Acute Uncomplicated Pyelonephritis in Adults

Acute Uncomplicated Pyelonephritis in AdultsAcute Uncomplicated Pyelonephritis in Adults

Acute Uncomplicated Pyelonephritis in Adults

Introduction

Pyelonephritis, commonly known as upper urinary tract infection, is a bacterial infection that results from bacteria ascending into the kidneys from the lower urinary tract. Other times, these bacteria reach the kidneys through the bloodstream. In the US, over 250,000 cases are diagnosed on a yearly basis, with the majority being females. 15 to 17 women out of every 10,000 women are hospitalized due to pyelonephritis. (1) It can be severe in pregnant women, infants, and neonates.

This article discusses pyelonephritis, symptoms, causes, and general aspects of managing the infection in adult patients.

EPIDEMIOLOGY (2-3)

Annually, about 250,000 office visits in the united states are due to pyelonephritis. It is also responsible for 200,000 hospital admissions on an annual basis. Pyelonephritis shows a very high incidence in women between the ages of 15 and 29, with Escherichia Coli being the most frequent (90%) cause in uncomplicated cases. Other organisms are prevalent in complicated cases of pyelonephritis. (2) 15-17 cases per 10,000 females and 3-5 cases per 10,000 males are reported annually. (3) 20-30% of pregnant women with untreated asymptomatic bacteriuria (ABU) develop acute pyelonephritis. In the United States in 2014, it has been reported a 35% and 10% resistance of E Coli to trimethoprim-sulfamethoxazole and fluoroquinolones, respectively. Globally, the resistance of extended-spectrum beta-lactamase-producing uropathogens to third- and fourth-generation cephalosporins, is on the rise. (2)

ETIOLOGY (2,5)

As we know, acute pyelonephritis can be caused by the ascent of bacteria from the lower urinary tract to the renal parenchyma and the pelvic calyceal system. The majority of UTIs are caused by gram-negative bacteria; however, gram-positive bacteria can also play a role. It is important to note that the causative organism can vary based on the population group.

 The most common bacteria that ascend into the kidneys are:

  • Escherichia coli: approximately 90% of pyelonephritis is caused by this bacterium. (2)

10 % of cases of pyelonephritis are caused by the following species: (2)

  • Klebsiella Pneumoniae
  • Proteus Mirabilis
  • Staphylococcus saprophyticus
  • Enterococcus Faecalis
  • Pseudomonas Aeruginosa

Pyelonephritis can also be caused by a hematogenous spread of bacteria, especially in immunocompromised patients and neonates. The major culprit in the spread of bacteria through the bloodstream is Staphylococcus Aureus. (4)

Both complicated and uncomplicated UTIs can be caused by E. Coli both in men and women. Complicated infections commonly isolated in hospitals and care facilities are a result of Proteus Mirabilis, Enterococcus spp, and Pseudomonas Aeruginosa infection. (5)

Coagulase-positive Staphylococci can invade the kidney from hematogenous spread, resulting in renal abscesses. (5)

PATHOPHYSIOLOGY (6-7)

The kidneys are highly vascularized sterile organs that contain approximately a million nephrons. The nephrons filter waste products from the blood. The filtrate flows through the nephrons into the tubule-epithelium, where it is absorbed and secreted as urine. During a bacterial invasion, these adhere to and colonize the tubule epithelium causing a change in its physiology and histology. The colonization of this microenvironment leads to an alteration in vascular coagulation, epithelial breakdown, immune cell recruitment, vascular leakage, and general tissue damage. The final result of these alterations is a significant loss of oxygen within the affected tissue, edema containing polymorphonuclear cells, and necrosis.

Staphylococcus aureus bacteremia and endocarditis can lead to the hematogenous spread of bacteria into the upper urinary tract. This also causes necrosis or abscess within the renal parenchyma.

CLASSIFICATION

Pyelonephritis can be classified into:

Uncomplicated pyelonephritis: these cases generally present in women with mild symptoms requiring outpatient treatment. By definition, there are no known structural or functional abnormalities of the urinary tract, no comorbidities, and no relevant kidney disease.

