Helio S. Sader

Activities of dalbavancin against a worldwide collection of 81,673 gram-positive bacterial isolates.

ABSTRACT Dalbavancin, a long-acting lipoglycopeptide, was evaluated against 81,673 isolates of staphylococci, enterococci, and streptococci collected from 33 countries during worldwide resistance surveillance (2002 to 2007). Regardless of susceptibility to oxacillin, comparable potencies for dalbavancin against Staphylococcus aureus and coagulase-negative staphylococci from all countries were noted (MIC90, 0.06 to 0.12 μg/ml). Vancomycin-susceptible Enterococcus spp. had dalbavancin MIC90s comparable to those for staphylococci, whereas vancomycin-resistant strains were more resistant (MIC50, >4 μg/ml). β-Hemolytic and viridians group streptococci were very susceptible to dalbavancin (MIC90, ≤0.03 μg/ml). Overall, dalbavancin was ≥16-fold more active than vancomycin against the monitored gram-positive species.

Eight-year (2002-2009) Summary of the Linezolid (Zyvox® Annual Appraisal of potency and Spectrum; ZAAPS) Program in European Countries

Abstract The linezolid surveillance network (ZAAPS program) has been monitoring linezolid activity and susceptibility rates for eight years (2002-2009) in European medical centers. Samples from 12-24 sites annually in 11 countries were monitored by a central laboratory design using reference MIC methods with international and regional interpretations (EUCAST). A total of 13,404 Gram-positive pathogens were tested from 6 pathogen groups. Linezolid remained without documented resistance from 2002 through 2005, but beginning in 2006 resistant strains emerged at very low rates among Staphylococcus aureus (G2576T mutant in ireland, 2007), coagulase-negative staphylococci (CoNS; usually Staphylococcus epidermidis, France and italy in 2006-2009) and enterococci (Enterococcus faecium in Germany [2006, 2008, 2009] and E. faecalis in Sweden [2008], United Kingdom [2008] and Germany [2009]); all but one strain having a target mutation. A mobile cfr was detected in an italian CoNS strain (2008 and 2009), and clonal spread was noted for linezolid-resistant strains (pfGe results). Overall the linezolid susceptibility rates were >99.9, 99.7 and 99.6% for S. aureus, CoNS and enterococci, respectively; and all streptococcal strains were susceptible (MIC90, 1 mg/L). In conclusion, the ZAAPS program surveillance confirmed high, sustained levels of linezolid activity from 2002-2009 and without evidence of MIC creep or escalating resistance in Gram-positive pathogens across monitored European nations.

Antimicrobial Spectrum and Potency of Dalbavancin Tested Against Clinical Isolates from Europe and North America (2003): Initial Results from an International Surveillance Protocol

Abstract Dalbavancin is a bactericidal dimethylaminopropyl amide glycopeptide derivative possessing an extended serum elimination half-life in humans that allows onceweekly dosing for the therapy of Gram-positive infections. Strains from this baseline surveillance protocol in North America (NA; USA and Canada) and Europe (EU, 14 countries) were sampled in 2003. A total of 7,765 Gram-positive isolates (3,695 from NA and 4,070 from EU) were tested by reference broth microdilution methods against dalbavancin and 10 comparator agents. Species were analyzed separately by resistance phenotypes such as methicillin- (oxacillin-) resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE) and penicillin- resistant Streptococcus pneumoniae. Dalbavancin and other glycopeptides were very active against staphylococci (n=4648) with dalbavancin being 16- to 32- fold more potent than vancomycin (MIC90, 0.06 versus 2 mg/L). MRSA rates were greater (31.6%) in NA than in EU (26.1%). Quinupristin/dalfopristin resistance (MIC, ≥ 2 mg/L; 0.1 - 0.5%) was documented more often in EU compared to NA. Dalbavancin (MIC50, 0.03 - 0.06 mg/L) was active against enterococci, except VanA resistance phenotypes. VRE rates were lower in EU (8.3%) then in NA (35.9%) from this resistance-enhanced enterococcal collection. Streptococci (dalbavancin MIC90, 0.016 - 0.03 mg/L) were generally most susceptible to glycopeptides (100.0%), quinupristin/dalfopristin (98.6 - 100.0%) and linezolid (100.0%); but dalbavancin was 16-fold more active than comparators. All vancomycin-susceptible enterococci and > 90% of vanB VRE had dalbavancin MIC values at ≤ 1 mg/L, but vanA VRE strains had dalbavancin MIC results ranging from 0.06 to > 8 mg/L (median MIC, ≥ 8 mg/L). Dalbavancin MIC values were not adversely influenced by geographic region or resistance phenotype (except vanA VRE). Infrequently isolated Gram-positive organisms such as Bacillus spp. (MIC90, 0.12 mg/L), Corynebacterium spp. (MIC90, 0.12 mg/L), Listeria monocytogenes (MIC90, 0.25 mg/L) and Micrococcus spp. (MIC90, 0.03 mg/L) were very susceptible to dalbavancin. In conclusion, these 2003 baseline resistance surveillance findings confirm the potent dalbavancin activity compared to several comparator agents against important Gram-positive pathogens. This high volume international survey indicates potential therapeutic roles for dalbavancin against many troublesome resistant Gram-positive phenotypes.

