Acute Pyelonephritis

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Acute pyelonephritis is a potentially organ- and/or life-threatening infection that often leads to renal scarring. Acute pyelonephritis results from bacterial invasion of the renal parenchyma. Bacteria usually reach the kidney by ascending from the lower urinary tract. Bacteria may also reach the kidney via the bloodstream. Timely diagnosis and management of acute pyelonephritis has a significant impact on patient outcomes.^{[1, 2]} See the image below.

The classic presentation in patients with acute pyelonephritis is as follows:

Fever – This is not always present, but when it is, it is not unusual for the temperature to exceed 103°F (39.4°C)

Costovertebral angle pain – Pain may be mild, moderate, or severe; flank or costovertebral angle tenderness is most commonly unilateral over the involved kidney, although bilateral discomfort may be present

Nausea and/or vomiting – These vary in frequency and intensity, from absent to severe; anorexia is common in patients with acute pyelonephritis

Gross hematuria (hemorrhagic cystitis), unusual in males with pyelonephritis, occurs in 30-40% of females, most often young women, with the disorder.

Symptoms of acute pyelonephritis usually develop over hours or over the course of a day but may not occur at the same time. If the patient is male, elderly, or a child or has had symptoms for more than 7 days, the infection should be considered complicated until proven otherwise.

The classic manifestations of acute pyelonephritis observed in adults are often absent in children, particularly neonates and infants. In children aged 2 years or younger, the most common signs and symptoms of urinary tract infection (UTI) are as follows:

Failure to thrive

Feeding difficulty

Fever

Vomiting

Elderly patients may present with typical manifestations of pyelonephritis, or they may experience the following:

Fever

Mental status change

Decompensation in another organ system

Generalized deterioration

See Clinical Presentation for more detail.

In the outpatient setting, pyelonephritis is usually suggested by a patient’s history and physical examination and supported by urinalysis results. Urine specimens can be collected through the following methods:

Clean catch

Urethral catheterization

Suprapubic needle aspiration

Urinalysis can include the following:

Dipstick leukocyte esterase test (LET) – Helps to screen for pyuria

Nitrite production test (NPT) – To screen for bacteriuria

Examination for hematuria (gross and microscopic) and proteinuria

Urine culture is indicated in any patient with pyelonephritis, whether treated in an inpatient or outpatient setting, because of the possibility of antibiotic resistance.

Imaging studies that may be used in assessing acute pyelonephritis include the following:

Computed tomography (CT) scanning – To identify alterations in renal parenchymal perfusion; alterations in contrast excretion, perinephric fluid, and nonrenal disease; gas-forming infections; hemorrhage; inflammatory masses; and obstruction

Magnetic resonance imaging (MRI) – To detect renal infection or masses and urinary obstruction, as well as to evaluate renal vasculature

Ultrasonography – To screen for urinary obstruction in children admitted for febrile illnesses and to examine patients for renal abscesses, acute focal bacterial nephritis, and stones (in xanthogranulomatous pyelonephritis)

Scintigraphy – To detect focal renal abnormalities

CT and MR urography – Used in the evaluation of hematuria

See Workup for more detail.

Antibiotic therapy is essential in the treatment of acute pyelonephritis and prevents progression of the infection. Urine culture and sensitivity testing should always be performed, and empirical therapy should be tailored to the infecting uropathogen.^[3]

Patients presenting with complicated pyelonephritis should be managed as inpatients and treated empirically with broad-spectrum parenteral antibiotics.

Outpatient care

Outpatient treatment is appropriate for patients who have an uncomplicated infection that does not warrant hospitalization. Patients presenting with acute pyelonephritis can be treated with a single dose of a parenteral antibiotic followed by oral therapy, provided that they are monitored within the first 48 hours.

Inpatient care

Inpatient care includes the following:

Supportive care

Monitoring of urine and blood culture results

Monitoring of comorbid conditions for deterioration

Maintenance of hydration status with IV fluids until hydration can be maintained with oral intake

IV antibiotics until defervescence and significant symptomatic improvement occur; convert to an oral regimen tailored to urine or blood culture results

Surgery

In addition to antibiotics, surgery may be necessary to treat the following manifestations of acute pyelonephritis:

Renal cortical abscess (renal carbuncle): Surgical drainage (if patients do not respond to antibiotic therapy); other surgical options are enucleation of the carbuncle and nephrectomy

Renal corticomedullary abscess: Incision and drainage, nephrectomy

Perinephric abscess: Drainage, nephrectomy

Calculi-related urinary tract infection (UTI): Extracorporeal shockwave lithotripsy (ESWL) or endoscopic, percutaneous, or open surgery

Renal papillary necrosis: CT scan ̶ guided drainage or surgical drainage with debridement

Xanthogranulomatous pyelonephritis: Nephrectomy

See Treatment and Medication for more detail.

