Geographic variations in garenoxacin (BMS284756) activity tested against pathogens associated with skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (2000)

The antimicrobial activity of garenoxacin, a des-(6)F quinolone (formally BMS284756 and T-3811), was evaluated against 2,537 skin and soft tissue infection (SSTI) isolates from the SENTRY Antimicrobial Surveillance Program. Strains isolated in 2000 from Europe, North and Latin America were tested at a central laboratory using reference broth microdilution methods. The rank order of the seven most frequent SSTI pathogens was: Staphylococcus aureus (39.9%), Pseudomonas aeruginosa (12.1%), Escherichia coli (9.7%), Enterococcus spp. (7.7%), Klebsiella spp. (5.8%), Enterobacter spp. (5.6%) and coagulase-negative staphylococci (CoNS; 4.2%). Garenoxacin exhibited a four-fold greater activity (MIC(90), 0.06 microg/ml) compared to levofloxacin (MIC(90), 0.25 microg/ml) against oxacillin-susceptible S. aureus; and oxacillin-resistant staphylococci were more susceptible to garenoxacin (>/=90.5%) at Europe > North America). Continued development of garenoxacin as a treatment of pathogens that commonly cause SSTIs appears to be warranted.     

Potency and spectrum of garenoxacin tested against an international collection of skin and soft tissue infection pathogens: report from the SENTRY antimicrobial surveillance program (1999-2004)

The spectrum and potency of garenoxacin, a novel des-F(6)-quinolone, against a large international collection (11723 strains) of Gram-positive and Gram-negative bacterial pathogens that cause skin and soft tissue infections (SSTIs) were evaluated for the years 1999 to 2004. Consecutive nonduplicate bacterial isolates were collected from patients with documented community-acquired or nosocomial SSTI in >70 medical centers participating in the SENTRY Antimicrobial Surveillance Program in North America (37.4%), Europe (26.7%), Latin America (16.7%), and the Asia-Pacific region (19.2%). All isolates were tested using the reference broth microdilution methods against garenoxacin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and representative comparator agents used for the empiric or directed therapy for SSTI. Ranking pathogens producing SSTI during these years included Staphylococcus aureus (42.8%), Pseudomonas aeruginosa (11.1%), Escherichia coli (9.0%), Enterococcus spp. (7.3%), Klebsiella spp. (4.8%), Enterobacter spp. (4.7%), beta-hemolytic streptococci (4.3%), coagulase-negative staphylococci (4.0%), Proteus mirabilis (2.5%), and Acinetobacter spp. (2.1%). Garenoxacin was the most potent agent tested against S. aureus and was at least 2-fold more active than gatifloxacin (MIC(50), 0.06 mg/L) and 8-fold more active than levofloxacin (MIC(50), 0.25 mg/L). Furthermore, garenoxacin was 2- to 8-fold more potent than the fluoroquinolones against beta-hemolytic and viridans group streptococci, as well as up to 4-fold more active against enterococci. Garenoxacin was largely comparable with the comparator fluoroquinolones against E. coli, Klebsiella spp., and Acinetobacter spp., but it is less active than these agents against P. aeruginosa. In summary, garenoxacin was documented to be the most potent quinolone when tested against key Gram-positive pathogens (S. aureus, beta-hemolytic streptococci, viridans group streptococci, and enterococci) and was similar in activity to these agents against other species (Enterobacteriaceae and Acinetobacter spp.). These in vitro data suggest that garenoxacin warrants further clinical studies in SSTI, especially against staphylococci and streptococcal pathogens.     

Contemporary causes of skin and soft tissue infections in North America, Latin America, and Europe: report from the SENTRY Antimicrobial Surveillance Program (1998-2004)

The morbidity and cost for cure associated with skin and soft tissue infections (SSTIs) have recently become more complicated because of the increasing prevalence of multidrug-resistant pathogens associated with this healthcare problem. The SENTRY Antimicrobial Surveillance Program has been monitoring SSTI since 1997, and now presents data from 3 continents over a 7-year period (1998-2004). Isolates were tested by reference broth microdilution methods at a central laboratory using the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) methods and interpretative criteria. The predominant pathogens included Staphylococcus aureus (ranked 1st in all geographic regions), Pseudomonas aeruginosa, Escherichia coli, and Enterococcus spp. A considerable variation in the methicillin (oxacillin)-resistant S. aureus rate was noted between countries and continents, with the overall rate highest in North America (35.9%) compared with Latin America (29.4%) and Europe (22.8%). Vancomycin-resistant Enterococcus spp. increased in Europe (4.1%) and North America (6.2%) during the period, but remained low and relatively unchanged in Latin America. Among the P. aeruginosa isolates tested, susceptibility to imipenem was much lower in Latin America (65.3%) compared with the other regions (80.7-88.7%), and resistance being associated with an increase in metallo-beta-lactamase-producing strains in Latin America and in some European countries. Multidrug-resistant strains of P. aeruginosa were also more of a concern in Latin America (24.7%) compared with Europe (10.8%) or North America (3.2%). Latin America also had the highest occurrence of extended-spectrum beta-lactamase-producing isolates among E. coli (15.1%) and Klebsiella spp. (48.0%) when compared with other regions. Continued surveillance of pathogen prevalence and antimicrobial resistance patterns should provide information that is important to improve empiric care particularly in the hospital environment.     

