Abstract Anaerobes have been involved in many different types of urinary tract infection. This review describes the microbiology, diagnosis and management of urinary tract and genito-urinary suppurative infections caused by anaerobic bacteria. The types of infections of the urinary tract in which anaerobes have been involved include para- or periurethral cellulitis or abscess, acute and chronic urethritis, cystitis, acute and chronic prostatitis, prostatic and scrotal abscesses, periprostatic phlegmon, ureteritis, periureteritis, pyelitis, pyelonephritis, renal abscess, scrotal gangrene, metastatic renal infection pyonephrosis, perinephric abscess, retroperitoneal abscess and other infections. The anaerobes recovered in these studies were Gram-negative bacilli (including Bacteroides fragilis and pigmented Prevotella and Porphyromonas sp.), Clostridium sp., anaerobic Gram-positive cocci and Actinomyces sp. In many cases, they were recovered mixed with coliforms or streptococci. The recovery of anaerobes requires the administration of antimicrobial therapy that is effective against these organisms. These antimicrobials include metronidazole, chloramphenicol, clindamycin, a carbapenem, cefoxitin and the combination of a penicillin and a beta-lactamase inhibitor. Percutaneous drainage, open surgical drainage or nephectomy might be indicated for abscesses.
Infections caused by anaerobic bacteria are common and can be serious and life threatening. The recent increased recovery of these organisms has led to greater appreciation of the role anaerobes play in infections at all body sites, including the urinary and genito-urinary tracts.
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.1 Because of their fastidious nature, these organisms are difficult to isolate from infectious sites and are often overlooked. Their exact frequency is difficult to ascertain because of the inconsistent use of adequate methods for their isolation and identification. The lack of directing adequate therapy against these organisms might lead to clinical failures. Their isolation requires appropriate methods of collection, transportation and cultivation of specimens.1 Treatment of anaerobic infection is complicated by the slow growth of these organisms, by their polymicrobial nature and by the growing resistance of anaerobic bacteria to antimicrobials.
This review describes the microbiology and management of urinary tract and genito-urinary suppurative infections due to anaerobic bacteria.
Urinary tract infection
The majority of bacterial urinary tract infections (UTI) are caused by groups of Gram-negative aerobic or facultative anaerobic bacilli, which include Escherichia, Klebsiella, Aerobacter, Proteus and Pseudomonas spp. Non-pathogenic organisms such as Staphylococcus epidermidis might also be responsible for UTI. The clinical significance of other groups of organisms, including the obligate anaerobes (many strains of which are part of the fecal, vaginal and cervical flora), has received little attention in urinary tract disease.2,3
Hudac et al. found the incidence of recovery of anaerobic bacteria in 10 760 urine specimens to be 0.8% (27 instances).4 Several studies reported the isolation of anaerobes in UTI,1 but most lack sufficient clinical bacteriologic detail to evaluate the reliability of the data; however, there are some well-documented reports of all types of infections in adults.
Anaerobes have been involved in the following types of UTI: para- or periurethral cellulitis or abscess, acute and chronic urethritis, cystitis, acute and chronic prostatitis, prostatic and scrotal abscesses, periprostatic phlegmon, ureteritis, periureteritis, pyelitis, pyelonephritis, renal abscess, scrotal gangrene, metastatic renal infection pyonephrosis, perinephric abscess and retroperitoneal abscess.3,5,6 Moberg and Nord and Eggert-Kruse et al. observed an increase in the number of anaerobic bacteria in urine voided after prostatic massage of infertile men.7,8 Mohanty and Jolly evaluated 300 patients undergoing transurethral instrumentation (TUI).9 These patients had their urine cultured for aerobic and anaerobic organism preoperatively and postoperatively. An increase in the incidence of anaerobic UTI from 2% preoperatively to 14% postoperatively following TUI was documented. The authors concluded that TUI increases the incidence of anaerobic UTI.9 Shivde et al. studied the incidence of aerobic and anaerobic bacteruria in patients undergoing transrectal ultrasound-guided biopsies of the prostate.10 Post-procedure bacteruria due to anaerobic bacteria was detected in only five post-biopsy midstream urine samples (4.3%).
