Gary V. Doern

Antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in the United States during 1999--2000, including a comparison of resistance rates since 1994--1995.

ABSTRACT A total of 1,531 recent clinical isolates of Streptococcus pneumoniae were collected from 33 medical centers nationwide during the winter of 1999–2000 and characterized at a central laboratory. Of these isolates, 34.2% were penicillin nonsusceptible (MIC ≥ 0.12 μg/ml) and 21.5% were high-level resistant (MIC ≥ 2 μg/ml). MICs to all beta-lactam antimicrobials increased as penicillin MICs increased. Resistance rates among non-beta-lactam agents were the following: macrolides, 25.2 to 25.7%; clindamycin, 8.9%; tetracycline, 16.3%; chloramphenicol, 8.3%; and trimethoprim-sulfamethoxazole (TMP-SMX), 30.3%. Resistance to non-beta-lactam agents was higher among penicillin-resistant strains than penicillin-susceptible strains; 22.4% of S. pneumoniae were multiresistant. Resistance to vancomycin and quinupristin-dalfopristin was not detected. Resistance to rifampin was 0.1%. Testing of seven fluoroquinolones resulted in the following rank order of in vitro activity: gemifloxacin > sitafloxacin > moxifloxacin > gatifloxacin > levofloxacin = ciprofloxacin > ofloxacin. For 1.4% of strains, ciprofloxacin MICs were ≥4 μg/ml. The MIC90s (MICs at which 90% of isolates were inhibited) of two ketolides were 0.06 μg/ml (ABT773) and 0.12 μg/ml (telithromycin). The MIC90 of linezolid was 2 μg/ml. Overall, antimicrobial resistance was highest among middle ear fluid and sinus isolates of S. pneumoniae; lowest resistance rates were noted with isolates from cerebrospinal fluid and blood. Resistant isolates were most often recovered from children 0 to 5 years of age and from patients in the southeastern United States. This study represents a continuation of two previous national studies, one in 1994–1995 and the other in 1997–1998. Resistance rates with S. pneumoniae have increased markedly in the United States during the past 5 years. Increases in resistance from 1994–1995 to 1999–2000 for selected antimicrobial agents were as follows: penicillin, 10.6%; erythromycin, 16.1%; tetracycline, 9.0%; TMP-SMX, 9.1%; and chloramphenicol, 4.0%, the increase in multiresistance was 13.3%. Despite awareness and prevention efforts, antimicrobial resistance with S. pneumoniae continues to increase in the United States.

Prevalence of antimicrobial resistance among respiratory tract isolates of Streptococcus pneumoniae in North America: 1997 results from the SENTRY antimicrobial surveillance program.

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%.

Worldwide Prevalence of Antimicrobial Resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997–1999

The in vitro activities of numerous antimicrobials against clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis from patients with bloodstream and respiratory tract infections in the United States, Canada, Europe, Latin America, and the Asia-Pacific region were studied in the SENTRY Antimicrobial Surveillance Program. Penicillin resistance (minimum inhibitory concentration, > or =2 microg/mL) was noted in all 5 geographic regions, and a high and increasing rate of macrolide resistance among S. pneumoniae isolates was observed. Elevated rates of resistance to clindamycin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline were seen. beta-Lactamase-mediated resistance in H. influenzae to amoxicillin and variable trimethoprim-sulfamethoxazole resistance by region were documented. Resistance to several drugs continues to emerge among pneumococci worldwide, but more stable resistance patterns have been noted for H. influenzae and M. catarrhalis. Continued surveillance of this pathogen group appears to be prudent.

Bloodstream Infections Due to Candida Species: SENTRY Antimicrobial Surveillance Program in North America and Latin America, 1997-1998

ABSTRACT An international program of surveillance of bloodstream infections (BSI) in the United States, Canada, and Latin America detected 306 episodes of candidemia in 34 medical centers (22 in the United States, 6 in Canada, and 6 in Latin America) in 1997 and 328 episodes in 34 medical centers (22 in the United States, 5 in Canada, and 7 in Latin America) in 1998. Of the 634 BSI, 54.3% were due to Candida albicans, 16.4% were due to C. glabrata, 14.9% were due to C. parapsilosis, 8.2% were due to C. tropicalis, 1.6% were due to C. krusei, and 4.6% were due to other Candida spp. The percentage of BSI due to C. albicans decreased very slightly in the United States between 1997 and 1998 (56.2 to 54.4%;P = 0.68) and increased in both Canada (52.6 to 70.1%; P = 0.05) and Latin America (40.5 to 44.6%;P = 0.67). C. glabrata was the second most common species observed overall, and the percentage of BSI due toC. glabrata increased in all three geographic areas between 1997 and 1998. C. parapsilosis was the third most prevalent BSI isolate in both Canada and Latin America, accounting for 7.0 and 18.5% of BSI, respectively. Resistance to fluconazole (MIC, ≥64 μg/ml) and itraconazole (MIC, ≥1.0 μg/ml) was observed infrequently in both 1997 (2.3 and 8.5%, respectively) and 1998 (1.5 and 7.6%, respectively). Among the different species ofCandida, resistance to fluconazole and itraconazole was observed in C. glabrata and C. krusei, whereas isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to both fluconazole (98.9 to 100% susceptible) and itraconazole (96.4 to 100% susceptible). Isolates from Canada and Latin America were generally more susceptible to both triazoles than U.S. isolates were. Continued surveillance appears necessary to detect these important changes.

