INTRODUCTION — Emphysematous urinary tract infections (UTIs) are infections of the lower or upper urinary tract associated with gas formation. They may manifest as cystitis, pyelitis, or pyelonephritis.

Diabetes mellitus is a major risk factor for these infections and is also associated with an increased risk of asymptomatic bacteriuria and certain symptomatic UTIs such as cystitis, renal and perinephric abscess, and Candida infections [1-3]. These issues are discussed elsewhere. (See "Asymptomatic bacteriuria in adults" and "Acute simple cystitis in women" and "Renal and perinephric abscess" and "Candida infections of the bladder and kidneys" and "Susceptibility to infections in persons with diabetes mellitus" and "Acute complicated urinary tract infection (including pyelonephritis) in adults".)

PATHOGENESIS — The pathogenesis of emphysematous UTIs is poorly understood. Elevated tissue glucose levels in diabetic patients may provide a more favorable microenvironment for gas-forming microbes. However, bacterial gas production does not fully explain the pathologic and clinical manifestations of emphysematous UTIs [4,5].

MICROBIOLOGY — These infections are usually due to Escherichia coli or Klebsiella pneumoniae [4-8]; other causative organisms include Proteus, Enterococcus, Pseudomonas, Clostridium, and, rarely, Candida spp [9,10]. (See "Candida infections of the bladder and kidneys".)

RISK FACTORS — Diabetes mellitus and urinary tract obstruction are the major risk factors for emphysematous urinary tract infections (UTIs). In different series, diabetes was present in more than 80 percent of patients with emphysematous pyelonephritis [4,6,11-13], at least 50 percent of patients with emphysematous pyelitis, and 60 to 70 percent of patients with emphysematous cystitis [5,14]. In addition, most patients were women, similar to the female predominance with acute cystitis and pyelonephritis [4,5,14], and most patients were over age 60 [4,5,14].

One of the largest published experiences comes from a retrospective study of 48 patients in Taiwan who were diagnosed with either emphysematous pyelonephritis or emphysematous pyelitis [4]. Diabetes was present in 96 percent and urinary tract obstruction in 22 percent. The mean patient age was 60 years (range 37 to 83 years) and women outnumbered men 6:1. Similar findings were noted in a literature review of 135 patients with emphysematous cystitis: diabetes was present in 67 percent, the mean age was 66 years, and women accounted for 64 percent of cases [14].

In other smaller series of patients with emphysematous pyelonephritis, urinary tract obstruction was present in 0 to 50 percent of patients with diabetes [6,12,13]. In contrast, obstruction was present in all six patients without diabetes in two reports [4,13]. The main causes of urinary tract obstruction were papillary necrosis and, less often, ureteral calculi [6].

DIAGNOSIS — The diagnosis of a gas-forming UTI is usually made by plain films of the abdomen and/or computed tomography (CT). Such radiographs reveal air in the renal parenchyma, bladder, or surrounding tissue in 50 to 85 percent of cases. CT scanning is more sensitive than plain films and may show the extent of gas formation and any obstructing lesions in the urinary tract [4-6].

Imaging, particularly CT scanning, has also been used to classify emphysematous pyelonephritis, which in turn can help make estimates of prognosis and guide therapy. (See 'Prognostic classification' below.)

EMPHYSEMATOUS PYELONEPHRITIS AND PYELITIS — Emphysematous pyelonephritis is a gas-producing, necrotizing infection involving the renal parenchyma and, in some cases, perirenal tissue [4,6,11,15-17]. Emphysematous pyelitis (ie, gas in the renal pelvis (image 1)) or cystitis (image 2) can occur with or without associated emphysematous pyelonephritis [4,5,14].

Clinical features — The clinical features of emphysematous pyelonephritis and emphysematous pyelitis are indistinguishable from those seen in severe, acute pyelonephritis. Most patients complain of fevers, chills, flank or abdominal pain, nausea, and vomiting. The onset of symptoms may be abrupt or evolve slowly over two to three weeks. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults".)

Laboratory testing usually reveals hyperglycemia, leukocytosis, elevated serum creatinine, and pyuria. Acute anuric renal failure is an uncommon complication of emphysematous pyelonephritis that can be seen in patients with bilateral infection or unilateral disease in a solitary functioning kidney [18].

In the series of 48 patients cited above, bacteremia was present in 54 percent [4]. All organisms isolated from blood cultures were simultaneously found in cultures of the urine or renal pus. E. coli (69 percent) and K. pneumoniae (29 percent) were the predominant pathogens. Two patients had a polymicrobial infection with E. coli plus group B Streptococcus or Proteus.

