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Background: Intestinal colonization resistance is mainly exerted by commensal anaerobes., Objectives: To assess whether exposure to non-carbapenem antibiotics with activity against intestinal anaerobes (namely, piperacillin/tazobactam, amoxicillin/clavulanate and metronidazole) may promote the acquisition of gut colonization with ceftriaxone-resistant Gram-negative bacteria (CFR-GNB) in ICU patients., Patients and Methods: All patients with a first stay >3 days in a single surgical ICU over a 30 month period were retrospectively included. Rectal carriage of CFR-GNB (i.e. ESBL-producing Enterobacteriaceae, AmpC-hyperproducing Enterobacteriaceae, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and CFR Acinetobacter baumannii) was routinely screened for at admission then weekly. The impact of anti-anaerobe antibiotics was investigated in propensity score (PS)-matched cohorts of patients exposed and not exposed to these drugs and through PS-based inverse probability of treatment weighting on the whole study cohort, treating in-ICU death or discharge as competing risks for CFR-GNB acquisition., Results: Among the 352 included patients [median ICU stay 16 (9-30) days, in-ICU mortality 12.2%], 120 (34.1%) acquired one or more CFR-GNB, mostly AmpC-hyperproducing Enterobacteriaceae (17.6%) and P. aeruginosa (14.8%). Exposure to anti-anaerobe antibiotics was the main predictor of CFR-GNB acquisition in both the PS-matched cohorts [adjusted HR (aHR) 3.92, 95% CI 1.12-13.7, P = 0.03] and the whole study cohort (aHR 4.30, 95% CI 1.46-12.63, P = 0.01). Exposure to other antimicrobials-especially ceftriaxone and imipenem/meropenem-exerted no independent impact on the likelihood of CFR-GNB acquisition., Conclusions: Exposure to non-carbapenem antibiotics with activity against intestinal anaerobes may predispose to CFR-GNB acquisition in ICU patients. Restricting the use of these drugs appears to be an antibiotic stewardship opportunity., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The incidence of spinal surgical site infections (SSIs) remains stable at less than 10%. Surgical reinterventions may be hampered by decubitus, treatment-related adverse events, and cost. In the context of emergence of bacterial resistance, a short duration of antimicrobial treatment is of critical importance. If the duration of treatment for SSI is currently 12 weeks, the aim of our study was to assess the efficacy of an antimicrobial treatment shortened to 6 weeks., Methods: This prospective study was carried out from November 2014 to July 2016 in an 827-bed teaching hospital. After surgical management of SSIs, patients received broad-spectrum antibiotics intravenously for 10 days and orally for the remainder, for a total of 6 weeks. Success was defined as absence of relapse, superinfection, or surgical failure at the end of treatment and at 1-year follow-up., Results: Eighty-five patients were included in this study. The median delay between initial surgery and diagnosis of SSI was 16 days. In 65 cases (76.4%), SSIs were monomicrobial; among these, Staphylococcus aureus was found in 30 cases (46%). Failure was observed in 7 cases (8.2%), with more than half caused by anaerobic bacteria., Conclusions: Surgical management of SSI followed by a 6-week antibiotic treatment is associated with favorable outcome. Anaerobic bacteria seem to play a role in the occurrence of relapses. A 6-week reduction in antibiotic treatment leads to reduction in cost and, likely, also to reduction in the emergence and spread of resistant microorganisms., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Eggerthella lenta is a anaerobic gram-positive bacilli associated with polymicrobial intraabdominal infections. Recently, E. lenta was recognized as an important cause of anaerobic bloodstream infections (BSIs) associated with high mortality. Eggerthella lenta has been reported to have high minimal inhibitory concentrations (MICs) to piperacillin-tazobactam (TZP), a broad-spectrum antibiotic with anaerobic coverage commonly used in multiple centers for empiric treatment of abdominal sepsis., Methods: We describe a retrospective population-based analysis of invasive E. lenta infections from 2009 through 2015. A logistic regression analysis for 30-day mortality risk factors was conducted., Results: We identified 107 E. lenta infections, 95 (89%) were BSIs, 11 (10%) skin and soft tissue infections, and 1 intraabdominal abscess. Polymicrobial infections were found in 40%; 72% of isolates were from a gastrointestinal source, most commonly appendicitis (33%) of which two-thirds were perforated. TZP MIC50 and MIC90 for E. lenta isolates were 32 μg/mL and 64 μg/mL, respectively. The overall 30-day mortality for BSI was 23% and was independently associated with empiric TZP monotherapy (odds ratio [OR], 4.4; 95% confidence interval [CI], 1.2-16; P = .02) and intensive care unit stay (OR, 6.2; 95% CI, 1.4-27.3; P = .01). Thirty-day mortality rates were significantly influenced by the use of different TZP MIC breakpoints., Conclusions: Our results demonstrate the increased recognition of E. lenta as an anaerobic opportunistic pathogen and highlight the need for improved empiric antimicrobial guidelines and TZP MIC breakpoints with better correlation to clinical outcomes to guide appropriate management of invasive E. lenta infections.

Objectives: To use Monte Carlo simulation with an integrated pharmacokinetic-pharmacodynamic (PK-PD) model to evaluate guideline-recommended antimicrobial prophylaxis (AP) regimens with anaerobic coverage in abdominal surgery., Methods: AP regimens were tested in simulated subjects undergoing elective abdominal surgery using relevant PK models and pathogen distributions in surgical site infections (SSIs). Predicted cumulative target attainment was the percentage of simulated subjects with free (unbound) antimicrobial plasma concentrations above the MICs for potential SSI pathogens., Results: Cefazolin plus metronidazole covered SSI aerobes in 70% and the Bacteroides fragilis group in 99% of subjects, whereas cefoxitin only covered aerobes and anaerobes in 63% and 27% of cases, respectively. The broad-spectrum ceftriaxone plus metronidazole covered aerobes in 82% and anaerobes in 99% of simulations, while ertapenem covered aerobes in 88% and anaerobes in 90% of cases. Clindamycin covered the B. fragilis group in only 11% of cases. For cefazolin, 2 g doses maintained target attainment in simulated subjects from 80 to 120 kg, whereas 1 g doses were associated with lower target attainment against potential Gram-negative pathogens even in those <80 kg. For gentamicin, 3 mg/kg doses were comparable to the suggested 5 mg/kg, but superior to the traditional 1.5 mg/kg., Conclusions: This study demonstrates the use of PK-PD to inform decisions regarding AP in abdominal surgery. In this case, the findings support avoiding cefoxitin, avoiding clindamycin for anaerobic coverage, selecting 2 g doses of cefazolin even in patients <80 kg and using 3 mg/kg doses of gentamicin., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Infections due to anaerobic bacteria can be severe and life-threatening. Susceptibility testing of anaerobes is not frequently performed in laboratories, but such testing is important to direct appropriate therapy. Anaerobic resistance is increasing globally, and resistance trends vary by geographic region. An overview of a variety of susceptibility testing methods for anaerobes is provided, and the advantages and disadvantages of each method are reviewed. Specific clinical situations warranting anaerobic susceptibility testing are discussed., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To collect recent data on the susceptibility of anaerobes to antimicrobial agents with known activity against anaerobes, and to compare them with results from previous Belgian multicentre studies., Methods: Four hundred and three strict anaerobic clinical isolates were prospectively collected from February 2011 to April 2012 in eight Belgian university hospitals. MICs were determined by one central laboratory for 11 antimicrobial agents using Etest methodology., Results: According to EUCAST breakpoints, >90% of isolates were susceptible to amoxicillin/clavulanate (94%), piperacillin/tazobactam (91%), meropenem (96%), metronidazole (92%) and chloramphenicol (98%), but only 70% and 40% to clindamycin and penicillin, respectively. At CLSI recommended breakpoints, only 71% were susceptible to moxifloxacin and 79% to cefoxitin. MIC50/MIC90 values for linezolid and for tigecycline were 1/4 and 0.5/4 mg/L, respectively. When compared with survey data from 2004, no major differences in susceptibility profiles were noticed. However, the susceptibility of Prevotella spp. and other Gram-negative bacilli to clindamycin decreased from 91% in 1993-94 and 82% in 2004 to 69% in this survey. Furthermore, the susceptibility of clostridia to moxifloxacin decreased from 88% in 2004 to 66% in 2011-12 and that of fusobacteria from 90% to 71%., Conclusions: Compared with previous surveys, little evolution was seen in susceptibility, except a decline in activity of clindamycin against Prevotella spp. and other Gram-negative bacteria, and of moxifloxacin against clostridia. Since resistance was detected to all antibiotics, susceptibility testing of anaerobic isolates is indicated in severe infections to confirm appropriateness of antimicrobial therapy.

