Clinical Clues to Diagnosis of Anaerobic Infections

Infections caused by anaerobic bacteria are common and may be serious and life-threatening. Anaerobes are the predominant components of the bacterial flora of normal human skin and mucous membranes, and are therefore a common cause of bacterial infections of endogenous origin. Infections due to anaerobic bacteria can evolve all body systems and sites (1). The predominant ones include: abdominal, pelvic, respiratory, and skin and soft tissues infections. Because of their fastidious nature, they are difficult to isolate from infectious sites and are often overlooked. Failure to direct therapy against these organisms often leads to clinical failures. Their isolation requires appropriate methods of collection, transportation, and cultivation of specimens. Treatment of anaerobic bacterial infection is complicated by the slow growth of these organisms, which makes diagnosis in the laboratory possible only after several days, by their often polymicrobial nature and by the growing resistance of anaerobic bacteria to antimicrobial agents.

The diagnosis of anaerobic infections may be difficult, but is expedited by recognition of certain clinical signs. These signs are summarized in Table 1. Even though many of the clues are not specific, the presence of several of them in a patient can be still suggestive of an anaerobic infection.

Predisposing conditions and bacteriologic hints should alert the clinician, who may apply diagnostic procedures to ascertain the nature of the pathogens and the extent of the infection. Bacteriologic findings suggestive of anaerobic infection are listed in Table 2.

Almost all anaerobic infections originate from the patient's own microflora. Poor blood supply and tissue necrosis lower the oxidation-reduction potential and favor the growth of anaerobes. Any condition that lowers the blood supply to an affected area can predispose to anaerobic infection. Therefore, foreign body, malignancy, surgery, edema, shock, trauma, colitis, and vascular disease may predispose to anaerobic infection. Previous infection with aerobic or facultative organisms also may make the local tissue conditions more favorable for the growth of anaerobic organisms. The human defense mechanisms also may be impaired by anaerobic conditions (2).

ASSOCIATION OF INFECTIONS WITH MUCOSAL SURFACES

The source of bacteria involved in most of the anaerobic infections is the normal indigenous flora of an individual. The mucous surfaces of the child becomes colonized with aerobic and anaerobic flora within a short time after birth (3,4). Anaerobic bacteria are the most common residents of the skin and mucous membrane surfaces (5) and outnumber aerobic bacteria in the normal oral cavity and gastrointestinal tract at a ratio of 10:1 and 1000:1, respectively (6). Examples of these mucous and skin surfaces are the oral, and nasal cavities, the gastrointestinal lumen and the conjunctiva, the skin surfaces of different locations, and the sebaceous glands. It is not surprising, therefore, that a large proportion of anaerobic bacteria that are part of the normal mucous membrane flora can be recovered from infection in proximity to these sites.

The inoculum of organisms that may penetrate into an infectious site such as human bite, or perforated gut, usually is complex and contains a mixture of aerobic or anaerobic flora. Although the inoculum of certain organisms that possess greater pathogenicity such as

TABLE 1 Clues to Diagnosis of an Anaerobic Infection

Infection adjacent to a mucosal surface Foul-smelling lesion or discharge

Classic presentation of an anaerobic infection (e.g., Necrotic gangrenous tissue, gas gangrene, abscess formation) Free gas in tissue or discharges

Bacteremia or endocarditis with no growth on aerobic blood cultures

Infection related to the use of antibiotics effective against aerobes only (e.g., ceftazidime, old quinolones, aminoglycosides, trimethoprim-sulfamethoxazole) Infection related to tumors or other destructive processes Septic thrombophlebitis Infection following animal or human bite

Black discoloration of exudates containing Pigmented Prevotella or Porphyromonas which may fluoresce under ultraviolet light "Sulfur granules" in discharges caused by actinomycosis

Clinical condition predisposing to anaerobic infection (following maternal amnionitis, perforation of bowel, etc.) Source: From Ref. 1.

Bacteroides fragilis can be initially small, they may become the predominant isolates as the infection progresses.