Complicated pyelonephritis: these cases could show evidence of structural, anatomical, and functional abnormalities of the urinary tract, comorbidities, and impaired renal function. Pyelonephritis in men is considered a complicated pyelonephritis. (8)

It usually requires hospitalization to prevent life-threatening complications such as sepsis, septic shock, or multi-organ failure.

RISK FACTORS (1)

There are a variety of risk factors that increase a patient’s probability of presenting with complicated pyelonephritis: (1)

  • Kidney stones
  • Urinary tract obstruction
  • Abnormal urinary tract
  • Diabetes
  • Pregnancy
  • Immunocompromised state.

SYMPTOMS

Pyelonephritis is a clinical syndrome characterized by the following urinary symptoms:

  • Urinary frequency
  • Urinary Urgency
  • Dysuria

The clinical  picture is accompanied by other systemic symptoms such as:

  • Fever: this is not a constant symptom, but when present, the temperature is usually over 103 Fahrenheit or 39.4 degrees Celsius. In the absence of fever, the patient may present with chills and malaise.
  • Nausea or vomiting: for some patients, these symptoms may be mild; for others, they can be severe while presenting with anorexia and dehydration.
  • Costovertebral angle or flank pain: the pain intensity can vary from mild to moderate or severe tenderness. It is usually unilateral, resulting from the inflammation of the affected kidney. Some cases may present with bilateral discomfort or pain. Lower back pain or suprapubic pain may also be present.
  • Hematuria: this is frequent in 30 to 40% of females with pyelonephritis, especially young women. (3) It is very uncommon to find hematuria in male patients.

In elderly patients, the typical symptoms are present and accompanied by

  • Fever
  • Mental status change
  • Generalized deterioration
  • Decompensation in one or more organs

CRITERIA FOR HOSPITALIZATION (4)

A patient can be treated as an outpatient if stable. If the below factors are present, consider inpatient treatment. (4)

  • Pregnancy
  • Emesis (inability to reliably keep down oral medications)
  • Sepsis parameters, systemic inflammatory response syndrome (SIRS)
  • Complicated pyelonephritis infection (including men)

DIAGNOSIS (9-11)

In diagnosing pyelonephritis, there are multiple factors that should be considered.

  • Clinical presentation (fever, flank pain, vomiting, hematuria, etc.)
  • Physical examination should include costovertebral angle percussion, abdominal examination, and possibly pelvic examination.
  • Urinalysis is often used to detect UTIs. A clean-catch, midstream sample, or catheterized specimen should be obtained in cases where pyelonephritis is suspected. The urine sample should be received in the laboratory within one hour of collection (or stored at 4°C and tested within 18 hours) to reduce the risk of overgrowth of bacteria.
  • Clean-catch dipstick leukocyte esterase test to screen for the presence of pyuria; this test has high sensitivity and specificity for detecting more than 10 WBC/mm3 in urine. Positive pyuria is not specific and does not always indicate clinical UTI. A positive dipstick is nitrite positive, leucocyte positive, or both. However, the clinical presentation is a key factor, as a dipstick can be a false positive.
  • Bacteriuria alone is not a disease and usually does not require treatment. For symptomatic UTIs, most patients have more than 10 leukocytes/mm3; however, negative tests for bacteriuria may occur because of the low bacterial burden. Organisms like E. coli, Klebsiella spp., Enterobacter spp., Proteus spp., Staphylococcus spp., and Pseudomonas spp. reduce nitrate to nitrite in the urine, and the presence of nitrite in urinalysis is another marker of UTIs.
  • A urine culture sample with antibiotic susceptibility testing should be taken before starting empiric treatment. This will help optimize a definitive antibiotic treatment regimen once the culture result is available. In most cases of symptomatic UTIs, bacterial colonization of 100,000 CFU/mL or more is present, indicating a 95% probability of infection. (9).
  • Consider doing a full blood count, electrolytes, urea, and creatinine test, especially in febrile patients.
  • In stable uncomplicated patients, imaging is not a requirement but should be done in patients who require hospitalization or in ambulatory patients who show no improvement at their 72 hours of follow-up.
  • In patients with pyelonephritis, the first-line imaging study is ultrasound. Ultrasound is useful in assessing for local complications of pyelonephritis, such as hydronephrosis, renal infarct, renal abscess, and perinephric collections.
  • A second-line imaging option is a CT scan which is more sensitive in evaluating the urinary tract than an ultrasound. It is not considered the first-line imaging technique as a result of its ionizing radiation dose.
  • Pregnancy testing should be performed for all women of childbearing age.