Among the Gram-positive anaerobic bacteria associated with clinical infections, the Gram-positive anaerobic cocci (GPAC) are the most prominent and account for approximately 25-30% of all isolated anaerobic bacteria from clinical specimens. Still, routine culture and identification of these slowly growing anaerobes to the species level has been limited in the diagnostic laboratory, mainly due to the requirement of prolonged incubation times and time-consuming phenotypic identification. In addition, GPAC are mostly isolated from polymicrobial infections with known pathogens and therefore their relevance has often been overlooked. However, through improvements in diagnostic and in particular molecular techniques, the isolation and identification of individual genera and species of GPAC associated with specific infections have been enhanced. Furthermore, the taxonomy of GPAC has undergone considerable changes over the years, mainly due to the development of molecular identification methods. Existing species have been renamed and novel species have been added, resulting in changes of the nomenclature. As the abundance and significance of GPAC in clinical infections grow, knowledge of virulence factors and antibiotic resistance patterns of different species becomes more important. The present review describes recent advances of GPAC and what is known of the biology and pathogenic effects of Anaerococcus, Finegoldia, Parvimonas, Peptoniphilus and Peptostreptococcus, the most important GPAC genera isolated from human infections., (© 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.)

Background: Appropriate antimicrobial therapy results in improved clinical outcomes in complicated intra-abdominal infections (cIAIs). Recent in vitro studies have reported increasing moxifloxacin resistance of Bacteroides species, thereby cautioning empiric use in infections with these organisms., Methods: This pooled analysis of 4 randomized clinical trials (2000-2010) evaluated the comparative efficacy of moxifloxacin in cIAIs, including infection with anaerobic organisms. The intent-to-treat population included 1209 patients who received moxifloxacin (745 microbiologically valid cases) and 1193 patients who received comparator agents (741 microbiologically valid cases)., Results: Overall clinical success rates in the per-protocol population were 85.6% (817 of 955 patients) for moxifloxacin and 87.8% (860 of 979 patients) for comparators. Of 642 pretherapy anaerobes from moxifloxacin-treated patients, 561 (87.4%) were susceptible at ≤2 mg/L, 34 (5.3%) were intermediate at 4 mg/L, and 47 (7.3%) were resistant at ≥8 mg/L. Moxifloxacin achieved similar clinical success rates against all anaerobes including those isolated from patients infected with Bacteroides fragilis (158 [82.7%] of 191 patients), Bacteroides thetaiotaomicron (74 [82.2%] of 90 patients) and Clostridium species (37 [80.4%] of 46 patients). The overall clinical success rate for all anaerobes was 82.3%. For all anaerobes combined, the clinical success rate was 83.1% (466 of 561 patients) for a minimum inhibitory concentration (MIC) of ≤2 mg/L, 91.2% (31 of 34 patients) for an MIC of 4 mg/L, 82.4% (14 of 17 patients) for an MIC of 8 mg/L, 83.3% (5 of 6 patients) for an MIC of 16 mg/L, and 66.7% (16 of 24 patients) for an MIC of ≥32 mg/L., Conclusions: Moxifloxacin demonstrated clinical success for intra-abdominal infections caused by both aerobic and anaerobic isolates. More than 87% of baseline anaerobic isolates from intra-abdominal infections were susceptible to moxifloxacin, and efficacy was maintained beyond the current susceptibility breakpoint MIC of ≤2 mg/L against major anaerobes.

Metronidazole has been used for the treatment of infections for >45 years and is still successfully used for the treatment of trichomoniasis, amoebiasis, and giardiasis. Anaerobic bacterial infections caused by Bacteroides species, fusobacteria, and clostridia respond favorably to metronidazole therapy. Good clinical results in the treatment of vaginosis due to Gardnerella vaginalis have also been reported. Rates of resistance to metronidazole are still generally low; however, several studies have reported decreased susceptibility among Bacteroides species, as well as different mechanisms of resistance. Metronidazole-resistant Helicobacter pylori strains have been described, but combination therapy (eg, metronidazole, amoxicillin, or clarithromycin plus omeprazole) is still recommended for eradication of this pathogen in patients with gastroduodenal ulcers. Metronidazole is considered to be a cost-effective drug because of its low cost, good activity against pathogenic anaerobic bacteria, favorable pharmacokinetic and pharmacodynamic properties, and minor adverse effects. Metronidazole is still the criterion standard for therapy of anaerobic infections, as was described by Tally and colleagues 35 years ago.

Background: The rationale and lessons learned through the evolution of the National Survey for the Susceptibility of Bacteroides fragilis Group from its initiation in 1981 through 2007 are reviewed here. The survey was conceived in 1980 to track emerging antimicrobial resistance in Bacteroides species., Methods: Data from the last 11 years of the survey (1997-2007), including 6574 isolates from 13 medical centers, were analyzed for in vitro antimicrobial resistance to both frequently used and newly developed anti-anaerobic agents. The minimum inhibitory concentrations of the antibiotics were determined using agar dilution in accordance with Clinical and Laboratory Standards Institute recommendations., Results: The analyses revealed that the carbapenems (imipenem, meropenem, ertapenem, and doripenem) and piperacillin-tazobactam were the most active agents against these pathogens, with resistance rates of 0.9%-2.3%. In the most recent 3 years of the survey (2005-2007), resistance to some agents was shown to depend on the species, such as ampicillin-sulbactam against Bacteroides distasonis (20.6%) and tigecycline against Bacteroides uniformis and Bacteroides eggerthii ( approximately 7%). Very high resistance rates (>50%) were noted for moxifloxacin and trovafloxacin, particularly against Bacteroides vulgatus. During that period of study, non-B. fragilis Bacteroides species had >40% resistance to clindamycin. Metronidazole-resistant Bacteroides strains were also first reported during that period., Conclusions: In summary, resistance to antibiotics was greater among non-B. fragilis Bacteroides species than among B. fragilis and was especially greater among species with a low frequency of isolation, such as Bacteroides caccae and B. uniformis. The emergence of resistance among the non-B. fragilis Bacteroides species underscores the need for speciation of B. fragilis group isolates and for clinicians to be aware of associations between species and drug resistance.

