eMedicine Specialties > Nephrology > Tubulointerstitial Diseases of the Kidney

Pyelonephritis, Acute

William H Shoff, MD, DTM&H, Director, PENN Travel Medicine, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania
Judith Green-McKenzie, MD, MPH, Associate Professor of Emergency Medicine, Director of Clinical Practice and Associate Director of Occupational Medicine, Department of Emergency Medicine, University of Pennsylvania School of Medicine, University Hospital; Christopher Edwards, MD, Staff Physician, Department of Emergency Medicine, University of Pennsylvania Medical School; Amy J Behrman, MD, Associate Professor, Department of Emergency Medicine, Director, Division of Occupational Medicine, University of Pennsylvania School of Medicine; Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania; Director of Education and Research, PENN Travel Medicine

Updated: Jan 7, 2009

Introduction

Background

Acute pyelonephritis is a potentially organ- and/or life-threatening infection that characteristically causes some scarring of the kidney with each infection and may lead to significant damage to the kidney (any given episode), kidney failure, abscess formation (eg, nephric, perinephric), sepsis, or sepsis syndrome/shock/multiorgan system failure. More than 250,000 cases occur in the United States each year (1995 estimate), and approximately 200,000 patients require hospitalization (1997 data). Wide variation exists in the clinical presentation, severity, options, and disposition of acute pyelonephritis.

Diagnosing and managing acute pyelonephritis is not always straightforward. In the age range of 5-65 years, it typically presents in the context of a symptomatic (eg, dysuria, frequency, urgency, gross hematuria, suprapubic pain) urinary tract infection (UTI) with classic upper urinary tract symptoms (eg, flank pain, back pain) with or without systemic symptoms (eg, fever, chills, abdominal pain, nausea, vomiting) and signs (eg, fever, costovertebral angle tenderness) with or without leukocytosis. However, it can present with nonspecific symptoms.

A number of studies using immunochemical markers have shown that many women, who initially present with lower tract symptoms, actually have pyelonephritis. This group of young women is often identified when short-course therapy for uncomplicated cystitis fails. In the extremes of age, the presentation may be so atypical that pyelonephritis is not in the differential diagnosis. In the infant, the presentation may be feeding difficulty or fever. In the elderly, the presentation may be mental status change or fever. Acute pyelonephritis is complex, and there is no consistent set of signs and symptoms that are 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 lower UTI, less substantial data are available regarding the appropriate antibiotic choice or duration of therapy for acute pyelonephritis, but useful recommendations can be made. An additional cause for concern is the growing antimicrobial resistance to accepted standards of treatment. The current emphasis on cost effectiveness and the advent of newer antibiotics have led clinicians to reevaluate the benefit of hospitalization to treat patients with acute pyelonephritis; however, if the patient is managed as an outpatient, he or she should have 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. Most cases of uncomplicated pyelonephritis in young women can be managed successfully on an outpatient basis.

Pathophysiology

Acute pyelonephritis results from bacterial invasion of the renal parenchyma. In all age groups, episodes of bacteriuria occur commonly, but most are asymptomatic (ABU) and do not lead to infection. Infection is influenced by bacterial factors and host factors.

Most bacterial data are derived from research with Escherichia coli, which accounts for 70-90% of uncomplicated UTIs and 21-54% of complicated UTIs. 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, protectins, siderophores, 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 leukocytes (PMN), 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 are epidemiologically associated with prostatitis, pyelonephritis (70-90% of strains), and sepsis. This same family of adhesins in associated with less than 20% of 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 iron uptake, an essential element for bacteria, and possibly adhesion. Protectins include lipopolysaccharide (LPS) coatings (resist phagocytosis), Tra T and Iss (both resist action of complement), and Omp T (cleave host defense proteins, such as immunoglobulins).

Toxins, including alpha hemolysin, cytotoxic necrotizing factor-1, cytolethal distending toxin, and secreted autotransporter toxin, affect various host cell functions; LPS shed from a membrane or released by bacterial lysis leads to cytokine release. No single VF is sufficient or necessary to promote pathogenesis. It seems that a multiple VFs are necessary to ensure pathogenesis, although adhesins play an important role.

Bacterial strains producing ABU may provide, in some instances (controversial), a measure of protection against symptomatic infections from UPEC and other organisms; but, it 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. The frequency of ABU in preschool girls is less than 2%; in pregnant women, 2-9.5%; in women aged 65-80 years, 18-43%; in men aged 65-80 years, 1.5-15.3%; in women older than 80 years, 18-43%; and in men older than 80 years, 5.4-21%. There is considerable morbidity associated with ABU in pregnancy, renal transplantation, and genitourinary surgery (see Table 1).

Table 1. Asymptomatic Bacteriuria: Incidence, Morbidity, Screening, and Treatment¹

As noted above, UPEC account for most infections in uncomplicated pyelonephritis and a significant portion to most infections in complicated pyelonephritis. Other microorganisms commonly isolated are Staphylococcus saprophyticus, Klebsiella pneumoniae, Proteus mirabilis, enterococci, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter species. This is the same spectrum of organisms cultured with UTIs. In 10-15% of symptomatic UTI cases, bacteria are not cultured using routine methods, although they typically respond to antibiotic therapy. In some UTI cases, using selective media, Gardnerella vaginalis, Mycoplasma hominis, and Ureaplasma urealyticum have been cultured. These UTI 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, such as interleukin-8 (IL-8), 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 mitigate 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 values lead to significantly reduced or absent phagocytosis. Other important factors are the flushing action of urine flow in the ureter and bladder, the inhibiting of attachment of type 1 fimbriae E coli to uroepithelial cells by tubular cell–secreted Tamm-Horsfall protein, and the inhibiting of attachment by some surface mucopolysaccharides on the uroepithelial cells.

When a UTI or pyelonephritis becomes complicated (complicated UTI), host defenses are compromised, thereby increasing the likelihood of infection. The definition of a complicated UTI is an infection of the urinary tract involving urinary tract structural abnormalities, urinary tract functional abnormalities, metabolic abnormalities predisposing to UTIs, unusual pathogens, recent antibiotic use, recent urinary tract instrumentation, or a combination of these such that the efficacy of antibiotics is reduced. These abnormalities include but are not limited to obstruction (congenital or acquired), stents, vesicoureteral reflux, incomplete bladder emptying, use of spermicide, diabetes mellitus, atrophic vaginal mucosa, prostatitis, immunodeficiency (congenital or acquired), unusual organisms (eg, Mycoplasma, Pseudomonas), urea-splitting organisms (eg, Proteus, sometimes E coli, Klebsiella, Pseudomonas, Staphylococcus), medullary scars, and pregnancy.

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. Intrinsic obstruction occurs with bladder outlet obstruction, cystocele, fungus ball, papillary necrosis, stricture, and urinary stone. The probability of stone passage decreases while the probability of obstruction increases with increasing size of the stone. Nonetheless, stones as small as 2 mm have resulted in obstruction, while 8 mm stones have occasionally passed spontaneously. Extrinsic obstruction occurs with chronic constipation (particularly in children), prostatic swelling/mass (eg, hypertrophy, infection, cancer), and retroperitoneal mass.

Incomplete bladder emptying may be medication related (eg, anticholinergics). Spermicide nonoxynol-9 inhibits the growth of lactobacilli, which produce hydrogen peroxide. Frequent sexual intercourse causes local mechanical trauma to the urethra in both partners. Diabetes mellitus produces autonomic bladder neuropathy, glucosuria, leukocyte dysfunction, microangiopathy, and nephrosclerosis; additionally, it leads to recurrent bladder instrumentation secondary to the neuropathy. Atrophic vaginal mucosa in postmenopausal women predisposes to the colonization of urinary tract pathogens and UTIs due to the higher pH (5.5 vs 3.8) and the absence of lactobacilli. Bacterial prostatitis (acute or chronic) produces bacteriuria, while nonbacterial prostatitis and pelviperineal pain syndrome (prostadynia) do not.

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 (urea-splitting), yielding ammonia, bicarbonate, and carbonate, leading to a more alkaline urine, allowing 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 (XGP). Additionally, the organisms can sequester in the struvite stones protected from the host’s immune system. Proteus species are the most common urea-splitting organisms; however, E coli, Klebsiella, Pseudomonas, and Staphylococcus can produce urease; therefore, they sometimes are also involved in staghorn calculus formation.

Pregnancy (hormonal and mechanical changes) predisposes a woman to upper urinary traction infections. Hydroureter of pregnancy, secondary to both hormonal and mechanical factors, is manifested as dilatation of the renal pelvis and ureters (left > right) with the ureters containing up to 200 mL 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.

Although there are many instances when more than one factor is involved, in any given episode of acute pyelonephritis, the presence of any one of these factors, as described above, should raise the clinician’s index of suspicion.

Occult upper UTIs (pyelonephritis) occur in 15-50% (or more) of all UTIs, based on several studies on localization of organisms within the urinary tract. If the host is healthy, particularly young, premenopausal women, without any of the complicating factors listed above, then the occult pyelonephritis can be considered an uncomplicated infection. However, if the host is male, elderly, or a child, or if the host has had symptoms for more than 7 days, then the infection should be considered complicated until proven otherwise.