INDICATIONS FOR URGENT IMAGING IN THE EMERGENCY UNIT (9-11)

  • Patient’s risk factors: immunosuppression, single kidney, renal transplant, diabetes, recurrent episodes, or congenital abnormalities.
  • Clinical suspicion: any concern for obstruction, abnormal renal function, sepsis, or failure to respond to antibiotics.
  • Diagnosis: equivocal diagnosis or if a serious alternative diagnosis is being considered.

Figure 1 Algorithm on indications for urgent imaging for patients with pyelonephritis. (9)

MANAGEMENT (4,12)

Uncomplicated pyelonephritis/Outpatient treatment (extracted from ref 4 and 12)

  • Empiric, initial, oral, outpatient treatment: if local rates of  colifluoroquinolone resistance are low (< 10%):
    • Ciprofloxacin 500 mg PO twice daily x 7 d.
    • Ciprofloxacin extended-release 1000 mg PO daily x 7 d.
    • Levofloxacin 750 mg PO daily x 5-7 d.
  • Consider an initial dose of a parenteral agent, particularly if fluoroquinolone resistance is >10%. Then complete treatment as guided by antimicrobial sensitivity results.
  • Ceftriaxone1 gm IM or IV x 1.
  • Gentamicin5 mg/kg IM or IV x 1.
  • Ciprofloxacin400 mg IV x 1.
  • Modify initial treatment based upon results of urine culture and sensitivity.
  • Oral trimethoprim-sulfamethoxazole (160/800 mg [1 double-strength tablet] twice daily for 14 days) is an appropriate choice for therapy if the uropathogen is known to be susceptible. If trimethoprim-sulfamethoxazole is used when the susceptibility is not known, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone or a consolidated 24-h dose of an aminoglycoside, is recommended.
  • Oral β-lactam agents are less effective than other available agents for the treatment of pyelonephritis.If an oral β-lactam agent is used, an initial intravenous dose of a long-acting parenteral antimicrobial, such as 1 g of ceftriaxone or a consolidated 24-h dose of an aminoglycoside, is recommended.
Complicated Pyelonephritis /Inpatient treatment (extracted from ref. 4 and 12)

Use local antibiotic susceptibility data to guide initial empiric therapy.

o   Ciprofloxacin 400 mg IV q12h (if local fluoroquinolone resistance rates < 10%).

o   Levofloxacin 500 mg IV once daily (if local fluoroquinolone resistance rates < 10%).

o   Ceftriaxone 1 g IV once daily (with or without an aminoglycoside, e.g., gentamicin

5 mg/kg IV daily).

o   Gentamicin 5 mg/kg IV once daily (with or without ampicillin 2 grams IV q4h).

o   Tobramycin 5 mg/kg IV once daily (with or without ampicillin 2 grams IV q4h).

o   Piperacillin/tazobactam 3.375 g IV q6h (with or without an

aminoglycoside, e.g., gentamicin 5 mg/kg IV daily).

o   Meropenem 2 grams IV q8h.

Duration: typically, 48h parenteral therapy or until afebrile, then switch to oral therapy

based upon susceptibility data to complete 7d (fluoroquinolone) or 14d (TMP-SMX) course.

If beta-lactam is used to complete therapy, a 10-14 days duration is needed.

Suspected or proven Enterococcus spp. infection: ampicillin 2 g IV q4h plus

an aminoglycoside (e.g., gentamicin 5 mg/kg IV daily) for initial therapy, then complete

10-14 d therapy with amoxicillin if susceptible.