Acute pyelonephritis is a potentially organ- and/or life-threatening infection that characteristically causes scarring of the kidney.^[4]An episode of acute pyelonephritis may lead to significant renal damage; acute kidney injury; abscess formation (eg, nephric, perinephric); sepsis; or sepsis syndrome, septic shock, and multiorgan system failure.

A population-based study of acute pyelonephritis in the United States found overall annual rates of 15–17 cases per 10,000 females and 3–4 cases per 10,000 males.^[5]

Diagnosing and managing acute pyelonephritis is not always straightforward. Wide variation exists in the clinical presentation, severity, options, and disposition of the disease.

Patients in the age range of 5-65 years typically present with lower urinary tract infection (UTI) symptoms (eg, dysuria, frequency, urgency, gross hematuria, suprapubic pain) and classic upper UTI symptoms (eg, flank pain, back pain), with or without systemic signs and symptoms (eg, fever, chills, abdominal pain, nausea, vomiting, costovertebral angle tenderness) and with or without leukocytosis. However, acute pyelonephritis can present as nonspecific symptoms.

A number of studies using immunochemical markers have shown that many women who initially present with lower urinary tract symptoms actually have pyelonephritis. Their pyelonephritis is often identified when short-course therapy for uncomplicated cystitis fails.

With patients at the extremes of age, the presentation may be so atypical that pyelonephritis is not in the differential diagnosis. Infants may present with feeding difficulty or fever, and the elderly may have mental status change or fever.

Acute pyelonephritis is complex, and there is no consistent set of signs and symptoms that is both sensitive and specific for the diagnosis. Therefore, clinicians must maintain a high index of suspicion.

In contrast to the plethora of data available for the treatment of cystitis, less substantial data are available regarding the appropriate antibiotic choice or duration of therapy for acute pyelonephritis. An additional cause for concern is the growing resistance of uropathogens to standard agents. Nevertheless, useful recommendations can be made.

The current emphasis on cost-effectiveness and the advent of newer antibiotics have led clinicians to reevaluate the benefit of hospitalization in patients with acute pyelonephritis. Most cases of uncomplicated pyelonephritis in young women can be managed successfully on an outpatient basis. However, outpatient management of acute pyelonephritis requires close follow-up care. The first follow-up visit should occur in 1-2 days, depending on the clinician’s estimation of the severity of the infection. Any deterioration or unsatisfactory improvement warrants admission for intravenous antibiotics and evaluation for any complications. (See Treatment.)

Complicated pyelonephritis results from structural and functional abnormalities, urologic manipulations, or underlying disease; it includes pyelonephritis in men and in the elderly. Any patient with complicated pyelonephritis should be referred, if possible, to a physician trained in the management of these cases (eg, a nephrologist, urologist, or infectious disease specialist). The patient will require ongoing management, including repeat cultures, metabolic studies, and appropriate imaging studies.

Acute pyelonephritis results from bacterial invasion of the renal parenchyma. Bacteria usually reach the kidney by ascending from the lower urinary tract.^[6]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.^[7]

Bacteria may also reach the kidney via the bloodstream. Hematogenous sources of gram-positive organisms, such as Staphylococcus, are intravenous drug abuse and endocarditis. Experimental evidence suggests that hematogenous spread of gram-negative organisms to the kidney is less likely unless an underlying problem exists, such as an obstruction. Little or no evidence supports lymphatic spread of uropathogens to the kidney.

Most bacterial data are derived from research with Escherichia coli, which accounts for 70-90% of uncomplicated UTIs and 21-54% of complicated UTIs (ie, UTIs that are secondary to anatomic or functional abnormalities that impair urinary tract drainage; are associated with metabolic disorders; or involve unusual pathogens). A subset of E coli, the uropathogenic E coli (UPEC), also termed extraintestinal pathogenic E coli (ExPEC), accounts for most clinical isolates from UTIs.

