Infections caused by anaerobic bacteria are common, and may be serious and life-threatening. Anaerobes predominant in the bacterial flora of normal human skin and mucous membranes, and are a common cause of bacterial infections of endogenous origin. Infections due to anaerobes can evolve all body systems and sites. The predominate ones include: abdominal, pelvic, respiratory, and skin and soft tissues infections. Because of their fastidious nature, they are difficult to isolate 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 only possible after several days, by their often polymicrobial nature and by the growing resistance of anaerobic bacteria to antimicrobial agents.

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Predisposing conditions and Clinical Clues for Diagnosis of Anaerobic Infections

CONDITIONS PREDISPOSING TO ANAEROBIC INFECTIONS

Exposure of a sterile sites to high inoculum of indigenous mucous membrane flora predisposing to anaerobic infections. Poor blood supply and tissue necrosis that lower the oxidation-reduction potential favours the growth of anaerobic bacteria. Any condition that lowers the blood supply to an affected area can predispose to such infection. These include: trauma, foreign body, malignancy, surgery, edema, shock, colitis and vascular disease. Other predisposing conditions include diabetes mellitus, splenectomy, immunosuppression, hypogammaglobinemia, neutropenia, leukaemia, collagen vascular disease and cytotoxic drugs. Previous infection with aerobic or facultative organisms may make the local tissue conditions favourable for the growth of anaerobic bacteria. The human defences can be impaired by anaerobic conditions and anaerobic bacteria. The noted effects include impairments in phagocytosis and intracellular killing (often caused by encapsulated anaerobes1 and by succinic acid produced by Bacteroides spp.), inhibition of chemotaxis (by Fusobacterium, Prevotella and Porphyromonas spp.), degradation of serum proteins by proteases (by Bacteroides spp.) and production of leukotoxins (by Fusobacterium spp.).2
Suppuration, abscess formation, thrombophlebitis and gangrenous destruction of tissue associated with gas formation are the hallmarks of anaerobic infection. Anaerobes are especially common in chronic infections, and after failure of therapy with ineffective antimicrobials (i.e. aminoglycosides, trimethoprim–sulfamethoxazole and earlier quinolones). The diagnosis of anaerobic infections may be difficult, but is expedited by recognition of certain clinical signs noted in Table 1. Even though many of the clues are not specific the presence of several of them together can be suggestive.


Certain infections are likely to involve anaerobes, and their presence should always be assumed. These include: brain abscess, oral or dental infections, bites, aspiration pneumonia, lung abscess, peritonitis after perforation of viscus, amnionitis, endometritis, septic abortions, tubo-ovarian abscess, abscesses in and around the oral and rectal areas, pus-forming necrotizing infections of soft tissue or muscle, and post surgical infections following procedures on the oral or gastrointestinal tract or female pelvic area. Certain solid malignant tumors, such as colon, uterine and bronchogenic carcinomas, and necrotic tumors of the head and neck, have the tendency to become infected with anaerobic bacteria.3 The anoxic conditions in the tumour and exposure to the endogenous adjacent mucous flora may predispose to these infections.

                                             

                                      
                                                  Spectrum of anaerobic infections

REFERENCES

1.   Brook I, Myhal LA, Dorsey HC. Encapsulation and pilus formation of Bacteroides sp. J Infect 1991;25:251–7.
2.   Hofstad T. Virulence determinants in non-spore-forming anaerobic bacteria. Scand J Infect Dis 1989;(suppl62):15–24.
3.    Brook I, Frazier EH. Aerobic and anaerobic infection associated with malignancy.
Support Care Cancer. 1998;6:125-31.








CLINICAL CLUES TO DIAGNOSIS OF ANAEROBIC INFECTIONS

The diagnosis of anaerobic infections may be difficult, but is expedited by recognition of certain clinical signs1 noted in Table 1. Even though many clues are not specific the presence of some of them together can be suggestive of an anaerobic infection.

