Comparative surveillance study of telavancin activity against recently collected gram-positive clinical isolates from across the United States.

Telavancin is an investigational, rapidly bactericidal lipoglycopeptide antibiotic that is being developed to treat serious infections caused by gram-positive bacteria. A baseline prospective surveillance study was conducted to assess telavancin activity, in comparison with other agents, against contemporary clinical isolates collected from 2004 to 2005 from across the United States. Nearly 4,000 isolates were collected, including staphylococci, enterococci, and streptococci (pneumococci, beta-hemolytic, and viridans). Telavancin had potent activity against Staphylococcus aureus and coagulase-negative staphylococci (MIC range, 0.03 to 1.0 microg/ml), independent of resistance to methicillin or to multiple agents. Telavancin activity was particularly potent against all streptococcal groups (MIC(90)s, 0.03 to 0.12 microg/ml). Telavancin had excellent activity against vancomycin-susceptible enterococci (MIC(90), 1 microg/ml) and was active against VanB strains of vancomycin-resistant enterococci (MIC(90), 2 microg/ml) but less active against VanA strains (MIC(90), 8 to 16 microg/ml). Telavancin also demonstrated activity against vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus strains (MICs, 0.5 microg/ml to 1.0 microg/ml and 1.0 microg/ml to 4.0 microg/ml, respectively). These data may support the efficacy of telavancin for treatment of serious infections with a wide range of gram-positive organisms.

In vitro activity of telavancin against recent Gram-positive clinical isolates: results of the 2004-05 Prospective European Surveillance Initiative.

OBJECTIVES: Telavancin is a novel semi-synthetic lipoglycopeptide currently in late-stage clinical development for the treatment of serious infections due to Gram-positive bacteria. The objective of this study was to provide a baseline prospective assessment of its in vitro activity against a large and diverse collection of Gram-positive clinical isolates from Europe and Israel. METHODS: Gram-positive clinical isolates, collected between October 2004 and December 2005 from 36 hospital laboratories in 15 countries, were tested by broth microdilution using CLSI methodology. RESULTS: In total, 3206 isolates were collected. Telavancin had potent activity against Staphylococcus aureus and coagulase-negative staphylococci (MIC range < or =0.015 to 2 mg/L), independent of resistance to methicillin or to multiple drugs. Telavancin had particularly strong activity against streptococcal isolates (MIC range < or =0.001 to 0.5 mg/L), including penicillin-resistant and multiple drug-resistant Streptococcus pneumoniae and erythromycin non-susceptible beta-haemolytic and viridans group streptococci. Telavancin also had excellent activity against vancomycin-susceptible enterococci (MIC(90) 0.5 mg/L), and although its MICs were elevated against VanA strains (Enterococcus faecalis MIC(90) 8 mg/L and Enterococcus faecium MIC(90) 4 mg/L), its MIC(90) was substantially lower than observed with available glycopeptides. CONCLUSIONS: Telavancin has potent in vitro activity against contemporary Gram-positive clinical isolates from diverse geographic areas in Europe and Israel.

Antimicrobial resistance trends among sinus isolates of Streptococcus pneumoniae in the United States (2001-2005).

OBJECTIVE: To test the susceptibility of Streptococcus pneumoniae sinus isolates collected across the United States against commonly used antimicrobial agents. STUDY DESIGN AND SETTING: S. pneumoniae sinus isolates (N = 847) collected as part of the Tracking Resistance in the US Today Surveillance Program from 2001 to 2005 were tested against 8 antimicrobial agents. RESULTS: In ascending order, the relative activities (% susceptible) were penicillin (51.8%), trimethoprim/sulfamethoxazole (TMP/SMX) (57.6%), erythromycin (59.5%), cefuroxime (62.0%), amoxicillin/clavulanate (85.5%), clindamycin (86.1%), levofloxacin (99.4%), and linezolid (100%; for 2004 and 2005 respiratory seasons, only). Resistance rates over the 5 years remained generally stable, although resistance to amoxicillin/clavulanate nearly doubled (from 6.5% to 12.9%). Forty percent of isolates were resistant to >or=2 agents tested. CONCLUSIONS AND SIGNIFICANCE: Susceptibility trends among sinus S. pneumoniae isolates appear to have stabilized over the past 5 years. Resistance rates remain elevated for penicillin and macrolides, whereas the high prevalence of multidrug resistance remains a concern.

