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ACUTE PYELONEPHRITIS

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Acute pyelonephritis is a potentially organ- and/or life-

threatening infection that characteristically causes

scarring of the kidney.An episode of acute pyelonephritis may lead to:

kidney failure;

abscess formation (eg, nephric, perinephric);

sepsis

septic shock,

multiorgan system failure.

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PathophysiologyAcute pyelonephritis results from bacter ia l invasion of the

renal parenchyma.

Bacteria usually reach the kidney by ascending from the

lower urinary tract.

In all age groups, episodes of bacteriuria occur commonly,

but most are asymptomatic and do not lead to infection.

The development of infection is influenced by bacterial

factors and host factors. Bacteria may also reach the kidney via the

bloodstreamMost bacterial data are derived from research with

Escherichia coli, which accounts for 70-90% of

uncomplicated UTIs and 21-54% of complicated UTIs

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Pathogen

s

Staphylococcus

saprophyticus

Klebsiella pneumoniae

Proteus mirabilis

Enterococci

S aureus

Pseudomonas aeruginosa

Enterobacter s ecies

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Complicated infection

Complicated UTI is an infection of the urinary tract in

which the efficacy of antibiotics is reduced because ofthe presence of one or more of the following:

Structural abnormalities of the urinary tract

Functional abnormalities of the urinary tract

Metabolic abnormalities predisposing to UTIs

Unusual pathogens

Recent antibiotic use

Recent urinary tract instrumentation

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Obstruction is the most important factor.

It negates the flushing effect of urine flow; allows

urine to pool (urinary stasis)=>providing bacteriaa medium in which to multiply;

=>changes intrarenal blood

flow, affecting neutrophil delivery.

Obstruction may be extrinsic or intrinsic.

Extrinsic obstruction : chronic constipation ,

prostatic swelling/mass (eg, hypertrophy, infection,cancer), and retroperitoneal mass.

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Intrinsic obstruction occurs with bladder outlet

obstruction, cystocele, fungus ball, papillary necrosis,

stricture, and urinary stones.

Atrophic vaginal mucosa in postmenopausalwomen predisposes to the colonization of urinary

tract pathogens and UTIs because of the higher pH

(5.5 vs 3.8) and the absence of lactobacilli.

Bacterial prostatitis (acute or chronic) produces

bacteriuria,

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Pregnancy produces hormonal and mechanical

changes that predispose the woman to upper urinary

traction infections.

Hydroureter of pregnancy, secondary to both

hormonal and mechanical factors, manifests

as dilatation of the renal pelvis and ureters(greater on the left than on the right), with the

ureters containing up to 200 mL of urine.

Progesterone decreases ureteral peristalsisand increases bladder capacity.

Diabetes mellit s prod ces a tonomic bladder ne ropath

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Diabetes mellitus produces autonomic bladder neuropathy,

glucosuria, leukocyte dysfunction, microangiopathy, and

nephrosclerosis.

Complicated UTIs in patients who have diabetes mellitus

include the following:

Renal and perirenal abscess

Emphysematous pyelonephritis

Emphysematous cystitis

Fungal infections

Xanthogranulomatous pyelonephritis

Papillary necrosis

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Bacteria % Uncomplicated % Complicated

Gram negative

Escherichia coli 70-95 21-54

Proteus mirabilis 1-2 1-10

Klebsiella spp 1-2 2-17

Citrobacter spp < 1. 5

Enterobacter spp < 1 2-10Pseudomonas aeruginosa < 1 2-19

Other < 1 6-20

Gram positive

Coagulase-negative staphylococci 5-10 1-4Enterococci 1-2 1-23

Group B streptococci < 1 1-4

Staphylococcus aureus < 1 1-23

Other < 1 2

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History

The classic presentation =triad : fever, costovertebral

angle pain, and nausea and/or vomiting.

Symptoms may be minimal to severe and usually

develop over hours or over the course of a day.

symptoms develop over several days and may even

be present for a few weeks before the patient seeks

medical care.

Symptoms of cystitis : urinary frequency, hesitancy,

lower abdominal pain, and urgency.

G h t i (h h i titi ) i t i

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Gross hematuria (hemorrhagic cystitis) is present in

30-40% of pyelonephritis cases in females, most often

young women.

Gross hematuria is unusual in males and should

prompt consideration of a more serious cause.

Pain may be :

mild, moderate, or severe

unilateral /bilateral.

in the back (lower or middle) and/or the suprapubicarea. Patients may describe suprapubic symptoms as

discomfort, heaviness, pain, or pressure.

Upper abdominal pain is unusual, and radiation of pain

to the groin is suggestive of a ureteral stone.

