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Emphysematous Cystitis

Illustrative Case Report and Review of the Literature

Grupper, Moti MD; Kravtsov, Alexander MD; Potasman, Israel MD

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doi: 10.1097/MD.0b013e3180307c3a
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Gas-producing infections are usually considered fulminant and dramatic, and may occur in almost any organ or system. Gas in the urinary tract may be due to a variety of pathologic entities, including gas-forming infections, infarction, or a fistula with a hollow viscus. Air may be introduced into the genitourinary tract by instrumentation, during surgical procedures, or as a result of external penetrating trauma24. Gas-forming infections of the urinary tract are sporadic, and may involve any part of this system61.

Emphysematous cystitis (EC) is a rare complication of lower urinary tract infection (UTI), which results from primary infection of the urinary bladder with gas-producing pathogens47. EC or "cystitis emphysematosa" was originally described only as a pathologic entity. The pathologic changes were first described in a diabetic female dog in 192622. Mills described a series of 12 autopsy cases in 1930, of whom 8 were female and none was diabetic33-36. In all cases, pathologic examination of the urinary bladder mucosa demonstrated varying degrees of gas-containing vesicles, inflammation, and hemorrhage. These autopsy findings set the basis for the recognition of EC as a distinct clinical entity, and this was firmly established in the following years. The central role of UTI in the pathogenesis of EC was established over the subsequent 30 years4. The complete clinical picture and outcome of EC are poorly defined. Because the diagnosis of EC is obtained in most cases by means of radiologic examination, a field that has been revolutionized over the past few decades with the introduction and widespread acceptance of computerized tomography (CT), we elected to review the relevant literature covering the past 20 years.


A 70-year-old woman presented to the emergency department complaining of generalized weakness, macrohematuria, lower abdominal pain, and dysuria lasting 3 days. She denied fever, chills, nausea, vomiting, diarrhea, previous events of hematuria, or urinary retention. Her past medical history was significant for type 2 diabetes mellitus (DM), complicated by diabetic retinopathy and nephropathy (baseline creatinine of 2 mg/dL), essential hypertension, and hyperlipidemia. She did not use alcohol or tobacco.

Ten days earlier, the patient had been hospitalized for 3 days with a diagnosis of hyperglycemia, uncontrolled blood pressure, and UTI, manifested by dysuria and lower abdominal pain for 2 weeks, but no chills or fever. On that occasion, blood count showed 13,100 white blood cells (WBC)/mL. Urinalysis was remarkable for large numbers of WBC, and 8-10 red blood cells (RBC) per high-power field (HPF). A urinary catheter was not inserted. A plain abdominal film showed no evidence of nephrolithiasis, ileus, free air, or air in the bladder. The patient was treated with intravenous (IV) cefuroxime for 2 days, her symptoms subsided, and she was discharged. She was prescribed oral cefuroxime-axetil for a further 4 days. The result of urine culture, received after discharge, revealed 106 colonies of Escherichia coli, resistant to ampicillin; first-, second-, and third-generation cephalosporins; and ofloxacin.

On readmission, the patient was in no acute distress. Blood pressure was 173/86 mm Hg, pulse was 121/minute, and rectal temperature was 36.9 °C. The physical examination was significant only for mild suprapubic tenderness, without peritoneal signs or flank tenderness on percussion. Laboratory evaluation revealed a WBC count of 18,100/mL with 90% polymorphonuclears, and the C-reactive protein (CRP) was 101.3 mg/dL. Serum glucose level was 460 mg/dL, urea level was 77 mg/dL, and creatinine was 2 mg/dL. Blood pH was 7.36, with a bicarbonate level of 25.5. Urinalysis revealed large numbers of RBC/HPF, with no WBC. Ultrasonographic examination of the urinary system demonstrated normal-sized kidneys with thin parenchyma, and renal calculi on the left side. Suspicion was raised of a staghorn calculus in the left kidney. The patient was admitted with a presumed diagnosis of UTI. Empiric treatment was commenced with IV ceftriaxone. The following day, due to persistent abdominal pain and the ultrasonographic findings, an abdominal CT scan was performed without contrast. The CT (Figure 1) revealed the presence of a thickened bladder wall, with intramural and intraluminal gas bubbles and opacification of the perivesicular fat. The presence of a staghorn calculus in the left kidney was confirmed. A diagnosis was made of EC, and a urinary catheter was inserted, which drained macrohematuria with a large number of blood clots, but without pneumaturia. The empiric treatment was changed on the second hospitalization day to piperacillin/tazobactam plus gentamicin. In the days following this, the patient's condition improved, the urine cleared, and her laboratory tests gradually normalized. Urine culture grew 106 colonies of E.coli, with a resistance pattern identical to that observed during the prior hospitalization. Blood cultures obtained on admission were negative. A repeat abdominal CT scan (Figure 2), combined with cystoscopy, was performed 9 days after admission, demonstrating a significant decrease in the number of intramural gas bubbles and the amount of intraluminal gas. The perivesicular fat opacification had cleared. No pathology was seen on cystoscopy. The patient was treated with IV antibiotics for a total of 8 days, and was discharged on oral amoxicillin/clavulanate for a further 14 days. On last follow-up, 45 days post-discharge, she was asymptomatic.