Comparative Antimicrobial Potency of Meropenem Tested Against Gram-Negative Bacilli: Report from the MYSTIC Surveillance Program in the United States (2004)

Abstract The Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) Program is a longitudinal resistance surveillance network of more than 100 medical centers worldwide monitoring the susceptibility of bacterial pathogens to carbapenems and other broad-spectrum agents. In 2004 (year six), the antimicrobial activity of 12 broad-spectrum agents was assessed against 2,799 Gram-negative bacterial isolates submitted from 15 United States (USA) medical centers using Clinical and Laboratory Standards Institute (CLSI; formerly NCCLS) recommended methods. Meropenem continued to demonstrate a high potency with MIC90 values 4- to 32- fold lower than imipenem against the Enterobacteriaceae. The wide spectrum of activity for meropenem against all Gram-negative isolates was demonstrated by the overall rank order of percentage susceptibility at CLSI breakpoints: amikacin (96.5%) > meropenem (96.0%) > imipenem (95.8%) > piperacillin/tazobactam (91.5%) > tobramycin (91.4%) > cefepime (91.2%) > ceftazidime (89.0%) > gentamicin (88.0%) > aztreonam (81.5%) > levofloxacin (80.5%) > ciprofloxacin (80.2%) > ceftriaxone (69.1%). Only the aminoglycosides (84.5%) and carbapenems (76.1 - 83.8%) exhibited acceptable levels of susceptibility against the Acinetobacter spp. isolates as this species group became more resistant to all antimicrobial classes. A continued increase in the resistance rate for both ciprofloxacin and levofloxacin over the six years was observed, most alarming among Escherichia coli (20.2 - 20.7%) and indole-positive Proteus species (34.4 - 42.2%) isolates, some documented as clonal. Continued surveillance of these broad-spectrum antimicrobial agents appears warranted to monitor the potency and spectrum of activity against Gram-negative pathogens causing serious infections and the emergence of new or novel resistance mechanisms that could compromise carbapenem therapy.

Antimicrobial Activity of Daptomycin Tested Against Gram-Positive Strains Collected in European Hospitals: Results from 7 Years of Resistance Surveillance (2003-2009)

Abstract Daptomycin is a cyclic lipopeptide approved by the European medicines Agency (EMEA) for the treatment of complicated skin and soft tissue infections (cSSTI) and Staphylococcus aureus bacteremia and endocarditis. We evaluated the in vitro activity of daptomycin and comparators tested against clinical isolates from European hospitals over a 7-year period (2003-2009). A total of 36,769 consecutive isolates were collected in 34 medical centers located in 13 European countries, turkey and Israel. the collection included S. aureus (18,352; 27.2% oxacillin-resistant [MRSA]); coagulase-negative staphylo-cocci (CoNS; 6,874), Enterococcus spp. (7,241; 9.4% vancomycin-resistant),β-hemolytic (3,009), viridans group streptococci (1,176), and Streptococcus bovis/gallolyticus (107). The organisms were isolated mainly from patients with bloodstream infection (56%) or cSSTI (23%). Daptomycin was very active against S. aureus and CoNS (MIC50/90, 0.25/0.5 mg/L for both organisms), and its activity was not adversely influenced by oxacillin resistance. All Enterococcus faecalis strains were susceptible to daptomycin (MIC50/90, 1/1 mg/L). Daptomycin (MIC50/90, 2/2 mg/L; 100.0% susceptible) and linezolid (MIC50/90, 1/2 mg/L; 99.7% susceptible) were the most active agents tested against vancomycin-resistant E. faecium. Vancomycin-resistant and -susceptible enterococcal strains were equally susceptible to daptomycin. Daptomycin was also active against β-hemolytic streptococci (MIC50/90, 0.06/0.25 mg/L; 100.0% susceptible), viridans group streptococci (MIC50/90, 0.25/0.5 mg/L; 99.8% susceptible) and S. bovis (MIC50/90, 0.06/0.12 mg/L; 100.0% susceptible). In summary, daptomycin was very potent against this large collection (36,769) of Gram-positive organisms isolated in European hospitals, and its activity remained stable across the 7-year period evaluated (2003-2009), using reference methods and interpretive criteria. Decreases in daptomycin potency were not observed since EMEA approval and widespread clinical use, and emerging resistance to other compounds did not adversely influence daptomycin activity against contemporary Gram-positive species.

