Robert Badal

Kaohsiung Medical University, Kao-hsiung-shih, Kaohsiung, Taiwan

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Publications (140)115.18 Total impact

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    ABSTRACT: The prevalence of carbapenemase enzymes continues to increase. Among the Ambler class B enzymes is the New Delhi metallo-β-lactamase (NDM). This particular enzyme is capable of hydrolyzing nearly all β-lactam antimicrobial agents and has spread rapidly, becoming a global problem. Therapeutic treatment options for patients infected with isolates which produce this enzyme are difficult to manage as cross-resistance to other antimicrobial classes is common. The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a global surveillance study evaluating antimicrobial susceptibility of numerous Gram-negative bacterial species recovered from intra-abdominal and urinary tract infections. Clinical and Laboratory Standards Institute methods and molecular analysis identified 134 isolates of Enterobacteriaceae (nine species) and one Acinetobacter sp. with blaNDM genes. These isolates were collected in nine countries, and >95% of the isolates possessed the NDM-1 variant. MIC90 values were >4mg/L and >8mg/L for ertapenem and imipenem, respectively. No tested β-lactam or β-lactamase-inhibitor combination had activity against these isolates. Resistance to amikacin (79.9%) and levofloxacin (82.8 %) was common. Nearly all isolates encoded additional enzymes including AmpC cephalosporinases and extended-spectrum β-lactamases (ESBLs). There is an urgent need for infection control and continued global monitoring of isolates which harbor this enzyme as evidenced by recent outbreaks. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 11/2014; · 4.57 Impact Factor
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    ABSTRACT: We characterized Escherichia coli ST131 isolates among 116 carbapenemase-producing strains. Of isolates from 16 countries collected during 2008-2013, 35% belonged to ST131 and were associated with blaKPC, H30 lineage, and virotype C. This study documents worldwide incidents of resistance to "last resort" antimicrobial drugs among a common pathogen in a successful sequence type.
    Emerging infectious diseases. 11/2014; 20(11):1928-31.
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    ABSTRACT: Background: Pathogens in some long-term care (LTC) facilities have been reported to have high antimicrobial resistance with a large proportion of multi-drug resistant (MDR) strains. Using data from the Tigecycline Evaluation and Surveillance Trial (TEST), Enterobacteriaceae from LTC settings were compared to other inpatient and outpatient settings in Europe and North America. Methods: 512 Enterobacteriaceae isolates from various specimen sources were collected from LTC facilities, and 27,569 Enterobacteriaceae from inpatient and outpatient settings in 15 countries in Europe and North America from 2011 to 2013. MICs were determined at each site using CLSI broth microdilution method and interpreted according to CLSI/FDA guidelines. Isolates were categorized as MDR if resistant to ≥3 drug classes. Results: MIC90 (mcg/ml), % susceptible (%S), and % MDR among Enterobacteriaceae from each setting are shown below. %S values ≥ 90% are shaded. Of the species with n >10, Enterobacter cloacae had the highest proportion of MDR strains in LTC and inpatient settings (41.4% and 39.8%, respectively), whereas Citrobacter freundii had the highest for outpatients (34.7%). Conclusion: A significantly higher proportion of Enterobacteriaceae were MDR in LTC settings than in inpatients and outpatients. All study drugs showed lower susceptibility in LTC isolates than in the other two settings. Amikacin, meropenem, and tigecycline were the only drugs studied that showed only minor differences in %S between the three settings. These three agents also demonstrated the highest in vitro activity against Enterobacteriaceae, with susceptibility >90% in all three settings. Empiric therapy decisions should take into account the high proportion of MDR isolates in LTC settings.