Carbapenem susceptibilities of Gram-negative pathogens in intra-abdominal and urinary tract infections: updated report of SMART 2015 in China.

BACKGROUND: To evaluate the susceptibility rates of aerobic and facultative Gram-negative bacterial isolates from Chinese intra-abdominal infections (IAI) and urinary tract infections (UTI) focusing on carbapenems and comparing their effectiveness between 2014 and 2015. METHODS: A total of 2318 strains in 2015 (1483 from IAI and 835 from UTI) and 2374 strains in 2014 (1438 from IAI and 936 from UTI) were included in the analysis. Antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. Hospital acquired (HA) IAI and UTI were defined as isolates sampled > 48 h and community acquired (CA) as isolates sampled < 48 h after admission. RESULTS: The main species derived from IAI and UTI in 2015 were Escherichia coli (50.86%) and Klebsiella pneumoniae (19.20%). Susceptibilities of Escherichia coli IAI and UTI strains to imipenem (IPM) and ertapenem (ETP) were > 90% in 2014 and 2015, while the susceptibilities to IPM and ETP of Klebsiella pneumoniae IAI strains were >  80% in 2014 but dropped to ≤80% in 2015 for UTI strains. Susceptibilities of IAI Enterobacteriaceae strains to IPM and ETP in 2015 were lowest in the colon and abscesses, and Enterobacteriaceae susceptibilities of UTI and IAI isolates to IPM and ETP were lowest in medical, pediatric and surgery intensive care units (ICUs) in 2015. CONCLUSIONS: IPM and ETP were effective in vitro against Enterobacteriaceae isolated from IAIs and UTIs in 2014 and 2015, but susceptibility to carbapenems in UTIs markedly decreased in 2015.

Post Syrian war impact on susceptibility rates and trends in molecular characterization of Enterobacteriaceae.

OBJECTIVE: Describe susceptibility and molecular profiles among Enterobacteriaceae pathogens and to explore if war, among other factors, can affect antimicrobial resistance. METHODS: Clinical isolates from the Study for Monitoring Antimicrobial Resistance Trends associated with urinary tract and intra-abdominal infections between 2011 and 2015 were identified in Lebanon and Jordan. Susceptibility testing and molecular characterization were performed as per standard methods. RESULTS: A total of 1486 Enterobacteriaceae pathogens (including unusual pathogens) were identified. Incidence rates of  extended spectrum ß-lactamases were high with an overall higher prevalence of resistance in Jordan compared with Lebanon. CTX-M-15 was the most prevalent extended spectrum ß-lactamases produced and OXA-48 the most reported carbapenemases subtype. CONCLUSION: Changes in healthcare system due to war could impact regional resistance patterns and which requires a continuous surveillance program and containment plan.

Update of incidence and antimicrobial susceptibility trends of Escherichia coli and Klebsiella pneumoniae isolates from Chinese intra-abdominal infection patients.

