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ABSTRACT: 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 β-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 β-lactamase-producing strains, although the activity against extended-spectrum β-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.
Clinical Therapeutics 04/2013; · 2.32 Impact Factor
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ABSTRACT: Abstract 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 β-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.
Surgical Infections 03/2013; · 1.80 Impact Factor
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ABSTRACT: 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 beta-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 (GNB) 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:: 1,248 GNB were collected from pediatric IAIs by 113 labs in 40 countries from 2008 to 2010. Susceptibility was determined by CLSI broth microdilution. Susceptibility rates (%S) were determined for species with ≥10 isolates. RESULTS:: 62% of isolates came from general pediatric wards and 38% from pediatric ICUs. The overall ESBL-positive rate was 11.0% for E. coli, and 38.9% for K. 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 GNB 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 since only carbapenems inhibited most of these pathogens.
The Pediatric Infectious Disease Journal 02/2013; · 3.58 Impact Factor
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George G Zhanel,
Christopher D Lawson,
Heather Adam,
Frank Schweizer,
Sheryl Zelenitsky,
Philippe R S Lagacé-Wiens,
Andrew Denisuik,
Ethan Rubinstein,
Alfred S Gin, Daryl J Hoban,
Joseph P Lynch,
James A Karlowsky
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ABSTRACT: Avibactam (formerly NXL104, AVE1330A) is a synthetic non-β-lactam, β-lactamase inhibitor that inhibits the activities of Ambler class A and C β-lactamases and some Ambler class D enzymes. This review summarizes the existing data published for ceftazidime-avibactam, including relevant chemistry, mechanisms of action and resistance, microbiology, pharmacokinetics, pharmacodynamics, and efficacy and safety data from animal and human trials. Although not a β-lactam, the chemical structure of avibactam closely resembles portions of the cephem bicyclic ring system, and avibactam has been shown to bond covalently to β-lactamases. Very little is known about the potential for avibactam to select for resistance. The addition of avibactam greatly (4-1024-fold minimum inhibitory concentration [MIC] reduction) improves the activity of ceftazidime versus most species of Enterobacteriaceae depending on the presence or absence of β-lactamase enzyme(s). Against Pseudomonas aeruginosa, the addition of avibactam also improves the activity of ceftazidime (~fourfold MIC reduction). Limited data suggest that the addition of avibactam does not improve the activity of ceftazidime versus Acinetobacter species or most anaerobic bacteria (exceptions: Bacteroides fragilis, Clostridium perfringens, Prevotella spp. and Porphyromonas spp.). The pharmacokinetics of avibactam follow a two-compartment model and do not appear to be altered by the co-administration of ceftazidime. The maximum plasma drug concentration (C(max)) and area under the plasma concentration-time curve (AUC) of avibactam increase linearly with doses ranging from 50 mg to 2,000 mg. The mean volume of distribution and half-life of 22 L (~0.3 L/kg) and ~2 hours, respectively, are similar to ceftazidime. Like ceftazidime, avibactam is primarily renally excreted, and clearance correlates with creatinine clearance. Pharmacodynamic data suggest that ceftazidime-avibactam is rapidly bactericidal versus β-lactamase-producing Gram-negative bacilli that are not inhibited by ceftazidime alone.Clinical trials to date have reported that ceftazidime-avibactam is as effective as standard carbapenem therapy in complicated intra-abdominal infection and complicated urinary tract infection, including infection caused by cephalosporin-resistant Gram-negative isolates. The safety and tolerability of ceftazidime-avibactam has been reported in three phase I pharmacokinetic studies and two phase II clinical studies. Ceftazidime-avibactam appears to be well tolerated in healthy subjects and hospitalized patients, with few serious drug-related treatment-emergent adverse events reported to date.In conclusion, avibactam serves to broaden the spectrum of ceftazidime versus ß-lactamase-producing Gram-negative bacilli. The exact roles for ceftazidime-avibactam will be defined by efficacy and safety data from further clinical trials. Potential future roles for ceftazidime-avibactam include the treatment of suspected or documented infections caused by resistant Gram-negative-bacilli producing extended-spectrum ß-lactamase (ESBL), Klebsiella pneumoniae carbapenemases (KPCs) and/or AmpC ß-lactamases. In addition, ceftazidime-avibactam may be used in combination (with metronidazole) for suspected polymicrobial infections. Finally, the increased activity of ceftazidime-avibactam versus P. aeruginosa may be of clinical benefit in patients with suspected or documented P. aeruginosa infections.
