Activity of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in Greece and Italy-SMART 2017-2021.

PURPOSE: The current study evaluated the in vitro activities of ceftolozane/tazobactam (C/T), imipenem/relebactam (IMI/REL), and comparators against recent (2017-2021) clinical isolates of gram-negative bacilli from two countries in southern Europe. METHODS: Nine clinical laboratories (two in Greece; seven in Italy) each collected up to 250 consecutive gram-negative isolates per year from lower respiratory tract, intraabdominal, urinary tract, and bloodstream infection samples. MICs were determined by the CLSI broth microdilution method and interpreted using 2022 EUCAST breakpoints. ß-lactamase genes were identified in select ß-lactam-nonsusceptible isolate subsets. RESULTS: C/T inhibited the growth of 85-87% of Enterobacterales and 94-96% of ESBL-positive non-CRE NME (non-Morganellaceae Enterobacterales) isolates from both countries. IMI/REL inhibited 95-98% of NME, 100% of ESBL-positive non-CRE NME, and 98-99% of KPC-positive NME isolates from both countries. Country-specific differences in percent susceptible values for C/T, IMI/REL, meropenem, piperacillin/tazobactam, levofloxacin, and amikacin were more pronounced for Pseudomonas aeruginosa than Enterobacterales. C/T and IMI/REL both inhibited 84% of P. aeruginosa isolates from Greece and 91-92% of isolates from Italy. MBL rates were estimated as 4% of Enterobacterales and 10% of P. aeruginosa isolates from Greece compared to 1% of Enterobacterales and 3% of P. aeruginosa isolates from Italy. KPC rates among Enterobacterales isolates were similar in both countries (7-8%). OXA-48-like enzymes were only identified in Enterobacterales isolates from Italy (1%) while GES carbapenemase genes were only identified in P. aeruginosa isolates from Italy (2%). CONCLUSION: We conclude that C/T and IMI/REL may provide viable treatment options for many patients from Greece and Italy.

Activity of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected in central and northern Europe (Belgium, Norway, Sweden, Switzerland)-SMART 2017-21.

Objectives: To evaluate the in vitro activities of ceftolozane/tazobactam and imipenem/relebactam against clinical isolates of Gram-negative bacilli collected in four central and northern European countries (Belgium, Norway, Sweden, Switzerland) during 2017-21. Methods: Participating clinical laboratories each collected up to 250 consecutive Gram-negative isolates per year from patients with bloodstream, intraabdominal, lower respiratory tract or urinary tract infections. MICs were determined by CLSI broth microdilution and interpreted using 2022 EUCAST breakpoints. ß-Lactamase genes were identified in select ß-lactam-non-susceptible isolate subsets. Results: Ninety-five percent of all Enterobacterales (n = 4158), 95% of ESBL-positive non-carbapenem-resistant Enterobacterales (non-CRE) phenotype Escherichia coli and 85% of ESBL-positive non-CRE phenotype Klebsiella pneumoniae were ceftolozane/tazobactam susceptible. By country, 88% (Belgium), 91% (Sweden, Switzerland) and 96% (Norway) of ESBL-positive non-CRE phenotype Enterobacterales were ceftolozane/tazobactam susceptible. Greater than ninety-nine percent of non-Morganellaceae Enterobacterales and all ESBL-positive non-CRE phenotype Enterobacterales were imipenem/relebactam susceptible. Ceftolozane/tazobactam (96%) and imipenem/relebactam (95%) inhibited most Pseudomonas aeruginosa (n = 823). Both agents retained activity against ≥75% of cefepime-resistant, ceftazidime-resistant and piperacillin/tazobactam-resistant isolates; 56% and 43% of meropenem-resistant isolates were ceftolozane/tazobactam susceptible and imipenem/relebactam susceptible, respectively. By country, 94% (Belgium), 95% (Sweden) and 100% (Norway, Switzerland) of P. aeruginosa were ceftolozane/tazobactam susceptible and 93% (Sweden) to 98% (Norway, Switzerland) were imipenem/relebactam susceptible. Carbapenemase gene carriage among Enterobacterales and P. aeruginosa isolates was generally low (<1%) or completely absent with one exception: an estimated 2.7% of P. aeruginosa isolates from Belgium carried an MBL. Conclusions: Recent clinical isolates of Enterobacterales and P. aeruginosa collected in four central and northern European countries were highly susceptible (≥95%) to ceftolozane/tazobactam and imipenem/relebactam.