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background: IAI and SW infections present major challenges for hospitalized patients. Monitoring the resistance profiles expressed by the causative organisms is important. Therefore, data from the Tigecycline European Surveillance Trial (TEST) program were analyzed for the resistance patterns observed throughout Europe. Methods: Isolates were collected and tested locally by broth microdilution according to appropriate CLSI guidelines. Results of this study were based on isolates tested from 26 European countries from 2004 2013. Results: Antimicrobial: Percent Susceptible: IAI/SWa Organism (n): IAI/SW TIG AK AMP CFT LEV MER PT VAN Acinetobacter spp 163/1546 na/na 66/70 na/na 28/35 50/58 53/70 45/55 na/na Enterobacter spp 615/2478 96/96 98/98 2/4 53/65 84/89 96/98 68/78 na/na E. coli 1122/1748 100/100 99/99 38/32 84/76 74/64 99/100 91/90 na/na ESBL 128/311 100/100 94/96 na/na na/na 25/22 98/99 74/73 na/na K. pneumoniae 485/1156 97/96 96/95 2/3 75/67 79/73 95/93 78/76 na/na ESBL 82/266 94/96 88/88 na/na 4/0 89/34 89/88 32/43 na/na P. aeruginosa 367/2439 na/na 93/93 na/na na/na 70/67 65/76 76/75 na/na S. marcescens 101/861 94/96 99/98 5/4 78/83 93/93 96/99 87/94 na/na E. faecalis 366/1067 100/100 na/na 98/99 na/na 74/8 na/na na/na 98/99 E. faecium 381/356 100/100 na/na 21/17 na/na 17/17 na/na na/na 91/90 S. aureus, MSSA 100/3250 100/100 na/na na/na na/na 95/92 na/na na/na 100/100 S. aureus, MRSA 42/1302 100/100 na/na na/na na/na 12/16 na/na na/na 100/100 S. agalactiae 27/955 100/100 100/100 100/100 100/100 100/98 100/100 na/na 100/100 A na = breakpoints not defined or non-applicable, TIG (tigecycline; FDA breakpoints), AK (amikacin), AMP (ampicillin), CFT (Ceftriaxone), MER (meropenem), LEV (levofloxacin) PT (piperacillin/tazobactam), VAN (vancomycin) Conclusion: Against Enterobacteriaceae, including ESBL-producers, TIG, AK and MER were the most active agents; against gram-positive cocci TIG resistance was not encountered. For Acinetobacter spp. all agents demonstrated poor activity; against P. aeruginosa AK and PT were the most active agents. Given the propensity of the bacteria associated with IAI and SW infections, continued monitoring of antimicrobial activity in Europe is warranted.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background: Enterobacteriaceae play a significant role in LRT infections in at risk patients, especially in the healthcare associated environment. Treatment options are increasingly limited due to increased resistance to cephalosporins and other antimicrobials, thus warranting careful monitoring of resistance trends. The purpose of this study was to determine the in vitro activity of Tigecycline and other key antibiotics against LRT isolates of Enterobacteriaceae obtained from patients in North American and European hospitals. Methods: From 2009-2013 8,361 Enterobacteriaceae from LRT specimens were obtained from geographically distributed sites as part of the multi-year Tigecycline Evaluation Surveillance Trial (TEST). MICs were determined by the local laboratory using supplied microdilution panels and interpreted according to CLSI guidelines. Results: Percent Susceptible 2009 2010 2011 2012 2013 NAa EUa NA EU NA EU NA EU NA EU Drug n = 440 601 576 1472 537 1100 943 1683 390 619 Amikacin 98.0 97.5 97.9 97.4 98.3 95.8 98.3 98.5 98.7 99.0 Cefepime 92.7 91.4 93.6 90.0 92.0 86.9 93.4 88.5 90.8 90.6 Ceftriaxone 73.9 72.1 72.1 67.7 75.6 69.7 80.3 71.0 78.2 71.1 Levofloxacin 83.4 84.2 86.6 82.1 84.4 81.4 87.6 83.6 85.4 83.4 Meropenem 96.4 97.2 96.2 98.7 97.8 96.5 97.3 97.0 96.2 97.7 Pip-Tazob 83.4 80.4 85.2 78.9 83.6 79.3 86.2 83.1 88.2 85.0 Tigecycline 98.0 94.7 96.4 96.4 96.8 97.7 96.3 97.0 96.2 97.0 aNA: North America, EU: Europe; Pip-Tazo = piperacillin/tazobactam Conclusion: Tigecycline, amikacin and meropenem consistently demonstrated the highest % susceptibility (> 95%) against LRT isolates of Enterobacteriaceae regardless of study year or geographic region. Ceftriaxone was less active against European isolates than against North American isolates overall irrespective of study year possibly due to extended-spectrum β-lactamase prevalence in Europe vs. North America. Levofloxacin susceptibility was stable in the mid-80% range over all years. Tigecycline is not indicated for lower respiratory tract infections caused by Enterobacteriaceae.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background: Because of their resistance to many antimicrobials, Pseudomonas aeruginosa and Acinetobacter baumannii remain pathogens of interest in intra-abdominal infections (IAI), representing approximately 10% and 3%, respectively, of aerobic gram-negative pathogens in IAI globally. This report from the Study for Monitoring Antimicrobial Resistance Trends (SMART) evaluates the susceptibility of P. aeruginosa and A. baumannii from IAI in the USA between 2009 and 2013. Methods: 27 US laboratories each collected up to 100 consecutive aerobic or facultative gram-negative isolates from IAI each year. Susceptibility was determined using the CLSI broth microdilution method and breakpoints. Linear trends in susceptibility were assessed with the Cochran-Armitage test. Results: Susceptibility trends and prevalence of 967 P. aeruginosa and 199 A. baumannii isolates are shown below. N and % of all gram-negative pathogens are listed in the legend. A sensitivity analysis was