Anaerobes belonging to the indigenous flora of the oral cavity can be recovered from various infections adjacent to that area such as cervical lymphadenitis (7,8); subcutaneous abscesses (9) and burns (10) in proximity to the oral cavity; human and animal bites (11); paronychia (12); tonsillar and retropharyngeal abscesses (13); chronic sinusitis (14); chronic otitis media (15); periodontal abscess (16); thyroiditis (17); aspiration pneumonia (18); empyema (19), and bacteremia associated with one of the above infections (20). The predominant anaerobes recovered in these infections are species of anaerobic gram-negative bacilli including pigmented Prevotella and Porphyromonas, Prevotella oralis, Fusobacterium, and gram-positive anaerobic cocci (Peptostreptococcus spp.) which are all part of the normal flora, the mucous surfaces of the oral, pharyngeal, and sinus flora (Table 3).

A similar correlation exists in infections associated with the gastrointestinal tract. Such infections include peritonitis that develops after rupture of appendix (21), liver and spleen abscesses (22), abscesses and burns (10) near the anus, intra-abdominal abscess (23), and bacteremia associated with any of these infections (20). The anaerobes that predominate in these infections are Bacteroides spp. (predominantly B. fragilis group), clostridia (including Clostridium perfringens), and Peptostreptococcus spp.

Another site where a correlation exists between the normal flora and the anaerobic bacteria isolated from infected sites is the genitourinary tract. These infections include amnionitis, septic abortion, and other pelvic inflammations (24). The anaerobes usually isolated from these sites are species of Prevotella and Fusobacterium and Peptostreptococcus spp. Organisms belonging to the vaginal-cervical flora are also important pathogens of neonatal infections.

TABLE 2 Bacteriological Finding Suggestive of Anaerobic Infection

Inability to grow in aerobic cultures, organisms seen on Gram stain of the original material

Typical morphology for anaerobes on Gram stain

Anaerobic growth on proper media containing antibiotic-suppressing aerobes

No growth or routine bacterial culture ("sterile-pus")

Growth in anaerobic zone of fluid or agar media

Growth anaerobically on media containing paromomycin, kanamycin, neomycin, or vancomycin Gas, foul-smelling odor in specimen or bacterial culture Characteristic colonies on anaerobic plates

Young colonies of pigmented Prevotella and Porphyromonas may fluoresce red under ultraviolet light, and older colonies produce a typical dark pigment Characteristic colonies on agar plates under anaerobic conditions (e.g., Clostridium perfringens, Fusobacterium nucleatum)

Source: From Ref. 1.

TABLE 3 Recovery of Anaerobic Bacteria in Patients3

Pigmented

Prevotella and

Peptostrepto-

Clostridium

Bacteroides

Porphyromonas,

P. bivia and

Fusobac-

Infection

coccus spp.

spp.

fragilis group

Prevotella oralis

P. disien

terium spp.

Bacteremia

1

1

2

1

G

1

Central nervous

2

1

1

2

G

1

system

Head and neck

3

1

1

3

G

3

Thoracic

2

1

1

3

G

3

Abdominal

3

3

3

1

1

1

Obstetric-

3

2

1

1

2

1

gynecology

Skin and soft

2

1

2

2

1

1

tissue

a Frequency of recovery in anaerobic infections: 0 = none, 1 =rare (1-33%), 2=common (34-66%), 3=very common (67-100%).

a Frequency of recovery in anaerobic infections: 0 = none, 1 =rare (1-33%), 2=common (34-66%), 3=very common (67-100%).

FOUL-SMELLING SPECIMEN OR DISCHARGE FROM AN INFECTED AREA

The presence of putrid smell is the most specific clue for anaerobic infection and is caused by-products of metabolic end products of the anaerobic organisms, which are mostly organic acids. However, the absence of a foul-smelling discharge does not exclude anaerobic infection as not all anaerobic bacteria produce it. In deep-seated infections, these odors cannot always be appreciated.

THE PRESENCE OF GANGRENOUS NECROTIC TISSUE

The presence of anoxic conditions can result in the formation of gangrenous necrotic tissue. This anoxic condition predisposes for anaerobic infection, because anaerobes benefit and proliferate under such conditions.