Acute pyelonephritis usually occurs secondary to bacteria ascending from the lower urinary tract. Hematogenous spread to the kidney can occur. Sources for gram-positive organisms, such as Staphylococcus, are intravenous drug abuse and endocarditis. Hematogenous spread to the kidney by gram-negative organisms appears less likely based on the observation that experimental pyelonephritis is difficult to reproduce by intravenous introduction of gram-negative bacilli, unless an underlying problem, such as an obstruction, exists. Little or no evidence supports lymphatic spread of uropathogens to the kidney.

Frequency

United States

There are at least 250,000 cases of diagnosed pyelonephritis in the United States annually (1995 estimate) with 192,000 admissions (1997 National Inpatient Sample database). Lower UTIs predispose to pyelonephritis.

From 1988-1994, there were an estimated 12.7 million UTIs annually in women according to the National Health and Nutrition Examination Survey III. In men, the estimated incidence for the same period was 2 million UTIs. Several studies suggest that 15-50% of these infections are occult pyelonephritis, but these infections may be considered uncomplicated if the host is healthy, outside the extremes of age, and without any complicating factors. If complicating factors are present (see Pathophysiology), then the presence of pyelonephritis must be considered, even in the absence of typical signs and symptoms thereof.

Acute pyelonephritis develops in 20-30% of pregnant women with untreated 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, as is the case with non-upper UTIs. In children 2 years and younger, the most common symptoms of UTI are failure to thrive, feeding difficulty, fever, and vomiting. In children, up to 25% of patients with UTI and no signs or symptoms of pyelonephritis do have bacteria demonstrable in the upper tract.

Mortality/Morbidity

Pyelonephritis causes considerable morbidity, but these data can only be extrapolated from the morbidity data for acute lower UTIs. 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 bed-ridden.

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). The genitourinary (GU) system is the source of severe sepsis in 9.1% of all cases annually (approximately 750,000). The mortality for these GU-related cases is 16.1%. Overall severe sepsis mortality 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 >85 y). In the age range of 0-4 years, the mortality is 5%; for ages 5-50 years, it is less than 3%. Severe sepsis, in general, treated with early goal-directed therapy has been shown to reduce in-hospital mortality from 46.5% to 30.5% (see Treatment).

Rarely, acute pyelonephritis can cause acute renal failure (ARF) in children, healthy adults, and pregnant women. When this occurs, characteristically, there is a slower recovery compared to other causes of ARF. In most instances, other factors are thought to contribute to the ARF, that is, medications, hypovolemia, obstruction, or sepsis.

In women, mortality is increased in those older than 65 years; it is also increased with septic shock, bedridden status, and immunosuppression. Morbidity (prolonged hospital stay) is increased with a change in initial treatment, diabetes mellitus, and long-term indwelling catheter.

In men, mortality is increased in those older than 65 years; it is also increased with septic shock, bedridden status, and recent use of antibiotics (within 1 mo). Morbidity (prolonged hospital stay) is increased in those older than 65 years and also with a change in initial treatment, diabetes mellitus, and long-term indwelling catheter.

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 VUR, and is thought to be congenital. Most females do not have demonstrable scarring on initial imaging in infancy, but they subsequently develop it. Patients with scarring are at risk for hypertension and renal insufficiency. Factors that increase this risk are delay in treatment of UTIs/pyelonephritis, recurrent UTIs, urinary obstruction, and VUR.

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 Tc99m-labeled dimercaptosuccinic acid scanning 10 years later. Subsequent UTIs do not appear to affect the risk of future scarring.

Acute pyelonephritis during pregnancy leads to acute renal dysfunction (creatinine, 1.2) in 2% of cases (20-25% in the past), acute renal failure in 0.03% of cases, acute respiratory distress syndrome (bilateral chest x-ray 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, and sepsis (positive blood cultures) in 17% of cases. Renal scarring has been demonstrated to be 4 times more likely after pyelonephritis in pregnant women than in nonpregnant women.

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 to all renal transplant cases with or without the occurrence of pyelonephritis at any time after the transplant up to 96 months (25-30%).

Race

No racial predilection of pyelonephritis has been demonstrated.

Sex

• Pyelonephritis is significantly more common in females than in males. This separation narrows considerably with increasing age, especially in patients aged 65 years and older. Quantitative information regarding bacteriuria and UTI reflects this observation about pyelonephritis (see Frequency).
• The prevalence rate of bacteriuria in young nonpregnant women is 1-3%. The prevalence rate in adult men is less than or equal to 0.1%. After age 65 years, the prevalence rates for women and men are 20% and 10%, respectively. Approximately 10-30% of women develop a symptomatic UTI at some point in their lives (see Frequency).

Age

See Morbidity/Mortality for a discussion regarding the role of age in pyelonephritis.

Clinical

History

• Patients may present with minimal or severe symptoms. Symptoms usually develop over hours or over the course of a day. Infrequently, symptoms develop over days and may even be present for a few weeks before a patient presents for evaluation.
• Symptoms of lower UTI may or may not be present to varying degrees.
  • Internal dysuria usually refers to the urinary tract. External dysuria most commonly refers to the vagina.
  • Symptoms may include urinary frequency, hesitancy, lower abdominal pain, and urgency.
  • Gross hematuria (hemorrhagic cystitis) is present in 30-40% of female cases, most often young adults. It may occur in males but is unusual and a more serious cause must be considered.
  • The description of suprapubic symptoms varies and may include discomfort, heaviness, pain, or pressure.
• Symptoms of acute pyelonephritis may be present to varying degrees.
  • Severity of pain may be mild, moderate, or severe. Flank pain may be unilateral or sometimes bilateral. Discomfort or pain may be present in the back (lower or middle) and/or the suprapubic area. Upper abdominal pain is unusual, and radiation of pain to the groin is suggestive of a ureteral stone.
  • Fever is not always present. When present, it is not unusual for the temperature to exceed 103°F (39.4°C).
  • The patient may demonstrate rigor, and chills may be present in the absence of demonstrated fever.
  • Malaise and weakness may also be present.
  • Gastrointestinal symptoms vary. Anorexia is common. Nausea and vomiting vary in frequency and intensity from absent to severe. Diarrhea occurs infrequently.

Physical

• Vital signs
  • There may or may not be a fever. The temperature may be greater than 103°F (39.4°C), or it may be subnormal in patients with associated sepsis.
  • Tachycardia may or may not be present, depending on associated fever, dehydration, and sepsis.
  • Blood pressure is usually within the reference range, unless the patient has underlying hypertension; in cases of underlying hypertension, the pressure may be elevated above the patient's baseline. A systolic blood pressure less than 90 mm Hg suggests shock secondary to sepsis or perinephric abscess.
• Appearance
  • The patient's appearance is variable. Most commonly, the patient is uncomfortable or appears ill.
  • Patients usually do not have a toxic appearance unless an underlying problem, such as sepsis, perinephric abscess, or significant dehydration, is present.
• Abdominal examination
  • Suprapubic tenderness usually ranges from mild to moderate without rebound. Abdominal tenderness other than in the suprapubic area suggests another diagnosis. Usually, abdominal rebound, rigidity, or guarding is not found.
  • Bowel sounds are often normoactive.
  • Flank or costovertebral angle (CVA) tenderness is most commonly unilateral over the involved kidney, although bilateral discomfort may be present. Discomfort varies from absent to severe. This is usually not subtle and may be elicited with mild or moderately firm palpation.
• Pelvic examination
  • 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.
  • If any doubt remains as to the diagnosis, if any signs or symptoms of urethritis or vaginitis are present, or if a history of dyspareunia is present, a gynecologic cause of the symptoms should be pursued.

Causes

When considering the cause of acute pyelonephritis, there are 3 considerations.

The first consideration is what uropathogens are typically cultured and at what frequency (see Table 2).

Second, UTIs that are complicated indicate a high risk for upper UTI or occult pyelonephritis in the absence of signs and symptoms typical of acute pyelonephritis. A complicated UTI is defined as a UTI in the presence of at least one of several factors that will reduce the efficacy of antimicrobial therapy, leading to failure of therapy (eg, progression to overt pyelonephritis, sepsis, renal failure, abscess formation, worsening clinical condition, resistant organism), relapse, or persistence of infection (see Table 3). Any patient with a complicated UTI should be referred, if possible, to a nephrologist, a urologist, an infectious disease specialist, or another physician trained to managed complicated UTIs. The patient will require ongoing management, including repeat cultures, metabolic studies, and appropriate imaging studies.

The third consideration in the management of acute pyelonephritis is what organisms are involved in complicated UTIs and what are their antimicrobial sensitivities (see Table 2).