UPEC derives commonly from the phylogenetic groups B2 and D, which express distinctive O, K, and H antigens. UPEC genes encode several postulated virulence factors (VFs), including adhesins, siderophores, protectins, and toxins, as well as having the metabolic advantage of synthesizing essential substances.

Adhesins have specific regions that attach to cell receptor epitopes in a lock-and-key fashion. Mannose-sensitive adhesins (usually type 1 fimbriae) are present on essentially all E coli. They contribute to colonization (eg, bladder, gut, mouth, vagina) and possibly pathogenesis of infection; however, they also attach to polymorphonuclear neutrophils (PMNs), leading to bacterial clearance.

Mannose-resistant adhesins permit the bacteria to attach to epithelial cells, thereby resisting the cleansing action of urine flow and bladder emptying. They also allow the bacteria to remain in close proximity to the epithelial cell, enhancing the activity of other VFs.

The P fimbriae family of adhesins is epidemiologically associated with prostatitis, pyelonephritis (70-90% of strains), and sepsis. This family of adhesins is associated with less than 20% of asymptomatic bacteriuria (ABU) strains. The AFA/Dr family is associated with diarrhea, UTI, and particularly pyelonephritis in pregnancy. The S/F1C family is associated with neonatal meningitis and UTI.

Siderophores are involved in iron uptake, an essential element for bacteria, and possibly adhesion. Protectins and their contributions to virulence include the following:

Lipopolysaccharide (LPS) coatings: resist phagocytosis

Tra T and Iss: resist action of complement

Omp T: cleave host defense proteins (eg, immunoglobulins)

Toxins, which affect various host cell functions, include the following:

Alpha-hemolysin

Cytotoxic necrotizing factor–1

Cytolethal distending toxin

Secreted autotransporter toxin

No single VF is sufficient or necessary to promote pathogenesis. Apparently, multiple VFs are necessary to ensure pathogenesis, although adhesins play an important role.

Bacterial strains that produce ABU may in some instances provide a measure of protection against symptomatic infections from UPEC and other organisms. On the other hand, ABU may also cause increased morbidity and mortality. Once bacteriuria is established, these strains appear to stop producing adhesins, allowing them to survive and persist without producing an inflammatory reaction.

As noted above, UPEC account for most uncomplicated pyelonephritis cases and a significant portion of complicated pyelonephritis cases. The following microorganisms are also commonly isolated:

Staphylococcus saprophyticus

Klebsiella pneumoniae

Proteus mirabilis

Enterococci

S aureus

Pseudomonas aeruginosa

Enterobacter species

This is the same spectrum of organisms cultured in cystitis. In 10-15% of symptomatic cystitis cases, cultures using routine methods remain negative, although the symptoms typically respond to antibiotic therapy. In some cases, cultures using selective media have grown Gardnerella vaginalis, Mycoplasma hominis, and Ureaplasma urealyticum. These data cannot be extended to acute pyelonephritis, but they do illustrate the difficulties in isolating the causative organism.

Evidence suggests that the pathogenesis of pyelonephritis takes a 2-step path. First, UPEC attaches to the epithelium and triggers an inflammatory response involving at least 2 receptors, glycosphingolipid (GSL) and Toll-like receptor 4 (TLR4). In the mouse model, GSL is the primary receptor and TLR4 is recruited and is an important receptor for the release of chemokines. When TLR4 is genetically absent, an asymptomatic carrier state develops in the infected mice.

Second, as a result of the inflammatory response, chemokines (eg, interleukin-8 [IL-8], which is chemotactic for PMNs) are released and attach to the neutrophil-activating chemokine receptor 1 (CXCR1), allowing PMNs to cross the epithelial barrier into the urine. In children prone to pyelonephritis, for example, CXCR1 expression has been shown to be significantly lower than in control subjects.

Several other host factors militate against symptomatic UTI. Phagocytosis of bacteria in urine is maximized at pH 6.5-7.5 and osmolality of 485 mOsm; values deviating from these ranges lead to significantly reduced or absent phagocytosis. Other important factors are the flushing action of urine flow in the ureter and bladder, the inhibition of attachment of type 1 fimbriae E coli to uroepithelial cells by tubular cell–secreted Tamm-Horsfall protein, and the inhibition of attachment by some surface mucopolysaccharides on the uroepithelial cells.

