In spite of the enormous importance of the gastrointestinal (GI) tract microflora in the physiology and pathophysiology of the host and in specific infections and diseases, we are not yet very knowledgeable about the makeup of this flora and its activities. This is related to the extreme diversity and complexity of the GI flora and the fact that most of this flora is either entirely unknown to us or cannot yet be cultured on artificial media. The advent of molecular methods to detect and characterize the GI microflora has led to an explosion of knowledge in this field. We had thought until relatively recently, for example, that the esophagus and stomach were essentially sterile except for a transient flora descending from the oral cavity. Some of the newer techniques available permit high-throughput analysis of the flora, and of its metabolic and other activities, so that our knowledge of this field is expanding rapidly. It is an exciting time; impressive and significant discoveries are reported each year.

Anaerobic infections are common and some are serious, with a high mortality rate. They are easily overlooked because special precautions are needed for specimen collection and transport to do good bacteriologic studies and because some clinical laboratories fail to grow many or most anaerobes (a number of laboratories do not even do anaerobic cultures).

ABSTRACT The activities of BMS-284576, clinafloxacin, moxifloxacin, sitafloxacin, trovafloxacin, imipenem, cefoxitin, and clindamycin against 589 Bacteroides fragilis group isolates were determined. The activity of BMS-284576 was comparable to that of trovafloxacin. Sitafloxacin and clinafloxacin were the most active quinolones, and moxifloxacin was the least active. B. fragilis was the most susceptible of the species, and Bacteroides vulgatus was the most resistant. Association of specific antibiotic resistance with Bacteroides species was noted for all quinolones.

Background: Several newer generation fluoroquinolones have demonstrated good in vitro activity against Bacteroides species; particularly when first introduced. However, resistance of Bacteroides to quinolones appears to be increasing.Materials and methods: From 1994 to 2001, consecutive non-duplicated Bacteroides isolates from clinical specimens in 12 US hospitals were sent to the Tufts anaerobe laboratory for identification and susceptibility testing. NCCLS recommended methodology for testing was employed. Breakpoints of 8 mg/L for trovafloxacin and 4 mg/L for moxifloxacin were used to examine susceptibility trends.Results: In total, 4434 isolates were analysed. The geometric mean MIC increased significantly for clinafloxacin, trovafloxacin and moxifloxacin. Resistance to trovafloxacin (breakpoint of 8 mg/L) and moxifloxacin (breakpoint of 4 mg/L) increased from 8% to 25% and from 30% to 43%, respectively. Increased resistance was observed for all Bacteroides species, for all sites of isolation, and in 11 of 12 participating hospitals. Bacteroides vulgatus and isolates from decubitus ulcers were associated with increased resistance. During 2001, trovafloxacin and moxifloxacin resistance among blood isolates was 27% and 52%, respectively. The association between increased resistance and year of isolation remained significant after adjustment for hospital, species and site of isolation.Conclusions: Fluoroquinolone resistance among Bacteroides isolated in the US has markedly increased during the years 1994 to 2001. High rates of resistance among blood isolates are of particular concern.

Mechanisms responsible for the rapid tissue destruction in gas gangrene are not well understood. To examine the early effects of Clostridium perfringens exotoxins on tissue perfusion, a rat model of muscle blood flow was developed. Intramuscular injection of a clostridial toxin preparation containing both phospholipase C (PLC) and theta-toxin caused a rapid (1-2 min) and irreversible decrease in blood flow that paralleled formation of activated platelet aggregates in venules and arterioles. Later (20-40 min), aggregates contained fibrin and leukocytes, and neutrophils accumulated along vascular walls. Flow cytometry confirmed that these clostridial toxins or recombinant PLC induced formation of P-selectin-positive platelet aggregates. Neutralization of PLC activity in the clostridial toxin preparation completely abrogated human platelet responses and reduced perfusion deficits. It is concluded that tissue destruction in gas gangrene is related to profound attenuation of blood flow initiated by activation of platelet responses by PLC.

Clostridium perfringens gas gangrene is a fulminant infection, and radical amputation remains the single best treatment. It has been hypothesized that rapid tissue destruction is related to tissue hypoxia secondary to toxin-induced vascular obstruction, and previous studies demonstrated that phospholipase C (PLC) caused a rapid and irreversible decrease in skeletal muscle blood flow that paralleled the formation of intravascular aggregates of activated platelets, fibrin, and leukocytes. In this study, flow cytometry demonstrated that PLC stimulated platelet/neutrophil aggregation in a gpIIbIIIa-dependent fashion. Pretreatment of animals with heparin or depletion of leukocytes reduced blood-flow deficits, and aggregate formation caused by PLC. It is concluded that fulminant tissue destruction in gas gangrene results from profound attenuation of blood flow caused by PLC-induced, gpIIbIIIa-mediated formation of heterotypic platelet/polymorphonuclear leukocyte aggregates. Therapeutic strategies that target gpIIbIIIa may prevent vascular occlusion, maintain tissue viability, and provide an alternative to radical amputation for patients with this infection.