In vitro activity of ceftolozane/tazobactam against multidrug-resistant Pseudomonas aeruginosa from patients in Western Europe: SMART 2017-2020.

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections compromise both empirical and definitive antimicrobial therapies. The Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program identified 943 MDR P. aeruginosa (from a total of 4086 P. aeruginosa isolates [23.1%]) collected at 32 clinical laboratories in six countries in Western Europe from 2017 to 2020. Minimum inhibitory concentrations (MICs) for ceftolozane/tazobactam and 10 comparator agents were determined by broth microdilution and interpreted using 2021 EUCAST breakpoints. ß-lactamase genes were identified in selected isolate subsets. Most isolates of P. aeruginosa in Western Europe (93.3%) were ceftolozane/tazobactam-susceptible. A total of 23.1% of P. aeruginosa isolates were MDR. Of these, 72.0% were ceftolozane/tazobactam-susceptible, which is similar to that for ceftazidime/avibactam (73.6%) but >40% higher than for carbapenems, piperacillin/tazobactam, third- and fourth-generation cephalosporins, and levofloxacin. Metallo-ß-lactamases (MBLs) were carried by 8.8% of molecularly characterized MDR P. aeruginosa, and 7.6% of molecularly characterized MDR isolates carried Guiana Extended Spectrum (GES) carbapenemases. MBLs were identified in isolates from all six countries, ranging from 3.2% of all P. aeruginosa isolates from Italy to 0.4% of all isolates from the United Kingdom. Acquired ß-lactamases were not identified in 80.0% of molecularly characterized MDR P. aeruginosa isolates. Percentages of MDR isolates without detected ß-lactamases were higher in the United Kingdom (97.7%), Spain (88.2%), France (88.1%), and Germany (84.7%) than in Portugal (63.0%) and Italy (61.3%), where carbapenemases were more prevalent. Ceftolozane/tazobactam is an important treatment option for patients infected with MDR P. aeruginosa that are not susceptible to first-line antipseudomonal agents.

In vitro activity of imipenem/relebactam against piperacillin/tazobactam-resistant and meropenem-resistant non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa collected from patients with bloodstream, intra-abdominal and urinary tract infections in Western Europe: SMART 2018-2020.