The anaerobic bacteria isolated in these studies were Gram-negative bacilli (including Bacteroides fragilis and pigmented Prevotella and Porphyromonas sp.), Clostridium sp. (including Clostridium perfringens), Peptostreptococcus sp. and Actinomyces sp.1,5–10 In many instances, these bacteria were mixed with coliforms or streptococci.
Using suprapubic aspiration, Brook recovered anaerobic bacteria from young females with UTI: three with pyelonephritis and two with cystitis.2 Two of the girls had prior recurrent UTI. The organisms isolated were three isolates of B. fragilis and one each of Prevotella melaninogenica, Peptostreptococcus asaccharolyticus and Bifidobacterium adolescentis. Polymicrobial infection was present in three patients; in two of the patients B. fragilis was present with Escherichia coli, and two anaerobes were present in the other patient. All patients were treated with antimicrobial agents for 10–14 days and responded well to therapy. Two of the patients had a recurrence of UTI with aerobic organisms within 6–8 months.
Most acute UTI are confined to the lower urinary tract, but persistence or recurrence might lead to progression involving the renal pelvis and parenchyma, producing pyelonephritis.
The patient's fecal flora is usually the source of the bacteria causing UTI. Because anaerobes are the major component of the fecal flora, it is not surprising that they are recovered in some cases of UTI.
The usual route of infection is an ascending one from external genitalia and the periurethral region, rather than a hematogenous one. The periurethral region of healthy females probably forms a barrier against UTI, and the bacterial flora at that region has been found to influence the acquisition of infections.11 Anaerobes constitute 95% of the total colony-forming units (CFU) of organisms per square centimeter of the periurethral area of healthy females.12
Colonization of the males urethra with anaerobic bacteria is related to sexual activity.13 A higher prevalence of potential uropathogens was found in the subpreputial area in uncircumcised young men as compared to circumcised individuals.14 Aerobic Gram-negative rods and streptococci, strict anaerobes and genital mycoplasmas were more common in uncircumcised males. The presence of anaerobes in the periurethral region in females, and in the urethra in males, might explain the mode of infection of these organisms.
Other than through the urethra, anaerobes might also invade the urinary tract by an ascending route, by direct extension from adjacent organs such as the uterus or bowel, or by way of the bloodstream. Bran et al. showed that urethral trauma can introduce organisms from the urethra to the bladder.15 Alling et al. demonstrated that patients with indwelling urethral catheters have a high incidence of anaerobes recovered from urine.16 Sapico et al. found that patients with indwelling Foley catheters can show anaerobes along with aerobes and facultative organisms in the urine.17
Favorable growth conditions for anaerobes might be present at times in the urinary tracts. Adequate requirements include the availability of nutrients and low enough oxygen tension that permits the growth of fastidious anaerobes.18 A low oxygen tension might exist when facultative anaerobes or aerobes are present at an infected site. These organisms consume the available oxygen for their own growth and create ideal conditions for anaerobic growth. After introduction into the bladder or other parts of the urinary tract, some anaerobes are capable of growing well in the urine itself.19
The medullary tissues derive their metabolic energy from anaerobic glycolysis to a greater extent than cortical tissue. Anaerobic glycolysis of the inner medulla is relatively unaffected by the hypertonic environment of the medulla.19 The low medullary blood flow, plasma skimming and countercurrent flow all promote de-creased oxygen supply to the medullary tissues, thus assisting the growth of anaerobes in cases of pyelonephritis. The oxygen tension of the urine is sharply decreased in the dehydrated patient, which predisposes the patient to anaerobic UTI.20
The clinical presentation and diagnosis of UTI do not differ whether anaerobic bacteria or aerobic and facultative bacteria are responsible for the infection. Symptoms might be absent, especially in the chronic form of the disease. The onset might be gradual or abrupt. Fever might be as high as 40.3°C (104.5°F), accompanied by chills. Urinary frequency, urgency, incontinence, dysuria, prostration, anorexia, vomiting and pallor might occur.
Clinical signs include dull or sharp pain and tenderness in the kidney area or abdomen. Hypertension and chronic renal failure might occur in long-standing and severe cases. Jaundice might occur, particularly in early infancy. Anemia is found in cases of long-standing infection. Leukocytosis usually ranges from 15 000 to 35 000/cµ mm.