Stable antimicrobial susceptibility rates for clinical isolates of Pseudomonas aeruginosa from the 2001-2003 tracking resistance in the United States today surveillance studies.

From 2001 to 2003, rates of susceptibility to piperacillin-tazobactam (86%), ceftazidime (80%), ciprofloxacin (68%), and levofloxacin (67%) did not decrease or decreased by <1.5%, whereas the rate of susceptibility to gentamicin decreased by 3.2% (from 75.5% to 72.3%) and the rate of susceptibility to imipenem decreased by 5.6% (from 84.4% to 78.8%), for 2394 clinical isolates of Pseudomonas aeruginosa collected in the Tracking Resistance in the United States Today surveillance studies. Rates of multidrug resistance (i.e., resistance to > or =3 antimicrobial agents) increased from 7.2% in 2001 to 9.9% in 2003 and were significantly higher for isolates from the East North Central and Mid-Atlantic regions of the United States than for isolates from other regions. Analysis of minimum inhibitory concentrations (MICs) suggested that combining an antipseudomonal beta -lactam with ciprofloxacin or levofloxacin would yield a 3.4%-7.1% increase in the percentage of isolates susceptible to the combination, compared with the beta -lactam alone. Ratios of the area under the serum concentration-time curve values for free drug to modal MICs for ciprofloxacin and levofloxacin were similar and were >125 (target ratio), whereas those ratios for gatifloxacin and moxifloxacin were significantly lower. Ongoing surveillance of P. aeruginosa is essential.

Susceptibility of antimicrobial-resistant urinary Escherichia coli isolates to fluoroquinolones and nitrofurantoin.

In vitro surveillance data from across the United States indicate that approximately 10%-20% of urinary Escherichia coli isolates from female outpatients are resistant to trimethoprim-sulfamethoxazole (TMP-SMX). Alternative therapies for uncomplicated urinary tract infections in women include fluoroquinolones and nitrofurantoin, but the activities of these agents against TMP-SMX-resistant isolates are rarely reported. Among TMP-SMX-resistant urinary E. coli isolates tested in US laboratories from 1998 through 2001, 9.5% (5767 of 60,414) were resistant to ciprofloxacin and 1.9% (1214 of 63,817) were resistant to nitrofurantoin; 10.4% of ciprofloxacin-resistant isolates (683 of 6560) were resistant to nitrofurantoin. An association between resistance to fluoroquinolones and nitrofurantoin in E. coli has not been previously reported and warrants further study.

Regional trends in antimicrobial resistance among clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States: results from the TRUST Surveillance Program, 1999-2000.

The ongoing TRUST (Tracking Resistance in the United States Today) study, which began monitoring antimicrobial resistance among respiratory pathogens in 1996, routinely tracks resistance at national and regional levels. The 1999-2000 TRUST study analyzed 9499 Streptococcus pneumoniae, 1934 Haemophilus influenzae, and 1108 Moraxella catarrhalis isolates that were prospectively collected from 239 laboratories across the 9 US Bureau of the Census regions. Penicillin-resistant S. pneumoniae varied significantly by region, from 8.3% to 24.8% (P<.001). In each region, penicillin resistance closely predicted resistance to other beta-lactams, macrolides, and trimethoprim-sulfamethoxazole. Levofloxacin resistance was 0.5% nationally (regional range, 0.1%-1.0%). Multidrug resistance also varied significantly (P<.001) by region. beta-Lactamase production among H. influenzae varied significantly (regional range, 24.0%-34.6%) and M. catarrhalis (86.2%-96.8%) also varied by region. Notable variation in regional antimicrobial resistance rates (S. pneumoniae) and beta-lactamase production (H. influenzae, M. catarrhalis) exists throughout the United States.

Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998-2002).

To identify factors associated with antimicrobial resistance, data were analyzed from 27,828 isolates of Streptococcus pneumoniae submitted to the Tracking Resistance in the United States Today (TRUST) surveillance program during 4 consecutive respiratory seasons. From the 1998-1999 season to the 2001-2002 season, the prevalence of azithromycin resistance increased by 4.8% to 27.5%, the prevalence of penicillin resistance increased by 3.7% to 18.4%, the prevalence of ceftriaxone resistance increased by 0.5% to 1.7%, and the prevalence of levofloxacin resistance increased by 0.3% to 0.9%. Isolates recovered from patients <18 years of age and lower respiratory tract specimens had elevated rates of penicillin, azithromycin, and trimethoprim-sulfamethoxazole resistance (P<.00001); penicillin resistance correlated with coresistance to trimethoprim-sulfamethoxazole (87.3%), azithromycin (76.3%), ceftriaxone (9.1%), and levofloxacin (1.3%) (P<.00001). Only 62 (0.2%) of 27,828 isolates were concurrently resistant to penicillin and levofloxacin. Minimum inhibitory concentrations (MICs) of penicillin correlated strongly with MICs of ceftriaxone (R2=0.90), trimethoprim-sulfamethoxazole (R2=0.53), and azithromycin (R2=0.41). Patient age, specimen source, and penicillin resistance were factors associated with antimicrobial resistance, particularly for nonfluoroquinolone antimicrobial agents.

The application of information technology to regional, national, and global surveillance of antimicrobial resistance.

Establishing local, national, and global surveillance networks for monitoring the dissemination of antimicrobial resistance and detecting the emergence of new resistance mechanisms has been recommended by the American Society for Microbiology Task Force on Antibiotic Resistance and other national organizations. While the need to develop and deploy surveillance strategies cannot be argued, the design and implementation of effective regional, national, and global surveillance networks is a daunting task with geographic, participatory, logistic, and funding challenges. Using information technology to capture, combine, collate, and analyze daily clinical microbiology laboratory data would seem to be a far more robust and logical approach to surveillance than traditional centralized studies that generally focus on only a few bacterial species or on isolates from a single body site. Information technology allows long-term, continuous tracking of antimicrobial resistance trends among large numbers of isolates over a broad range of species, and across entire regions or countries. The rationale for wanting to use networks of clinical laboratories for surveillance is obvious: susceptibility data are generated every day by thousands of laboratories located around the world, and most of these laboratories perform antimicrobial susceptibility testing on the bacterial species that pose the greatest public health problems. By virtue of information technology, large volumes of data can readily be managed and stored to allow timely and thorough analysis on institutional, regional, national, and global levels.

The activity of levofloxacin and other antimicrobials against clinical isolates of Streptococcus pneumoniae collected worldwide during 1999-2002.

Streptococcus pneumoniae is the most important causative bacterial pathogen in respiratory infections. Globally, increasing levels of resistant strains highlight the need for continued surveillance programs to guide antibiotic choice. The current study compared susceptibility results of 4,788 strains of S. pneumoniae collected during 2001-2002 to susceptibility results from 3,884 strains collected from the same hospitals during 1999-2000. Participant centers were dispersed throughout five regions. By region, the prevalence of penicillin-resistant S. pneumoniae and percentage change from the previous 1999-2000 study was Mexico (26.0%, 12.5%), Brazil (7.9%; 5.5%), Asia (China, Hong Kong, South Korea, Thailand) (44.1%; 0.8%), Europe (France, Germany, Italy, Spain, UK) (11.1%; -0.6%) and South Africa (7.9; -1.8%). Multidrug-resistant (MDR) strains of S. pneumoniae were most frequently isolated from Asia (36.3%) compared with approximately 5% in the other four regions. Increases in the incidence of MDR isolates in Mexico (13.5%), Brazil (1.7%) and Asia (6.1%) were reported with no increases in MDR in South Africa and Europe. Levofloxacin resistance was rarely associated with MDR phenotypes. Levofloxacin maintained an MIC(90) of 1 microg/ml against the isolates collected from all five regions with no change during the study periods, despite differences in levofloxacin resistance rates between regions or nations (0%-3.2%). The prevalence of levofloxacin resistance (MIC > or =8 microg/ml) increased only slightly over the study period in Europe (0.3%-0.7%) and in Asia (3.0-3.2%), but little or no change was seen in Mexico (3.8%-0%) or Brazil or South Africa, where no levofloxacin resistant isolates were detected in either study period.

