Helen T. Fernandez

In Vitro Activities of the New Semisynthetic Glycopeptide Telavancin (TD-6424), Vancomycin, Daptomycin, Linezolid, and Four Comparator Agents against Anaerobic Gram-Positive Species and Corynebacterium spp.

ABSTRACT Telavancin is a new semisynthetic glycopeptide anti-infective with multiple mechanisms of action, including inhibition of bacterial membrane phospholipid synthesis and inhibition of bacterial cell wall synthesis. We determined the in vitro activities of telavancin, vancomycin, daptomycin, linezolid, quinupristin-dalfopristin, imipenem, piperacillin-tazobactam, and ampicillin against 268 clinical isolates of anaerobic gram-positive organisms and 31 Corynebacterium strains using agar dilution methods according to National Committee for Clinical Laboratory Standards procedures. Plates with daptomycin were supplemented with Ca2+ to 50 mg/liter. The MICs at which 90% of isolates tested were inhibited (MIC90s) for telavancin and vancomycin were as follows: Actinomyces spp. (n = 45), 0.25 and 1 μg/ml, respectively; Clostridium difficile (n = 14), 0.25 and 1μ g/ml, respectively; Clostridium ramosum (n= 16), 1 and 4 μg/ml, respectively; Clostridium innocuum (n = 15), 4 and 16 μg/ml, respectively; Clostridium clostridioforme (n= 15), 8 and 1 μg/ml, respectively; Eubacterium group (n = 33), 0.25 and 2μ g/ml, respectively; Lactobacillus spp. (n= 26), 0.5 and 4 μg/ml, respectively; Propionibacterium spp. (n = 34), 0.125 and 0.5 μg/ml, respectively; Peptostreptococcus spp. (n = 52), 0.125 and 0.5 μg/ml, respectively; and Corynebacterium spp. (n = 31), 0.03 and 0.5 μg/ml, respectively. The activity of TD-6424 was similar to that of quinupristin-dalfopristin for most strains except C. clostridioforme and Lactobacillus casei, where quinupristin-dalfopristin was three- to fivefold more active. Daptomycin had decreased activity (MIC > 4 μg/ml) against 14 strains of Actinomyces spp. and all C. ramosum, Eubacterium lentum, and Lactobacillus plantarum strains. Linezolid showed decreased activity (MIC > 4 μg/ml) against C. ramosum, two strains of C. difficile, and 15 strains of Lactobacillus spp. Imipenem and piperacillin-tazobactam were active against >98% of strains. The MICs of ampicillin for eight Clostridium spp. and three strains of L. casei were >1 μg/ml. The MIC90 of TD-6424 for all strains tested was ≤2 μg/ml. TD-6424 has potential for use against infections with gram-positive anaerobes and deserves further clinical evaluation.

In Vitro Activities of Ramoplanin, Teicoplanin, Vancomycin, Linezolid, Bacitracin, and Four Other Antimicrobials against Intestinal Anaerobic Bacteria

ABSTRACT By using an agar dilution method, the in vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, and five other agents were determined against 300 gram-positive and 54 gram-negative strains of intestinal anaerobes. Ramoplanin was active at ≤2 μg/ml against 287 of 300 (95.7%) gram-positive organisms, including 18 strains of Clostridium difficile for which MICs of ramoplanin were 0.25 to 0.5 μg/ml; for 3 of these, linezolid MICs were 8 to 16 μg/ml. Nineteen Clostridium innocuum strains for which the vancomycin MIC at which 90% of strains were inhibited was 16 μg/ml were susceptible to ramoplanin at 0.06 to 0.25 μg/ml and to teicoplanin at 0.125 to 1.0 μg/ml. All strains of Eubacterium, Actinomyces, Propionibacterium, and Peptostreptococcus spp. were inhibited by ≤0.25 μg of ramoplanin per ml and ≤1 μg of vancomycin per ml. Ramoplanin was also active at ≤4 μg/ml against 15 of 22 of the Prevotella and Porphyromonas strains tested, but ramoplanin MICs for all 31 strains of the Bacteroides fragilis group, the Fusobacterium mortiferum-Fusobacterium varium group, and Veillonella spp. were ≥256 μg/ml. Ramoplanin displays excellent activity against C. difficile and other gram-positive enteric anaerobes, including vancomycin-resistant strains; however, it has poor activity against most gram-negative anaerobes and thus potentially has a lesser effect on the ecological balance of normal fecal flora.

