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Renew interest and enthusiasm for anaerobes stem from both technological improvements (culture media, production of an adequate anaerobic atmosphere, identification methods) and greater awareness on the part of clinicians. Anaerobic infections were historically treated empirically, targeting the species known to be involved in each type of infection. Prevotella, fusobacteria, and Gram-positive cocci (GPAC) were considered responsible for infections above the diaphragm whereas for intra-abdominal infections, Bacteroides of the fragilis group (BFG), GPAC and clostridia were predominantly implicated. The antibiotic susceptibility of anaerobes was only taken into consideration by the clinician in the event of treatment failure or when faced with infections by multidrug-resistant bacteria (MDR). The evolution of antibiotic resistance together with clinical failures due to the absence of detection of hetero-resistant clones has resulted in a greater need for accessible antibiotic susceptibility testing (AST) and disc diffusion method. Improved isolation and identification of anaerobes, along with the availability of accessible and robust methods for performing AST, will ensure that treatment, whether empirical or guided by an antibiogram, will lead to better outcomes for anaerobic infections., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In anaerobic infections, the relationship between clinical failure and antibiotic resistance is difficult to demonstrate, especially in mixed anaerobic-aerobic infections. Single isolates of anaerobes in cases of bacteraemia revealed that treatment failures were due to inappropriate therapy. We review here cases, where the empiric treatment was unsuccessful due to resistance of anaerobic bacteria to the administered agents and where the change of the antibiotic allowed the patients to be cured. Many therapeutic failures could be linked to the lack of timely detection of resistance, including heteroresistance of the anaerobes. Disk diffusion or Etest methodology may be suitable, at least for rapidly growing anaerobes, to detect both resistance and heteroresistance to antibiotics widely used for empirical therapy., Competing Interests: Declaration of competing interest We declare no conflict of interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

For decades, the term "anti-anaerobic" has been commonly used to refer to antibiotics exhibiting activity against anaerobic bacteria, also designated as anaerobes. This term is used in various situations ranging from infections associated with well-identified pathogens like Clostridioides difficile, or Fusobacterium necrophorum in Lemierre's syndrome, that require specific antibiotic treatments to polymicrobial infections generally resulting from the decreased permeability of anatomical barriers (e.g., intestinal translocation and stercoral peritonitis) or infectious secondary localizations (e.g., brain abscess and infectious pleurisy). In these cases, the causal bacteria generally remain unidentified and the antimicrobial treatment is empirical. However, major progress in the knowledge of human bacterial microbiotas in the last 10 years has shown how diverse are the species involved in these communities. Here, we sought to reappraise the concept of anti-anaerobic spectrum in the light of recent advances in the microbiota field. We first highlight that the term anaerobic itself does not represent the tremendous diversity of the bacteria it spans, and then we stress that the antibiotic susceptibility profiles for most anaerobic bacteria remain unaddressed. Furthermore, we provide examples challenging the relevance of the "anti-anaerobic" spectrum from a clinical and ecological perspective., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Of 69 clinical isolates of Finegoldia magna tested, 36% presented high-level MICs of erythromycin (>256 μg/ml), harboring erm(A) (n = 20) or erm(B) (n=5). Of nine isolates exhibiting an inducible resistance phenotype to macrolides-lincosamides-streptogramins B, four (44%) were susceptible with a potential risk of treatment failure due to emergence of resistant mutants., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Bacteroides thetaiotaomicron maybe one of the most adaptable intestinal bacteria due to its complex genome. Known to be an opportunistic pathogenic anaerobe, B. thetaiotaomicron has recently been described as a symbiont with anti-inflammatory properties. In this study, peptide mass finger printing technique was used to identify the stress proteins (maybe anti-stress proteins for the host) extracted from B. thetaiotaomicron grown under nutrient starvation (without heme, blood or bile) prior to be placed in an aerobic solution containing a mild non-ionic detergent derived from cholic acid. We focus here on proteins related to stress, knowing that superoxide dismutase was previously identified in the extract. In parallel, the morphology of the bacterial cells was observed using electronic microscopy before and after the extraction process. The effective antioxidant effect of the extract was evaluated in vitro against hydrogen peroxide. This work highlights the B. thetaiotaomicron ability to produce a large amount of stress proteins and to remain viable during the extraction. Budding vesicles were observed on its cell wall. The extraction process did not exceed 20 h in order to preserve the bacterial viability that decreased significantly after 24 h in preliminary studies. In our experimental conditions, an inhibitory effect of the extract was found against hydrogen peroxide. Animal models of inflammation will later check in vivo if this extract of anti-stress proteins is able to counter the respiratory burst beginning an inflammation process., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Inflammatory bowel diseases (IBD) patients are abnormally colonized by adherent-invasive Escherichia coli (AIEC). NOD2 gene mutations impair intracellular bacterial clearance. We evaluated the impact of antibiotic treatment on AIEC colonization in wildtype (WT) and NOD2 knockout mice (NOD2KO) and the consequences on intestinal inflammation., Methods: After 3 days of antibiotic treatment, mice were infected for 2 days with 10⁹ CFU AIEC and sacrificed 1, 5, and 60 days later. In parallel, mice were challenged with AIEC subsequent to a dextran sodium sulfate (DSS) treatment and sacrificed 9 days later. Ileum, colon, and mesenteric tissues were sampled for AIEC quantification and evaluation of inflammation., Results: Without antibiotic treatment, AIEC was not able to colonize WT and NOD2KO mice. Compared with nontreated animals, antibiotic treatment led to a significant increase in ileal and colonic colonization of AIEC in WT and/or NOD2KO mice. Persistent AIEC colonization was observed until day 5 only in NOD2KO mice, disappearing at day 60. Mesenteric translocation of AIEC was observed only in NOD2KO mice. No inflammation was observed in WT and NOD2KO mice treated with antibiotics and infected with AIEC. During DSS-induced colitis, colonization and persistence of AIEC was observed in the colon. Moreover, a dramatic increase in clinical, histological, and molecular parameters of colitis was observed in mice infected with AIEC but not with a commensal E. coli strain., Conclusions: Antibiotic treatment was necessary for AIEC colonization of the gut and mesenteric tissues and persistence of AIEC was dependent on NOD2. AIEC exacerbated a preexisting DSS-induced colitis in WT mice., (Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.)