Abdominal CT demonstrating gas bubbles in the urinary bladder wall (arrows).
Abdominal CT demonstrating nearly complete resolution of gas bubbles in the urinary bladder wall, with residual gas bubbles (arrow), and normal-appearing bladder wall (arrowhead).


We conducted a computer-based search (MEDLINE, National Library of Medicine, Bethesda, MD) of the English-language literature for the years 1986-2006 describing patients with a diagnosis of EC or cystitis emphysematosa. We excluded cases that demonstrated gas in any other part of the urinary tract or another body organ, or a fistula between the urinary bladder and adjacent organs. From each publication we excerpted the following data: age and sex, regular use of alcohol, the presence of DM, all comorbidities, known or newly discovered urinary tract pathology, and the presence of symptoms and signs suggestive of UTI on initial presentation (dysuria, urinary urgency, increased urinary frequency, abdominal pain, flank pain, urinary retention, hematuria, chills, nausea and/or vomiting, systemic fever, abdominal or flank tenderness). We also recorded the presence of pneumaturia elicited from the medical history or as a result of urinary catheterization, impaired level of consciousness, reduced systolic blood pressure, and the presence of peritoneal signs. We looked for the following blood tests: glucose, creatinine, CRP and WBC, as well as the results of blood cultures, if taken, urinalysis, and urine cultures. We recorded the imaging modalities used (plain abdominal X-ray, intravenous pyelogram, ultrasound, CT, lower gastrointestinal barium enema, endoscopy, or cystoscopy), the results, and the time from presentation to the diagnosis of EC. We also recorded details of the treatment during hospitalization: length of antibiotic treatment and length of hospitalization, use of urinary drainage, presence of local complications, any surgical procedure related to the UTI that was carried out, and outcome (dead or alive) at the last follow-up available. When there was no information regarding a certain parameter, we recorded the data as "not available," and the case in question was excluded from the denominator for that particular parameter only in the analysis. Numerical values of data were recorded when available. For the purpose of data analysis in the present study, we have introduced a number of definitions (Table 1). The time interval from presentation to the diagnosis of EC was assumed to be ≤24 hours if the diagnosis was made during the patient's evaluation on presentation. Surgical procedures that were not reported were assumed to have not been carried out. In the single case where the outcome was not reported, the patient was assumed to be alive at last follow-up.

Definitions Used for Data Assessment


Fifty-three cases met our inclusion criteria for analysis. Only 1 case description was excluded on technical grounds. There were 38 non-English-language studies of EC in the years we surveyed. Nine of these originated from Japan, and the remainder were from a range of European countries. These articles were not included in the current analysis because of an apparent lack of geographical clustering, and for technical reasons. Twenty-three of the non-English-language articles were not eligible for any analysis because they were either incompatible with our inclusion criteria, lacked data on the English-language abstract, or had no English-language abstract. The remaining eligible 15 non-English-language articles reported 25 cases in their abstracts; the mean age of these patients was 68.9 ± 10.6 years. Of the 25 cases, 14 (56%) were female, and 18 (72%) were diabetic.

Clinical, laboratory, and radiologic characteristics of eligible (English language) cases for the current analysis are presented in Table 2. The mean age of the patients was 67 ± 15 years (range, 23-90 yr). The majority of patients were female, and DM was present in 62.2%. Twelve (22.6%) of the patients had documented immunosuppressive comorbidity (2 suffered from malnutrition, 4 abused alcohol, 2 were receiving immunosuppressive therapy, 1 had solid cancer, and 3 had hematologic malignancy); 4 of these cases also had DM. The most common urinary tract pathologies reported were neurogenic bladder (5 cases), and a history of recurrent UTI (4 cases). Of the 53 cases, 12 (22.6%) had neither immunosuppressive comorbidity nor DM.

Prevalence of Clinical, Laboratory, and Radiologic Findings in 53 Cases of Emphysematous Cystitis*

In 8 of 45 eligible cases (17.8%), there was nothing in the medical history to indicate a diagnosis of UTI (1 or more symptoms such as abdominal pain, flank pain, urinary retention, dysuria, frequency, urgency, hematuria, or pneumaturia). Classic symptoms of UTI (1 or more of dysuria, urinary frequency, or urinary urgency) were present in only 24 of 45 eligible cases (53.3%).