In Vitro Activities of Dalbavancin and Nine Comparator Agents against Anaerobic Gram-Positive Species and Corynebacteria

ABSTRACT Dalbavancin is a novel semisynthetic glycopeptide with enhanced activity against gram-positive species. Its comparative in vitro activities and those of nine comparator agents, including daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin, against 290 recent gram-positive clinical isolates strains, as determined by the NCCLS agar dilution method, were studied. The MICs of dalbavancin at which 90% of various isolates tested were inhibited were as follows: Actinomyces spp., 0.5 μg/ml; Clostridium clostridioforme, 8 μg/ml; C. difficile, 0.25 μg/ml; C. innocuum, 0.25 μg/ml; C. perfringens, 0.125 μg/ml; C. ramosum, 1 μg/ml; Eubacterium spp., 1 μg/ml; Lactobacillus spp., >32 μg/ml, Propionibacterium spp., 0.5 μg/ml; and Peptostreptococcus spp., 0.25 μg/ml. Dalbavancin was 1 to 3 dilutions more active than vancomycin against most strains. Dalbavancin exhibited excellent activity against gram-positive strains tested and warrants clinical evaluation.

In Vitro Activities of Daptomycin, Vancomycin, Quinupristin- Dalfopristin, Linezolid, and Five Other Antimicrobials against 307 Gram-Positive Anaerobic and 31 Corynebacterium Clinical Isolates

ABSTRACT The activities of daptomycin, a cyclic lipopeptide, and eight other agents were determined against 338 strains of gram-positive anaerobic bacteria and corynebacteria by the NCCLS reference agar dilution method with supplemented brucella agar for the anaerobes and Mueller-Hinton agar for the corynebacteria. The daptomycin MICs determined on Ca2+-supplemented (50 mg/liter) brucella agar plates were one- to fourfold lower than those determined in unsupplemented media. Daptomycin was highly active (MICs, ≤2 μg/ml) against many strains including 36 of 37 peptostreptococci, 37 of 48 isolates of the Eubacterium group, and all strains of Propionibacterium spp., Clostridium perfringens, Clostridium difficile, and other Clostridium spp. It was fourfold or greater more active than vancomycin against Clostridium innocuum and 16 of 34 strains of vancomycin-resistant lactobacilli. Three strains of C. difficile for which quinupristin-dalfopristin and linezolid MICs were >8 μg/ml were inhibited by <1 μg of daptomycin per ml. Daptomycin MICs were ≥4 μg/ml for most strains of Clostridium clostridioforme, Clostridium paraputrificum, Clostridium tertium, and Clostridium ramosum; the isolates were generally more resistant to other antimicrobials. Daptomycin was two- to fourfold less active against Actinomyces spp. than vancomycin, quinupristin-dalfopristin, or linezolid. Twenty-nine of 31 strains of Corynebacterium spp., including Corynebacterium jeikeium, Corynebacterium amycolatum, and Corynebacterium pseudodiphtheriticum, were inhibited by ≤0.25 μg of daptomycin per ml. For two strains of “Corynebacterium aquaticum,” 8 μg of daptomycin per ml was required for inhibition. Daptomycin demonstrated very good activities against a broad range of gram-positive organisms including vancomycin-resistant C. innocuum and lactobacillus strains and quinupristin-dalfopristin- and linezolid-resistant C. difficile strains.

In Vitro Activity of Moxifloxacin against 923 Anaerobes Isolated from Human Intra-Abdominal Infections

ABSTRACT The in vitro activity of moxifloxacin against 923 recent anaerobic isolates obtained from pretreatment cultures in patients with complicated intra-abdominal infections was studied using the CLSI M11-A-6 agar dilution method. Moxifloxacin was active against 87% (96 of 110) Bacteroides fragilis strains at ≤1 μg/ml and 87% (79 of 90) B. thetaiotaomicron strains at ≤2 μg/ml. Species variation was seen, with B. uniformis, B. vulgatus, Clostridium clostridioforme, and C. symbiosum being least susceptible and accounting for most of the resistant isolates; excluding the aforementioned four resistant species, 86% (303 of 363) of Bacteroides species isolates and 94% (417 of 450) of all other genera and species were susceptible to ≤2 μg/ml of moxifloxacin. Overall, moxifloxacin was active against 763 of 923 (83%) of strains at ≤2 μg/ml, supporting its use as a monotherapy for some community-acquired intra-abdominal infections.