In the present study, two pre-analytic processes for mass spectrometric bacterial identification were compared: the time-consuming reference method, chemical extraction, and the direct smear technique directly using cultured colonies without any further preparation. These pre-analytic processes were compared in the identification of a total of 238 strains of anaerobic bacteria representing 34 species. The results showed that 218/238 strains were identified following chemical extraction, 185 identifications (77.7%) were secured to both genus and species [log(score) > 2.0] whereas 33 identifications (14%) were secured to genus only [log(score) between 1.7 and 2.0]. Following direct smear, 207/238 anaerobic bacteria were identified, 158 identifications (66.4%) were secured to both genus and species [log(score) > 2.0] whereas 49 identifications were secured to genus only [log(score) between 1.7 and 2.0]. Twenty strains were not identified [log(score) < 1.7] by MALDI-TOF MS following chemical extraction whereas 31 strains were not identified with the direct smear technique. Although direct smear led to a significant decrease of the log(score) values for the Clostridium genus and the Gram positive anaerobic bacteria (GPAC) group (p < 0.0001, Wilcoxon test), identification to both species and genus were not changed. However these differences were not statistically significant (p = 0.1, Chi square). Therefore, MALDI-TOF MS identification following the direct smear technique appears to both non-inferior to the reference method and relevant for anaerobic bacteria identification., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We compared retrospectively vancomycin and teicoplanin trough serum levels after loading doses and, subsequently, after high daily doses, in 52 patients (26 in each group) who had developed infections after implantation of an orthopedic device. The target trough serum level was > 25 mg/l. Trough levels were significantly higher at 2 days (±1) and 5 days (±1) in patients who received teicoplanin compared with patients who received a continuous perfusion of vancomycin (26.1 vs. 16 mg/l at day 2 ± 1, P = 0.01; 27.8 vs. 19.9 mg/l at day 5 ± 1, P = 0.01). One of the 26 patients taking vancomycin reached the target trough serum level by day 2 (±1), whereas 10 of the 26 patients taking teicoplanin reached the target by that time (P = 0.002). At day 5 (±1), 6/26 patients taking vancomycin reached the target, versus 13/26 patients taking teicoplanin (P = 0.04). However, physicians should remain cautious when administering teicoplanin empirically because of the higher MIC₉₀ values observed for coagulase-negative staphylococci compared with vancomycin.

