INTRODUCTION — Emphysematous urinary tract infections (UTIs) are infections of the lower or upper urinary tract associated with gas formation. They may involve the bladder (cystitis), renal pelvis (pyelitis), or kidney (pyelonephritis). Diabetes mellitus is a major risk factor for these infections [1-3].
This topic discusses emphysematous UTIs. Acute complicated UTIs not complicated by gas formation and renal abscesses are discussed in detail elsewhere. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults" and "Renal and perinephric abscess".)
MICROBIOLOGY AND PATHOGENESIS — Emphysematous UTIs are usually due to Escherichia coli or Klebsiella pneumoniae. These two organisms account for 65 to 100 percent of the isolates described in various retrospective reports [4-8].
Other reported causative organisms include Proteus, Enterococcus, Pseudomonas, Clostridium, and, rarely, Candida spp and Aspergillus [7,9-11]. Some infections are polymicrobial.
The pathogenesis of emphysematous UTIs is poorly understood. Among patients with diabetes mellitus, elevated tissue glucose levels 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].
RISK FACTORS — Diabetes mellitus and urinary tract obstruction are the major risk factors for emphysematous UTIs. They occur more commonly in females. Emphysematous pyelonephritis has also been rarely reported in renal transplant recipients .
As an example, in one of the largest single retrospective series, which included 48 patients in Taiwan who were diagnosed with either emphysematous pyelonephritis or emphysematous pyelitis, 96 percent had diabetes mellitus and 22 percent had urinary tract obstruction . The mean patient age was 60 years (range 37 to 83 years) and females outnumbered males 6:1.
In other case series, diabetes mellitus was documented in more than 80 percent of patients with emphysematous pyelonephritis [4,6,13-15], at least 50 percent of patients with emphysematous pyelitis, and 60 to 70 percent of patients with emphysematous cystitis [5,16].
Urinary tract obstruction has been reported in 0 to 50 percent of patients with diabetes mellitus [6,14,15]. In contrast, obstruction was present in all six patients without diabetes in two reports [4,15]. The main causes of urinary tract obstruction were papillary necrosis and, less often, ureteral calculi .
EMPHYSEMATOUS PYELONEPHRITIS AND PYELITIS — Emphysematous pyelonephritis is a gas-producing, necrotizing infection involving the renal parenchyma and, in some cases, perirenal tissue [4,6,13,17-19]. Emphysematous pyelitis (ie, gas in the renal pelvis (image 1)) or cystitis (image 2) can occur with or without associated emphysematous pyelonephritis [4,5,16]. (See 'Emphysematous cystitis' below.)
●Typical presentation – The clinical features of emphysematous pyelonephritis and 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", section on 'Clinical manifestations'.)
As an example, in a systematic review of 37 studies including over 1000 patients with emphysematous pyelonephritis, the most common presenting symptoms and signs were :
•Pyuria – 87 percent
•Fever – 80 percent
•Flank pain or costovertebral angle tenderness – 63 to 74 percent
•Tachycardia – 65 percent
•Dysuria – 60 percent
Pneumaturia and palpable crepitus were each reported in fewer than 10 percent.
Other common laboratory findings include hyperglycemia, leukocytosis, and elevated serum creatinine.
●Complications – Emphysematous pyelonephritis can be complicated by acute kidney injury (reported in 60 percent in the systematic review described above) and septic shock (19 percent) . Bacteremia is also relatively common. In one series of 48 patients, bacteremia was documented in 54 percent, and all organisms isolated from blood were simultaneously found in cultures of urine or renal pus .
Acute anuric kidney injury is an uncommon complication of emphysematous pyelonephritis that can be seen in patients with bilateral infection or unilateral disease in a solitary functioning kidney .
Rarely, perirenal extension can progress to pneumomediastinum .
Diagnosis — The diagnosis of emphysematous pyelitis or pyelonephritis is typically made when computed tomography (CT) is performed in a patient with acute complicated UTI (ie, UTI with fever or signs of upper tract involvement) and demonstrates air in the collecting system (pyelitis) or in the renal parenchyma and/or the surrounding tissues (pyelonephritis).