conducted for P. aeruginosa susceptibility using only the 12 sites that submitted isolates in all 5 years. The significant increasing trends for ceftazidime and piperacillin-tazobactam were confirmed, the trend for cefepime approached significance (p=0.08), and an additional significant increasing trend was found for levofloxacin (p=0.03). Conclusion: P. aeruginosa's prevalence was stable at around 12% of gram-negative pathogens isolated from IAI in the USA from 2009 to 2013. Its susceptibility to cefepime, ceftazidime and piperacillin-tazobactam showed statistically significant change (p<0.05), with these drugs demonstrating increasing susceptibility. A. baumanniis prevalence was lower and decreased significantly over the 5 years, but its susceptibility remained stable for all tested drugs between 2009 and 2013. Resistance does not appear to be increasing in these difficult-to-treat IAI pathogens.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background: Community-associated (CA) and hospital-associated (HA) intra-abdominal infections (IAI) are a major cause of morbidity and, if not properly treated, mortality. The Study for Monitoring Antimicrobial Resistance Trends (SMART) has tracked epidemiology and susceptibility of aerobic gram-negative pathogens (GNP) causing IAI since 2002; this report summarizes the findings for pediatric patients in the U.S. during 2010-2013. Methods: 23 U.S. hospitals each collected up to 100 non-selected, consecutive GNP per year, including 300 pediatric GNP in 2010-2013. Organisms were classified as either CA or HA if isolated <48h or ≥48h from admission. Susceptibility and ESBL phenotypes were determined using CLSI broth microdilution. Results: Shown below is the susceptibility of the top 4 species and of all GNP combined (using appropriate CLSI breakpoints and assuming 0% susceptible for species with no breakpoints for any given drug). Only selected agents are shown (one agent per major drug class tested). Analysis of extended-spectrum β-lactamase (ESBL) phenotypes showed 4%, 6%, and 4% of E. coli and 13%, 13%, and 0% of K. pneumoniae (albeit with small n's) to be ESBL-positive in all, HA, and CA IAI, respectively. Conclusion: Although the top 4 species found in HA and CA IAI were identical, the proportion of E. coli was significantly different: 41% in HA IAI vs. 55% in CA IAI. P. aeruginosa and E. cloacae tended to be more prevalent in HA IAI. Susceptibility was frequently lower in HA than CA. Of the agents tested, AMK had the highest in vitro activity vs. all GNP. ETP showed excellent activity vs. Enterobacteriaceae. Differences in species prevalence and susceptibility between HA and CA pediatric IAI indicate a need for different treatment options for these infections.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: C-760 In Vitro Activity of Ceftaroline against Contemporary Staphylococcus aureus Isolates (2013) from Latin American Countries: AWARE Surveillance Program D. Hoban1, M. Hackel1, R. Badal1, E. Reiszner2 and J. Ambler2 1IHMA Inc. Schaumburg, IL. USA 2AstraZeneca Pharmaceuticals, Waltham, MA, USA Background: Ceftaroline (CPT), the active metabolite of ceftaroline fosamil is the first cephalosporin with enhanced anti-staphylococcal activity (including methicillin-resistant S. aureus [MRSA]) indicated for the treatment of adults with complicated skin and soft tissue infections (cSSTI) and community-acquired pneumonia (CAP). This report from AWARE, a global CPT surveillance program, summarizes the in vitro activity of CPT against S. aureus isolates collected in Latin America (LA). Methods: Susceptibility testing of 1,182 S. aureus isolates (488 methicillin-susceptible S. aureus, 694 MRSA) collected in 2013 from 22 hospitals, in 6 LA countries (Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela). Isolates were sourced from specimens from patients with SSTI (abscess, burn, carbuncle, cellulitis/erysipelas, decubitus, furuncle, impetiginous lesions, skin ulcer, wound) and lower respiratory tract infections (bronchial washing, bronchial alveolar lavage, endotracheal aspirate, sputum). Testing was performed by broth microdilution and MIC results were interpreted according to CLSI performance standards. Results: Of the 1,182 S. aureus tested 88.4% were CPT susceptible. All MSSA isolates were CPT susceptible (MIC range 0.06-0.5 mg/L, MIC90 0.25 mg/L). CPT activity against MRSA isolates is summarized in the table. Conclusions: All MSSA isolates were susceptible in vitro to CPT. Marked diversity in susceptibility across LA countries was observed in vitro with MRSA (%S ranged from 31.2% in Chile to 100% in Colombia). Across the LA region 80.3% of MRSA were reported as susceptible, 19.6% as intermediate and 0.1% (1 isolate) as resistant with an MIC of 4 mg/L.