A major impact on the study of anaerobic infections. The Wardsworth Anaerobic Bacteriology Manual, developed by Finegold and Colleagues, is a standard reference used extensively throughout the world. He is staff physician in the Infectious Diseases Section of the VA Medical Center West Los Angeles, professor of Medicine and of Microbiology and Immunology at the University of California School of Medicine, Los Angeles, and the current editor of Clinical Infectious Diseases

Anaerobic bacteria comprise facultative, aerotolerant, microaerophilic, and obligate anaerobes. The latter are usually subdivided into moderate and strict according to their sensitivity towards oxygen. Most anaerobic bacteria involved in human infections are moderate obligate anaerobes. Anaerobic bacteria commonly inhabit the mucous membranes and skin of man and various animals. They are prevalent in the oral cavity and pharynx, the gastrointestinal tract, especially the terminal ileum and large bowel, the genitourinary tract orifices, and on the skin. The indigenous microflora is the source of virtually all anaerobic bacteria involved in disease. Exceptions are those caused by Clostridium tetani, Clostridium botulinum and Clostridium difficile. Anaerobic infections are common, although a decrease has been reported during the 1990s in the relative frequencies of properly collected specimens yielding anaerobic bacteria particularly from bacteremia [1]. Nevertheless, anaerobic bacteria are still frequent causes of diseases associated with severe morbidity and high mortality. Since special precautions are needed in collecting, transporting, processing and culturing anaerobic bacteria, they are easily overlooked in the clinical setting. More important, however, is that many laboratories are unable to culture many or most of the anaerobic bacteria commonly present in clinical infections. Even when proper specimens are collected, some hospitals do not have adequate laboratory support for the handling of anaerobic organisms. The aim of the present review is to provide a primer on anaerobic bacteria and anaerobic infections for the uninitiated, emphasizing general principles, treatment and clinical bacteriology.

The objective of this study was to compare ticarcillin/clavulanate given at 3.1 g every 6 hours with imipenem/cilistatin given at 500 mg every 6 hours for the treatment of infections associated with gangrenous or perforated appendicitis. One hundred thirty-seven patients were found to have gangrenous or perforated appendicitis and received the study medication for 3 to 5 days in a double-blinded, randomized manner. Clinical success was similar for the two treatment groups, 96.9 and 95.9 per cent in the ticarcillin/clavulanate and imipenem/cilistatin groups, respectively (P = 0.99; 95% confidence interval for the difference was -5.6% to 7.6%). Bacteriologic success at the end of therapy was similar in the two groups, 100 and 98.4 per cent in the ticarcillin/clavulanate and imipenem/cilistatin groups, respectively (P = 0.99; 95% confidence interval for the difference was -1.8% to 4.7%). The occurrence of adverse events related to treatment was similar for the two groups (P = 0.31) and led to study withdrawal for four patients (one with ticarcillin/clavulanate and three with imipenem/cilistatin). Ticarcillin/clavulanate given at 3.1 g every 6 hours is as effective and as safe as imipenem/cilistatin given at 500 mg every 6 hours for treatment of gangrenous or perforated appendicitis.

ABSTRACT Antimicrobial resistance, including plasmid-mediated resistance, among the species of the Bacteroides fragilis group is well documented. An analysis of the in vitro susceptibility of B. fragilis group species referred between 1995 and 1996 as well as during a 7-year (1990 to 1996), prospective, multicenter survey of over 4,000 clinical isolates of B. fragilis group species was undertaken to review trends in the percent resistance to and geometric mean MICs of the antibiotics tested. There was a trend toward a decrease in the geometric mean MICs of most β-lactam antibiotics, while the percent resistance to most agents was less affected. Within the species B. fragilis, the geometric mean MICs showed significant (P < 0.05) decreases for piperacillin-tazobactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, cefotetan, and cefmetazole; a significant increase was observed for clindamycin and cefoxitin. For the non-B. fragilis species, a significant decrease in the geometric mean MICs was observed for meropenem, ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, and cefmetazole; a significant increase was observed for cefoxitin. Significant increases in percent resistance were observed within theB. fragilis strains for ticarcillin and ceftizoxime and within the non-B. fragilis isolates for cefotetan. Significant increases in percent resistance among all B. fragilis group species were observed for clindamycin, while imipenem showed no significant change in resistance trends. The trend analysis for trovafloxacin was limited to 3 years, since the quinolone was tested only in 1994, 1995, and 1996. During the 7 years analyzed, there was no resistance to metronidazole or chloramphenicol observed. The data demonstrate that resistance among the B. fragilisgroup species has decreased in the past several years, the major exception being clindamycin. The majority of the resistance decrease has been for the β-lactams in B. fragilis, compared to other species. The reasons for these changes are not readily apparent.