CT is the preferred imaging modality as it is more sensitive than other modalities and can delineate the extent of gas formation and any obstructing lesions in the urinary tract [4-6]. CT findings have also been used for prognostic classification of emphysematous pyelonephritis. (See 'Prognosis' below.)
Air associated with emphysematous UTI can also be detected on plain films of the abdomen, with a reported sensitivity ranging from 50 to 85 percent [4-6,20]. Similarly, one systematic review reported that the accuracy of renal ultrasound for detecting emphysematous pyelonephritis was 68 percent .
Differential Diagnosis — The clinical presentation of emphysematous pyelitis or pyelonephritis is similar to that of severe, acute pyelonephritis, xanthogranulomatous pyelonephritis, renal abscess, or acute papillary necrosis. These conditions have distinct imaging findings and are discussed in detail elsewhere. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Clinical manifestations' and "Xanthogranulomatous pyelonephritis" and "Renal and perinephric abscess", section on 'Clinical manifestations' 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. CT findings can help differentiate between these possibilities.
Care team and supportive management — Patients with emphysematous pyelitis or pyelonephritis should be managed by or in concert with a urologist and with a specialist in infectious diseases. Many such patients warrant urologic intervention for obstruction and drainage of gas and purulent material. As drainage can typically be done percutaneously, interventional radiology is also often involved in the care of these patients.
Patients who are severely ill may need medical management of sepsis or septic shock. (See "Evaluation and management of suspected sepsis and septic shock in adults".)
Other aspects of medical care include optimizing glucose control or addressing other underlying risk factors for UTI. (See "Management of diabetes mellitus in hospitalized patients".)
Isolated emphysematous pyelitis — For patients with gas limited to the collecting system, antimicrobial therapy alone is likely sufficient to treat the infection, unless obstruction is also present, in which case intervention to relieve the obstruction is also warranted (see 'Relief of obstruction, if present' below). The approach to antimicrobial therapy is the same as that for patients with renal or perirenal involvement. (See 'Antibiotic therapy' below.)
Although data are limited on the management of such cases, case series that included small numbers of patients with isolated emphysematous pyelitis treated with antibiotics alone (in addition to management of obstruction, if needed) have reported good outcomes (resolution of infection without need for further intervention) [23-26].
Renal or perirenal involvement — The management of emphysematous pyelonephritis includes antibiotic therapy, relief of any urinary tract obstruction, and drainage of gas and purulent material. We suggest reserving nephrectomy for persistent or worsening infection despite these interventions.
Antibiotic therapy — Antibiotic therapy is warranted for all patients with emphysematous pyelonephritis or pyelitis. Given the severity of infection, we suggest hospitalization and initial therapy with parenteral antibiotics. Empiric antibiotic selection (table 1) and selection and duration of directed antibiotic therapy are the same as those for hospitalized patients with acute complicated UTI and are discussed in detail elsewhere. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Empiric antimicrobial therapy'.)
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 tailored to culture results to complete a two-week course. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Directed antimicrobial therapy'.)
Relief of obstruction, if present — If the emphysematous infection is associated with urinary tract obstruction (eg, as evidenced by hydronephrosis), correction of the obstruction is warranted. In case series and retrospective studies of patients with emphysematous pyelonephritis and obstruction, both percutaneous nephrostomy catheters and ureteral stents have been used [7,8,24,26,27].
Percutaneous drainage — For individuals who have emphysematous pyelonephritis, with gas in the renal parenchyma, with or without extension of gas into the extrarenal space, we suggest percutaneous drainage of the gas and purulent material in addition to antibiotic therapy. For patients who are not severely ill and whose infection is limited to a single kidney without extrarenal extension or discrete abscess, deferring drainage is a reasonable option. One small, retrospective case series found that 10 of 14 patients with such limited disease without obstruction responded well to antibiotic treatment alone without any drainage procedures . We generally reserve surgical management (nephrectomy or open drainage) for patients who do not respond to this initial nonsurgical treatment. (See 'Monitoring and management of poor response' below.)