Aims: To study the impact of added 2,4-dinitrotoluene (DNT) on the anaerobic bacterial community in marine sediment collected from an unexploded ordnance dumping site in Halifax Harbour., Methods and Results: Marine sediment was spiked with 2,4-DNT and incubated under anaerobic conditions in the presence and absence of lactate. Indigenous bacteria in the sediment removed 2,4-DNT with subsequent formation of its mono- and diamino-derivatives under both conditions. PCR-DGGE and nucleotide sequencing were used to monitor the change in the bacterial population in sediment caused by the presence of 2,4-DNT. The results showed that denaturing gradient gel electrophoresis banding patterns of sediment microcosms treated with 2,4-DNT were different from controls that did not receive 2,4-DNT. Bacteroidetes, Firmicutes and delta-Proteobacteria were present in sediment incubated in the absence of 2,4-DNT. However, several gamma-Proteobacteria became dominant in sediment in the presence of 2,4-DNT, two of which were 99% similar to Shewanella canadensis and Shewanella sediminis. In the presence of both 2,4-DNT and lactate, two additional delta-Proteobacteria were enriched, one closely related (98% similarity) to Desulfofrigus fragile and the other affiliated (96% similarity) to Desulfovibrio sp. In contrast, none of the above four Proteobacteria were enriched in sediment incubated with lactate alone., Conclusions: Presence of 2,4-DNT led to a significant change in bacterial population of marine sediment with the enrichment of several gamma- and delta-Proteobacteria., Significance and Impact of the Study: Our results provided the first evidence on the impact of the pollutant 2,4-DNT on the indigenous bacterial community in marine sediment, and provided an insight into the composition of bacterial community that degrade 2,4-DNT.

Objectives: The aim of this study was to determine the anaerobic spectrum of activity of REP3123, a novel diaryldiamine that inhibits bacterial methionyl-tRNA synthetases in Gram-positive bacteria., Methods: Fifty recent clinical isolates of Clostridium difficile from patients diagnosed with C. difficile infection and 223 other intestinal normal flora anaerobes were tested for their susceptibility to REP3123 and four or five comparator agents by the agar dilution method using supplemented Brucella agar with 5% laked sheep blood., Results: All strains of C. difficile were inhibited by 0.5-1 mg/L REP3123, including those resistant to moxifloxacin and clindamycin. REP3123 lacked activity against many normal flora anaerobes in the gut, including Clostridium ramosum, bifidobacteria, lactobacilli of the Lactobacillus casei-rhamnosus-plantarum group and Gram-negative anaerobes., Conclusions: REP3123 demonstrated good potency against C. difficile, but limited activity against many other intestinal anaerobic species, thus, in theory, maintaining the colonization resistance barrier.

Objectives: To compare the intrinsic activity of pradofloxacin, a new fluoroquinolone developed for use in veterinary medicine, with other fluoroquinolones, against anaerobic bacteria isolated from dogs and cats., Methods: One hundred and forty-one anaerobes were isolated from dogs and cats and comparative MICs of pradofloxacin, marbofloxacin, enrofloxacin, difloxacin and ibafloxacin were determined according to standardized agar dilution methodology., Results: Pradofloxacin exerted the greatest antibacterial activity followed by marbofloxacin, enrofloxacin, difloxacin and ibafloxacin. Based on the distinctly lower MIC(50), MIC(90) and mode MIC values, pradofloxacin exhibited a higher in vitro activity than any of the comparator fluoroquinolones., Conclusions: Pradofloxacin, a novel third-generation fluoroquinolone, has broad-spectrum anti-anaerobe activity and offers utility as single-drug therapy for mixed aerobic/anaerobic infections.

Objectives: The degree of penetration of an antibiotic into the infected site is an important criterion for therapeutic success. Ertapenem is a new carbapenem, exhibiting activity against most Gram-positive and Gram-negative aerobic and anaerobic bacteria commonly recovered from community-acquired infections. However, no studies concerning its diffusion into bone and synovial tissue are available. Our objective was to quantify ertapenem bone and synovial tissue penetration and to compare our data with the MIC(90)s for causative pathogens., Patients and Methods: In an open-label study, 18 patients who were undergoing elective total hip replacement received a single, parenteral, 1 g dose of ertapenem. One serum, one cortical and cancellous bone and one synovial tissue sample was collected per patient a median [interquartile range (IQR)] of 1.6 (1.5-1.7), 12.4 (11.9-13.1) or 23.8 h (22.6-25.2) later and analysed by HPLC., Results: The median (IQR) serum concentrations of ertapenem were 70.1 (56.1-75.9), 10.0 (9.1-11.2) and 2.6 mg/L (2.3-3.0), respectively, at the different time points. The median (IQR) cancellous bone tissue concentrations were 13.2 (10.2-14.8), 1.9 (1.7-2.1) and 0.6 microg/g (0.4-0.6) at the different time points, corresponding to a median (IQR) tissue/serum penetration ratio of 0.19 (0.18-0.23). The median (IQR) cortical bone tissue concentrations were 8.0 (6.5-9.5), 1.3 (1.2-1.3) and 0.3 microg/g (0.3-0.4) at the different time points, corresponding to a median (IQR) tissue/serum penetration ratio of 0.13 (0.12-0.14). The median (IQR) synovial tissue concentrations were 26.2 microg/g (22.7-28.4), 4.0 mg/L (3.7-4.4) and 1.0 mg/L (0.9-1.2) at the different time points, corresponding to a median (IQR) tissue/serum penetration ratio of 0.41 (0.39-0.42)., Conclusions: The concentrations after an ertapenem 1 g dose achieved in cancellous and cortical bone tissue and in synovial tissue were greater than the MIC(90)s for most aerobic organisms for 24 h, and for 12 to 24 h for anaerobic bacteria in healthy volunteers undergoing total hip replacement.