Table 2. Bacterial Etiology of Urinary Tract Infections¹

Differential Diagnoses

Workup

Laboratory Studies

• In the outpatient setting, pyelonephritis is usually suggested based on the history and physical examination and is supported by urinalysis results, which should include microscopic analysis. Other lab studies are used to evaluate for complicating conditions and to assist in determining if the patient should be admitted.
• Most easily diagnosed cases occur in women, both pregnant and nonpregnant. Men, patients at the extremes of age, patients harboring subclinical pyelonephritis, and patients who are hospitalized may present with an insidious onset. This section presents information relative to the perspective of pyelonephritis versus UTIs, in general.
• Urinalysis
  • Gross hematuria occurs infrequently with pyelonephritis and is more common with lower UTI (hemorrhagic cystitis). When present, the differential should include calculi, cancer, glomerulonephritis, tuberculosis, trauma, and vasculitis.
  • 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), although the numbers may be smaller, particularly in those with subacute pyelonephritis.
  • The dipstick leukocyte esterase test (LET) helps screen for pyuria. LET results have a sensitivity of 75-96% and a specificity of 94-98% for detecting more than 10 WBC/hpf. The nitrite production test (NPT) for bacteriuria has 92-100% sensitivity and 35-85% specificity and may be falsely negative in the presence of diuretic use, low dietary nitrate, or organisms that do not produce nitrate reductase (eg, Enterococcus, Pseudomonas, Staphylococcus). Combined, the LET-NPT has a sensitivity of 79.2% and a specificity of 81%, which is too low for it to be used as the only screening study for bacteriuria.
  • Microscopic examination may reveal hematuria, but other causes should be considered, particularly calculi. This is especially true if the patient does not respond to therapy. White cell casts are suggestive of pyelonephritis; however, centrifuge speeds (>2000 rpm) used for urinalysis sediment preparation often fracture them and lead to their absence in the sediment.
  • Proteinuria is expected (up to 2 g/d). When it exceeds 3 g/d, glomerulonephritis should be considered.
  • The presence of a single bacterium in an unspun urine specimen by oil-immersion microscopic examination is equivalent to at least 105 organisms. Bacteria are identified much more easily on a stained versus an unstained specimen.
• Urine culture
  • Urine culture is indicated in any patient with pyelonephritis, whether treated in an inpatient or an outpatient setting, because of the possibility of antibiotic resistance.
  • Specimens can be collected by clean catch, catheter, or suprapubic puncture (rarely performed or indicated).
• Blood cultures
  • Blood cultures are indicated in any patient who is being admitted or who has already been admitted.
  • Approximately 12-20% are positive for infection. Bacteremia has not been associated with a poor outcome unless sepsis or another significant comorbidity is present.

Imaging Studies

• Imaging studies are rarely indicated for the diagnosis of acute pyelonephritis in the adult who presents with typical signs and symptoms. Imaging may be warranted if the presentation is atypical or confusing. It is also warranted if the patient deteriorates or does not respond to therapy, as illustrated by the following scenarios, in which the important considerations are nephrolithiasis, obstructive uropathy, and perinephric abscess:
  • The patient has a fever or positive blood culture results that persist for longer than 48 hours.
  • The patient’s condition suddenly worsens.
  • Toxicity persists for longer than 72 hours.
  • The patient has a complicated UTI (see Causes).
• The purpose is to evaluate immediately for an organ- or life-threatening complication. Contrast-enhanced helical/spiral computed tomography scan (CECT) is the imaging study of choice when there is suspicion for the development of a complication of acute pyelonephritis, both in adults and in children. A recent study demonstrated in an experimental model that CECT, magnetic resonance imaging (MRI), and dimercaptosuccinic acid 99m-technetium (99mTc-DMSA) scintigraphy were equivalent in their sensitivity and reliability to detect acute pyelonephritis. Clinical experience is still limited with MRI in this setting, and there are the issues of cost and availability. 99mTc-DMSA scintigraphy is used more often in children to image the urinary tract to lessen radiation exposure.
• Imaging early in the presentation of acute pyelonephritis may be more useful than previously thought. In one recent study, 16% of cases admitted for acute pyelonephritis were found to have new and clinically significant abnormalities on renal imaging with ultrasound (US) or computed tomography (CT) at the time of admission. Independent of this observation, there are certain patients who warrant imaging at the time of admission, including those with AIDS, poorly controlled diabetes, an organ transplant (particularly renal), another immunocompromised state, sepsis syndrome, or septic shock, because of the increased risk of a complication.
• The following studies have been used in the diagnosis of acute pyelonephritis:
  • As mentioned above, CECT is the imaging study of choice in adults. It is more sensitive than ultrasound and intravenous pyelogram (25% sensitivity), and it can more readily identify alterations in renal parenchymal perfusion, alterations in contrast excretion, perinephric fluid, and nonrenal disease.
  • Noncontrast helical/spiral CT findings may be normal in acute pyelonephritis with mild parenchymal involvement, but the findings are usually positive when the involvement is moderated or severe. It is the standard study for demonstrating gas-forming infections, hemorrhage, inflammatory masses, and obstruction. It also has 97% accuracy in identifying renal stones.
  • US can sometimes detect acute pyelonephritis, but a negative study does not exclude the possibility. Power Doppler US is superior to color Doppler US in the detection of pyelonephritis but remains inferior to CECT. It is useful in screening for urinary obstruction in children admitted for febrile illnesses. It can help differentiate solid and cystic structures, detect hydronephrosis and stones, and measure blood flow.
  • 99mTc-DMSA scintigraphy is almost as sensitive clinically as CECT in detecting focal renal abnormalities during acute pyelonephritis in adults. 99mTc-DMSA scintigraphy is not used much in adults because the focal abnormalities are not specific; rather, they are consistent with abscess, cyst, infarct, pyelonephritis, or tumor. Additionally, it is much less available in the acute setting than CECT. In children, it is the preferred study to lessen radiation exposure from CT scans. It is excellent for helping detect inflammation, scarring, and the distribution of renal function between kidneys. DMSA is a radiotracer that localizes to the renal cortex.
  • Experience with MRI in evaluating acute pyelonephritis is limited but growing. It is a suitable alternative in the patient with iodinated-dye allergy. It can evaluate the genitourinary system prenatally, renal infection/masses/vasculature, and urinary obstruction, using gadolinium-enhanced MRI, a nonnephrotoxic dye study.
• CT urography and MR urography are evolving modalities that allow evaluation of the renal parenchyma and urothelium, according to one comprehensive study. Currently used in the evaluation of hematuria, these modalities will become more applicable to the study of other urological problems.
• Imaging may be required to make the diagnosis in infants and children in whom pyelonephritis presents insidiously.
• Imaging studies in conjunction with urological procedures, including cystoscopy and excretory urography, may be used during a follow-up examination to evaluate for urinary tract abnormalities that can predispose the patient to infection.
• Patients with complicated UTIs should be considered for follow-up imaging to assess the urinary tract.

Procedures

• Urine specimens obtained for examination and culture should approximate the urine contained in the bladder as closely as possible. The 3 procedures for collecting such a urine specimen are clean catch, urethral catheterization, and suprapubic needle aspiration.
  • Clean catch
    • When properly collected, a clean-catch specimen adequately reflects the microbiology of the urine in the bladder.
    • This technique can be performed by ambulatory females aged 6 years and older who do not have any limiting physical handicap. The presence of a large number of epithelial cells after microscopic examination suggests that the specimen is not a true clean catch and is rendered unreliable for culture because of contamination with vaginal contents. Importantly, the patient should wash only the area where urine is passed, wash front to back, hold the cup by the outside, and keep the labia spread while collecting the urine. This is to ensure that the urine goes into the cup without touching the labia.
    • This technique can also be performed by ambulatory males aged 6 years and older who do not have any limiting physical handicap. Specimens are usually reliable. Importantly, the patient should clean the head of the penis, retract the foreskin (in uncircumcised males), maintain a good stream, and hold the cup by the outside. In the presence of epispadias or hypospadias, care must be taken to maintain a good stream while collecting the specimen.
  • Urethral catheterization
    • This engenders a small risk of introducing bacteria into the sterile bladder environment.
    • Several indications justify this risk when a urine culture is necessary, including (1) inability or difficulty voiding urine even with hydration, (2) marked obesity or redundant labia in females, (3) ill patients who cannot reliably perform the procedure, (4) performance of a urological procedure during which a specimen can be collected, and (5) children aged 2-6 years (unless a clinician-assisted clean-catch specimen cannot be collected).
  • Suprapubic needle aspiration
    • This technique is rarely used.
    • It is indicated when (1) another alternative is lacking, (2) the need exists to exclude contamination from other methods of collection, (3) the need exists to verify the presence of an infecting organism that is otherwise considered a contaminant, and (4) the need exists to verify infection in infants who have a positive culture result from a specimen obtained from a strap-on device.

Histologic Findings

Features of acute pyelonephritis include suppurative necrosis or abscess formation within the renal substance. Features of chronic pyelonephritis (chronic interstitial nephritis) include papillary atrophy and blunting, interstitial fibrosis with inflammatory infiltrate (ie, lymphocytes, plasma cells, neutrophils [occasional]), tubules (ie, dilated with possible colloid casts, contracted with atrophy of epithelium), and concentric fibrosis about the parietal layer of the Bowman capsule.