Activity of cefditoren against beta-lactamase-positive and -negative Haemophilus influenzae and Moraxella catarrhalis.

Cefditoren is a novel broad-spectrum oral cephalosporin. To determine the influence of beta-lactamase production on cefditoren activity, 1,170 H. influenzae and 641 M. catarrhalis isolated during 2000 were tested by NCCLS broth microdilution methodology (M7-A5, 2000). Against H. influenzae the potency of cefditoren (MIC(90,) 0.015 microg/mL) was similar to that of ceftriaxone (MIC(90,) < or = 0.015 microg/mL) and levofloxacin (MIC(90,) 0.015 microg/mL), and its MIC distribution was unaffected by beta-lactamase production. In comparison, the beta-lactamase status of M. catarrhalis affected the potency of all beta-lactams tested, including cefditoren, as well as trimethoprim-sulfamethoxazole. However, regardless of the presence of beta-lactamase, cefditoren demonstrated potent activity, as concentrations of 0.5 and 1 microg/mL inhibited 93.1 and 100% of M. catarrhalis isolates, respectively. We conclude that cefditoren is highly active in vitro against beta-lactamase-positive H. influenzae and M. catarrhalis.

In vitro susceptibility of recent clinical isolates of pneumococci to the investigational cephalosporin cefditoren.

From February to June 2000, 2,597 isolates of Streptococcus pneumoniae were prospectively collected from 146 clinical laboratories across the United States (US) and tested to evaluate the in vitro activity of cefditoren, an investigational oral cephalosporin. In all, 2,492 isolates (96.0%) had a cefditoren MIC of 0.5 microg/mL or less, 74 isolates (2.8%) had an MIC of 1 microg/mL, 30 isolates (1.2%) had an MIC of 2 microg/mL, and 1 isolate (<0.1%) had an MIC of 4 microg/mL. Among the beta-lactams tested, the rank order of potency (MIC(90,) microg/mL) was cefditoren (0.5) > ceftriaxone (1) > amoxicillin-clavulanate (2) > cefuroxime (4) > cefprozil (8). Penicillin-resistant isolates (n = 443; 17.1%) were inhibited by lower concentrations (MIC(90,) microg/mL; MIC range,) of cefditoren (1; 0.03-4) than ceftriaxone (2; 0.25- > 2), amoxicillin-clavulanate (8; 0.5- > 8), cefuroxime (16; 2- > 16), and cefprozil (32; 2- > 32). Cefditoren MIC(90)s against cefuroxime-resistant (n = 640) and ceftriaxone-resistant (n = 89) isolates were 1 and 2 microg/mL, respectively. All isolates with reduced susceptibility to cefditoren (MIC, 2 or 4 microg/mL; n = 31) were resistant to penicillin, cefuroxime, and ceftriaxone. The potent in vitro activity of cefditoren against a recent US collection of pneumococci as demonstrated in this study supports its continued development for oral empiric therapy in outpatients with respiratory tract infections.

Antimicrobial susceptibilities of Streptococcus pyogenes isolated from respiratory and skin and soft tissue infections: United States LIBRA surveillance data from 1999.