Epidemiology of Candidemia: 3-Year Results from the Emerging Infections and the Epidemiology of Iowa Organisms Study

ABSTRACT Bloodstream infections due to Candida species cause significant morbidity and mortality. Surveillance for candidemia is necessary to detect trends in species distribution and antifungal resistance. We performed prospective surveillance for candidemia at 16 hospitals in the State of Iowa from 1 July 1998 through 30 June 2001. Using U.S. Census Bureau and Iowa Hospital Association data to estimate a population denominator, we calculated the annual incidence of candidemia in Iowa to be 6.0 per 100,000 of population. Candida albicans was the most common species detected, but 43% of candidemias were due to species other than C. albicans. Overall, only 3% of Candida species were resistant to fluconazole. However, Candida glabrata was the most commonly isolated species other than C. albicans and demonstrated some resistance to azoles (fluconazole MIC at which 90% of the isolates tested are inhibited, 32 μg/ml; 10% resistant, 10% susceptible dose dependent). C. glabrata was more commonly isolated from older patients (P = 0.02) and caused over 25% of candidemias among persons 65 years of age or older. The investigational triazoles posaconazole, ravuconazole, and voriconazole had excellent in vitro activity overall against Candida species. C. albicans is the most important cause of candidemia and remains highly susceptible to available antifungal agents. However, C. glabrata has emerged as an important and potentially antifungal resistant cause of candidemia, particularly among the elderly.

Evidence for Transfer of CMY-2 AmpC β-Lactamase Plasmids between Escherichia coli and Salmonella Isolates from Food Animals and Humans

ABSTRACT Escherichia coli is an important pathogen that shows increasing antimicrobial resistance in isolates from both animals and humans. Our laboratory recently described Salmonellaisolates from food animals and humans that expressed an identical plasmid-mediated, AmpC-like β-lactamase, CMY-2. In the present study, 59 of 377 E. coli isolates from cattle and swine (15.6%) and 6 of 1,017 (0.6%) isolates of human E. coli from the same geographic region were resistant to both cephamycins and extended-spectrum cephalosporins. AnampC gene could be amplified with CMY-2 primers in 94.8% of animal and 33% of human isolates. Molecular epidemiological studies of chromosomal DNA revealed little clonal relatedness among the animal and human E. coli isolates harboring the CMY-2 gene. The ampC genes from 10 animal and human E. coli isolates were sequenced, and all carried an identical CMY-2 gene. Additionally, all were able to transfer a plasmid containing the CMY-2 gene to a laboratory strain of E. coli. CMY-2 plasmids demonstrated two different plasmid patterns that each showed strong similarities to previously describedSalmonella CMY-2 plasmids. Additionally, Southern blot analyses using a CMY-2 probe demonstrated conserved fragments among many of the CMY-2 plasmids identified in Salmonella andE. coli isolates from food animals and humans. These data demonstrate that common plasmids have been transferred between animal-associated Salmonella and E. coli, and identical CMY-2 genes carried by similar plasmids have been identified in humans, suggesting that the CMY-2 plasmid has undergone transfer between different bacterial species and may have been transmitted between food animals and humans.

Antimicrobial Resistance among Gram-Negative Bacilli Causing Infections in Intensive Care Unit Patients in the United States between 1993 and 2004