Treatment

Medical Care

• Supportive care
  • Rest
  • Antipyretics as needed
  • Oral or parenteral pain medications as needed
  • Oral or parenteral antiemetics as needed
  • Urinary tract analgesics to relieve dysuria (up to 3 d)
  • Intravenous or oral fluids to maintain hydration status
• Reasons for hospital admission
  • Cannot tolerate oral intake
  • Unstable social situation (eg, possibility of poor compliance or poor follow-up)
  • Unstable vital signs
  • Severe signs and symptoms
  • Pregnancy
  • Comorbid disorders that increase the complexity of management or the complication rate (eg, diabetes mellitus, chronic lung disease, congenital or acquired immunodeficiency syndrome)
• 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. Urine culture collected at the initiation of therapy should be checked in 48 hours to determine antibiotic efficacy.
  • When using an oral-only regimen, the initial dose should be administered at the time of the evaluation.
  • See Medication for a list of other acceptable antibiotics that are not discussed here.
  • The etiology of community-acquired infections is usually E coli or other Enterobacteriaceae. Infections usually involve women aged 18-50 years and, infrequently, men of the same age. Accepted outpatient regimens include the following:
    • Administer ceftriaxone (1 g IV/IM) or gentamicin (single 24-h dose or divided q8h) or tobramycin (single 24-h dose or divided q8h) on day 1, followed by an oral fluoroquinolone from day 2 to days 10-14. For pediatric dosing, see Medication.¹
    • Prescribe oral fluoroquinolone for 10-14 days.^1,2
    • Prescribe amoxicillin-clavulanate potassium for 14 days.
    • Prescribe trimethoprim-sulfamethoxazole or trimethoprim or oral cephalosporin for 14 days. Use only if the organism is known to be sensitive.
    • If beta-lactam drugs and fluoroquinolones are contraindicated, administer aztreonam parenterally; as such, the patient will need to be admitted.  
  • The fluoroquinolone course can be shortened to a 7-day course, instead of 10-14 days, in healthy, young women with uncomplicated pyelonephritis; a similar course probably could be used in healthy, young men without any complicating comorbidity, particularly if there is a prompt response to therapy.^3,4
  • Studies have demonstrated the efficacy of levofloxacin (750 mg/d for 5 d) in the treatment of uncomplicated pyelonephritis and complicated UTI.^2,1 This same regimen has also been demonstrated to be safe and efficacious in comparison with ciprofloxacin (400-500 mg bid for 10-14 d).²
  • Growing data suggest that oral antibiotic therapy alone versus parenteral antibiotic only or initial parenteral antibiotic therapy followed by oral antibiotic therapy are all equally efficacious, although most of the studies are small.⁵  
  • Some clinicians believe that initiating therapy with an intravenous or intramuscular dose of medication reduces the risk of therapeutic failure; other clinicians believe that an oral course is sufficient. Data exist to support both assertions. One prospective study supports using oral therapy alone in patients who can tolerate oral intake, lack signs of sepsis, and do not show signs of obstruction or renal suppuration on urinary tract ultrasonography findings. Another study (prospective, randomized, unblinded) in a controlled, hospital setting compared oral versus intravenous ciprofloxacin for the initial management of severe pyelonephritis. Both regimens were equally efficacious. If the patient can tolerate oral medication, there is no indication for admission, and the patient can be monitored closely to ensure good compliance. An oral antibiotic therapy only regimen appears to have increasing efficacy. 
  • If enterococci are suggested based on Gram stain results, then ampicillin or vancomycin can replace fluoroquinolone. If any doubt exists as to the diagnosis, then coverage of both Enterobacteriaceae and enterococci is acceptable.
  • Enterococci have a higher incidence in hospitalized and other institutionalized patients. Ampicillin or amoxicillin should be included in the regimen. If the patient is allergic to penicillin, then vancomycin should be substituted.
  • Admit patients who appear toxic, if they are not already hospitalized. Refer to Sepsis, Bacterial if this diagnosis is being considered. If complicated acute pyelonephritis is suggested, use one of the following regimens:
    • Treat patients parenterally until they improve clinically. Complete the course of therapy with an oral agent selected based on culture results.
    • Acceptable regimens include the following: (1) ampicillin and an aminoglycoside, (2) cefepime, (3) imipenem, (4) meropenem, (5) piperacillin-tazobactam, or (6) ticarcillin-clavulanate. If the patient is allergic to penicillin, substitute vancomycin.
    • Vancomycin or linezolid are options if enterococci are a consideration.

Surgical Care

Elective surgery is performed to reverse conditions that predispose the kidney to recurrent infections and renal damage. These conditions include congenital anomalies, fistulae involving the urogenital tract, prostatic hypertrophy, renal calculi, and vesicoureteral reflux.

An emergent surgical condition may be indicated by a patient with fever or positive blood culture results persisting longer than 48 hours, a patient with a deteriorating condition, or a patient who appears toxic for longer than 72 hours. The etiology may not be immediately evident, but an unexpected change in the clinical picture warrants immediate evaluation for potential surgical intervention. The following is a list of conditions that are in the differential diagnosis of surgical conditions relative to patients presenting with acute pyelonephritis who do not respond to standard therapy.

• Renal cortical abscess (renal carbuncle)
  • This is an uncommon condition that is usually caused by the hematogenous spread of S aureus. It occurs 3 times more commonly in men than in women. Microabscesses develop in the cortex and coalesce to form a circumscribed abscess that may or may not communicate with the collecting system. This process takes days to months. Patient presentation includes fever, chills, back pain, abdominal pain, flank mass, and urinary symptoms if the collecting system is involved.
  • Blood culture results are usually negative. Diagnosis is best made using CT scan, although ultrasonography can be useful in distinguishing among an abscess, a cyst, and a tumor. Treatment includes parenteral antibiotics for 10-14 days, incision and drainage, enucleation of the carbuncle, nephrectomy, or any combination of these therapies. If parenteral antibiotic therapy is successful, oral therapy is instituted for an additional 2-4 weeks.
• Renal corticomedullary abscess
  • This condition is usually associated with a urinary tract abnormality such as vesicoureteral reflux or obstruction. It is commonly caused by Enterobacteriaceae.
  • The pathology represents a spectrum of disease, as follows:
    • Acute focal bacterial nephritis (eg, acute lobar nephroma, focal pyelonephritis) that affects a single renal lobe with interstitial inflammation represented by marked polymorphonuclear leukocytes
    • Acute multifocal bacterial nephritis with a similar process throughout the kidney that produces liquefaction and abscess formation
    • XGP with chronic parenchymal infection, granulomatous tissue, and perirenal fibrosis (see Xanthogranulomatous pyelonephritis below)
    • Emphysematous pyelonephritis with severe, necrotizing infection (discussed separately below)
  • Men and women are equally affected by these conditions, although XGP affects women more often than men. The presentation of the first 3 described entities includes fever, chills, abdominal pain, flank pain, nausea, vomiting, urinary symptoms (may be absent), flank mass (60%), hepatomegaly (30%), draining sinus in the flank (rare), leukocytosis, bacteriuria/pyuria (normal urine in 30%), and bacteremia (acute forms of disease).
  • CT scan is the preferred imaging method. Treatment includes parenteral antibiotics for 48 hours (usually successful), incision and drainage, and nephrectomy. If antibiotic therapy is successful, oral therapy is instituted for an additional 2 weeks.
• Emphysematous pyelonephritis
  • Emphysematous pyelonephritis is a severe, necrotizing form of acute multifocal bacterial nephritis with extension of the infection through the renal capsule. This leads to the presence of gas within the kidney substance and in the perinephric space. Persons with diabetes (with or without obstruction) account for 85-100% of cases, although some cases have occurred in patients who had obstruction without diabetes. Females outnumber males (2-6:1).
  • Emphysematous pyelonephritis occurs on the left side in approximately two thirds of cases. The etiology is usually Enterobacteriaceae (E coli, 60%), with some reported cases of Streptococcus species and Candida species. A triad of diabetes, obstruction, and remote or recent pyelonephritis should raise clinical suspicion. Patient presentation includes fever, chills, abdominal pain, nausea, vomiting, flank pain, flank mass (50%), crepitation (over thigh or flank), urinary symptoms, and pyuria.
  • CT scan is the preferred imaging method to use in the diagnosis and to help localize the gas pattern to the collecting system, intrarenal, or perinephric. Plain radiographs (85%) and ultrasonography can help detect renal emphysema but do not help in localization. Considerable mortality is associated with this entity. When gas is within the kidney only, the mortality rate is 60% (antibiotic therapy with surgical drainage); when gas extends to the perinephric space, the mortality rate is 80% (antibiotic therapy only); when nephrectomy is performed, the mortality rate is 20%.
• Perinephric abscess
  • The suppurative material of the abscess is located between the renal capsule and the surrounding renal fascia. The material is secondary to chronic or recurrent pyelonephritis, rupture or extension of a suppurative process from within the kidney, or dissemination (blood, lymph) or direct extension from other sites of infection. Although it is usually confined to the perinephric space, it may extend to the colon, flank, groin, lung (empyema, nephrobronchial fistula), paracervical area, peritoneal cavity, psoas muscle, skin surface, or subphrenic space.
  • Development is insidious. Patient presentation includes fever, chills, unilateral flank pain (70%), dysuria (40%), nausea, vomiting, weight loss (25%), flank tenderness, CVA tenderness, abdominal tenderness (60%), referred pain (ie, hip, thigh, or knee), flank or abdominal mass (<50%), pyuria (70%), sterile urine (40%), and bacteremia (40%). One third of patients are diagnosed upon admission; another third are diagnosed at autopsy. This diagnosis is not usually readily apparent; a high index of clinical awareness is necessary.
  • CT scan is the preferred diagnostic study. Ultrasound findings may be falsely negative in 36% cases. MRI may help define extension better than CT scan. The mortality rate is 20-50%, but this rate can be decreased with early recognition, surgical drainage, and antimicrobial therapy (not adequate alone). Antibiotics should include an aminoglycoside and an antistaphylococcal agent. If Pseudomonas species are considered or demonstrated, an antipseudomonal beta-lactam antibiotic should be added. For enterococci, an aminoglycoside and ampicillin are recommended. Other organisms that have been reported include tuberculosis and fungi. Nephrectomy may be necessary.
• Obstructing calculus
  • Obstructing calculi may pass with time, hydration, and analgesia.
  • In the presence of acute infection, they must be removed immediately using cystoscopy or open surgical procedure.
• Renal papillary necrosis
  • Most patients with renal papillary necrosis have diabetes. Patient presentation is similar to that for pyelonephritis.
  • The imaging study of choice is retrograde pyelography. Confirmatory evidence is histologic verification of voided medullary tissue, which may occur only at autopsy. Treatment is admission for intravenous antibiotics (see Medical Care). If the response is not good, CT-guided drainage or surgical drainage with debridement is indicated.
• Xanthogranulomatous pyelonephritis
  • This rare form of pyelonephritis is almost always associated with chronic obstruction (ie, staghorn calculus [75% cases], another calculus, stricture, or tumor). In adults, the female-to-male ratio is 3:1; in children, it is 1.1:1.
  • It is a chronic infection that finally manifests acutely with fever and flank pain or tenderness, and it may be complicated by a flank mass, cutaneous fistula, septic arthritis, or hematochezia if extension has occurred beyond the renal capsule. Kidney function is absent (71%) or poor (25%) in almost all cases. Diagnosis is difficult preoperatively.
  • The imaging study of choice is CT scan. Ultrasound images may suggest the diagnosis in the presence of an enlarged kidney and a staghorn calculus.
  • The treatment of choice is nephrectomy after the patient is stabilized. See Xanthogranulomatous Pyelonephritis for more information.
• Staghorn calculus: 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 (see Pathophysiology) and can grow rapidly and branch out.
  • If left untreated, they 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 XGP.
  • The treatment of choice is to remove the whole stone. Fragments left behind remain infected and will grow again.