Occurrence and antimicrobial resistance pattern comparisons among bloodstream infection isolates from the SENTRY Antimicrobial Surveillance Program (1997-2002)

The empiric treatment of patients with bloodstream infections (BSI) has become more complicated in an era of increasing antimicrobial resistance. The SENTRY Antimicrobial Surveillance Program has monitored BSI from patients in medical centers worldwide since 1997. During 1997-2002, a total of 81,213 BSI pathogens from North America, Latin America, and Europe were tested for antimicrobial susceptibility. S. aureus, E. coli, and coagulase-negative staphylococci were the three most common BSI pathogens in all three regions each year. Prevalence variability was noted in regions for some species, including higher rates of isolation of E. coli in Europe, Enterococcus spp. in North America, and Gram-negative enteric and nonenteric species in Latin America. Patient age analysis showed the most common BSI pathogen among neonates was coagulase-negative staphylococci and among elderly patients, E. coli. Resistance among BSI pathogens was much more prevalent in nosocomial infections and in patients in intensive care units (ICUs); age differences were also noted. Geographically, oxacillin-resistant S. aureus (39.1%, 2002) and vancomycin-resistant enterococci (17.7%, 2002) were highest in North America, and extended-spectrum beta-lactamase-producing Klebsiella spp. (35.8-46.7%) and multidrug-resistant P. aeruginosa (18.7%, 2002) were highest in Latin America. Activity of commonly used antimicrobial agents remained relatively stable in North America, except in the case of vancomycin-resistant enterococci (20% decline between 1997 and 2002). An epidemiologic investigation of oxacillin-resistant S. aureus in North America identified 10 significant clones (ribotypes) and the common resistance patterns associated with them. Surveillance of BSI pathogens is needed to determine trends of resistance and provide useful information regarding patient risk factors and geographic differences.     

Antimicrobial susceptibility among organisms from the Asia/Pacific Rim, Europe and Latin and North America collected as part of TEST and the in vitro activity of tigecycline

OBJECTIVES: To describe antimicrobial susceptibility among bacterial isolates associated with hospital infections collected from 266 centres in Asia/Pacific Rim (n = 1,947), North America (n = 24,283), Latin America (n = 1,957) and Europe (n = 8,796). METHODS: Isolates were collected from blood, respiratory tract, urine, skin, wound, body fluids and other defined sources between January 2004 and August 2006. Only one isolate per patient was accepted. In vitro MICs for the isolates were determined according to the CLSI (formerly NCCLS) guidelines. RESULTS: Key organisms collected were Acinetobacter baumannii (n = 2,902), Enterobacter spp. (n = 5,731), Escherichia coli (n = 6,504), Klebsiella pneumoniae (n = 4,916), Pseudomonas aeruginosa (n = 5,128), Serratia marcescens (n = 2,313), Enterococcus faecalis (n = 2,701), Enterococcus faecium (n = 1,035) and Staphylococcus aureus (n = 5,753). Rates of methicillin resistance among S. aureus and of vancomycin resistance among enterococci were highest in North America (2,016/3,809, 52.9% and 571/2,544, 22.4%, respectively) and lowest in Europe (337/1,340, 25.1% and 36/916, 3.9%, respectively). Tigecycline was the only antimicrobial to maintain activity against all Gram-positive isolates (MIC(90) values of 93% susceptibility in all regions) antimicrobials against the Gram-negative species, except for A. baumannii and P. aeruginosa. Piperacillin/tazobactam and amikacin were the most active against P. aeruginosa. Extended-spectrum beta-lactamase producers among K. pneumoniae occurred most frequently in Latin America (124/282, 44.0%). CONCLUSIONS: Tigecycline is a novel broad-spectrum antimicrobial that is active against the common organisms associated with infections.     

Characteristics of pathogens causing urinary tract infections in hospitals in North America: results from the SENTRY Antimicrobial Surveillance Program, 1997.