Objectives: Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections. The aim of this study was to determine the antimicrobial activity of retapamulin by determining the minimal inhibitory concentration (MIC) values of this new drug and comparators against a wide range of anaerobic bacteria of human origin., Methods: The in vitro activity of retapamulin and six comparators (amoxicillin, amoxicillin/clavulanic acid, ceftriaxone, imipenem, clindamycin and metronidazole) was evaluated against 232 anaerobic clinical isolates. MICs were determined by the CLSI reference agar dilution method (M11-A6)., Results: Ceftriaxone, clindamycin and amoxicillin/clavulanic acid resistance rates were 54%, 42% and 9.6%, respectively, within the Bacteroides fragilis group. Despite high resistance rates to various antibiotics, retapamulin inhibited 37/52 (71%) strains of the B. fragilis group and 85/87 (98%) of the other Gram-negative bacilli at a concentration of 2 mg/L or less. All the investigated strains of Clostridium perfringens were inhibited by 1 mg/L retapamulin. Three strains of C. difficile and one strain of C. clostridioforme demonstrated decreased susceptibility to retapamulin. Based on inhibitory concentrations, retapamulin was more active than clindamycin, metronidazole and ceftriaxone against Propionibacterium acnes and anaerobic Gram-positive cocci, as all isolates were inhibited by

Objectives: To collect recent data on the susceptibility of anaerobes and to compare them with results from previous studies., Methods: Four hundred and forty-three anaerobic clinical isolates from various body sites were prospectively collected from October 2003 to February 2005 in nine Belgian hospitals. MICs were determined for nine anti-anaerobic and three recently developed antibiotics., Results: Most gram-negative bacilli except Fusobacterium spp. were resistant to penicillin. Piperacillin/tazobactam, metronidazole, chloramphenicol, meropenem and amoxicillin/clavulanic acid were very active against all groups, but only 86% of Bacteroides fragilis group strains were susceptible to the latter. Cefoxitin, cefotetan and clindamycin were less active. In particular, only 62%, 52% and 48% of B. fragilis group strains were susceptible, respectively. Clindamycin shows a continuing decrease in activity, as 83% were still susceptible in 1987 and 66% in 1993-94. Anti-anaerobic activity of the new antibiotics is interesting, with MIC50 and MIC90 of 1 and >32 mg/L for moxifloxacin, 2 and 4 mg/L for linezolid and 0.5 and 8 mg/L for tigecycline., Conclusions: The susceptibility of anaerobic bacteria remains stable in Belgium, except for clindamycin, which shows a continuous decrease in activity. However, for each of the tested antibiotics, at least a few resistant organisms were detected. Consequently, for severe infections involving anaerobic bacteria, it could be advisable to perform microbiological testing instead of relying on known susceptibility profiles. Periodically monitoring background susceptibility remains necessary to guide empirical therapy.

Objectives: Dalbavancin is a new lipoglycopeptide antibiotic active in vitro against most Gram-positive bacteria. It is administered parenterally as a weekly regimen, is eliminated both in urine and faeces, and has t(1/2) in plasma of 8.5 days. Investigating the impact of antibiotics on endogenous microflora is important since alteration of the balance may facilitate colonization by new potentially pathogenic strains or enable microorganisms in the normal flora to develop resistance. The purpose of the present study was to investigate the effect of administration of dalbavancin on the intestinal flora of healthy subjects., Methods: Six women and six men, 18-40 years, received a single 30 min intravenous infusion of 1 g dalbavancin. Plasma and faeces were collected over several weeks for determination of dalbavancin concentration and analysis of faecal flora. Faecal specimens were cultured on non-selective and selective media. Different colony types were counted, isolated in pure culture and identified to genus level. All new colonizing bacteria were tested for susceptibility to dalbavancin., Results: Plasma dalbavancin concentrations at 2, 21 and 60 days after administration were 35.8-208.7, 3.9-22.1 and 0.5-2.9 mg/L, respectively. The faecal concentrations of dalbavancin were 6.8-73.4 mg/kg on day 5 and 7.4-26.4 mg/kg on day 14. Dalbavancin was not detectable in faeces on day 60. There was some impact on numbers of enterococci and Escherichia coli and no changes in numbers of lactobacilli, clostridia and bacteroides. No Clostridium difficile strains were recovered. No new colonizing aerobic and anaerobic bacteria resistant to dalbavancin were found., Conclusions: Dalbavancin has no major ecological effect on the human normal intestinal microflora.

The usefulness of fluoroquinolones for the treatment of mixed aerobic and anaerobic infections has been investigated since these agents started being used in clinical practice. Newer compounds have increased in vitro activity against anaerobes, but clinically relevant susceptibility breakpoints for these bacteria have not been established. Pharmacodynamic analyses and corroboration by new data from clinical trials have enhanced our knowledge concerning the use of fluoroquinolones to treat selective anaerobic pathogens. These studies suggest that newer agents could be useful in the treatment of several types of mixed aerobic and anaerobic infections, including skin and soft-tissue, intra-abdominal, and respiratory infections. The major concerns with expanding the use of fluoroquinolones to treat anaerobic infections have been reports of increasing resistance in Bacteroides group isolates and the impact of these antibiotics on the incidence of Clostridium difficile-associated disease.

Objectives: Routine susceptibility testing of all anaerobic organisms is not advocated, but it is useful for laboratories to test periodically for anaerobic organisms and provide local susceptibility data to guide therapy. This study reports the national trend of antibiotic susceptibility of clinically significant anaerobes in New Zealand., Methods: Clinical isolates were tested using standardized methods against a range of antibiotics commonly used to treat anaerobic infections. Susceptibility was determined using NCCLS criteria. The change in susceptibility trends between this study and earlier studies was measured by comparing the geometric mean of the MIC., Results: A total of 364 anaerobes were tested. Penicillin had poor activity against Bacteroides spp., Prevotella spp., Eubacterium spp., Clostridium tertium and Veillonella spp. In general, Fusobacterium spp., Bacteroides ureolyticus, Propionibacterium spp., Clostridium perfringens and anaerobic streptococci isolates, with the exception of Peptostreptococcus anaerobius, were penicillin susceptible. Amoxicillin/clavulanate showed good activity against most anaerobes, but resistance was seen with Bacteroides fragilis group and P. anaerobius isolates. Cefoxitin was more active than cefotetan, particularly against non-B. fragilis species, Eubacterium spp. and P. anaerobius. Meropenem and imipenem showed good activity against all anaerobes, with only 2 and 4% of Bacteroides spp., respectively, showing resistance. With the exception of Propionibacterium acnes isolates, which are predictably resistant, metronidazole was active against all anaerobes tested. There has been little change in susceptibility since 1997., Conclusions: Metronidazole, cefoxitin, piperacillin/tazobactam and amoxicillin/clavulanate remain good empirical choices when anaerobes are expected in our setting. No clinically relevant changes in susceptibility over time were found.

Objectives: The aim of the study was to analyse the susceptibility of unique and non-duplicate aerobic and anaerobic isolates from surgical patients to a novel des-F(6)-quinolone (garenoxacin) and other selected antimicrobial agents., Methods: Eleven hundred and eighty-five aerobic and anaerobic isolates from general, vascular, cardiothoracic and otolaryngologic surgical patients were tested for susceptibility to garenoxacin and seven other antibiotics (ciprofloxacin, moxifloxacin, levofloxacin, piperacillin/tazobactam, imipenem, clindamycin and metronidazole) using the referenced microbroth and agar-dilution method., Results: Garenoxacin exhibited greater antimicrobial activity than comparator quinolones such as ciprofloxacin, levofloxacin and other antimicrobials when tested against selected gram-positive organisms. The in vitro aerobic and anaerobic activity of garenoxacin was similar to that of moxifloxacin. All fluoroquinolones tested were effective against most gram-negative facultative anaerobes including Escherichia coli. Garenoxacin and moxifloxacin demonstrated similar in vitro antimicrobial activity against selected anaerobic gram-positive and gram-negative anaerobic bacteria such as members of the Bacteroides fragilis group. Overall, the in vitro activity of the advanced spectrum quinolones against anaerobic surgical isolates compared favourably with selected comparator agents, metronidazole, imipenem and piperacillin/tazobactam., Conclusions: These findings suggest that 82.4% of aerobic surgical isolates were susceptible to a concentration of garenoxacin < or = 1.0 mg/L, whereas 84.5% of the anaerobic isolates were susceptible to a garenoxacin concentration < or = 1.0 mg/L. Garenoxacin may be a valuable surgical anti-infective for treatment of serious head and neck, soft tissue, intra-abdominal and diabetic foot infections.