Drugs 02/2013; · 4.23 Impact Factor
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ABSTRACT: 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 β-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 β-lactam/β-lactamase inhibitor combinations generally decreased over time. Further monitoring of the susceptibility to ertapenem and other antibiotics through SMART is warranted.
International journal of antimicrobial agents 01/2013; · 3.03 Impact Factor
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ABSTRACT: In 2009-2010, 3646 urinary tract isolates of Enterobacteriaceae spp. were isolated from hospitalized patients in North America and Europe. Extended-spectrum beta-lactamase (ESBL) production was detected in 8.5% and 8.8% of Escherichia coli and Klebsiella pneumoniae, respectively, in North America and in 17.6% and 38.9% for Europe, respectively. The carbapenems (ertapenem and imipenem) were the most active agents in vitro, with ampicillin-sulbactam the least active. Molecular characterization of about 50% of ESBL-positive isolates identified the presence of bla(CTX-M) genes in over 90% of Escherichia coli from both continents. bla(KPC) was more common in North American isolates of K. pneumoniae than in European isolates (21.4% versus 6.9%). bla(TEM) and AmpC genes were infrequent. Enterobacteriaceae spp. isolated from hospitalized patients with urinary tract infections in both North America and Europe are often resistant to commonly used antimicrobials with bla(CTX-M) genes common in both Escherichia coli and K. pneumoniae.
Diagnostic microbiology and infectious disease 07/2012; 74(1):62-7. · 2.45 Impact Factor
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ABSTRACT: Broth microdilution (Clinical and Laboratory Standards Institute) was used to evaluate the antimicrobial susceptibility of 1549 Pseudomonas aeruginosa clinical isolates collected in Canada between January 2008 and October 2011. The percentage of isolates susceptible was as follows: amikacin 92.0%, ceftazidime 83.5%, ciprofloxacin 74.3%, colistin 93.4%, gentamicin 76.8%, meropenem 82.7%, and piperacillin-tazobactam 83.6%. Antimicrobial susceptibility did not change significantly between 2008 and 2011, with the exception of increasing susceptibility to gentamicin (P < 0.0001).
Diagnostic microbiology and infectious disease 06/2012; 73(4):361-4. · 2.45 Impact Factor
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ABSTRACT: Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to β-lactam drugs among
Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired
upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment
of upper RTIs and as alternatives for patients allergic to β-lactams. Macrolide resistance is increasing among pneumococci
and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated
by erm(A) [erm(TR)] and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species producing an efflux pump (mef) and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper
RTIs; however, continuous monitoring of the local resistance patterns is essential.
Current Infectious Disease Reports 04/2012; 7(3):175-184.
