Daptomycin in vitro activity tested against Gram-positive strains collected from European and Latin American medical centers in 2003

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 < or = 4 mg/L. In addition, 99.4 and 97.3% of isolates were inhibited at daptomycin MIC of < or = 2 and < or = 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.     

Telavancin Activity against gram-positive bacteria isolated from patients with skin and skin-structure infections

Telavancin is approved in the United States and Canada for the treatment of complicated skin and skin structure infections (cSSSI) in adults caused by susceptible Gram-positive organisms. The antimicrobial activity of telavancin and comparators was evaluated against 5,027 (2007-2008) Gram-positive bacteria responsible for SSSI in medical centers in Asia-Pacific, European, Latin American, and North American regions. Telavancin was active against Staphylococcus aureus (MIC??(/)??, 0.12/0.25 mg/l; 100.0% susceptible) and coagulase-negative staphylococci (MIC??(/)??, 0.12/0.25 mg/l). telavancin inhibited all Enterococcus faecalis, including four strains displaying a VanB phenotype, at ≤ 1 mg/L (MIC??(/)??, 0.25/0.5 mg/l), except for two isolates with a VanA phenotype (MIC, >2 mg/l). Vancomycin-susceptible and VanB vancomycin-resistant E. faecium were inhibited by telavancin at ≤ 0.25 mg/L, while this drug exhibited elevated MIC values (≥ 0.5 mg/l) against E. faecium of VanA phenotype (MIC??(/)??, 2/>2 mg/l). Telavancin was potent against β-haemolytic streptococci (MIC??(/)??, 0.03/0.12 mg/l; 100.0% susceptible) and viridans group streptococci (MIC??(/)??, 0.03/0.06 mg/l; 100.0% susceptible). These in vitro data document the activity of telavancin against contemporary Gram-positive isolates and support its clinical use for the treatment of cSSSI caused by the indicated pathogens.     

ZAAPS Program results for 2010: an activity and spectrum analysis of linezolid using clinical isolates from 75 medical centres in 24 countries

Abstract

The Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) Program monitors the in vitro activities of linezolid and comparator agents for Gram-positive organisms in Latin America, Europe, Canada, and the Asia-Pacific. For the 2010 Program a total of 6305 Gram-positive strains were collected from 75 medical centres on five continents (24 countries). Reference broth microdilution susceptibility tests were performed on organisms from the following groups: Staphylococcus aureus (2875), coagulase negative staphylococci (CoNS) (855), enterococci (787), Streptococcus pneumoniae (926), viridans group and other streptococci (325), and beta-haemolytic streptococci (507). Linezolid demonstrated a 99·81% susceptibility rate among 6305 strains tested from 24 nations. Of the resistant isolates, four linezolid-resistant strains of enterococci (two each for Enterococcus faecalis and Enterococcus faecium) were found in four nations (China, Thailand, Germany, and Brazil). Eight CoNS (Staphylococcus epidermidis, Staphylococcus hominis) isolates were observed to be resistant to linezolid (MIC, ≧8 μg/ml). Two strains from Mexico were determined to be from an ongoing epidemic, and investigations showed that isolates from Italy and Brazil were also from circulating resistant clones discovered in earlier years. MRSA rates varied by region and between nations, as did resistances to other potential therapeutic agent options frequently listed for MRSA therapy such as clindamycin, fluoroquinolones and trimethoprim/sulfamethoxazole. In summary, the 2010 ZAAPS Program demonstrated that linezolid activity remains stable around the world with >99% susceptibility.     

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.     

Antimicrobial activity of daptomycin tested against gram-positive strains collected in European hospitals: results from 7 years of resistance surveillance (2003-2009)

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 staphylococci (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 (MIC(50/90), 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 (MIC(50/90), 1/1 mg/l). Daptomycin (MIC(50/90), 2/2 mg/l; 100.0% susceptible) and linezolid (MIC(50/90), 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 (MIC(50/90), 0.06/0.25 mg/l; 100.0% susceptible), viridans group streptococci (MIC(50/90), 0.25/0.5 mg/l; 99.8% susceptible) and S. bovis (MIC(50/90), 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.     

Telavancin activity tested against Gram-positive clinical isolates from European,Russian and Israeli hospitals (2011–2013) using a revised broth microdilution testing method: redefining the baseline activity of telavancin

Objectives: To reassess the activity of telavancin when tested against Gram-positive clinical pathogens recovered from hospitalized patients in European and adjacent regions using a revised broth microdilution method.