Diagnosis of lower UTI (cystitis) is based on at least two consecutive positive urine cultures and signs of urgency and dysuria. Acute pyelonephritis should be diagnosed by obtaining at least two consecutive positive urine cultures and should be based on a history of fever, chills, flank pain, nausea and vomiting, frequency, urgency, dysuria and elevated sedimentation rate (above 30 mm/h). Because anaerobes are part of the normal urethral flora, voided specimens are unreliable for the diagnosis of UTI caused by these bacteria. Suprapubic aspiration of the bladder is the best method for obtaining an adequate culture.
Finegold et al. recovered anaerobes from 14 of 100 random urine specimens.18 Follow-up studies failed to isolate obligate anaerobes from 19 specimens of ‘urethral’ urine, and ‘midstream’ urine yielded anaerobes in mixed culture in 13 instances. The anaerobic bacteria recovered from the voided specimens represented normal urethral flora. In this study, anaerobes were recovered in counts of 103−104/mL or greater on a number of occasions.18 Thus, even a quantitative culture is not helpful in distinguishing between infection and the presence of anaerobes as normal flora.
Segura et al. confirmed the validity of suprapubic bladder puncture for the documentation of anaerobic UTI.21 Suprapubic bladder aspirations were done in two groups of patients: in one group aerobic cultures did not reveal organisms that were present in significant numbers on Gram stain, and a second group required suprapubic bladder aspiration for other reasons, such as an inability to void. Of 5781 patients studied, 1.3% with significant bacteruria had anaerobic organisms involved. Of the 10 taps that were positive for anaerobes, there was one instance in which an anaerobe was recovered in pure culture; this was an isolate of B. fragilis in a patient with known renal tuberculosis. Five of the patients had two anaerobes recovered.
With improvements and simplification in the techniques of recovery of anaerobic bacteria, and with the use of proper methods for their collection and transportation to the laboratory, the yield of anaerobes in UTI might increase. The recovery of aerobic or facultative organisms from the urine of a patient with UTI does not exclude the possibility of the concomitant presence of an anaerobe. It is recommended that appropriate cultures for anaerobes be obtained in symptomatic cases where routine aerobic cultures fail to yield bacterial growth, and where Gram stain shows bacteria to be present in the urine sediment.
Surgical repair of obstructive lesions is indicated. Increased fluid intake might help in clearing the infection in the acute stage.
Administration of appropriate antibiotic therapy is required. A prolonged course of therapy (2–6 months or longer) might be needed, especially for recurrent infections. Repeated urinalysis and culture should be performed 48 h after initiation of treatment and at intervals of 1–2 months for at least a year.
Acute uncomplicated infection, which is often caused by enteric organisms such as E. coli is generally treated by oral sulfonamides, trimethoprim-sulfamethoxazole, ampicillin or a quinolone (in adults). At least 10 days of therapy is required for patients with presumed pyelonephritis, reflux or urinary tract abnormalities, and for those who have not yet been evaluated radiographically. A shorter course of therapy (3–4 days) can be given to those not suspected of having pyelonephritis or for those with a normal urinary tract.22
The fluroquinolones are used in adults and not in children because of their potential harmful effect on cartilage. However, their use in children might be considered whenever resistance to other antimicrobials exists. Acutely ill patients might be treated with parenteral agents (one of the antibiotics mentioned above or an aminoglycoside such as gentamicin).
The isolation of anaerobes might have important implications for the choice of antimicrobial agents. Most anaerobic organisms are sensitive to penicillin and cephalosporins. Most anaerobes, however, are resistant to sulfonamides and the older quinolones, and all are highly resistant to aminoglycosides. Furthermore, B. fragilis and a growing number of strains of Prevotella and Porphyromonas are also resistant to penicillin and cephalosporins.23
Isolation of anaerobes requires the administration of agents effective against these organisms. Penicillin or cephalosporins can be used against most anaerobic organisms; however, the recovery of penicillin-resistant organisms requires administration of appropriate antimicrobial agents such as clindamycin, chloramphenicol, ticarcillin, cefoxitin, metronidazole, carbopenems (i.e. imipenem) or the combination of a penicillin and a beta-lactamase inhibitor. Some of the newer quinolones have extended coverage against anaerobic bacteria (e.g. trovafloxacin).