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George G Zhanel,
Christopher D Lawson,
Sheryl Zelenitsky,
Brandon Findlay,
Frank Schweizer,
Heather Adam,
Andrew Walkty,
Ethan Rubinstein,
Alfred S Gin, Daryl J Hoban,
Joseph P Lynch,
James A Karlowsky
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ABSTRACT: Plazomicin (formerly ACHN-490) is a next-generation aminoglycoside that was synthetically derived from sisomicin by appending a hydroxy-aminobutyric acid substituent at position 1 and a hydroxyethyl substituent at position 6'. Plazomicin inhibits bacterial protein synthesis and exhibits dose-dependent bactericidal activity. Plazomicin demonstrates activity against both Gram-negative and Gram-positive bacterial pathogens, including isolates harboring any of the clinically relevant aminoglycoside-modifying enzymes. However, like older parenteral aminoglycosides, plazomicin is not active against bacterial isolates expressing ribosomal methyltransferases conferring aminoglycoside resistance. Plazomicin has been reported to demonstrate in vitro synergistic activity when combined with daptomycin or ceftobiprole versus methicillin-resistant Staphylococcus aureus, heteroresistant vancomycin-intermediate S. aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant S. aureus and against Pseudomonas aeruginosa when combined with cefepime, doripenem, imipenem or piperacillin-tazobactam. After intravenous administration of plazomicin to humans at a dose of 15 mg/ kg, the maximum concentraration was 113 μg/ml, the area under the curve(0-24) was 239 h·μg/ml, the half-life was 4.0 h and the steady-state volume of distribution was 0.24 L/kg. Results from a Phase II randomized, double-blind study in patients with complicated urinary tract infection and acute pyelonephritis including cases with concurrent bacteremia comparing plazomicin 15 mg/kg intravenously once daily for 5 days with levofloxacin 750 mg intravenously. for 5 days are anticipated in 2012. Human studies to date have not reported nephrotoxicity or ototoxicity, and lack of ototoxicity has been reported in the guinea pig model. Given reported increases in bacterial resistance to current antimicrobial agents and the lack of availability of new agents with novel mechanisms, plazomicin may become a welcomed addition to the antibacterial armamentarium pending positive results from large-scale clinical trials and other required clinical studies.
Expert Review of Anticancer Therapy 04/2012; 10(4):459-73. · 3.28 Impact Factor
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ABSTRACT: This study assessed the pharmacodynamics of ceftaroline against penicillin-intermediate and penicillin-resistant Streptococcus pneumoniae with elevated MICs of ceftaroline using an in vitro pharmacodynamic model.
Nine isolates of S. pneumoniae, including one penicillin-susceptible isolate, one penicillin-intermediate isolate and seven penicillin-resistant isolates, were tested. The pharmacodynamic model was inoculated with a concentration of 1 × 10(6) cfu/mL and ceftaroline was dosed twice daily (at 0 and 12 h) to simulate the fC(max) (maximum free concentration in serum) and t(1/2) (half-life in serum) obtained after 600 mg intravenous doses every 12 h (fC(max), 16 mg/L; t(1/2), 2.6 h). Ceftaroline was compared with ceftriaxone dosed once daily to simulate the fC(max) and t(1/2) obtained after a 1 g dose (fC(max), 18 mg/L; t(1/2), 8.0 h). Samples were collected over 24 h to assess viable growth and possible changes in ceftaroline MICs over time.
Ceftaroline fT(>MIC) (time of free serum concentration over the MIC) of 100% (ceftaroline MICs, ≤ 0.5 mg/L) was bactericidal (≥ 3 log(10) killing) against all isolates at 6 h and completely eradicated all organisms at 12 and 24 h. No bacterial regrowth occurred over the study period and no changes in ceftaroline MICs were observed. Upon ceftriaxone exposure, S. pneumoniae isolates with ceftriaxone MICs of 0.12 and 0.25 mg/L were eradicated, but isolates with ceftriaxone MICs of 1-8 mg/L resulted in initial bacterial reduction at 6 h with organism regrowth at 12 h and no reduction in organism concentration, relative to the starting inoculum, at 24 h.
Ceftaroline fT(>MIC) of 100% (ceftaroline MICs, ≤ 0.5 mg/L) was bactericidal (≥ 3 log(10) killing) and eradicated all S. pneumoniae at 12 and 24 h with no regrowth.
Journal of Antimicrobial Chemotherapy 03/2012; 67(7):1706-11. · 5.07 Impact Factor
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ABSTRACT: The worldwide dissemination of extended-spectrum-β-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 β-lactamase variants bla(SHV-129) and bla(KPC-11).
Journal of clinical microbiology 02/2012; 50(5):1632-9. · 4.16 Impact Factor
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ABSTRACT: 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.