Methanogenesis in rice field soils starts soon after flooding while potentially competing processes like reduction of sulphate and iron take place. Early methanogenesis is mainly driven by hydrogen, while later in the season acetate tends to become more important. Anaerobic ciliates are abundant during this period, and their endosymbionts use hydrogen produced by the ciliates to reduce carbon dioxide to methane. These endosymbiotic methanogens are protected from the competition for substrates with other bacteria that may control methanogenesis outside the protozoan cells. Thus, we focussed on early methanogenesis and on the potential contribution from ciliates and their endosymbionts. Only ciliates of the genus Metopus were found to harbour methanogens, as identified by the F(420)-fluorescence of the endosymbionts. We followed the population dynamics of the ciliates with time, and calculated the ratio of symbiotic methane production to overall methanogenesis. Symbiotic methane production was calculated from the species-specific numbers of methanogenic endosymbionts times the cell-specific methane production of the symbionts. According to this calculation, the symbionts' contribution to overall methane production was only 6.4% at the beginning and decreased with time. In a second experiment, colchicine and cycloheximide were used to inhibit all eukaryotes, comparing the remaining methane production rate to a control without inhibitors. In the inhibition experiment, the contribution from symbionts decreased from 40% to 6% during the first days after flooding, and dropped to near zero within 2 weeks. However, nearly all methane produced from H(2)/CO(2) could be attributed to the ciliates' symbionts between days 5 and 10 after flooding. Both experiments showed that the contribution of methanogenic symbionts to overall methane production is a transient phenomenon, restricted to the first 2 weeks.

The various problems associated with treating sulphate-containing wastewaters stem inherently from successful competitive interactions between sulphate reducing bacteria (SRB) and other bacteria involved in the process, resulting in the formation of H(2)S. Prevention of in-reactor sulphide generation by use of specific SRB inhibitors presents a potential solution. Nitrite has been reported to be a specific inhibitor of SRB but its possible toxicity to syntrophic and methanogenic members of the anaerobic consortium has not been investigated. In batch activity and toxicity tests, under both mesophilic and thermophilic conditions, nitrite, at concentrations of up to 150 mg L(-1), was found to be ineffective as a specific inhibitor of SRB, and was also shown to have an inhibitory effect on the activity of syntrophic and methane-producing bacteria in mesophilic and thermophilic digester sludge samples.

Fifty-three beta-lactamase-producing strains of oral bacteria isolated from patients with refractory periodontitis in Norway and USA were screened for the presence of the bla(TEM), bla(SHV), bla(OXA), bla(ampC), bla(cfxA), and bla(cepA/cblA) genes by the polymerase chain reaction (PCR). The PCR products were characterized by direct sequencing of the amplified DNA. Thirty-four of the 53 enzyme-producing strains (64%) were positive in one of the PCR assays. All beta-lactamase-producing Prevotella and Capnocytophaga spp. were CfxA positive. TEM-type beta-lactamases were identified in one strain each of Escherichia coli and Neisseria sp., and one strain of Citrobacter freundii possessed an AmpC-type beta-lactamase. Screening for gene cassettes and genes known to be associated with integrons did not reveal the presence of integrons in these oral bacteria. Sequence analyses showed that most CfxA positive Prevotella and Capnocytophaga isolates from patients with refractory periodontitis harboured variants of the CfxA2 and CfxA3 enzyme. The present study also showed that many different genetic determinants of beta-lactamase production are found in bacteria isolated from refractory periodontitis, many of which remain to be characterized.

Antibiotic-resistant anaerobic bacteria have become increasingly recognized as a confounding factor in the selection of therapeutic agents. The use of potent, broad-spectrum antibiotics as empirical therapy, along with appropriate adjunctive measures, has, in some ways, masked the magnitude of the antibiotic resistance problem that parallels that observed for nonanaerobic pathogens. The use of standardized testing methods that recognize resistance and an understanding of resistance mechanisms have become essential for the treatment of patients and the development of new agents.

In vitro susceptibility data were collected for co-amoxiclav and other antimicrobial agents against 1297 recent anaerobe isolates collected in Europe and the USA. The co-amoxiclav (amoxicillin/clavulanic acid) MIC(50/90)s (amoxicillin/clavulanic acid concentration in a ratio of 2:1, expressed in terms of amoxicillin concentration in mg/L) were 0.5/4 for Bacteroides fragilis, 96% susceptible) except E. corrodens (MIC(50/90) of >32/>64 mg/L), which is a capnophilic organism. Imipenem was also highly active against all species (>98% susceptible). Levofloxacin and clindamycin were the least potent agents tested, particularly against Bacteroides, Prevotella and Peptostreptococcus (levofloxacin susceptibility rates: Bacteroides 72.7%, Prevotella 71.5%, F. magna 72.4%; clindamycin susceptibility rates: Bacteroides 79.5%, Prevotella 92.1%, F. magna 84.7%).

Complicated intra-abdominal infections require a combination of surgery/drainage and antimicrobial therapy that is active against both the aerobic and the anaerobic bacteria that comprise the intestinal flora. Ertapenem, a parenteral carbapenem, is highly resistant to a wide variety of beta-lactamase enzymes, and has a broad spectrum of activity against bacteria associated with community-acquired infections including those of complicated intra-abdominal conditions. This article reviews the bacteriology of complicated intra-abdominal infections, their antimicrobial susceptibility, especially to anaerobes, the utility of animal models in these mixed infections, and the supportive clinical trials and in vitro susceptibility data that show ertapenem to be generally well tolerated and as effective as either piperacillin-tazobactam or ceftriaxone plus metronidazole in the therapy of complicated intra-abdominal infections.

Ertapenem, a Group 1 carbapenem, is the most recent beta-lactam antibiotic to enter clinical practice in the USA and Europe. While structurally a carbapenem, the overall molecular structure of ertapenem has been modified to focus its antibacterial spectrum on important community-acquired aerobic and anaerobic pathogens, and to increase its plasma half-life, permitting once-a-day dosing for this parenteral antibiotic. A number of chemical features are responsible for the unique properties of ertapenem. The inclusion of a trans-1-hydroxyethyl group in the structure of ertapenem enables the drug to maintain antibacterial efficacy against the vast majority of beta-lactamase-producing organisms. A critical 1beta-methyl substituent shields the beta-lactam carbonyl group and serves to reduce dehydropeptidase (DHP)-1 catalysed hydrolysis of the beta-lactam, enabling ertapenem to be administered without a DHP-1 inhibitor. A meta-substituted benzoic acid substituent increases the molecular weight and lipophilicity of the molecule, and the carboxylic acid moiety, ionized at physiological pH, results in ertapenem having a net negative charge. As a result, ertapenem is highly protein bound and has an extended half-life, permitting a once-a-day treatment regimen.