Complete resolution of symptoms ordinarily occurs in patients with uncomplicated cystitis or pyelonephritis. In cystitis, instrumentation can occasionally lead to bacteremia. Anaerobic bacteremia following urologic procedures has been reported.17 Repeated symptomatic UTI in patients with obstructive uropathy, neurogenic bladder, structural renal disease or diabetes more often progresses to chronic renal disease. When left untreated, UTI can progress to renal abscess, pyonephrosis, perinephric or retroperitoneal abscess. Anaerobes have been recovered in each of these conditions (Table 1).24
Table 1. Bacteriological characterization of suppurative genito-urinary infections
|No. of specimens||6||3||2||7||26||2||4||4||4|
|Type of bacterial growth|
| Aerobes only||0||0||0||1|| 2||0||0||0||1|
| Anaerobes only||2||0||1||1|| 5||1||3||3||1|
| Aerobes and anaerobes||4||3||1||5||19||1||1||1||2|
| Aerobes||6.7||1.3||1.0||0.9|| 0.9||0.2||0.7||0.2||0.7|
| Anaerobes||3||1.7||3.5||2.0|| 1.7||2.0||2.5||2.5||1.0|
|No. of specimens||3||7||15||6||3||2||3||6||103|
|Type of bacterial growth|
| Aerobes only||0||0|| 2||0||1||0||0||0|| 7|
| Anaerobes only||0||5|| 3||4||0||0||2||3|| 34|
| Aerobes and anaerobes||3||2||10||2||2||2||1||3|| 62|
| Aerobes ||1.0||0.4|| 1.0||0.5||2.0||1.0||0.7||0.7|| 0.8|
| Anaerobes||1.3||1.7|| 1.9||1.3||1.3||2.0||2.0||1.3|| 1.8|
|Total||2.3||2.1|| 2.9||1.8||3.3||3.0||2.7||2.0|| 2.6|
Genito-urinary suppurative infections: perinephric and renal abscesses
Perinephric and renal abscesses are rare.21–34 They are often misdiagnosed and, consequently, are frequently mistreated or treated too late. Newer imaging methods enable an earlier diagnosis and a more accurate anatomic identification, enabling a less invasive therapeutic approach.
The majority of suppurative genito-urinary infections involve anaerobic bacteria. Brook studied 103 patients (55 men and 48 women), 29 of them younger than 18 years old, with localized suppurative genito-urinary tract infections (Table 1).24 The 55 men had genital abscess. These included scrotal abscess (15), scrotal cyst abscess (3), scrotal wound (3), penile abscess (7), penile wound (6), testicular abscess (6), infected hydrocele (2), prostate abscess (3), kidney abscess (4), perinephric abscess (2) and periuretheral abscess (4). The 48 females had Bartholin's cyst abscess (26 patients), vulvar abscess, vaginal abscess and labial wound (4 each), labial cyst abscess (2), kidney abscess (2), perinephric abscess (1), periurethral abscess (3) and bladder abscess (2). Anaerobic bacteria only were found in 34 specimens (33%), aerobic bacteria only were present in 7 (7%), and mixed aerobic and anaerobic flora were present in 62 specimens (60%). A total of 275 isolates (189 anaerobic and 86 aerobic) were recovered, an average of 2.6 isolates per specimen (1.8 anaerobes and 0.8 aerobes). The predominant anaerobes isolated were Bacteroides sp. (103 isolates) and anaerobic cocci (53). The most frequently recovered aerobes were E. coli (26 isolates), S. aureus (10) and Proteus sp. (8).24
The predominate organisms isolated in perinephric and renal abscesses are S. aureus, Enterobacteriaceae (especially E. coli and including Salmonella sp.), Pseudomonas sp., Enterococcus sp., coagulase-negative staphylococci, Streptococcus sp., Actinomyces sp., fungi and Mycobacterium tuberculosis.25,28,33,34 Anaerobic bacteria were infrequently reported from children with perinephric and renal abscesses but were isolated in up to a quarter of cases in adults.5,24,31,32
Brook studied six cases of perinephric abscess and four cases of renal abscess in children and reported isolation of anaerobic bacteria of oral or gastrointestinal origin.29 Polymicrobial infections were described in nine children. A total of 20 organisms (2.0 per specimen), eight aerobic or facultative and 12 anaerobic, were recovered in the abscess specimens. The predominant isolates were Bacteroides fragilis group (7 isolates), E. coli (4) and S. aureus (2). Bacteria similar to those recovered in the abscesses were also isolated in the blood in seven cases and in the urine in four patients. Thirteen beta-lactamase-producing organisms (BLPO) were found in nine cases. The BLPO were all isolates of the B. fragilis group and two isolates of S. aureus, a single isolate of Prevotella melaninogenica and three of the four E. coli.