BACKGROUND: To evaluate in vitro susceptibilities of aerobic and facultative Gram-negative bacterial (GNB) isolates from intra-abdominal infections (IAIs) to 12 selected antimicrobials in Chinese hospitals from 2012 to 2014. METHODS: Hospital acquired (HA) and community acquired (CA) IAIs were collected from 21 centers in 16 Chinese cities. Extended spectrum beta-lactamase (ESBL) status and antimicrobial susceptibilities were determined at a central laboratory using CLSI broth microdilution and interpretive standards. RESULTS: From all isolated strains the Enterobacteriaceae (81.1%) Escherichia coli accounted for 45.4% and Klebsiella pneumoniae for 20.1%, followed by Enterobacter cloacae (5.2%), Proteus mirabilis (2.1%), Citrobacter freundii (1.8%), Enterobacter aerogenes (1.8%), Klebsiella oxytoca (1.4%), Morganella morganii (1.2%), Serratia marcescens (0.7%), Citrobacter koseri (0.3%), Proteus vulgaris (0.3%) and others (1.0%). Non- Enterobacteriaceae (18.9%) included Pseudomonas aeruginosa (9.8%), Acinetobacter baumannii (6.7%), Stenotrophomonas maltophilia (0.9%), Aeromonas hydrophila (0.4%) and others (1.1%). ESBL-screen positive Escherichia coli isolates (ESBL+) showed a decreasing trend from 67.5% in 2012 to 58.9% in 2014 of all Escherichia coli isolates and the percentage of ESBL+ Klebsiella pneumoniae isolates also decreased from 2012 through 2014 (40.4% to 26.6%), which was due to reduced percentages of ESBL+ isolates in HA IAIs for both bacteria. The overall susceptibilities of all 5160 IAI isolates were 87.53% to amikacin (AMK), 78.12% to piperacillin-tazobactam (TZP) 81.41% to imipenem (IMP) and 73.12% to ertapenem (ETP). The susceptibility of ESBL-screen positive Escherichia coli strains was 96.77%-98.8% to IPM, 91.26%-93.16% to ETP, 89.48%-92.75% to AMK and 84.86%-89.34% to TZP, while ESBL-screen positive Klebsiella pneumoniae strains were 70.56%-80.15% susceptible to ETP, 80.0%-87.5% to IPM, 83.82%-87.06% to AMK and 63.53%-68.38% to TZP within the three year study. Susceptibilities to all cephalosporins and fluoroquinolones were less than 50% beside 66.5% and 56.07% to cefoxitin (FOX) for ESBL+ Escherichia coli and Klebsiella pneumoniae strains respectively. CONCLUSIONS: The total ESBL+ rates decreased in Escherichia coli and Klebsiella pneumoniae IAI isolates due to fewer prevalence in HA infections. IPM, ETP and AMK were the most effective antimicrobials against ESBL+ Escherichia coli and Klebsiella pneumoniae IAI isolates in 2012-2014 and a change of fluoroquinolone regimens for Chinese IAIs is recommended.

Antimicrobial susceptibilities of aerobic and facultative gram-negative bacilli isolated from Chinese patients with urinary tract infections between 2010 and 2014.

BACKGROUND: The objective of this study was to investigate the distribution and susceptibility of aerobic and facultative Gram-negative bacilli isolated from Chinese patients with UTIs collected within 48 h (community acquired, CA) or after 48 h (hospital acquired, HA) of hospital admission. METHODS: From 2010 to 2014, the minimum inhibitory concentrations (MICs) of 12 antibiotics for 4,332 aerobic and facultative Gram-negative bacilli, sampled in 21 hospitals in 16 cities, were determined by the broth microdilution method. RESULTS: Enterobacteriaceae composed 88.5% of the total isolates, with Escherichia coli (E. coli) (63.2%) the most commonly isolated species, followed by Klebsiella pneumoniae (K. pneumoniae) (12.2%). Non-Enterobacteriaceae accounted for only 11.5% of all isolates and included mainly Pseudomonas aeruginosa (P. aeruginosa) (6.9%) and Acinetobacter baumannii (A. baumannii) (3.3%). Among the antimicrobial agents tested, the susceptibility rates of E.coli to the two carbapenems, ertapenem and imipenem as well as amikacin and piperacillin-tazobactam ranged from 92.5 to 98.7%. Against K. pneumonia, the most potent antibiotics were imipenem (92.6% susceptibility), amikacin (89.2% susceptibility) and ertapenem (87.9% susceptibility). Although non-Enterobacteriaceae did not show high susceptibilities to the 12 common antibiotics, amikacin exhibited the highest in vitro activity against P. aeruginosa over the 5-year study period, followed by piperacillin-tazobactam, imipenem, ceftazidime, cefepime, ciprofloxacin, and levofloxacin. The Extended Spectrum Beta-Lactamase (ESBL) rates decreased slowly during the 5 years in E. coli from 68.6% in 2010 to 59.1% in 2014, in K. pneumoniae from 59.7 to 49.2%, and in Proteus mirabilis (P. mirabilis) from 40.0 to 26.1%. However, the ESBL rates were different in 5 regions of China (Northeast, North, East, South and Middle-China). CONCLUSION: E. coli and K. pneumonia were the major pathogens causing UTIs and carbapenems and amikacin retained the highest susceptibility rates over the 5-year study period, indicating that they are good drug choices for empirical therapies, particularly of CA UTIs in China.

In Vitro Activity of Imipenem against Carbapenemase-Positive Enterobacteriaceae Isolates Collected by the SMART Global Surveillance Program from 2008 to 2014.

The Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program collected 103,960 isolates of Enterobacteriaceae from 2008 to 2014. From this isolate collection, all ertapenem-nonsusceptible isolates (MIC, ≥1 µg/ml; n = 3,428) and 9,371 isolates of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis with an ertapenem-susceptible extended-spectrum-ß-lactamase (ESBL)-positive phenotype were assessed for the presence of common carbapenemase genes using a Check-MDR CT101 microarray (Check-Points, Wageningen, the Netherlands) and published multiplex PCR assays. Testing identified 1,493 isolates that harbored a carbapenemase gene (1,485 ertapenem-nonsusceptible isolates and 8 ertapenem-susceptible ESBL-positive isolates) and accounted for 1.4% (1,493/103,960) of all isolates of Enterobacteriaceae The most frequently identified carbapenemase genes were the KPC (n = 794), OXA-48-like (n = 300), and NDM (n = 290) genes. Carbapenemase genes were most frequently identified in Klebsiella pneumoniae (n = 1,127), Escherichia coli (n = 149), and Enterobacter cloacae (n = 110). Among the carbapenemase-positive isolates, 66.7% (2/3), 37.0% (111/300), 20.0% (8/40), 3.3% (3/92), 2.3% (18/794), and 0% (0/290) of the isolates with genes for GES, OXA-48-like, IMP, VIM, KPC, and NDM, respectively, were susceptible to imipenem (MIC, ≤1 µg/ml). Isolates that tested as susceptible to imipenem were not uncommon among carbapenemase-positive isolates (9.4%, 141/1,493) and most frequently carried OXA-48-like enzymes (78.7%; 111/141); however, overall, these isolates remained rare (0.1%, 141/103,960). The practice of screening clinical isolates of Enterobacteriaceae that test as susceptible to carbapenems in vitro for the presence of carbapenemase genes remains controversial and requires further study.

Epidemiology and susceptibility of pathogens from SMART 2011-12 Turkey: evaluation of hospital-acquired versus community-acquired urinary tract infections and ICU- versus non-ICU-associated intra-abdominal infections.

Objectives: To describe the epidemiology and susceptibility of pathogens (including ESBL producers) from hospital-acquired (HA) versus community-acquired (CA) urinary tract infections (UTIs) and ICU- versus non-ICU-associated intra-abdominal infections (IAIs) in Turkey as a part of the SMART study. Methods: : For this report, Gram-negative pathogens (363 from UTIs and 458 from IAIs) were collected in 2011 and 2012 at six hospitals in Turkey. HA versus CA UTIs and ICU- versus non-ICU-associated IAIs were compared for the species isolated, percentage of ESBL-positive isolates by species and susceptibility for overall and individual Gram-negative species. Results: : Escherichia coli was the most common pathogen identified in HA (40.2%) and CA (73.9%) UTIs and ICU-associated (25.8%) and non-ICU-associated (43.3%) IAIs. The rate of ESBL-positive E. coli was significantly higher in HA than in CA UTIs (50.5% versus 38.2%, P < 0.001) and in non-ICU-associated than in ICU-associated IAIs (52.5% versus 29.2%, P = 0.029). Of the drugs studied, only amikacin was active against ≥90% of pathogens in UTIs, while ertapenem, imipenem and amikacin were active against ≥90% of E. coli ; and imipenem, amikacin and cefoxitin were active against ≥90% of Klebsiella pneumoniae in IAIs. Conclusions: Our findings demonstrated that E. coli continues to be the principal pathogen of UTIs and IAIs in Turkey. Along with a high rate of ESBL-positive isolates, high antimicrobial resistance among Gram-negative bacilli from either UTIs or IAIs was noted particularly in the case of HA UTIs and ICU-associated IAIs, with a higher likelihood of carbapenem- or amikacin-based therapy to provide the broadest activity against bacterial pathogens.

Epidemiology and Antimicrobial Susceptibility of Gram-Negative Pathogens Causing Intra-abdominal Infections in Pediatric Patients in Europe-SMART 2011-2014.