Complicated UTI is an infection of the urinary tract in which the efficacy of antibiotics is reduced because of the 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

Obstruction

Obstruction is the most important factor. It negates the flushing effect of urine flow; allows urine to pool (urinary stasis), providing bacteria a medium in which to multiply; and changes intrarenal blood flow, affecting neutrophil delivery. Obstruction may be extrinsic or intrinsic. Extrinsic obstruction occurs with chronic constipation (particularly in children), prostatic swelling/mass (eg, hypertrophy, infection, cancer), and retroperitoneal mass.

Intrinsic obstruction occurs with bladder outlet obstruction, cystocele, fungus ball, papillary necrosis, stricture, and urinary stones. With increasing size of stone, the probability of stone passage decreases while the probability of obstruction increases. Nonetheless, stones as small as 2 mm have resulted in obstruction, while 8-mm stones have occasionally passed spontaneously.

Infectious stones, urease stones, or triple-phosphate stones composed of magnesium ammonium phosphate or struvite and apatite account for 10-15% of all urinary stones. They develop secondary to the action of urea-splitting organisms and can grow rapidly and branch out (ie, staghorn calculi).

If left untreated, staghorn calculi will destroy the kidney and may cause the death of the patient. Complications include azotemia, hydropyonephrosis, perinephric abscess, pyelonephritis (severe or end-stage), sepsis, and xanthogranulomatous pyelonephritis.

Incomplete bladder emptying may be related to medication (eg, anticholinergics). The spermicide nonoxynol-9 inhibits the growth of lactobacilli. Lactobacilli produce hydrogen peroxide, which protects the vaginal ecosystem against pathogens. Frequent sexual intercourse causes local mechanical trauma to the urethra in both partners.

Atrophic vaginal mucosa in postmenopausal women 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, whereas nonbacterial prostatitis and pelviperineal pain syndrome (prostadynia) do not.

Unusual organisms include Mycoplasma, Pseudomonas, and urea-splitting organisms. Pseudomonas aeruginosa has several mechanisms that promote adherence, including alginate, other membrane proteins, pili, and surface-associated exoenzyme S.

Urea-splitting organisms produce urease, which hydrolyzes urea, yielding ammonia, bicarbonate, and carbonate; this leads to a more alkaline urine and allows crystal formation (staghorn calculus) from the supersaturation of carbonate apatite and struvite. Staghorn calculi continue to grow in size, leading to infection, obstruction, or both.

Complications of obstruction with superimposed infection include hydronephrosis, pyonephrosis, urosepsis, and xanthogranulomatous pyelonephritis. Additionally, the pathogens can sequester in the struvite stones, protected from the host’s immune system. Proteus species are the most common urea-splitting organisms. E coli, Klebsiella, Pseudomonas, and Staphylococcus can also produce urease, however, and are sometimes involved in staghorn calculus formation.

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 peristalsis and increases bladder capacity. The enlarging uterus displaces the bladder, contributing to urinary stasis. Complicated UTI can result from one or more diverse factors.

Diabetes mellitus produces autonomic bladder neuropathy, glucosuria, leukocyte dysfunction, microangiopathy, and nephrosclerosis; additionally, it leads to recurrent bladder instrumentation secondary to the neuropathy. 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

For more information on this topic, see the Medscape Reference article Pathophysiology of Complicated Urinary Tract Infections.

Uropathogens that cause the majority of acute pyelonephritis cases and the frequency with which they are cultured in uncomplicated versus complicated cases, are listed in Table 1. Unusual pathogens include mycobacteria, yeasts and fungi, and opportunistic pathogens such as Corynebacterium urealyticum.

Table 1. Bacterial Etiology of Urinary Tract Infections (Open Table in a new window)

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

Enterobacter spp

< 1

2-10

Pseudomonas aeruginosa

< 1

2-19

Other

< 1

6-20

Gram positive

Coagulase-negative staphylococci

5-10*

1-4

Enterococci

1-2

1-23

Group B streptococci

< 1

1-4

Staphylococcus aureus

< 1

1-23

Other

< 1

Adapted from Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin North Am. Jun 2003;17(2):303-32. [Medline].