Ertapenem is a Group 1 carbapenem that was licensed in the USA in November 2001 and in Europe in April 2002. Its safety profile has been assessed in 240 healthy volunteers participating in 12 clinical pharmacology studies and in 2046 patients enrolled in five Phase IIa and eight Phase IIb/III clinical trials. The most common drug-related adverse events (AEs) reported in trials comparing ertapenem and piperacillin-tazobactam and in trials comparing ertapenem and ceftriaxone were: diarrhoea (ertapenem versus piperacillin-tazobactam 5.0% versus 7.0%; ertapenem versus ceftriaxone 5.6% versus 5.9%); infused vein complications (ertapenem versus piperacillin-tazobactam 4.5% versus 7.9%; ertapenem versus ceftriaxone 3.2% versus 4.6%); nausea (ertapenem versus piperacillin-tazobactam 2.5% versus 3.4%; ertapenem versus ceftriaxone 3.4% versus 3.3%); and elevations in alanine aminotransferase levels (ertapenem versus piperacillin-tazobactam 8.8% versus 7.3%; ertapenem versus ceftriaxone 8.3% versus 6.9%). Most ertapenem-related AEs were reported as mild-to-moderate in intensity. Ertapenem was not associated with prolongation of the QTc interval. Local reactions of moderate-to-severe intensity at the infusion site were infrequent and occurred with similar frequency in the ertapenem and comparator treatment groups. No overall differences in safety were observed between elderly (aged > or = 65 years and > or = 75 years) and younger patients. Ertapenem, 1 g once a day given by intravenous infusion or intramuscular injection, was generally well tolerated and had overall safety and tolerability profiles similar to those of piperacillin-tazobactam and ceftriaxone.

Ertapenem is a long-acting, 1beta-methyl parenteral Group 1 carbapenem antibiotic that has a broad antibacterial spectrum and once-a-day dosing supported by clinical studies. Ertapenem is active against both Gram-positive and Gram-negative bacteria, including Enterobacteriaceae, Streptococcus pneumoniae and most species of anaerobic bacteria. Isolates from a variety of infections (intra-abdominal infections, skin/soft-tissue infections, community-acquired pneumonia, pelvic infections and urinary tract infections) are inhibited by ertapenem. It has restricted activity against nosocomial pathogens such as Pseudomonas aeruginosa, Acinetobacter species, methicillin-resistant staphylococci and enterococci. Ertapenem has potent activity against the majority of anaerobic isolates from intra-abdominal infections, and against most of the aerobes isolated from these infections, with the exceptions of the nosocomial pathogens mentioned above. MIC(90)s for most species of Enterobacteriaceae were <1 mg/L, significantly lower than those of imipenem. MIC(90)s for most Bacteroides fragilis group isolates ranged from 1 to 4 mg/L, and MIC(90)s were species specific for Clostridium, ranging from 0.06 mg/L for Clostridium perfringens to 4 mg/L for Clostridium clostridioforme. Ertapenem was equivalent to or better than piperacillin-tazobactam in activity against most anaerobic species isolated from these infections, and was more potent than piperacillin-tazobactam and ceftriaxone against the most common skin pathogens (e.g. methicillin-susceptible Staphylococcus aureus). Ertapenem was highly active against most of the pathogens isolated from patients with community-acquired pneumonia, except for isolates of methicillin-resistant S. aureus (which are infrequent causes of community-acquired infection); these isolates were also resistant to ceftriaxone. Resistance to ertapenem is most commonly attributable to a variety of mechanisms including alterations in penicillin-binding proteins in Gram-positive organisms, and combinations of potent metallo-beta-lactamase enzymes, porin protein defects and efflux pumps in Gram-negative organisms.

Objective: A sentinel study was carried out to determine the antimicrobial susceptibilities of Gram-positive anaerobic cocci (GPAC) freshly isolated from clinical material in diagnostic laboratories in England and Wales., Methods: A total of 113 GPAC isolates consisting predominantly of current or former members of the genus Peptostreptococcus was obtained from 17 sentinel laboratories in England and one in Wales. Minimum inhibitory concentrations (MICs) of 10 antimicrobial agents were determined by the Etest method. The agents tested were: penicillin, tetracycline, erythromycin, cefoxitin, clindamycin, chloramphenicol, imipenem, co-amoxiclav, piperacillin/tazobactam and metronidazole. MIC50 and MIC90 values for each drug-species combination were calculated whenever suitable numbers of each species were obtained., Results: Excellent spectra of activity (0% resistance) against GPAC were seen for metronidazole, piperacillin/tazobactam, cefoxitin, imipenem and chloramphenicol. Low degrees of resistance to co-amoxiclav (3.5%), clindamycin (7.1%), penicillin (7.1%) and significant degrees of resistance to tetracycline (41.6%) and erythromycin (27.4%) were detected. Some examples of putative macrolide-lincosamide linked resistance were noted in seven (6.2%) isolates of GPAC., Conclusion: This study is one of the largest susceptibility studies specifically on GPAC carried out to date and the resulting data may be of value to those involved in the empirical treatment of infections involving Gram-positive anaerobic cocci.

The core of the adenoids contains polymicrobial aerobic and anaerobic flora and also includes potential respiratory pathogens. Similar flora, although in higher numbers and with a higher frequency of pathogens, are found in inflamed or hypertrophic adenoids and many of these bacteria are resistant to antimicrobial agents. Exposure to antimicrobial therapy can alter the colonization patterns and select for resistant organisms. Production of beta-lactamase is one of the major mechanisms of resistance of these organisms. The adenoids of healthy individuals, in contrast to those with recurrent respiratory tract infections, are generally colonized by aerobic and anaerobic organisms that are capable of interfering with the growth of potential pathogens. Maintaining the beneficial effects of normal flora by avoiding unnecessary exposure to antimicrobial therapy may be a useful tool in preventing colonization of the adenoids by potential pathogens. This review discusses the unique microbiology of the adenoids in individuals with a variety of pathological conditions, the interactions between the various organisms and the effects of antimicrobial therapy on the microbial flora of the adenoids.

The in vitro activity of faropenem, an oral penem, was compared with those of penicillin, co-amoxiclav, cefoxitin, clindamycin, erythromycin and metronidazole against 106 isolates of anaerobic pathogens involved in systemic infections. The organisms tested comprised Porphyromonas gingivalis (29), Prevotella spp. (eight), Prevotella melaninogenica (seven), Prevotella intermedia (five), Actinomyces spp. (25), Fusobacterium nucleatum (14), Peptostreptococcus spp. (11), Bacteroides ureolyticus (five) and Bacteroides forsythus (two). The antimicrobial properties of faropenem were investigated by studying MICs, MBCs, time-kill kinetics and post-antibiotic effect (PAE). Faropenem was highly active against all the anaerobes tested (MIC(90) < or = 0.5 mg/L) and was bactericidal against both beta-lactamase-positive and -negative anaerobes, with a maximum bactericidal effect at 10 x MIC at between 12 and 24 h. In addition, faropenem had an in vitro PAE on all the tested isolates and this was not influenced by beta-lactamase production. Faropenem may be useful for treating infections caused by periodontal bacteria or oral flora.