When drainage is performed, we submit drainage specimens for culture to help guide antibiotic therapy; the urine culture results do not always correlate with culture of drainage or surgical specimens [7,8]. The drainage catheter generally stays in place until the patient is clinically improving and there is no longer significant drain output despite confirmation of correct positioning.
High-quality evidence to inform the optimal management of emphysematous pyelonephritis is unavailable, as data are mainly limited to retrospective reviews and case series. Historically, treatment of emphysematous pyelonephritis usually involved nephrectomy or open drainage along with systemic antibiotics [6,14,15,28,29]. However, more recent reports have described successful outcomes with percutaneous drainage in addition to antibiotics [4,6,7,23,25,30-32]. As an example, in a systematic review of 10 retrospective studies including 210 patients with emphysematous pyelonephritis, mortality associated with medical management plus percutaneous catheter drainage was lower than that with either medical management alone or medical management plus emergency nephrectomy (13.5 versus 50 and 25 percent, respectively) .
More extensive disease (ie, extrarenal extension of infection or involvement of both kidneys) and features of sepsis are associated with a higher risk of treatment failure with percutaneous drainage. (See 'Prognosis' below.)
Monitoring and management of poor response — For patients with emphysematous pyelonephritis, we reassess after 48 hours with clinical evaluation and repeat imaging to confirm position of the percutaneous drain and to evaluate the need for additional drainage. We also adjust the antibiotic regimen based on urine and drainage culture results. If the patient has lack of improvement or clinical deterioration despite optimizing antibiotic therapy and catheter drainage, consideration of nephrectomy is the next step.
This approach was evaluated in a prospective study of 39 patients with emphysematous pyelonephritis in India . In this study, patients were treated with antibiotics and percutaneous drainage. Repeat imaging was performed after three days, with additional drainage catheters placed if needed. If there continued to be no improvement despite additional drainage, early nephrectomy was performed. Patients who improved with percutaneous drainage but developed recurrent pyelonephritis or had poor function kidney on nuclear imaging underwent delayed nephrectomy. The overall mortality rate was 13 percent. Three of the seven patients who received early nephrectomy for lack of improvement died compared with 2 of the 24 patients who were treated with percutaneous drainage alone. There were no deaths among the four patients who underwent delayed nephrectomy.
Persistent infection (and need for nephrectomy) following initial nonsurgical management is more likely in individuals with more extensive disease or septic complications. As an example, in a retrospective study of 43 patients treated conservatively with antibiotics and percutaneous drainage, treatment failure occurred in 33 percent and was associated with hypoalbuminemia, need for emergency hemodialysis, and polymicrobial infection . In another study, extensive renal parenchymal destruction was associated with a need for nephrectomy .
Prognosis — In a systematic review of 37 studies including 1145 patients with emphysematous pyelonephritis and pyelitis, the overall pooled mortality rate was 12.5 percent; however, mortality varied by severity of disease . Extensive disease and certain complications including thrombocytopenia, acute kidney injury, confusion, hyponatremia, and septic shock have been associated with higher mortality rates.
Different prognostic classifications have been proposed [4,7,33]. One of the more commonly cited systems categorizes emphysematous pyelonephritis or pyelitis into four prognostic classes based upon the extent of disease on CT scan findings :
●Class 1: Gas in the collecting system only (ie, emphysematous pyelitis); in some patients, there may be severe obstruction at the site of the pyelitis
●Class 2: Gas in the renal parenchyma without extension to the extrarenal space
●Class 3: Extension into 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
A higher class (ie, more extensive disease) has been associated with an increased risk of poor outcomes. In the systematic review mentioned above, the pooled mortality rate associated with class 1 and 2 disease was 7.2 percent compared with 22.8 percent with class 3 and 4 . Similarly, in the retrospective study that developed this classification system, adverse outcomes and mortality were, with one exception, limited to class 3 or 4 disease . Among the 28 patients with class 3 disease, 6 (21 percent) died and 11 (39 percent) had percutaneous drainage procedures that were considered unsuccessful due to progressive or persistent lesions. Of the 11 who had unsuccessful percutaneous procedures, 7 underwent subsequent nephrectomy and 6 (86 percent) of those survived. Among the four patients with class 4 disease, three percutaneous procedures were considered unsuccessful, and two died .