    54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC),, Washington DC; 09/2014
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    ABSTRACT: Background: Ceftaroline (CPT), the active metabolite of ceftaroline fosamil, is a cephalosporin with in vitro activity against Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA), streptococci, and common Enterobacteriaceae (excluding strains producing serine β-lactamases). This report from AWARE, a global surveillance program, summarizes the in vitro activity of CPT and comparators against respiratory tract infection (RTI) pathogens collected in Latin America from 2012-13. Methods: RTI pathogens were collected from 17 medical centres in Argentina, Brazil, Chile, Colombia, Mexico, and Venezuela 2012-13. Sources included: sputum, endotracheal aspirate, bronchoalveolar lavage and bronchial brushings. MICs were determined by broth microdilution as specified by the CLSI and the results interpreted by CLSI breakpoints. Results: Susceptibility % for selected drugs and species are shown in the table below; values >=90% are shaded; na=no breakpoints, and "-" indicates not tested. Conclusions: Ceftaroline demonstrated excellent in vitro activity against S. pneumoniae with activity comparable to LVX, MXF and LZD. Activity against H. influenzae isolates was also excellent and comparable to AMX, CRO, and LVX. Ceftaroline activity against S. aureus was 79% (100% of MSSA isolates were susceptible). Ceftaroline activity against E. coli and K. pneumoniae was similar to AMX while ceftaroline had no activity against K. pneumoniae or E. coli producing serine β-lactamases (data not shown).
    54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC),, Washington, DC; 09/2014
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    ABSTRACT: The Study for Monitoring Antimicrobial Resistance Trends program monitors the activity of antibiotics against aerobic and facultative Gram-negative bacilli (GNBs) from intra-abdominal infections (IAIs) in patients worldwide.
    Chinese medical journal. 07/2014; 127(13):2429-33.
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    ABSTRACT: Activity of ceftaroline and comparators against Streptococcus pneumoniae from multiple specimen sources in the European region 2012: assessing worldwide antimicrobial resistance evaluation (AWARE) programme Hoban D.; Badal R.; Biedenbach D.; Hackel M.; Bouchillon S.; Ambler J. Objectives: Streptococcus pneumoniae (SP) remains a significant pathogen isolated from many infectious processes. Increasing penicillin, macrolide and cephalosporin resistance in SP increases the need for new effective antimicrobials. Ceftaroline, the active metabolite of ceftaroline fosamil, is a cephalosporin with in vitro activity against Gram-positive pathogens and common Gram-negative pathogens. The in vitro activity of ceftaroline and comparators against SP including resistant strains isolated across the European region in 2012 from the AWARE programme are reported. Methods: 62 medical centers in 17 European countries (Austria, Belgium, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Portugal, Romania, Russia, Spain, Sweden, Netherlands, Turkey and United Kingdom) collected 815 SP isolates from multiple specimen sources. MICs were performed as specified by CLSI using prepared broth microdilution panels and interpreted according to EUCAST guidelines and breakpoints. Results: The in vitro activity of ceftaroline and 7 comparator agents are shown in the table. Drugs % Susceptible/MIC90 (mg/L) All SP PSSP PISP PRSP MRSP CROSP Isolate # 815 556 206 53 228 17 CPT 99.1/0.12 100/0.008 100/0.12 86.8/0.5 96.9/0.12 58.8/0.5 CRO 85.4/1 99.8/0.03 68.5/2 0/>4 59.7/2 0/>4 CLI 80.5/>1 93.0/0.06 59.7/>1 30.1/>1 35.1/>1 41.2/>1 ERY 71.4/>1 89.0/1 37.9/>1 17.0/>1 0/>1 11.8/>1 LVX 99.3/1 100/1 97.1/1 100/1 98.3/1 100/1 LZD 100/1 100/1 100/1 100/1 100/1 100/2 MXF 99.4/0.25 100/0.25 98.1/0.25 98.1/0.25 97.8/0.25 100/0.25 PEN 68.2/2 100/0.03 0/2 0/>8 25.0/4 0/>8 CPT ceftaroline, CRO ceftriaxone, CLI clindamycin, ERY erythromycin, LVX levofloxacin, LZD linezolid, MXF moxifloxacin, PEN penicillin ALL SP: All S. pneumoniae, PSSP: penicillin-susceptible SP (penicillin MIC<=0.06 mg/L), PISP: penicillin-intermediate SP (penicillin MIC=0.12-2 mg/L), PRSP: penicillin-resistant SP (penicillin MIC>2mg/L), MRSP: macrolide-resistant SP (erythromycin MIC >0.5mg/L), CROSP: ceftriaxone-resistant SP (ceftriaxone MIC>2mg/L). Conclusions: Ceftaroline demonstrated excellent in vitro activity against SP with percent susceptible =>99% for penicillin-susceptible and intermediate strains. Activity was reduced for penicillin- (86.8%) and ceftriaxone-resistant (58.8%) strains. Overall, the susceptibility of SP to ceftaroline was comparable to levofloxacin and moxifloxacin at their respective EUCAST breakpoints.
    24th European Congress of Clinical Microbiology and Infectious Diseases, Barcelona, Spain; 05/2014
  • Journal of Global Antimicrobial Resistance. 05/2014;
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    ABSTRACT: The Study for Monitoring Antimicrobial Resistance Trends has been monitoring the activity of antimicrobials indicated for the treatment of intra-abdominal infections since 2004. This report documents the in vitro activity of several recommended antimicrobials against 3449 gram-negative bacilli isolated from the 30 and 25 participating sites in North America in 2010-2011, respectively, and characterizes the extended-spectrum beta-lactamases (ESBL) identified in ESBL-positive and ertapenem-non-susceptible isolates of Enterobacteriaceae. Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Klebsiella oxytoca, Citrobacter freundii, Enterobacter aerogenes, Serratia marcescens, and Morganella morgannii were the most common species isolated. The incidence of beta-lactamase production was 8.8% and 8.9% for E. coli and K. pneumoniae, respectively. Overall the most active antimicrobials were amikacin, piperacillin-tazobactam, imipenem, and ertapenem, although beta-lactamase production reduced the activity of most agents. Characterization of beta-lactamase genes determined that blaSHV, blaCTX-M, blaAmpC, and blaKPC were commonly found in most beta-lactamase-positive isolates.
    Diagnostic microbiology and infectious disease 04/2014; · 2.45 Impact Factor
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    ABSTRACT: 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.
    Journal of chemotherapy (Florence, Italy) 02/2014; · 0.83 Impact Factor
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    ABSTRACT: A sub-set of Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae and Proteus mirabilis collected for the Study for Monitoring Antimicrobial Resistance Trends (SMART) that were positive for the CLSI extended-spectrum beta-lactamase (ESBL) phenotypic confirmatory test (N=3,245) or had an ertapenem MIC of ≥0.5μg/ml (N=293) or both (N=467) were analyzed for ESBL genes. Most ESBL phenotype E. coli or K. pneumoniae possessed an ESBL gene (95.8% & 88.4%, respectively) or 93.1% if carbapenem non-susceptible K. pneumoniae were removed. This rate was lower for P. mirabilis (73.4%) and K. oxytoca (62.5%). Virtually all ESBL-positive isolates (99.5%) were cefotaxime non-susceptible (CLSI or EUCAST breakpoints). Fewer (82%) were ceftazidime non-susceptible (CLSI breakpoints). Also 21.1% of E. coli, 25% of K. oxytoca and 78.7% of P. mirabilis were ceftazidime-susceptible but ESBL-positive. This suggests CLSI breakpoints for ceftazidime are too high to detect ESBLs. The lower EUCAST breakpoints detected ESBLs in E. coli and K. oxytoca better, but 59.6% of ESBL-positive isolates of P. mirabilis were ceftazidime-susceptible. For isolates with ertapenem MIC ≥ 0.5μg/ml, more accurate ESBL phenotype analysis was observed for E. coli and K. pneumoniae (sensitivity >95% for both, specificity 94.4% and 54.1%, respectively). If carbapenemase-positive K. pneumoniae were excluded specificity increased to 78%. The positive predictive values for the ESBL phenotypic test with E. coli and K. pneumoniae were 97.6% and 81.8%, respectively and negative predictive values were 75.9% and 95.2%, respectively. We therefore suggest it would be prudent to confirm phenotypic ESBL-positive P. mirabilis, K. pneumoniae and K. oxytoca with molecular analysis.