Table 1: Clues to diagnosis of an anaerobic infection.
1.   Infection adjacent to a mucosal surface
2.   Foul-smelling lision or discharge
3.   Classic presentation of an anaerobic infection (e.g. Necrotic gangrenous tissue, gas gangrene, abscess formation)
4.   Free gas in tissue or discharges
5.   Bacteremia or endocarditis with no growth on aerobic blood cultures
6.   Infection related to the use of antibiotics effective against aerobes only (e.g. ceftazidime, old quinolones, aminoglicosides, trimetoprim-sulfamethoxazole)
7.   Infection related to tumors or other destructive processes
8.   Septic thrombophlebitis
9.   Infection following animal or human bite
10. Black discoloration of exudates containing Pigmented Prevotella or Porphyromonas which may fluoresce under ultraviolet light
11. “Sulfur granules” in discharges caused by actinomycosis
              12. Clinical condition predisposing to anaerobic infection (i. e. gut perforation)

Predisposing conditions and bacteriologic hints should alert the physician, 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.

Table 2. Bacteriological finding suggestive of anaerobic infection. .1,2
1.   Inability to grow in aerobic cultures, organisms seen on Gram stain of the original material
2.   Typical morphology for anaerobes on Gram stain
3.   Anaerobic growth on proper media containing antibiotic-suppressing aerobes
4.   No growth or routine bacterial culture (“sterile-pus”)
5.   Growth in anaerobic zone of fluid or agar media
6.   Growth anaerobically on media containing puromomycin Kanamycin, neomycin or vancomycin.
7.   Gas, foul-smelling odor in specimen or bacterial culture
8.   Characteristic colonies on anaerobic plates
9.   Young colonies of Pigmented Prevotella and Porphyromonas may fluoresce red under ultraviolet light, and older colonies produce a typical dark pigment
10. Characteristic colonies on agar plates under anaerobic conditions (e.g. Clostridium perfringensFusobacterium nucleatum).

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 anaerobic bacteria. Any condition that lowers the blood supply to an affected area of the body can predispose to anaerobic infection. Therefore, trauma, foreign body, malignancy, surgery, edema, shock, 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 bacteria.

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 anaerobic bacteria. Any condition that lowers the blood supply to an affected area of the body can predispose to anaerobic infection. Therefore, trauma, foreign body, malignancy, surgery, edema, shock, 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 bacteria.

The human defense mechanisms also may be impaired by anaerobic conditions. The ability of polymorphonuclear leukocytes to kill C. perfringens is lowered in anaerobic conditions2; however, another report demonstrated their ability to eliminate potential anaerobic pathogens even under anaerobic conditions.


Anaerobes belonging to the indigenous flora of the oral cavity can be recovered from various infections adjacent to that area, such as cervical lymphadenitis; subcutaneous abscesses and burns in proximity to the oral cavity; human and animal bites; paronychia; tonsillar and retropharyngeal abscesses; chronic sinusitis; chronic otitis media; periodontal abscess; thyroiditis; aspiration pneumonia; and bacteremia associated with one of the above infections. The predominant anaerobes recovered in these infections are species of anaerobic gram negative bacilli including pigmented Prevotella and Porphyromonas, P. oralis, Fusobacterium, and Gram-positive anaerobic cocci, 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 following rupture of appendix, liver abscess, abscess and burns near the anus, intraabdominal abscess and bacteremia associated with any of these infections. The anaerobes that predominate in these infections are Bacteroides species (predominantly B. fragilis group), clostridia (including C. perfringens), and Gram-positive anaerobic cocci.

Another site with a correlation between the normal flora and the anaerobic bacteria recovered from infected sites is the genitourinary tract. The infections involved are amnionitis, septic abortion, and other pelvic inflammations. The anaerobes usually recovered from these sites are species of Prevotella and Fusobacterium and Gram-positive anaerobic cocci. Organisms belonging to the vaginal-cervical flora are also important pathogens of neonatal infections.


