC)用于防止表皮伤口感染。在澳大利亚，TAO限于处方使用。本研究1 ）明确新霉素与其它氨基糖苷类比较的交叉耐药类型; 2 ）明确TAO和个别化合物对菌株，尤其是对莫匹罗星有抗药性的菌株的抗性水平和趋势(USA);3 ）建立TAO对于来自澳大利亚的病原体的抗性基准。来至美国的200株菌株（ z50 ％ 对庆大霉素有耐药性 ）用于交叉耐药性研究，其中包括金黄色葡萄球菌（ 110株 ） ，凝固酶阴性葡萄球菌（CoNS; 50株 ） ，铜绿假单胞菌（ 10株 ），大肠埃希氏菌（ 20 株）和其他肠杆菌属菌（ 10株 ），检测这些菌对于以下抗生素的耐药性，抗生素为TAO，杆菌肽，多黏菌素B ，新霉素，丁胺卡那霉素，庆大霉素，链霉素，妥布霉素，莫匹罗星。1997到2002年期间每年分离出五十株对庆大霉素有抗药性菌株来确定随时间的变化TAO对其的活性是否有所改变。300株澳大利亚分离的菌株(AGARS Program, 2002–2003)也对TAO的耐药性基准进行了研究。在这项研究的各个阶段都使用了培养基稀释法。将软膏进行1:100的稀释，TAO抑制所有凝固酶阴性葡萄球菌，铜绿假单胞菌，肠杆菌分离株，同时在交叉耐药性研究中金黄色葡萄球菌在这一浓度下对TAO有耐药性的为5%。1997年至2002年对TAO具有敏感性的类型在美国没有明显变化。对来自澳大利亚的病原体研究表明，TAO对于耐甲氧西林金黄色葡萄球菌的有效性为98％，对于肠杆菌，甲氧西林敏感性金黄色葡萄球菌，凝固酶阴性葡萄球菌，铜绿假单胞菌的有效性为100 ％，这些观察结果与在美国得到的结果几乎相同。对莫匹罗星有抗药性的金黄色葡萄球菌（ 5 ％ ）和凝固酶阴性葡萄球菌（ 47 ％ ）菌对TAO都具有敏感性。所有的革兰氏阴性菌对莫匹罗星都有耐药性，但被TAO中的新霉素和/或多黏菌素B组分所抑制。结论，氨基糖苷类抗性类型差异很大，并没有一个普遍的测试剂可以准确地预测新霉素的抗性。TAO在美国作为非处方药经过广泛使用，出现抗药性是很罕见的，且并不因数十年来非口服氨基糖苷类的使用而受到影响。 澳大利亚的监测表明，TAO对采集的菌株样本的高敏感性提供了将其转换为OTC药物的可能性。TAO与莫匹罗星相比有更广的抗菌谱，并可用于对付对莫匹罗星有耐药性的革兰氏阳性菌。
Diagnostic Microbiology and Infectious Disease 54 (2006) 63–71
Contemporary antimicrobial activity of triple antibiotic ointment:
a multiphased study of recent clinical isolates in the United States and Australia
Ronald N. Jones, Qing Li, Bruce Kohut, Douglas J. Biedenbach，Jan Bell, John D. Turnidge
Triple antibiotic ointment (TAO) containing neomycin, polymyxin B, and bacitracin was launched in the 1950s in the United States (USA) as a prescription product and then was used over the counter (OTC) since the 1970s (USA) to prevent superficial wound infections. In Australia, TAO has been restricted to prescription use. This study 1) determined cross-resistance patterns of neomycin compared with other aminoglycosides; 2) determined the level and trend of resistance to TAO and individual components especially versus mupirocin-resistant strains (USA); and 3) established the baseline TAO activity level against pathogens from Australia. A total of 200 strains (z50% gentamicinresistant) from the United States were used for the cross-resistance study including Staphylococcus aureus (110), coagulase-negative staphylococci (CoNS; 50), Pseudomonas aeruginosa (10), Escherichia coli (20), and other Enterobacteriaceae (10) tested against TAO, bacitracin, polymyxin B, neomycin, amikacin, gentamicin, streptomycin, tobramycin, and mupirocin. Fifty gentamicin-resistant isolates from each year (1997–2002) were used to determine the activity of TAO over time. Baseline resistance rates of TAO among 300 Australian isolates (AGARS Program, 2002–2003) were also studied. Reference broth microdilution methods were used in all phases of this study. At a 1:100 dilution of the ointment concentration, TAO inhibited all CoNS, Pseudomonas aeruginosa, and Enterobacteriaceae isolates, and resistance to TAO among Staphylococcus aureus at this concentration was only 5% in the cross-resistance study. Patterns of susceptibility in the United States did not significantly vary from 1997 to 2002. Australian pathogens showed that TAO was 98% active against methicillin-resistant Staphylococcus aureus and 100% for Enterobacteriaceae, methicillin-susceptible S. aureus, CoNS, and P. aeruginosa, the rates equivalent to those observed in the United States. Mupirocin-resistant S. aureus (5%) and CoNS (47%) were all TAO-susceptible. All Gram-negative species were also mupirocin-resistant, but inhibited by neomycin and/or polymyxin B components of TAO. In conclusion, aminoglycoside resistance patterns differ significantly, and none of the commonly tested agents could accurately predict neomycin resistance. TAO resistance was rare in the United States after extensive OTC use and was not adversely influenced by decades of parenteral aminoglycoside use. Australian surveillance showed high levels of TAO susceptibility in sampled isolates as a baseline for possible OTC availability. TAO maintains a wider spectrum of activity compared with mupirocin and was usable against mupirocin-resistant Gram-positive strains.