ABSTRACT During the 12-year period from 1993 to 2004, antimicrobial susceptibility profiles of 74,394 gram-negative bacillus isolates recovered from intensive care unit (ICU) patients in United States hospitals were determined by participating hospitals and collected in a central location. MICs for 12 different agents were determined using a standardized broth microdilution method. The 11 organisms most frequently isolated were Pseudomonas aeruginosa (22.2%), Escherichia coli (18.8%), Klebsiella pneumoniae (14.2%), Enterobacter cloacae (9.1%), Acinetobacter spp. (6.2%), Serratia marcescens (5.5%), Enterobacter aerogenes (4.4%), Stenotrophomonas maltophilia (4.3%), Proteus mirabilis (4.0%), Klebsiella oxytoca (2.7%), and Citrobacter freundii (2.0%). Specimen sources included the lower respiratory tract (52.1%), urine (17.3%), and blood (14.2%). Rates of resistance to many of the antibiotics tested remained stable during the 12-year study period. Carbapenems were the most active drugs tested against most of the bacterial species. E. coli and P. mirabilis remained susceptible to most of the drugs tested. Mean rates of resistance to 9 of the 12 drugs tested increased with Acinetobacter spp. Rates of resistance to ciprofloxacin increased over the study period for most species. Ceftazidime was the only agent to which a number of species (Acinetobacter spp., C. freundii, E. aerogenes, K. pneumoniae, P. aeruginosa, and S. marcescens) became more susceptible. The prevalence of multidrug resistance, defined as resistance to at least one extended-spectrum cephalosporin, one aminoglycoside, and ciprofloxacin, increased substantially among ICU isolates of Acinetobacter spp., P. aeruginosa, K. pneumoniae, and E. cloacae.

Survey of Bloodstream Infections Due to Gram-Negative Bacilli: Frequency of Occurrence and Antimicrobial Susceptibility of Isolates Collected in the United States,Canada, and Latin America for the SENTRY Antimicrobial Surveillance Program, 1997

During 1997, a total of 4,267 nosocomial and community-acquired bloodstream infections due to gram-negative organisms were reported from SENTRY hospitals in Canada (8 sites), the United States (30 sites), and Latin America (10 sites). Escherichia coli was the most common isolate (41% of all gram-negative isolates), followed by Klebsiella species (17.9%), Pseudomonas aeruginosa (10.6%), and Enterobacter species (9.4%). For all gram-negative isolates combined, the most active antimicrobials tested were meropenem, imipenem, and cefepime. The quinolones levofloxacin (MIC90, 2 microg/mL), ciprofloxacin (MIC90, 1 microg/mL), gatifloxacin (MIC90, 2 microg/mL), sparfloxacin (MIC90, 2 microg/mL), and trovafloxacin (MIC90, 2 microg/mL) were also active against most isolates. Bloodstream infection isolates from Latin America were uniformly more resistant to all classes of antimicrobial agents tested than were isolates from Canada or the United States. Resistance phenotypes consistent with extended-spectrum beta-lactamase production were also most common among E. coli and Klebsiella species from Latin America. Further investigation of the reasons for regional differences in resistance patterns is needed, as is ongoing surveillance to detect resistance trends and to guide antimicrobial use.

Antimicrobial Susceptibility Testing

There are few activities in the clinical microbiology laboratory that utilize more technologist time and laboratory resources than antimicrobial susceptibility testing (AST). It has been suggested that, at least in terms of direct relevance to the care of patients with infection, AST may be the

International surveillance of blood stream infections due to Candida species in the European SENTRY program: species distribution and antifungal susceptibility including the investigational triazole and echinocandin agents

The SENTRY Antimicrobial Surveillance Program, an international study of blood stream infections (BSIs), detected 170 episodes of candidemia in 20 European medical centers (13 nations) between January and December, 1997. Twenty-three percent of the candidal BSI occurred in patients hospitalized in an intensive care unit, 21% in patients in an internal medicine service, 13% in patients in a surgical service, and 9% in patients in an oncology service. Overall, 53% of the BSI were attributable to Candida albicans followed in prevalence by C. parapsilosis (21%), C. glabrata (12%), C. tropicalis (6%), C. famata (2%), C. krusei (1%), and C. inconspicua (1%). As observed previously in Canada and Latin America, C. parapsilosis and not C. glabrata, was the most common non-albicans species causing yeast BSI in Europe. The proportion of these candidemias attributable to C. albicans varied widely from 0-100% among the 20 European centers. Among the different species of Candida, resistance to fluconazole (MIC, > or = 64 micrograms/mL) and itraconazole (MIC, > or = 1.0 microgram/mL) was observed with C. glabrata and C. krusei and was observed more rarely among other species (e.g., C. inconspicua). Isolates of C. albicans, C. parapsilosis, C. tropicalis, and C. guilliermondii were all highly susceptible to both fluconazole and itraconazole. Furthermore, the investigational triazoles (BMS-207147, Sch 56592, and voriconazole) and an echinocandin (MK-0991) all demonstrated potent in vitro activity (MIC90s, 0.5, 0.5, 1.0, and 2.0 micrograms/mL, respectively) against these isolates. Continued surveillance at an international level will be important to monitor trends in species distribution and antifungal susceptibility among invasive strains of Candida.