Differential Diagnosis — The clinical presentation of emphysematous pyelonephritis or pyelitis can be similar to that of severe, acute pyelonephritis, xanthogranulomatous pyelonephritis (see "Xanthogranulomatous pyelonephritis"), or acute papillary necrosis. These conditions are discussed in detail elsewhere. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Clinical manifestations' and "Xanthogranulomatous pyelonephritis" and "Clinical manifestations and diagnosis of analgesic nephropathy".)

The differential diagnosis for the presence of air either in or adjacent to the renal parenchyma includes the following conditions: reflux of air from the bladder, air in a renal abscess, entero-renal or cutaneo-renal fistula formation, retroperitoneal perforation of abdominal viscus, psoas abscess with gas-forming organisms, or recent urologic or radiologic intervention such as nephrostomy insertion. Computed tomography (CT) findings can help differentiate between these possibilities.

Treatment — In the past, treatment of emphysematous pyelonephritis or pyelitis usually involved nephrectomy or open drainage along with systemic antibiotics [6,12,13,19,20]. In more recent reports, successful management with systemic antibiotics together with percutaneous catheter drainage (PCD) of gas and purulent material, as well as relief of urinary tract obstruction (if present), has been described [4,6,21-23]. A systematic review of 10 retrospective studies including 210 patients with emphysematous pyelonephritis noted that mortality associated with medical management plus percutaneous catheter drainage was significantly lower than medical management plus emergent nephrectomy (13.5 versus 25 percent, respectively) [23]. Regardless of whether drainage or surgery is performed, all patients require treatment with parenteral antibiotics; antibiotic selection is as outlined elsewhere for the management of acute pyelonephritis. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Management'.)

Prognostic classification — Based upon the findings seen on CT scan, two classification systems have been proposed to estimate prognosis and guide therapy. One classification system divided emphysematous pyelonephritis into two types [7]:

●Type I — Renal parenchymal necrosis with either absence of fluid collection or the presence of a streaky or mottled gas pattern

●Type II — Renal or perirenal fluid accompanied by a bubbly gas pattern or gas in the collecting system

Differences between the imaging results seen in types I and II may reflect the fact that vascular thrombosis is also present in type I. Patients with type I patterns had a more fulminant course characterized by a significantly shorter duration from symptom onset to diagnosis (4 versus 11 days) and a significantly higher mortality rate (69 versus 18 percent with type II). Also, type I was associated with necrosis and hemorrhagic infarction on pathologic examination compared with diffuse infiltration of inflammatory cells and abscess formation in type II. (See 'Risk factors for adverse outcomes' below.)

Emphysematous pyelonephritis or pyelitis may be alternatively categorized into four prognostic classes based upon CT scan findings [4]:

●Class 1: Gas in the collecting system only (ie, emphysematous pyelitis); this finding may be associated with severe obstruction at the site of the pyelitis in some patients

●Class 2: Gas in the renal parenchyma without extension to the extrarenal space

●Class 3A: Extension of gas or abscess to the perinephric space (defined as the area between the fibrous renal capsule and the renal fascia)

●Class 3B: Extension of gas or abscess to the pararenal space (defined as the space beyond the renal fascia and/or extension to adjacent tissues such as the psoas muscle)

●Class 4: Bilateral emphysematous pyelonephritis or a solitary functioning kidney with emphysematous pyelonephritis

Risk factors for adverse outcomes — Patient outcomes with emphysematous pyelonephritis or pyelitis vary with the classification system type and other factors. We prefer the classification system using four categories over the one using two, because the four-category system links the type of class to specific therapeutic approaches [4]. Adverse outcomes and mortality were with one exception limited to class 3 or 4 disease:

●Among the 16 patients with class 1 to 2 disease, there was one death (in a patient treated with antibiotics alone) and PCD was effective in all patients in whom it was attempted.

●Among the 28 patients with class 3 disease, six died (21 percent) and 11 (39 percent) had PCD procedures that were considered unsuccessful due to progressive or persistent lesions. Of the 11 who had unsuccessful PCD procedures, seven underwent subsequent nephrectomy and six (86 percent) of those survived.

●Among the four patients with class 4 (bilateral) disease, two died and three PCD procedures were considered unsuccessful.

Adverse outcomes in the patients with class 3 or 4 disease were closely linked to the presence or absence of four risk factors: thrombocytopenia, acute renal failure, impaired consciousness, and shock [4]. The success rate with PCD and antibiotics was 85 percent in patients with no or one risk factor compared with 8 percent in patients with two or more risk factors.