BACKGROUND: The most common type of intra-abdominal infection (IAI) is appendicitis, which occurs most frequently in children and young adults. Yet, few studies on the microbiology of pediatric IAI are available, which is problematic because antimicrobial therapy for IAI usually needs to be initiated before microbiological culture results are available. With this study, we aimed to assess whether resistance patterns in pediatric IAI in Europe that would help clinicians select empiric therapy can be identified. METHODS: Gram-negative pathogens (n = 1259) were collected from pediatric patients as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in 16 European countries from 2011 to 2014. Minimal inhibitory concentrations (MICs) and extended-spectrum ß-lactamase (ESBL) phenotype were determined by broth microdilution according to Clinical and Laboratory Standards Institute guidelines, and susceptibility was interpreted according to European Committee on Antimicrobial Susceptibility Testing guidelines. An IAI was defined as hospital- or community-associated if cultured ≥48 or <48 hours after admission, respectively. RESULTS: Overall, only imipenem and amikacin exceeded 90% susceptibility when all Gram-negative pathogens were combined, and ertapenem, cefepime, ceftazidime, piperacillin-tazobactam, and levofloxacin reached at least 85%. However, resistance, ESBL-positive, and multidrug-resistance (MDR) rates were substantially higher in isolates from patients with hospital-associated IAI than from those with community-associated IAI (eg, 14.1% vs 5.1% MDR isolates, respectively, among all Gram-negative pathogens), higher in isolates from intensive care units than in those from general wards, and higher in isolates from infants than in those from children ≥1 year of age. In addition, MDR rates varied markedly within Europe. CONCLUSIONS: These results indicate that empiric therapy of pediatric IAI in Europe should reflect not only regional and local resistance patterns but also higher resistance rates in hospital-associated infections, intensive care units, and infants.

Antimicrobial-resistant Pseudomonas aeruginosa and Acinetobacter baumannii From Patients With Hospital-acquired or Ventilator-associated Pneumonia in Vietnam.

PURPOSE: Multidrug-resistant bacterial pathogens are becoming a significant problem worldwide. Acinetobacter baumannii and Pseudomonas aeruginosa are problematic multidrug-resistant pathogens. This multicenter study in Vietnam determined the level of resistance to antimicrobial agents used to treat A baumannii and P aeruginosa infections in this country. METHODS: Five medical centers in Vietnam provided 529 P aeruginosa and 971 Acinetobacter species (904 A baumannii) isolates from patients with hospital-acquired or ventilator-associated pneumonia from 2012 to 2014. A central laboratory verified identification of the isolates and performed susceptibility testing using Clinical and Laboratory Standards Institute methods. FINDINGS: Resistance to cephalosporins, ß-lactam/ß-lactamase inhibitors, carbapenems, and fluoroquinolones was >90% against A baumannii. Aminoglycosides had only slightly better activity, with amikacin resistance >80%. Only colistin (MIC90, ≤0.25 mg/L) and tigecycline (MIC90, 4 mg/L) had appreciable activity against A baumannii. Similar activity was observed among the ß-lactams tested against P aeruginosa. Cefepime demonstrated the highest activity (60.1% susceptible), which was similar to doripenem (58.6% susceptible), the most active carbapenem tested. Amikacin was the most active aminoglycoside tested against P aeruginosa, with susceptibility of 81.7% compared with tobramycin (58.0%) and gentamicin (56.5%). Fluoroquinolones had limited activity against P aeruginosa with susceptibility to ciprofloxacin (55.0%). All P aeruginosa isolates had colistin MIC values ≤2 mg/L. IMPLICATIONS: The data from this 3-year longitudinal study in Vietnam demonstrate that 2 of the most common nonfermentative gram-negative pathogens associated with hospital-acquired and ventilator-associated pneumonia are significantly resistant to most of the available treatment options and require combination therapies unless new antimicrobial agents become available.

Discrepancy between genotypic and phenotypic extended-spectrum ß-lactamase rates in Escherichia coli from intra-abdominal infections in the USA.

Varying rates of false-positive results of phenotypic extended-spectrum ß-lactamase (ESBL) tests have been reported for different methods in different settings, species and geographic locations. This report describes discrepancies in Escherichia coli genotypic and phenotypic ESBL rates observed in a surveillance study of 29 US hospitals that participated in the Study for Monitoring Antimicrobial Resistance Trends (SMART). The ESBL phenotype was determined with the Clinical and Laboratory Standards Institute confirmatory broth microdilution test using cefotaxime and ceftazidime with and without clavulanate. Genes encoding ESBLs, carbapenemases and plasmidic AmpC ß-lactamases were detected using a combination of microarray and multiplex PCR assays. Among 168 molecularly characterized phenotypically ESBL-positive E. coli isolates from intra-abdominal infections, 4.8 % were genotypically negative from 2009 to 2012 and 29.5 % in 2013. Because of the high rate of false-positive phenotypic ESBL results in 2013, the 5-year phenotypic ESBL trend was skewed and showed a statistically significant increase (P<0.05) in ESBL-positive E. coli in the USA, which was not seen using the genotypic ESBL rates. The majority of false-positive phenotypic profiles had ceftazidime MICs of 2 µg ml-1 and a ≥3 doubling dilution decrease in MIC for only one of the two antimicrobial agents. False-positive ESBL results can adversely impact epidemiological surveillance and patient care (including inappropriate treatment, unnecessary patient isolation and higher costs). Careful evaluation and comparison of phenotypic and genotypic test results can yield the greatest insight, but the most accurate (and faster) detection of ESBL producers is usually based on molecular data.

