Anaerobic bacteria can cause a variety of endogenous infections [1]. Because of their persistent nature, they are difficult to isolate from infection sites and are often overlooked [2]. Moreover, anaerobes play a key role in maintaining the balance between the host and its colonizing organisms; anaerobic infections occur when the harmonious relationship between the host and bacteria has been disrupted. Mixed infections may arise in the head and neck region (e.g., chronic sinusitis, chronic otitis media, Ludwig's angina, and periodontal abscesses) [3]. Brain abscesses and subdural empyema are the most common anaerobic infections of the central nervous system [4,5]. Anaerobes are also responsible for pleuropulmonary diseases, such as aspiration pneumonia, necrotizing pneumonia, lung abscess, and empyema [6]. In addition, these organisms play an important role in various intra-abdominal infections, such as peritonitis and intra-abdominal and liver abscesses. They are frequently isolated in female genital tract infections, such as salpingitis, pelvic peritonitis, tuboovarian abscess, vulvovaginal abscess, septic abortion, and endometritis. Anaerobic bacteria are also often found in bacteremia and infections of the skin, soft tissues, and bones [1,2]. Their isolation requires appropriate methods of collection, transportation, and cultivation of specimens [7]. Treatment is complicated by their slow growth, polymicrobial nature, and growing resistance to antimicrobial agents. Antimicrobial therapy is often the only form of treatment required, or may be an important adjunct to a surgical approach. Because anaerobes are generally recovered in association with aerobic organisms, the choice of antimicrobial agents should provide coverage for both types of pathogens [8].

Despite a relatively low incidence, anaerobic infection remains associated with significant mortality rates. Recent estimates of case fatality rates in patients with clinically significant anaerobic bacteremia range from 25% to 44% [9]. The aims of this study were to determine the clinical features of a broad range of obligate anaerobic organisms isolated from, for example, blood, cerebrospinal fluid, peritoneal fluid, and pleural fluid, and to define the factors independently associated with mortality.

The study was conducted at Severance Hospital at Yonsei University College of Medicine in Seoul, Korea, from January 1996 to December 2003. The facility is a 1,544-bed, tertiary care referral center with hematopoietic stem cell and solid organ transplant specialty services. This study examined 1,050 consecutive adult patients (>17 years old), with 3,169 specimens from sterile fluid and abscess cultures for anaerobic bacteria that were retrospectively identified from clinical microbiology records. Following the first positive anaerobic culture, outcome data were collected from the patients' medical and clinical microbiology laboratory records for 30 days, until discharge or death. The data were based on mortality within 30 days following the first positive blood culture.

The primary endpoint was death, recorded as the number of days after detection of the positive culture results for anaerobic bacteria. The following variables were assessed: personal information (i.e., age and sex), dates of admission and discharge, mode of acquisition (nosocomial or community-acquired), type of infection (polymicrobial or monomicrobial), source of infection, culture results, types of surgeries and procedures performed during hospitalization, diagnosis at discharge, and presence of concurrent underlying disease (e.g., heart, liver, lung, or kidney disease, hypertension, diabetes, malignancy, immunosuppression). The presence of an underlying disease was based on the description made by the physician. Each disease variable was similarly defined; a patient was only considered to have a disease if it was documented as ongoing at the time of the positive culture results. Immunosuppression was said to be present if the patient had a history of solid organ transplant, AIDS, pregnancy, or was undergoing high-dose steroid therapy.

Specimens for anaerobic cultures were primarily biopsy samples or needle aspirates; swabs made up only a minor part of the specimens. All specimens were transported and incubated in anaerobic systems. Colonies present on blood agar media were evaluated through aerotolerance tests, catalase tests, Gram staining, and susceptibility tests. Sources of infection were determined by radiological, surgical, or microbiological evidence of barrier compromise or infectious pathology, such as abscess or necrosis. The origin of bacteremia was also defined by radiological, surgical, or microbiological evidence. A case was designated bacteremia if no other proven focus was discovered.