Objectives: Film coatings based on blends of Eurylon 6 HP-PG (a hydroxypropylated and pregelatinized high amylose starch) and ethylcellulose were to be evaluated as promising coating materials for site-specific drug delivery to the colon of patients suffering from inflammatory bowel diseases., Methods: Pellet starter cores containing 60% 5-aminosalicylic acid were prepared by extrusion/spheronization and coated with different Eurylon 6 HP-PG:ethylcellulose blends at various coating levels. Drug release was measured in media simulating the contents of the upper gastrointestinal tract (in the presence and absence of enzymes) as well as in media simulating the contents of the colon., Key Findings: 5-Aminosalicylic acid release could effectively be suppressed in 0.1 N HCl and phosphate buffer pH 6.8, optionally containing pepsin or pancreatin, but occurred as soon as the pellets came into contact with culture medium inoculated with faecal samples from inflammatory bowel disease patients. This can be attributed to the partial degradation of the starch derivative by enzymes secreted by bacteria present in the colon of these patients., Conclusions: The presented drug delivery system is adapted to the pathophysiological conditions in inflammatory bowel disease patients. Furthermore, drug release remained unaltered upon 1 year open storage., (© 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society of Great Britain.)

Background: Linezolid therapy has shown high rates of clinical success in patients with osteomyelitis and prosthetic joint infections caused by Gram-positive cocci. Recent studies have demonstrated that linezolid/rifampicin combination therapy prevents the emergence of rifampicin-resistant mutations in vitro. However, linezolid/rifampicin combination-related haematological and neurological toxicities have not been evaluated., Objectives: To assess the tolerability of prolonged linezolid/rifampicin combination therapy compared with other linezolid-containing regimens in patients with bone and joint infections., Methods: We reviewed the medical records of 94 patients who had received linezolid for >4 weeks after bone and joint infections. Anaemia was defined as a ≥2 g/dL reduction in haemoglobin, leucopenia as a total leucocyte count <4 × 10(9)/L, and thrombocytopenia as a reduction in platelet count to <75% of baseline., Results: Anaemia was less frequent among patients on linezolid/rifampicin combination therapy than among patients on linezolid alone or in combination with other drugs (9.3%, 44% and 52%, respectively; P<0.01). In multivariate analysis, age and treatment group were independently associated with anaemia. Thrombocytopenia was reported in 44% of patients on linezolid/rifampicin combination therapy, in 48% of patients on linezolid alone and in 57.7% of patients on other linezolid-containing regimens. Age was the only variable associated with thrombocytopenia (P=0.019) in univariate analysis., Conclusions: Linezolid/rifampicin combination therapy was associated with a significantly reduced incidence of anaemia among patients with bone and joint infections, but it did not have an effect on thrombocytopenia and peripheral neuropathy rates. Linezolid/rifampicin combination therapy was not associated with poor clinical outcomes.