Abdominal tenderness was found in 65.6% of eligible cases, but frank peritoneal signs in only 6.2%. It is interesting that pneumaturia was noted after catheterization in 70% of eligible patients. Eight of the patients with urinary retention were completely asymptomatic, and evidence of retention was found only on objective testing.

Urinalysis was bloodless in only 6 cases (17.6%), whereas either leukocyturia or blood was present in all eligible cases. Only 2 of the cases with elevated serum creatinine had a prior diagnosis of chronic renal failure, and 4 were reported to have had a previously normal creatinine level.

Gas in the urinary bladder wall or lumen was demonstrated in all of the 53 cases, either on plain abdominal film or CT, or both. CT demonstrated gas in the urinary bladder wall in 94.4% of eligible cases, and in the bladder lumen alone in the 2 remaining cases. Radiologic diagnosis was based on plain abdominal X-ray alone in 6 of 53 cases (11.3%). Abnormal sonographic appearance of the urinary bladder was demonstrated in 46.1% of eligible cases, with findings of multiple echoes consistent with gas in 5 of 6 cases, and a thickened bladder wall in the remaining case. Gas was demonstrated either by plain X-ray or abdominal CT in all other cases not identified by ultrasound.

A urinary tract pathogen was isolated in 90.4% of cases. E. coli was the most prevalent pathogen (57.4%), followed by Klebsiella pneumonia (21.3%). Other isolates included Enterococcus, Candida, and Clostridium perfringens in 1, 2, and 2 cultures, respectively. In 4 of the cases, the culture was polymicrobial. Over the years, E. coli and Klebsiella pneumonia have consistently been the dominant urinary isolates.

Clostridium perfringens, Candida albicans, and E. coli were isolated in the blood cultures of 2, 1, and 1 of the cases, respectively.

The median time from presentation to diagnosis in the 32 evaluable cases was up to 24 hours. In 6 of 32 eligible cases (18.7%), diagnosis was established more than 24 hours after presentation (range, 2-9 days). In 4 of these cases, none of the classic complaints indicative of a UTI was present, with macrohematuria and mild urinary urgency present in the remaining 2 cases. No complication, surgery, or mortality was reported in any of these 6 cases.

Antibiotic treatment was administered in all 53 cases. Of the 30 cases for which data were available regarding specific antibiotic treatment, most of the patients received beta-lactams (60%). The median length of the treatment period was 10 days (20 evaluable cases). The median length of hospitalization was up to 7 days (18 evaluable cases).

A complicated course was present in 10 cases (18.8%). Laparotomy was deemed necessary in 8 patients (15%) on the grounds of peritoneal signs, pneumoperitoneum, or perivesical abscess. In all of these cases, the pathologic process on laparotomy was confined to, or originated from, the urinary bladder. Total cystectomy, partial cystectomy, cystostomy, and bladder lavage were performed in 4 of these cases. No details concerning the exact surgical procedure were available for the other 4 cases. Two other patients had major sequelae directly attributable to the process of EC. One of these patients required treatment in a hyperbaric chamber, following a suspicion of cerebral air embolism due to altered mental status and femoral venous gas bubbles on abdominal CT. The other patient had hydronephrosis requiring bilateral percutaneous nephrostomy. This group of 10 complicated cases was not significantly different from the uncomplicated group for any of the demographic or comorbidity parameters examined (2-sided t test or chi-square; Table 3).

Demographic and Comorbidity Parameters of Complicated and Uncomplicated Cases*

Five of the 53 patients (9.4%) were reported dead at the time of last follow-up. There was no discussion regarding the contribution of EC to mortality in any of these cases. The precise time from diagnosis of EC to death was explicitly reported in only 1 case (21 days).


We found that most cases of EC occur in elderly, diabetic women. A 62.2% rate of DM is remarkable. The prevalence of DM in the general population is estimated at 8.6% in people over 20 years old45. DM is probably overrepresented among patients with symptomatic UTI40, although there is still room for debate on this point. In the present study, however, we found the rate to be 7 times higher. Our figures thus concur with those of Bailey4, who found that DM occurred in 15/19 (80%) of the cases with EC. The advanced age of the present cohort is in agreement with the fact that complicated UTI (for example, pyelonephritis and perinephric abscesses) appears to occur more frequently among older individuals with DM than among those without47.