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Fever

is not always present.

it is not unusual for the temperature to exceed 103F

(39.4C).

Gastrointestinal symptoms.

Anorexia is common.

Nausea and vomiting vary in frequency and intensity

from absent to severe.

Diarrhea occurs infrequently.

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Elderly patients may present with typical manifestations of

pyelonephritis, or they may experience fever, mental status

change, decompensation in another organ system, orgeneralized deterioration.

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Complicated pyelonephritis

A history of the following indicates an inc reased r is kof

complicated pyelonephritis:

Structural abnormalities of the urinary tract

Functional abnormalities of the urinary tract

Metabolic abnormalities predisposing to UTIs

Recent antibiotic use

Recent urinary tract instrumentation

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abdominal examination:

suprapubic tenderness usually ranges from mild tomoderate without rebound.

Abdominal tenderness other than in the suprapubic

area suggests another diagnosis.

Patients usually do not have rigidity or guarding, and

bowel sounds are often normally active.

Flank or costovertebral angle (CVA) tenderness is mostcommonly unilateral over the involved kidney, although

bilateral discomfort may be present.

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In women: a pelvic examination should be performed.

Tenderness of the cervix, uterus, and adnexa should be

absent. Any positive finding suggests an additional or

alternative diagnosis

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Complications

Complications occur more often in patients with diabetes

mellitus, chronic renal disease, sickle cell disease, renal

transplant (particularly during the first 3 months), AIDS,

and other immunocompromised states.

Complications may involve any of the following:

Acute renal failure

Chronic renal damage leading to hypertension and renal

failure

Sepsis syndromes

Renal papillary

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Acute Abdomen and

Pregnancy

Acute Bacterial Prostatitis

Appendicitis

Cervicitis

Chronic Bacterial Prostatitis

Chronic Pyelonephritis

Cystitis in Females

Endometritis

Pelvic Inflammatory Disease

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Approach Considerations

In the outpatient setting, pyelonephritis is usuallysuggested by the history and physical examination

and supported by urinalysis results, which should

include microscopic analysis.

Other laboratory studies are used to identifycomplicating conditions and to assist in determining

whether the patient should be admitted.

Easily diagnosed cases typically occur in women,both pregnant and nonpregnant.

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Collection of Urine Specimens

Urine specimens obtained for urinalysis and culture

should approximate the urine contained in the bladderas closely as possible.

The 3 procedures for collecting such a urine specimen

are:

clean catch,

urethral catheterization,

suprapubic needle aspiration.

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Urinalysis

Pyuria is defined as more than 5-10 WBCs per high-power field (hpf)on a specimen spun at 2000 rpm for 5 minutes. Almost all patients with

pyelonephritis have significant pyuria (>20 WBCs/hpf).

The dipstick leukocyte esterase test (LET) helps screen for pyuria.

LET results have a sensitivity of 75-96% and a specificity of 94-98% fordetecting more than 10 WBC/hpf.

The nitrite production test (NPT) for bacteriuria has 92-100%

sensitivity and 35-85% specificity.

Combined, the LET-NPT has a sensitivity of 79.2% and a specificity of81%, which is too low for it to be used as the only screening study for

bacteriuria.

Gross hematuria occurs infrequently with pyelonephritis

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Gross hematuria occurs infrequently with pyelonephritis

and is more common with cystitis (hemorrhagic cystitis).

When gross hematuria is present, the differential should

include calculi, cancer, glomerulonephritis, tuberculosis,trauma, and vasculitis.

Microscopic hematuria may be present in patients with

uncomplicated acute pyelonephritis, but other causes

should be considered, particularly calculi

Microscopic hematuria may be present in patients with

uncomplicated acute pyelonephritis, but other causes should

be considered, particularly calculi.

White cell casts are suggestive of pyelonephritis

Proteinuria is expected (up to 2 g/day). When it exceeds 3

g/day, glomerulonephritis should be considered.

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Urine and Blood CulturesUrine culture is indicated in any patient with pyelonephritis,

whether treated in an inpatient or an outpatient setting,

because of the possibility of antibiotic resistance.