Introduction. Piperacillin/tazobactam and carbapenems are important agents for the treatment of serious Gram-negative infections in hospitalized patients. Resistance to both agents is a significant concern in clinical isolates of Enterobacterales and Pseudomonas aeruginosa; new agents with improved activity are needed.Gap Statement. Publication of current, region-specific data describing the in vitro activity of newer agents such as imipenem/relebactam (IMR) against piperacillin/tazobactam-resistant and carbapenem-resistant Enterobacterales and P. aeruginosa are needed to support their clinical use.Aim. To describe the in vitro activity of IMR against non-Morganellaceae Enterobacterales (NME) and P. aeruginosa isolated from bloodstream, intra-abdominal and urinary tract infection samples by hospital laboratories in Western Europe with a focus on the activity of IMR against piperacillin/tazobactam-resistant and meropenem-resistant isolates.Methodology. From 2018 to 2020, 29 hospital laboratories in six countries in Western Europe participated in the SMART global surveillance programme and contributed 9487 NME and 1004 P. aeruginosa isolates. MICs were determined by CLSI broth microdilution testing and interpreted by EUCAST (2021) breakpoints. ß-Lactamase genes were identified in selected isolate subsets (2018-2020) and oprD sequenced in molecularly characterized P. aeruginosa (2020).Results. IMR (99.4 % susceptible), amikacin (98.0 %), meropenem (97.7 %) and imipenem (97.6 %) were the most active agents against NME; 83.1 % of NME were piperacillin/tazobactam-susceptible. Relebactam increased imipenem susceptibility of NME from Italy by 8.3 %, from Portugal by 2.9 %, and from France, Germany, Spain and the UK by <1 %. In total, 96.4 % of piperacillin/tazobactam-resistant (n=1601) and 73.7 % of meropenem-resistant (n=152) NME were IMR-susceptible. Also, 0.4 % of NME were MBL-positive, 0.9 % OXA-48-like-positive (MBL-negative) and 1.5 % KPC-positive (MBL-negative). Amikacin (95.4 % susceptible) and IMR (94.1 %) were the most active agents against P. aeruginosa; 81.7 % of isolates were imipenem-susceptible and 79.6 % were piperacillin/tazobactam-susceptible. Relebactam increased susceptibility to imipenem by 12.5 % overall (range by country, 4.3-17.5 %); and by 30.7 % in piperacillin/tazobactam-resistant and 24.3 % in meropenem-resistant P. aeruginosa. In total, 1.6 % of P. aeruginosa isolates were MBL-positive. Seven of eight molecularly characterized IMR-resistant P. aeruginosa isolates from 2020 were oprD-deficient.Conclusion. IMR may be a potential treatment option for bloodstream, intra-abdominal and urinary tract infections caused by NME and P. aeruginosa in Western Europe, including infections caused by piperacillin/tazobactam-resistant and meropenem-resistant isolates.

Activity of ceftolozane/tazobactam and imipenem/relebactam against clinical gram-negative isolates from Czech Republic, Hungary, and Poland-SMART 2017-2020.

Antimicrobial susceptibility was determined for clinical gram-negative isolates from Czech Republic, Hungary, and Poland, where published data for ceftolozane/tazobactam (C/T) and imipenem/relebactam (IMI/REL) is scarce. C/T was active against 94.3% of Enterobacterales, 10-18% higher than the tested cephalosporins and piperacillin/tazobactam. IMI/REL was the most active tested agent against non-Morganellaceae Enterobacterales (99.7% susceptible). C/T was the most active among all studied agents except colistin against Pseudomonas aeruginosa (96.0% susceptible); susceptibility to IMI/REL was 90.7%. C/T maintained activity against 73.7-85.3% of ß-lactam-resistant or multidrug-resistant P. aeruginosa subsets. C/T and IMI/REL could represent important treatment options for patients from these countries.

In vitro activity of imipenem/relebactam against piperacillin/tazobactam-resistant and meropenem-resistant non-Morganellaceae Enterobacterales and Pseudomonas aeruginosa collected from patients with lower respiratory tract infections in Western Europe: SMART 2018-20.

Objectives: To describe the in vitro activity of imipenem/relebactam against non-Morganellaceae Enterobacterales (NME) and Pseudomonas aeruginosa recently isolated from lower respiratory tract infection samples by hospital laboratories in Western Europe. Methods: From 2018 to 2020, 29 hospital laboratories in six countries in Western Europe participated in the SMART global surveillance programme and contributed 4414 NME and 1995 P. aeruginosa isolates. MICs were determined using the CLSI broth microdilution method and interpreted by EUCAST (2021) breakpoints. ß-Lactamase genes were identified in selected isolate subsets (2018-20) and oprD sequenced in molecularly characterized P. aeruginosa (2020). Results: Imipenem/relebactam (99.1% susceptible), amikacin (97.2%), meropenem (96.1%) and imipenem (95.9%) were the most active agents tested against NME; by country, relebactam increased imipenem susceptibility from <1% (France, Germany, UK) to 11.0% (Italy). A total of 96.0% of piperacillin/tazobactam-resistant (n = 990) and 81.1% of meropenem-resistant (n = 106) NME were imipenem/relebactam-susceptible. Only 0.5% of NME were MBL positive, 0.9% were OXA-48-like-positive (MBL negative) and 2.8% were KPC positive (MBL negative). Amikacin (91.5% susceptible) and imipenem/relebactam (91.4%) were the most active agents against P. aeruginosa; 72.3% of isolates were imipenem-susceptible. Relebactam increased susceptibility to imipenem by 34.4% (range by country, 39.1%-73.5%) in piperacillin/tazobactam-resistant and by 37.4% (3.1%-40.5%) in meropenem-resistant P. aeruginosa. Only 1.8% of P. aeruginosa isolates were MBL positive. Among molecularly characterized imipenem/relebactam-resistant P. aeruginosa isolates from 2020, 90.9% (30/33) were oprD deficient. Conclusions: Imipenem/relebactam appears to be a potential treatment option for lower respiratory tract infections caused by piperacillin/tazobactam- and meropenem-resistant NME and P. aeruginosa in Western Europe.

