Doern G V, Brueggemann A B, Pierce G, Holley H P, Rauch A
Clinical Microbiology Laboratories, University of Massachusetts, Worcester 01655, USA.
Antimicrob Agents Chemother. 1997 Feb;41(2):292-7. doi: 10.1128/AAC.41.2.292.
A total of 1,537 clinical isolates of Haemophilus influenzae were recovered in 30 U.S. medical center laboratories between 1 November 1994 and 30 April 1995 and were characterized in a central laboratory with respect to serotype and beta-lactamase production and the in vitro activities of 15 oral antimicrobial agents. Overall, 36.4% of the isolates were found to produce beta-lactamase. The rank order of activity of six cephalosporins on the basis of MICs was cefixime > cefpodoxime > cefuroxime > loracarbef > or = cefaclor > cefprozil. On the basis of current National Committee for Clinical Laboratory Standards (NCCLS) breakpoints ages of isolates found to be resistant or intermediate to these agents were as follows: 0.1, 0.3, 6.4, 16.3, 18.3, and 29.8, respectively (National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 4th ed. M7-A4, 1995). Azithromycin was, on a weight basis, the most potent of the macrolides tested in this study, followed by erythromycin and then clarithromycin. Azithromycin was typically fourfold more active than erythromycin, which was, in turn, slightly more active than clarithromycin. However, when compared on the basis of the frequency of resistance determined by using current NCCLS breakpoints, there was essentially no difference between azithromycin and clarithromycin, i.e., 0.5 and 1.9%, respectively (P = 0.086). Interpretive breakpoints for erythromycin MIC tests versus H. influenzae have not been developed. Resistance to other non- beta-lactam agents was variable, as follows: trimethoprim-sulfamethoxazole, 9.0%; chloramphenicol, 0.2%; tetracycline, 1.3%; and rifampin, 0.3%. Two conspicuous findings in this study were the identification of 39 strains H. influenzae that were beta-lactamase negative but ampicillin intermediate or resistant (BLNAR) and, even more surprisingly, 17 beta-lactamase-positive isolates that were resistant to amoxicillin-clavulanate (BLPACR). Strains of H. influenzae in the first group have heretofore been very uncommon; organisms in the second group have not previously been described in the literature. The percentages of all study isolates comprised of BLNAR and BLPACR organisms were 2.5 and 1.1, respectively. Overall resistance to ampicillin was thus 38.9%, and that to amoxicillin-clavulanate was 4.5%.
1994年11月1日至1995年4月30日期间，美国30家医学中心实验室共分离出1537株流感嗜血杆菌临床分离株，并在中心实验室对其血清型、β-内酰胺酶产生情况以及15种口服抗菌药物的体外活性进行了鉴定。总体而言，36.4%的分离株被发现可产生β-内酰胺酶。基于最低抑菌浓度（MIC），六种头孢菌素的活性排序为：头孢克肟＞头孢泊肟＞头孢呋辛＞氯碳头孢≥头孢克洛＞头孢丙烯。根据美国国家临床实验室标准委员会（NCCLS）当前的折点标准，发现对这些药物耐药或中介的分离株比例分别如下：0.1%、0.3%、6.4%、16.3%、18.3%和29.8%（美国国家临床实验室标准委员会。需氧菌稀释抗菌药敏试验方法，第4版。M7-A4，1995）。按重量计算，阿奇霉素是本研究中所测试的大环内酯类药物中活性最强的，其次是红霉素，然后是克拉霉素。阿奇霉素的活性通常比红霉素高四倍，而红霉素又比克拉霉素略强。然而，根据使用当前NCCLS折点标准确定的耐药频率进行比较时，阿奇霉素和克拉霉素之间基本没有差异，即分别为0.5%和1.9%（P = 0.086）。尚未制定针对流感嗜血杆菌的红霉素MIC试验的解释性折点标准。对其他非β-内酰胺类药物的耐药情况各不相同，如下：复方磺胺甲恶唑为9.0%；氯霉素为0.2%；四环素为1.3%；利福平为0.3%。本研究中有两个显著发现，一是鉴定出39株β-内酰胺酶阴性但对氨苄西林中介或耐药的流感嗜血杆菌（BLNAR），更令人惊讶的是，还有17株对阿莫西林-克拉维酸耐药的β-内酰胺酶阳性分离株（BLPACR）。第一组中的流感嗜血杆菌菌株此前非常罕见；第二组中的菌株此前在文献中未曾描述。所有研究分离株中，BLNAR和BLPACR菌株所占比例分别为2.5%和1.1%。因此，对氨苄西林的总体耐药率为38.9%，对阿莫西林-克拉维酸的耐药率为4.5%。
