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Pyelonephritis

Definition
Inflammation of the kidney and renal pelvis, usually as a result of a bacterial infection Acute pyelonephritis (focus of this topic) o Characterized by rapid onset of fever, chills, nausea, vomiting, diarrhea, and flank pain o Usually caused by Escherichia coli Chronic pyelonephritis o Chronic interstitial nephritis believed to result from bacterial infection of the kidney

Epidemiology

Acute pyelonephritis o Incidence 280 cases per 100,000 women in the community between ages 18 and 49 ~7% of patients require hospitalization. 2030% of pregnant women with asymptomatic bacteriuria subsequently develop pyelonephritis. o Sex More common among women

Risk Factors
Pregnancy Recent urinary tract infection (UTI) Sexual intercourse 3 times per week in the previous 30 days Diabetes Recent incontinence New sexual partner in the previous year Family history of UTI/pyelonephritis Urinary obstruction o Urinary calculus o Stricture o Tumor o Benign prostatic hypertrophy in men Neurogenic bladder Vesicoureteral reflux Insertive rectal intercourse (men) HIV infection and low CD4+ cell counts Bladder catheterization

Etiology

Renal parenchymal infection, most often secondary to ascending infection from lower urinary tract

May occur from hematogenous spread (bacteremia, fungemia)


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Most common among chronically ill or immunocompromised patients Causative agents o Most common: gram-negative bacilli E. coli causes ~80% of acute infections in patients without catheters, urologic abnormalities, or calculi. Proteus, Klebsiella, and occasionally Enterobacter species account for a smaller proportion of uncomplicated infections. These organisms, along with Serratia and Pseudomonas, assume increasing importance in: o Recurrent infections o Infections associated with catheters or other urologic manipulation, calculi, or obstruction o Staphylococcus saprophyticus accounts for 10 15% of acute symptomatic UTIs in young women. o Enterococci and Staphylococcus aureus are associated with some UTIs. S. aureus in a urine culture should arouse concern about a hematogenous source of kidney infection (bacteremia). o Mycoplasma hominis has been isolated from renal tissues of patients with pyelonephritis and is probably responsible for some of these infections as well.

Associated Conditions
Klebsiella and Proteus species predispose to renal stone formation and are isolated more frequently from patients with calculi.

Symptoms & Signs


Symptoms generally develop rapidly over a few hours or a day. o Fever o Shaking chills o Nausea o Vomiting o Abdominal pain o Diarrhea o Generalized muscle tenderness o In some cases, symptoms of cystitis (dysuria, frequency, urgency, suprapubic pain)

Physical examination o Fever o Tachycardia o Marked tenderness on deep pressure in 1 or both costovertebral angles (flank tenderness) or on deep abdominal palpation

Differential Diagnosis
The differential diagnosis is broad, encompassing other clinical syndromes of abdominal pain and fever that include but are not limited to: o Cholecystitis o Appendicitis o Diverticulitis o Tubo-ovarian abscess o Pelvic inflammatory disease o Bowel ischemia o Urinary calculus o Splenic infarct o Hepatitis o Spinal osteomyelitis

Diagnostic Approach

Assess hemodynamic status. Identify predisposing factors. Identify organism (through blood/urine cultures). Exclude ureteral obstruction. Consider pregnancy testing.

Laboratory Tests
Urinalysis o Pyuria: very sensitive and specific marker by chamber-count microscopy Dipstick less sensitive o Hematuria o Leukocyte casts seen infrequently but pathognomonic for a renal source of pyuria (rather than a lower tract source) o Bacteria in urine (although their absence does not exclude the diagnosis) o Nitrite test: less useful Sensitivity: 3580% Does not detect organisms that are unable to reduce nitrate to nitrite (enterococci, staphylococci) Complete blood count o Leukocytosis Urine culture Blood cultures: positive in a minority of cases of pyelonephritis

Blood urea nitrogen and creatinine measurements for evaluation of renal function Pregnancy test if menses are irregular or contraception history is questionable

Imaging
Imaging is not necessary in the initial diagnostic evaluation of most cases of pyelonephritis, but is warranted: o In cases of recurrent/relapsing pyelonephritis o To exclude other diagnostic possibilities o When there is clinical suspicion of nephrolithiasis or obstructive uropathy o In most male patients, who generally should be considered to have complicated infections Contrast-enhanced CT is the most reliable imaging test for identification of pyelonephritis. Imaging is indicated after antimicrobial therapy has begun if: o Blood cultures remain persistently positive o Fever persists for > 72 hours o The patients clinical status suddenly worsens

Diagnostic Procedures

Not indicated in most cases If an obstruction is found: o It must be corrected or bypassed. o Samples of material from the obstructed region should be collected and microbiologic information obtained. Site of care Assess the severity of illness, considering the possibility of early sepsis syndrome. If necessary, establish hemodynamic stability with intravenous fluid resuscitation. o Determine whether the patient can tolerate oral intake. o Inpatient care should be considered if:
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Treatment Approach

The patient cannot maintain hydration or take medications by mouth. Concerns exist about compliance. The diagnosis is uncertain. The patient is severely ill (high fevers, pain, debility). The patient is pregnant.