This study evaluated current levels of antimicrobial resistance and associated demographic trends among clinical isolates of Streptococcus pyogenes in the United States as part of the LIBRA surveillance initiative. In 1999, 2,742 isolates of S. pyogenes (2,039 respiratory; 405 skin and soft tissue; 148 blood) were collected from 324 clinical laboratories and centrally tested for antimicrobial susceptibility by the broth microdilution method. All isolates were susceptible to penicillin (MIC(90,) < or = 0.06 microg/mL), ceftriaxone (MIC(90,) < or =0.03 microg/mL), vancomycin (MIC(90,) 0.5 microg/mL), levofloxacin (MIC(90,) 1 microg/mL), and moxifloxacin (MIC(90,) 0.25 microg/mL). Twenty-four (0.9%) azithromycin-intermediate (MIC, 1 microg/mL) and 170 (6.2%) azithromycin-resistant (MIC, > or = 2 microg/mL) isolates were identified. Regionally, azithromycin resistance varied by < 5%, ranging from 3.0% in New England to 7.7% in the Pacific region. Azithromycin resistance was significantly higher (P < 0.001) among patients aged 15-64 years (8.3%) than patients < or =14 years (4.3%). This study found higher rates of macrolide resistance among S. pyogenes than previously reported in the United States and suggests that macrolide resistance is common among respiratory isolates from both younger and older patients. Fluoroquinolones (moxifloxacin > levofloxacin) demonstrated potent in vitro activity against all isolates of S. pyogenes tested, including those from skin and soft tissue infections. Given the higher rates of macrolide resistance reported in other countries and the seriousness of invasive infections, continued antimicrobial surveillance of S. pyogenes in the United States would be prudent.

Epidemiology and antibiotic susceptibility of bacteria causing skin and soft tissue infections in the USA and Europe: a guide to appropriate antimicrobial therapy.

Susceptibility data for all organisms associated with a range of skin and soft tissue infections (SSTI) in hospitalised patients were studied. Data were reported by clinical laboratories in the USA, France, Germany, Italy and Spain during 2001 which participate in The Surveillance Network (TSN). Staphylococcus aureus, Enterococcus spp. and coagulase-negative staphylococci (CNS), Escherichia coli and Pseudomonas aeruginosa were the most prevalent pathogens in all countries. MRSA was detected in 44.4, 34.7, 12.4, 41.8 and 32. 4% of S. aureus in each country, respectively. The majority of MRSA were cross resistant to other compound classes tested except for vancomycin (100% susceptible) trimethoprim-sulphamethoxazole with range 1.7% (France) to 15.9% (Italy) resistant, and gentamicin with range 12.2% (France) to 87.0% (Italy) resistant. More than 99.0% of MSSA tested susceptible to ceftriaxone and >94.9% to trimethoprim-sulphamethoxazole. 87.2% (France) to 94.6% of MSSA (Germany) were ciprofloxacin susceptible; 73.2% (USA) to 86.6% (Spain) were erythromycin susceptible; 85.4% (Italy) to 99.2% (France) were gentamicin susceptible. MSSA were more frequently found and generally more antibiotic susceptible from out patients. Overall, 100% of Streptococcus agalactiae and Streptococcus pyogenes were susceptible to penicillin, ceftriaxone and cefotaxime. Macrolide resistance was common among S. agalactiae (20.7%, Germany to 10%, Italy and Spain), S. pyogenes (19.2%, France to 11.1%, USA) and viridans streptococci (25.7%, France to 14.1%, Germany). Vancomycin-resistant Enterococcus spp. were uncommon outside the USA (17.5%) and Italy (7.4%). For all countries susceptibility of E. coli was 100% to imipenem, >98.7% to amikacin, >96.0% to ceftriaxone and cefotaxime. Susceptibility of E. coli isolates to ciprofloxacin was 77.6% in Spain to 94.3% in Germany. Klebsiella spp., Proteus spp., Citrobacter spp. and Enterobacter spp. displayed varying susceptibilities between countries to drugs tested. Putative extended spectrum beta-lactamase expression in E. coli remained rare comprising 4-5% of isolates in USA, Italy and Spain and in France and Germany <2%. For P. aeruginosa piperacillin-tazobactam, amikacin, imipenem and ceftazidime were the most active compounds tested irrespective of region. Surveillance data should be considered when selecting empirical therapy for treating SSTI.