In this study, no evidence of anaerobic infection was detected in brain abscess specimens. Based on the National Nosocomial Infection Surveillance System (NNISS) guidelines, the infection was deemed to be nosocomial if a positive culture was drawn more than 48 h following admission to the hospital [10]. Appropriate coverage was defined as culture-directed antibiotic coverage given at adequate doses. Inappropriate coverage was defined as non-culture-directed coverage at inadequate doses, but was deemed acceptable if it was non-culture-directed (especially when cultures were negative) but showed signs of clinical improvement.

The results were expressed as the mean±standard deviation (SD), or as a proportion of the total number of patients or isolates. For continuous variables, mean values were compared using a two- sample t-test for independent samples. Differences in proportions were compared using a χ² test. All tests of significance were two-tailed and α was set at 0.05. Mortality was evaluated using univariate and multivariate Cox proportional hazard models. All statistical analyses were performed using the SPSS software program (version 12.0; SPSS Inc., Chicago, IL, USA).

Neoplasms, hematologic disorders, organ transplant, recent surgery, diabetes mellitus, and the use of cytotoxic agents or corticosteroids are predisposing factors for anaerobic infection [2]. This study also showed that anaerobic infections often occurred in patients with cancer when the balance between the host and bacteria was disrupted.

In many patients, pain and pus discharge at the affected site were the chief complaints, whereas few patients presented with shock. Consistent with the findings of Cheon et al. [11], the most common presenting symptom in bacteremia patients was fever (70%).

The appropriate management of anaerobic infection depends on suspicion and appropriate documentation of the bacteria causing infection [12]. In this study, inappropriate anaerobic antibiotics prescriptions at the time of diagnosis (p=0.014) and the lack of postoperative antibiotics (p=0.019) were associated with a poor prognosis resulting in mortality. Regarding the use of antibiotics, Hecht noted that antibiotic-resistant anaerobic bacteria have become increasingly recognized as a confounding factor in the selection of therapeutic agents [13]. Although appropriate therapy for anaerobic infections has been associated with significant reductions in mortality, most clinical laboratories still do not perform routine anaerobic susceptibility tests [14,15]. In a previous 8-yr study, resistance to antimicrobial agents, such as piperacillin, cefotaxime, and clindamycin, was not uncommon among 913 clinical isolates of B. fragilis group organisms, and antimicrobial susceptibility testing was deemed necessary before using one of these drugs [16]. Thus, concentrating on an appropriate narrow-spectrum of antibiotics is important.

Procedures such as abscess drainage, necrotic tissue debridement, and closed-space infection decompression are important adjuncts to a medical approach [12]. However, this study did not find a correlation between surgical intervention and mortality.

Shin et al. [17] reported that B. fragilis and Peptostreptococcus magnus were most frequently isolated in anaerobic bacterial infections. However, in this study, the most common pathogens were B. fragilis (41.8%) followed by Clostridium spp. The most common concomitant aerobic isolate was E. coli, which is why a relationship between the development of intestinal tract cancer and intra-abdominal infection was postulated, although the results reported here were not statistically significant.

This study, which examined patients with infections due to a broad range of anaerobic pathogens, found that age and liver disease were strong, independent risk factors for mortality in multivariate analysis. Crude rather than attributable mortality was reported because the relative contribution of anaerobic infections to the overall mortality rate could not be reliably ascertained. The data demonstrate a 29.7% crude mortality rate for clinically significant anaerobic infections. The majority of previous studies on patients with anaerobic infections, which included a broad range of anaerobic pathogens, also reported mortality as crude mortality rates and published estimates ranging from 25% to 44% [9,18]. In several cases, mortality was assessed with reference to discharge from the hospital, or the interval of antibiotic treatment [18].

The present study provides a recent perspective on the clinical significance of infections due to a broad range of anaerobic species. When combined with careful clinical assessment, this information may be helpful in determining the clinical significance of cultures with anaerobic organisms. The strength of this study is the diversity of the study population and the relatively large sample size examined.

The present study, however, has certain limitations. First, as with any retrospective review, potential for selection bias and data omission exists. Second, not all analyzed variables were necessarily included in the present study; thus, both liver disease and the severity of illness should be included as independent variables in future studies to confirm their association with mortality. Despite these limitations, strong and independent associations were demonstrated among age, underlying liver disease, and mortality.