Blood cultures are indicated in any patient who is being

admitted or who has already been admitted. Approximately

12-20% of patients have cultures that are positive for

infection

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Indications for Imaging Studies

Imaging may be required to make the diagnosis in infants

and children in whom pyelonephritis presents insidiously.Imaging is warranted at the time of admission in patients

with the following conditions:

AIDSPoorly controlled diabetes

Organ transplant (particularly renal)

Other immunocompromised state

Sepsis syndromeSeptic shock

Indications for imaging studies are as follows:

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Fever or positive blood culture results that persist for

longer than 48 hours

Sudden worsening of the patients condition

Toxicity persisting for longer than 72 hours

Complicated UTI

Computed Tomography

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Contrast-enhanced helical/spiral computed

tomography (CECT) is the imaging study of choice,

both in adults and in children with acute

pyelonephritis.CECT is more sensitive than ultrasonography and

intravenous pyelography (which has only 25%

sensitivity), and it can more readily identify alterations

in renal parenchymal perfusion, alterations in contrastexcretion, perinephric fluid, and nonrenal disease.

Ultrasonography

Ultrasonography (US) can sometimes detect acutepyelonephritis, but a negative study does not exclude

the possibility.

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CT and MR Urography

CT urography and MR urography are evolving modalities

that surpass intravenous urography, which was the prior

mainstay of urinary tract imaging.

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Approach Considerations

Ambulatory younger women who present with signsand symptoms of uncomplicated acute pyelonephritis

may be candidates for outpatient therapy. (They must

be otherwise healthy and must not be pregnant.)

In addition, they must be treated initially in theemergency department (ED) with vigorous oral or IV

fluids, antipyretic pain medication, and a dose of

parenteral antibiotics.

Admission is usually appropriate for :

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Admission is usually appropriate for :

patients who are severely ill,

pregnant,

elderly

who have comorbid disorders that increase thecomplexity of management or the complication rate

(eg, diabetes mellitus, chronic lung disease, congenital

or acquired immunodeficiency).

Admission may also be advisable for patients whosesocial situation is unstable, because of the possibility of

poor compliance or poor follow-up.

Antibiotic Selection

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Antibiotic Selection

Antibiotic selection is typically empirical, because the

results of blood or urine cultures are rarely available by

the time a decision must be made.Initial selection should be guided by local antibiotic

resistance patterns.

Culture results from specimens collected before the

initiation of therapy should be checked in 48 hours todetermine antibiotic efficacy.E coli or other Enterobacteriaceae => Acceptable

regimens may include fluoroquinolones, cephalosporins,

penicillins, extended-spectrum penicillins, carbapenems,

and aminoglycosides.enterococci => ampicillin or vancomycin can replace the

fluoroquinolone. If any doubt exists as to the diagnosis,

coverage of both Enterobacteriaceae and enterococci is

acceptable.

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Regimens for complicated cases

With complicated acute pyelonephritis, treat patients

parenterally until defervescence and improvement in the clini

condition warrants changing to oral antibiotics. Complete the

course of therapy with an oral agent selected on the basis of

culture results

Acceptable regimens include the following:

Ampicillin and an aminoglycoside

Cefepime

Imipenem

MeropenemPiperacillin-tazobactam

Ticarcillin-clavulanate

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Outpatient Treatment

Antibiotic therapy

Patients presenting with acute pyelonephritis can be

treated with a single dose of a parenteral antibioticfollowed by oral therapy, provided they are monitored

within the first 48 hours.

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First-line therapy

ciprofloxacin (Cipro) 500 mg PO BID for 7d orciprofloxacin extended-release (Cipro XR) 1000 mg PO da

for 7d or

levofloxacin (Levaquin) 750 mg PO daily for 5d

If fluoroquinolone resistance is thought to be >10%, administa single dose of ceftriaxone (Rocephin) 1g IV or a consolidat

24-hour dose of an aminoglycoside (gentamicin 7 mg/kg IV o

tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)

cefaclor 500 mg PO TID for 7d

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Second-line therapy

trimethoprim/sulfamethoxazole* 160 mg/800 mg(Bactrim DS, Septra DS) 1 tablet PO BID for 14d

If trimethoprim/sulfamethoxazole is used when the

susceptibility is not known, an initial single IV dose of

the following may also be given: ceftriaxone (Rocephin)1 g IV or a consolidated 24-h dose of an

aminoglycoside (gentamicin 7 mg/kg IV or tobramycin 7

mg/kg IV or amikacin 20 mg/kg IV)

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Alternative therapy

Oral beta-lactams are not as effective for treating

pyelonephritis; however, if they are used, administerwith a single dose of ceftriaxone (Rocephin) 1 g IV or a

consolidated 24-h dose of an aminoglycoside

(gentamicin 7 mg/kg IV or tobramycin 7 mg/kg IV or

amikacin 20 mg/kg IV)amoxicillin-clavulanate (Augmentin) 500 mg/125 mg

PO BID for 14d or

amoxicillin-clavulanate (Augmentin) 250 mg/125 mg

PO TID for 3-7d orcefaclor 500 mg PO TID for 7d