Antibiotic susceptibility of bacteria most commonly isolated from bone related infections: the role of cephalosporins in antimicrobial therapy.

Bone infections, which can be acute or chronic, often require aggressive antibiotic therapy, whether treated at home or in the community. Surveillance programmes are essential tools in the monitoring of antimicrobial resistance and can act as a resource to maintain effective prescribing. The Surveillance Network (TSN), which collects organism and patient-specific data from a network of laboratories across the United States, was used to analyse susceptibility of common bacterial species isolated from bone infections during 2000-2002. Narrow-spectrum antimicrobials such as vancomycin, quinupristin-dalfopristin and linezolid demonstrated good activity against Staphylococcus aureus and streptococci, and were active against 100% of isolates. However, Gram-negative species were also commonly isolated from these sites of infection. Later-generation cephalosporins, represented by ceftriaxone, cefotaxime and cefepime, exhibited a broad spectrum of activity including Enterobacteriaceae, streptococci and methicillin-susceptible S. aureus, but they were not active against methicillin-resistant S. aureus (MRSA) and showed variable activity against Pseudomonas aeruginosa. Using ceftazidime as a marker for extended spectrum beta-lactamase (ESBL) expression, less than 3% of Escherichia coli or Klebsiella pneumoniae expressed this phenotype. Based on current in vitro activity, the third-generation cephalosporins provide broad-spectrum coverage useful for the empirical therapy of suspected bone infections, especially for patients treated in the community or hospitalised with community-acquired infections.

Apparent plateau in beta-lactamase production among clinical isolates of Haemophilus influenzae and Moraxella catarrhalis in the United States: results from the LIBRA Surveillance initiative.

Haemophilus influenzae (n=2791) and Moraxella catarrhalis (n=1249) isolated from patient specimens during 1999 were collected from 290 laboratories participating in a moxifloxacin surveillance study as part of the LIBRA Surveillance initiative. Isolates were tested for in vitro susceptibility to a panel of agents suitable for the treatment of respiratory tract infections. beta-Lactamase production was identified in 32.2% of H. influenzae and 94.2% of M. catarrhalis. These percentages differed by less than 1.5% from results of a study conducted in 1997-1998 and were similar to results from other recent US surveillance studies. Resistance among H. influenzae to trimethoprim-sulphamethoxazole increased considerably, from 2% in the 1997-1998 study (n=6588 H. influenzae) to 15.5% in the current study. One isolate of H. influenzae had an MIC of 8 mg/l to both levofloxacin and moxifloxacin; all other isolates had MICs of < or =0.5 mg/l and < or =0.25 mg/l, respectively. beta-Lactamase production was found to confer ampicillin resistance in nearly all isolates. For M. catarrhalis, beta-lactamase-negative isolates had MICs < or =0.12-0.25 mg/l for ampicillin and < or =0.03-0.12 mg/l for ceftriaxone. In contrast, beta-lactamase production resulted in MICs of < or = 0.12->16 mg/l for ampicillin and < or = 0.03-4 mg/l for ceftriaxone. All M. catarrhalis had MICs < or =0.12 mg/l for moxifloxacin and < or =1 mg/l for levofloxacin. In summary, antimicrobial susceptibilities and the prevalence of beta-lactamase production in H. influenzae and M. catarrhalis in the United States has remained essentially unchanged from 1997-1998 to 1999.

Susceptibility to fluoroquinolones among commonly isolated Gram-negative bacilli in 2000: TRUST and TSN data for the United States. Tracking Resistance in the United States Today. The Surveillance Network.