Journal of chemotherapy (Florence, Italy) 01/2012; 24(1):6-11. · 1.08 Impact Factor
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ABSTRACT: Changes in the epidemiology of Streptococcus pneumoniae were reported worldwide after the introduction of the 7-valent pneumococcal vaccine, particularly an increase in multi-drug resistant (MDR) 19A strains. Subsequently, a 13-valent pneumococcal vaccine (PCV-13) has been introduced. This study assessed the incidence of S. pneumoniae serotypes in all age groups prior to the introduction of PCV-13 in Canada (2007-2009). Eight hundred S. pneumoniae isolates from respiratory specimens and blood cultures were collected as part of a Canadian surveillance study (CANWARD) from patients in 15 tertiary-care centers. Serotyping was performed by the Quellung method and antimicrobial susceptibility testing was performed by broth microdilution in accordance with the Clinical and Laboratory Standards Institute guidelines. The most common serotypes were 19A (8.6%), 3 (7.3%), 22F (6.0%), 4 (4.6%), 5 (4.4%), and 11A (4.4%); and the first serotype 6D isolate in Canada was identified. Serotypes 5, 7F, and 19A were significantly (p<0.001) more frequently isolated from bloodstream infections. Considerable serotype variability was noted for different age groups: 15B (p<0.01) and 19A (p<0.001) were more frequently isolated from children ≤2 years old. Overall, 46.4% of currently circulating S. pneumoniae serotypes in Canada are included in PCV-13. Notably, 87.5% of MDR-S. pneumoniae were covered by PCV-13. Accordingly, PCV-13 will provide coverage against a significant proportion of circulating S. pneumoniae strains in Canada, including the critical antimicrobial-resistant strains.
Microbial drug resistance (Larchmont, N.Y.) 12/2011; 18(2):176-82. · 1.99 Impact Factor
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ABSTRACT: Clinical isolates of the Bacteroides fragilis group (n = 387) were collected from patients attending nine Canadian hospitals in 2010-2011 and tested for susceptibility to 10 antimicrobial agents using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. B. fragilis (59.9%), Bacteroides ovatus (16.3%), and Bacteroides thetaiotaomicron (12.7%) accounted for ~90% of isolates collected. Overall rates of percent susceptibility were as follows: 99.7%, metronidazole; 99.5%, piperacillin-tazobactam; 99.2%, imipenem; 97.7%, ertapenem; 92.0%, doripenem; 87.3%, amoxicillin-clavulanate; 80.9%, tigecycline; 65.9%, cefoxitin; 55.6%, moxifloxacin; and 52.2%, clindamycin. Percent susceptibility to cefoxitin, clindamycin, and moxifloxacin was lowest for B. thetaiotaomicron (n = 49, 24.5%), Parabacteroides distasonis/P. merdae (n = 11, 9.1%), and B. ovatus (n = 63, 31.8%), respectively. One isolate (B. thetaiotaomicron) was resistant to metronidazole, and two isolates (both B. fragilis) were resistant to both piperacillin-tazobactam and imipenem. Since the last published surveillance study describing Canadian isolates of B. fragilis group almost 20 years ago (A.-M. Bourgault et al., Antimicrob. Agents Chemother. 36:343-347, 1992), rates of resistance have increased for amoxicillin-clavulanate, from 0.8% (1992) to 6.2% (2010-2011), and for clindamycin, from 9% (1992) to 34.1% (2010-2011).
Antimicrobial Agents and Chemotherapy 12/2011; 56(3):1247-52. · 4.84 Impact Factor
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Diagnostic microbiology and infectious disease 08/2011; 71(3):323-4. · 2.45 Impact Factor
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ABSTRACT: Escherichia coli is the most important uropathogen. The Study for Monitoring Antimicrobial Resistance Trends program collected 1643 E. coli isolates in 2009-2010 from urinary tract infection (UTI) specimens of hospitalized patients in countries worldwide. Ertapenem and imipenem were the most active agents tested, inhibiting >98% of all E. coli phenotypes. Overall, 17.9% of isolates were extended-spectrum beta-lactamase (ESBL) producers. The highest ESBL rate was from the Asia/Pacific region (27.7%). Amikacin and piperacillin-tazobactam achieved 90% inhibition levels only for ESBL-negative isolates. Ciprofloxacin and levofloxacin were not effective for ESBL-positive isolates, with only 14.6% and 15.9% susceptible, respectively. These observations highlight the need for continued monitoring of susceptibility of E. coli isolated from hospitalized patients with UTIs.