Abscesses are generally diagnosed in otherwise healthy individuals, but some factors increase the risk. These risk factors include: urinary tract conditions (infection, anomalies such as reflux and obstruction, urinary tract stones, neurogenic bladder, polycystic disease, tumor, peritoneal dialysis), primary infection elsewhere with subsequent seeding (originating from skin, dental, cardiac, respiratory, genital, abdominal, gastrointestinal, intravascular catheter and intravenous drug abuse), surgery (of the urinary tract including transplantation, and abdominal), immunodeficiency states, trauma to the kidney and diabetes mellitus.26–28,30,33–42
Hematogenous infection is often caused by S. aureus, which can originate from the skin or another infection site or appears spontaneously.5,16Enterobacteriaceae are generally recovered from an abscess that follows UTI.
Enterobacteriaceae are the main isolate in perinephric abscess. Bacterial invasion of the perinephric space is through direct extension from an intrarenal abscess or by vesicoureteral reflux, urinary tract obstruction or surgery of the urinary tract or abdomen. S. aureus generally causes perinephric abscesses through hematogenous seeding from a distant primary site.
Predisposing factors for anaerobic involvement are those that allow for their dissemination to the kidney and perinephric area from another infectious site.5,24,29,31,32 Local spread can originate from a perforated viscus, or through hematogenous spread from the upper respiratory tract or dental sites.29 The anaerobic organisms isolated from those abscesses are similar to those that colonize the mucous membranes of the site of origin. This association might enable the clinician to initiate empiric antimicrobial therapy, even before abscess drainage. Anaerobic bacteria that originate from the oral cavity (i.e. oral Gram-negative bacilli) were recovered in renal abscesses associated with respiratory infections, whereas enteric anaerobes (i.e. B. fragilis group) were present in abscesses that were associated with an abdominal origin.24,29
A high recovery rate of anaerobic bacteria in perinephric abscesses was especially apparent in those with obstruction leading to urinary extravasation,32,42–44 renal transplantation,45 perforation of the colon,46 and in a necrotic tumor.47–49 Anaerobes were present in renal abscesses in adults in association with seeding during anaerobic bacteremia, or in association with altered renal architecture.32 In the later cases, stasis and necrosis of tissue are important factors. Similarly, associated predisposing conditions were also found in the children.29 However, in contrast to adults,32 renal stones were not observed in children.29
Oral administration of antibiotics for treatment of UTI can cause ecologic disturbances in the normal intestinal microflora.50 Suppression of the normal microflora might lead to reduced gut colonization resistance with subsequent overgrowth of pre-existing, naturally resistant microorganisms. Beta-lactam antibiotics suppress both the aerobic and anaerobic intestinal microflora with overgrowth of ampicillin-resistant Enterobacteriaceae. Fluoroquinolones eliminate or strongly suppress intestinal Enterobacteriaceae and only slightly affect enterococci and anaerobic bacteria. However, the use of fluoroquinolones might increase the selective pressure on the emergence of UTI due to anaerobic bacteria. An example of such a phenomena was the effect of prophylactic trimethoprim given to women during pelvic radiotherapy. This increased the incidence of infections due to fastidious or anaerobic organisms.51
The clinical presentation and diagnosis of genito-urinary suppurative infections caused by anaerobic bacteria are not different from those caused by aerobic and facultative bacteria. Symptoms are generally non-specific and include lethargy, decreased appetite, weight loss, nausea and vomiting. Their duration is generally 1–3 weeks before diagnosis. They are typically associated with fever (89%) and with unilateral pain in the flank or abdomen or tenderness in the costovertebral angle.25,27–29,33,35–39,42 Pain can be also referred to other sites. Other findings might include scoliosis caused by splinting of the affected side, pain on bending to the other side and chest abnormalities (e.g. reduced respiratory excursion, lower rib tenderness, pulmonary dullness, lowered breath sounds and rales on the abscess side).
