Antibiotic resistance among clinical isolates of Haemophilus influenzae in the United States in 1994 and 1995 and detection of beta-lactamase-positive strains resistant to amoxicillin-clavulanate: results of a national multicenter surveillance study

Abstract

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%.

Antibiotic Susceptibilities Among Recent Clinical Isolates of Haemophilus influenzae and Moraxella catarrhalis from Fifteen Countries

“…In recent reports of studies conducted in North America and Europe, the rates of b-lactamase production found in Moraxella catarrhalis isolates have exceeded 90%, with minor geographic variation [2,4,5,6,8,9]. Most of the Moraxella catarrhalis isolates in the present study were resistant to ampicillin, presumably due to b-lactamase production, as suggested by other reports, but the MIC90 scores remained low for amoxicillin/clavulanate, cefaclor, loracarbef, cefuroxime, azithromycin and ciprofloxacin ( Table 2).…”

“…BLNAR isolates are not only characterized by ampicillin resistance (MIC64 mg/ml), they are also distinguished by reduced susceptibility to amoxicillin/clavulanate and other b-lactam antibiotics [4]. In contrast, clinical isolates of Moraxella catarrhalis, as documented in recent North American and European studies, have reported rates of b-lactamase production of 1 90%, with minor geographic variation [2,4,5,8,9]. Presently, resistance to antibiotics other than ampicillin has not emerged as a concern with regard to Moraxella catarrhalis [2,4].…”

“…Another less common mechanism of resistance in Haemophilus influenzae is the alteration of penicillinbinding proteins, resulting in b-lactamase-negative and ampicillin-resistant (BLNAR) isolates. Isolates with this mechanism of resistance were first reported in 1980 [7] and continue to be isolated, albeit at low frequencies (0.04-2.5%) [2][3][4]8]. BLNAR isolates are not only characterized by ampicillin resistance (MIC64 mg/ml), they are also distinguished by reduced susceptibility to amoxicillin/clavulanate and other b-lactam antibiotics [4].…”

Clinical bacteriology and immunology in acute otitis media in children

“…Serotypes or serogroup 19F, 23F, and United States. 19,20 BLNAR strains had been isolated at low frequencies in the 1980s, but BLNAR strains have rapidly increased at the rate of 19.5% in the 1990s. 22 Recently, the rate of BLNAR was 58.1% in Korea, 37% in Japan, 0%-33% in Europe, and 4%-10.1% in the USA.…”

High nasopharyngeal carriage of β-lactamase-negative ampicillin-resistant Haemophilus influenzae in north Indian school-going children

“…The prevalence of BLNAR increased up to 2.5%-10.1% in 1994-1995. 10 A recent study reported the BLNAR H. infl uenzae in European countries to range from 1.5% to 33.9%. 11 In Japan Hasegawa et al 12 reported 5.8% and 34.5% in BLNAR in 2000 and 2004, respectively.…”