The exact mechanism of gas formation in emphysematous infections is unclear. A proposed explanation in diabetic patients includes production of CO2 by infecting microorganisms demonstrating gas-forming ability. This is made feasible by fermentation of the high glucose concentration in the urine and tissues, leading to the accumulation of acids, and thus lowering the local pH. Gas-forming microorganisms produce enzymes, which convert the acids to CO2 when the pH reaches 6 or lower. A variety of fermentation pathways has evolved in microorganisms, including lactic acid fermentation (Streptococcus, Lactobacillus), alcohol fermentation (a large number of yeasts and a smaller number of bacteria), mixed acid (formic acid) fermentation (most Enterobacteriaceae), butyric acid fermentation (Clostridium), butanediol fermentation (Enterobacter), and propionic acid fermentation (Propionibacterium). The fermentation capabilities of these pathogens, which are not always considered to be classical gas producers, may explain their involvement in emphysematous infections21. Because emphysematous infections of the urinary tract may occur in nondiabetic patients, it has been proposed that urinary lactose or tissue proteins may serve as substrates for gas formation. A unifying mechanism for the different patient populations suggested that the pathogenesis of gas bubble formation involves rapid catabolism of any type, resulting in increased production of gas. In addition, there is impaired transportation of the formed gas, due to local inflammation or obstructive uropathy increasing the local pressure and impairing the circulation, or vascular disease (for example, in diabetes). The accumulation of gas further increases the local pressure and may lead to infarction of the adjacent tissues. The infarcted tissue might in turn provide a good culture medium for gas-forming pathogens, augmenting the barrier to gas transportation and thus creating a vicious circle61.

Our data indicate that the clinical presentation of EC is nonspecific, and can range from minimally symptomatic UTI to a scenario of peritonitis and septic shock. The most common symptom among eligible cases was abdominal pain, but the classic symptoms of UTI were reported in only approximately 50% of the cases. As opposed to a prevalence of only 50% in the usual form of bacterial cystitis49, in the present study blood was present in urine (microhematuria or gross hematuria) in 82.3% of cases. This may indicate a more invasive process in patients with EC than in those with the usual form of bacterial cystitis.

As symptoms are of no help in reaching a diagnosis, appropriate diagnostic imaging is imperative to establish the diagnosis of EC. Our data indicate that abdominal and pelvic CT is the most valuable imaging modality for the diagnosis of EC. Plain X-ray radiography (Figure 3) has reportedly been regarded as a highly sensitive tool, but findings on plain X-ray may be confused with rectal gas, emphysematous vaginitis, pneumatosis cystoides intestinalis, and gas gangrene of the uterus, resulting in poor specificity. The use of CT, intravenous pyelogram, cystoscopy, and/or lower gastrointestinal imaging is important for ruling out a colo-vesical fistula secondary to diverticulitis of the colon, colonic carcinoma, or less commonly, Crohn disease24. Based on our review, the sensitivity of ultrasound is low (only 46.1%), but it was conducted in only 13 of 53 cases (24.5%), thus limiting our ability to evaluate its usefulness. There is no specific information regarding the use of magnetic resonance imaging (MRI) for the diagnosis of EC, but because gas-forming infections can cause signal voids, which are difficult to interpret on MRI, the value of MRI seems limited in this condition50.

A plain abdominal X-ray demonstrating the presence of pelvic gas (arrow) in a case of emphysematous cystitis. From Asada S et al. (N Engl J Med 2003;349:258). Copyright © 2003 Massachusetts Medical Society. All rights reserved.

EC usually runs a benign course, but complications may arise in up to 19% of cases. Five of the patients in the current series died, but it was difficult to establish a direct connection between their death and EC. Forty-six years ago, Bailey4 described a more benign course among cases: none of the patients underwent a surgical procedure, and the 2 cases of death were not attributable to EC. We believe that the course of the disease in the current series derives from the fact that the patients whose cases we reviewed were significantly older (67 ± 15 vs. 54 ± 19.1 yr; p = 0.0036, 2-sided t test).

The present study has a number of limitations. As with all retrospective reports, the data were incomplete. In addition, the rarity of EC implies that each center reports its occurrence anecdotally. Therefore, to obtain as many valuable data as possible, we included every description of a case with that diagnosis, even if the article did not set out specifically to such a description. These factors may have been responsible for less than optimal data in some of the cases. Nevertheless, it is unlikely that a prospective study of EC would be conducted, leaving the retrospective analysis of existing data as the only practical tool. In addition, since the present study is a review of case reports, it is possible that there is a publication bias toward cases with a complicated course.

In conclusion, clinicians should be aware of the clinical entity of EC. Based on our findings, suspicion of this disease should be aroused by abdominal pain in a diabetic patient, with or without a clinical presentation suggestive of UTI, especially when hematuria is present. In such cases, we suggest conducting a plain abdominal X-ray for screening, followed by abdominal CT when urinary bladder gas is present.


We thank Richard Lincoln and Ellen Bamberger, MD, for proofreading the manuscript.


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