Background: Meropenem is a carbapenem that has an excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The major objective of the present study was to assess the in vitro activity of meropenem compared to imipenem and piperacillin/tazobactam, against 1071 non-repetitive isolates collected from patients with bacteremia (55%), pneumonia (29%), peritonitis (12%) and wound infections (3%), in 15 French hospitals in 2006. The secondary aim of the study was to compare the results of routinely testings and those obtained by a referent laboratory., Method: Susceptibility testing and Minimum Inhibitory Concentrations (MICs) of meropenem, imipenem and piperacillin/tazobactam were determined locally by Etest method. Susceptibility to meropenem was confirmed at a central laboratory by disc diffusion method and MICs determined by agar dilution method for meropenem, imipenem and piperacillin/tazobactam., Results: Cumulative susceptibility rates against Escherichia coli were, meropenem and imipenem: 100% and piperacillin/tazobactam: 90%. Against other Enterobacteriaceae, the rates were meropenem: 99%, imipenem: 98% and piperacillin/tazobactam: 90%. All Staphylococci, Streptococci and anaerobes were susceptible to the three antibiotics. Against non fermeters, meropenem was active on 84-94% of the strains, imipenem on 84-98% of the strains and piperacillin/tazobactam on 90-100% of the strains., Conclusions: Compared to imipenem, meropenem displays lower MICs against Enterobacteriaceae, Escherichia coli and Pseudomonas aeruginosa. Except for non fermenters, MICs90 of carbapenems were <4 mg/L. Piperacillin/tazobactam was less active against Enterobacteriaceae and Acinetobacter but not P. aeruginosa. Some discrepancies were noted between MICs determined by Etest accross centres and MICs determined by agar dilution method at the central laboratory. Discrepancies were more common for imipenem testing and more frequently related to a few centres. Overall MICs determined by Etest were in general higher (0.5 log to 1 log fold) than MICs by agar dilution.

The aim of this study was to identify novel polymeric films allowing for the site-specific delivery of drugs to the colon of patients suffering from inflammatory bowel diseases. Ethylcellulose was blended with different types of bacteria-sensitive starch derivatives. The water uptake and dry mass loss kinetics of the systems were monitored upon exposure to media simulating the contents of the stomach, small intestine and colon (including fresh fecal samples from Crohn's Disease and Ulcerative Colitis patients). Importantly, ethylcellulose:Nutriose FB 06 and ethylcellulose:Peas starch N-735 films showed highly promising water uptake and dry mass loss kinetics in all the investigated media, indicating their potential to minimize premature drug release in the upper gastro-intestinal tract, and allowing for controlled release once the colon is reached. This can be attributed to the fact that the starch derivatives serve as substrates for the enzymes, which are secreted by the bacteria present in the colon of inflammatory bowel disease patients. Thus, the identified new polymeric films are adapted to the pathophysiological conditions in the gastro-intestinal tract in the disease state. Furthermore, Nutriose is known to provide pre-biotic effects, which can be of great benefit for these patients.

The aim of this study was to prepare and characterize novel types of polymer coated pellets allowing for the site-specific delivery of drugs to the colon. 5-Aminosalicylic acid (5-ASA)-loaded beads were prepared by extrusion-spheronization and coated with different Nutriose:ethylcellulose blends. In vitro drug release from these systems was measured under various conditions, including the exposure to fresh fecal samples from inflammatory bowel disease patients under anaerobic conditions. Nutriose is a starch derivative, which is preferentially degraded by enzymes secreted by the microflora in the colon of Crohn's disease and ulcerative colitis patients. Interestingly, the release of 5-ASA (which is commonly used for the local treatment of inflammatory bowel diseases) could effectively be suppressed upon exposure to release media simulating the conditions in the upper GIT, irrespective of the degree of agitation and presence or absence of enzymes. But as soon as the pellets came into contact with fecal samples of inflammatory bowel disease patients, the release rate significantly increased and the drug was released in a time-controlled manner. Thus, this novel type of colon targeting system is adapted to the pathophysiology of the patient. Furthermore, culture media containing specific colonic bacteria are presented providing an interesting potential as substitutes for fresh fecal samples.