Supportive care
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Use analgesics for pain. Administer antiemetics if necessary. Antibiotic therapy The choice of empiric antimicrobial therapy depends on the site of care. Patients who fail to respond within 72 hours or who experience a relapse after therapy should be evaluated for unrecognized suppurative foci, calculi, or urologic disease.
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Specific Treatments
Antibiotic therapy: general information The choice of antibiotic depends on bacterial susceptibilities. Although the optimal route and duration of therapy have not been established, a 7- to 14-day course of a fluoroquinolone, an aminoglycoside, or a third-generation cephalosporin is usually adequate. o Some experts recommend a full 14-day course of -lactam regimens. o Some suggestion of higher success rates than with 7-day -lactam courses Neither ampicillin nor trimethoprim-sulfamethoxazole (TMP-SMX) should be used as initial therapy because > 25% of strains of E. coli causing pyelonephritis are now resistant to these drugs in vitro. Nitrofurantoin should not be used for treatment of pyelonephritis because of its unreliable tissue penetration.

Mild to moderate illness No nausea or vomiting Can usually be managed on an outpatient basis Give an oral quinolone for 714 days (doses below) or Single-dose ceftriaxone (1 g IV) or gentamicin (35 mg/kg IV) followed by o Oral TMP-SMX (160/800 mg; double-strength tablet) PO bid for 14 days if the isolate is sensitive Quinolone dosing (for adults with normal renal function) o Ciprofloxacin: 500 mg every 12 hours o Levofloxacin: 250500 mg/d

Severe illness or possible urosepsis

Hospitalization is required, with administration of intravenous antibiotics until defervescence. Parenteral regimen options for uncomplicated pyelonephritis in women include: o Fluoroquinolone (doses for adults with normal renal function)

Ciprofloxacin: 400 mg every 12 hours Ofloxacin: 400 mg every 12 hours Levofloxacin: 500 mg/d o Ceftriaxone: 12 g/d o Gentamicin: 1 mg/kg every 8 hours (with or without ampicillin, 1 g every 6 hours) o Aztreonam: 1 g every 812 hours For complicated infectionsi.e., those associated with catheterization, instrumentation, urologic abnormalities (anatomic or functional), stones, obstruction, immunosuppression, renal disease, or diabetesin men or women, consider the regimens above or obtain broader coverage with: o Imipenem/cilastatin: 250500 mg every 68 hours or o Ticarcillin/clavulanate: 3.1 g every 46 hours After defervescence, the patient can be switched to an oral quinolone, cephalosporin, or TMP-SMX for 14 days, depending on organism sensitivities. o Severe illness in patients with complicated infection may require treatment for 21 days.

Pregnant patients Manage with hospitalization and parenteral antibiotic therapygenerally with a cephalosporin or an extendedspectrum penicillin. Give continuous low-dose prophylaxis with nitrofurantoin to women who have recurrent infections during pregnancy.

Monitoring
Patients who fail to respond within 72 hours or who experience a relapse after therapy should be evaluated for unrecognized suppurative foci, calculi, or urologic disease. Imaging is indicated to exclude obstructing urinary calculus, perinephric abscess, or obstructive uropathy if, after antimicrobial therapy has begun: o Blood cultures remain persistently positive o Fever persists for >72 hours

o The patients clinical status deteriorates suddenly Routine post-treatment cultures are not necessary for asymptomatic patients. Recurrence of symptoms within 2 weeks after completion of treatment should prompt repeat urine culture and antibiotic sensitivity testing. o If the same species persists, imaging by CT or ultrasonography should be performed to assess for collections or other foci of infection (e.g., stones). If imaging is unrevealing, consider retreatment for 2 weeks with a different agent.

Complications
Perinephric abscess Urosepsis o Bacteremia and seeding of other foci o Death Renal insufficiency Papillary necrosis Emphysematous pyelonephritis Repeated upper UTIs o Repeated infections often represent relapse rather than reinfection, particularly if they occur within 2 weeks of a treatment course. o A vigorous search for renal calculi or an underlying urologic abnormality should be undertaken. If neither is found, 6 weeks of antimicrobial therapy may eradicate an unresolved focus of infection. Upper UTIs during pregnancy are associated with increased incidences of: o Low-birth-weight infants o Premature delivery o Neonatal death

Prognosis

Acute uncomplicated pyelonephritis in adults rarely progresses to renal functional impairment and chronic renal disease. Manifestations of acute pyelonephritis usually respond to therapy within 4872 hours, except in cases with: o Papillary necrosis o Abscess formation o Urinary obstruction In severe pyelonephritis, fever subsides more slowly and may not disappear for several days, even after the start of appropriate antibiotic treatment.