Aims: In vitro studies have suggested that fructo-oligosaccharides (FOS) and resistant starch (two fermentable non-digestible carbohydrates) display different fermentation kinetics. This study investigated whether these substrates affect the metabolic activity and bacterial composition of the intestinal microflora differently depending on the caecocolonic segment involved., Methods and Results: Eighteen rats were fed a low-fibre diet (Basal) or the same diet containing raw potato starch (RPS) (9%) or short-chain FOS (9%) for 14 days. Changes in wet-content weights, bacterial populations and metabolites were investigated in the caecum, proximal and distal colon and faeces. Both substrates exerted a prebiotic effect compared with the Basal diet. However, FOS increased lactic acid-producing bacteria (LAPB) throughout the caecocolon and in faeces, whereas the effect of RPS was limited to the caecum and proximal colon. As compared with RPS, FOS doubled the pool of caecal fermentation products, while the situation was just the opposite distally. This difference was mainly because of the anatomical distribution of lactate, which accumulated in the caecum with FOS and in the distal colon with RPS. Faeces reflected these impacts only partly, showing the prebiotic effect of FOS and the metabolite increase induced by RPS., Conclusions: This study demonstrates that FOS and RPS exert complementary caecocolonic effects., Significance and Impact of the Study: The RPS and FOS combined ingestion could be beneficial by providing health-promoting effects throughout the caecocolon.

Abscesses that develop as a result of introduction of the normal flora into a normally sterile body site are often polymicrobial. This review summarizes past studies published by our group on the microbiology of polymicrobial abscesses that occur at various body sites. Staphylococcus aureus and Group A beta-haemolytic streptococci are the most prevalent aerobes in skin and soft tissue abscesses and are isolated at all body sites. In contrast, organisms that colonize the mucous membranes predominated in infections adjacent to these membranes. In this fashion, organisms of the gastrointestinal and cervical flora (enteric Gram-negative bacilli and Bacteroides fragilis group) were found most often in intra-abdominal and buttock and leg lesions. Group A beta-haemolytic streptococci, pigmented Prevotella and Porphyromonas spp., and Fusobacterium spp. were most commonly found in lesions of the mouth, head, neck and fingers. These organisms probably reached these sites from the oral cavity, where they are part of the normal flora. Drainage of the abscess is the treatment of choice. Appropriate management of these mixed aerobic and anaerobic infections may also require the administration of antimicrobials that are effective against both the aerobic and anaerobic components of the infections.

A continuous flow reactor system was developed to evaluate the efficacy of antimicrobial treatments against sulfate-reducing bacterial biofilms. An annular reactor operating at a nominal dilution rate of 0.5 h(-1) was fed one-tenth strength Postgate C medium diluted in 1.5% NaCl and was inoculated with a mixed culture enriched from oilfield-produced water on the same medium. Thin biofilms developed in this reactor after 2 days of operation. The activity of these biofilms resulted in approximately 50 mg S l(-1) of sulfide at steady state prior to biocide treatment. Biocide efficacy was quantified by recording the time required for sulfide production to recover following an antimicrobial treatment. In a control experiment in which pure water was applied, the time required to reach 10 mg S l(-1) sulfide after the treatment was 1.7+/-1.2 h, whereas the time to reach this level of sulfide after a pulse dose of 500 mg l(-1) glutaraldehyde was delayed to 61+/-11 h. Nitrite treatment suppressed sulfide production as long as the nitrite concentration remained above 15 mg N l(-1). Sulfide production recovered more rapidly after nitrite treatment than it did after glutaraldehyde treatment.

This study compared the in vitro activities of ertapenem, ceftriaxone, co-amoxiclav, ciprofloxacin and piperacillin-tazobactam against 314 aerobic bacteria and of ertapenem, piperacillin-tazobactam, cefoxitin, ceftriaxone, chloramphenicol, ticarcillin-clavulanate, ampicillin-sulbactam, clindamycin and metronidazole against 500 anaerobic bacteria from 212 patients with acute pelvic infection. Antimicrobial susceptibilities were determined by broth microdilution (aerobes) or agar dilution (anaerobes), following NCCLS guidelines. The most common isolates were Enterobacteriaceae and Peptostreptococcus spp. Ertapenem was the most active drug tested against Enterobacteriaceae (100% susceptible) and anaerobes (99.8% susceptible); the least active agents were co-amoxiclav (79% of Enterobacteriaceae susceptible) and ceftriaxone (85.9% of anaerobes susceptible). All agents tested had excellent activity against beta-haemolytic streptococci and methicillin-susceptible Staphylococcus aureus.

A 5-laboratory study was performed that used the National Committee for Clinical Laboratory Standards (NCCLS) reference agar dilution method with 3 media formulations to determine whether the use of different media would affect minimum inhibitory concentration (MIC) results. Wilkins-Chalgren, Brucella-based blood agar (BRU), and Wilkins-Chalgren agar plus blood (WCB) and 6 antibiotics (clindamycin, cefoxitin, ceftizoxime, piperacillin, metronidazole, and trovafloxacin) were evaluated with 58 isolates. The MIC values were compared, and a significant correlation of >0.80 was demonstrated for all media and each antibiotic/organism group. The cumulative rate of errors for all antibiotics was 0.1%. These data indicate that a change in the NCCLS reference medium for testing of anaerobic bacteria susceptibility to either BRU or WCB will not affect the MIC results for the antibiotics and organisms evaluated.

Susceptibility testing of anaerobes has been described for approximately 45 years, some 15 years fewer than descriptions for aerobic organisms. During that time period, >16 methods, >16 media, and a host of other variables have been described in the United States literature, culminating in the most recent standards published by the National Committee for Clinical Laboratory Standards (NCCLS) in 2001. These new guidelines include a single agar dilution reference method as well as an alternative minimal inhibitory concentration method validated by extensive multilaboratory collaborative trials. In addition, the Food and Drug Administration-approved E-test has proved valuable as a user-friendly alternative to NCCLS methods. Highlights of the "evolution" of various methods, their variations and their failures, factors that affected the development of the current standards, and the rationale for susceptibility testing of anaerobes are discussed herein.

A multilaboratory study compared the growth of 30 fastidious anaerobes, using 5 different agar media: Wilkins-Chalgren (WC), WC with either whole or laked sheep blood, and Brucella supplemented with vitamin K(1) and hemin and either laked or whole sheep blood. The media were compared for quality and quantity of growth. Experiments were conducted either entirely in an anaerobic chamber or inoculated in ambient air with anaerobic incubation. The results showed that (1) any medium plus whole or laked blood was better than unsupplemented WC, (2) whole blood and laked blood additives gave similar results, (3) supplemented Brucella with whole or laked blood was superior to WC and WC with whole or laked blood, and (4) anaerobic and aerobic inoculation with anaerobic incubation gave similar results. Brucella agar supplemented with whole or laked blood supports the growth of fastidious anaerobic species better than the WC agars do.