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 . The success rate with percutaneous drainage 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.
Another classification system incorporated the extent of disease as categorized above with other potential risk factors for adverse outcomes . It assigned one point for each of the following: age >50 years, total leukocyte count ≥12,000 or ≤4000, body mass index (BMI) ≥30 or ≤18, platelets ≤100,000/microL, serum creatinine ≥3, albumin ≤2.5 g/dL, class 2 or 3 disease according to classification above, sodium ≤130, ≥2 comorbidities, or multidrug-resistant organism.
●Among those with a score of 0 through 4 (good category): Only 1 of 48 patients (2 percent) needed emergency nephrectomy after initial antibiotics and percutaneous drainage.
●Among those with a score of 5 through 7 (intermediate category): Three of 21 (14 percent) needed emergency nephrectomy after initial antibiotics and percutaneous drainage, and 4 of 21 (19 percent) died.
●Among those with a score of 8 through 10 (poor category): All 3 patients in the poor category died.
EMPHYSEMATOUS CYSTITIS — Emphysematous cystitis is a rare type of acute complicated UTI characterized by gas formation in the wall and lumen of the bladder. Emphysematous cystitis is usually an isolated process but can rarely occur in patients who have concurrent emphysematous pyelonephritis . (See 'Emphysematous pyelonephritis and pyelitis' above.)
●Clinical features – The clinical presentation of emphysematous cystitis is variable. In one review of 135 cases, 7 percent were asymptomatic and identified incidentally on imaging . The most common presenting feature is abdominal pain, occurring in 80 percent in one review of 53 cases . In that review, the classic symptoms of acute cystitis (dysuria, urinary frequency, and urinary urgency) occurred in only about one-half of patients, as did fever, nausea, vomiting, urinary retention, and gross hematuria. Pneumaturia after bladder catheterization occurred in 7 of 10 patients. Bacteremia was present in approximately one-half of cases.
●Diagnosis and differential diagnosis – The diagnosis of emphysematous cystitis is generally made in patients found to have air within the bladder wall (image 2), with or without intraluminal air, on abdominal imaging. The diagnosis is typically made with abdominal computed tomography (CT), although radiographs demonstrating a curvilinear area of radiolucency outlining the bladder wall are also diagnostic. Intraluminal air alone is less specific for emphysematous cystitis and can also occur following bladder instrumentation (eg, cystoscopy or catheterization) or 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). If only intraluminal air is identified on imaging, we reserve the diagnosis of emphysematous cystitis for individuals who have other consistent features (abdominal pain or other symptoms referable to the bladder, pyuria, and bacteriuria) and do not have evidence of or concern for a fistulous connection to the gastrointestinal tract and have not had recent instrumentation.
●Management – Emphysematous cystitis can usually be successfully treated with antibiotic therapy alone [5,16]. Given the potential for complicated infection, particularly among patients with poorly controlled diabetes mellitus, we suggest initial therapy with parenteral antibiotics. However, outpatient treatment with oral antibiotics may be reasonable for select individuals with mild or no symptoms and well-controlled comorbidities. Empiric antibiotic selection (table 1) and selection and duration of directed antibiotic therapy are the same as those for acute complicated UTI and are discussed in detail elsewhere. (See "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Empiric antimicrobial therapy' and "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Directed antimicrobial therapy'.)
Other aspects of medical care include optimizing glucose control or addressing other underlying risk factors for UTI. (See "Management of diabetes mellitus in hospitalized patients".)
Bladder irrigation may be needed if blood clots are present, and bladder catheterization is often required if the patient cannot adequately void. Rarely, bladder debridement or partial or total cystectomy is warranted for patients with progressive infection despite medical therapy.