* S saprophyticus

Epidemiologic data on the incidence of pyelonephritis are limited. A population-based study of acute pyelonephritis in the United States found overall annual rates of 15-17 cases per 10,000 females and 3-4 cases per 10,000 males.^[5]At least 250,000 cases of pyelonephritis are diagnosed annually in the United States. The cost of treating acute pyelonephritis has been estimated to be $2.14 billion per year.^[5]

Acute pyelonephritis develops in 20-30% of pregnant women with untreated asymptomatic bacteriuria (ABU) (2-9.5%), most often during the late second and early third trimesters. The incidence of pyelonephritis in infants and children is difficult to ascertain because of the infrequency of typical symptoms. Up to 25% of children with UTI and no signs or symptoms of pyelonephritis do have bacteria demonstrable in the upper urinary tract.

No racial predilection of pyelonephritis has been demonstrated. Pyelonephritis is significantly more common in females than in males, although this difference narrows considerably with increasing age, especially in patients aged 65 years and older. In females, pyelonephritis shows a trimodal distribution, with an elevated incidence in girls aged 0-4 years, a peak in women 15-35 years of age, and a gradual increase after age 50 years to another peak at 80 years of age.^[5]

In males, the age distribution of pyelonephritis is bimodal. Males also demonstrate a peak incidence of pyelonephritis at 0-4 years of age. Rates gradually increase after 35 years of age and peak at 85 years of age.^[5]

Acute pyelonephritis shows a seasonal variation. In Washington state, cases occurred most frequently during the months of July and August among females and during August and September in the male population.^[5]

Timely diagnosis and management of acute pyelonephritis has a significant impact on the outcome. Any patient with acute pyelonephritis who deteriorates suddenly or does not respond to conventional therapy may have a complication, resistant organism, or unrecognized comorbidity.

Pyelonephritis causes considerable morbidity, but these data can only be extrapolated from the morbidity data for acute lower urinary tract infections. Specifically, acute cystitis in women produces approximately 6.1 days with symptoms, 2.4 days of restricted activity, 1.2 days that the patient is unable to work or attend class, and 0.4 days bedridden.

For patients with pyelonephritis who have an organ-threatening infection, the follow-up examination is important to be sure that the patient is progressing satisfactorily and that recovery is complete. Failure to diagnose these complications in a timely fashion could predispose the patient to a poor outcome. Pregnant patients with pyelonephritis are at significant risk for premature labor.

Kofteridis et al found that acute pyelonephritis is linked to bacteremia, longer hospital stays, and higher mortality in patients with diabetes mellitus.^[8]In a retrospective study of 206 elderly patients, 88 of whom had diabetes, bacteremia occurred in 30.7% of patients with diabetes but in only 11% of the control patients. Moreover, compared with the control patients, patients with diabetes had longer-lasting fevers (median, 4.5 vs 2.5 days), longer hospital stays (median, 10 vs 7 days), and higher mortality (12.5% vs 2.5%).

Mortality is higher in patients older than 65 years; it is also higher with septic shock, bedridden status, and immunosuppression. In men, mortality is also increased with use of antibiotics during the previous month. Morbidity (prolonged hospital stay) in both men and women is increased with a change in initial treatment, diabetes mellitus, and long-term indwelling catheter.

In healthy, nonpregnant women with uncomplicated disease, the prognosis is excellent for full recovery and minimal damage to the kidney. In healthy men without any known complicating conditions, the prognosis is good for full recovery; however, urologic evaluation is recommended to rule out an underlying complicating condition. In infants and children, the prognosis is good. Importantly, children should undergo a urologic evaluation after the first episode to rule out structural abnormalities.

Uncomplicated pyelonephritis is not a fatal disease in the antibiotic era. Pyelonephritis becomes a potentially fatal disease when secondary conditions develop, such as emphysematous pyelonephritis (20-80% mortality rate), perinephric abscess (20-50% mortality rate), or one of the sepsis syndromes (>25% overall mortality rate).

In emphysematous pyelonephritis, the mortality rate is 60% in cases in which the gas is localized to the renal parenchyma, regardless of treatment. The mortality is 80% if the gas has spread in the perinephric space and the patient is treated with antibiotics alone. In emphysematous pyelitis, the mortality rate is 20%.

