Acute pyelonephritis is a urinary tract infection that has progressed to the kidneys. It typically causes flank pain, nausea, fever and tenderness. Laboratory tests show pyuria on urinalysis and culture usually isolates E. coli bacteria. Acute pyelonephritis can be uncomplicated or complicated by conditions like obstruction or infection with resistant bacteria. Uncomplicated cases are usually treated initially with oral fluoroquinolones as outpatients. Complicated or severe cases require hospitalization and intravenous antibiotics along with treatment of underlying conditions. Proper diagnosis, culture and treatment duration are important to resolve the infection.

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. 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. 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. 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. 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.

6. REFERENCES Jernelius, H, Zbornik, J, Bauer, CA. One or three weeks'
treatment of acute pyelonephritis? A double-blind comparison,
using a fixed combination of pivampicillin plus pivmecillinam. Acta
Stamm, WE, Hooton, TM, Johnson, JR, et al. Urinary tract Med Scand 1988; 223:469.
infections: From pathogenesis to treatment. J Infect Dis 1989;
159:400. Johnson, JR, Vincent, LM, Wang, K, et al. Renal
ultrasonographic correlates of acute pyelonephritis. Clin Infect Dis
Pinson, AG, Philbrick, JT, Lindbeck, GH, Schorling, JB. 1992; 14:15.
Fever in the clinical diagnosis of acute pyelonephritis. Am J Emerg
Med 1997; 15:148. Sandberg, T, Stokland, E, Brolin, I, et al. Selective use of
excretory urography in women with acute pyelonephritis. J Urol
Fairley, KF, Carson, NE, Gutch, RC, et al. Site of infection 1989; 141:1290.
in acute urinary tract infection in general practice. Lancet 1971;
2:615. Kanel, KT, Kroboth, FJ, Schwentker, FN, Lecky, JW. The
intravenous pyelogram in acute pyelonephritis. Arch Intern Med
Stamm, WE. Measurement of pyuria and its relation to 1988; 148:2144.
bacteriuria. Am J Med 1983; 75:53.
Meyrier, A, Condamin, MC, Pernet, M, et al. Frequency of
Kass, EH. Asymptomatic infections of the urinary tract. development of early cortical scarring in acute primary
Trans Assoc Am Physicians 1956; 69:56. pyelonephritis. Kidney Int 1989; 35:696.
Czaja, CA, Scholes, D, Hooton, TM, Stamm, WE. Nicolle, LE. A practical guide to the management of
Population-based epidemiologic analysis of acute pyelonephritis. complicated urinary tract infection. Drugs 1997; 53:583.
Clin Infect Dis 2007; 45:273.
Ward, G, Jorden, RC, Severance, HW. Treatment of
pyelonephritis in an observation unit. Ann Emerg Med 1991;
20:258.
Gupta, K, Scholes, D, Stamm, WE. Increasing prevalence
of antimicrobial resistance among uropathogens causing acute
uncomplicated cystitis in women [see comments]. JAMA 1999;
281:736.
Talan, DA, Krishnadasan, A, Abrahamian, FM, et al.
Prevalence and risk factor analysis of trimethoprim-
sulfamethoxazole- and fluoroquinolone-resistant Escherichia coli
infection among emergency department patients with
pyelonephritis. Clin Infect Dis 2008; 47:1150.
Johnson, L, Sabel, A, Burman, WJ, et al. Emergence of
fluoroquinolone resistance in outpatient urinary Escherichia coli
isolates. Am J Med 2008; 121:876.
Warren, JW, Abrutyn, E, Hebel, JR, et al. Guidelines for
antimicrobial treatment of uncomplicated acute bacterial cystitis and
acute pyelonephritis in women. Clin Infect Dis 1999; 29:745.
Hooper, DC, Wolfson, JS. Fluoroquinolone antimicrobial
agents. N Engl J Med 1991; 324:384.
Mombelli, G, Pezzoli, R, Pinoja-Lutz, G, et al. Oral vs
intravenous ciprofloxacin in the initial empirical management of
severe pyelonephritis or complicated urinary tract infection. Arch
Intern Med 1999; 159:53.
Talan, DA, Stamm, WE, Hooton, TM, et al. Comparison of
ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days)
for acute uncomplicated pyelonephritis pyelonephritis in women: a
randomized trial. JAMA 2000; 283:1583.
Klausner, HA, Brown, P, Peterson, J, et al. A trial of
levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400
mg and/or 500 mg twice daily for 10 days in the treatment of acute
pyelonephritis. Curr Med Res Opin 2007; :.