24 Pyelonephritis


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24 Pyelonephritis

  1. 1. Clinical manifestations diagnosis and treatment of ACUTE UNCOMPLICATED acute pyelonephritis PYELONEPHRITIS Clinical manifestations — INTRODUCTION — The clinical manifestations of acute uncomplicated pyelonephritis ACUTE PYELONEPHRITIS IS A URINARY TRACT INFECTION THAT HAS include ¨ PROGRESSED FROM THE LOWER URINARY TRACT TO THE UPPER URINARY TRACT. Most episodes of acute pyelonephritis are o flank pain, uncomplicated but hospitalization may be required [1] . o abdominal or pelvic pain, o nausea, vomiting, o fever (≥ 37.8ºC), and/or costovertebral angle tenderness Acute uncomplicated pyelonephritis typically occurs in healthy, young women and must be distinguished from : FEVER HAS BEEN STRONGLY CORRELATED WITH THE DIAGNOSIS o acute complicated pyelonephritis and from OF ACUTE PYELONEPHRITIS; THUS, PATIENTS WITH CLINICAL o chronic pyelonephritis MANIFESTATIONS OF ACUTE PYELONEPHRITIS IN THE ABSENCE OF FEVER SHOULD BE EVALUATED FOR ALTERNATIVE DIAGNOSES [2] . Acute complicated pyelonephritis is progression of upper urinary Symptoms of cystitis may or may not be present [3] . tract infection to : o emphysematous pyelonephritis, o renal corticomedullary abscess, In some cases, the presentation may mimic pelvic inflammatory o perinephric abscess, or disease. Rarely, patients with acute pyelonephritis present with : o papillary necrosis o sepsis, o multiple organ system dysfunction, o shock, and/or acute renal failure Chronic pyelonephritis is an uncommon cause of chronic tubulointerstitial disease due to recurrent infection, such as infection in association with a chronically obstructing kidney stone Diagnosis — (possibly producing xanthogranulomatous pyelonephritis) or vesicoureteral reflux [= ουρητηροκυστική παλινδρόμηση]. The diagnosis of acute uncomplicated pyelonephritis can usually be made from the history, physical examination, and laboratory Affected patients can present with weeks to months of insidious evaluation. symptoms. The physical examination should focus on vital signs and evaluation of the abdomen, pelvis, and the costovertebral angles. In the setting of vaginal symptoms or poorly localized tenderness, a pelvic examination should be performed to distinguish pelvic inflammatory disease from acute uncomplicated pyelonephritis. Pregnancy testing is also appropriate. A urinalysis should be performed to evaluate for pyuria, which is present in virtually all patients with acute pyelonephritis. THE ABSENCE OF PYURIA STRONGLY SUGGESTS AN ALTERNATIVE DIAGNOSIS OR THE PRESENCE OF AN OBSTRUCTING LESION [4] .