Subsequently a meta-analysis of seven retrospective cohort studies examined 23 risk factors in 175 patients with emphysematous pyelonephritis [24]. The overall mortality rate was 25 percent. Four major risk factors were significantly associated with an increased risk of mortality:

●Bilateral emphysematous pyelonephritis (class 4 in the above classification)

●On imaging, renal parenchymal necrosis with either no fluid content or a streaky/mottled gas pattern (type I in the initial classification system cited above) [7]. Type I was associated with a significantly higher mortality than type II in both the report of this classification system (69 versus 18 percent) [7] and in the series of 48 cases (36 versus 12 percent) [4].

●Conservative therapy, defined as fluid resuscitation and antimicrobials without PCD

●Thrombocytopenia

Similar results were noted in a prospective study of 39 patients with emphysematous pyelonephritis in India [25]. In this study patients were treated with medical management plus PCD. Repeat imaging was performed after three days and additional drainage tubes were placed if needed. If there was no clinical improvement, early nephrectomy was performed. Patients who improved with medical management plus PCD underwent delayed nephrectomy if they developed recurrent pyelonephritis or had a poorly functioning kidney on nuclear imaging. The overall mortality rate was 13 percent. Thrombocytopenia, renal failure, altered mental status, and severe hyponatremia were significantly associated with mortality. Renal parenchymal destruction of >50 percent based on CT significantly predicted the need for nephrectomy and predicted death. The early nephrectomy group had a higher mortality rate (three of seven) whereas the PCD-treated patients had a lower mortality rate (2 of 24). There were no deaths among patients who had initial PCD followed by delayed nephrectomy.

A separate retrospective study of 44 patients diagnosed with emphysematous pyelonephritis (8 with class 1 disease, 12 with class 2, 11 with class 3A, 7 with class 3B, 4 with class 4, and 2 with unknown class) from 2001 to 2013 at the National Taiwan University Hospital found a survival rate of 88.6 percent (39 of 44) despite only one patient undergoing immediate nephrectomy [26]. Need for emergent hemodialysis, shock on presentation, altered mental status, severe hypoalbuminemia (albumin <0.3 g/dL), inappropriate empiric antibiotic treatment, and polymicrobial infection were more common in non-survivors than survivors. Severe hypoalbuminemia was independently associated with failure of therapy with antibiotics +/- PCD or indwelling catheter placement. It is not known whether the albumin concentration itself is important or whether low albumin is just a marker of poor health.

Suggested approach — Published data are limited on the management of emphysematous pyelitis and pyelonephritis. Based upon the observations in the preceding section, we suggest the following approach to the treatment of emphysematous pyelitis or pyelonephritis according to disease class; it is generally similar to that advocated by the authors of the above cited review of 48 cases [4].

●All patients are treated with parenteral antibiotics. Antibiotic selection is as outlined elsewhere for the management of acute pyelonephritis. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Management'.)

The optimal time to transition from intravenous to oral antibiotics and the total duration of antibiotic therapy are unknown. In general, we administer parenteral antibiotics until the patient is stable and has clinically improved (eg, normalizing temperature and white blood cell counts, improved sense of wellbeing). Then, we transition the patient to oral antibiotics to complete a two-week course.

●Patients with class 1 disease (pyelitis) who do not have abscess formation or obstruction can be treated with antibiotics alone [21]. Other patients with class 1 disease and patients with class 2 disease should be treated with antibiotics plus percutaneous catheter drainage (PCD) and, if present, relief of urinary tract obstruction [27]. However, one small, retrospective case series found that 10 of 14 patients with class 2 disease without obstruction responded well to medical treatment alone without any drainage procedures [28].

●Patients with class 3A or 3B disease at low risk (defined as none or one of the following risk factors: thrombocytopenia, acute renal failure, impaired consciousness, or shock) can initially be treated with antibiotics plus PCD and, if present, relief of urinary tract obstruction. However, given the lack of confirmatory evidence beyond the one study [4], some urologists feel that early nephrectomy is warranted in all patients with class 3 disease.

●Nephrectomy is indicated in all patients in whom PCD is unsuccessful.

●Patients with class 3A or 3B disease with two or more of the above risk factors should be treated with antibiotics plus immediate nephrectomy.

●Patients with class 4 disease (bilateral involvement or infection is a solitary functioning kidney) should initially be treated with antibiotics plus bilateral percutaneous catheter drainage and, if present, relief of urinary tract obstruction. Nephrectomy is a last option.

EMPHYSEMATOUS CYSTITIS

Clinical presentation — Two reviews of published cases of emphysematous cystitis revealed the following clinical features [5,14]:

●As with emphysematous pyelonephritis and pyelitis, there was a predominance of older women with diabetes.

●Abdominal pain was the most common symptom of emphysematous cystitis, occurring in up to 80 percent of cases. By comparison, the classic symptoms of acute cystitis (dysuria, urinary frequency, and urinary urgency) occurred in only about one-half of patients.

●Pneumaturia after bladder catheterization occurred in 7 of 10 patients in one series [5].