In Vitro Activity of Oral Antimicrobial Agents against Pathogens Associated with Community-Acquired Upper Respiratory Tract and Urinary Tract Infections: A Five Country Surveillance Study.

INTRODUCTION: Bacterial infections that cause community-acquired urinary tract infections (CA-UTI) and upper respiratory tract infections (CA-URTI) are most frequently treated empirically. However, an increase in antimicrobial resistance has become a problem when treating outpatients. METHODS: This study determined the in vitro activities of oral antibiotics among 1501 pathogens from outpatients with CA-UTI and CA-URTI in medical centers during 2012 and 2013 from Argentina, Mexico, Venezuela, Russia, and the Philippines. Minimal inhibitory concentrations (MICs) were determined using broth microdilution and susceptibility defined by Clinical Laboratory Standards Institute (CLSI) and European Committee for Antimicrobial Susceptibility Testing (EUCAST) criteria. RESULTS: Ceftibuten (MIC50, ≤0.25 mg/L) was more potent in vitro compared to other ß-lactams against Enterobacteriaceae from CA-UTI. Susceptibility to fluoroquinolones using CLSI criteria varied: Argentina and Mexico (50%), the Philippines (60%), Venezuela (70%), and Russia (80%). Fosfomycin susceptibility was >90% against Enterobacteriaceae in each country. Susceptibility among Enterobacteriaceae to trimethoprim-sulfamethoxazole was 30.6-75.6% and nitrofurantoin susceptibility also varied among the countries and was higher when EUCAST breakpoints were applied (65->90%) compared to CLSI (52-84%). All Haemophilus influenzae isolates from CA-URTI were susceptible to ceftibuten, cefixime, cefpodoxime, and cefuroxime using CLSI breakpoint criteria. EUCAST criteria produced intermediate and resistant MIC values for these oral cephalosporins. Country-specific susceptibility variation for fluoroquinolones, macrolides, and trimethoprim-sulfamethoxazole was observed among Streptococcus pneumoniae and Streptococcus pyogenes from CA-URTI. CONCLUSION: This study demonstrated that antimicrobial susceptibility patterns varied in the five countries investigated among pathogens from CA-UTI and CA-URTI. FUNDING: Merck & Co. Inc., Kenilworth, New Jersey, USA.

Susceptibility patterns and ESBL rates of Escherichia coli from urinary tract infections in Canada and the United States, SMART 2010-2014.

Increasing antimicrobial resistance in urinary tract infections (UTI) is a concern. To evaluate resistance trends, 3498 Escherichia coli UTI isolates were collected from 2010 to 2014 in the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Canada and United States (US). ESBL phenotype and susceptibility were determined using CLSI microdilution and breakpoints. US ESBL rates increased in 2010-2014 (7.8-18.3%, P < 0.0001), especially among hospital-associated (HA) infections, males, and older patients (≥65 years). Overall, ESBL rates in Canada showed no significant trend (10.4-13.0%. P = 0.079), and were lower than US rates in recent years, but increased significantly among community-associated (CA) infections, females, and older patients. In the US, but not Canada, susceptibility to cephalosporins and fluoroquinolones among 2013-2014 isolates was significantly lower in isolates from HA than CA UTI, males than females, and ≥65- than <65-year-olds. These observations confirm increasing resistance in E. coli. Subgroup analyses like these may help direct empirical therapy.

Pathogen Prevalence and Antimicrobial Susceptibility Among Enterobacteriaceae Causing Hospital-associated Intra-abdominal Infections in Adults in the United States (2012-2013).