  2. 2. White cell casts indicate a renal origin for the pyuria. Other urinalysis parameters lack adequate sensitivity for evaluation of Treatment — pyelonephritis. Initial treatment includes supportive care and initiation of empiric Nitrite testing, for example, has a sensitivity of 35 to 80 percent; it is antibiotic therapy. not useful for detecting presence of organisms unable to reduce nitrate to nitrite, such as enterococci and staphylococci. Inpatient management is appropriate in the following circumstances: o Severe illness with high fevers, pain, and Urine culture and antimicrobial susceptibility testing of o marked debility Inability to maintain oral hydration or uropathogens should be performed in the setting of acute o take oral medications pyelonephritis. o Pregnancy o Concerns about patient compliance Up to 95 percent of episodes of pyelonephritis are associated with >10(5) CFU per mL of organisms, although some patients with pyelonephritis have colony counts of 10(3) to 10(4) CFU per mL [5] . Outpatient management is safe and effective for patients with mild to moderate illness who can be stabilized with rehydration and If the urine sample for culture is obtained through a newly-inserted antibiotics in an outpatient facility and discharged on oral antibiotics catheter, some clinicians consider a colony count of ≥ 10(2) CFU under close supervision. per mL sufficient for diagnosis of pyelonephritis. In an emergency department report of 44 patients with The lower colony counts are extrapolated from studies of cystitis pyelonephritis, for example, a 12 hour observation period with but have not been systematically evaluated in the setting of parenteral antibiotic therapy, followed by completion of outpatient pyelonephritis. oral antibiotics was effective management for 97 percent of patients [7] . Urine gram stain may be helpful for rapid preliminary diagnostic purposes and for guiding the choice of empiric therapy pending culture results. Empiric antibiotics — Empiric antibiotic selection should be guided by knowledge of the epidemiology of antimicrobial susceptibility when available, since rates Imaging studies are not routinely required for diagnosis of acute of antibiotic resistance fluctuate with patterns of antibiotic use in the uncomplicated pyelonephritis but can be helpful in certain community. circumstances. In a report of 4342 urine isolates from patients with cystitis in the mid 1990s, the prevalence of resistance to trimethoprim-sulfamethoxazole rose from 9 to 18 percent over a five year period [8] . Microbiology — In comparison, resistance to ciprofloxacin and aminoglycosides was very low. Escherichia coli is the most common cause of acute pyelonephritis. However, a subsequent study in this region demonstrated that In a report of over 2700 uropathogens isolated from patients with antibiotic resistance trends had reversed [6] . acute pyelonephritis, Escherichia coli accounted for about 82 percent of isolates in women and about 73 percent in men [6] . Among E. coli isolates from over 3200 patients in the late 1990s, there was a decrease in trimethoprim-sulfamethoxazole resistance together Klebsiella pneumoniae was next in frequency, accounting for 2.7 with an increase in the rate of ciprofloxacin resistance (24 to 13 percent percent of isolates in women and 6.2 percent in men. and 1.7 to 3.4 percent, respectively) [6] . Staphylococcus saprophyticus accounted for less than 3 percent of These changes paralleled a reduction in the use of trimethoprim- isolates sulfamethoxazole and an increase in the use of a fluoroquinolone for management of outpatient urinary tract infections (53 to 32 percent and 35 to 61 percent, respectively). Risk for pyelonephritis due to an organism resistance to trimethoprim- sulfamethoxazole or fluoroquinolones appears to vary substantially by region, and risk stratification cannot reliably predict patients at for infection with resistant organisms [9,10] . Recent antibiotic use should be considered in the selection of an empiric regimen pending culture and susceptibliity data.