 

Selected Drug Comments (extracted from ref. 12)

Drug Recommendation
Amoxicillin Use for mild-to-moderate acute uncomplicated pyelonephritis caused by Enterococcus or to complete a 14d course of therapy for same, which began with parenteral ampicillin. Employ only after susceptibility data returns.
Ampicillin For infections caused by Enterococcus spp., this parenteral agent (with or without an aminoglycoside) can be used initially for severe cases of acute uncomplicated pyelonephritis. Use PO amoxicillin to complete a 14d course of treatment.
Cefazolin It may be considered an alternative agent for susceptible pathogens. One observational, non-randomized study showed it to be non-inferior to ceftriaxone for acute pyelonephritis vis-a-vis clinical response, length of hospital stay, and 30-day readmission rates for cystitis or pyelonephritis. (12)
Ceftriaxone Active against most Enterobacteriaceae and can be used to commence outpatient therapy followed by oral therapy. However, there is no demonstrated long-term post-antibiotic effect as noted with aminoglycosides.
Ceftazidime Active against most Gram-negative organisms, including P. Aeruginosa. Attains good levels in urine.
Ceftolozane/tazobactam When compared with levofloxacin for the treatment of patients with pyelonephritis or complicated lower UTI, this agent was more likely to be associated with microbiological cure and was non-inferior in achieving clinical cure.
Moxifloxacin This fluoroquinolone is not a good choice for UTIs as it attains poor urine levels with mostly hepatic excretion.
Nitrofurantoin Not recommended for acute pyelonephritis as it does not attain therapeutic levels in renal parenchyma.
Ciprofloxacin Fluoroquinolones (FQ) are the first-line empiric treatment for acute pyelonephritis.
Levofloxacin Fluoroquinolones (FQ) are the first-line empiric treatment for acute pyelonephritis.
Gentamicin An effective modality along when given IV or IM or given as the first dose in outpatient treatment. In light of the proven post-antibiotic effect of aminoglycosides, this regimen may be preferable when combined parenteral and oral outpatient treatment is used. Single-dose therapy has not been associated with an adverse impact on the kidneys. All aminoglycosides are associated with the risk of ototoxicity beginning with the first dose.
Tobramycin An effective modality along when given IV or IM or given as the first dose in outpatient treatment. In light of the proven post-antibiotic effect of aminoglycosides, this regimen may be preferable when combined parenteral and oral outpatient treatment is used. Single-dose therapy has not been associated with an adverse impact on the kidneys. All aminoglycosides are associated with the risk of ototoxicity beginning with the first dose.
Amikacin The use of amikacin should be limited to those patients with organisms found to be resistant to other aminoglycosides.
Fosfomycin Do not use oral preparation for severe pyelonephritis because of limited systemic absorption. The drug has been used for acute uncomplicated pyelonephritis at higher dosing by IV preparation [12-16 g IV per day in 3 or 4 divided doses].

Pathogen-Specific Therapy (extracted from ref. 12)

Pathogen 1st Line Agent 2nd Line Agent
Enterobacteriaceae, including Escherichia Coli Outpatient Regimens:

Ciprofloxacin

Levofloxacin

Outpatient Regimens:

TMP/SMX

Cephalexin

Cefpodoxime

Cefixime

Ceftriaxone

Gentamicin

Enterobacteriaceae, including Escherichia Coli Inpatient regimen (until afebrile x 48h, then outpatient regimen)

Ciprofloxacin

Levofloxacin

Gentamicin ± ampicillin

Tobramycin ± ampicillin

Ceftriaxone ± gentamicin

Staphylococcus Saprophyticus Outpatient regimens:

Ciprofloxacin

Levofloxacin

Inpatient regimens (Give IV until afebrile X 48h, then PO for total 14d):

Ciprofloxacin

Levofloxacin

Ceftriaxone ± gentamicin

Outpatient regimens:

Amoxicillin/clavulanate

DIFFERENTIAL DIAGNOSIS (3)

Differential diagnosis should be carried out with the following conditions.

  • Acute abdomen and pregnancy
  • Acute bacterial prostatitis
  • Appendicitis
  • Cervicitis
  • Chronic bacterial prostatitis
  • Chronic pyelonephritis
  • Cystitis
  • Endometritis
  • Pelvic inflammatory disease
  • Urethritis

COMPLICATIONS (3)

Complications tend to appear in patients with chronic kidney disease, sickle cell disease, diabetes mellitus, kidney transplant (especially within the first three months of transplant), AIDS, and other immunocompromising diseases.