In a review of 53 cases of emphysematous cystitis, 9 percent were successfully treated with oral antibiotics; the remainder received initial parenteral therapy . The median hospital duration was 7 days (among the 18 with reported data) and the median antibiotic duration was 10 days (among the 20 with reported data). Complications occurred in 10 (18 percent), 8 of whom proceeded to laparotomy for peritoneal signs, pneumoperitoneum, or perivesical abscess. A similar proportion (10 percent) of patients required combined medical and surgical therapy in a separate review of 135 cases . In these reviews, the overall mortality rates were 7 and 10 percent [5,16]. However, some of the patients who died also had emphysematous pyelonephritis, and overall, the contribution of emphysematous cystitis to mortality was uncertain.
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
●Definitions – Emphysematous urinary tract infections (UTIs) are infections of the bladder (cystitis), renal pelvis (pyelitis), or kidney (pyelonephritis) that are characterized by gas formation. (See 'Introduction' above.)
●Microbiology – Escherichia coli and Klebsiella pneumoniae account for most cases. (See 'Microbiology and pathogenesis' above.)
●Risk factors – The major risk factors are diabetes mellitus and urinary tract obstruction. These infections primarily occur in females at a mean age of about 60 years.
●Emphysematous pyelitis or pyelonephritis
•Clinical presentation and diagnosis – Clinical features are indistinguishable from those seen in severe, acute pyelonephritis (fever, flank or abdominal pain, nausea). The diagnosis is made in a patient with UTI (symptomatic pyuria and bacteriuria) who has air in the collecting system, renal parenchyma, and/or perirenal tissue on computed tomography (CT). (See 'Clinical features' above and 'Diagnosis' above.)
•Management of isolated pyelitis – For patients with gas limited to the collecting system, antimicrobial therapy, with relief of any urinary tract obstruction, is generally sufficient to treat the infection. (See 'Isolated emphysematous pyelitis' above.)
•Management of renal or perirenal involvement – For patients with involvement of the kidneys or extrarenal space, we suggest percutaneous drainage of gas and purulent material rather than no intervention (Grade 2C), in addition to antimicrobial therapy and relief of any obstruction. The drainage catheter generally stays in place until the patient has clinically improved and there is no significant drain output despite confirmation of correct positioning. Patients who are not severely ill and have limited involvement of a single kidney may reasonably forgo initial drainage. (See 'Renal or perirenal involvement' above.)
For patients with renal or perirenal involvement, even those with extensive or bilateral disease, we also suggest percutaneous drainage rather than nephrectomy as the initial strategy to remove renal or perirenal gas and purulent material (Grade 2C). We reserve nephrectomy for patients who have no improvement or have clinical deterioration despite optimized antibiotic therapy and catheter drainage.
Data are limited to small observational studies but suggest that percutaneous drainage is associated with lower mortality than either medical management alone or initial nephrectomy.
•Prognosis – Overall mortality is estimated at 12 percent but varies widely. Extensive extrarenal or bilateral disease and septic complications, including thrombocytopenia, acute kidney injury, confusion, hyponatremia, and shock, have been associated with mortality and failure of percutaneous management. (See 'Prognosis' above.)
●Emphysematous cystitis – This typically presents with abdominal pain; the classic symptoms of cystitis (dysuria, urinary frequency and urgency) occur in about one-half of patients. The diagnosis is made in patients with UTI (symptomatic pyuria and bacteriuria) who have air within the bladder wall (image 2), with or without intraluminal air, on abdominal imaging. Antimicrobial therapy alone is typically sufficient. (See 'Emphysematous cystitis' above.)
●Antimicrobial therapy – For patients with emphysematous UTI, we suggest initial therapy with parenteral antibiotics (Grade 2C) given the potential for severe infection. Outpatient treatment with oral antibiotics is a reasonable alternative for selected individuals with emphysematous cystitis who have mild or no symptoms and well-controlled comorbidities. Empiric antibiotic selection (table 1) and selection and duration of directed antibiotic therapy are the same as those for acute complicated UTI and are discussed in detail elsewhere. (See 'Antibiotic therapy' above and "Acute complicated urinary tract infection (including pyelonephritis) in adults", section on 'Management'.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Daniel J Sexton, MD, who contributed to an earlier version of this topic review.
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