    Journal of Medical Microbiology 01/2014; · 2.30 Impact Factor
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    ABSTRACT: Treatment options for multidrug-resistant pathogens remain problematic in many regions and individual countries, warranting ongoing surveillance and analysis. Limited antimicrobial susceptibility information is available for pathogens from Vietnam. This study determined the bacterial susceptibility of aerobic gram-negative pathogens of intra-abdominal infections (IAIs) among patients in Vietnam during 2009–2011. A total of 905 isolates were collected from four medical centers in this investigation as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). Antimicrobial susceptibility and extended-spectrum beta-lactamase (ESBL) rates among the appropriate species were determined by a central laboratory using Clinical and Laboratory Standards Institute (CLSI) methods. Among the species collected, Escherichia coli (48.1% ESBL-positive), and Klebsiella pneumoniae (39.5% ESBL-positive) represented the majority (46.4%) of the isolates submitted for this study. Ertapenem MIC90 values were lowest for these two species at 0.12 and 0.25 μg/ml, and remained unchanged for ESBL-positive isolates. Imipenem MIC90 values were also the same for all isolates and ESBL-positive strains at 0.25 and 0.5 μg/ml, respectively. Ertapenem MIC90 values for additional species with sufficient numbers for analysis, including Enterobacter cloacae, Proteus mirabilis, Acinetobacter baumannii, and Pseudomonas aeruginosa, were 1, 0.06, >4, and >4 μg/ml, respectively. Analysis of beta-lactamases in a subset of 132 phenotypically ESBL-positive Enterobacteriaceae demonstrated that CTX-M variants, particularly CTX-M-27 and −15, were the predominant enzymes. High resistance rates in Vietnam hospitals dictate continuous monitoring as antimicrobial inactivating enzymes continue to spread throughout Asia and globally.
    Diagnostic Microbiology and Infectious Disease. 01/2014;
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    ABSTRACT: Background: The IDSA and the SIS updated guidelines for IAI therapy in 2010. The Study for Monitoring Antimicrobial Resistance Trends (SMART) is a longitudinal surveillance study that has tracked the in vitro activity of drugs commonly used to treat IAI since 2002. This report summarizes in vitro activity of amikacin (AK), ampicillin-sulbactam (AS), cefepime (CPE), cefotaxime (CFT), cefoxitin (CFX), ceftazidime (CAZ), ceftriaxone (CAX), ciprofloxacin (CP), ertapenem (ETP), imipenem (IMP), levofloxacin (LVX), and piperacillin-tazobactam (PT), against aerobic gram-negative bacilli (GNB) isolated in 2012 from IAI in the US. Methods: 12 laboratories in the US each collected up to 100 consecutive isolates of GNB from IAI in 2012 for a total of 991 isolates. Isolates were sent to a central laboratory for confirmation of identification; ESBL status and broth microdilution susceptibility were determined using CLSI broth microdilution. IAI was defined as hospital-associated (HA) or community-associated (CA) if cultured ≥48 hours or <48 hours post admission, respectively. Statistical significance was determined using Fisher's exact test. Results: The 2 most prevalent species, E. coli and K. pneumoniae, accounted for 55% of all isolates, and had ESBL rates in HA/CA of 8%/7% and 15%/7%, respectively. 97% of 794 Enterobacteriaceae were ETP susceptible (S). Susceptibility (with 95% confidence limits) of all isolates combined, using breakpoints appropriate for each species (0% S assumed for species with no breakpoints for any given drug) is summarized by HA and CA, below; asterisks by drug names indicate a significant difference (p<0.05) between HA and CA values. s Conclusion: ESBL rates in IAI in the US are relatively unchanged from earlier SMART reports, and remain much lower than reported in most countries, leading to higher levels of susceptibility to cephalosporins and fluoroquinolones than typically seen internationally. All study drugs except AK and IMP had significantly lower %S in HA than in CA. AK (97.8%) and ETP (97.2%) were the most active vs. Enterobacteriaceae, while AK (86.2%) and CAZ (78.7%) were the most active vs. non-Enterobacteriaceae. SMART data can be useful to help guide evolving IAI treatment guidelines to reflect resistance trends.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
