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

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

Update of dalbavancin spectrum and potency in the USA: report from the SENTRY Antimicrobial Surveillance Program (2011)

Dalbavancin (DAL) is an investigational lipoglycopeptide with a prolonged serum half-life allowing once weekly dosing. DAL potency was assessed in the 2011 SENTRY Antimicrobial Surveillance Program among 1555 isolates sampled from all 9 US Census regions. Monitored Gram-positive cocci included Staphylococcus aureus (SA; 1,036/50.4% MRSA), coagulase-negative staphylococci (CoNS; 115), Enterococcus faecalis (25), E. faecium (31), Streptococcus pyogenes (155), Streptococcus agalactiae (153), and viridans group streptococci (VGS; 40). All susceptibility (S) testing used Clinical and Laboratory Standards Institute reference broth microdilution methods and interpretations. DAL (MIC_50/90, 0.06/0.06 μg/mL) was 8- and 16-fold more active than daptomycin (DAP) and vancomycin (VAN), respectively against SA, with MSSA and MRSA having the same MIC₉₀ results. CoNS was slightly more DAL-S (MIC₅₀, ≤0.03μg/mL). The highest staphylococcal DAL MIC was only 0.25 μg/mL. β-Haemolytic streptococci (βHS) and VGS had DAL MIC results ranging from ≤0.03 to 0.25 μg/mL (MIC₉₀, 0.06–0.12 μg/mL), and only enterococci showed elevated DAL MIC results. VanA phenotype–resistant E. faecalis or E. faecium had DAL MIC values at ≥1 μg/mL; VanB strains were DAL-S (MIC, ≤0.25 μg/mL). All cited DAL quantitative values were consistent with earlier surveillance data (2006–2009), without evidence of MIC creep. In conclusion, year 2011 SENTRY Program data for DAL documents sustained potent activity against SA, CoNS, βHS, VGS, and VAN-S enterococci, which averaged 4- to 32-fold greater than VAN, DAP, or linezolid.     

Activity of fosfomycin when tested against US contemporary bacterial isolates

Fosfomycin and comparators were susceptibility tested against over 2200 contemporary clinical isolates from US medical centers. Fosfomycin was active against Enterobacterales (MIC_50/90, 4/16?μg/mL), including multidrug-resistant isolates. Potent activity was exhibited against gram-positive organisms, including Staphylococcus aureus (MIC_50/90, 4/8?μg/mL). Fosfomycin may provide a promising alternative option for treatment of infections where resistant bacteria may occur.     

Resistance Surveillance in Italy: Four-Year Results from the MYSTIC Program

Abstract

The MYSTIC program is an international, multicenter surveillance study that compares the activity of meropenem, in centers that are prescribers, with that of imipenem, ceftazidime, piperacillin/tazobactam, ciprofloxacin and gentamicin. These Italian data are from 3 centers (neutropenia, cystic fibrosis and intensive care units). A total of 2,072 (238 Gram-positive and 1,834 Gramnegative) aerobic microorganisms were collected during the study. Pseudomonas aeruginosa (33.4%) was the most isolated species followed by Escherichia coli (14.4%). All except one Enterobacteriaceae strain isolated were fully susceptible to meropenem. Moreover, the activity of meropenem against Enterobacteriaceae was about eight-fold greater than that of imipenem and four- to eight-fold more active than that of ceftazidime. Meropenem was highly active against non-fermentative Gram-negative microorganisms, exceeding the activity of most of the other antimicrobial agents tested. Moreover, meropenem showed increasing activity during the 4 years of study (starting from 86.2% in 1997 to 94.0% in 2000). In conclusion, our results indicate that meropenem has excellent potency and spectrum of activity despite being prescribed for the treatment of seriously ill patients, and appears to be a reliable option for the initial empirical treatment of serious nosocomial infections.     

Dissemination and genetic context analysis of blaVIM-6 among Pseudomonas aeruginosa isolates in Asian-Pacific Nations

VIM-6, previously reported in two strains from Singapore recovered in 2000, was detected in 16 isolates collected in 2006 in India (12 isolates), Indonesia (two), Korea and the Philippines (one each). High genetic variability was observed among VIM-6-producing isolates (12 ribotypes and 11 pulsed-field gel electrophoresis types), but clones were observed in India and Indonesia; bla_VIM-6-carrying integrons of 3.9 kb and 5 kb were detected, and two of five Indian hospitals yielded isolates with both integrons. These two integrons, bla_VIM-6 was located in the first position, followed by bla_OXA-10 and aacA4. The 5-kb integrons also harboured aadAl and a 331-bp open reading frame encoding a putative efflux pump.     

Beta-lactam susceptibilities and prevalence of ESBL-producing isolates among more than 5000 European Enterobacteriaceae isolates

In vitro susceptibility to 15 β-lactam antibiotics was evaluated using Enterobacteriaceae isolated during the SENTRY Antimicrobial Surveillance Program. Piperacillin/tazobactam was the most active penicillin against Escherichia coli, Proteus mirabilis, Klebsiella oxytoca and Klebsiella pneumoniae (94.9%, 98.3%, 87.4% and 82.9% of isolates susceptible). Of the cephalosporins, cefepime was most effective against Escherichia coli, Proteus mirabilis and Enterobacter cloacae (99.2%, 96.3% and 95.2% of isolates susceptible, respectively) and cefoxitin against Klebsiella oxytoca and Klebsiella pneumoniae (98.6% and 95.6% of isolates susceptible). Carbapenems had excellent activity (≥99.5% of all isolates). ESBL-production was confirmed with the ESBL–Etest and disk diffusion test in 1.3% of Escherichia coli isolates, 18.4% of Klebsiella pneumoniae, 12.6% of Klebsiella oxytoca and 5.3% of Proteus mirabilis isolates.     