Urinary tract infection (UTI) is common and involves pathogens with changing susceptibility patterns. The SENTRY Antimicrobial Surveillance Program evaluates international pathogen incidence patterns to detect and manage the emergence of resistant strains. We describe the antimicrobial resistance patterns among 1617 pathogens recovered from UTIs during the third-quarter of 1997 in North America (United States and Canada), as part of this worldwide program. The isolates were tested against more than 50 antimicrobial agents (20 reported) by reference broth microdilution methods, and selected isolates were characterized by pulsed-field gel electrophoresis (PFGE) and automated ribotyping. The five most frequently isolated species were Escherichia coli (48.6%), Enterococcus spp. (13.7%), Klebsiella spp. (12.0%), Pseudomonas aeruginosa (6.2%), and Enterobacter spp. or Proteus mirabilis (3.8% each). For each nation, imipenem and cefepime produced the widest spectrum of coverage among the beta-lactams and amikacin was best among the aminoglycosides. For Gram-negative species, high resistance among beta-lactam antimicrobial agents was noted especially for various penicillins against E. coli (37.9% to 42.8%) and for the cephalosporins tested against enterococci (99.4% and 100%). Approximately 7.0% of enterococci in the USA were vancomycin-resistant (88% with Van A). P. aeruginosa provided the most consistent levels of resistance, but the following agents were most active against these organisms: amikacin (96.6 to 97.4% susceptible), tobramycin (89.5 to 100.0%), piperacillin/tazobactam (89.5 to 100.0%), piperacillin (89.5 to 96.6%), imipenem (89.7 to 92.1%), cefepime (77.6 to 89.7%), and ceftazidime (82.9 to 86.2%). E. coli (2.2 to 2.7%), K. pneumoniae (6.2 to 6.4%), and a single Enterobacter cloacae strain produced extended-spectrum beta-lactamases; and five other Enterobacter spp. were likely to have expressed chromosomally mediated (Amp C) Stably derepressed cephalosporinases with associated resistance to ceftazidime (16.7 to 21.2% resistance). These data demonstrated that several UTI isolates in SENTRY hospitals have high levels of resistance to various classes of antimicrobial agents with little evidence of clonal dissemination.     

Assessment of pathogen frequency and resistance patterns among pediatric patient isolates: report from the 2004 SENTRY Antimicrobial Surveillance Program on 3 continents

Selecting empiric or directed therapy for pathogens isolated from pediatric patients can be problematic. Many antimicrobial agents are not indicated for use in pediatric patients, and regional variations of resistance mechanisms have been reported. The purpose of this study was to analyze antimicrobial resistance patterns and pathogen occurrence rates in pediatric-aged patient infections on 3 continents using data from the SENTRY Antimicrobial Surveillance Program. A total of 3537 clinical isolates were collected from 47 medical centers in 2004. With a protocol that dictated a sampling of 80 consecutive isolates from children (< or =18 years of age), all samples were forwarded to a central laboratory for reference susceptibility testing. Broth microdilution methods and current Clinical and Laboratory Standards Institute breakpoint criteria were used. The 15 most frequently observed pathogens accounted for 93.6% of all isolates. Staphylococcus aureus was the most common pathogen isolated in North America (27.4%) and Europe (19.0%), but Escherichia coli was most common in Latin America (19.3%). All Streptococcus pneumoniae strains from North America and Latin America were susceptible to the newer fluoroquinolones, gatifloxacin and levofloxacin. However, 2 S. pneumoniae strains from Italy were resistant to gatifloxacin, levofloxacin, and ciprofloxacin (> or =4 microg/mL). Ribotype and pulsed-field gel electrophoresis patterns found that these resistant pneumococci were clonal. Numerous strains of Klebsiella spp. (22.5%), E. coli (4.5%), and Proteus mirabilis (4.9%) exhibited phenotypic extended-spectrum beta-lactamase resistance patterns. Four Pseudomonas aeruginosa strains (3 from Latin America and 1 from Europe) were multidrug resistant, 2 P. aeruginosa isolates from Turkey were resistant to polymyxin B (> or =4 microg/mL), and 8.7% of Stenotrophomonas maltophilia isolates from Latin America were resistant to the "drug of choice", trimethoprim/sulfamethoxazole. Physicians should be aware of pathogen occurrences that vary by children's age, geographic location, and prior antimicrobial exposure. Therefore, continued surveillance will be necessary to monitor emerging antimicrobial resistance in the pediatric patient population, especially because new agents such as the fluoroquinolones are used to a greater extent in this age group.     

Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogens in hospitalized patients in Latin America: report from the second year of the SENTRY antimicrobial surveillance program (1998)

The potency and spectrum of various antimicrobial agents tested against 434 bacterial isolates causing urinary tract infection (UTI) in hospitalized patients in Latin America were evaluated. The genotypes of the extended-spectrum beta-lactamase-producing and selected multi-resistant isolates were also evaluated by molecular typing techniques. Escherichia coli (60.4%) was the most common aetiological agent causing UTI, followed by Klebsiella spp. (11.2%) and Pseudomonas aeruginosa (8.3%). In contrast, Enterococcus spp. isolates caused only 2.3% of UTIs. Fewer than 50% of E. coli isolates were susceptible to broad-spectrum penicillins. The resistance rates to ciprofloxacin and the new quinolones were also high among these isolates. The molecular characterization of ciprofloxacin-resistant E. coli showed that most of them have a double mutation in the gyrA gene associated with a single mutation in the parC gene. The Klebsiella pneumoniae isolates studied demonstrated high resistance rates to beta-lactam drugs, including broad-spectrum cephalosporins. The carbapenems were the compounds with the highest susceptibility rate among these isolates (100.0% susceptible) followed by cefepime (91.7% susceptible). Meropenem, imipenem and cefepime were also the most active drugs against Enterobacter spp. Among P. aeruginosa isolates, meropenem (MIC(50), 2 mg/L) was the most active compound, followed by imipenem (MIC(50), 4 mg/L), cefepime (MIC(50), 8 mg/L) and ceftazidime (MIC(50), 16 mg/L). The results presented in this report confirm that bacterial resistance continues to be a great problem in Latin American medical institutions.     

Urinary tract infection trends in Latin American hospitals: report from the SENTRY antimicrobial surveillance program (1997-2000)

Urinary tract infections (UTI) are one of the most common infectious diseases diagnosed in outpatients as well as in hospitalized patients. The objective of this study was to report the frequency of occurrence and antimicrobial susceptibility of uropathogens collected in Latin America between 1997 to 2000 through the SENTRY Antimicrobial Surveillance Program. Antimicrobial susceptibility testing was performed and results interpreted using reference broth microdilution methods. In the 4 year period, a total of 1961 urine isolates from hospitalized patients were included. The patients' mean age was 51.3 years and most of the infections occurred among women (65.6%). Esherichia coli was the most frequent pathogen isolated followed by Klebsiella spp., Pseudomonas aeruginosa, and Proteus mirabilis. Among the E. coli isolates, piperacillin/tazobactam, aztreonam, extended-spectrum cephalosporins, carbapenems and amikacin constitute reasonable therapeutic options for treatment of serious UTI in Latin America (91.0-100.0% susceptible). High resistance rates to fluoroquinolones (17.5-18.9%) and trimethoprim/sulfamethoxazole (>45.0%) were observed among the E. coli. In contrast, nitrofurantoin displayed susceptibility rate of > 87.0%. Against Klebsiella spp. infections, the only effective therapeutic option would be the carbapenems due to the high number of isolates (>30.0%) producing extended-spectrum beta-lactamases (ESBL). Even the new fluoroquinolones showed limited activity against Klebsiella spp. (72.1-88.6% susceptible) and the P. aeruginosa isolates showed high resistance rates to most antimicrobial agents tested. The results of this survey endorse the importance of Enterobacteriaceae as cause of UTI in Latin America. Our results also demonstrate that the uropathogens isolated in the Latin American medical centers exhibit high resistance to various classes of antimicrobial agents. Carbapenem-resistant P. aeruginosa, ciprofloxacin-resistant E. coli, ESBL-producing K. pneumoniae constitute serious problem in this geographic region.     

Influence of patient age on the frequency of occurrence and antimicrobial resistance patterns of isolates from hematology/oncology patients: report from the Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program (North America)

The Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance Program (CANCER) monitored the susceptibility of pathogens recovered in hematology/oncology centers from 2000 to 2002. A total of 3970 isolates from 32 hospitals (26 United States, 6 Canada) were analyzed at a central location (JMI Laboratories, North Liberty, IA) for trends in pathogen occurrence and reference antimicrobial susceptibility profiles. The top 5 ranking pathogens were Staphylococcus aureus (19.3%), coagulase-negative staphylococci (CoNS) (14.1%), Escherichia coli (13.4%), Enterococcus spp. (10.2%), and Klebsiella spp. (9.5%). A total of 35.5% of S. aureus and 78.8% of CoNS were resistant to oxacillin, whereas 22.0% of Enterococcus spp. were resistant to vancomycin. E. coli and Klebsiella spp. were highly susceptible (>90%) to piperacillin/tazobactam, 3rd-generation cephalosporins, and ciprofloxacin, but 3.9% and 2.4% of these species, respectively, met screening criteria for extended spectrum beta-lactamase production. Enterobacter spp. were less susceptible to piperacillin/tazobactam, ceftazidime, and ceftriaxone (83.7-88.2%) because of Amp C production and were most inhibited by cefepime and imipenem. Amikacin and polymyxin B were very active against Pseudomonas aeruginosa (97.4-97.7% susceptible). Prevalence of S. aureus, E. coli, Enterobacter spp., and Klebsiella spp. increased significantly (+48% to 98%) with age, whereas CoNS and viridans group streptococci decreased markedly (-62% to 69%) with advancing age. The isolation of Gram-positive pathogens declined (55% to 47%) with age (< or =14 to > or =65 years). Fluoroquinolones generally exhibited decreased susceptibility with increased age against nearly all listed pathogens. Oxacillin resistance rates for S. aureus increased with age (6-46%) as did vancomycin resistance rates for enterococci (nil in < or =14 years group to 18-24% in adults). Pathogens infecting neutropenic patients did not reflect greater resistance than those found in the general hospitalized patients. Gram-positive organisms were only slightly more predominant (53.4%), and cited age-related variations in pathogen occurrence and/or susceptibility patterns by species must be considered for empiric regimes for hematology and oncology patients.     