PURPOSE: Selection and prompt initiation of the appropriate empiric antimicrobial therapy are critical to decrease morbidity and mortality and shorten the length of hospitalization among patients with hospital-associated intra-abdominal infections (HA-IAIs). Therapeutic choices for the treatment of patients with HA-IAI require careful consideration. This study was conducted to evaluate the antimicrobial susceptibility of common pathogens collected from adult patients with HA-IAI in the United States. METHODS: Gram-negative bacilli (N = 1285) were collected during 2012-2013 from SMART (Study for Monitoring Antimicrobial Resistance Trends). Isolates were tested at a central laboratory by using Clinical and Laboratory Standards Institute methods and interpretation of susceptibility to 12 antimicrobial agents. FINDINGS: Most of the isolates (80.8%) were Enterobacteriaceae, and Escherichia coli was the most common species. Susceptibility to frequently used antimicrobial agents for treating IAI showed that ertapenem, imipenem, and amikacin were more active than other agents against Enterobacteriaceae, including multidrug-resistant isolates. More than 92% of E coli, including extended-spectrum ß-lactamase (ESBL) producers, and Klebsiella pneumoniae isolates were susceptible to ertapenem, imipenem, and amikacin. Cefepime was the most active (>90% susceptibility) cephalosporin against all species except K pneumoniae (86.6%) but with much reduced activity against isolates with ESBLs. Piperacillin/tazobactam had reduced activity against Enterobacter species (70.4%-76.4% susceptible) and ESBL-producing K pneumoniae (22.5% susceptible). Fluoroquinolones exhibited poor activity against E coli (overall susceptibility <70%). IMPLICATIONS: Proper empiric antimicrobial treatment, including combining appropriate agents, of HA-IAI requires detailed understanding of the epidemiology of common pathogens and antimicrobial resistance patterns. In light of rising rates of antimicrobial resistance, ongoing surveillance is critical for clinical decision-making.

Regional differences and trends in antimicrobial susceptibility of Acinetobacter baumannii.

Acinetobacter baumannii, although representing a small percentage of Gram-negative bacilli isolates in intra-abdominal infections (IAIs) and urinary tract infections (UTIs), is frequently multidrug-resistant (MDR) and can pose difficult therapeutic challenges. From 2011 to 2014, 2337 A. baumannii were collected from IAIs and UTIs at 453 hospital sites in 48 countries as part of the SMART ongoing surveillance initiative. Current susceptibility and multidrug resistance, defined as resistance to at least three of the tested drug classes, were determined in a subset of 1011 isolates from 2013 to 2014. A. baumannii comprised 0.7-4.6% of all aerobic and facultative Gram-negative bacilli isolated in six global regions. MDR rates were lowest in North America (47%) and highest in Europe and the Middle East (>93%), with higher rates in ICUs than in non-ICU wards in almost all regions. Antimicrobial susceptibility profiles varied by region but resistance was high everywhere, with no drug inhibiting >70% of A. baumannii isolates in any region. Susceptibility to imipenem was highest in North America (64%) and lowest in Europe and the Middle East (≤11%). Amikacin overall was the most active of the studied agents, including against MDR isolates (of which 11-38% were susceptible). Trend analysis of only those countries that contributed isolates in each study year (2011-2014) demonstrated an increasing trend in MDR rates in the Middle East as well as decreasing susceptibility to several single antimicrobial agents in Africa, Europe and the Middle East. These patterns and trends can help direct antimicrobial therapy and infection control efforts.

Antimicrobial Susceptibilities of Aerobic and Facultative Gram-Negative Bacilli from Intra-abdominal Infections in Patients from Seven Regions in China in 2012 and 2013.