From January to May 2000, as part of the Tracking Resistance in the United States Today (TRUST) surveillance initiative, clinical isolates of Enterobacteriaceae (n=2519) and non-fermentative Gram-negatives (n=580) were prospectively collected from 26 hospital laboratories across the United States. Isolates were tested for susceptibility to three fluoroquinolones (ciprofloxacin, levofloxacin, gatifloxacin) and seven other agents. In addition, data for the same period were collected from The Surveillance Network (TSN) Database-USA, an electronic surveillance network that receives data from more than 200 laboratories in the US. Both surveillance methods produced similar results. Against isolates of Enterobacteriaceae, imipenem was the most active agent, followed by the fluoroquinolones; > or = 86.7% of isolates of all species of Enterobacteriaceae except Providencia spp. were susceptible to fluoroquinolones by TRUST and TSN surveillance. TRUST identified differences in susceptibility to the three fluoroquinolones of > or = 2% for Citrobacter spp., Enterobacter cloacae, Proteus mirabilis and Serratia marcescens. Isolates of P. mirabilis were considerably more susceptible to levofloxacin (94.0%) than to ciprofloxacin (87.7%) and gatifloxacin (87.7%). Other results from TRUST included Pseudomonas aeruginosa being slightly more susceptible to ciprofloxacin (73.5%) and levofloxacin (73.0%) than gatifloxacin (71.0%). Imipenem was the only compound with significant activity (95.1% susceptible, TRUST; 87.4% susceptible, TSN) against Acinetobacter baumannii, but it was inactive against Stenotrophomonas maltophilia. S. maltophilia isolates were more susceptible to levofloxacin and gatifloxacin (77.7-79.8%) than ciprofloxacin (29.7-33.0%). Against 513 urinary isolates of Escherichia coli in TRUST, levofloxacin, gatifloxacin and ciprofloxacin were equipotent. Age and gender had no clear effect on the activity of levofloxacin, ciprofloxacin or gatifloxacin. Similar results for all three fluoroquinolones were seen in outpatients and inpatients. TRUST and TSN data indicated that resistance rates had not changed appreciably for any compound studied since a similar study conducted in 1999. TRUST centralized in vitro and electronic (TSN) surveillance methods provided an effective strategy for monitoring trends in resistance.

Antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in two successive respiratory seasons in the US.

Antimicrobial susceptibilities of clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis were determined in two consecutive respiratory seasons in the US and suggested that national susceptibilities to commonly tested antimicrobials changed only slightly from the 1999-2000 to the 2000-2001 respiratory season. However, a significant regional variation in S. pneumoniae susceptibilities was observed, as was a decrease in beta-lactamase rates among H. influenzae from the 1999-2000 to 2000-2001 respiratory seasons.

Phenotypic and genotypic analysis of levofloxacin-resistant clinical isolates of Streptococcus pneumoniae collected in 13 countries during 1999-2000.

During 1999-2000, 5015 isolates were collected from 13 countries and tested against levofloxacin. Overall, levofloxacin resistance minimum inhibitory concentration (MIC>or =8 mg/l) was found in 40 isolates (0.8%). The highest resistance rates were in Hong Kong (8.0%), China (3.3%) and Spain (1.6%). Levofloxacin retained an MIC(90) of 1 mg/l in all countries. Pulsed-field gel electrophoresis analysis of resistant isolates demonstrated the presence of clones in countries where levofloxacin resistance exceeded 1%, suggesting that the elevated resistance rates could result from resistant clones within participating hospitals. DNA-sequence analysis of the quinolone-resistance-determining regions of gyrA, gyrB, parC and parE genes showed that the most common mutations were in GyrA (Ser81Phe), ParC (Ser79Phe, Lys137Asn) and ParE (Ile460Val), accounting for 40% of the isolates tested. Levofloxacin-resistant isolates were generally non-susceptible to other fluoroquinolones tested. Future studies to characterise resistant isolates by other molecular methods may ensure that the appropriate counter-measures can be taken to control the spread of resistant isolates.