Skin and soft tissue infections in Latin American medical centers: four-year assessment of the pathogen frequency and antimicrobial susceptibility patterns

We report the results of pathogen frequency and antimicrobial susceptibility of isolates collected from skin and soft tissue infections (SSTIs) in Latin American medical centers during the first 4 years (1997-2000) of the SENTRY Antimicrobial Surveillance Program. Ten laboratories participated each year distributed among nine cities in six countries. A total of 1,789 bacterial isolates were susceptibility tested by reference broth microdilution at the coordinating central laboratory. Results from isolates collected during the year 2000 were compared with those from isolates collected during the prior three years. Selected carbapenem-resistant Pseudomonas aeruginosa were genotyped by automated ribotyping to evaluate the occurrence of clonal, epidemic dissemination. The five most frequently isolated species were (n/%): Staphylococcus aureus (584/32.8%), Escherichia coli (233/13.1%), P. aeruginosa (211/11.9%), Enterococcus spp. (137/7.7%), and Klebsiella spp. (127/5.8%). The most problematic antimicrobial resistances were related to the high prevalence of multi-drug resistant (MDR) Gram-negative bacilli. Carbapenem resistance among non-fermentative Gram-negative bacilli was much higher than that reported in other regions evaluated in the SENTRY Program. Only 74.9% of P. aeruginosa and 84.9% of Acinetobacter spp. were considered susceptible to imipenem. The antimicrobial susceptibility rates of P. aeruginosa decreased during the study period for most antimicrobial agents evaluated. More than 40% of K. pneumoniae and nearly 10% of E. coli showed an extended spectrum beta-lactamase phenotype. Only 73.4% of E. coli and 76.0% of Enterobacter spp. were susceptible to ciprofloxacin. The molecular typing of carbapenem-resistant P. aeruginosa demonstrated clonal dissemination in two institutions. These reported results indicate that rates of resistance among isolates causing SSTI continue to raise in Latin America, with specific concerns for the high prevalence of MDR Gram-negative bacilli. National and international surveillance programs as a guide to focusing intervention strategies should assist in the control of escalating antimicrobial resistance in this geographic area.     

Comparative activities of cefepime and piperacillin/tazobactam tested against a global collection of Escherichia coli and Klebsiella spp. with an ESBL phenotype

Cefepime exhibits more stability to hydrolysis by extended-spectrum beta-lactamases (ESBLs) compared with other cephalosporins, and piperacillin/tazobactam may be active against these pathogens because of the enzyme inhibitory activity of tazobactam. Thus, we evaluated the in vitro activity of these 2 antimicrobials against a large collection of isolates with an ESBL phenotype. A total of 50,637 clinical isolates (34,367 Escherichia coli and 16,270 Klebsiella spp.) collected from more than 80 medical centers (1998-2004) were tested by reference broth microdilution methods, and isolates with an ESBL phenotype (MIC, > or = 2 microg/mL for aztreonam or ceftazidime or ceftriaxone) were submitted to a clavulanate inhibition test (confirmation of ESBL production). Among isolates from North America, 3.9% of E. coli and 8.6% of Klebsiella spp. showed an ESBL phenotype, whereas among isolates from the rest of the world (ROW) (Europe, Latin America, and Asia), 7.7% of E. coli and 28.3% of Klebsiella spp. exhibited this pattern. Confirmation rates varied from 21.6% of E. coli in North America to 52.8% of Klebsiella spp. in the row Among E. coli from North America, cefepime (90.3% susceptibility) was generally more active than piperacillin/tazobactam (82.7%), especially among ESBL-not-confirmed (97.0% versus 85.5%). Cefepime also showed reasonable activity against Klebsiella spp. from North America (89.4% susceptibility). In general, isolates from North America exhibited higher susceptibility rates to both beta-lactams compared with isolates from the ROW, and ESBL-not-confirmed strains showed generally higher susceptibility rates than ESBL-confirmed organisms.     