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During our studies of the bacterial etiology of appendicitis, we often isolated a previously undescribed anaerobic gram-negative rod. This organism resembled the Bacteroides fragilis group because it was resistant to bile and because of its special-potency-disk pattern (resistant to vancomycin, kanamycin, and colistin), but unlike the B. fragilis group, this bacterium produced brown pigment on media containing hemolysed blood. The cellular fatty acid pattern, with iso-C15:0 being the predominant acid, was most closely related to the fatty acid profile of Porphyromonas species; however, this organism differed from Porphyromonas species by being bile-resistant and by not producing butyrate as a metabolic endproduct. Enzymatic activities of 31 isolates were determined with use of the API ZYM system and Rosco diagnostic tablets. These profiles were different from those of Prevotella, Porphyromonas, and related species. This organism was isolated from 40% of appendiceal tissue samples; no obvious qualitative or quantitative difference in rates of isolation from patients with inflamed or normal appendices was observed.

Table 1.Strains used in a study to identify Porphyromonas endo-Porphyromonas endodontalis has been isolated almost excludontalis -like organisms.sively from the oral cavity.P. endodontalis is a key pathogen in endodontic infections such as infected root canals and abscesses Organism AHN no.WAL no.Source [1].We report herein the isolation of P. endodontalis-like organisms (PELOs) from extraoral sources.These organisms have a PELO 11186 . . .Feces close phenotypic resemblance to oral isolates of P. endodontalis; PELO 11239 . . .Feces however, their taxonomic position warrants reassessment.The aim PELO 11253 . . .Feces of this study was to describe the isolation and characterization of PELO 11260 . . .FecesPELOs and the laboratory tests useful in their identification.

Journal Article Pasteur: The Anaerobic Life and the Anaerobes Get access Madeleine Sebald, Madeleine Sebald Unité des Anaérobies, Institut Pasteur, Paris, France; and Medical Serrice, Wadsworth Veterans Affairs Medical Center, and Department of Medicine, UCLA School of Medicine, Los Angeles, California Reprints or correspondence: Dr. Madeleine Sebald, Unité des Anaérobies, Institut Pasteur, 75724 Paris Cédex 15, France. Search for other works by this author on: Oxford Academic PubMed Google Scholar Sydney M. Finegold Sydney M. Finegold Unité des Anaérobies, Institut Pasteur, Paris, France; and Medical Serrice, Wadsworth Veterans Affairs Medical Center, and Department of Medicine, UCLA School of Medicine, Los Angeles, California Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 20, Issue Supplement_2, June 1995, Page S111, https://doi.org/10.1093/clinids/20.Supplement_2.S111 Published: 01 June 1995

The optimal antibacterial regimen for the treatment of patients with mixed intra-abdominal infections remains to be established. Since advanced (gangrenous and perforated) appendicitis with peritonitis probably represents the most reproducible clinical model of this disease process, we performed a randomised double-blind study comparing 2 single-agent regimens (ceftizoxime 2g every 12 hours and cefoxitin 2g every 6 hours) in the treatment of advanced appendicitis with peritonitis. 109 evaluable patients (84 male, 25 female) aged 12 to 70 (mean 28) years were randomised, 53 to ceftizoxime and 56 to cefoxitin. 75 patients (69%) had perforation and 34 (31%) exhibited gangrene, with the mean duration of abdominal pain and mean white blood cell (WBC) count on admission being significantly greater in the group with perforation [71 vs 46 hours and 16.9 vs 14.8 ×109/L, respectively (p < 0.05)]. Bacteria were recovered from the peritoneal cultures of all patients, with a mean of 3.3 aerobes and 8.8 anaerobes per specimen, representing a 600% increase in bacterial recovery compared with previous reports. The clinical cure rate was 51 of 53 (96%) for ceftizoxime vs 47 of 56 (84%) for cefoxitin (p = 0.06), or 90% overall. We conclude that single-agent antibacterial therapy with either of these 2 drugs is safe and very effective in patients with advanced appendicitis with peritonitis, and that the number of bacteria associated with this condition is much greater than previously believed.