Diagnostic microbiology and infectious disease 08/2011; 70(4):507-11. · 2.45 Impact Factor
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ABSTRACT: From January 2007 to December 2009, an annual Canadian national surveillance study (CANWARD) tested 2,943 urinary culture pathogens for antimicrobial susceptibilities according to Clinical and Laboratory Standards Institute guidelines. The most frequently isolated urinary pathogens were as follows (number of isolates, percentage of all isolates): Escherichia coli (1,581, 54%), enterococci (410, 14%), Klebsiella pneumoniae (274, 9%), Proteus mirabilis (122, 4%), Pseudomonas aeruginosa (100, 3%), and Staphylococcus aureus (80, 3%). The rates of susceptibility to trimethoprim-sulfamethoxazole (SXT) were 78, 86, 84, and 93%, respectively, for E. coli, K. pneumoniae, P. mirabilis, and S. aureus. The rates of susceptibility to nitrofurantoin were 96, 97, 33, and 100%, respectively, for E. coli, enterococci, K. pneumoniae, and S. aureus. The rates of susceptibility to ciprofloxacin were 81, 40, 86, 81, 66, and 41%, respectively, for E. coli, enterococci, K. pneumoniae, P. mirabilis, P. aeruginosa, and S. aureus. Statistical analysis of resistance rates (resistant plus intermediate isolates) by year for E. coli over the 3-year study period demonstrated that increased resistance rates occurred only for amoxicillin-clavulanate (from 1.8 to 6.6%; P < 0.001) and for SXT (from 18.6 to 24.3%; P = 0.02). For isolates of E. coli, in a multivariate logistic regression model, hospital location was independently associated with resistance to ciprofloxacin (P = 0.026) with higher rates of resistance observed in inpatient areas (medical, surgical, and intensive care unit wards). Increased age was also associated with resistance to ciprofloxacin (P < 0.001) and with resistance to two or more commonly prescribed oral agents (amoxicillin-clavulanate, ciprofloxacin, nitrofurantoin, and SXT) (P = 0.005). We conclude that frequently prescribed empirical agents for urinary tract infections, such as SXT and ciprofloxacin, demonstrate lowered in vitro susceptibilities when tested against recent clinical isolates.
Antimicrobial Agents and Chemotherapy 07/2011; 55(7):3169-75. · 4.84 Impact Factor
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ABSTRACT: Urinary tract infections (UTIs) are among the most prevalent infectious diseases in the general population. They cause a substantial financial burden in the community and are associated with significant morbidity and mortality, particularly in hospitals. With increased rates of antimicrobial resistance, especially in the Asia-Pacific region, treatment of complicated UTIs (cUTIs) can be challenging for clinicians. Consideration of an optimal antimicrobial agent should be based on local resistance patterns, patient-specific factors, pharmacokinetic and pharmacodynamic principles, and cost. In the Asia-Pacific region, nearly half of Escherichia coli urinary isolates were resistant (including intermediate and resistant) to levofloxacin or ciprofloxacin and ≥30% were resistant to third-generation cephalosporins (cefotaxime, ceftriaxone, and ceftazidime) and cefepime. Overall, 33% of urinary E. coli isolates exhibited extended-spectrum β-lactamase (ESBL)-producing phenotypes. Prevalence of ESBL-producing urinary E. coli was highest in India (60%), followed by Hong Kong (48%) and Singapore (33%). All urinary isolates of E. coli were susceptible to both ertapenem and imipenem. All urinary isolates of Klebsiella pneumoniae were susceptible to imipenem and 4% of them were resistant to ertapenem. Care should be exercised when using trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolones, and cephalosporins for the empirical treatment of UTIs, particularly cUTI among moderately to severely ill patients. Empiric antimicrobial treatment for serious cUTIs in which risk factors for resistant organisms exist should include broad-spectrum antibiotics such as carbapenems (ertapenem, imipenem, meropenem, and doripenem) and piperacillin-tazobactam. Aminoglycosides, tigecycline, and polymyxins (colistin or polymyxin B) can be used for the treatment of multidrug-resistant organisms or serious cUTIs when first-line options are deemed inappropriate or patients fail therapy. Because of considerable variability in different countries, local epidemiological data is critical in the effective management of UTIs in the Asia-Pacific region.