Potency and spectrum of tigecycline tested against an international collection of bacterial pathogens associated with skin and soft tissue infections (2000-2004)

The antimicrobial activity of tigecycline, a novel glycylcycline, was evaluated against 5289 bacterial isolates recovered from hospitalized patients with skin and soft tissue infections during 2000-2004. Strains were submitted from >70 medical centers in North America, Latin America, and Europe, and were tested centrally using reference broth microdilution methods. The top 10 ranking pathogens (95% of total) recovered included Staphylococcus aureus (55.2%), Enterococcus spp. (9.6%), Pseudomonas aeruginosa (6.4%), Escherichia coli (5.6%), beta-hemolytic streptococci (5.0%), coagulase-negative staphylococci (4.9%), Enterobacter spp. (2.8%), Klebsiella spp. (2.6%), Proteus mirabilis (1.7%), and indole-positive Proteae (1.2%). All staphylococci (S. aureus and coagulase-negative staphylococci), enterococci, beta-hemolytic streptococci, viridans group streptococci, and E. coli were inhibited by < or =2 microg/mL of tigecycline; in addition, 97% of Klebsiella spp., 95% of Enterobacter spp., and 97% of Acinetobacter spp. were inhibited at this concentration. Only P. aeruginosa and all Proteae (MIC90, 16 microg/mL) displayed elevated MIC values to tigecycline. The broad spectrum of activity exhibited by this glycylcycline included tetracycline-resistant organism subsets, as well as oxacillin-resistant S. aureus, vancomycin-resistant enterococci, and extended-spectrum beta-lactamase-producing enteric bacilli strains. Tigecycline represents a new choice among broad-spectrum parenteral agents for the common Gram-positive and -negative pathogens producing serious infections of skin and soft tissues.     

Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit

The antimicrobial activity of tigecycline and selected antimicrobials was evaluated against bacterial pathogens isolated from patients hospitalized in intensive care units (ICUs) worldwide. A total of 9093 isolates were consecutively collected in >70 medical centers in North America (4157), South America (1830), Europe (3034), and the Asia-Australia (72) areas. The isolates were collected from the bloodstream (68.5%), respiratory tract (13.6%), skin/soft tissue (5.5%), and urinary tract (2.0%) infections in the 2000-2004 period, and susceptibility was tested by reference broth microdilution methods. The most frequently isolated pathogens were Staphylococcus aureus (32.1%), Enterococcus spp. (13.7%), coagulase-negative staphylococci (CoNS; 13.0%), Pseudomonas aeruginosa (8.4%), and Escherichia coli (7.9%). All Gram-positive pathogens (5665) were inhibited at < or =1 microg/mL of tigecycline. Resistance to oxacillin was detected in 43.5% of Staphylococcus aureus and in 85.0% of CoNS, and resistance to vancomycin was observed in 18.6% of enterococci. Tigecycline was very active against Enterobacteriaceae (1876 strains tested) with an MIC90 of < or =1 microg/mL, except for Serratia spp. (2 microg/mL). Extended-spectrum beta-lactamase (ESBL) phenotype was detected in 10% of E. coli and 31% of Klebsiella spp., whereas 28% of Enterobacter spp. were resistant to ceftazidime (AmpC enzyme production). These resistance phenotypes did not adversely affect tigecycline activity. Tigecycline and trimethoprim/sulfamethoxazole were the most active compounds against Stenotrophomonas maltophilia (MIC90, 2 and 1 microg/mL respectively). Tigecycline was also active against Acinetobacter spp. (MIC90, 1 microg/mL), but P. aeruginosa showed decreased susceptibility to tigecycline (MIC90, 16 microg/mL). In summary, isolates from ICU patients worldwide showed high rates of antimicrobial resistance. The most alarming problems detected were vancomycin resistance among enterococci, ESBL-mediated beta-lactam resistance and fluoroquinolone resistance among Enterobacteriaceae, and carbapenem resistance among P. aeruginosa and Acinetobacter spp. Tigecycline exhibited potent in vitro activity against most of clinically important pathogenic bacteria (except P. aeruginosa) isolated from ICU patients and may represent an excellent option for the treatment of infections in this clinical environment.     