Dysuria, or frequency, is common when the abscess is preceded by a UTI. An abscessis hard to palpate in adults, can be palpated in approximately 5% of children and is more likely to be found in infants. An abscess should be suspected in patients with a predisposing condition, especially if they fail to respond to therapy of pyelonephritis.
Laboratory findings include elevated white blood count and erythrocyte sedimentation rate. Microscopic pyuria can be found in 46% of patients, positive urine culture can be found in 52% of patients and positive blood culture can be found in 34% of patients.49
Abscess content should be obtained by aspiration, or at the time of surgery, for Gram stain and culture. Culture and stain for aerobic and anaerobic bacteria, fungi and mycobacteria should be obtained.
Ultrasonography is initially performed in those who are unresponsive to antibiotic treatment for pyelonephritis. However, ultrasonography and renal cortical scintigraphy might not distinguish between abscess and uncomplicated pyelonephritis unless there is a distinctively rimmed, round mass with central liquefaction. Enhanced computed tomography (CT) is the most reliable imaging modality for the diagnosis of renal and perinephric abscesses.31,49 Serial renal ultrasound studies can document progress in those recovering from a renal abscess. However, resolution of the ultrasonographic abnormality lags behind clinical and laboratory improvement, and often takes months to resolve.
The initial therapeutic approach includes intravenous administration of antibiotic therapy. Percutaneous drainage, open surgical drainage, or nephectomy might be indicated if this fails. Initial empiric antibiotic therapy should include agents effective against S. aureus and Enterobacteriaceae. Third-generation cephalosporins (i.e. cefotaxime), although effective against Enterobacteriaceae, do not provide adequate coverage against S. aureus. Similarly, although beta-lactamase-resistant penicillins (i.e. nafcillin) are active against S. aureus, they are not effective against beta-lactamase-producing anaerobic bacteria.23 Alternatively, a pencillinase-resistant penicillin such as nafcillin or oxacillin, plus an aminoglycoside is an adequate combination.
Because many of the anaerobic bacteria isolated in these abscesses are resistant to penicillins, through the production of beta-lactamase,23 antimicrobials effective against these organisms should be used in treating perinephric and renal abscesses in which these organisms are suspected or isolated. These antimicrobials include metronidazole, chloramphenicol, clindamycin, a carbapenem (i.e. imipenem), cefoxitin and the combination of a penicillin and a beta-lactamase inhibitor (i.e. ticarcillin or amoxicillin plus clavulanate).23,52 The older fluoroquinolones (ciprofloxacin, ofloxacin) are effective against Enterobacteriaceae, but are not active against anaerobic bacteria. The newer fluoroquinolones (gatifloxacin and trovafloxacin) are more effective against anaerobic bacteria.
Consideration should be given to the addition or replacement of an antimicrobial ineffective against aerobic bacteria with an agent with anti-anaerobic activity, especially with underlying chronic obstructive disease or in those not responding to therapy. Therapy should be adjusted according to the abscess culture results. Therapy directed at the spectrum of potential pathogens should not be reduced based on blood or urine culture results only, because these do not always correlate with the recovery of isolates from abscess specimens.24,26
The duration of parenteral therapy depends on the patient response and whether percutaneous or surgical drainage is accomplished. At least 14 days of therapy is appropriate in conjunction with abscess drainage in those with uncomplicated infection. Without drainage, 6 weeks or more of therapy might be needed.52,53 Therapeutic drainage, can be performed without significant morbidity, which avoids the need for open drainage under general anesthesia. Aspiration is usually performed with ultrasonographic guidance.54,55
Open surgical drainage is generally performed when antimicrobial therapy and percutaneous drainage fail. Such drainage was used in the past when an abscess ruptured into an adjacent space. Presently, however, a percutaneous approach usually allows for adequate drainage. Nephrectomy is carried out only for those with massive abscess where the involved kidney is unlikely to stay functional.
Bacteremia can result in the spread of infection to other sites. Other complications include extension of the infection to the kidney or perinephric space, or loss of renal function. These complications can cause more tissue destruction and organ dysfunction and can lead to the rupture of the kidney into an adjacent space (pulmonary, abdominal).