Comparative activities of six different fluoroquinolones against 9,682 clinical bacterial isolates from 20 European university hospitals participating in the European SENTRY surveillance programme

The in-vitro activities of gatifloxacin, trovafloxacin, levofloxacin, sparfloxacin, ofloxacin, and ciprofloxacin were tested against 9,682 clinical bacterial isolates from 20 European university hospitals participating in the European SENTRY surveillance programme. Gatifloxacin and trovafloxacin exhibited the highest activities against Gram-positive cocci, while levofloxacin, ofloxacin, ciprofloxacin, and gatifloxacin were the most active against Enterobacteriaceae. Ciprofloxacin and levofloxacin showed the highest antimicrobial activities against Pseudomonas spp., while gatifloxacin and trovafloxacin were the most active against Acinetobacter spp. and Stenotrophomonas maltophilia. All Haemophilus spp. and Moraxella catarrhalis isolates were fully susceptible to all quinolones tested. Overall, the new quinolones, showed improved activity against Gram-positive cocci and Gram-negative non-fermenters while retaining their broad-spectrum activity against Gram-negative bacilli.     

Antimicrobial activity evaluations of gatifloxacin, a new fluoroquinolone: contemporary pathogen results from a global antimicrobial resistance surveillance program (SENTRY, 1997)

Objectives: To investigate the in vitro potency and spectrum of activity of gatifloxacin and five comparator fluoroquinolones tested against over 23 000 clinical isolates from diverse geographic and clinical sources in the Americas.
Methods: Gram-negative, Gram-positive and fastidious bacterial isolates were tested against gatifloxacin, ciprofloxacin, levofloxacin, ofloxacin, sparfloxacin and trovafloxacin using broth microdilution methods recommended by the National Committee for Clinical Laboratory Standards (NCCLS).
Results: Gatifloxacin demonstrated a potency and spectrum very similar to those of other new fluoroquinolones such as levofloxacin, sparfloxacin, and trovafloxacin. Gatifloxacin was particularly active against the Enterobacteriaceae (94.8% susceptible at ≤2 mg/L), Acinetobacter spp. (77.2%), Stenotrophomonas maltophilia (75.1%), Streptococcus pneumoniae (99.8%), other Streptococcus spp. (≥98.9%), and various Staphylococcus spp. (79.2–100.0%). Trovafloxacin was the most similar comparison drug overall.
Conclusions: These results indicate a potential therapeutic role for gatifloxacin that would widen the potency or spectrum of fluoroquinolones, particularly against Gram-positive species, when considering its favorable bioavailability.     

Antimicrobial susceptibility of bacteria causing urinary tract infections in Latin American hospitals: results from the SENTRY Antimicrobial Surveillance Program (1997)

Objectives: To evaluate the antimicrobial susceptibility patterns among 469 pathogens isolated as a significant cause of urinary tract infections in 10 Latin American medical centers.
Methods: Consecutively collected isolates were susceptibility tested by broth microdilution methods, and selected isolates were characterized by molecular typing methods.
Results: Escherichia coli and Klebsiella spp. isolates revealed high rates of resistance to broad-spectrum penicillins and to fluoroquinolones. Ceftazidime MICs of ≥2 mg/L, suggesting the production of extended-spectrum β-lactamases (ESBLs), were observed in 37.7% of K. pneumoniae and 8.3% of Escherichia coli isolates. Enterobacter spp. isolates were characterized by high resistance rates to ciprofloxacin (35%) and to ceftazidime (45%), but they generally remained susceptible to cefepime (95% susceptible). Pseudomonas aeruginosa and Acinetobacter spp. were highly resistant to ciprofloxacin and ceftazidime. Imipenem was active against 80% of P. aeruginosa and 93% of Acinetobacter spp. isolates.
Conclusions: Our results demonstrate a high level of resistance to various classes of antimicrobial agents among isolates causing nosocomial urinary tract infections in Latin American hospitals. Clonal dissemination of ESBL-producing K. pneumoniae strains was infrequent.     

Echinocandin and triazole antifungal susceptibility profiles for Candida spp., Cryptococcus neoformans, and Aspergillus fumigatus: application of new CLSI clinical breakpoints and epidemiologic cutoff values to characterize resistance in the SENTRY Antimicrobial Surveillance Program (2009)

The SENTRY Antimicrobial Surveillance Program monitors global susceptibility and resistance rates for newer and established antifungal agents. The echinocandins displayed excellent potency against both Candida spp. and Aspergillus fumigatus in 2009 samples. Using the new Clinical and Laboratory Standards Institute breakpoint values for the echinocandins when testing Candida spp., we demonstrate low but measurable rates of resistance to all 3 echinocandins (anidulafungin, caspofungin, and micafungin) when tested against Candida glabrata. Three of the 8 isolates demonstrating in vitro echinocandin resistance harbored fks resistance mutations, including 1 C. glabrata. The triazoles, with the exception of itraconazole, also exhibited excellent potency and low levels of resistance when tested against clinical isolates of Candida spp., Cryptococcus neoformans, and A. fumigatus. Overall, echinocandin and triazole resistance rates were minimal; however, the distinct increase in echinocandin resistance observed among C. glabrata strains warrants further surveillance associated with molecular support.