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    ABSTRACT: Background: The Study for Monitoring Antimicrobial Resistance Trends (SMART) has monitored gram-negative pathogens (GNP) from urinary tract infections (UTI) since late 2009. To help with empiric therapy decisions in Latin America (LA), this report summarizes occurrence and susceptibility of pathogens (including extended-spectrum β-lactamase [ESBL] producers) in hospital- (HA) and community-associated (CA) UTI in 2010-2012 in this region. Methods: Labs in 11 countries collected up to 50 consecutively isolated GNP per year from hospitalized patients with UTI. Susceptibility and ESBL phenotypes were determined by microdilution per CLSI guidelines for 3,581 GNP. A UTI was defined as HA or CA if cultured ≥48 hours or <48 hours post admission, respectively. Results: The top 10 species (comprising 97% of all isolated species) are shown below with ESBL and susceptibility rates for selected drugs. Values ≥90% are bolded. n % ESBL % Susceptible Amikacin Cefotaxime Ceftazidime Cipro Ertapenem Pip-Tazo Row Labels HA CA HA CA HA CA HA CA HA CA HA CA HA CA HA CA E. coli 978 1244 32 22 96 98 65 76 72 80 47 57 99 100 88 92 K. pneumoniae 291 245 48 35 86 89 43 61 46 64 46 59 87 93 58 73 P. aeruginosa 129 87 66 53 NB NB 62 60 52 36 NB NB 59 61 P. mirabilis 98 95 14 8 96 97 81 86 96 92 77 81 100 1001 94 97 E. cloacae 61 31 87 90 38 45 46 45 62 45 79 87 66 65 A. baumannii 32 19 25 21 9 5 16 26 13 16 NB NB 13 16 M. morganii 25 17 96 100 72 71 92 76 56 65 100 100 100 100 E. aerogenes 21 17 90 100 57 59 67 65 81 94 95 100 76 82 C. freundii 21 16 100 94 52 69 71 75 52 63 95 94 76 94 S. marcescens 21 13 86 100 62 85 71 92 81 85 90 100 71 100 Top 10 species2 1677 1784 90 93 55 69 66 76 50 57 87 93 78 87 1 Rounded up (99.6%). 2Susceptibility was calculated for 10 top species combined; 0% susceptibility assumed for species with no breakpoints for any given drug. NB=No breakpoint. Conclusion: * ESBL rates were higher in HA than CA infections in Latin America, but even CA rates were high compared to global rates reported previously. * Susceptibility was almost always lower in HA UTI GNP. * Due to high ESBL rates in the two most frequently isolated UTI GNP, options for empiric UTI therapy are limited, especially in HA infections. Of the drugs studied, only amikacin was active against ≥90% of both HA and CA pathogens, and ertapenem (and imipenem; data not shown) against ≥90% of CA pathogens.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
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    ABSTRACT: Background: ICU admission has been identified as a risk factor for extended-spectrum β-lactamase (ESBL) infections, especially in Klebsiella .This report from the Study for Monitoring Antimicrobial Resistance Trends (SMART) summarizes the occurrence of ESBL producers in IAI in 2010-2012 in North America (NA), comparing ICU and non-ICU wards. Methods: 29 sites in the US and Canada collected up to 100 consecutively isolated gram-negative pathogens (GNP) from adults with IAI per year. Susceptibility and ESBL phenotypes were determined by microdilution per CLSI and plate manufacturer guidelines for 4,249 GNP. An IAI was defined as hospital-associated (HA) or community-associated (CA) if cultured ≥48 hours or <48 hours post admission, respectively. ESBL rates were compared with the Fisher exact