Objectives: The EBIIA (Etude épidémiologique Bactério-clinique des Infections Intra-Abdominales) study was designed to describe the clinical, microbiological and resistance profiles of community-acquired and nosocomial intra-abdominal infections (IAIs)., Patients and Methods: From January to July 2005, patients undergoing surgery/interventional drainage for IAIs with a positive microbiological culture were included by 25 French centres. The primary endpoint was the epidemiology of the microorganisms and their resistance to antibiotics. Multivariate analysis was carried out using stepwise logistic regression to assess the factors predictive of death during hospitalization., Results: Three hundred and thirty-one patients (234 community-acquired and 97 nosocomial) were included. The distribution of the microorganisms differed according to the type of infection. Carbapenems and amikacin were the most active agents in vitro against Enterobacteriaceae in both community-acquired and nosocomial infections. Against Pseudomonas aeruginosa, amikacin, imipenem, ceftazidime and ciprofloxacin were the most active agents in community-acquired infections, while imipenem, cefepime and amikacin were the most active in nosocomial cases. Against the Gram-positive bacteria, vancomycin and teicoplanin were the most active in both infections. Against anaerobic bacteria, the most active agents were metronidazole and carbapenems in both groups. Empirical antibiotic therapy adequately targeted the pathogens for 63% of community-acquired and 64% of nosocomial peritonitis. The presence of one or more co-morbidities [odds ratio (OR) = 3.17; P = 0.007], one or more severity criteria (OR = 4.90; P < 0.001) and generalized peritonitis (OR = 3.17; P = 0.006) were predictive of death., Conclusions: The principal results of EBIIA are a higher diversity of microorganisms isolated in nosocomial infections and decreased susceptibility among these strains. Despite this, the adequacy of treatment is comparable in the two groups.

The activity of telithromycin and comparator antibacterials was examined in isolates of Streptococcus pneumoniae and Haemophilus influenzae isolated from patients with community-acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB), or sinusitis during year 5 (2003-2004) of the Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin global resistance surveillance study. Among S. pneumoniae, penicillin nonsusceptibility and erythromycin resistance were 35.7% and 36.0%, respectively. beta-Lactamase was produced by 12.3% of H. influenzae isolates. beta-Lactamase-negative ampicillin-resistant strains, mainly from Japan, comprised 5.2% of global H. influenzae isolates. Telithromycin and levofloxacin were the most active agents tested against S. pneumoniae and H. influenzae (>99% of isolates susceptible) isolated from patients with CAP, AECB, or bacterial sinusitis. Amoxicillin-clavulanate, levofloxacin, and telithromycin were the most active agents against multidrug-resistant S. pneumoniae.

Objectives: The aim was to compare the in vitro effects of amoxicillin and ampicillin on the oxidative metabolism of polymorphonuclear neutrophils (PMNs)., Methods: Superoxide radical anion production by PMNs, stimulated or not by various exogenous stimulants and in contact with increasing antibiotic concentrations, was measured using spectrophotometric methods., Results: Whereas a pro-oxidative action of amoxicillin on PMNs was obtained without exogenous stimulation or with opsonized zymosan (OZ), the O(2)(-) production by PMNs incubated with ampicillin did not increase significantly., Conclusions: This amoxicillin pro-oxidative effect could be due to the activation of the PMN NADPH oxidase, to its induction by a membrane effect or via the OZ pathway. It probably reinforces amoxicillin intrinsic bactericidal action and might partly explain the severe rashes sometimes occurring with amoxicillin treatment.

Bacteroides thetaiotaomicron, a bowel anaerobic commensal, seems to release enzymes detoxifying reactive oxygen species according to our recent work. This opportunistic pathogen would be beneficial in the case of an inflammatory process. To explore its role after an oxidative or nutritive stress, six to seven separate experiments were performed. The bacteria were grown on media restricted in growth factors or supplemented with bile. Their viability was checked after surface protein extraction. The extracts underwent 2D electrophoresis. Gel images were statistically analysed to construct "master" gels. Proteins were identified (peptide-mass fingerprinting technique). The effect of each extract on superoxide anions was evaluated (spectrophotometric method). Superoxide dismutase was identified and a major superoxide anion inhibition was shown by extracts obtained after a nutritive and oxidative stress without significant bacterial death. So, a therapeutic antioxidant potential is firmly hoped for. [figure: see text]

We report the first case of intrafamily transmission of a C-MRSA clone harbouring toxic shock syndrome toxin-1 (TSST-1). Because of the risk of this clone to spread in the community, family members of these patients should be screened to detect and prevent the diffusion of recurrent or new infections.

In this report, we review one case of bacteremia infection due to Dialister pneumosintes. The patient was admitted in post-partum with vaginosis and suppurative thrombosis of the ovarian veina. D. pneumosintes was isolated in pure culture from the three blood culture flasks. Identification of this bacterium was difficult and requires the amplification and partial sequencing of the 16S rRNA gene. The patients had favorable outcome after antibiotic treatment.