The complications of acute pyelonephritis include:

  • Impaired renal function or renal failure
  • Acute kidney injury
  • Chronic kidney damage can lead to hypertension and kidney failure
  • Sepsis
  • Renal papillary necrosis
  • Preterm labor in pregnancy
  • Xanthogranulomatous pyelonephritis
  • Renal abscess
  • Emphysematous pyelonephritis
  • Tuberculosis of the kidney, which results from hematogenous spread

Disclosures:

The author does not report any conflict of interest.

Disclaimer:

This information is for educational purposes and is not intended to treat disease or supplant professional medical judgment. Physicians should follow local policy regarding the diagnosis and management of medical conditions.

References:

  1. Arkan AA, Nada AB, Faisal AH, Wejdan AA, Rowaa MA, Raghad FA, Huda TH, Reem ZA, Fatima AA, Jawaher MA Pyelonephritis: Diagnosis, and Management Approach,J Biochem Tech (2020) 11(1): 135-138 ISSN: 0974-2328
  2. Herness J, Buttolph A, Hammer NC. Acute pyelonephritis in adults: rapid evidence review. American Family Physician. 2020 Aug 1;102(3):173-80.
  3. Tibor Fulop MD. Acute Pyelonephritis [Internet]. Practice Essentials, Background, Pathophysiology. Medscape; 2022 [cited 09-23-2022]. Available from: https://emedicine.medscape.com/article/245559-overview#a4
  4. Melia, Michael. “Pyelonephritis, Acute, Uncomplicated.” Johns Hopkins ABX Guide, The Johns Hopkins University, Johns Hopkins Guide, 2016.  www.hopkinsguides.com/hopkins/view/Johns_Hopkins_ABX_Guide/540458/all/Pyelonephritis__Acute__Uncomplicated [cited 09-23-2022].
  5. Sobel JD, Kaye D. Urinary tract infections. In: Mandell GL, Bennett JE, eds. Principles and Practice of Infectious Diseases, 8th ed. Philadelphia: Elsevier Saunders, 2014:886-913.
  6. Roberts JA. Etiology and pathophysiology of pyelonephritis. American Journal of Kidney Diseases. 1991 Jan 1;17(1):1-9.
  7. Mulvey MA, Klumpp DJ, Stapleton AE. Urinary tract infections: molecular pathogenesis and clinical management. John Wiley & Sons; 2020 Jul 10. P. 503–522. doi:10.1128/9781555817404.ch20
  8. Hooton TM. Uncomplicated urinary tract infection. New England Journal of Medicine. 2012 Mar 15;366(11):1028-37. https://doi.org/10.1056/nejmcp1104429.
  9. Tintinali J, Gabor K, Stapczynski J. Emergency Medicine: A Comprehensive Study Guide 7th edition. American College of Emergency Physicians. 2012.
  10. Peter C, George J, Anne-Maree K, Murray l, Anthony FT. Textbook of Adult Emergency Medicine 3rd edition 2011.
  11. Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, Moran GJ, Nicolle LE, Raz R, Schaeffer AJ, et al. International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis. 2011 Mar 1; 52(5):e103-20
  12. Kalpana G, Thomas MH, Kurt GN, Björn W, Richard C, Loren GM, Gregory JM, Lindsay EN, Raul R, Anthony JS, David ES, International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases, Clinical Infectious Diseases, Volume 52, Issue 5, 1 March 2011, Pages e103–e120, https://doi.org/10.1093/cid/ciq257

See Also

Initial Management of Hip Fractures in Adults

Community Acquired Pneumonia in Adults

About the Author

Franco Cuevas, MD
Franco Cuevas is a physician who graduated from the National University of Córdoba, Argentina. He practices general medicine in the Emergency Department at Sanatorio de la Cañada, Córdoba. His focus is on writing medical content to improve physicians' access to relevant medical information for daily practice. He has participated in some research projects and has a special joy in teaching and writing about medical concepts.

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