To evaluate the antimicrobial susceptibility of Gram-negative bacilli that caused hospital-acquired and community-acquired intra-abdominal infections (IAIs) in China between 2012 and 2013, we determined the susceptibilities to 12 antimicrobials and the extended-spectrum ß-lactamase (ESBL) statuses of 3,540 IAI isolates from seven geographic areas in China in a central laboratory using CLSI broth microdilution and interpretive standards. Most infections were caused by Escherichia coli (46.3%) and Klebsiella pneumoniae (19.7%). Rates of ESBL-producing E. coli (P = 0.031), K. pneumoniae (P = 0.017), and Proteus mirabilis (P = 0.004) were higher in hospital-acquired IAIs than in community-acquired IAIs. Susceptibilities of enterobacteriaceae to ertapenem, amikacin, piperacillin-tazobactam, and imipenem were 71.3% to 100%, 81.3% to 100%, 64.7% to 100%, and 83.1% to 100%, respectively, but imipenem was ineffective against P. mirabilis (<20%). Although most ESBL-positive hospital-acquired isolates were resistant to third- and fourth-generation cephalosporins, the majority were susceptible to cefoxitin (47.9% to 83.9%). Susceptibilities of ESBL-positive isolates to ampicillin-sulbactam (<10%) were low, whereas susceptibilities to ciprofloxacin (0% to 54.6%) and levofloxacin (0% to 63.6%) varied substantially. The prevalences of cephalosporin-susceptible E. coli and K. pneumoniae were higher in the northeastern and southern regions than in the central and eastern regions, reflecting the ESBL-positive rates in these areas, and were lowest in the Jiangsu-Zhejiang (Jiang-Zhe) area where the rates of carbapenem resistance were also highest. Ertapenem, amikacin, piperacillin-tazobactam, and imipenem are the most efficacious antibiotics for treating IAIs in China, especially those caused by E. coli or K. pneumoniae. Resistance to cephalosporins and carbapenems is more common in the Jiang-Zhe area than in other regions in China.

Characterization of extended-spectrum beta-lactamases and antimicrobial resistance of Klebsiella pneumoniae in intra-abdominal infection isolates in Latin America, 2008-2012. Results of the Study for Monitoring Antimicrobial Resistance Trends.

The Study for Monitoring Antimicrobial Resistance Trends has monitored the in vitro activity of several recommended antimicrobials used in the management of intra-abdominal infections (IAIs) globally since 2002. In this report, we document the changing susceptibility patterns to recommended antimicrobials in Klebsiella pneumoniae isolates from patients with IAIs in 11 Latin American countries between 2008 and 2012 and describe the beta-lactamases encoded by phenotypically extended-spectrum beta-lactamase (ESBL)-positive and ertapenem-nonsusceptible isolates. Overall, the incidence of phenotypically ESBL-positive K. pneumoniae did not change significantly from 2008 (40.4%) to 2012 (41.2%) (P > 0.05). However, trend analysis documented an increase in isolates encoding K. pneumoniae carbapenemase (KPC) or both KPC and an ESBL. Decreasing susceptibility (P < 0.05) was noted for cefepime, ceftazidime, ceftriaxone, ertapenem, and imipenem among all K. pneumoniae, as well as for cefepime, cefotaxime, cefoxitin, ceftriaxone, ertapenem, and imipenem among ESBL-positive isolates, while susceptibility of ESBL-negative isolates to ampicillin-sulbactam actually increased (P < 0.05).

Susceptibility trends and molecular characterization of Gram-negative bacilli associated with urinary tract and intra-abdominal infections in Jordan and Lebanon: SMART 2011-2013.

OBJECTIVES: To investigate phenotypic and genotypic patterns of antimicrobial resistance among Gram-negative bacilli associated with urinary tract infection (UTI) and intra-abdominal infection (IAI) in medical centres of Jordan and Lebanon. METHODS: Gram-negative bacilli from the SMART study, collected between the years 2011 and 2013, were first identified at local laboratories. These isolates were shipped to a central laboratory where re-identification, susceptibility testing, and molecular characterization were performed using standard methods. RESULTS: Among the 523 UTI-associated isolates, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were the most frequent (70%, 14%, and 5%, respectively). E. coli, K. pneumoniae, and Pseudomonas aeruginosa were the most frequent species among the 527 IAI-associated isolates (46%, 14%, and 12%, respectively). Incidence rates of extended-spectrum beta-lactamase (ESBL) producers among UTI-associated E. coli, K. pneumoniae, and P. mirabilis were 43%, 54%, and 4%, respectively. Corresponding rates among IAI-associated isolates were 49%, 56%, and 12%, respectively. Acinetobacter baumannii and P. aeruginosa isolates showed very disturbing low susceptibility patterns. CTX-M-15 was the most prevalent ESBL produced. Seventeen isolates were non-susceptible to carbapenems (estimated prevalence of 1.6%). CONCLUSIONS: The alarmingly high rates of ESBL production and emergence of carbapenemases emphasize the urgent need to develop antimicrobial stewardship initiatives and to maintain antimicrobial resistance surveillance systems.

Resistance Rates of Intra-Abdominal Isolates from Intensive Care Units and Non-Intensive Care Units in the United States: The Study for Monitoring Antimicrobial Resistance Trends 2010-2012.