Methods: 11?601 consecutive, non-duplicate isolates originating from 36 institutions among 18 countries recovered between 2011 and 2013 were tested for susceptibility using a revised broth microdilution method for telavancin. Interpretive telavancin breakpoints appropriate for the method were those recently approved by the FDA and EUCAST, as available.

Results: Telavancin (MIC_50/90, 0.03/0.06?mg/l; 100.0% susceptible) was equally potent against methicillin-susceptible ((MSSA) and methicillin-resistant (MRSA) Staphylococcus aureus. All Enterococcus faecalis was susceptible to telavancin (MIC_50/90, 0.12/0.12?mg/l) and inhibited at the susceptibility breakpoint (i.e. ≤?0.25?mg/l), except for VanA-phenotype vancomycin-resistant isolates (telavancin MIC, >1?mg/l). Telavancin (?≤?0.015/0.03?mg/l) was active against vancomycin-susceptible Enterococcus faecium, while higher MIC values were obtained for VanA strains. Telavancin (both MIC₅₀ and MIC₉₀, ≤?0.015?mg/l) was potent against Streptococcus pneumoniae, beta-haemolytic streptococci (MIC_50/90, ≤?0.015/0.06?mg/l) and viridans group streptococci (MIC_50/90, ≤?0.015/0.03?mg/l).

Conclusions: Telavancin exhibited potent activity against this contemporary (2011–2013) collection of organisms, inhibiting indicated pathogens at or below the FDA/EUCAST-approved breakpoints for susceptibility. VanA-phenotype enterococci were less susceptible to telavancin, a feature observed using the previous testing method. These results redefine telavancin's activity against isolates from Europe.     

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 (MIC_50/90, 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 (MIC_50/90, 1/1 mg/L). Daptomycin (MIC_50/90, 2/2 mg/L; 100.0% susceptible) and linezolid (MIC_50/90, 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 (MIC_50/90, 0.06/0.25 mg/L; 100.0% susceptible), viridans group streptococci (MIC_50/90, 0.25/0.5 mg/L; 99.8% susceptible) and S. bovis (MIC_50/90, 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.     

Antimicrobial spectrum and potency of dalbavancin tested against clinical isolates from Europe and North America (2003): initial results from an international surveillance protocol

Dalbavancin is a bactericidal dimethylaminopropyl amide glycopeptide derivative possessing an extended serum elimination half-life in humans that allows once-weekly 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, > or = 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 < or = 1 mg/L,but vanA VRE strains had dalbavancin MIC results ranging from 0.06 to > 8 mg/L (median MIC, > or = 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.     

Activity of daptomycin and selected antimicrobial agents tested against Staphylococcus aureus from patients with bloodstream infections hospitalized in European medical centers

Daptomycin is a cyclic lipopeptide with potent bactericidal activity against Gram-positive organisms and has been approved by the United States Food and Drug Administration for the treatment of Staphylococcus aureus bacteremia and infectious endocarditis (right-side). We evaluated the activity of daptomycin against bloodstream infection S. aureus strains from 4,799 patients hospitalized in 32 medical centers (12 European countries, Turkey and Israel) with bloodstream infections (BSI) during a 5-year period (2002-2006). Intravenous catheters were the source of infection in 15% of cases, and those strains were analyzed separately. All strains were susceptibility tested by reference broth microdilution methods utilizing calcium supplementation (50 mg/L) when testing daptomycin. Bactericidal activity of daptomycin and vancomycin were evaluated against a subset of 50 randomly selected strains. Daptomycin (MIC(50/90), 0.25/0.5 mg/L), vancomycin (MIC (50/90), 1/1 mg/L), and linezolid (MIC(50/90), 2/2 mg/L), were highly active (>99.9% susceptibility) against the strains evaluated; and daptomycin was the most potent (lowest MIC(90) ) among these compounds. Resistance rates to oxacillin and levofloxacin were generally elevated, especially when an intravenous catheter was the source of infection.     