The genitourinary system is the source of severe sepsis in 9.1% of all cases annually. The mortality for these GU-related cases is 16.1%. Overall mortality from severe sepsis significantly increases with chronic renal disease (36.7%), acute renal dysfunction (38.2%), and age older than 64 years (25-42% with progressively increasing age to older than 85 years). In the age range of 0-4 years, the mortality is 5%; for ages 5-50 years, it is less than 3%.

Rarely, acute pyelonephritis can cause acute kidney injury (AKI) in children, healthy adults, and pregnant women. When this occurs, characteristically, recovery proceeds more slowly than with AKI from other causes. In most instances, other factors are thought to contribute to the ARF (eg, medications, hypovolemia, obstruction, sepsis).

In children, renal scarring can be detected in 6-15% after a febrile UTI. Of these patients, almost all males and some females have demonstrable renal scarring and a globally small kidney with smooth renal outlines in infancy, usually associated with vesicoureteral reflux (VUR) and thought to be congenital. Most female infants do not have demonstrable scarring on initial imaging, but they subsequently develop it. Delay in treatment of cystitis or pyelonephritis, recurrent UTIs, urinary obstruction, and VUR increase the risk of scarring.

Acute pyelonephritis (single episode; first UTI ever in one half of cases) in an adult woman leads to renal scarring in 46%, as demonstrated by scintigraphic scanning 10 years later. Subsequent UTIs do not appear to affect the risk of future scarring.

Renal scarring has been demonstrated to be 4 times more likely after pyelonephritis in pregnant women than in nonpregnant women. In addition, acute pyelonephritis during pregnancy is associated with the following complications:

Acute renal dysfunction (elevated creatinine) in 2% of cases (20-25% in the past)

Acute renal failure in 0.03% of cases

Acute respiratory distress syndrome (bilateral chest radiograph infiltrates and hypoxemia without pulmonary hypertension) in 1-8% of cases

Low birth weight (< 2500 g) in 7% of cases

Preterm delivery (< 37 wk gestation) in 5% of cases (6-50% in the past)

Recurrence prior to delivery in 18-20% of cases

Sepsis (positive blood cultures) in 17% of cases

Acute renal transplant pyelonephritis occurring in the first 3 months after transplant has a significant association with graft loss (>40%) by 96 months, as compared with all renal transplant cases with or without the occurrence of pyelonephritis at any time after the transplant up to 96 months (25-30%).

Patients must take antibiotics as directed and complete the course as prescribed. This minimizes the risk of recurrence and the development of resistant organisms.

Avoidance of dehydration is important for both patient well-being and kidney function. When under stress, men typically drink only enough liquid to replace two thirds of the loss. When ill, individuals drink less and predispose themselves to dehydration. Unavoidable daily water loss is 1.5 L, of which approximately 500 mL is replaced by the oxidation of carbohydrates. Because patients cannot measure urine specific gravity at home, they should drink enough water or other liquid to produce light-colored urine, almost like water.

For patient education information, see the Kidneys and Urinary System Center, as well as Urinary Tract Infections and Blood in the Urine.

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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

Enterobacter spp

< 1

2-10

Pseudomonas aeruginosa

< 1

2-19

Other

< 1

6-20

Gram positive

Coagulase-negative staphylococci

5-10*

1-4

Enterococci

1-2

1-23

Group B streptococci

< 1

1-4

Staphylococcus aureus

< 1

1-23

Other

< 1

Adapted from Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin North Am. Jun 2003;17(2):303-32. [Medline].

* S saprophyticus

First-line therapy

Ciprofloxacin (Cipro) 500 mg PO BID for 7d or

Ciprofloxacin extended-release (Cipro XR) 1000 mg PO daily for 7d or

Levofloxacin (Levaquin) 750 mg PO daily for 5d

If fluoroquinolone resistance is thought to be >10%, administer a single dose of ceftriaxone (Rocephin) 1g IV or a consolidated 24-hour dose of an aminoglycoside (gentamicin 7 mg/kg IV or tobramycin 7 mg/kg IV or amikacin 20 mg/kg IV)

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)

Alternative therapy

Oral beta-lactams are not as effective for treating pyelonephritis; however, if they are used, administer with 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 or

Cefaclor 500 mg PO TID for 7d

*Should generally be avoided in elderly patients because of the risk of affecting renal function.