Survey of blood stream infections attributable to gram-positive cocci: frequency of occurrence and antimicrobial susceptibility of isolates collected in 1997 in the United States, Canada, and Latin America from the SENTRY Antimicrobial Surveillance Program. SENTRY Participants Group

The SENTRY Antimicrobial Surveillance Program was established in January, 1997 to monitor the predominant pathogens and antimicrobial resistance patterns of nosocomial and community-acquired infections via a network of sentinel hospitals in the United States (30 sites), Canada (eight sites), Latin America (10 sites), and Europe (24 sites). During the first 12-month study period (January to December, 1997), a total of 9519 blood stream infections (BSI) were reported by SENTRY participants in the U.S. (6150), Canada (1727), and Latin America (1642). The Gram-positive cocci, Staphylococcus aureus, coagulase-negative staphylococci (CoNS), enterococci, and streptococci accounted for 53.9% (5131 infections) of all BSI (56.5% U.S., 55.7% Canada, and 42.9% Latin America). The staphylococci, Enterococcus spp., S. pneumoniae, beta-hemolytic streptococci, and viridans group streptococci accounted for 6 of the top 11 BSI pathogens in the U.S. and Canada, whereas only S. aureus (1st), CoNS (3rd), and Enterococcus spp. (9th) were among the top 11 pathogens in Latin American hospitals. The results of this survey affirm the importance of Gram-positive cocci as causes of BSI in both North America and Latin America and demonstrate that important antimicrobial resistance exists among isolates of staphylococci, streptococci, and enterococci from all three geographic regions. This includes oxacillin-resistance among S. aureus (26.9% U.S., 29.2% Latin America, and 4.0% Canada) and CoNS (71.5% U.S., 68.4% Latin America, and 65.6% Canada), penicillin resistance among viridans group streptococci (48.5% U.S., 45.1% Canada, and 33.3% Latin America) and pneumococci (36.1% U.S., 27.5% Canada, and 65.6% Latin America), high-level resistance (HLR) to aminoglycosides among enterococci (27.2 to 70.1% U.S., 33.3 to 75.7% Canada and 16.7 to 51.5% Latin America), and macrolide resistance among beta-hemolytic streptococci (12.4 to 14.2% U.S., 10.5 to 12.3% Canada, and 0.0 to 4.0% Latin America), viridans group streptococci (32.4 to 39.7% U.S., 22.5-35.2% Canada, and 20.0% Latin America), and pneumococci (10.0 to 10.6% U.S., 9.8-10.8% Canada, and 9.4-18.7% Latin America). BSI isolates of Gram-positive cocci from the U.S. and Latin America were considerably more resistant than those from Canada. New agents with Gram-positive activity will be essential for optimal treatment of BSI attributable to Gram-positive cocci in both North and Latin America.     

Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.     

Epidemiology and frequency of resistance among pathogens causing urinary tract infections in 1,510 hospitalized patients: a report from the SENTRY Antimicrobial Surveillance Program (North America)

Bacterial urinary tract infections (UTIs) are an important cause of septicemia resulting in high mortality rates, prolonged hospital stays and increased healthcare costs. Periodic reviews of pathogen frequency and susceptibility patterns impact on appropriate antimicrobial usage, leading to more effective prescribing practices. As part of the SENTRY Antimicrobial Surveillance Program (SENTRY, 1998), participants collected 50 consecutive UTI pathogens from patients hospitalized in 31 medical centers (26 in the United States and five in Canada) and forwarded subcultures to the coordinating center. Thirty-four antimicrobial agents were tested including two investigational compounds (quinupristin/dalfopristin [Q/D], gatifloxacin). The rank order of the 32 species identified during the study was: Escherichia coli (46.9%) > Enterococcus spp. (12.8%) > Klebsiella spp. (11.0%) > Pseudomonas aeruginosa (7.5%) > Proteus mirabilis (5.0%) > coagulase-negative staphylococci (CoNS; 3.4%). This pathogen rank order did not change from 1997 to 1998, but resistance patterns changed. Clonal spread of confirmed extended spectrum beta-lactamase-producing strains was not observed, but co-resistance was elevated for aminoglycosides, tetracyclines, sulfonamides, and fluoroquinolones. P. aeruginosa was most susceptible to amikacin (97.3%) > piperacillin +/- tazobactam (92.0-95.6%) > cefepime = imipenem (91.2%) > ceftazidime (85.8%). Fluoroquinolone resistance was greater in P. aeruginosa (24.8-39.8%) > P. mirabilis (5.3-13.3%) > Enterobacter spp. (6.7-8.9%) > Klebsiella spp. (4.2-7.8%) > E. coli (3.0-3.8%). Only 5% of enterococci were resistant to vancomycin. These results emphasize the need for continued surveillance studies for common infections which establish baseline resistance patterns by geographic areas, and have the potential to detect epidemics or direct local epidemiologic interventions.     

Spectrum and activity of three contemporary fluoroquinolones tested against Pseudomonas aeruginosa isolates from urinary tract infections in the SENTRY Antimicrobial Surveillance Program (Europe and the Americas; 2000): more alike than different!