In vitro activity of imipenem/relebactam against Gram-negative ESKAPE pathogens isolated in 17 European countries: 2015 SMART surveillance programme.

Objectives: Relebactam is an inhibitor of class A ß-lactamases, including KPC ß-lactamases, and class C ß-lactamases, and is currently under clinical development in combination with imipenem. The objective of the current study was to evaluate the in vitro activity of imipenem/relebactam against Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) submitted by clinical laboratories in 17 European countries to the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance programme in 2015. Methods: MICs were determined using the CLSI standard broth microdilution method and interpreted using EUCAST clinical breakpoints. Relebactam was tested at a fixed concentration of 4 mg/L in combination with doubling dilutions of imipenem. Imipenem/relebactam MICs were interpreted using breakpoints for imipenem. Results: Rates of susceptibility to imipenem and imipenem/relebactam for isolates of P. aeruginosa (n = 1705), K. pneumoniae (n = 1591) and Enterobacter spp. (n = 772) were 72.0/94.7%, 88.7/94.8% and 95.6/96.8%, respectively. Relebactam restored imipenem susceptibility to 81.1%, 54.2% and 26.5% of imipenem-non-susceptible isolates of P. aeruginosa (n = 477), K. pneumoniae (n = 179) and Enterobacter spp. (n = 34). Most imipenem/relebactam-non-susceptible isolates carried MBLs, OXA-48 or GES carbapenemases. Relebactam did not increase the number of isolates of A. baumannii (n = 486) susceptible to imipenem. Conclusions: Relebactam restored susceptibility to imipenem for the majority of imipenem-non-susceptible isolates of P. aeruginosa and K. pneumoniae tested as well as some isolates of imipenem-non-susceptible Enterobacter spp. Based on our results, imipenem/relebactam appears to be a promising therapeutic option for treating patients with infections caused by antimicrobial-resistant Gram-negative bacilli.

Susceptibility of gram-negative aerobic bacilli from intra-abdominal pathogens to antimicrobial agents collected in the United States during 2011.

OBJECTIVES: During 2011, a total of 1442 gram-negative pathogens from intra-abdominal infections were collected as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) from 19 hospital sites within the United States. Susceptibility to ertapenem and comparators and molecular analysis of ertapenem resistant isolates was performed. METHODS: Extended-spectrum beta-lactamase ESBL (ESBL) isolates were determined using the Clinical and Laboratory Standards Institute's recommended phenotypic test. Isolates were identified to the species level, and tested for antimicrobial susceptibility using custom MicroScan dehydrated broth microdilution panels ESBLs and carbapenemases were characterized using the Check-Points microarray. Strain typing of Klebsiella pneumoniae was performed by rep-PCR on the DiversiLab System. RESULTS: The majority of isolates were Escherichia coli (36%), K. pneumoniae (18.6%), Pseudomonas aeruginosa (12.1%) and Enterobacter cloacae (8.4%). Incidence of ESBL-positive isolates was 12.7%, 9.7%, 3.6% and 3.1% for K. pneumoniae, E. coli, Proteus mirabilis and Klebsiella oxytoca, respectively. Against the majority of isolates and species tested, the most active antibiotics were amikacin, ertapenem, and imipenem, with the carbapenems being the most active in vitro, including against ESBL-positive isolates of E. coli. All other antibiotics exhibited diminished activity. Against K. pneumoniae, the carbapenems were notably less active against ESBL-positive isolates though their activity against this sub-population was still the highest of all antibiotics tested; however, 41.1% (14 of 34) of the phenotypically ESBL-positive K. pneumoniae co-produced a carbapenemase (KPC2 or KPC3), and >90% of the isolates producing only an ESBL remained susceptible to ertapenem. CONCLUSIONS: Further monitoring of susceptibility of intra-abdominal isolates is warranted due to limited therapeutic options available to physicians.