BACKGROUND: Enterobacteriaceae (3,235 isolates), Pseudomonas aeruginosa (476 isolates), and Acinetobacter baumannii (106 isolates) from inpatient intra-abdominal infections (IAIs) were collected for the 2010-2012 Study for Monitoring Antimicrobial Resistance Trends (SMART) program in the United States. This report evaluates the in vitro activity of several antimicrobial agents recommended for treatment of IAIs and compares profiles of isolates from intensive care units (ICUs) and non-intensive care units (non-ICUs). METHODS: Gram-negative bacilli from hospitalized patients with IAIs were obtained each year from 2010-2012 from hospitals in the United States and tested for susceptibility to 12 antibiotics according to 2012 Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The most active agents against members of the Enterobacteriaceae family from both ICUs and non-ICUs were amikacin, ertapenem, and imipenem-cilastatin, whereas the least active agent was ampicillin-sulbactam. Amikacin was the only agent with good activity against P. aeruginosa, whereas none of the agents tested exhibited substantial activity against A. baumannii. Amikacin, ceftazidime, ceftriaxone, ciprofloxacin, levofloxacin, and imipenem-cilastatin were significantly less active against Enterobacteriaceae from ICU patients, whereas cefepime and ceftazidime were significantly less active against P. aeruginosa from ICU patients. Intensive care unit isolates were more likely to be multi-drug-resistant than non-ICU isolates, although there was no difference in extended-spectrum ß-lactamase (ESBL) production rates between the two patient groups. CONCLUSIONS: Despite increasing resistance trends, in this study amikacin, ertapenem, and imipenem-cilastatin were shown to have good in vitro activity against the most frequently isolated gram-negative bacilli from IAIs in ICU and non-ICU settings.

Trends in susceptibility of Escherichia coli from intra-abdominal infections to ertapenem and comparators in the United States according to data from the SMART program, 2009 to 2013.

Antimicrobial resistance in Enterobacteriaceae, including resistance to carbapenems, is increasing worldwide. However, using U.S. Study for Monitoring Antimicrobial Resistance Trends (SMART) data for 2009 to 2013, no statistically significant decreasing susceptibility trends were found overall for Escherichia coli isolates from patients with intra-abdominal infections. In the subset of isolates from community-associated infections, susceptibility to levofloxacin decreased significantly and the increasing rate of multidrug-resistant E. coli approached statistical significance. In 2013, ertapenem, imipenem, and amikacin showed the highest susceptibility rates (≥99%) and fluoroquinolones the lowest (<70%). The 10 non-ertapenem-susceptible isolates (0.3% of all E. coli isolates) encoded one or more carbapenemases, extended-spectrum ß-lactamases (ESBLs), AmpC ß-lactamases, or non-ESBL ß-lactamases.

Epidemiology and antimicrobial susceptibility of Gram-negative aerobic bacteria causing intra-abdominal infections during 2010-2011.

The study for monitoring antimicrobial resistance trends (SMART) surveillance program monitors the epidemiology and trends in antibiotic resistance of intra-abdominal pathogens to currently used therapies. The current report describes such trends during 2010-2011. A total of 25,746 Gram-negative clinical isolates from intra-abdominal infections were collected and classified as hospital-associated (HA) if the hospital length of stay (LOS) at the time of specimen collection was ≥48 hours, community-associated (CA) if LOS at the time of specimen collection was <48 hours, or unknown (no designation given by participating centre). A total of 92 different species were collected of which the most common was Escherichia coli: 39% of all isolates in North America to 55% in Africa. Klebsiella pneumoniae was the second most common pathogen: 11% of all isolates from Europe to 19% of all isolates from Asia. Isolates were from multiple intra-abdominal sources of which 32% were peritoneal fluid, 20% were intra-abdominal abscesses, and 16.5% were gall bladder infections. Isolates were further classified as HA (55% of all isolates), CA (39% of all isolates), or unknown (6% of all isolates). The most active antibiotics tested were imipenem, ertapenem, amikacin, and piperacillin-tazobactam. Resistance rates to all other antibiotics tested were high. Considering the current data set and high-level resistance of intra-abdominal pathogens to various antibiotics, further monitoring of the epidemiology of intra-abdominal infections and their susceptibility to antibiotics through SMART is warranted.