The Journal of infection 06/2011; 63(2):114-23. · 4.13 Impact Factor
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ABSTRACT: During 2004-2009, 20004 isolates of Staphylococcus aureus were collected from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.). Of these isolates, 8249 (41.2%) were meticillin-resistant S. aureus (MRSA) and 11755 (58.8%) were meticillin-susceptible S. aureus (MSSA). A total of 4.0%, 5.3% and 3.0% of all S. aureus, MRSA and MSSA isolates, respectively, exhibited vancomycin minimum inhibitory concentrations (MICs) ≥ 2 μg/mL. Whilst no vancomycin-resistant S. aureus were encountered in this study and the majority of these isolates remained susceptible to vancomycin at the Clinical and Laboratory Standards (CLSI) breakpoint of 2 μg/mL, the total number of isolates with MICs creeping up to 2 μg/mL and above increased in all S. aureus from 4.0% in 2004 to 7.7% in 2009 (P < 0.001). Moreover, in MRSA this phenotype increased from 5.6% in 2004 to 11.1% in 2009 (P < 0.001). The increase was also notable for MSSA, which rose from 2.6% in 2004 to 5.6% in 2009 (P < 0.001). Of the 12 antibiotics tested, linezolid, minocycline, tigecycline and vancomycin were the most active agents by susceptibility against all S. aureus, all MRSA and all MSSA isolates. Against MRSA isolates with vancomycin MICs ≥ 2 μg/mL, susceptibility to vancomycin decreased from 100% in 2004 to 95.77% in 2009 (P > 0.05). Similarly, in MSSA isolates susceptibility to vancomycin decreased from 100% in 2004 to 91.07% in 2009 (P > 0.05). These data suggest that although the number of isolates of S. aureus with reduced susceptibility to vancomycin has increased significantly from 2004 to 2009, this upward creep of MICs has not yet impacted significantly on the overall susceptibility of vancomycin against either MRSA or MSSA.
International journal of antimicrobial agents 03/2011; 37(3):219-24. · 3.03 Impact Factor
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ABSTRACT: The CANWARD study (Canadian Ward Surveillance Study) assessed the antimicrobial susceptibility of a variety of available agents against 15 644 pathogens isolated from patients in Canadian hospitals between 2007 and 2009. The most active (based on MIC data) agents against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci were daptomycin, linezolid, tigecycline, and vancomycin (MRSA only) with MIC(90)'s (μg/mL) of 0.25 and 2, 2 and 2, 0.5 and 0.12, and 1, respectively. The most active agents against extended-spectrum β-lactamase-producing Escherichia coli were colistin (polymyxin E), doripenem, ertapenem, meropenem, and tigecycline with MIC(90)'s (μg/mL) of 1, ≤ 0.12, 0.25, ≤ 0.12, and 1, respectively. The most active agents against Pseudomonas aeruginosa were amikacin, cefepime, ceftazidime, colistin, doripenem, meropenem, and piperacillin-tazobactam with MIC(90)'s (μg/mL) of 32, 16, 32, 2, 4, 8, and 64, respectively. Overall, the most active agents versus Gram-positive cocci from Canadian hospitals were vancomycin, linezolid, daptomycin, and tigecycline and versus Gram-negative bacilli were amikacin, cefepime, doripenem, ertapenem (excluding Pseudomonas aeruginosa), meropenem, piperacillin-tazobactam, and tigecycline (excluding Pseudomonas aeruginosa).
Diagnostic microbiology and infectious disease 03/2011; 69(3):291-306. · 2.45 Impact Factor
