Acute Pyelonephritis Medication
- Author: Tibor Fulop, MD, FASN, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Antibiotic therapy is essential in the treatment of acute pyelonephritis and prevents progression of the infection. Urine culture and sensitivity testing should always be performed, and when results become available, empirical therapy should be tailored to the infecting uropathogen.
Patients presenting with complicated pyelonephritis should be managed as inpatients and treated empirically with broad-spectrum parenteral antibiotics. Depending on patient presentation, antibiotic therapy can be completed with oral therapy. Antibiotics are administered for at least 10-14 days. On the basis of patient presentation, longer duration of therapy may be needed.
Sulfonamides such as trimethoprim-sulfamethoxazole(TMP-SMX) have bacteriocidal activity and are used in the treatment of pyelonephritis.
This drug combination is designed to take advantage of the synergy between trimethoprim and sulfonamides. TMP-SMX activity covers common urinary tract pathogens, both aerobic gram-positive and gram-negative bacteria, except Pseudomonas aeruginosa.
Oral trimethoprim-sulfamethoxazole (160 mg/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. This agent has been given an A-I rating in the 2010 IDSA guidelines for treating pyelonephritis.
Fluoroquinolones are acceptable agents for the treatment of pyelonephritis because they are highly effective against gram-negative and gram-positive bacteria. A major concern with fluoroquinolones is the development of resistance among uropathogens and other organisms. Oral fluoroquinolones are a treatment option for patients not requiring hospitalization where the prevalence of resistance of community uropathogens does not exceed 10%. According to the IDSA 2010 guidelines, if the prevalence of fluoroquinolone resistance exceeds 10%, an initial 1-time intravenous dose of a long-acting parenteral antimicrobial or a consolidated 24-hour dose of an aminoglycoside, is recommended. Fluoroquinolones should be avoided during pregnancy.
Oral ciprofloxacin is recommended for patients who do not need hospitalization. Dosing recommendations include 500 mg twice daily for 7 days, with or without an initial 400-mg dose of intravenous ciprofloxacin. Patients can also be given a once-daily regimen of ciprofloxacin extended release at a dosage of 1000 mg for 7 days.
Levofloxacin is also recommended as an oral antibiotic for patients with pyelonephritis not requiring hospitalization. Recommended dose includes the administration of levofloxacin 750 mg for 5 days.
Cephalosporins, Second Generation
Oral beta-lactams are not as effective for treating pyelonephritis. Based on the IDSA 2010 guidelines, however, if they are used, they should be administered with a single dose of ceftriaxone (Rocephin) 1 g IV ora consolidated 24-hour dose of an aminoglycoside.
Cefaclor is indicated for the treatment of pyelonephritis, caused by Escherichia coli, Proteus mirabilis, Klebsiella species, and coagulase-negative staphylococci. Cefaclor, 500 mg 3 times a day for 7 days, is recommended for outpatient treatment of pyelonephritis.
Cephalosporins, Third Generation
Third-generation cephalosporins are broad-spectrum and have bactericidal activity. These drugs are the most active against serious gram-negative pathogens and have some activity against gram-positive pathogens.
Ceftriaxone is a parenteral regimen that can be administered once daily in patients with pyelonephritis requiring hospitalization. For patients with mild to moderate pyelonephritis, a dosage of 1 g every 24 hours is recommended.
Cefotaxime has bactericidal activity. It is indicated for the treatment of genitourinary infections caused by Escherichia coli, Enterococcus species, and Klebsiella species, among others. For moderate to severe infections, the usual dose is 1-2 g IV or IM every 8 hours.
Ceftazidime has broad-spectrum activity against gram-negative organisms, including Pseudomonas, and lower efficacy against gram-positive organisms. It is approved for the treatment of complicated and uncomplicated cystitis caused by Pseudomonas aeruginosa; Enterobacter species; Proteus species, including Proteus mirabilis and indole-positive Proteus; Klebsiella species; and E coli.
Cefepime is a fourth-generation drug, which possesses the gram-negative activity of the third-generation agents and the gram-positive activity of the first-generation drugs.
Cefepime is a fourth-generation cephalosporin. It is indicated for the treatment of uncomplicated and complicated cystitis, including (1) pyelonephritis caused by E coli or Klebsiella pneumoniae when the infection is severe or (2) pyelonephritis caused by E coli, Klebsiella pneumoniae, or Proteus mirabilis when the infection is mild to moderate, including cases associated with concurrent bacteremia with these microorganisms.