The spectrum and potency of ciprofloxacin, gatifloxacin and levofloxacin was compared to that of 10 other agents against urinary tract isolates of Pseudomonas aeruginosa among patients in the year 2000 SENTRY Antimicrobial Surveillance Program (Europe, Latin America, North America). Dramatic differences were observed between isolates in geographic areas with the most fluoroquinolone-resistant strains detected in Latin America (54.5% resistance) compared to resistance rates of 40.8-43.7% and 28.3-29.2% for Europe and North America, respectively. Overall, no significant differences were observed between the spectrums of these fluoroquinolones (37.1-38.8% resistance) for therapy of P. aeruginosa urinary tract infections in hospitalized patients. Generally, in this world wide sample, aminoglycosides, carbapenems (imipenem, meropenem), cefepime, and piperacillin with or without tazobactam possessed a wider range of activity and spectrum versus current P. aeruginosa clinical isolates.     

Antimicrobial resistance and molecular epidemiology of vancomycin-resistant enterococci from North America and Europe: a report from the SENTRY antimicrobial surveillance program

Increases in prevalence of vancomycin-resistant enterococci (VRE) have been documented globally since its emergence in the 1980s. A SENTRY Antimicrobial Surveillance Program (2003) objective monitored VRE isolates with respect to antimicrobial susceptibility trends, geographic resistance variability, and clonal dissemination. In 2003, VRE isolates from North America (United States and Canada, n = 839, 26 sites) and Europe (n = 56, 10 sites) were susceptibility tested using Clinical and Laboratory Standards Institute (CLSI) reference methodologies. Based on resistance profiles, 155 isolates displayed similar multidrug-resistant (MDR) profiles and were temporally related; these were subsequently submitted for typing by pulsed-field gel electrophoresis (PFGE). Most of the submitted isolates were Enterococcus faecium (91.0%) and Enterococcus faecalis (7.8%). Among VRE, the VanA phenotype was more prevalent in North America (76%) than Europe (40%), and all isolates had elevated resistance rates to other antimicrobial classes including the following: 1) chloramphenicol resistance among E. faecalis being greater in North America than in Europe (28.6% versus 7.1%, respectively) but reversed among E. faecium (0.5% and 15.0%, the latter due to clonal occurrences); 2) ciprofloxacin resistance in North America >99% for both species and in Europe varying from 85.7% to 87.5%; 3) rare occurrences of linezolid resistance in North America (0.8% to 1.8%) due to G2576U ribosomal mutation; 4) higher quinupristin/dalfopristin resistance observed among European E. faecium strains (10.0% versus 0.6%); and 5) higher rifampin resistance rates among European E. faecalis (21.4% versus 5.4%). Thirty-five MDR epidemic clusters were identified by PFGE in 21 North American and 2 European medical centers including the following: 1) VanA (20 sites, 27 clonal occurrences) and VanB (1 site, 2 clonal occurrences); 2) elevated quinupristin/dalfopristin MIC results (not vatD/E, 3 sites); and 3) chloramphenicol resistance (chloramphenicol acetyltransferase-positive strains, 3 sites). The esp gene, part of the putative E. faecium pathogenicity island and a marker for the clonal complex-17 lineage, was detected in 76% of vancomycin-resistant E. faecium. Clonal spread appears to be a dominant factor of MDR VRE dissemination on both continents, and further monitoring is critical to assist in the control of these resistant pathogens.     

Occurrence and antimicrobial susceptibility patterns of pathogens isolated from skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 2000)

A total of 1,404 bacterial isolates were recovered from skin and soft tissue infections (SSTIs) from hospitalized patients in 24 sites in the United States (US) and 5 Canadian medical centers as part of the SENTRY Antimicrobial Surveillance Program. Isolates were collected between October and December, 2000. The rank order of pathogens was: Staphylococcus aureus (45.9%), Pseudomonas aeruginosa (10.8%), Enterococcus spp. (8.2%), Escherichia coli (7.0%), Enterobacter spp. (5.8%) and Klebsiella spp. (5.1%). The same order was observed in the US and Canada. Of note, almost 30% of S. aureus were oxacillin-resistant. Vancomycin resistance among enterococci was low (7.8%) representing a marked decrease from earlier SENTRY Program reports. Several antimicrobial agents remained very active against P. aeruginosa and Enterobacteriaceae isolates. In particular amikacin, cefepime, and the carbapenems (imipenem and meropenem) showed an excellent spectrum of activity (>95% susceptible). Extended-spectrum beta-lactamase production was observed in both E. coli (7.1%) and Klebsiella spp. (11.3%). Cefepime remained highly active, even against ceftazidime-resistant isolates of Enterobacter spp. The results of this study have identified the most common causes of SSTIs in hospitalized patients in North America, and can be used to make informed decisions concerning standards of empiric treatment for SSTIs in this region.