Etiology, extended-spectrum ß-lactamase rates and antimicrobial susceptibility of gram-negative bacilli causing intra-abdominal infections in patients in general pediatric and pediatric intensive care units--global data from the Study for Monitoring Antimicrobial Resistance Trends 2008 to 2010.

BACKGROUND: Antimicrobial resistance has been increasing for several years and is often higher in intensive care units (ICUs) than in other facilities. The spread of extended-spectrum ß-lactamases (ESBLs) in particular has profoundly impacted antimicrobial efficacy and usage. The Study for Monitoring Antimicrobial Resistance Trends has monitored the in vitro activity of ertapenem and several comparators against aerobic gram-negative bacteria from intra-abdominal infections (IAIs) for many years. This report summarizes susceptibility levels and epidemiology for key IAI pathogens cultured from general pediatric medical wards and pediatric ICUs globally. METHODS: 1248 gram-negative bacteria were collected from pediatric IAIs by 113 labs in 40 countries from 2008 to 2010. Susceptibility was determined by Clinical and Laboratory Standards Institute broth microdilution. Susceptibility rates (%S) were determined for species with ≥10 isolates. RESULTS: Sixty-two percent of isolates came from general pediatric wards and 38% from pediatric ICUs. The overall ESBL-positive rate was 11.0% for Escherichia coli and 38.9% for Klebsiella pneumoniae; the ESBL-positive rate for E. coli was twice as high in ICU as non-ICU. Most study drugs inhibited >90% of ESBL-negative isolates, but only the carbapenems inhibited >90% of ESBL-positive E. coli and only imipenem inhibited >90% of ESBL-positive K. pneumoniae. CONCLUSIONS: Amikacin, imipenem and ertapenem were the most active against gram-negative bacteria from pediatric IAIs, followed closely by the fluoroquinolones and cefepime. Other cephalosporins were often <90% active. ESBL rates were 38.9% for K. pneumoniae and 11.0% for E. coli. Therapy for pediatric IAIs should take into consideration local ESBL rates because only carbapenems inhibited most of these pathogens.

Epidemiology and susceptibility of Gram-negative appendicitis pathogens: SMART 2008-2010.

BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) has tracked the in vitro activity of ertapenem and comparators against aerobic gram-negative bacteria from intra-abdominal infections since 2002. This report describes the epidemiology and susceptibility for clinical isolates associated with appendicitis, collected from 2008 to 2010. METHODS: A total of 1,720 gram-negative bacilli were collected from patients with appendicitis in 122 hospitals in 39 countries worldwide; of these, 23% of isolates were from pediatric patients (≤ 17 years old). Minimum inhibitory concentrations (MICs) and extended-spectrum ß-lactamase (ESBL) phenotypes were determined by broth microdilution and interpreted using Clinical and Laboratory Standards Institute guidelines. RESULTS: The global ESBL-positive rate was 16.3%, ranging from 2.2% for Proteus mirabilis to 16.6% for Escherichia coli and 20.1% for Klebsiella pneumoniae. The ESBL-positive rates differed by age group (17.7% in adults vs. 11.4% in children) and by geographic region, with significantly higher rates in Asia/Pacific (28.0%) and significantly lower rates in North America (9.1%), Africa/Middle East (4.8%), and Europe (4.4%). Amikacin, imipenem-cilastatin, piperacillin-tazobactam, and ertapenem were the most active of the tested agents against aerobic gram-negative appendicitis pathogens across pediatric and adult age groups and across geographic regions, including ESBL-positive isolates. Cefepime and ceftazidime were active against ≥ 90% of global pediatric isolates. E. coli, by far the most frequently isolated species (68% in adults and 75% in pediatric patients), was significantly less susceptible in adults than in pediatric patients (p<0.05; Fisher exact test) to all tested agents except amikacin, ertapenem, imipenem-cilastatin, piperacillin-tazobactam, and ampicillin-sulbactam (with the latter showing low activity in both age groups). CONCLUSIONS: These in vitro data suggest that amikacin, imipenem-cilastatin, piperacillin-tazobactam, and ertapenem would perform well against aerobic gram-negative bacilli associated with appendicitis in both adults and children, especially in regions with high rates of ESBL-positive E. coli.

Antimicrobial susceptibility of inpatient urinary tract isolates of gram-negative bacilli in the United States: results from the study for monitoring antimicrobial resistance trends (SMART) program: 2009-2011.

BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends is an ongoing global surveillance program that has monitored the susceptibilities of Gram-negative bacilli from inpatient urinary tract infections (UTIs) since late 2009. OBJECTIVE: This analysis reports on the in vitro susceptibility of 2,135 isolates collected by 24 US sites from hospitalized patients with UTIs between 2009 and 2011. METHODS: Minimum inhibitory concentrations and susceptibility were determined according to the guidelines of the Clinical and Laboratory Standards Institute. RESULTS: Of the isolates collected, 88.6% (1,892) were Enterobacteriaceae, which included 48.9% (n = 1,045) Escherichia coli, 14.5% (n = 310) Klebsiella pneumoniae, 6.4% (n = 136) Proteus mirabilis, 2.5% (n = 54) Klebsiella oxytoca, and 16.3% (n = 347) other Enterobacteriaceae species. Overall, 6.8% of E coli, 10.3% of K pneumoniae, 3.7% of P mirabilis, and 11.1% of K oxytoca isolates were extended-spectrum ß-lactamase-producing strains. Of the Enterobacteriaceae isolates, 67.5% were community associated and 26.9% were hospital associated (5.7% had no demographics). Highest overall rates of activity for the study period were seen with amikacin, ertapenem, and imipenem. The least active antimicrobials tested were ampicillin-sulbactam, ciprofloxacin, and levofloxacin. CONCLUSIONS: Ertapenem, imipenem, and amikacin were the most active study drugs against extended-spectrum ß-lactamase-producing strains, although the activity against extended-spectrum ß-lactamase-producing K pneumoniae did not exceed 69% throughout the study period. The results of the Study for Monitoring Antimicrobial Resistance Trends surveillance study document the rates of antimicrobial resistance in UTI pathogens in the United States, which can assist health care practitioners in selecting the appropriate treatment for UTIs.

Monitoring the global in vitro activity of ertapenem against Escherichia coli from intra-abdominal infections: SMART 2002-2010.

During 2002-2010, a total of 30840 Escherichia coli clinical isolates from intra-abdominal infections were collected globally in the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance programme. The incidence of extended-spectrum ß-lactamase (ESBL)-producing isolates ranged from 9.2% in 2002 to 21.2% in 2010. The highest rates were observed in Asia (38.3%) and Latin America (22.9%) and the lowest rates in Africa (6.3%), North America (6%) and South Pacific (5.8%). Global susceptibility trends showed that there were only minor fluctuations in susceptibility to ertapenem and imipenem, with no significant decrease over time. Against ESBL-positive isolates, ertapenem susceptibility significantly increased during 2002-2010 globally. Moreover, susceptibility to ertapenem in the different geographical regions studied was also high, with only minor fluctuations generally observed. Notably, in Asia where the highest ESBL-positives rates (38.3%) were observed, susceptibility to ertapenem had actually significantly increased in this population during the 9-year study period. By contrast, susceptibility to amikacin, cephalosporins, fluoroquinolones and ß-lactam/ß-lactamase inhibitor combinations generally decreased over time. Further monitoring of the susceptibility to ertapenem and other antibiotics through SMART is warranted.