FREE GAS IN TISSUES

Gas formation is caused by the metabolic end products such as amines and organic acids that are released by the multiplying anaerobic organism and is enhanced by anoxic conditions. However, some aerobic organisms, such as Escherichia coli, also can produce gas in infected tissues. The formation of gas can be detected by palpation or by radiographic examination of the involved area.

THE ABSENCE OF GROWTH IN AEROBIC CULTURES OF INFECTED AREAS

The lack of bacterial growth in aerobic cultures is of particular significance in putrid specimens obtained before administration of antimicrobial therapy. This also can occur in anaerobic bacteremia, in which aerobic blood cultures do not reveal the infecting organisms. An additional clue to the presence of anaerobes could be the presence of bacterial forms in properly performed Gram stain preparations in which the aerobic bacterial cultures show no growth. Many laboratories assume that failure to cultivate anaerobes in thioglycolate broth excludes anaerobes from the infection, but thioglycolate broth inoculated in room air would not provide adequate anaerobic conditions. Furthermore, overgrowth of rapid-growing aerobic organisms, which often are present in many mixed infections, may mask the presence of slower growing anaerobes.

INFECTION THAT PERSISTS AFTER ADMINISTRATION OF ANTIBIOTICS

Most anaerobes are susceptible to penicillins, although many anaerobic gram-negative bacilli are resistant to that drug (25). Other commonly used antibiotics to which almost all anaerobes are resistant are the aminoglycosides and the "older" quinolones (i.e. ciprofloxacin). Therefore, persistence or recurrence of an infection in the face of either of these, or other antimicrobial agents to which anaerobes are resistant, should arouse suspicion to the presence of anaerobic bacteria in the infection.

CLINICAL SITUATIONS PREDISPOSING TO ANAEROBIC INFECTION

Any exposure of the sterile body cavity to indigenous mucous surface flora can result in infection. Anaerobes are especially common in chronic infections. Certain infections are very likely to involve anaerobes as important pathogens and their presence should always be assumed. Such infections include brain abscess, oral or dental infections, human or animal bites, aspiration pneumonia and lung abscesses, peritonitis following perforation of viscus, amnionitis, endometritis, septic abortions, tubo-ovarian abscess, abscesses in and around the oral and rectal areas, and pus forming necrotizing infections of soft tissue or muscle. Conditions that decrease the redox potential predispose to anaerobic conditions. The list of these and other general conditions that predispose to anaerobic infection is presented in Table 4. Certain malignant tumors such as colonic, uterine and bronchogenic carcinomas, and necrotic tumors of the head and neck have the tendency to become infected with anaerobic bacteria (26). The anoxic conditions in the tumor and exposure to the endogenous adjacent mucous flora may predispose for these infections.

The newborn, and especially those suffering from fetal distress or are delivered following maternal amniotic infection, are prone to anaerobic infection. Examples of such infections are the occurrence of neonatal pneumonia after aspiration of infected amniotic fluid (27) or the introduction of anaerobic bacteria indigenous to the vaginal-cervical area into the insertion site of the fetal-monitoring needle, an event that can cause scalp abscess and osteomyelitis (28).

ANAEROBIC INFECTIONS AS A CLUE TO MEDICAL CONDITIONS

An anaerobic infection can provide a clue and a warning to the presence of an underlying medical problem. Brain abscess may be due to an underlying dental infection such as

TABLE 4 Clinical Conditions that Predispose to Anaerobic Infection

Reduced redox potential Anoxia or destruction of tissue Foreign body Obstruction and stasis Vascular insufficiency Burns

Infection caused by aerobic bacteria or mycobacteria Tumor Neonatal conditions Maternal aminionitis Fetal distress Fetal monitoring General conditions Collagen vascular disease Corticosteroids Diabetes mellitus Hypogammaglobulinemia Neutropenia Immunosuppression Cytotoxic drug Splenectomy

Malignancy (colon, lung, leukemia, uterus)

Surgery or trauma of oral, gastrointestinal or urogenital areas

Bites

Aspiration of oral secretions

Therapy with antibiotics ineffective against anaerobes periodontitis or periopical abscess and lung abscess can be a clue to underlying bronchogenic malignancy. Malignant disease can be first detected because of an anaerobic infection. Malignancy or other process in the colon can induce sepsis with Clostridium spp. (especially Clostridium septicum) (29) or arthritis caused by Eubacterium lentum (30) or emerge first as abdominal wall myonecrosis (31). Capnocytophaga which is member of the oral microflora can cause sepsis in patients with leukemia (32).

