[Show abstract][Hide abstract] ABSTRACT: The comparative in vitro activity of SMT19969, a novel, narrow spectrum, non-absorbable agent, was studied against 50 ribotype defined C. difficile strains plus 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, 0.125-0.5 μg/ml, MIC90 0.25 μg/ml), including ribotype 027 strains, than fidaxomicin (range, 0.06-1 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 might have 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 MIC90 values of >512, >512, 64 and 64 μg/ml respectively. Clostridium species showed varied susceptibility with C. innocuum being susceptible (MIC90 1μg/ml) and C. ramosum and C. perfringens being non-susceptible (MIC90 >512μg/ml). Activity against Lactobacillus spp. (range, 0.06->512 μg/ml, MIC90 >512 μg/ml) was comparable to fidaxomicin and varied by species and strain. Gram positive aerobic cocci (S. aureus, E. faecalis, E. faecium and streptococci) showed high SMT19969 MIC90 values (128->512 μg/ml).
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Biapenem is a carbapenem being developed in combination with RPX7009, a new inhibitor of serine β-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 MIC90 for biapenem-RPX7009 was 1 μg/ml and 4 μg/ml for meropenem. Other B. fragilis group species showed MIC90 of 0.5 μg/ml for both agents. The MIC90s for biapenem-RPX7009 for Prevotella spp. was 0.25 μg/ml, Fusobacterium nucleatum and F. necrophorum 0.125 μg/ml, F. mortiferum 2 μg/ml, F. varium 0.5 μg/ml, Gram-positive cocci and rods ≤0.5 μg/ml, and for clostridia 0.03-8 μg/ml. Against 5 B. fragilis strains harboring a known metallo-beta-lactamase, biapenem-RPX7009 MICs were comparable to those other carbapenems (≥32 μg/ml). Against Bacteroides strains with imipenem MIC of 2 μg/ml, biapenem-RPX7009 had MICs of 0.5-2 μg/ml, and 0.5-32 μg/ml for meropenem, doripenem and ertapenem. For strains with imipenem MICs of 4 μg/ml, the MICs for biapenem-RPX7009 were 4-16 μg/ml and 8->32 μg/ml for meropenem, doripenem, and ertapenem. The inhibitor RPX7009 had no antimicrobial activity when tested alone, and showed little or no potentiation of biapenem vs. anaerobes. Biapenem-RPX7009 showed activity comparable to imipenem and was superior to meropenem, doripenem and ertapenem against imipenem non-susceptible Bacteroides spp.
[Show abstract][Hide abstract] ABSTRACT: 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 (MIC90s, ≤0.015 μg/ml); and more active than cefazolin (MIC90, 0.5 μg/ml) doxycycline (MIC90, 0.125 μg/ml), azithromycin (MIC90, 0.5 μg/ml), ampicillin-sulbactam (MIC90, 0.125 μg/ml), and SMX-TMP (MIC90, 0.125 μg/ml). Ceftaroline was also very active against all S. aureus isolates (MIC90, 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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 β-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
[Show abstract][Hide abstract] ABSTRACT: 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.
Further testing and analysis of the microbial data was performed. Susceptibility results were correlated with the clinical outcomes reported previously.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] 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 < or =1 microg/ml. One strain of Prevotella oralis was nonsusceptible at 8 microg/ml.
[Show abstract][Hide abstract] ABSTRACT: 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.
International Journal of Antimicrobial Agents 10/2006; 28(3):244-8. DOI:10.1016/j.ijantimicag.2006.03.028 · 4.26 Impact Factor
[Show abstract][Hide abstract] 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 < or =1 microg/ml, including 15 of 16 strains of C. difficile with elevated linezolid MICs of 8 and 16 microg/ml, all 32 strains with moxifloxacin MICs of > or =4 microg/ml, and all 16 strains resistant to clindamycin. Daptomycin MICs were also < or =1 microg/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 microg/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.
[Show abstract][Hide abstract] ABSTRACT: Tests of dalbavancin's in vitro activity against 209 aerobic and 120 anaerobic isolates from pretreatment diabetic foot infections showed an MIC(90) of < or =0.125 microg/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 MIC(90)s for MSSA and MRSA of 0.5 and 1 microg/ml for vancomycin, 4 and 4 microg/ml for linezolid, 0.5 and 0.5 microg/ml for daptomycin, and 0.25 and >8 microg/ml for clindamycin.
[Show abstract][Hide abstract] ABSTRACT: The in vitro activity of 11 antimicrobials was tested against 74 recent anaerobic isolates obtained from pretreatment cultures in pediatric patients with complicated intra-abdominal infections using the CLSI M11-A-6 agar dilution method. Carbapenems, beta-lactamase inhibitor combinations and metronidazole retained good activity, while all Bacteroides fragilis group species produced beta-lactamase and were penicillin resistant and 43% were either intermediately susceptible or resistant to clindamycin. Cefoxitin had moderate activity against B. fragilis but poor activity against Bacteroides thetaiotaomicron and other B. fragilis group isolates.
[Show abstract][Hide abstract] ABSTRACT: Using the NCCLS agar dilution method, we studied the in vitro activity of retapamulin (SB-275833) against 141 clinical isolates of Propionibacterium species, including seven multiresistant strains, and found retapamulin to be the most active agent among those tested with MICs of < or = 1 microg/ml against all isolates.