  3. 3. Oral antibiotics — We favor an oral fluoroquinolone such as Q Routine follow-up management — o levofloxacin (500 to 750 mg orally once daily) or Patients initially treated with parenteral therapy who improve o ciprofloxacin (500 mg orally twice daily) clinically and can tolerate oral fluids may transition to oral antibiotic therapy. for initial empiric treatment of acute pyelonephritis (show table 2) [11,12] . Fluoroquinolone serum levels achieved with oral and intravenous dosing are equivalent, and the modes of delivery are equally The newer fluoroquinolone moxifloxacin should be avoided effective clinically [13] . because of uncertainty regarding effective concentrations in urine. We favor a 7-day course of antibiotics for mild to moderately ill patients with a prompt response to treatment and with infecting o Trimethoprim-sulfamethoxazole (1 double strength tablet strains that are susceptible to the chosen antibiotic [11] : orally twice daily), or o trimethoprim (200 mg orally once daily) can be used if the In a study of 255 women with uncomplicated pyelonephritis infecting strain is known to be susceptible. comparing a 7-day course of ciprofloxacin to a 14-day course of trimethoprim-sulfamethoxazole, patients treated with ciprofloxacin had a more favorable clinical cure rate than those treated with trimethoprim-sulfamethoxazole (96 versus 83 percent ) [14] . If gram-positive cocci are observed on Gram stain, enterococcus or S. saprophyticus should be suspected and amoxicillin (500 mg A five-day course of oral levofloxacin 750 mg once daily was as orally three times daily or 875 mg orally twice daily) should be effective as a ten-day course of ciprofloxacin [15] . added to the treatment regimen until the causative organism is identified. This levofloxacin regimen has FDA approval for uncomplicated pyelonephritis only and is not appropriate for complicated AMPICILLIN AND SULFONAMIDES SHOULD NOT BE pyelonephritis. USED FOR EMPIRIC THERAPY BECAUSE OF THE HIGH RATE OF RESISTANCE AMONG CAUSATIVE PATHOGENS. However, beta lactam regimens should be administered for a full 14-day course given failure rates with a shorter duration of therapy [16] . o Cefpodoxime (200 mg orally twice daily) or o cefixime (400 mg orally once daily) may also be effective for the treatment of acute uncomplicated The duration of antibiotic therapy need not be extended in the pyelonephritis, although published data are limited. setting of bacteremia in the absence of other complicating factors; there is no evidence that bacteremia portends a worse prognosis Cefixime likely has limited activity against S. saprophyticus. [13] . Surveillance blood cultures to demonstrate clearance of bacteremia are appropriate, although follow-up urine cultures are not needed in patients with acute pyelonephritis whose symptoms Parenteral antibiotics — resolve on antibiotics. We favor ceftriaxone or fluoroquinolones (in areas where fluoroquinolone resistance is relatively low) for initial empiric treatment of hospitalized patients with acute uncomplicated pyelonephritis Some clinicians favor fluoroquinolones over ceftriaxone given their excellent genitourinary penetration. Patients with beta-lactam or fluoroquinolone resistance or hypersensitivity may be treated with aztreonam (1 g IV every 8 to 12 hours).
  4. 4. Persistent symptoms — Patients with persistent clinical symptoms on antibiotic therapy should ACUTE COMPLICATED be evaluated for complicated pyelonephritis with radiographic imaging and additional laboratory investigation PYELONEPHRITIS — PATIENTS WITH DELAYED RESPONSE TO THERAPY SHOULD Complicated pyelonephritis is progression of upper urinary tract RECEIVE A LONGER COURSE OF ANTIBIOTICS (14 TO 21 DAYS), infection to : EVEN IN THE ABSENCE OF EVIDENCE FOR COMPLICATED o renal corticomedullary abscess, DISEASE. o perinephric abscess, o emphysematous pyelonephritis, or o papillary necrosis Patients with recurrent symptoms within a few weeks of treatment for pyelonephritis should have repeat urine culture and antimicrobial susceptibility testing. Risk factors for progression to complicated pyelonephritis include : If the pathogen isolated is the same isolate as in the initial episode o urinary tract obstruction, with the same susceptibility profile, a repeat course of treatment with o urologic dysfunction, another antibiotic agent should be instituted. o antibiotic resistant pathogen(s), and In addition, radiographic studies should be performed to evaluate for o diabetes (particularly for emphysematous pyelonephritis and complicated pyelonephritis. papillary necrosis) Clinical manifestations — Imaging — In addition to the clinical manifestations of uncomplicated pyelonephritis discussed above, complicated pyelonephritis MAY Patients with persistent fever or clinical symptoms after 48 to 72 BE ASSOCIATED WITH WEEKS TO MONTHS OF hours