The In Vitro Activity of Trospectomycin against Anaerobic Bacteria

Abstract

The authors evaluated the activity of trospectomycin, a new aminocyclitol which is characterized by good antibacterial and broad spectrum activity, in comparison with clindamycin and ampicillin on a sample of recent isolates: Bacteroides fragilis (15 strains), Bacteroides urealyticus (5 strains), Bacteroides vulgatus (5 strains), Bacteroides spp. (15 strains), Prevotella melaninogenica (6 strains), Porphyromonas asaccha-rolytica (7 strains), Mobiluncus spp. (3 strains), Peptococcus niger (3 strains), Peptococcus variabilis (9 strains), Peptococcus spp (30 strains), Peptostreptococcus anaerobius (5 strains), Peptostreptococcus asaccharolyticus (3 strains), Peptostreptococcus spp. (25 strains) and Propioni-bacterium spp. (7 strains). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for all strains by microtiter serial dilutions in Wilkins-Chalgren broth in an anaerobic chamber in an atmosphere of 10% H₂, 10% CO₂, 80% N₂. All the drugs tested exert their activity against Gram-positive and Gram-negative anaerobic isolates. In particular, trospectomycin is quite active against Gram-positive cocci (MIC 90 = 4 - 8 mg/l), Gram-negative rods (MIC 90 = 8 - 16 mg/l), Gram-positive rods (MIC 90 = 4 mg/l) and Mobiluncus spp. (MIC 90 = 0.5 mg/l).     

In-vitro activity of ceftriaxone combined with newer agents against MRSA

In this study, in vitro synergism in combinations of agents as ceftriaxone/dalbavancin, ceftriaxone/linezolid and ceftriaxone/daptomycin against MRSA strains were investigated. Thirty clinical MRSA strains were tested. The minimum inhibitory concentrations of all antibiotics were determined using reference broth microdilution method. In-vitro activities of antibiotics combined against the strains were tested using two-dimensional checkerboard microdilution method. Results were interpreted as follows: synergy = FICI ≤0.5; ‘no interaction’ effect = FICI ?0.5-≤4; antagonism = FICI ?4. The MIC₅₀, MIC₉₀ and MIC_range of ceftriaxone, daptomycin, dalbavancin and linezolid were found as 128, 1024 and 16-2048 mg/L; 1, 1 and 0.5–1 mg/L; 0.12, 0.12 and 0.03–0.12 mg/L; and 1, 2 and 1–2 mg/L, respectively. Our results showed that the frequency of synergistic effects (FICI: ≤0.5) of three combinations were all at the same rate of 77% (23/30). No in vitro antagonism (FICI >4) was observed.     

Activity of tedizolid against gram-positive clinical isolates causing infections in Europe and surrounding areas (2014–2015)

Activities of tedizolid and comparators were evaluated against gram-positive isolates responsible for skin and skin structure infections, pneumonia, and bloodstream infections. Non-duplicate gram-positive isolates (8011) were collected from 20 European countries/regions.

Tedizolid (0.12?mg/L) showed similar results of minimum inhibitory concentration required to inhibit the growth of 50% of organisms (MIC₅₀) regardless of pathogen/group or infection type, except for coagulase-negative staphylococci, Enterococcus faecalis, and viridans group streptococci (VGS), against which tedizolid had MIC₅₀ values of 0.06, 0.25, and 0.06?mg/L, respectively. Similar results of tedizolid MIC₅₀ and minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC₉₀) (MIC_50/90, 0.12/0.12?mg/L) were obtained against methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus. Tedizolid, linezolid, and daptomycin were active against enterococci. Tedizolid (MIC₉₀, 0.12–0.25?mg/L), ceftaroline (MIC₉₀, 0.12?mg/L), and vancomycin (MIC₉₀, 0.25–0.5?mg/L) had the lowest MIC₉₀ values against Streptococcus pneumoniae and VGS, whereas ceftaroline (MIC₉₀, ≤0.015?mg/L), penicillin (MIC₉₀, ≤0.06?mg/L), ceftriaxone (MIC₉₀, ≤0.06–0.12?mg/L), and tedizolid (MIC₉₀, 0.12?mg/L) were the most potent against β-haemolytic streptococci.

Tedizolid displayed potent activity against gram-positive isolates from Europe, regardless of infection type.     

Comparative antimicrobial spectrum and activity of BMS284756 (T-3811; a desfluoroquinolone) tested against an international collection of staphylococci and enterococci, including in vitro test development and intermethod comparisons