Activity of Mupirocin and 14 Additional Antibiotics against Staphylococci Isolated from Latin American Hospitals: Report from the SENTRY Antimicrobial Surveillance Program

Abstract A total of 1,346 Staphylococcus aureus (SA) and 498 coagulase-negative staphylococcal (CoNS) strains isolated from 11 Latin American medical centers between 2000 and 2001 were tested against mupirocin and other antimicrobial agents by reference broth microdilution method as part of the SENTRY Antimicrobial Surveillance Program. Oxacillin resistance (OR) was detected in 38.6% of S. aureus and in 78.1% of CoNS. The overall resistance rate to mupirocin was low among S. aureus (3.1%; MIC ≥8 μd/ml) but significantly higher among ORSA compared to oxacillin-susceptible SA (5.4% versus 1.7%; p <0.001). Mupirocin-resistant S. aureus, strains were detected in 9 of 11 centers, with individual center rates varying between 1.8 and 15.7%. Mupirocin resistance rates were high among CoNS (27.5%) and varied widely (10.0 to 48.9%) among the monitored Latin American medical centers. Mupirocin resistance rates appear to be increasing and routine monitoring for potential resistance seems prudent.

Correlation of Cefoxitin MICs with the Presence of mecA in Staphylococcus spp.

ABSTRACT This report describes the results of an 11-laboratory study to determine if a cefoxitin broth microdilution MIC test could predict the presence of mecA in staphylococci. Using breakpoints of ≤4 μg/ml for mecA-negative and ≥6 or 8 μg/ml for mecA-positive isolates, sensitivity and specificity based on mecA or presumed mecA for Staphylococcus aureus at 18 h of incubation were 99.7 to 100% in three cation-adjusted Mueller-Hinton broths tested. For coagulase-negative strains at 24 h of incubation, breakpoints of ≤2 μg/ml for mecA-negative and ≥4 μg/ml for mecA-positive isolates gave sensitivity and specificity of 94 to 99% and 69 to 80%, respectively.

Antimicrobial Susceptibility Profile of Contemporary Clinical Strains of Stenotrophomonas maltophilia Isolates: Can Moxifloxacin Activity Be Predicted by Levofloxacin MIC Results?

Abstract The susceptibility profile of 763 Stenotrophomonas maltophilia isolates was evaluated against 16 antimicrobials by the CLSI reference broth microdilution method. Minocycline (MIC90, 1 μg/ml; 100.0% susceptible) was the most active compound, followed by doxycycline (MIC90, 4 μg/ml; 99.6% susceptible), trimethoprim/sulfamethoxazole (MIC90, 1 μg/ml; 97.8% susceptible), and tigecycline (MIC90, 2 μg/ml). An excellent correlation between levofloxacin (MIC90, 4 μg/ml; 86.5% susceptible by published breakpoint criteria) and moxifloxacin (MIC90, 2 μg/ml) MIC results was observed indicating that moxifloxacin could be further evaluated as a therapeutic option for S. maltophilia infections.

Daptomycin In Vitro Activity Tested Against Gram-Positive Strains Collected from European and Latin American Medical Centers in 2003

Abstract Daptomycin, a cyclic lipopeptide, was susceptibility tested against clinical bacterial isolates consecutively collected in hospitals located in Europe (4,731 strains) and Latin America (1,007 strains) in 2003 as part of a continuing surveillance program. The bacterial isolates tested were Gram-positive pathogens that included staphylococci, streptococci and enterococci. The isolates were tested for susceptibility using broth microdilution methods (broth with 50 mg/L Ca++ for testing daptomycin). All isolates, except two Enterococcus faecium strains from Europe, were inhibited at daptomycin MIC of ≤4 mg/L. In addition, 99.4 and 97.3% of isolates were inhibited at daptomycin MIC of ≤2 and ≤1 mg/L, respectively. Except for one Staphylococcus aureus and one viridans group streptococci from Europe and one coagulase-negative staphylococci from Latin America, all staphylococcal and streptococcal isolates were inhibited by 1 mg/L of daptomycin. Resistance to other compounds (vancomycin, oxacillin, and penicillin) did not influence daptomycin activity. The activity of daptomycin was very similar in both geographic regions evaluated and demonstrated the same MIC distribution as isolates evaluated in studies in the United States. The results of this study showed that daptomycin continues to be very active against clinical isolates of Gram-positive cocci isolated in Europe and Latin America.

Contemporary Prevalence of BRO β-Lactamases in Moraxella catarrhalis: Report from the SENTRY Antimicrobial Surveillance Program (North America, 1997 to 2004)

ABSTRACT A total of 7,860 community-acquired Moraxella catarrhalis isolates (SENTRY Antimicrobial Surveillance Program, 1997 to 2004) were tested by broth microdilution methods, and 399 randomly selected strains from North American sites were tested for BRO-1 and BRO-2 by PCR methods. Several antimicrobials remained very active, including amoxicillin-clavulanate (MIC90s, ≤0.25 μg/ml), azithromycin (MIC90s, ≤0.12 μg/ml), ceftriaxone (MIC90s, 0.5 μg/ml), and levofloxacin (MIC90s, ≤0.03 to 0.06 μg/ml). The BRO-2 incidence rates by year were 3 to 4% overall (96 to 97% for BRO-1) and were the highest in Canada (7.9%), with the incidence in the United States being only 2.0%.