Malignancy is often associated with the development of local or systemic anaerobic infection (26). Systemic infections may reflect compromises in host defenses at several levels. Infections may be due to alterations in local conditions at the site of the neoplasm, allowing bacteria to gain access to the blood. The humural immunity, the bactericidal plasma action, and the intracellular killing properties of neutrophils, monocytes, and macrophages may be compromised (33-36).

Local conditions at the neoplasm site can also predispose to infection. The condition in the tumor may predispose for an anaerobic-aerobic infection. Tumors may outgrow their blood supply and become necrotic. The lowered oxygen tension may, therefore, favor the growth of anaerobic organisms. A tumor can extend into surrounding tissues, causing barrier breakthrough onto mucosal and epithelial surfaces. Alimentary tract inflammatory and focal necrosis can be found in the colonic mucosa in leukemia (37-39) and after cancer chemotherapy (40). Another factor underlying the increased susceptibility of patients with cancer to infection and bacteremia is their overall poor nutritional status (34).

Insufficient blood supply of rapidly growing solid tumors can lead to the presence of tissue hypoxia. Vaupel (41) demonstrated that tumor oxygenation powerfully predicts the prognosis of patients receiving radiotherapy for intermediate and advanced stage cancer of the uterine cervix. Hypoxia is also known to decrease the efficiency of the currently used anticancer modalities like surgery, chemotherapy, and radiotherapy. Therefore, hypoxia seems to be a major limitation in current anticancer therapy.

Clostridium spp. possesses a selective colonization ability of hypoxic/necrotic areas within the tumor. The anaerobic environment within the tumor provided this oxygen sensitive organism with adequate conditions for proliferation. The use of non-pathogenic Clostridium spp. to deliver toxic agents to the tumor cells is under investigation takes advantage of this unique phenomena (42).

Anaerobic glycolysis is significantly increased in tumor tissue, with a resulting accumulation of lactic acid in this tissue and its environment. Spores of non-pathogenic Clostridium spp. can localize and germinate in neoplasms and produce extensive lysis of tumors without concomitant effect on normal tissue (43). Clostridium septicemia originating from an infection within tumor lesions has been reported (44-47). C. septicum infection is highly associated with the presence of a malignancy, either known or occult at the time infection occurs. Occult tumors are mostly situated in the cecal area of the bowel. Predisposing conditions for this type of infection are hematologic malignancies, colon carcinoma, neutropenia, diabetes mellitus, and disruption of the bowel mucosa (48,49).

Bacteremia due to gram-negative anaerobic bacilli is also common in patients with solid tumors (47). Felner and Dowell (50) reported that 57 of 250 (23%) of patients with "Bacteroides" (B. fragilis group, Fusobacterium spp., and pigmented Prevotella spp.) bacteremia had malignancy as a predisposing condition. The most common one were adenocarcinoma of the colon and uterine or cervical tumors.

Many bacterial infections in adults and children with malignancies are polymicrobial in nature (47). The bacteria isolated from many of these patients originated from the normal flora of the skin or the mucous membrane at or adjacent to the site of the infection.

CONCLUSIONS

The diagnosis of anaerobic infections can be expedited by the early recognition of certain clinical signs. Predisposing conditions and microbiological hints can alert the physician to the presence of anaerobic infection. Most anaerobic infections originate from the patient's own endogenous microflora. Poor blood supply and tissue necrosis lower the oxidation-reduction potential and can favor the growth of anaerobic bacteria. Conditions that lower the local blood supply can predispose to anaerobic infection at that site. These conditions include: trauma, foreign body, malignancy, surgery, edema, shock, colitis, and vascular disease. An anaerobic infection can provide a clue and a warning to the presence of an underlying medical problem.

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  • Audrey
    What are the characteristics or clues to an anaerobic infection?
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