Faropenem, a new oral beta-lactam agent with a penem structure, was very active against 405 aerobic and anaerobic bite isolates. It inhibited 232 of 236 (98%) aerobic isolates, including all Pasteurella spp. and Eikenella corrodens at < or = 0.25 mg/L, and 164/169 (97%) anaerobic isolates, at < or = 1 mg/L. The 10 isolates that required > or = 2 mg/L for inhibition were one strain each of Acinetobacter lwoffi, Corynebacterium minutissimum, Bacteroides ovatus, Lactobacillus delbrueckii and Peptostreptococcus tetradius, plus Corynebacterium 'aquaticum' (two strains) and Veillonella sp. (three strains).

In a recently completed study of once-a-day ertapenem versus piperacillin-tazobactam every 6 h in the treatment of complicated skin and skin-structure infections, 540 patients were randomized in a 1rcolon;1 ratio and assigned to 1 of 2 strata: those with a complicating underlying disease or all others. The most common infections in the study were deep soft-tissue abscess (18.9%), followed by diabetic lower extremity infection (18.1%); 7.0% of these were perineal cellulitis/abscess. With the exception of methicillin-resistant Staphylococcus aureus, almost all of the predominant aerobic pathogens were susceptible to both study drugs. Eighty-seven patients (16%) had >/=1 anaerobe identified in their baseline wound cultures, with a total of 232 anaerobic isolates. Of the 141 anaerobes tested for susceptibility, 97.2% were susceptible to ertapenem and 97.9% to piperacillin-tazobactam. Ertapenem had excellent in vitro activity against the most common aerobic pathogens and almost all anaerobes recovered from patients with infections of the skin and skin structures.

An open-label, multicenter study was performed to assess bacteriologic findings associated with chronic bacterial maxillary sinusitis in adults. Seventy aerobic (52.2%) and 64 anaerobic (47.8%) pathogens were recovered from clinically evaluable patients at baseline (before therapy). The most commonly isolated anaerobes were Prevotella species (31.1%), anaerobic streptococci (21.9%), and Fusobacterium species (15.6%). The aerobes most frequently recovered included Streptococcus species (21.4%), Haemophilus influenzae (15.7%), Pseudomonas aeruginosa (15.7%), and Staphylococcus aureus and Moraxella catarrhalis (10.0% each). Recurrences of signs or symptoms of bacterial maxillary sinusitis associated with anaerobes were twice as frequent as were those associated with aerobes when counts of anaerobes were > or =10(3) cfu/mL. A pathogenic role for Granulicatella species in cases of chronic sinusitis was documented for the first time.

The anti-anaerobic activity of AZD2563, a new oxazolidinone, was compared with that of eight other agents against 201 Gram-positive and 99 Gram-negative anaerobes. MIC(50) and MIC(90) values (mg/L) for the 201 Gram-positive organisms were as follows: AZD2563, 1.0/4.0; linezolid, 1.0/4.0; quinupristin/dalfopristin, 0.5/1.0; amoxicillin, 0.25/1.0; clindamycin, 0.25/8.0; metronidazole, 0.5/>16.0; vancomycin, 0.5/2.0; teicoplanin, 0.125/0.25; and meropenem, 0.06/1.0. AZD2563, linezolid, vancomycin, teicoplanin and quinupristin/dalfopristin were mainly active against Gram-positive anaerobes, with no useful activity against Gram-negative anaerobes.

Genes encoding resistance to mercury and to antibiotics are often carried on the same mobile genetic element and so it is possible that mercury-containing dental materials may select for bacteria resistant to mercury and to antibiotics. The main aim of this study was to determine whether the prevalence of Hg-resistant oral bacteria was greater in children with mercury amalgam fillings than in those without. A secondary aim was to determine whether the Hg-resistant isolates were also antibiotic resistant. Bacteria in dental plaque and saliva from 41 children with amalgam fillings and 42 children without such fillings were screened for mercury resistance by cultivation on a HgCl(2)-containing medium. Surviving organisms were identified and their susceptibility to mercury and to several antibiotics was determined. Seventy-eight per cent and 74% of children in the amalgam group and amalgam-free group, respectively, harboured Hg-resistant bacteria; this difference was not statistically significant. Nor was there any significant difference between the groups in terms of the proportions of Hg-resistant bacteria in the oral microflora of the children. Of Hg-resistant bacteria, 88% and 92% from the amalgam group and the amalgam-free group, respectively, were streptococci; 41% and 33% were resistant to at least one antibiotic, most frequently tetracycline. The results of this study show that there was no significant difference between children with amalgam fillings and those without such fillings with regard to the prevalence, or the proportion, of Hg-resistant bacteria in their oral microflora. The study also found that Hg-resistant bacteria were common in children regardless of whether or not they had amalgam fillings and that many of these organisms were also resistant to antibiotics.

The in vitro potency of BAL 9141, a new pyrrolidinone cephalosporin, was tested against non-duplicate strains of anaerobic bacteria. The MIC(50) was 1 mg/L against Actinomyces species, Clostridium species, Gram-positive anaerobic cocci, Porphyromonas species, Fusobacterium species, Lactobacillus species, Prevotella species and Veillonella species. The MIC(50) was 16 mg/L for Bacteroides fragilis and other Bacteroides species. BAL 9141 was not active against cefoxitin-resistant Bacteroides fragilis.

The effect of 5 days' administration of quinupristin/dalfopristin (RP59500) on the faecal microflora was evaluated in healthy volunteers. Twenty healthy volunteers received 7.5 mg/kg of quinupristin/dalfopristin infused over 1 h twice daily for 5 days and four received a matched placebo. Faecal samples were collected before, during and after treatment (days -1/-2, 6, 8, 14/15, 35 +/- 2, 60 +/- 4, 90 +/- 4). In the treated volunteers, anaerobes, including sporulating and Gram-negative bacteria, decreased slightly during treatment, whereas numbers of enterococci and Enterobacteriaceae increased significantly (P < 0.01). Counts of anaerobes and enterococci resistant to erythromycin or to quinupristin/dalfopristin increased significantly (P < 0.01) during treatment and returned slowly to their baseline levels after the end of treatment. Mean faecal antibiotic concentrations reached 291 +/- 184 and 42 +/- 22 microg/g of faeces for quinupristin and dalfopristin, respectively, by the fifth day of treatment. Counts of yeasts were not influenced significantly by the treatment. No emergence of glycopeptide-resistant enterococci, Staphylococcus aureus, Pseudomonas aeruginosa or Clostridium difficile was observed. No episode of diarrhoea was reported. In conclusion, quinupristin/dalfopristin administration was associated with a temporary shift towards resistance of the endogenous flora and a temporary increase in counts of enterobacteria and enterococci. However, no decrease in colonization resistance towards exogenous potentially pathogenic bacteria was observed and the observed modifications disappeared within 12 weeks after the end of quinupristin/dalfopristin administration.