Low frequency of ertapenem-resistant intra-abdominal isolates of Escherichia coli from Latin America: susceptibility, ESBL-occurrence, and molecular characterisation (SMART 2008-2009).

The Study for Monitoring Antimicrobial Resistance Trends is an ongoing multi-year surveillance study that tracks worldwide antimicrobial resistance trends among aerobic and facultatively anaerobic Gram-negative bacilli isolated from intra-abdominal infections. During 2008-2009, 1366 isolates of Escherichia coli were collected from 19 investigator sites in 11 Latin American countries. Of the 1366 isolates, 323 (23.6%) were extended spectrum beta-lactamase (ESBL)-positive. Overall, the most effective agents tested were imipenem, ertapenem, and amikacin with susceptibilities of ≥96%. Against ESBL-positive isolates, only imipenem and ertapenem exhibited susceptibility ≥90%. Based on the use of the new Clinical and Laboratory Standards Institute clinical breakpoints for ertapenem (resistance ≥1 µg/ml), resistance to ertapenem among all E. coli isolates was only 0.3% (4/1366) throughout the region, ranging from 0% in several countries up to 1.2% in Ecuador. Against ESBL-positive isolates only, resistance to ertapenem in Latin America overall was 0.9% (3/323), with a maximum of 9.1% (1/11) observed in Argentina.

Trending 7 years of in vitro activity of tigecycline and comparators against Gram-positive and Gram-negative pathogens from the Asia-Pacific region: Tigecycline Evaluation Surveillance Trial (TEST) 2004-2010.

A total of 10948 clinical isolates was collected throughout the Asia-Pacific region as part of the Tigecycline Evaluation Surveillance Trial (TEST) during 2004-2010, consisting of 7549 Gram-negative and 3399 Gram-positive pathogens. Susceptibility trends for all species demonstrated several significant species-dependent susceptibility changes to multiple antibiotics. The most notable was minocycline, for which significant decreases in susceptibility (P<0.001) were observed for six of the ten species studied. In contrast, statistically significant susceptibility changes for tigecycline were observed in only two of the ten species, namely Klebsiella pneumoniae and Serratia marcescens. Seven years following the introduction of tigecycline into clinical use, this agent remains highly active against a wide range of pathogens from the Asia-Pacific region.

Using nucleic acid microarrays to perform molecular epidemiology and detect novel ß-lactamases: a snapshot of extended-spectrum ß-lactamases throughout the world.

The worldwide dissemination of extended-spectrum-ß-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae is a major concern in both hospital and community settings. Rapid identification of these resistant pathogens and the genetic determinants they possess is needed to assist in clinical practice and epidemiological studies. A collection of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis isolates, including phenotypically ESBL-positive (n = 1,093) and ESBL-negative isolates (n = 59), obtained in 2008-2009 from a longitudinal surveillance study (SMART) was examined using an in vitro nucleic acid-based microarray. This approach was used to detect and identify bla(ESBL) (bla(SHV), bla(TEM), and bla(CTX-M) genes of groups 1, 2, 9, and 8/25) and bla(KPC) genes and was combined with selective PCR amplification and DNA sequencing for complete characterization of the bla(ESBL) and bla(KPC) genes. Of the 1,093 phenotypically ESBL-positive isolates, 1,041 were identified as possessing at least one bla(ESBL) gene (95.2% concordance), and 59 phenotypically ESBL-negative isolates, used as negative controls, were negative. Several ESBL variants of bla(TEM) (n = 5), bla(SHV) (n = 11), bla(CTX-M) (n = 19), and bla(KPC) (n = 3) were detected. A new bla(SHV) variant, bla(SHV-129), and a new bla(KPC) variant, bla(KPC-11), were also identified. The most common bla genes found in this study were bla(CTX-M-15), bla(CTX-M-14), and bla(SHV-12). Using nucleic acid microarrays, we obtained a "molecular snapshot" of bla(ESBL) genes in a current global population; we report that CTX-M-15 is still the dominant ESBL and provide the first report of the new ß-lactamase variants bla(SHV-129) and bla(KPC-11).