Short-term mortality rates from acute pyelonephritis are highest among patients who:
o o o o

Are > 65 years of age Have septic shock Are bedridden Are immunosuppressed

Prevention
Women who experience frequent symptomatic UTIs (at least 3 per year) are candidates for long-term administration of low-dose antibiotics. Prophylaxis should be initiated only after bacteriuria has been eradicated with a full-dose treatment regimen. o A daily or thrice-weekly single dose of TMP-SMX (80/400 mg), TMP alone (100 mg), or nitrofurantoin (50 mg) should be effective. o Norfloxacin and other fluoroquinolones are also used. o These women should: Avoid spermicide use. Void soon after intercourse. Consider prophylaxis after intercourse if episodes are temporally related to intercourse. All pregnant women should be screened for bacteriuria in the first trimester and treated if bacteriuria is demonstrated. Postmenopausal women who are not taking oral estrogen replacement therapy can effectively manage recurrent UTIs with topical intravaginal estrogen cream. Other candidates for antibiotic prophylaxis o Men with chronic prostatitis o Patients undergoing prostatectomy (intraoperatively and perioperatively) Prophylaxis is generally discouraged for patients with long-term indwelling catheters and asymptomatic bacteriuria. o In these cases, prophylaxis often results in an increasingly resistant flora. o The recommended approach is the removal of the catheter and a short course of treatment with an appropriate antibiotic. o If the catheter cannot be removed, treat bacteriuria only if the patient develops symptoms or is at high risk for bacteremia.
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ICD-9-CM
590.0_ Chronic pyelonephritis, (with vs. without lesion of renal medullary necrosis specified by fifth digit) 590.1_ Acute pyelonephritis, (with vs. without lesion of renal medullary necrosis specified by fifth digit) 590.80 Pyelonephritis (not specified as acute or chronic), unspecified

See Also Internet Sites


Professionals o Pyelonephritis ClinicalTrials.gov o Guidelines National Guidelines Clearinghouse Patients o Pyelonephritis (Kidney Infection) in Adults National Kidney and Urologic Diseases Information Clearinghouse o Kidney infection (pyelonephritis) MedlinePlus

Nephrolithiasis Urinary Tract Infection

General Bibliography
Brown JS et al: Urologic complications of diabetes. Diabetes Care28:177, 2005 [PMID:15616253] Czaja CA et al: Population-based epidemiologic analysis of acute pyelonephritis. Clin Infect Dis 45:273, 2007 [PMID:17599303] Johnson JR: Treatment and prevention of urinary tract infections, in Urinary Tract Infections: Molecular Pathogenesis and Clinical Management, HLT Mobley, JW Warren (eds). Washington, DC, ASM Press, 1996, pp 95 118 Liu H, Mulholland SG: Appropriate antibiotic treatment of genitourinary infections in hospitalized patients. Am J Med 118 Suppl 7A:14S, 2005 [PMID:15993673] Lundstedt AC et al: Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection. J Infect Dis 195:1227, 2007 [PMID:17357062] Ramchandani M et al: Possible animal origin of humanassociated, multidrug-resistant, uropathogenic Escherichia coli. Clin Infect Dis40:251, 2005 [PMID:15655743] Scholes D et al: Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med 142:20, 2005 [PMID:15630106]

Stamm WE, Schaeffer AJ (eds): The State of the Art in the Management of Urinary Tract Infections. Am J Med 113(Suppl 1A):1S84S, 2002 Talan DA et al: Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial. JAMA 283:1583, 2000 Mar 22-29 [PMID:10735395] Warren JW et al: Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis 29:745, 1999 [PMID:10589881] This topic is based on Harrisons Principles of Internal Medicine, 17th edition, chapter 282, Urinary Tract Infections, Pyelonephritis, and Prostatitis by WE Stamm.

PEARLS
Lower UTI (cystitis) is not commonly associated with systemic signs/symptoms. o Fever or nausea/vomiting in the setting of UTI usually suggests upper-tract disease. UTIs due to Klebsiella and Proteus species are associated with renal stones. Uncomplicated UTI is uncommon among men. o Men who present with pyelonephritis should be assumed to have complicated infection and should undergo imaging of the urinary tract to identify a predisposing factor. Isolation of S. aureus from a urine culture should raise concern about hematogenous infection and prompt an evaluation of blood cultures.