test. Results: Escherichia coli, K. pneumoniae, Proteus mirabilis, and K. oxytocacomprised 64% of all IAI GNP. Prevalence rates of each species and ESBL rates are shown below: ICU wards Non-ICU wards HA CA Total HA CA Total All organisms n 471 343 814 1640 1795 3435 E. coli n 167 136 303 623 743 1366 Prevalence (%) 35.5 39.7 37.2 38.0 41.4 39.8 ESBL+ rate (%) 12.0* 2.9* 7.9 10.9 7.4 9.0 K. pneumoniae n 77 66 143 271 331 602 Prevalence (%) 16.3 19.2 17.6 16.5 18.4 17.5 ESBL+ rate (%) 11.7 9.1 10.5 11.1 7.3 9.0 P. mirabilis n 15 14 29 44 86 130 Prevalence (%) 3.2 4.1 3.6 2.7 4.8 3.8 ESBL+ rate (%) 0 0 0 6.8 1.2 3.1 K. oxytoca n 11 15 26 61 77 138 Prevalence (%) 2.3 4.4 3.2 3.7 4.3 4.0 ESBL+ rate (%) 9.1 6.7 7.7 4.9 5.2 5.1 * HA and CA significantly different (p<0.05). Note: Differences between ICU and non-ICU wards not significant (p>0.05). Conclusion: * While higher ESBL rates in ICU than non-ICU wards have been reported elsewhere, our results for IAI GNP showed no significant differences in NA. * Clearer differences are seen between HA and CA infections, with ESBL rates tending to be higher in HA IAI in both ICU and non-ICU settings (but only statistically significant for E. coli in ICUs). * These results concur with a 2004 CDC National Nosocomial Infections Surveillance report with similar rates of K. pneumoniae and E. coli resistant to 3rd gen. cephalosporins in US ICU and non-ICU wards. Although ICU admission has been reported to be a risk factor for ESBL infection, our data suggest that may not be the case in NA.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013
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    ABSTRACT: Background: The Tigecycline Evaluation Surveillance Trial (TEST) has monitored the in vitro susceptibility of organisms from a variety of sources, including intra-abdominal infections (IAI) since 2004. This analysis of TEST data was done to compare the susceptibility of organisms from IAI, 2010-2012, including the occurrence of extended-spectrum beta-lactamase (ESBL) producers. Methods: 4,396 clinically significant IAI isolates collected from 781 cumulative sites worldwide were analyzed in this survey. Isolates were identified to the species level at the participating sites and confirmed by the central laboratory. MICs were determined by each site using supplied broth microdilution panels and interpreted according to CLSI and FDA (tigecycline) guidelines. Results: Percentage of ESBL+ isolates were: Africa (8.3), Asia (42.5), Europe (16.5), Latin America (24.5), Middle East (23.5), North America (6.8) and South Pacific (0). % susceptible is shown below; values ≥90% are shaded. Organism (n) % Susceptible Gram positive AMP LEV MIN PEN PT TIG VAN Enterococcus spp. (740) 57 44 50 56 na 99 81 S. aureus (203) 13 61 98 12 53 100 100 S. aureus, MRSA (95) na 25 97 na na 100 100 Gram negative AK FEP CAZ MER MIN PT TIG Acinetobacter spp. (182) 54 45 27 51 82 43 na Enterobacter spp. (671) 97 90 53 96 63 67 93 E. coli (1275) 98 88 78 99 76 91 100 Klebsiella spp. (826) 95 81 69 95 68 74 94 All ESBL+* (343) 89 34 1 96 48 57 95 P. aeruginosa (386) 88 76 na 66 na 70 na Serratia spp. (113( 94 94 71 96 60 85 94 AK- amikacin; AMP- ampicillin; FEP- cefepime; CAZ- ceftazidime; LEV- levofloxacin; MER- meropenem; MIN- minocycline; PEN- penicillin; PT- piperacillin-tazobactam; TIG- tigecycline; VAN- vancomycin *ESBL isolates include E. coli, K. oxytoca, and K. pneumoniae Conclusion: TIG, VAN, and MIN all demonstrated potent activity against S. aureus, including MRSA, from IAI. TIG was the only compound tested with %S greater than 90% against Enterococcus spp., including vancomycin-resistant isolates. AMK, MER and TIG were the most active in vitro against gram-negative organisms, with MER and TIG inhibiting >95% of ESBL+ organisms tested.
    IDWeek 2013 Meeting of the Infectious Diseases Society of America; 10/2013