Susceptibility of Klebsiella pneumoniae isolates from intra-abdominal infections and molecular characterization of ertapenem-resistant isolates.

A total of 2,841 clinical isolates of Klebsiella pneumoniae from intra-abdominal infections worldwide were collected in the Study for Monitoring Antimicrobial Resistance Trends (SMART) during 2008 and 2009. Overall, 22.4% of isolates had extended-spectrum ß-lactamases (ESBLs). The most active antibiotics among the 11 tested were imipenem, amikacin, and ertapenem, though even these, like all other comparators, were less consistently active against ESBL-positive isolates than against ESBL-negative isolates. Globally, 6.5% of isolates were ertapenem resistant based on the June 2010 clinical breakpoints published by the Clinical and Laboratory Standards Institute, with MICs of ≥1 µg/ml. Molecular characterization of 43 isolates with ertapenem MICs of ≥4 µg/ml showed that they variously produced CTX-M or SHV ESBLs combined with altered impermeability and/or had KPC (n = 28), OXA-48 (n = 3), or VIM (n = 1) carbapenemases. Further monitoring of ertapenem susceptibility and molecular characterization of ertapenem-resistant isolates are needed.

Antimicrobial susceptibility profiles of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections in the Asia-Pacific region according to currently established susceptibility interpretive criteria.

OBJECTIVES: The Study for Monitoring Antimicrobial Resistance Trends (SMART) was intended to reveal the evolving profiles of antimicrobial resistance among Gram-negative pathogens causing intra-abdominal infections (IAIs) from Asia-Pacific region in 2009. METHODS: A total of 3577 aerobic and facultative Gram-negative bacilli associated with IAIs were collected from 32 centers in 12 countries. The in vitro susceptibilities of these isolates to 12 antimicrobial agents were determined using the broth microdilution method. Susceptibility results for selected species of Enterobacteriaceae were also compared using different MIC interpretive criteria recommended by the Clinical and Laboratory Standards Institute in 2009 (M100-S19), in January 2010 (M100-S20), in June 2010 (M100-S20-U) and the European Committee on Antimicrobial Susceptibility Testing in 2010 (EUCAST-2010). RESULTS: Enterobacteriaceae comprised 89.5% of the isolates of which Escherichia coli was the most common species (56.7%). Enterobacteriaceae showed poor susceptibility to ampicillin-sulbactam in China (25.3%) and India (19%), and to fluoroquinolones in India (23.4%) and China (37.7%). The rates of extended-spectrum ß-lactamase (ESBL)-producing E. coli (36.8%) and Klebsiella pneumoniae (26.3%) remained high. The resistance of ESBL-producing K. pneumoniae to carbapenems also increased, especially to ertapenem (9.9%). Using M100-S20 criteria, 19% of ESBL-producing E. coli and 9% of ESBL-producing K. pneumoniae were susceptible to ceftazidime; 5% and 10% were susceptible to cefepime, respectively. Using M100-S20-U guidelines, the susceptibility rates of ESBL-producing K. pneumoniae (88%) and Enterobacter cloacae (69%) to ertapenem were substantially decreased from those determined using M100-S20. CONCLUSIONS: These up-to-date epidemiology and antimicrobial resistance surveillance data are crucial to select appropriate treatment of IAIs.