The study was initiated to determine the in vitro activity and MIC/disk test comparisons of BMS284756, a new des-fluoro(6)-quinolone, against isolates of staphylococci and enterococci from the SENTRY Antimicrobial Surveillance Program, 2000. Isolates were tested by reference broth microdilution and standardized disk diffusion methods. Against 3,789 strains of gram-positive cocci from the SENTRY Program (2000), the BMS284756 MIC90 and percentage susceptible at < or = 2 and < or = 4 microg/ml were: Staphylococcus aureus (4 microg/ml; 89.3 and 97.1%), coagulase-negative staphylococci (CoNS; 4 microg/ml; 86.1 and 96.0%) and enterococci (> 4 microg/ml; 62.0 and 76.2%). Also tested were selected staphylococci (300 strains) and enterococci (102 strains) by two standardized methods. The activity of BMS284756 was highly correlated with oxacillin resistance among staphylococci. Oxacillin-susceptible staphylococci were all inhibited by BMS284756 at < or = 0.5 microg/ml, whereas oxacillin-resistant strains required inhibitory concentrations of > or = 1 microg/ml. Excellent correlation was observed between the MIC and 5-microg disk zone diameter for staphylococci and enterococci (r=0.91 to 0.93). Among vancomycin-susceptible enterococci, 67% of Enterococcus faecalis, 25% of E. faecium, and 76% of other Enterococcus spp. isolates were inhibited by BMS284756 at < or = 2 microg/ml. All vancomycin-resistant enterococci (VRE; 11 E. faecalis and 15 E. faecium) were inhibited by > or = 2 microg/ml of BMS284756. Among the non-VRE, non-faecium enterococcal isolates (n=64), 62% were inhibited by < or = 0.5 microg/ml. BMS284756 showed excellent activity against oxacillin-susceptible staphylococci and moderate activity against enterococci other than VRE and E. faecium. Acceptable correlations were observed between MIC and disk test results for both tested genus groups.     

Comparative in vitro potency and kill curve activity of tedizolid and linezolid against Gram-positive bacteria isolated from Chinese hospitalized patients in 2013–2016

We compared the kill-curve activity of tedizolid and linezolid at clinically relevant (total or free plasma, lung) concentrations against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae (PRSP) isolated from Chinese patients. Tedizolid had greater in vitro potency than linezolid against staphylococci, streptococci and enterococci species (tedizolid minimum inhibitory concentration (MIC) range: ≤ 0.016–0.5?µg/mL; linezolid MIC range: 0.25–2?µg/mL). In kill-curve experiments, growth of MRSA was inhibited at tedizolid concentration of 0.6?µg/mL (i.e. 4.8 × MIC; MIC = 0.125?µg/mL) and linezolid concentration of 2?µg/mL (2× MIC; MIC = 1?µg/mL). Against PRSP, tedizolid at a concentration of 0.25?µg/mL (representing its MIC) was bacteriostatic, but exerted a bactericidal effect at higher concentrations. Results were similar for linezolid, however, even at 21?µg/mL, a small proportion of organisms survived beyond 24?h. The results demonstrated the potency of tedizolid against clinical strains of Gram-positive pathogens supporting its use as a suitable alternative to linezolid in Chinese patients.     

Comparative In- Vitro Activity of Piperacillin and Piperacillin Plus Tazobactam Towards Beta-Lactamase Producing Clinical Isolates

Summary

The authors evaluated the in-vitro antibacterial activity of piperacillin alone and of piperacillin combined with tazobactam, a new beta-lactamase inhibitor, on 398 clinical isolates, both Gram-positive and Gram-negative. The piperacillin/tazobactam combination was evaluated in the fixed ratio 8:1. The vast majority of the microorganisms tested had reduced susceptibility to piperacillin (minimum inhibitory concentration (MIC) range 0.12— > 256 mg/1) due to beta-lactamase production.

The following results were obtained: against Haemophilus influenzae, tazobactam was effective in reducing the MICs of piperacillin by 512 fold. The activity of piperacillin/tazobactam was lower against Pseudomonas sp., while some activity was demonstrated against some strains of Klebsiella. Good activity was seen not only against methicillin-susceptible (MS) staphylococci but also against some methicillin-resistant (MR) strains. In the latter, the combination of piperacillin/tazobactam was active only if the strains showed beta-lactamase production. These findings are interesting above all in regard to the synergistic effect demonstrated against MR beta-lactamase producing staphylococci and the Klebsiella-Enterobacter-Serratia (KES) group.     

In vitro activities of antimicrobial cationic peptides; melittin and nisin,alone or in combination with antibiotics against Gram-positive bacteria

Abstract

The in vitro activities of two antimicrobial cationic peptides, melittin and nisin alone and in combination with frequently used antibiotics (daptomycin, vancomycin, linezolid, ampicillin, and erythromycin), were assessed against clinical isolates of methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus and Enterococcus faecalis. Using the broth microdilution method, minimum inhibitory concentration (MIC) ranges of melittin and nisin against all strains were 2–8 μg/ml and 2–32 μg/ml respectively. In combination studies performed with the microdilution checkerboard method using a fractional inhibitory concentration index of ?0·5 as borderline, synergistic interactions occurred more frequently with nisin–ampicillin combination against MSSA and nisin–daptomycin combination against E. faecalis strains. The results of the time-killing curve analysis demonstrated that the concentration dependent rapid bactericidal activity of nisin, and that synergism or early synergism was detected in most strains when nisin or melittin was used in combination with antibiotics even at concentrations of 0·5×MIC.     