of appropriate antimicrobial therapy for uncomplicated INSIDIOUS, NONSPECIFIC SIGNS AND SYMPTOMS pyelonephritis should undergo radiologic evaluation of the upper SUCH AS MALAISE, FATIGUE, NAUSEA, OR urinary tract with ultrasound or computed tomography (CT) scan. ABDOMINAL PAIN. These modalities are useful for evaluating obstruction, abscess, or other complications of pyelonephritis [17-19] . Patients with complicated pyelonephritis due to urolithiasis may Resolution of radiographic hypodensities may lag behind clinical present with renal colic and gross or microscopic hematuria. improvement by up to three months [20] . These findings should prompt consideration of xanthogranulomatous pyelonephritis, a variant of chronic pyelonephritis that may be confused with renal cell carcinoma. Diagnosis — ACUTE COMPLICATED PYELONEPHRITIS IS ASSOCIATED WITH PYURIA AND BACTERIURIA, although these findings may be absent if the infection does not communicate with the collecting system or if the collecting system is obstructed. Urine culture with antimicrobial susceptibility testing should be performed. Parameters for interpretation of urine colony counts are as outlined above for acute uncomplicated pyelonephritis
  5. 5. Microbiology — E. coli is the most common cause of complicated o pyelonephritis. SUMMARY AND RECOMMENDATIONS o Other pathogens including: o Citrobacter sp, Acute uncomplicated pyelonephritis is a urinary tract infection that o Enterobacter sp, has progressed from the lower urinary tract to the upper urinary o Pseudomonas aeruginosa, tract. o enterococci, Acute complicated pyelonephritis is progression of acute o Staphylococcus aureus, and pyelonephritis to emphysematous pyelonephritis, renal o fungi account for a higher proportion in complicated than corticomedullary abscess, perinephric abscess, or papillary uncomplicated pyelonephritis [21] necrosis. S. saprophyticus is an uncommon cause of complicated UTI. It is frequently associated with an underlying condition such as obstruction, urologic dysfunction, diabetes, or infection with an antibiotic-resistant pathogen. Treatment — Clinical manifestations of pyelonephritis include flank pain, nausea, vomiting, fever (≥ 37.8ΊC) and/or costovertebral angle tenderness. Patients with complicated pyelonephritis should be managed initially Laboratory evaluation should include urinalysis (to evaluate for as inpatients. pyuria), urine culture and antimicrobial susceptibility testing. Underlying urinary tract anatomic or functional abnormalities (such as Most episodes of pyelonephritis are associated with >10(5) CFU obstruction or neurogenic bladder) should be addressed in per mL of organisms, although some patients with pyelonephritis consultation with an urologist [21] . have colony counts of 10(3) to 10(4) CFU per mL. Antibiotics alone may not be successful unless such underlying For patients able to tolerate oral antibiotics, we suggest an oral conditions are corrected. fluoroquinolone for initial empiric treatment of acute uncomplicated pyelonephritis For patients unable to tolerate oral antibiotics, we suggest Broad-spectrum parenteral antibiotics should be used for empiric intravenous ceftriaxone or a fluoroquinolone for initial empiric treatment of complicated pyelonephritis parenteral treatment of acute uncomplicated pyelonephritis Antimicrobial therapy subsequently must be tailored to individual For patients with complicated pyelonephritis, we suggest broad- patient circumstances with consideration of the results of spectrum parenteral susceptibility testing and prior recent antibiotic therapy. Subsequent choice and duration of antibiotic therapy must be Transitioning to oral antibiotic therapy is as outlined above for acute tailored to antimicrobial susceptibility findings and clinical uncomplicated pyelonephritis circumstances. Imaging (ultrasonography or computed tomography) is warranted in the setting of persistent fever or clinical symptoms after 48 to 72 Antibiotics should be administered for at least 10 to 14 days, although a hours of appropriate antimicrobial therapy to evaluate for longer duration of therapy may be warranted for patients with obstruction, abscess, or other complications of pyelonephritis. underlying complicating factors. THE FIVE-DAY REGIMEN OF LEVOFLOXACIN 750 MG ONCE DAILY HAS FDA APPROVAL FOR UNCOMPLICATED PYELONEPHRITIS ONLY AND IS NOT APPROPRIATE FOR COMPLICATED PYELONEPHRITIS.
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