Tracking the implementation of NCCLS M100-S12 expanded-spectrum cephalosporin MIC breakpoints for nonmeningeal isolates of Streptococcus pneumoniae by clinical laboratories in the United States during 2002 and 2003.

BACKGROUND: The Performance Standards for Antimicrobial Susceptibility Testing, Twelfth Informational Supplement, M100-S12, published by the National Committee for Clinical Laboratory Standards (NCCLS) in January 2002 introduced distinct minimum inhibitory concentration (MIC) interpretative breakpoints for ceftriaxone, cefotaxime, and cefepime for nonmeningeal isolates of Streptococcus pneumoniae. Previously, a single set of interpretative breakpoints was used for both meningeal and nonmeningeal isolates. METHODS: To estimate the rate of adoption of the M100-S12 interpretive breakpoints by clinical laboratories, antimicrobial susceptibility test results for ceftriaxone and cefotaxime from nonmeningeal S. pneumoniae isolates were studied using data collected from January 2002 to June 2003 by The Surveillance Network Database--USA (TSN, an electronic surveillance database. RESULTS: Of the 262 laboratories that provided data that could be evaluated, 67.6% had adopted the M100-S12 breakpoints one and one-half years after they were published. CONCLUSIONS: The NCCLS M100-S12 recommendation to interpret MICs to expanded-spectrum cephalosporins using two distinct sets of breakpoints for meningeal and nonmeningeal isolates of S. pneumoniae was steadily implemented by clinical microbiology laboratories in the United States following their initial publication in January 2002. The use of these new breakpoints more accurately reflects the clinical activities of expanded-spectrum cephalosporins than did the single set of interpretative breakpoints previously used for both meningeal and nonmeningeal isolates.

Emerging resistance among bacterial pathogens in the intensive care unit--a European and North American Surveillance study (2000-2002).

BACKGROUND: Globally ICUs are encountering emergence and spread of antibiotic-resistant pathogens and for some pathogens there are few therapeutic options available. METHODS: Antibiotic in vitro susceptibility data of predominant ICU pathogens during 2000-2 were analyzed using data from The Surveillance Network (TSN) Databases in Europe (France, Germany and Italy), Canada, and the United States (US). RESULTS: Oxacillin resistance rates among Staphylococcus aureus isolates ranged from 19.7% to 59.4%. Penicillin resistance rates among Streptococcus pneumoniae varied from 2.0% in Germany to as high as 20.2% in the US; however, ceftriaxone resistance rates were comparably lower, ranging from 0% in Germany to 3.4% in Italy. Vancomycin resistance rates among Enterococcus faecalis were < or = 4.5%; however, among Enterococcus faecium vancomycin resistance rates were more frequent ranging from 0.8% in France to 76.3% in the United States. Putative rates of extended-spectrum beta-lactamase (ESBL) production among Enterobacteriaceae were low, <6% among Escherichia coli in the five countries studied. Ceftriaxone resistance rates were generally lower than or similar to piperacillin-tazobactam for most of the Enterobacteriaceae species examined. Fluoroquinolone resistance rates were generally higher for E. coli (6.5% - 13.9%), Proteus mirabilis (0-34.7%), and Morganella morganii (1.6-20.7%) than other Enterobacteriaceae spp (1.5-21.3%). P. aeruginosa demonstrated marked variation in beta-lactam resistance rates among countries. Imipenem was the most active compound tested against Acinetobacter spp., based on resistance rates. CONCLUSION: There was a wide distribution in resistance patterns among the five countries. Compared with other countries, Italy showed the highest resistance rates to all the organisms with the exception of Enterococcus spp., which were highest in the US. This data highlights the differences in resistance encountered in intensive care units in Europe and North America and the need to determine current local resistance patterns by which to guide empiric antimicrobial therapy for intensive care infections.