Consultations

Consultation is indicated if the infection is complicated. Most cases of acute pyelonephritis occur in adult women and are readily managed without consultation. The following are reasons for consulting various subspecialists.

• A urologist may be consulted regarding patients with ureteral or urethral obstruction, urinary stones, urogenital abnormality, recurrent pyelonephritis, or for the first episode of pyelonephritis in an infant or child.
• A renal specialist may be consulted regarding patients with acute renal failure or advanced chronic renal failure or for neonates or infants.
• An infectious diseases specialist may be consulted regarding patients with an unusual or resistant pathogen, those who are immunocompromised, patients with persisting fever (>48 h) or toxicity (>72 h), or patients whose blood culture results are positive beyond 48 hours.
• An obstetrician may be consulted for patients who are pregnant.

Diet

A regular diet is permitted as tolerated. Special dietary considerations, such as those associated with diabetes mellitus, should be honored. Hydration status is very important.

• If oral intake is not tolerated, intravenous hydration is warranted. Intravenous fluids should include 1 L of 5% dextrose in saline to reverse any existing ketosis, regardless of whether ketones are detected in the urine. Additional intravenous hydration is accomplished with saline.
• If admission is not indicated and the patient will be monitored in an outpatient setting, hydration status should be normalized with intravenous fluids; the physician should not assume that the patient can or will accomplish this with oral hydration alone.
• When hydrating intravenously, exercise caution regarding conditions that might be adversely affected by improper amounts of fluid, saline, or glucose.

Activity

Rest is essential for recovery. Activity should be minimized. Patients who are treated in an outpatient setting should not return to work for 2 weeks in order to allow time for the infection to be eliminated. This time also allows the patient to recuperate physical strength. This recommendation can be tempered in special circumstances as warranted by the clinician.

Medication

Several classes of drugs may be required for the management of pyelonephritis. These pharmaceuticals include antibiotics, analgesics, antipyretics, and antiemetics. Only antibiotics and urinary tract analgesics are specifically addressed. Symptomatic management using analgesics, antipyretics, and antiemetics is accomplished by oral or parenteral means according to the clinical condition of the patient.

Nitrofurantoin is not used for the treatment of pyelonephritis or any other infection at the tissue level. It is included in this drug list because it is discussed in Special Concerns as asymptomatic bacteriuria therapy and postcoital therapy. It is also discussed in Deterrence/Prevention for uncomplicated UTI therapy and continuous therapy.

Norfloxacin lacks significant efficacy compared to the other fluoroquinolones listed below and is not recommended for the treatment of pyelonephritis. Moxifloxacin is another fluoroquinolone that is not recommended for pyelonephritis because tissue levels may not be sufficient to irrigate the infecting organism.

Other antibiotics reported to be effective in the management of acute pyelonephritis include parenteral penicillins, third-generation cephalosporins (eg, cefotaxime), oral fluoroquinolones (eg, enoxacin, lomefloxacin, ofloxacin), parenteral fluoroquinolones (eg, lomefloxacin), and aminoglycosides (eg, amikacin).

Antibiotics

Therapy should cover all likely pathogens in the context of this clinical setting. Antibiotic selection should be guided by blood or urine culture sensitivity results whenever feasible.

Ciprofloxacin (Cipro)

Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, S epidermidis, and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth.

Dosing

Adult

250-500 mg PO bid for 7-14 d

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Levofloxacin (Levaquin)

For pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.

Dosing

Adult

Inpatient: 500 mg/d IV until patient improves clinically, then switch to PO to complete 7-d course; if necessary, can be extended to 14 d
Outpatient: 500 mg PO/IV at time of diagnosis, followed by 500 mg/d PO to complete 7-d course; if necessary, can be extended to 14 d

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Ceftriaxone (Rocephin)

Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.

Dosing

Adult

Uncomplicated infection: 250 mg IM once; not to exceed 4 g/d
Severe infection: 1-2 g IV qd or divided bid; not to exceed 4 g/d

Pediatric

<7 days: Not established
>7 days: 25-50 mg/kg/d IV/IM; not to exceed 125 mg/d
Infants and children: 50-75 mg/kg/d IV/IM divided q12h; not to exceed 2 g/d

Interactions

Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; caution in breastfeeding and allergy to penicillin

Gentamicin (Garamycin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.
Not the DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be given IV/IM.

Dosing

Adult

Serious infection and normal renal function: 3 mg/kg/d IV q8h
Loading dose and maintenance dose: 1-2.5 mg/kg IV and 1-1.5 mg/kg IV, respectively, q8h
Extended dosing regimen for life-threatening infections: 5 mg/kg/d IV/IM q6-8h
Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion

Pediatric

<5 years: 2.5 mg/kg/dose IV/IM q8h
>5 years: 1.5-2.5 mg/kg/dose IV/IM q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults

Interactions

Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)

Contraindications

Documented hypersensitivity; non–dialysis-dependent renal insufficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Ampicillin (Principen, Omnipen, Marcillin)

Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.

Dosing

Adult

250-500 mg PO q6h; 500 mg to 1.5 g IM q4-6h; 500 mg to 3 g IV q4-6h; not to exceed 12 g/d

Pediatric

50-100 mg/kg/d PO divided q4-6h; 100-400 mg/kg/d IM/IV divided q4-6h

Interactions

Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Amoxicillin (Amoxil, Trimox)

Interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria.

Dosing

Adult

250-500 mg PO q8h; not to exceed 3 g/d

Pediatric

20-50 mg/kg/d PO divided q8h

Interactions

Reduces efficacy of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment; may enhance chance of candidiasis

Vancomycin (Vancocin)

Potent antibiotic directed against gram-positive organisms and active against Enterococcus species. Useful in treatment of septicemia and skin structure infections. Indicated for patients who cannot receive or did not respond to penicillins and cephalosporins or patients who have infections with resistant staphylococci. For penetrating abdominal injuries, combine with an agent active against enteric flora and/or anaerobes.
To avoid toxicity, current recommendation is to assay trough levels after third dose drawn 0.5 h prior to next dosing. Use CrCl to adjust dose in patients diagnosed with renal impairment.
Used in conjunction with gentamicin for prophylaxis in penicillin-allergic patients undergoing gastrointestinal or genitourinary procedures.

Dosing

Adult

500 mg to 2 g/d IV divided tid/qid 7-10 d

Pediatric

40 mg/kg/d IV divided tid/qid 7-10 d

Interactions

Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in renal failure and neutropenia; red man syndrome is caused by IV infusion that is too rapid (dose given over a few min) but rarely happens when dose given as 2-h administration or as PO or IP administration; red man syndrome is not an allergic reaction

Cephalexin (Keflex)

First-generation cephalosporin that arrests bacterial growth by inhibiting bacterial cell wall synthesis. Bactericidal activity against rapidly growing organisms. Primary activity against skin flora; used for skin infections or prophylaxis in minor procedures.

Dosing

Adult

250-1000 mg PO q6h for 10-14 d; not to exceed 4 g/d

Pediatric

25-50 mg/kg/d PO q6h; not to exceed 3 g/d

Interactions

Coadministration with aminoglycosides increases nephrotoxic potential

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal impairment

Nitrofurantoin (Macrobid, Macrodantin)

Synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.

Dosing

Adult

50-100 mg/dose PO q6h

Pediatric

<1 month: Not established
>1 month: 5-7 mg/kg/d PO divided q6h; not to exceed 400 mg/d
Long-term therapy: 1-2 mg/kg/d PO divided 12-24 h; not to exceed 100 mg/d

Interactions

Anticholinergics may delay gastric emptying and increase absorption, increasing nitrofurantoin bioavailability; antacids made of magnesium salts may decrease effects by decreasing absorption; high doses of probenecid concurrently decrease renal clearance and increase toxicity

Contraindications

Documented hypersensitivity; renal insufficiency (CrCl <60 mL/min), anuria, or oliguria

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May cause severe and irreversible peripheral neuropathy that can be fatal; renal impairment, diabetes, electrolyte imbalance, anemia, and vitamin B deficiency increase risk for adverse effects; prolonged use of antibiotics may result in fungal or bacterial overgrowth of resistant or nonsusceptible organisms

Trimethoprim and sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)

Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except P aeruginosa.

Dosing

Adult

160 mg TMP/800 mg SMZ PO q12h for 10-14 d

Pediatric

<2 months: Do not administer
>2 months: 15-20 mg/kg/d, based on TMP, PO tid/qid for 14 d

Interactions

May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine

Contraindications

Documented hypersensitivity; megaloblastic anemia due to folate deficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholism, elderly persons, those receiving anticonvulsant therapy, or those with malabsorption syndrome); hemolysis may occur in those with G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Norfloxacin (Noroxin)

Fluoroquinolone with activity against pseudomonads, streptococci, MRSA, S epidermidis, and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth.

Dosing

Adult

400 mg PO bid for 3-21 d; not to exceed 800 mg/d

Pediatric

<18 years: Not recommended
>18 years: Administer as in adults

Interactions

Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Ampicillin and sulbactam (Unasyn)

Drug combination of beta-lactamase inhibitor with ampicillin. Interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.
Used for treatment of pyelonephritis. Both ampicillin and sulbactam are excreted in the urine.

Dosing

Adult

3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6h; not to exceed 4 g/d sulbactam or 8 g/d ampicillin

Pediatric

Not established

Interactions

Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reactions

Tobramycin (Nebcin)

Used in skin, bone and skin-structure infections caused by Staphylococcus aureus, P aeruginosa, E coli, and Klebsiella, Proteus, and Enterobacter species. Indicated in treatment of staphylococcal infections when penicillin or potentially less-toxic drugs are contraindicated and when bacterial susceptibility and clinical judgment justify its use. Dosing regimens are numerous and are adjusted on basis of CrCl and changes in volume of distribution.

Dosing

Adult

Serious infections and normal renal function: 3 mg/kg IV/IM q8h
Extended dosing regimen for life-threatening infections: 5 mg/kg IV/IM q6-8h
Usual loading dose: 1-2.5 mg/kg IV; maintenance dose, 1-1.5 mg/kg IV q8h
Each regimen must be followed by at least trough level drawn on third or fourth dose 0.5 h before dosing; may draw peak level 0.5 h after 30-min infusion

Pediatric

<5 years with normal renal function: 2.5 mg/kg IV/IM q8h
>5 years: 1.5-2.5 mg/kg IV/IM q8h or 6-7.5 mg/kg/d IV/IM divided q8h; not to exceed 300 mg/d; adjustments for renal function as needed; monitor levels as in adults

Interactions

Effects decrease when used concurrently with gentamicin

Contraindications

Documented hypersensitivity; mycobacterial, viral, and fungal infections of the eye; steroid combinations after uncomplicated removal of a foreign body from cornea should also avoid using this product

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Do not use in deep-seated ocular infections or in those that may become systemic; prolonged use of antibiotics, may result in bacterial or fungal overgrowth of nonsusceptible organisms

Aztreonam (Azactam)

A monobactam, not a beta-lactam, antibiotic that inhibits cell wall synthesis during bacterial growth. Active against gram-negative bacilli but very limited gram-positive activity and not useful for anaerobes. Lacks cross-sensitivity with beta-lactam antibiotics. May be used in patients allergic to penicillins or cephalosporins.
Duration of therapy depends on severity of infection and continued for at least 48 h after patient asymptomatic or evidence of bacterial eradication obtained. Doses smaller than indicated should not be used.
Transient or persistent renal insufficiency may prolong serum levels. After initial loading dose of 1 or 2 g, reduce dose by one half for estimated ClCr of 10-30 mL/min/1.73 m². When only serum creatinine concentration available, the following formula (based on sex, weight, and age) can approximate ClCr. Serum creatinine should represent a steady state of renal function.
Males: ClCr = [(weight in kg)(140 - age)] divided by (72 X serum creatinine in mg/dL)
Females: 0.85 X above value
In patients with severe renal failure (ClCr <10 mL/min/1.73 m²), those supported by hemodialysis, usual dose of 500 mg, 1 g, or 2 g, is given initially.
Maintenance dose is one fourth of usual initial dose given at usual fixed interval of 6, 8, or 12 h.
For serious or life-threatening infections, supplement maintenance doses with one-eighth of initial dose after each hemodialysis session.
Elderly persons may have diminished renal function. Renal status is a major determinant of dosage in these patients. Serum creatinine may not be an accurate determinant of renal status. Therefore, as with all antibiotics eliminated by kidneys, obtain estimates of ClCr, and make appropriate dosage modifications. Insufficient data are available regarding IM administration to pediatric patients or dosing in pediatric patients with renal impairment. Administered IV only to pediatric patients with normal renal function.

Dosing

Adult

500-1000 g q8-12h IV/IM

Pediatric

90-120 mg/kg/d divided q6-8h IV/IM

Interactions

Tetracyclines may reduce effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal insufficiency

Meropenem (Merrem IV)

Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. Effective against most gram-positive and gram-negative bacteria.
Has slightly increased activity against gram-negatives and slightly decreased activity against staphylococci and streptococci compared to imipenem.

Dosing

Adult

1 g IV q8h

Pediatric

40 mg/kg IV q8h

Interactions

Probenecid may inhibit renal excretion of meropenem, increasing meropenem levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Dosage adjustments (adult adjustments)
CrCl (mL/min) 10-50: 0.5-1 g q12h
CrCl <10: 0.5 g/d
Hemodialysis (HD): As for CrCl <10, with an extra 0.5 g after HD
Pseudomembranous colitis and thrombocytopenia may occur, requiring immediate discontinuation of medication

Piperacillin and Tazobactam sodium (Zosyn)

Anti-pseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.

Dosing

Adult

3/0.375 g (piperacillin 3 g and tazobactam 0.375 g) IV q6h

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Tetracyclines may decrease effects of piperacillin; high concentrations of piperacillin may physically inactivate aminoglycosides if administered in same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels; high dose parenteral penicillins may result in increased risk of bleeding

Contraindications

Documented hypersensitivity; severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, and purulent or septic arthritis should not be treated with an oral penicillin during the acute stage

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Perform CBCs prior to initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients diagnosed with hepatic insufficiencies; perform urinalysis and BUN and creatinine determinations during therapy and adjust dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions

Ticarcillin and clavulanate potassium (Timentin)

Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active growth.
Anti-pseudomonal penicillin plus beta-lactamase inhibitor that provides coverage against most gram-positives, most gram-negatives, and most anaerobes.

Dosing

Adult

3.1 g IV q4-6h

Pediatric

75 mg/kg IV q6h

Interactions

Tetracyclines may decrease effects of ticarcillin; high concentrations of ticarcillin may physically inactivate aminoglycosides if administered in same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels

Contraindications

Documented hypersensitivity; severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, and purulent or septic arthritis should not be treated with oral penicillin during acute stage

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Perform CBCs prior to initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients diagnosed with hepatic insufficiencies; perform urinalysis and BUN and creatinine determinations during therapy and adjust dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions

Imipenem and cilastatin (Primaxin)

For treatment of multiple organism infections in which other agents do not have wide spectrum coverage or are contraindicated due to potential for toxicity.

Dosing

Adult

Base initial dose on severity of infection, and administer in equally divided doses; dose may range from 250-500 mg q6h IV for a maximum of 3-4 g/d
Alternatively, 500-750 mg q12h IM or intra-abdominally

Pediatric

Infants >3 months and children <12 years: 15-25 mg/kg/dose IV q6h
Fully susceptible organisms: Not to exceed 2 g/d
Infections with moderately susceptible organisms: Not to exceed 4 g/d
>12 years: Administer as in adults

Interactions

Coadministration with cyclosporine may increase CNS adverse effects of both agents; coadministration with ganciclovir may result in generalized seizures

Contraindications

Documented hypersensitivity; known hypersensitivity to amide local anesthetics; children with CNS infections (increased seizure risk); children <30 kg with renal impairment (lack of data)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in renal insufficiency (adult adjustments)
CrCl (mL/min) 80-50: 0.5 g q6-8h
CrCl 50-10: 0.5 g q8-12h
Hemodialysis (HD): 0.25-0.5 g after HD, then q12h
Adjust dose in renal insufficiency; avoid use in children <12 y with CNS infections
Caution with history of seizures, hypersensitivity to penicillins, cephalosporins, or other beta lactam antibiotics

Urinary analgesics

Indicated when patient has dysuria to such an extent that it disrupts activities of daily living.

Phenazopyridine (Pyridium, Urodine, Urogesic)

Azo dye excreted in urine, where it exerts a topical analgesic effect on urinary tract mucosa. Compatible with antibacterial therapy and can help relieve pain and discomfort before antibacterial therapy controls infection. Used for symptomatic relief of pain, burning, urgency, frequency, and other discomfort arising from irritation of lower urinary tract mucosa caused by infection, trauma, surgery, endoscopic procedures, or passage of sounds or catheters. Analgesic action may reduce or eliminate need for systemic analgesics or narcotics.

Dosing

Adult

200 mg tid PO pc for 2 d

Pediatric

<6 years: Not established
6-12 years: 12 mg/kg/d divided tid PO for 2 d
>12 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; renal insufficiency

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal insufficiency; yellowish tinge of skin or sclera may indicate accumulation because of impaired renal excretion (discontinue therapy); treatment of UTI with phenazopyridine should not exceed 2 d because no evidence exists indicating this is more beneficial than the antibiotic alone following 2 d of therapy; dye may stain clothing

Follow-up

Further Inpatient Care

• Continue supportive care.
• Monitor urine and blood culture results.
• Monitor comorbid conditions for deterioration.
• Maintain hydration status with intravenous fluids until hydration can be maintained with oral intake.
• Maintain intravenous antibiotics until defervescence and significant symptomatic improvement occur. Convert to an oral regimen guided by urine or blood culture results.

Further Outpatient Care

• Continue supportive care by prescribing antiemetics, antipyretics, analgesics, and urinary tract analgesics as needed.
• Complete a 14-day course of oral antibiotics. Recent evidence suggests that when treating a young, healthy female, the course of treatment can be shortened to 7 days from 14 days, if the antibiotic being used is a fluoroquinolone. Healthy young males should complete a 14-day course.
• Obtain follow-up urine culture results in any patient with a complicated UTI (see Causes), a complicated course, or increased risk of infection.
• Urine cultures are generally not indicated in healthy, nonpregnant women with resolved symptoms.
• Rest is essential for recovery. Activity should be minimal. The patient should not return to work for 2 weeks in order to allow time for the infection to be eliminated and for the patient to recuperate physical strength. Temper this recommendation depending on the physical condition of the patient and the presence of comorbid conditions.
• If the patient is not admitted at the time of diagnosis, follow-up reevaluation is important in 1-2 days to be sure the patient is progressing properly. A good rule based on common sense is that if the managing clinician is concerned that the patient may not respond well to outpatient management but still thinks the patient deserves a trial at home, then the initial follow-up visit should take place in 24 hours. If the clinician thinks that patient will do quite well with outpatient management, the initial follow-up visit can take place in 48 hours.
• If the patient thinks that he or she is not progressing well or is getting worse, then the patient should be evaluated emergently for consideration for admission and intravenous antibiotics.
• All patients with a complicated UTI (see Causes) should be considered for outpatient follow-up imaging of their urinary tract to evaluate for abnormalities that predispose to further infections.

Inpatient & Outpatient Medications

• Antipyretics may be beneficial.
• Use oral and parenteral antiemetics as needed. Early in the course of the illness, parenteral medication is often necessary to reduce morbidity from symptoms.
• Use oral and parenteral analgesics as needed. Early in the course of the illness, parenteral medication is often necessary to reduce morbidity from symptoms. Nonsteroidal medications and narcotics are complementary and do not assume that one is better than the other.
• Parenteral antibiotics are often initially administered at the time of diagnosis, regardless of whether the patient is admitted or discharged home. Continuing intravenous antibiotics for the admitted patient is essential until defervescence and improvement in the clinical condition warrants changing to oral antibiotics to complete the course. Once the patient is improved, due consideration can be given to discharge and close follow-up care in an outpatient setting.
• Urinary tract analgesics may be beneficial if the patient has dysuria to such an extent that it disrupts the activities of daily living.

Transfer

• When patients are treated in an inpatient setting, the facility to which they are admitted should be able to provide an appropriate level of care for pyelonephritis and any comorbid conditions. If the admitting facility is unable to provide an appropriate level of care, the patient should be transferred to a facility that is able to meet that patient's needs.

Deterrence/Prevention

• Prevention of pyelonephritis involves identifying clinical situations that could lead to pyelonephritis and developing a strategy to decrease that likelihood. These strategies may include a change in contraceptive behavior, administration of prophylactic antibiotics, or early identification and treatment of UTIs. Several such strategies are elaborated below. Failure of these strategies to eliminate infection, recurrence of infection, or relapse (reinfection <14 d after completing an appropriate regimen) indicates the need to refer the patient for systematic evaluation for predispositional anatomic, functional, or structural abnormalities.
• Children with recurrent UTIs or urinary tract structural abnormalities require prompt evaluation of urinary tract symptoms and appropriate treatment.
• Premenopausal or postmenopausal women with recurrent, uncomplicated UTIs
  • In this population, recurrent UTIs may be defined as 2-2.6 UTIs per year, which occur in approximately 25% of women who develop acute uncomplicated UTIs.
  • Various behavioral and nutritional techniques have been recommended to decrease the recurrence of UTIs in young women. Daily cranberry juice intake has been suggested to be beneficial, but no conclusive evidence has been found. Behavioral techniques, such as postcoital voiding and front-to-back wiping after defecation, have been considered efficacious measures for lessening the risk of UTI; however, in a study of college-aged women, they accorded no benefit. Additionally, oral contraceptive use and tampon use were not associated with UTIs.
  • If the patient is using a diaphragm with spermicide for contraception, another method of contraception should be substituted so that spermicide-associated colonization of the vagina by uropathogens is avoided.
  • If the patient has 3 or more UTIs per year, postcoital or continuous antibiotic therapy is recommended for 6 months, followed by a reevaluation. Postcoital regimens include trimethoprim-sulfamethoxazole at 40 mg/200 mg, cephalexin at 125-250 mg, and nitrofurantoin at 50 mg (effective in pregnancy). Regimens for continuous dosing (daily or 3 times/wk) include trimethoprim-sulfamethoxazole at 40 mg/200 mg, trimethoprim at 100 mg, norfloxacin at 200 mg, nitrofurantoin at 200 mg, and cephalexin at 125-250 mg.
  • If the patient has fewer than 3 UTIs per year, patient-initiated therapy is recommended using standard regimens, such as single-dose therapy or 3-day therapy. Referral for urological evaluation is indicated if the patient is not responding, if the patient has any complicating condition, or if the patient has a relapse. Refer to Urinary Tract Infection, Females for more information.
• Catheter-related infections or neurogenic bladder
  • Indwelling catheters have a cumulative incidence rate of bacteriuria of 3-10% per day. Two strategies for reducing bacteriuria and its sequelae are removal of the catheters as soon as possible and keeping the closed system closed. After the indwelling catheter is removed, alternative strategies for emptying the bladder that reduce but do not eliminate the risk of infection are condom catheters, intermittent catheterization (1-3% risk of bacteriuria per catheterization), intraurethral catheters, and suprapubic catheters.
  • Situations in which treatment of asymptomatic bacteriuria are indicated include culture of Serratia marcescens, clearance of an organism responsible for an infection cluster in an institution, and clearance of an organism in a high-risk patient (eg, neutropenic, posttransplantation, pregnant).
• Chronic bacterial prostatitis
  • This condition produces recurrent bacteriuria interspersed with prolonged periods without bacteriuria.
  • Treatment involves 2-3 months of a fluoroquinolone that has good prostate penetration. The goal of therapy is to eradicate infection from the prostate.
• Renal transplant recipients
  • The frequency of UTIs (35-79%) and the potential morbidity of transplant pyelonephritis are relatively high in this population.
  • Transplant recipients typically receive prophylaxis with trimethoprim-sulfamethoxazole for at least the first 6-12 months following transplantation.
  • The antibiotic chosen may be modified depending on local organism sensitivities.

Complications

• Complications occur more often in patients with diabetes mellitus, chronic renal disease, sickle cell disease, renal transplant (particularly the first 3 mo), AIDS, and other immunocompromised states. Sometimes, determining if the entities listed below are occurring as a complication of pyelonephritis or presenting in the absence of pyelonephritis with signs and symptoms suggestive of pyelonephritis is difficult. The important point is to have a high index of suspicion because they are associated with markedly increased morbidity and mortality.
  • Abscess formation (see Surgical Care): This may include renal cortical abscess, renal corticomedullary abscess, or perinephric abscess.
  • Emphysematous formation (gas in tissues): This may occur (see Surgical Care), and recognizing it is critical. Treatment may include nephrectomy.
  • Emphysematous pyelitis (pneumopyonephrosis): This involves gas that is localized to the collecting system. Diabetes mellitus is present in 85-100% of patients. The left kidney is more affected than the right. Presentation is similar to pyelonephritis. On plain radiographs, the gas pattern is noted in the renal pelvis and may be seen in the ureter. The patient should be admitted and treated with intravenous antibiotics (see Medical Care). The mortality rate is 20%.
  • Emphysematous cystitis (cystitis emphysematosa): This involves gas that is localized to the bladder secondary to a bladder infection. Gas in the bladder is more frequently related to a fistula between the bladder and the colon or vagina than to a gas-producing infection. As many as 80% of patients are diabetic. Patient presentation is similar to that for pyelonephritis. Plain radiographs may demonstrate gas in the bladder wall or lumen, an air-fluid level in the bladder, or a cobblestone appearance to the bladder wall. CT scan is the study of choice to help localize the gas to the proper organ. Treatment involves intravenous antibiotics (see Medical Care) and relief of any outlet obstruction. This condition is not as serious as the other 2 previously described emphysematous conditions.
  • Acute renal failure (see Acute Renal Failure)
  • Chronic renal damage leading to hypertension and renal failure
  • Sepsis syndromes (see Sepsis, Bacterial)
  • Renal papillary necrosis (see Surgical Care)
  • Xanthogranulomatous pyelonephritis (see Surgical Care)

Prognosis

• 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 children, the prognosis is good. Importantly, children should undergo a urological evaluation after the first episode to rule out structural abnormalities.
• If the patient has a known complicating condition, urological evaluation is indicated to determine the status of the complicating condition and the status of the kidney (see Causes).

