Intra-Abdominal Anaerobic Infections: Bacteriology and Therapeutic Potential of Newer Antimicrobial Carbapenem, Fluoroquinolone, and Desfluoroquinolone Therapeutic Agents

SUPPLEMENT ARTICLE Intra-Abdominal Anaerobic Infections: Bacteriology and Therapeutic Potential of Newer Antimicrobial Carbapenem, Fluoroquinolone, and Desfluoroquinolone Therapeutic Agents Ellie J. C. Goldstein R. M. Alden Research Laboratory, Santa Monica, and UCLA School of Medicine, Los Angeles, California Intra-abdominal infection includes a wide variety of markedly different conditions, ranging from primary and secondary peritonitis to intrahepatic infection to diverticulitis, appendicitis, and intra-abdominal abscess, that are lumped together because of anatomical coincidence. The most serious infections are due to viscus inflammation and perforation and almost always involve a mixture of aerobic and anaerobic intestinal flora. The intestinal colonic flora contains 1012 bacteria/ gm of feces, which are predominantly anaerobic, and anaerobic species outnumber aerobes by 1000 to 1. Although anaerobes are ubiquitous commensals and aid in “colonization resistance,” some genera and species are also consummate opportunistic pathogens. Bacteroides fragilis, which accounts for only 0.5% of the normal colonic flora, is recognized as the single most important anaerobic pathogen. Properties that contribute to its virulence include its capsular polysaccharide, adherence potential, piliation, and toxin production. All colorectal surgeons who responded to a survey [1] reported the use of preoperative bowel preparations prior to surgery, and 86.5% add oral and parenteral antimicrobials to the regimen to prevent infection. Once peritoneal contamination occurs, the body attempts to defend against this invasion via lymphatic clearance, phagocytosis, sequestration of fibrin, and anatomical localization. Anaerobes act synergistically with facultative organisms to induce abscess formation more readily than either mixtures of facultative or anaerobic bacteria alone and may protect the aerobes from phagocytosis and other body defenses. The facultative bacteria also promote the infectious process by lowering the environment’s oxidation-reduction potential and facilitating the growth of anaerobes. BIPHASIC MIXED INFECTION Reprints or correspondence: Dr. Ellie J. C. Goldstein, 2021 Santa Monica Blvd., Suite 740 East, Santa Monica, CA 90404 (). Clinical Infectious Diseases 2002; 35(Suppl 1):S106–11  2002 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2002/3505S1-0020$15.00 S106 • CID 2002:35 (Suppl 1) • Goldstein Beginning in 1973, Onderdonk et al. [2, 3] developed an animal model to simulate intra-abdominal sepsis. They noted that a biphasic infection developed. After Intra-abdominal infections are biphasic, synergistic processes with early peritonitis and bacteremia due to aerobes and a later abscess component due to anaerobes. Although Bacteroides fragilis is the most commonly recognized pathogen, other anaerobes, including other members of the B. fragilis–group species, are major components of infection. Anaerobic bacteremia is often associated with an intra-abdominal source. New antimicrobial agents with anaerobic activity are in various stages of development for the therapy of intraabdominal infections. The in vitro activity and the currently available sparse clinical data are reviewed for a new carbapenem (ertapenem), several fluoroquinolones (trovafloxacin, moxifloxacin, and gemifloxacin), and a desfluoroquinolone (BMS-284756). RELATIVE FREQUENCY OF ANAEROBES B. fragilis is one of the most recognized anaerobic pathogens and is the anaerobe most often isolated from anaerobic bacteremia as well as intra-abdominal infections. Yet it is but one member of a group of isolates that include other virulent pathogens such as Bacteroides thetaiotaomicron, Bacteroides distasonis, Bacteroides vulgatus, Bacteroides ovatus, and Bacteroides uniformis, and each has its own ecological niche. In a study done at 2 community medical centers, Goldstein et al. [5] noted that the B. fragilis group accounted for 34.6% of all anaerobes isolated (relative frequency), of which B. fragilis itself was the most common isolate and accounted for 18.9%. B. fragilis was more likely to be associated with bacteremia and accounted for 46% of intra-abdominal isolates. Although community hospital laboratories do not usually attempt to isolate or identify the majority of anaerobes in clinical mixed specimens because of costs and other considerations, a recent study from 17 countries worldwide on the anaerobic bacteriology of intra-abdominal infections showed similar results [6]. We [6] isolated 1001 anaerobes from 427 clinical specimens that yielded an average of 3 aerobes (range, 0–9) and 2.3 anaerobes (range, 0–13) per specimen. The B. fragilis–group species accounted for 455 (45.5%) of 1001 anaerobes isolated, of which B. fragilis accounted for 134 strains (135/1001, 13.4%) and was present in 31.4% of all intra-abdominal specimens. These results compared favorably with those of a survey of the literature [7] that found an overall mean of 1.2 aerobes and 0.9 anaerobes per patient specimen. Bennion et al. [7] studied 30 patients with gangrenous (n p 12) and perforated (n p 18) appendicitis and found 2.7 aerobes and 7.4 anaerobes recovered per specimen. Escherichia coli was by far the most frequent aerobe isolated and was present in 92% and 78% of gangrenous and perforated appendicitis specimens, respectively. B. fragilis was found in 7 (58%) of 12 cases with gangrenous appendicitis and in 15 (83%) of 18 of cases of perforated appendicitis. However, their specimens included appendiceal tissue, although they excluded the lumen as well as peritoneal fluid and abscess contents. Brook [8] found similar results for children with perforated appendicitis. In their study, Bennion et al. [7, 9, 10] isolated a previously undescribed and distinct anaerobic bacteria, now named Bilophila wadsworthia, in approximately half the patients. Using many of these same cohort of patients, Baron et al. [11] compared the microbiology of acute and complicated appendicitis with several controls and concluded that “some bacteria traverse the intact appendiceal wall prior to perforation and that progressive infection and subsequent tissue damage and necrosis” allows increased genera and species of bacteria to traverse into the peritoneal cavity. Amazingly, “on a population basis, diagnosis of appendicitis has not improved with the availability of advanced diagnostic testing” [12]. Approximately 2 million intra-abdominal procedures are performed each year in the United States. If one estimates that there is a 15% infection rate, including a 4% incidence of abscess formation, it has been extrapolated that the yearly economic impact of abscess alone is 1$1 billion [3]. ASSOCIATED BACTEREMIA Anaerobic bacteremia has long been associated with intraabdominal processes. It accounts for ∼4% (0.5%–9%) of all bacteremias or ∼1 case per 1000 admissions, with various geographic, demographic, and especially age-rela (...truncated)