First-line therapy

Ciprofloxacin (Cipro) 400 mg IV q12h for 10-14d or

Levofloxacin (Levaquin) 250 mg IV q24h for 10d or

Levofloxacin (Levaquin) 750 mg IV q24h for 5d

Second-line therapy

Extended-spectrum cephalosporins or penicillins:

Ampicillin-sulbactam (Unasyn) 1.5 g IV q6h or

Piperacillin-tazobactam (Zosyn) 3.375 g IV q6h or

Ticarcillin-clavulanate (Timentin) 3.1 g IV 4-6h or

Cefotaxime (Claforan) 1-2 g IV q8h or

Ceftriaxone (Rocephin) 1 g IV q24h or

Ceftazidime (Fortaz, Tazicef) 2 g IV q8h

All of the above can be administered with or without an aminoglycoside (except in pregnant patients); see Aminoglycosides, below

Carbapenems:

Meropenem (Merrem) 500 mg IV q8h or

Ertapenem (Invanz) 1 g IV q24h or

Doripenem (Doribax) 500 mg IV q8h

Monobactam (for patients with penicillin allergy):

Aztreonam (Azactam) 1 g IV q8-12h

Alternative therapy

Aminoglycosides (because of their potential nephrotoxicity, aminoglycoside antibiotics should be reserved for patients with serious and potentially life-threatening infections, and their dosage and blood levels should be carefully monitored to minimize the risk of nephrotoxicity):

Gentamicin 3 mg/kg/day IV/IM in 3 divided doses or 7 mg/kg/day pulsed dosing or

Tobramycin 3 mg/kg/day IV/IM in 3 divided doses or 7 mg/kg/day pulsed dosing or

Amikacin 10 mg/kg/day IV/IM in 3 divided doses or 20 mg/kg/day pulsed dosing

Mild to moderate pyelonephritis

Ceftriaxone (Rocephin) 1 g IV q24h or

Cefepime (Maxipime) 1 g IV q12h or

Cefotaxime (Claforan) 1-2 g IV q8h or

Ceftazidime (Fortaz, Tazicef) 2 g IV q8h or

Ampicillin 1-2 g IV q6h plus gentamicin IV 1.5 mg/kg q8h

Severe pyelonephritis

If patient is immunocompromised and/or has incomplete urinary drainage:

Ticarcillin-clavulanate (Timentin) 3.1 g IV q6h or

Ampicillin-sulbactam (Unasyn) 1.5 g IV q6h or

Piperacillin-tazobactam (Zosyn) 3.375 g IV q6h

Neonates

Infants 6 weeks to 3 years of age

Children 3-6 years of age

Children 6-11 years of age

UTI frequency (%)

1.5-3

1.2

Female-to-male ratio

1:1.5

10:1

30:1

Route of infection

Blood

Ascending

Signs and symptoms

Failure to thrive, fever, hypothermia, irritability, jaundice, poor feeding, sepsis, vomiting

Diarrhea, failure to thrive, fever, irritability, poor feeding, strong-smelling urine, vomiting

Abdominal pain, dysuria, enuresis, fever, gross hematuria, meningismus, strong-smelling urine, urinary urgency, urinary frequency, vomiting

Dysuria, enuresis, fever, flank pain or tenderness, urinary urgency, urinary frequency

Predominant organism

Klebsiella species

E coli

E coli, Proteus species in older boys

E coli

Management

Admit for intravenous ampicillin and gentamicin and further evaluation

Follow adult guidelines, but avoid fluoroquinolones, which are theoretically contraindicated due to potential effects on the musculoskeletal system

Tibor Fulop, MD, PhD, FACP, FASN Professor of Medicine, Department of Medicine, Division of Nephrology, Medical University of South Carolina College of Medicine; Attending Physician; Medical Services, Ralph H Johnson VA Medical Center

Tibor Fulop, MD, PhD, FACP, FASN is a member of the following medical societies: American Academy of Urgent Care Medicine, American College of Physicians, American Society of Diagnostic and Interventional Nephrology, American Society of Hypertension, American Society of Nephrology, International Society for Apheresis, International Society for Hemodialysis, Magyar Orvosi Kamara (Hungarian Chamber of Medicine), Southern Society for Clinical Investigation

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Fresenius Medical Care, Hungary; Dialysis Clinic Inc., USA.

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc<br/>Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Vecihi Batuman, MD, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation