Prevalence of Antimicrobial Resistance Among Respiratory Tract Isolates of Streptococcus pneumoniae in North America: 1997 Results from the SENTRY Antimicrobial Surveillance Program

Gary V. Doern 0 1 Michael A. Pfaller 0 1 Kari Kugler 0 1 Juliana Freeman 0 1 Ronald N. Jones 0 1 0 Received 8 December 1997; revised 20 May 1998. Grant support: The SENTRY Antimicrobial Surveillance Program is sup- ported by a grant from Bristol-Myers Squibb Company. ogy , C606 GH , University of Iowa College of Medicine , Iowa City, Iowa 52242 1 From the Medical Microbiology Division, Department of Pathology, University of Iowa College of Medicine , Iowa City, Iowa As part of the ongoing multinational SENTRY antimicrobial resistance surveillance program, a total of 1,047 respiratory tract isolates of Streptococcus pneumoniae, 845 from 27 United States medical centers and 202 from seven Canadian institutions, were collected between February and June 1997 and characterized in a central laboratory. In the United States, the overall percentages of penicillin-intermediate strains and strains with high-level resistance to penicillin were 27.8% and 16.0%, respectively. In Canada, these values were 21.8% and 8.4%, respectively. Among the 31 centers in the United States and Canada that contributed at least 19 isolates, the combined rate of intermediate plus resistant strains varied between 24.0% and 67.8%. The in vitro activity of 19 other antimicrobials was assessed against all study isolates. Overall rates of resistance among selected agents in the United States and Canada, respectively, were as follows: amoxicillin, 18.1% and 10.5%; cefaclor, 38.3% and 26.2%; cefuroxime, 19.5% and 12.9%; cefpodoxime, 18.6% and 11.4%; cefepime, 8.2% and 4.5%; cefotaxime, 4.0% and 3.0%; macrolides (i.e., erythromycin, azithromycin, and clarithromycin), 11.7% - 14.3% and 5.0% - 7.4%; clindamycin, 3.5% and 3.5%; chloramphenicol, 3.9% and 4.0%; tetracycline, 10.2% and 10.9%; and trimethoprim-sulfamethoxazole, 19.8% and 15.8%. - Penicillin-resistant Streptococcus pneumoniae (PRSP) was described for the first time in 1964 [1]. Two levels of penicillin resistance exist in pneumococci: intermediate (MICs, 0.12 1 mg/mL) and high level (MICs, 2 mg/mL) [2, 3]. Since its original description, PRSP has become a major problem in many parts of the world [4]. See editorial response by Mufson on pages 771 3. Until the early 1990s, however, PRSP remained uncommon in the United States [5, 6]. The latest large multicenter surveillance study conducted in this country during the 1980s revealed an overall rate of penicillin resistance of only 3.8%, with the vast majority of nonsusceptible isolates having only intermediate levels of resistance [6]. By 1992, however, the rate of penicillin resistance had jumped to 17.8% [7]. Since then, four large multicenter surveillance studies have been performed in the United States [8 11]. These studies have documented a steady increase in the prevalence of PRSP in the United States during the past 5 years. In 1993, the overall resistance rate was 22.3% [8]; by 1994 1995 it had reached 24.6% [9]. During the latter part of 1995, penicillin resistance was noted in 27.2% of clinical isolates of S. pneumoniae [10]. The most recent systematic nationwide surveillance study in the United States revealed an overall rate of penicillin resistance of 34.6% during 1996 [11]. Similarly, in Canada, PRSP remained uncommon during the 1980s [12, 13]. However, a 1994 1995 multicenter national surveillance study noted an overall resistance rate of 11.7% among S. pneumoniae isolates in Canada [14]. The principal mechanism of penicillin resistance is the production of altered penicillin-binding proteins [15, 16]. With S. pneumoniae, all b-lactam antimicrobials bind to the same or related penicillin-binding proteins to manifest their antimicrobial effect [17, 18]. As a result, penicillin resistance of S. pneumoniae leads in all cases to at least some degree of cross-resistance to penicillin congeners, cephalosporins, b-lactam/b-lactamase-inhibitor combinations, and carbapenems [19 22]. It is not surprising, therefore, that as penicillin resistance of S. pneumoniae has emerged as a problem, resistance has become apparent to other b-lactams, including even extended-spectrum third-generation cephalosporins [8 10]. Resistance among pneumococci is not restricted to only b-lactam agents. Resistance to non-b-lactams such as the macrolides, tetracyclines, chloramphenicol, fluoroquinolones, and trimethoprim-sulfamethoxazole (TMP-SMZ) is now also observed, and the percentage of strains resistant to some of these agents (e.g., TMP-SMZ) is apparently increasing [8, 9]. The question arises, what are current rates of resistance in North America with this important human pathogen? In an attempt to answer this important question, a multicenter study was conducted in the United States and Canada between February and June 1997 as part of the ongoing SENTRY multinational antimicrobial resistance surveillance program. Materials and Methods Isolates. During the 5-month period of February through June 1997, a total of 845 isolates of S. pneumoniae recovered in the clinical microbiology laboratories of 27 medical centers in the United States and 202 isolates recovered in the laboratories of 7 Canadian hospitals were shipped to the coordinating laboratory, at the University of Iowa College of Medicine (Iowa City), where stock cultures were prepared in defibrinated rabbit blood and frozen at 0707C. Only isolates judged to be the cause of lower respiratory tract infections were submitted. All isolates were chosen randomly from different patients. None of these isolates had been recovered from blood. Frozen isolates were thawed and subcultured twice on 5% sheep blood agar plates prior to further characterization. Antimicrobial susceptibility tests. At the coordinating study center, the identity of isolates was confirmed, and MICs of penicillin and the other 19 antimicrobial agents listed in table 1 were determined by a reference broth-microdilution method [23]. Drugs were obtained as laboratory-grade powders from their respective manufacturers and tested over concentration ranges that yielded on-scale MIC values with 98% of organism-antimicrobial combinations. Mueller-Hinton broth, supplemented with 3% lysed horse blood (100 mL per well), was used as a growth medium. The final inoculum concentration was 5 1 105 cfu/mL. Trays were incubated for 20 24 hours at 357C in ambient air prior to determination of MICs. The MIC was defined as the lowest concentration of a particular agent tested that yielded no visible evidence of growth of the test organism. S. pneumoniae ATCC (American Type Culture Collection) 49169 was used as a control organism throughout this study. Among the 845 isolates of S. pneumoniae recovered in medical center laboratories in the United States, only 56.2% were susceptible to penicillin (MICs, 0.06 mg/mL), 27.8% were intermediate (MICs, 0.12 1 mg/mL), and 16.0% had high-level resistance to penicillin (MICs, 2 mg/mL). The percentages of susceptible, intermediate, and resistant isolates fr (...truncated)