In vitro activity of DS-2969b and comparator antimicrobial agents against Clostridioides (Clostridium) difficile, methicillin-resistant Staphylococcus aureus, and other anaerobic bacteria.

The in vitro activity of DS-2969b, a novel GyrB inhibitor, and six comparator agents was studied against 101 recent North American Clostridioides difficile isolates, 46 other intestinal anaerobes and 51 strains of methicillin-resistant Staphylococcus aureus. The MIC ranges (MIC90s) of DS-2969b against C. difficile and S. aureus were 0.03-0.125 (0.125) µg/ml and 0.125-1 (0.5) µg/ml, respectively. DS-2969b showed the greatest activity of the agents tested. There was no difference in MICs of DS-2969b among different ribotypes.

Anti-anaerobic activity of serum from patients treated with tigecycline for skin/soft tissue infections.

To gain additional data concerning the anti-anaerobic activity of tigecycline in serum, we analyzed blood samples from six patients with a complicated skin/soft tissue infection who were receiving IV tigecycline 50 mg every 12 h. Venous blood samples were obtained after multiple doses of tigecycline at 1, 6 and 12 h after the initiation of a 1 h IV infusion. Sera from these samples were tested to determine serum inhibitory and bactericidal activity over time against 4 anaerobic bacteria (Bacteroides fragilis, Peptoniphilus asaccharolyticus, Prevotella bivia and Finegoldia magna). An analysis of serum titers found that tigecycline exhibited early (1 h) and prolonged (12 h) inhibitory activity against each study isolate. Moreover, it provided bactericidal activity for 12 h against these strains with the exception of F. magna. Tigecycline was found to exhibit antibacterial activity at serum concentrations below the MICs of the anaerobic bacteria tested. This finding further supports that the antimicrobial activity of tigecycline can be greater than that suggested by the free fraction of drug and that serum appears to enhance this antibacterial activity.

In vitro activity of ceftaroline against 623 diverse strains of anaerobic bacteria.

The in vitro activities of ceftaroline, a novel, parenteral, broad-spectrum cephalosporin, and four comparator antimicrobials were determined against anaerobic bacteria. Against Gram-positive strains, the activity of ceftaroline was similar to that of amoxicillin-clavulanate and four to eight times greater than that of ceftriaxone. Against Gram-negative organisms, ceftaroline showed good activity against beta-lactamase-negative strains but not against the members of the Bacteroides fragilis group. Ceftaroline showed potent activity against a broad spectrum of anaerobes encountered in respiratory, skin, and soft tissue infections.

The effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus.

The in vivo effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus were examined over time after anthelmintic treatment of sheep. Twenty merino sheep, (12 months old) were allocated to five treatment groups and infected with ivermectin-resistant H. contortus. Thirty one days later, the sheep were treated with intraruminal ivermectin capsules, oral ivermectin, oral moxidectin or injectable moxidectin at the manufacturer's recommended dosages, or left untreated. At various times up to 112 days after treatment, faecal egg counts (FEC) were determined and development rates of infective larvae (L3) cultured in faeces or on agar were measured. Eggs in faecal cultures from ivermectin capsule treated sheep showed reduced L3 development percentages in comparison to faecal cultures from untreated sheep. Eggs from ivermectin capsule treated sheep, isolated from faeces, and cultured on agar showed similar L3 development to eggs from control sheep. These results demonstrate an inhibitory effect of excreted ivermectin in faeces on larval development of ivermectin-resistant H. contortus. L3 development in faecal culture from animals receiving oral ivermectin were reduced for only 3 days after treatment. Faecal egg counts and development of L3 larvae in both culture systems from moxidectin treated sheep were low, due to the high efficacy of the drug. Egg counts in moxidectin treated sheep were reduced by approximately 90% 24h after treatment, before decreasing to almost 100% at 48h, suggesting that the current quarantine recommendation of holding sheep off pasture for 24h after treatment may still lead to some subsequent pasture contamination with worm eggs.

A multi-species model to assess the effect of refugia on worm control and anthelmintic resistance in sheep grazing systems.

OBJECTIVE: Develop a computer simulation model that uses daily meteorological data and farm management practices to predict populations of Trichostrongylus colubriformis, Haemonchus contortus and Teladorsagia (Ostertagia) circumcincta and the evolution of anthelmintic resistance within a sheep flock. Use the model to explore if increased refugia, provided by leaving some adult sheep untreated, would delay development of anthelmintic resistance without compromising nematode control. PROCEDURES: Compare model predictions with field observations from a breeding flock in Armidale, NSW. Simulate the impact of leaving 1-10% of adult sheep untreated in diverse sheep-grazing systems. RESULTS: Predicted populations of Tr. colubriformis and T. circumcincta were less than those observed in the field, attributed to nutritional stress experienced by the sheep during drought and not accounted for by the model. Observed variation in faecal egg counts explained by the model (R(2) ) for these species was 40-50%. The H. contortus populations and R(2) were both low. Leaving some sheep untreated worked best in situations where animals were already grazing or were moved onto pastures with low populations of infective larvae. In those cases, anthelmintic resistance was delayed and nematode control was maintained when 1-4% of adult stock remained untreated. CONCLUSIONS: In general, the model predicted that leaving more than 4% of adults untreated did not sufficiently delay the development of anthelmintic resistance to justify the increased production risk from such a strategy. The choice of a drug rotation strategy had an equal or larger effect on nematode control, and selection for resistance, than leaving 1-10% of adults untreated.

In vitro activities of tinidazole and metronidazole against Clostridium difficile, Prevotella bivia and Bacteroides fragilis.

Tinidazole, a 5-nitroimidazole similar to metronidazole, was studied against 40 Clostridium difficile, 10 Prevotella bivia and 11 Bacteroides fragilis clinical isolates. The geometric mean MICs of tinidazole and metronidazole were, respectively: C. difficile, 0.31 and 0.28 microg/mL; P. bivia, 2.33 and 1.52 microg/mL; B. fragilis, 0.5 and 0.71 microg/mL.

Comparative In vitro activities of ertapenem (MK-0826) against 1,001 anaerobes isolated from human intra-abdominal infections.

By using an agar dilution method, the comparative in vitro activities of ertapenem (MK-0826) were studied against 1,001 anaerobes isolated from human intra-abdominal infections in 17 countries worldwide. MK-0826 was uniformly active against all isolates, including all Bacteroides fragilis group species isolates, with the exception of 12 of 61 (20%) strains of Bilophila wadsworthia, 3 strains of lactobacilli, and 1 isolate of Acidaminococcus fermentans. Geographical variation in activity was not observed.

In vitro activities of ramoplanin, teicoplanin, vancomycin, linezolid, bacitracin, and four other antimicrobials against intestinal anaerobic bacteria.

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 or=256 microg/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.

Bacteriology of human bite wound infections.

This study was designed to define the bacteriology of infected soft-tissue wounds from human bites, and to compare this with the bacteriology of infected animal bites in humans as determined in previous studies. The specimens were collected from 57 patients presenting to emergency rooms at 12 locations around the country. Three hundred and eighty organisms were isolated (224 aerobes and 156 anaerobes), for an average of 6.6 per specimen. The most prevalent anaerobes recovered were Prevotella spp. (34%), while streptococci comprised 44% of all aerobic organisms, over half of which were in the "Streptococcus milleri" group, particularly S. anginosus. The study demonstrated that the pathogens in human bite infections differ considerably from those present in animal bites.