●Laboratory testing usually revealed pyuria and hematuria with positive urine cultures. The two most common pathogens were E. coli and K. pneumoniae, which accounted for 75 to 80 percent of cases. Other isolates have included Enterococcus and Candida and some infections are polymicrobial.

●Bacteremia was present in approximately one-half of cases [5].

Differential diagnosis — Air within the bladder wall is usually due to emphysematous cystitis (image 2); however, intra-luminal air can occur in the setting of an enterovesical, colovesical, or rectovesical fistula (which, in turn, may be due to diverticulitis (image 3), inflammatory bowel disease, or colorectal carcinoma). Intra-luminal air can also occur following cystoscopy or bladder catheterization.

Therapy — Emphysematous cystitis can usually be treated with medical therapy alone [5,14]. However, bladder irrigation may be needed if blood clots are present, and catheter placement is often required if the patient cannot adequately void. Rarely, bladder debridement and partial or total cystectomy are necessary. In a review of 135 published cases, 10 percent required combined medical and surgical therapy and the overall mortality rate in this group of patients was 7 percent [14].

Parenteral antibiotic selection is as outlined elsewhere for the management of pyelonephritis (see 'Suggested approach' above). The duration of antimicrobial therapy depends upon the clinical response. A review of 20 cases of emphysematous cystitis for which there were data on duration of treatment reported a median length of antibiotic treatment of 10 days [5].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Urinary tract infections in adults".)

SUMMARY AND RECOMMENDATIONS

General

●Emphysematous urinary tract infections (UTIs) are infections of the lower or upper urinary tract associated with gas formation. They can manifest as cystitis, pyelitis (gas in the renal pelvis), or pyelonephritis.

●The clinical features of emphysematous pyelonephritis are indistinguishable from those seen in severe acute pyelonephritis. E. coli and K. pneumoniae account for most cases. (See 'Clinical features' above.)

●Abdominal pain is the major clinical manifestation of emphysematous cystitis, while classic symptoms of cystitis (dysuria, urinary frequency, and urinary urgency) occur in about one-half of cases. Pneumaturia may be seen after bladder catheterization. (See 'Clinical presentation' above.)

●The major risk factors for emphysematous UTIs are diabetes and urinary tract obstruction. The infections primarily occur in women at a mean age of about 60 years. (See 'Risk factors for adverse outcomes' above.)

●The diagnosis of emphysematous UTIs is made by abdominal imaging; computed tomography is more sensitive than plain films and can detect obstructing lesions. (See 'Diagnosis' above.)

●Adverse outcomes and mortality are highest when there is extension of gas or abscess to the perinephric or pararenal space (class 3 disease) or involvement of both kidneys or a solitary functioning kidney (class 4 disease). (See 'Prognostic classification' above.)

Treatment

●We recommend parenteral antibiotic therapy for the treatment of all emphysematous upper urinary tract infections (Grade 1A). In certain cases, other interventions may be warranted, as below. Antibiotic selection is as outlined elsewhere for the management of acute pyelonephritis. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Management'.)

●For patients with class 1 disease (pyelitis) who do not have abscess formation or obstruction, we suggest treatment with antibiotics alone (Grade 2B). (See 'Suggested approach' above.)

●For other patients with class 1 disease and all patients with class 2 disease (gas limited to the renal parenchyma), we suggest treatment with percutaneous catheter drainage (PCD) and, if present, relief of urinary tract obstruction in addition to antibiotics (Grade 2B). (See 'Suggested approach' above.)

●Management of patients with class 3A or 3B disease (extension of gas or abscess into the perinephric or perirenal space) depends on the presence of the following risk factors: thrombocytopenia, acute renal failure, impaired consciousness, or shock (see 'Suggested approach' above):

•For such patients who have none or only one risk factor, we suggest treatment with PCD and, if present, relief of urinary tract obstruction in addition to antibiotics (Grade 2B). Nephrectomy should be performed if PCD is unsuccessful. However, some urologists feel that early nephrectomy is warranted in all patients with class 3 disease.

•For such patients with two or more of the above risk factors, we suggest immediate nephrectomy in addition to antibiotics (Grade 2B).

●For patients with class 4 disease (bilateral involvement or infection in a solitary functioning kidney) we suggest treatment with bilateral PCD and, if present, relief of urinary tract obstruction (Grade 2B). (See 'Suggested approach' above.)

●For patients with emphysematous cystitis who have intravesicular blood clots or cannot adequately void, bladder irrigation may be needed in addition to antibiotics. Otherwise, antibiotic therapy alone is usually sufficient. Approximately 10 percent of patients require surgery for debridement, or rarely, partial or total cystectomy. (See 'Emphysematous cystitis' above.)