Introduction: Recovery of the bacteria responsible for prosthetic joint infections is a major problem, which is due in part to the alteration of their ability to grow by storage during transportation to the laboratory., Methods: In this prospective study, we assessed the benefit of inoculating an enriched liquid medium (Rosenow's broth) with intraoperative samples from 72 patients with prosthetic joint revision due to infection. We compared the results of culture of specimens collected in a standard receptacle with the results for specimens collected in Rosenow's broth., Results and Interpretation: 144 samples were taken by each of the 2 collection methods for subsequent culture. Concordance between standard and Rosenow samples was observed for 52 of the 58 strains cultured on agar and for 42 of the 97 strains (p < 0.001) which grew only in liquid medium. Infection would not have been diagnosed in 26 patients (almost one-third of all patients) without combining sample collection in Rosenow's broth with standard collection. The bacteria that were not recovered from standard samples but which were recovered from those collected in Rosenow's broth included not only strict anaerobes, in particular Propionibacterium acnes, but also coagulase-negative staphylococci and streptococci.

Objectives: The intrinsic properties of the new antibiotic linezolid make it an attractive candidate for the treatment of chronic osteomyelitis. However, data regarding the tolerance of long-term linezolid administration are still lacking., Methods: The medical charts of patients given linezolid for >4 weeks were retrospectively analysed, especially their haematology. In a case-control study, we compared the respective characteristics of patients who developed anaemia during linezolid therapy and those who did not., Results: Forty-five adults with chronic osteomyelitis received 600 mg linezolid intravenously twice daily for 7 days, and then orally, for a mean total duration of 15.9 weeks (range, 6-36). Anaemia episodes requiring blood transfusion occurred in 13/45 patients (28.9%). Median time from treatment initiation to anaemia onset was 7.4 weeks (range, 4-16). Anaemia was significantly associated with premature linezolid therapy cessation (P = 0.0012). No linezolid-related thrombocytopenia was observed. By univariate analysis, four variables were associated with the occurrence of anaemia: age >58 years, alcohol abuse, diabetes mellitus and low haemoglobin before linezolid treatment. Logistic regression analysis revealed two independent risk factors for anaemia: age >58 years (OR = 20.5, 95% CI 0.69-599; P = 0.0001) and pre-treatment haemoglobin <10.5 g/dL (OR = 16.49, 95% CI 1.06-255; P = 0.04)., Conclusions: Profound anaemia may occur in adult patients with chronic osteomyelitis on prolonged linezolid therapy, and often necessitates linezolid cessation. These patients are likely to be aged >58 years and to have low pre-treatment haemoglobin. The results for the present series might help physicians to identify patients who should not be given long-term linezolid treatment for chronic osteomyelitis.

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%).

Necrotizing soft tissue infections (NSTI) are infrequent but life-threatening, and require prompt empirical antibiotic therapy. Current nosologic classifications have limited value because the criteria used are imprecise and their bacteriological specificity is uncertain. The aim of this study was to describe the bacterial flora and its antibiotic sensitivity in a cohort of patients with NSTI, and to derive guidelines for the choice of antimicrobial chemotherapy. This prospective study involved 120 patients. Aerobic and anaerobic bacteriological samples were taken from infected soft tissues. The species distribution and susceptibility of the isolates to various antibiotic (ATB) combinations were analyzed. The data were analyzed according to the type (cellulitis versus myonecrosis) and anatomical location of NSTI (abdomen and perineum; uterine cervix; limbs). The chi-square test was used to analyze qualitative variables, and Student's t test was used for quantitative variables. A total of 232 samples yielded bacterial isolates (122 aerobic, 110 anaerobic). The species distribution of anaerobes did not differ according to the nature of the involved tissue or the anatomic location. Gram-negative aerobes were more frequently isolated from abdominal, perineal and limb sites than from the cervix (p<0.05), while gram-positive aerobes showed the reverse distribution (p<0.05). Metronidazole was more effective than clindamycin on cervical isolates (95% vs 88%, p=0.0093). Among the broad-spectrum antibiotics tested, imipenem/cilastatin and piperacillin/tazobactam were equally effective against the different groups of bacteria (94% vs 88%, p=0.14), and were clearly more active than the other antibiotics (p<0.05), whatever the site of isolation, the bacterial species, and the type of NSTI. The five antibiotics tested showed similar efficacy against cervical isolates. These results suggest that the choice of antibiotic therapy for NSTI should depend on the anatomical site of involvement rather than the nature of the infection. For abdominal, perineal and limb NSTI, we recommend first-line treatment with a betalactam-inhibitor combination (piperacillin/tazobactam or ticarcillin/clavulanate) plus an agent active on gram-negative species (aminoglycoside or fluoroquinolone). For cervical NSTI, we recommend penicillin G/metronidazole, or amoxicillin/clavulanic acid.

