Comparative susceptibility of Gemella morbillorum to 13 antimicrobial agents.

The in vitro activity of 13 antimicrobials against clinical isolates of Gemella morbillorum showed good susceptibility to clindamycin, all beta-lactams agents studied except cefoxitin (MIC90, 4 µg/ml) and fluoroquinolones. There was 36% metronidazole resistance.

In Vitro Activity of Tedizolid Compared to Linezolid and Five Other Antimicrobial Agents against 332 Anaerobic Isolates, Including Bacteroides fragilis Group, Prevotella, Porphyromonas, and Veillonella Species.

Tedizolid's anaerobic activity is unappreciated. In this study, it was active against all 332 anaerobic isolates tested at ≤2 µg/ml except Bilophila wadsworthia and was more active than linezolid against Bacteroides fragilis group species (MIC90, 1 µg/ml versus 2 to 4 µg/ml). Tedizolid was active against Gram-positive anaerobes (MIC90 for clostridia, 0.25 to 1 µg/ml; MIC90 for anaerobic cocci, ≤0.06 to 0.25 µg/ml). Our data coupled with clinical reports indicate that clinicians should consider its use in mixed infections where Staphylococcus aureus and anaerobes are involved.

Comparative In Vitro Activity of Omadacycline against Dog and Cat Bite Wound Isolates.

Omadacycline was tested against 125 isolates recovered from infected cat and dog bites in humans. Its activity was similar to that of other compounds in the tetracycline class, and it was active against strains exhibiting tetracycline resistance. Against anaerobic isolates, resistance to tetracyclines was more prominent and omadacycline was the most active of the group. All isolates had omadacycline MICs of <1 µg/ml, with the exception of Eikenella corrodens, which showed reduced susceptibility to the entire tetracycline group.

Comparative In Vitro Activities of Relebactam, Imipenem, the Combination of the Two, and Six Comparator Antimicrobial Agents against 432 Strains of Anaerobic Organisms, Including Imipenem-Resistant Strains.

Relebactam is an important beta-lactamase inhibitor for certain aerobic organisms, but alone it has no antianaerobic activity, with most anaerobes having MICs of ≥32 µg/ml with the exception of a very few strains. There was no enhancement or antagonism of imipenem activity with the addition of relebactam, including activity against imipenem-resistant strains. The relebactam-imipenem combination had excellent overall activity against the anaerobes tested.

The underappreciated in vitro activity of tedizolid against Bacteroides fragilis species, including strains resistant to metronidazole and carbapenems.

Because Bacteroides fragilis has the ability to develop mechanisms of resistance to almost all antibiotics, we studied the comparative in vitro activity of tedizolid against 124 Bacteroides group species clinical isolates, including carbapenem, metronidazole and piperacillin-tazobactam resistant strains. Tedizolid had an MIC90 of 2 µg/ml (range, 0.5-4 µg/ml) and was 1-4 times more active than linezolid that had an MIC90 of 8 µg/ml (range, 2-16 µg/ml). It was also active (MICs 0.5-2 µg/ml) against the 27 ertapenem, 2 metronidazole and 12 piperacillin-tazobactam resistant strains tested. This suggests that tedizolid may be useful treating infections, including bacteremias, due to resistant B. fragilis group species, as well as, mixed skin and soft tissue infections such as diabetic foot infections caused by Gram-positive aerobes and B. fragilis group species.

Comparative in vitro activities of SMT19969, a new antimicrobial agent, against Clostridium difficile and 350 gram-positive and gram-negative aerobic and anaerobic intestinal flora isolates.

The comparative in vitro activity of SMT19969, a novel, narrow-spectrum, nonabsorbable agent, was studied against 50 ribotype-defined Clostridium difficile strains, 174 Gram-positive and 136 Gram-negative intestinal anaerobes, and 40 Gram-positive aerobes. SMT19969 was one dilution more active against C. difficile isolates (MIC range, 0.125 to 0.5 µg/ml; MIC90, 0.25 µg/ml), including ribotype 027 strains, than fidaxomicin (range, 0.06 to 1 µg/ml; MIC90, 0.5 µg/ml) and two to six dilutions lower than either vancomycin or metronidazole. SMT19969 and fidaxomicin were generally less active against Gram-negative anaerobes, especially the Bacteroides fragilis group species, than vancomycin and metronidazole, suggesting that SMT19969 has a lesser impact on the normal intestinal microbiota that maintain colonization resistance. SMT19969 showed limited activity against other Gram-positive anaerobes, including Bifidobacteria species, Eggerthella lenta, Finegoldia magna, and Peptostreptococcus anaerobius, with MIC90s of >512, >512, 64, and 64 µg/ml, respectively. Clostridium species showed various levels of susceptibility, with C. innocuum being susceptible (MIC90, 1 µg/ml) and C. ramosum and C. perfringens being nonsusceptible (MIC90, >512 µg/ml). Activity against Lactobacillus spp. (range, 0.06 to >512 µg/ml; MIC90, >512 µg/ml) was comparable to that of fidaxomicin and varied by species and strain. Gram-positive aerobic cocci (Staphylococcus aureus, Enterococcus faecalis, E. faecium, and streptococci) showed high SMT19969 MIC90 values (128 to >512 µg/ml).