                       Number of anaerobic bacteria in the gastrointestinal tract




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.
 Anaerobic bacteria are the most common residents of the skin and mucous membrane surfaces6 and outnumber aerobic bacteria in the normal oral cavity and gastrointestinal tract at a ratio of 10:1 and 1000:1, respectively.7 Examples of these mucous and skin surfaces are the oral, nasal, and sinus 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 anaerobes that are part of the normal mucous membrane flora can be recovered from infection in proximity to these sites.



ASSOCIATION OF INFECTIONS WITH MUCOSAL SURFACES

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 B. fragilis, can be initially small, they may become the predominant isolates as the infection evolves.

Table 3       Recovery of anaerobic bacteria in patients



Infection


Peptostrepto-coccus
 sp.


Clostridium 
sp.

Bacteroides fragilis 
group
Pigmented Prevotella and Porphyromonas P. oralis


P. bivia P. disien


Fusobacterium 
sp.







Bacteremia
1
1
2
1
0
1
Central nervous system
2
1
1
2
0
1
Head and neck
3
1
1
3
0
3
Thoracic
2
1
1
3
0
3
Abdominal
3
3
3
1
1
1
Obstetric-gynecology
3
2
1
1
2
1
Skin and soft tissue
2
1
2
2
1
1








Frequency of recovery in anaerobic infections: 0 = none, 1 = rare (1% to 33%), 2 = common (34% to 66%), 3 = very common (67% to 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 believed to be caused by products of metabolic end products of the anaerobic organisms, which are mostly organic acids. It must be remembered that 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.


FREE GAS IN TISSUES: Gas formation is caused by the metabolic end products released by the growing anaerobic organism and is enhanced by anoxic conditions. 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.







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 aerobes
Tumor


Neonatal conditions
Maternal aminionitis
Fetal distress
Fetal monitoring


General conditions
Collagen vascular disease
Corticosteroids
Diabetes mellitus
Hypogammaglobulinemia
Neutropenia
Immunosuppression
Cytotoxic drug
Splenectomy
Malignancy (color, lung, leukemia, uterus)
Surgery or Trauma of oral, gastrointestinal or uro-genital areas.
Bites
Aspiration
Therapy with antibiotics inefective against anaerobes


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 periodontitis or periopical abscess and lung abscess can be a clue to underlying brochogenic malignancy. Malignant disease can be first detected because of an anaerobic infection. Malignancy or other process in the colon can induce spesis with Clostridium sp. (especially Clostridium septicum29, or arthritis caused by Eubacterium lentum or emerge first as abdominal wall myonecrosis. Leukemia can generate Capnocytophaga sepsis.


REFERENCES

1. Finegold, S.M.: Anaerobic bacteria in human disease. New York, 1977, Academic Press.
2. Duerden BI.: Virulence factors in anaerobes. Clin Infect Dis.1994;18 Suppl 4:S253. 





CLINICAL SITUATIONS PREDISPOSING TO ANAEROBIC INFECTION

Exposure of the sterile body cavity to indigenous mucous surface flora will 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. ( 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. The anoxic conditions in the tumor and exposure to the endogenous adjacent mucous flora may predispose for these infections.





                              Anaerobes of the normal flora spreading after perforation 

INFECTION THAT PERSISTS AFTER ADMINISTRATION OF ANTIBIOTICSMost anaerobes are susceptible to penicillins, although many anaerobic gram negative bacilli are resistant to that drug. Other commonly used antibiotics to which almost all anaerobes are resistant are the aminoglycosides and the older quinolones. 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.

NO GROWTH IN AEROBIC CULTURES OF INFECTED AREASThe lack of 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 will 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.

THE PRESENCE OF GANGRENOUS NECROTIC TISSUEThe presence of anoxic conditions can result in the formation of gangrenous necrotic tissue. This anoxic condition predisposes for anaerobic infection, because anaerobes thrive under such conditions.