Patient Education

• 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 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 excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Urinary Tract Infections and Blood in the Urine.

Miscellaneous

Medicolegal Pitfalls

• Any poor outcome in a patient's illness could potentially raise a question of liability on the part of the physician managing that patient's case. Alternatively, in many instances good medical management decisions are made in a timely fashion but the outcome is still poor. Always keep in mind that the natural history of the disease may subvert even the best medical and surgical management possible.
• The following are clinical issues in the management of pyelonephritis that are important considerations with the potential for liability, particularly if complications arise or the outcome is poor:
  • 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.
  • Patients with diabetes are at increased risk for complications related to pyelonephritis. 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. Timely diagnosis and management has a significant impact on the outcome.
  • Infants and children who have had pyelonephritis should be evaluated for urinary tract abnormalities.
  • Any patient with acute pyelonephritis who deteriorates suddenly or does not respond to conventional therapy may have a complication, resistant organism, or unrecognized comorbidity.

Special Concerns

• Pregnancy issues
  • Physiological changes in the urinary tract predispose pregnant women to an increased risk of UTI and pyelonephritis, which may lead to preterm labor and kidney damage.
  • Hydroureter of pregnancy develops around the seventh week and progresses throughout the remainder of pregnancy; it resolves by 8 weeks postpartum. The ureters may dilate sufficiently to contain 200 mL of urine or more. In addition, the kidneys enlarge and bladder capacity may double. The left kidney is more affected than the right. The prevalence rate of bacteriuria in pregnancy is 2-25%, depending on the study criteria.
  • Symptomatic UTI (1-3% of all pregnancies) leads to premature labor in 20-50% of cases. The recommendation is that all pregnant women have a screening urine culture at 16 weeks' gestation. If the results are negative for a UTI, no additional cultures are indicated. If the patient has a history of recurrent UTIs, further cultures and other screening techniques (eg, nitrite dipstick or urine Gram stain) may be needed to detect the development of asymptomatic bacteriuria.
  • Accepted regimens for treating asymptomatic bacteriuria include amoxicillin (250 mg tid for 3 d or 7 d; 3-g single dose), cephalexin (2- or 3-g single dose), and nitrofurantoin (200-mg single dose; 100 mg qid for 3 d or 7 d). Successfully treated bacteriuria prevents pyelonephritis.
  • Presentation of pyelonephritis is similar in pregnant and nonpregnant females. The antibiotic regimen of choice is intravenous ampicillin and gentamicin. This is followed by an oral regimen to complete a 14-day course guided by results from susceptibility studies. Obtain an additional urine culture 1-2 weeks after the completion of therapy to verify eradication of the infection, and obtain monthly urine cultures until delivery to monitor the urine for recurrent infection.
  • Postcoital therapy with cephalexin or nitrofurantoin is recommended for prophylaxis against recurrent infection.
  • If the initial infection requires a second agent for clearing the infection or a recurrent infection occurs, suppressive therapy until delivery is indicated with nitrofurantoin (50 mg or 100 mg qhs).
  • Recurrent infection or persistent bacteriuria is an indication for urological evaluation 3-6 months after delivery.
• Geriatric issues
  • After age 65 years, at least 20% of women and 10% of men have bacteriuria. Several factors appear to account for this level of bacterial presence in the urinary tracts of elderly persons, as follows:
    • Obstructive uropathy (eg, urinary stones, prostatic hypertrophy, uterine prolapse, cystocele)
    • Decreased bactericidal activity in prostatic secretions
    • Perineal soiling with fecal matter in women with dementia
    • Neuromuscular disease
    • Increased instrumentation of urinary tract
    • Urinary catheters
    • Reduced Tamm-Horsfall protein secretion in the urine
    • Increased uropathogens in the postmenopausal vagina and introitus
  • The single most important factor predisposing the urinary tract to infection is obstruction in any form.
  • Elderly patients may present with pyelonephritis manifesting as abnormal urine coupled with fever, mental status change, decompensation in another organ system, or generalized deterioration. Alternatively, the presentation may include previously described signs and symptoms (see Clinical). If sepsis is suggested, refer to Sepsis, Bacterial. If an underlying condition is decompensating as a result of pyelonephritis, refer to the appropriate eMedicine article for management of the condition. Management principles remain the same as outlined above. The important issue is to consider the diagnosis in any elderly patient who presents with an acute medical condition.
• Pediatric issues
  • The manifestation of symptomatic UTI and pyelonephritis varies in the pediatric population depending on the age of the patient. The classic signs and symptoms observed in adults are often absent in children, particularly neonates and infants. When fever is present, pyelonephritis should be in the differential diagnosis.
  • Indications for immediate urological referral during acute pyelonephritis are abnormal electrolyte values associated with acidosis, elevated blood urea nitrogen level, hypertension, a palpable bladder, and voiding difficulty (dribbling, poor stream, straining).
  • Aside from the effects of acute infection, the overriding concern is progressive renal deterioration of an already compromised kidney (hypoplastic or dysplastic) secondary to scarring from recurrent pyelonephritis with or without associated obstruction.
  • The groups at greatest risk are infants and preschool-aged children. Initial management varies with patient age and presentation.
  • Close follow-up examination, regardless of whether the patient is initially admitted, is essential to ensure recovery. Immediate reevaluation is encouraged for any recurrence of symptoms because treatment of asymptomatic bacteriuria and long-term suppressive therapy have not been found to be efficacious.
  • Urological evaluation is necessary to establish the presence of any urological abnormality. The preferred imaging study for the diagnosis of acute pyelonephritis is DMSA scintigraphy. Ultrasonography is the imaging study of choice for the diagnosis of urinary tract structural abnormalities.
  • Age-related data adapted from Harwood-Nuss and colleagues and Hansson and colleagues are presented in Table 5.^6,7

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Keywords

infectious tubulointerstitial nephritis, kidney infection, renal infection, upper urinary tract infection, upper UTI, Escherichia coli, E coli, bacterial infection, gram-positive infection, uropathogens, urovirulent organisms, urinary obstruction, prostatic infection, calculi, urinary diversion procedure, infected cysts, urinary catheter, nephrostomy tubes, vesicoureteral reflux, neurogenic bladder, bladder abscess, renal abscess, perinephric abscess, diabetes mellitus, pregnancy complications, renal impairment, xanthogranulomatous pyelonephritis, XGP, malakoplakia, primary biliary cirrhosis, transplantation, neutropenia, AIDS, immunodeficiency, emphysematous pyelonephritis, sepsis

Contributor Information and Disclosures

Author

William H Shoff, MD, DTM&H, Director, PENN Travel Medicine, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania
William H Shoff, MD, DTM&H is a member of the following medical societies: American College of Physicians, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Glaxo Smith Kline Consulting fee Consulting; Glaxo Smith Kline Honoraria Speaking and teaching

Coauthor(s)

Judith Green-McKenzie, MD, MPH, Associate Professor of Emergency Medicine, Director of Clinical Practice and Associate Director of Occupational Medicine, Department of Emergency Medicine, University of Pennsylvania School of Medicine, University Hospital
Judith Green-McKenzie, MD, MPH is a member of the following medical societies: American College of Occupational and Environmental Medicine, American College of Physicians, American College of Preventive Medicine, National Medical Association, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Christopher Edwards, MD, Staff Physician, Department of Emergency Medicine, University of Pennsylvania Medical School
Christopher Edwards, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Amy J Behrman, MD, Associate Professor, Department of Emergency Medicine, Director, Division of Occupational Medicine, University of Pennsylvania School of Medicine
Amy J Behrman, MD is a member of the following medical societies: American College of Occupational and Environmental Medicine
Disclosure: Nothing to disclose.

Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM, Associate Professor, Department of Emergency Medicine, Hospital of the University of Pennsylvania; Director of Education and Research, PENN Travel Medicine
Suzanne Moore Shepherd, MD, MS, DTM&H, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American Society of Tropical Medicine and Hygiene, International Society of Travel Medicine, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Chike Magnus Nzerue, MD, Associate Dean for Clinical Affairs, Meharry Medical College
Chike Magnus Nzerue, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, and National Kidney Foundation
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Managing Editor

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine, Director of Nephrology Training Program, Kidney Disease Program, University of Louisville School of Medicine; Director, Metabolic Stone Clinic
Eleanor Lederer, MD 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, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
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Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
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