Evaluation of cycloserine-cefoxitin fructose agar (CCFA), CCFA with horse blood and taurocholate, and cycloserine-cefoxitin mannitol broth with taurocholate and lysozyme for recovery of Clostridium difficile isolates from fecal samples.

Cycloserine-cefoxitin fructose agar (CCFA), CCFA with horse blood and taurocholate (CCFA-HT), and cycloserine-cefoxitin mannitol broth with taurocholate and lysozyme (CCMB-TAL) were compared for recovery of Clostridium difficile from 120 stool specimens. Compared to CCFA, CCFA-HT enhanced C. difficile growth and improved recovery by 4%. In a separate study, 9% (8/91) of stool samples previously C. difficile negative on plate medium were C. difficile positive when cultured in CCMB-TAL.

Differences in distribution and antimicrobial susceptibility of anaerobes isolated from complicated intra-abdominal infections versus diabetic foot infections.

Few labs isolate and perform susceptibility tests on anaerobes; therefore, we studied the differences between 1185 anaerobes isolated from complicated intra-abdominal infections and 470 isolated from moderate to severe diabetic foot infections. They differed markedly in the distribution of species, including Bacteroides fragilis and anaerobic Gram-positive cocci, as well as in resistance patterns, especially to fluoroquinolones.

Comparative in vitro activity of ceftaroline, ceftaroline-avibactam, and other antimicrobial agents against aerobic and anaerobic bacteria cultured from infected diabetic foot wounds.

Foot infections are the most common infectious complication of diabetes. Moderate to severe diabetic foot infections (DFI) are typically polymicrobial with both aerobic and anaerobic organisms. The role of MRSA in these wounds has become an increasing concern. To determine if the addition of avibactam, a novel non-beta-lactam beta-lactamase inhibitor, to ceftaroline would be more active than ceftaroline alone, we tested 316 aerobic pathogens and 154 anaerobic recovered from patients with moderate to severe DFI, and compared ceftaroline with and without avibactam to other agents. Testing on aerobes was done by broth microdilution and by agar dilution for anaerobes, according to CLSI M11-A8, and M7-A8 standards. Ceftaroline-avibactam MIC90 for all Staphylococcus spp. including MRSA was 0.5 µg/mL, and for enterococci was 1 µg/mL. The MIC90s for enteric Gram-negative rods was 0.125 µg/mL. The addition of avibactam to ceftaroline reduced the ceftaroline MICs for 2 strains of resistant Enterobacter spp. and for 1 strain of Morganella. Against anaerobic Gram-positive cocci ceftaroline-avibactam had an MIC90 0.125 µg/mL and for clostridia 1 µg/mL. Avibactam improved ceftaroline's MIC90s for Bacteroides fragilis from >32 to 2 µg/mL and for Prevotella spp. from >32 to 1 µg/mL. Ceftaroline alone demonstrates excellent in vitro activity against most of the aerobes found in moderate to severe DFI. The addition of avibactam provides an increased spectrum of activity including the beta-lactamase producing Prevotella, Bacteroides fragilis and ceftaroline resistant gram-negative enteric organisms.

Comparative in vitro activities of GSK2251052, a novel boron-containing leucyl-tRNA synthetase inhibitor, against 916 anaerobic organisms.

We studied the comparative in vitro activity of GSK2251052, a novel boron leucyl-tRNA synthetase inhibitor, against 916 clinical anaerobic isolates using CLSI methods. The GSK MIC50/MIC90 for all isolates tested were 2 and 4 µg/ml, and the MIC90s against 302 Bacteroides fragilis and Bacteroides thetaiotaomicron strains were 4 and 8 µg/ml, respectively. All Clostridium perfringens strains had GSK2251052 MICs of >32 µg/ml. There was no relationship between increased MICs for any other antibiotics and that of GSK2251052.

In vitro activity of Biapenem plus RPX7009, a carbapenem combined with a serine ß-lactamase inhibitor, against anaerobic bacteria.

Biapenem is a carbapenem being developed in combination with RPX7009, a new inhibitor of serine ß-lactamases. Biapenem was tested alone and in combination with fixed concentrations of RPX7009 by agar dilution against 377 recent isolates of anaerobes. A separate panel of 27 isolates of Bacteroides spp. with decreased susceptibility or resistance to imipenem was also tested. Comparator drugs included meropenem, piperacillin-tazobactam, ampicillin-sulbactam, cefoxitin, ceftazidime, metronidazole, clindamycin, and tigecycline plus imipenem, doripenem, and ertapenem for the 27 selected strains. For recent consecutive strains of Bacteroides species, the MIC(90) for biapenem-RPX7009 was 1 µg/ml, with a MIC(90) of 4 µg/ml for meropenem. Other Bacteroides fragilis group species showed a MIC90 of 0.5 µg/ml for both agents. The MIC(90)s for biapenem-RPX7009 were 0.25 µg/ml for Prevotella spp., 0.125 µg/ml for Fusobacterium nucleatum and Fusobacterium necrophorum, 2 µg/ml for Fusobacterium mortiferum, 0.5 µg/ml for Fusobacterium varium, ≤ 0.5 µg/ml for Gram-positive cocci and rods, and 0.03 to 8 µg/ml for clostridia. Against 5 B. fragilis strains harboring a known metallo-beta-lactamase, biapenem-RPX7009 MICs were comparable to those of other carbapenems (≥ 32 µg/ml). Against Bacteroides strains with an imipenem MIC of 2 µg/ml, biapenem-RPX7009 had MICs of 0.5 to 2 µg/ml, with MICs of 0.5 to 32 µg/ml for meropenem, doripenem, and ertapenem. For strains with an imipenem MIC of 4 µg/ml, the MICs for biapenem-RPX7009 were 4 to 16 µg/ml, with MICs of 8 to >32 µg/ml for meropenem, doripenem, and ertapenem. The inhibitor RPX7009 had no antimicrobial activity when tested alone, and it showed little or no potentiation of biapenem versus anaerobes. Biapenem-RPX7009 showed activity comparable to that of imipenem and was superior to meropenem, doripenem, and ertapenem against imipenem-nonsusceptible Bacteroides spp.

Ceftaroline versus isolates from animal bite wounds: comparative in vitro activities against 243 isolates, including 156 Pasteurella species isolates.

More than 5 million Americans are bitten by animals, usually dogs, annually. Bite patients comprise ∼1% of all patients who visit emergency departments (300,000/year), and approximately 10,000 require hospitalization and intravenous antibiotics. Ceftaroline is the bioactive component of the prodrug ceftaroline fosamil, which is FDA approved for the treatment of acute bacterial skin and skin structure infections (ABSSSIs), including those containing methicillin-resistant Staphylococcus aureus (MRSA). There are no in vitro data about the activity of ceftaroline against Pasteurella multocida subsp. multocida and Pasteurella multocida subsp. septica, other Pasteurella spp., or other bite wound isolates. We therefore studied the in vitro activity of ceftaroline against 243 animal bite isolates. MICs were determined using the broth microdilution method according to CLSI guidelines. Comparator drugs included cefazolin, ceftriaxone, ertapenem, ampicillin-sulbactam, azithromycin, doxycycline, and sulfamethoxazole-trimethoprim (SMX-TMP). Ceftaroline was the most active agent against all 5 Pasteurella species, including P. multocida subsp. multocida and P. multocida subsp. septica, with a maximum MIC of ≤0.008 µg/ml; more active than ceftriaxone and ertapenem (MIC(90)s, ≤0.015 µg/ml); and more active than cefazolin (MIC(90), 0.5 µg/ml) doxycycline (MIC(90), 0.125 µg/ml), azithromycin (MIC(90), 0.5 µg/ml), ampicillin-sulbactam (MIC(90), 0.125 µg/ml), and SMX-TMP (MIC(90), 0.125 µg/ml). Ceftaroline was also very active against all S. aureus isolates (MIC(90), 0.125 µg/ml) and other Staphylococcus and Streptococcus species, with a maximum MIC of 0.125 µg/ml against all bite isolates tested. Ceftaroline has potential clinical utility against infections involving P. multocida, other Pasteurella species, and aerobic Gram-positive isolates, including S. aureus.

Comparative in vitro activities of LFF571 against Clostridium difficile and 630 other intestinal strains of aerobic and anaerobic bacteria.

The in vitro activities of LFF571, a novel analog of GE2270A that inhibits bacterial growth by binding with high affinity for protein synthesis elongation factor Tu, fidaxomicin, and 10 other antimicrobial agents were determined against 50 strains of Clostridium difficile and 630 other anaerobic and aerobic organisms of intestinal origin. LFF571 possesses potent activity against C. difficile and most other Gram-positive anaerobes (MIC(90), ≤ 0.25 µg/ml), with the exception of bifidobacteria and lactobacilli. The MIC(90)s for aerobes, including enterococci, Staphylococcus aureus (as well as methicillin-resistant S. aureus [MRSA] isolates), Streptococcus pyogenes, and other streptococci were 0.06, 0.125, 2, and 8 µg/ml, respectively. Comparatively, fidaxomicin showed variable activity against Gram-positive organisms: MIC(90)s against C. difficile, Clostridium perfringens, and Bifidobacterium spp. were 0.5, ≤ 0.015, and 0.125 µg/ml, respectively, but >32 µg/ml against Clostridium ramosum and Clostridium innocuum. MIC(90) for S. pyogenes and other streptococci was 16 and >32 µg/ml, respectively. LFF571 and fidaxomicin were generally less active against Gram-negative anaerobes.

In vitro activities of CB-183,315, vancomycin, and metronidazole against 556 strains of Clostridium difficile, 445 other intestinal anaerobes, and 56 Enterobacteriaceae species.

MICs of CB-183,315, a novel lipopeptide antibiotic, vancomycin, and metronidazole were determined for intestinal anaerobes and Enterobacteriaceae. The MIC(90)s for Gram-negative anaerobes were >8,192, 8,192, and 4 µg/ml for CB-183,315, vancomycin, and metronidazole, respectively. Against Enterobacteriaceae, the MIC(90)s were >8,192 µg/ml, 1,024 µg/ml, and 1,024 µg/ml, respectively. The CB-183,315 MIC(90) for Clostridium difficile was 0.5 µg/ml. Its lack of activity against normal fecal organisms makes it a promising new agent for treating C. difficile.

Activity of garenoxacin against 536 unusual anaerobes including 128 recovered from acute pelvic infections.

Garenoxacin, a des-(F)6-quinolone, was tested using the agar dilution method against 536 anaerobic bacteria, composed of 408 unusual strains from various sources and 128 pelvic isolates. Only 33/408 (8%) unusual isolates and 6/128 (4.7%) pelvic isolates had garenoxacin MICs ≥ 4 µg/mL, and 18 and 3 (4.4% and 2.3% of the respective totals) had MICs ≥ 8 µg/mL. Less susceptible unusual isolates included 7/15 Veillonella sp. from various clinical sources, 6/14 Fusobacterium varium from predominantly abdominal infections, 5/5 F. russii (cat bites), and 6/9 Actinomyces israelii. Overall, garenoxacin showed good activity against the isolates studied and has potential utility in mixed aerobic/anaerobic infections.

Infection after elective colorectal surgery: bacteriological analysis of failures in a randomized trial of cefotetan vs. ertapenem prophylaxis.

BACKGROUND: A randomized study comparing single-dose cefotetan and ertapenem prophylaxis for elective colorectal surgery in 1,002 patients found ertapenem to be significantly more effective (p < 0.001). Failures of prophylaxis were thought to involve organisms resistant to both antimicrobial agents, isolated most often from deep or superficial incision sites. METHODS: Further testing and analysis of the microbial data was performed. Susceptibility results were correlated with the clinical outcomes reported previously. RESULTS: Of the 216 aerobes tested, 62.6% were resistant to cefotetan and 44% to ertapenem. Enterococci and methicillin-resistant Staphylococcus epidermidis were the aerobes recovered most frequently, and Bacteroides thetaiotaomicron, Clostridium innocuum, and Eubacterium lentum were the most frequent anaerobes. Enterococcus faecalis usually was associated in mixed culture with Bacteroides fragilis group species. Approximately one-half of the 158 anaerobes (50.7%), including all the species above, were resistant to cefotetan; most of these (61.4%) came from superficial incision sites. Only one anaerobe (Desulfovibrio fairfieldensis), found in a superficial incisional infection, was resistant to ertapenem, and no ertapenem-resistant enteric bacteria were recovered. In vitro resistance was associated with therapeutic failure. CONCLUSIONS: The in vitro activity of ertapenem was superior to that of cefotetan against all anaerobic and many aerobic bacteria isolated from postoperative cultures of patients who failed prophylaxis with these agents. Our findings help to elucidate the results of the clinical trial.

In vitro activities of doripenem and six comparator drugs against 423 aerobic and anaerobic bacterial isolates from infected diabetic foot wounds.

Against 182 anaerobe and 241 aerobe strains obtained from diabetic foot infections, doripenem was the most active carbapenem against Pseudomonas aeruginosa (MIC(90), 2 microg/ml), more active than imipenem against Proteus mirabilis, and ertapenem was more active against Escherichia coli and Klebsiella spp. The MIC(50) and MIC(90) values were < or =0.125 microg/ml for methicillin-sensitive Staphylococcus aureus and all streptococci and 0.25/1 for Bacteroides fragilis.

Bacteriology of moderate-to-severe diabetic foot infections and in vitro activity of antimicrobial agents.

As part of a United States-based multicenter clinical trial, conducted from 2001 to 2004, that compared ertapenem to piperacillin-tazobactam for the treatment of moderate-to-severe diabetic foot infections (DFIs), we obtained 454 pretreatment specimens from 433 patients. After debridement, the investigators collected wound specimens, mostly by curettage or biopsy, and sent them to the R. M. Alden Research Laboratory for aerobic and anaerobic culture. Among the 427 positive cultures, 83.8% were polymicrobial, 48% grew only aerobes, 43.7% had both aerobes and anaerobes, and 1.3% had only anaerobes. Cultures yielded a total of 1,145 aerobic strains and 462 anaerobic strains, with an average of 2.7 organisms per culture (range, 1 to 8) for aerobes and 2.3 organisms per culture (range, 1 to 9) for anaerobes. The predominant aerobic organisms were oxacillin-susceptible Staphylococcus aureus (14.3%), oxacillin-resistant Staphylococcus aureus (4.4%), coagulase-negative Staphylococcus species (15.3%), Streptococcus species (15.5%), Enterococcus species (13.5%), Corynebacterium species (10.1%), members of the family Enterobacteriaceae (12.8%), and Pseudomonas aeruginosa (3.5%). The predominant anaerobes were gram-positive cocci (45.2%), Prevotella species (13.6%), Porphyromonas species (11.3%), and the Bacteroides fragilis group (10.2%). Pure cultures were noted for 20% of oxacillin-resistant Staphylococcus aureus cultures, 9.2% of Staphylococcus epidermidis cultures, and 2.5% of P. aeruginosa cultures. Two or more species of Staphylococcus were present in 13.1% of the patients. Ertapenem and piperacillin-tazobactam were each active against >98% of the enteric gram-negative rods, methicillin-sensitive S. aureus, and anaerobes. Among the fluoroquinolones, 24% of anaerobes, especially the gram-positive cocci, were resistant to moxifloxacin; 27% of the gram-positive aerobes but only 6% of the members of the family Enterobacteriaceae were resistant to levofloxacin. Moderate-to-severe DFIs are typically polymicrobial, and almost half include anaerobes. Our antibiotic susceptibility results can help to inform therapeutic choices.

In vitro activity of ceftobiprole against aerobic and anaerobic strains isolated from diabetic foot infections.

Against 443 aerobic and anaerobic bacteria isolated from diabetic foot infections, ceftobiprole MICs (microg/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 activity of azithromycin and nine comparator agents against 296 strains of oral anaerobes and 31 strains of Eikenella corrodens.

At this time in the USA there are no antimicrobials with specific indications for oral infections, and many of those currently used have limited efficacy against oral anaerobic strains. We tested the activity of azithromycin against a broad range of anaerobic oral pathogens and, at pH 8, found it to be effective against 98% of strains, including all fusobacteria and beta-lactamase-producing strains of Prevotella spp. All strains of Eikenella corrodens were also susceptible to azithromycin but resistant to erythromycin, clindamycin, metronidazole and cefalexin. Other comparator agents were penicillin, amoxicillin/clavulanic acid, tetracycline, levofloxacin and ciprofloxacin. Minimum inhibitory concentrations obtained on agar adjusted to pH 8 were generally one dilution lower than those obtained on agar at pH 7.