In Vitro Activity of Ceftobiprole against Aerobic and Anaerobic Strains Isolated from Diabetic Foot Infections

ABSTRACT Against 443 aerobic and anaerobic bacteria isolated from diabetic foot infections, ceftobiprole MICs (μg/ml) at which 90% of the isolates tested were inhibited were as follows: methicillin-resistant Staphylococcus aureus, 1; methicillin-susceptible S. aureus and Staphylococcus lugdunensis, 0.5; Anaerococcus prevotii, 0.125; Finegoldia magna, 0.5; Peptoniphilus asaccharolyticus, 1; Peptostreptococcus anaerobius, 4; Escherichia coli and Enterobacter species, 0.125; Klebsiella species, 2; and Pseudomonas aeruginosa, 8.

In Vitro Activities of Dalbavancin and 12 Other Agents against 329 Aerobic and Anaerobic Gram-Positive Isolates Recovered from Diabetic Foot Infections

ABSTRACT Tests of dalbavancins in vitro activity against 209 aerobic and 120 anaerobic isolates from pretreatment diabetic foot infections showed an MIC90 of ≤0.125 μg/ml against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and 120 anaerobes (Clostridium perfringens, other clostridia, Peptoniphilus asaccharolyticus, Finegoldia magna, and Anaerococcus prevotii), compared to respective MIC90s for MSSA and MRSA of 0.5 and 1 μg/ml for vancomycin, 4 and 4 μg/ml for linezolid, 0.5 and 0.5 μg/ml for daptomycin, and 0.25 and >8 μg/ml for clindamycin.

Comparative In Vitro Susceptibilities of 396 Unusual Anaerobic Strains to Tigecycline and Eight Other Antimicrobial Agents

ABSTRACT Tigecycline was tested against 396 strains of lesser-known anaerobic species encountered in human infections. It was active against all gram-positive strains and 228 of 232 gram-negative anaerobes at ≤1 μg/ml. One strain of Prevotella oralis was nonsusceptible at 8 μg/ml.

In Vitro Activities of Doripenem and Six Comparator Drugs against 423 Aerobic and Anaerobic Bacterial Isolates from Infected Diabetic Foot Wounds

ABSTRACT Against 182 anaerobe and 241 aerobe strains obtained from diabetic foot infections, doripenem was the most active carbapenem against Pseudomonas aeruginosa (MIC90, 2 μg/ml), more active than imipenem against Proteus mirabilis, and ertapenem was more active against Escherichia coli and Klebsiella spp. The MIC50 and MIC90 values were ≤0.125 μg/ml for methicillin-sensitive Staphylococcus aureus and all streptococci and 0.25/1 for Bacteroides fragilis.

In vitro activities of daptomycin, vancomycin, and penicillin against Clostridium difficile, C. perfringens, Finegoldia magna, and Propionibacterium acnes

ABSTRACT Daptomycin has in vitro activity against gram-positive anaerobic bacteria, although limited numbers of species have been tested. We studied the in vitro activities of daptomycin, vancomycin, and penicillin against more than 100 strains each of Clostridium difficile, C. perfringens, Finegoldia magna, and Propionibacterium acnes. Daptomycin Etest MICs and results from time-kill studies were determined for selected strains. For 392 of 421 strains (93%), daptomycin was inhibitory at ≤1 μg/ml, including 15 of 16 strains of C. difficile with elevated linezolid MICs of 8 and 16 μg/ml, all 32 strains with moxifloxacin MICs of ≥4 μg/ml, and all 16 strains resistant to clindamycin. Daptomycin MICs were also ≤1 μg/ml for all 16 F. magna strains resistant to clindamycin and all 32 strains resistant to tetracycline. Only one strain, a C. perfringens strain, had a MIC of >2 μg/ml to daptomycin. Eighty-five and 92.5% of the Etest MICs were within 1 dilution of the agar dilution method for all drugs at 24 and 48 h, respectively. In time-kill studies, a C. difficile strain was inhibited by both daptomycin and vancomycin at 1, 2, 4, 8, and 24 h; colony counts were decreased by 2.3 to 2.9 log at 24 h. Vancomycin was not bactericidal for C. perfringens; however, daptomycin showed bactericidal activity as early as 1 h at four and eight times the MIC and at 2 and 4 h at two and four times the MIC.