Comparative in vitro activity of ceftaroline and comparator agents against nosocomial Gram-negative and Gram-positive clinically significant bacterial isolates from patients in a teaching hospital in Kuwait

The objective was to test the in vitro activities of ceftaroline and comparator agents against clinical isolates of Gram-negative and Gram-positive bacteria. Isolates were identified with VITEK II. Susceptibility testing was with E test. A total of 1264 isolates were tested. Compared to other cephalosporins, ceftaroline demonstrated excellent in vitro activities (MIC₉₀, ≤0.5 mg/L) against Escherichia coli, Salmonella spp. and Haemophilus influenzae. When matched with the comparator cephalosporins, ceftaroline demonstrated the greatest activity against methicillin-susceptible Staphylococcus aureus (MSSA), with MIC₉₀ of 0.25 mg/L. Ceftaroline’s MIC₉₀s against both community-associated methicillin-resistant S. aureus (MRSA) and hospital-acquired MRSA were 0.5 and 1 mg/L, respectively. Major discrepancies were noted between E test and disc diffusion tests for ceftaroline only against 16 Gram-negative and 16 Gram-positive isolates. Ceftaroline demonstrated an excellent in vitro activity against the majority of clinically significant Gram-negative and Gram-positive isolates obtained from proven cases of bacterial infections.     

Comparison of teicoplanin and vancomycin in vitro activity on clinical isolates of Staphylococcus aureus

Abstract

Ninety-one clinical isolates of Staphylococcus aureus have been tested with the Kirby Bauer and the Etest® method to determine the susceptibility to glycopeptides in the 2007–2010 period. Five strains (5·5%) were resistant to vancomycin and nine (9·9%) to teicoplanin. Teicoplanin showed a median minimal inhibitory concentration (MIC) of 1 mg/l (range 0·125–24 mg/l), an MIC50 of 1 mg/l, and an MIC90 of 2 mg/l; vancomycin had a median MIC of 1·5 mg/l (range 0·38–4 mg/l), an MIC50 of 1·5 mg/l, and an MIC90 of 2 mg/l. More isolates were distributed on higher values of MIC for vancomycin. Inhibition halos induced by vancomycin-impregnated paper diskettes were slightly larger than those by teicoplanin. Glycopeptide resistance among methicillin-resistant Staphylococcus aureus in Italy is an underestimated phenomenon, possibly due to the described underestimation of glycopeptides MICs by the automatic broth microdilution method, when compared to agar MIC assays. A teicoplanin MIC creep, as reported for vancomycin, cannot be assumed.     

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.     

In vitro evaluation of BI 397, a novel glycopeptide antimicrobial agent.

BI 397, a semi-synthetic amide derivative of the experimental glycopeptide, MDL 62,476 (A40926), has excellent in vitro activity against a wide range of Gram-positive organisms. In this extensive study, 630 contemporary (1998-2000) Gram-positive isolates were selected from various resistance surveillance studies for their resistance patterns to fluoroquinolones, macrolides-lincosamides-streptogramins, beta-lactams and glycopeptide agents. The BI 397 spectrum of activity was similar to that of other glycopeptides with a MIC90 of < or =0.5 microg/ml for all tested isolates with the exception of vancomycin-resistant enterococci Van A; (MIC90, 32 microg/ml). BI 397 was more potent than vancomycin and teicoplanin against Staphylococcus aureus (2- to 8-fold), beta-haemolytic streptococci (equal to >16-fold), viridans group streptococci (equal to >32-fold), and Corynebacterium spp. including C. jeikeium (8- to >16-fold). BI 397 was also more active than quinupristin/dalfopristin against all Gram-positive organisms tested with the exception of oxacillin-susceptible S. aureus, against which it had equal activity. BI 397 has little activity against Haemophilus influenzae (MIC90, 64 microg/ml) or other Gram-negative bacilli (MIC90, >64 microg/ml). BI 397 exhibited bacteriostatic activity (like the vancomycin control) versus most species, but was bactericidal against tested Streptococcus pneumoniae. In vitro testing conditions with blood supplemented or free protein containing media elevated BI 397 MIC results, and the 30-microg disk seems acceptable for further disk diffusion test development. Animal pharmacokinetic data published elsewhere suggest that BI 397 may be dosed less frequently than teicoplanin and the results of early studies in humans are awaited with interest, especially when treating teicoplanin-refractory coagulase-negative staphylococci.