Minimal inhibition concentrations (MICs) were determined for linezolid (LZD) and compared with those of reference antibiotics against 265 anaerobes. For the Bacteroides fragilis group, MIC range for LZD was 2-4 mg/l. Strains resistant to the other antibiotics were detected including one strain of B. fragilis showing high level resistance to metronidazole (64 mg/l). LZD MIC(50) was 4 mg/l for prevotella and 1 mg/l for fusobacteria. LZD MICs were <1 mg/l for porphyromonas and veillonellae and

Unlabelled: AS A PRECAUTION: The new fluoroquinolones are clearly active on both Gram negative and Gram positive bacteria and on intracellular and strictly anaerobic bacteria, with excellent pharmacological properties. Nevertheless, there is a risk of resistant mutants appearing due to selective pressure, that would rapidly delete their activity. CONCENTRATIONS AVOIDING MUTATIONS: Among the definitions envisaged for the concept of a concentration that would prevent mutations or "mutation preventing concentration" (MPC), the most frequently retained is the concentration at which no mutant appears in the presence of a high inoculum. VALUES OF CONCENTRATIONS PREVENTING MUTATIONS: These have been established for Gram negative bacilli, for staphylococci methicillinsusceptible and for pneumococci. The MPC values are not correlated with those of the minimum inhibitory concentration (MIC), they are related to the bactericidal potential of fluoroquinolones., In Practice: Despite their limits, the MPC are of major interest for the prevention of mutants, which are always dangerous, since their underlying resistance mechanism is eventually unknown.

PEPTIDE-DEFORMYLASE: During protein synthesis in bacteria, a transformylase coding the fmt gene provides a formyl group on methionine before binding to the ARNm-ARNt complex. This tormylated methionine initiates the protein synthesis. The adjunction of an amino acid to the peptide chain leads to a peptide associated with a formylated methionine. The final stage requires a metallo-enzyme, peptide deformylase, which releases the peptide and regenerates the methionin. PEPTIDE-DEFORMYLASE INHIBITORS (PDF): Often rejected by the efflux pumps of Gram negative bacteria, PDF inhibitors are administered in the form of pro-drugs, capable of acting even in the bacteria that have lost their transformylase gene. TWO PRODUCTS: These are VCR 4887 developed by Versicor and Novartis and BB 83698 developed by British Biotechnology Genesoft. They are presently in the process of clinical predevelopment. They represent an important innovation and widen the range of new antibiotic classes.

Minimal inhibitory concentrations of moxifloxacin were compared with those of ofloxacin, ciprofloxacin, clindamycin, metronidazole and six beta-lactams for 159 anaerobes isolated from human clinical samples. Unlike other fluoroquinolones, moxifloxacin demonstrated high activity against the 76 strains of the Bacteroides fragilis group as the minimal inhibitory concentration(50) was 0.5 mg/l. Porphyromonas, Prevotella, Fusobacterium and Gram-positive anaerobic cocci were inhibited by 1 mg/l or less of moxifloxacin. It inhibited 93.7, 94.9 and 98% of the 159 strains investigated at concentrations of 1, 2 and 4 mg/l, respectively. Moxifloxacin was more potent than ofloxacin and ciprofloxacin against Gram-positive rods and anaerobic cocci. Its broad anaerobic spectrum in vitro is promising for the treatment of intra-abdominal and respiratory infections.