Aminopenicillins have a broad spectrum of are bactericidal activity against gram-positive and gram-negative organisms.
Penicillins such as ampicillin can be administered in combination with aminoglycosides for patients with pyelonephritis who require hospitalization. Ampicillin has bactericidal activity against susceptible organisms.
Oral beta-lactams are not as effective for treating pyelonephritis. If they are used, they should be administered with a single dose of ceftriaxone, 1 g IV, or a consolidated 24-hour dose of an aminoglycoside. Amoxicillin-clavulanate possesses the properties of a broad-spectrum antibiotic and a beta-lactamase inhibitor.
Extended-spectrum penicillins have a broad spectrum of bactericidal activity. They are used mainly in the treatment of patients with pyelonephritis requiring hospitalization. The extended-spectrum penicillins are also an option for pregnant patients with pyelonephritis.
Piperacillin-tazobactam is useful as empirical therapy before the identification of causative organisms, because of its broad spectrum of bactericidal activity against gram-positive and gram-negative organisms. The dosing recommendation for severe pyelonephritis is 3.375 g IV every 6 hours.
Ampicillin has a broad spectrum of bactericidal activity against many gram-positive and gram-negative aerobic and anaerobic bacteria. The presence of sulbactam in the ampicillin-sulbactam formulation effectively extends the spectrum of ampicillin to include many bacteria normally resistant to it and to other beta-lactam antibiotics. Ampicillin-sulbactam, 1.5 g IV every 6 hours, can be used for the treatment of pyelonephritis.
Ticarcillin has broad-spectrum bactericidal activity against many gram-positive and gram-negative bacteria. Clavulanate is a beta-lactam agent and is structurally related to the penicillins. Clavulanate possesses the ability to inactivate a wide range of beta-lactamase enzymes commonly found in microorganisms that are resistant to penicillins and cephalosporins. General dosing recommendation is administering 3.1 g IV every 4-6 hours.
Carbapenem antibiotics are broad-spectrum antibiotics that are structurally related to beta-lactam antibiotics. Carbapenems can be used in the treatment of patients with pyelonephritis requiring hospitalization. The extended-spectrum penicillins are also an option for pregnant patients with pyelonephritis.
Doripenem is approved for the treatment of complicated cystitis, including pyelonephritis that is caused by E coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Acinetobacter baumannii. The usual dosage is 500 mg IV every 8 hours. The duration of therapy can range from 10-14 days. Duration includes a possible switch to an appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated. Duration can be extended up to 14 days in patients with concurrent bacteremia.
Ertapenem is approved for the treatment of complicated cystitis, including pyelonephritis caused by Escherichia coli including cases with concurrent bacteremia or Klebsiella pneumoniae. Usual dosage is 1 g IV every 24 hours for 10-14 days. Duration includes a possible switch to an appropriate oral therapy after at least 3 days of parenteral therapy, once clinical improvement has been demonstrated.
Meropenem is a bactericidal broad-spectrum carbapenem antibiotic that is effective against most gram-positive and gram-negative bacteria. It can be administered at a dose of 500 mg IV every 8 hours.
Imipenem/cilastatin has bactericidal activity against a wide range of gram-negative and gram-positive organisms. It is an alternative treatment for pyelonephritis because infections resistant to other antibiotics (eg, cephalosporins, penicillin, aminoglycosides) have been shown to respond to treatment with imipenem-cilastatin. The general dosing recommendation is 500 mg IV every 6 hours.
Aminoglycosides are bactericidal antibiotics used primarily in the treatment of gram-negative infections. They are commonly used in combination with drugs such as ampicillin. For example, gentamicin, an aminoglycoside antibiotic that has gram-negative coverage, is used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Because of their potential nephrotoxicity, aminoglycosides should be reserved as a last resort, for use in resistant or life-threatening infections. In addition, aminoglycosides should be avoided during pregnancy.
Gentamicin is not the drug of choice for acute pyelonephritis. Consider using it when 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 the dose based on the creatinine clearance and changes in volume of distribution. Gentamicin may be given intravenously or intramuscularly.
Tobramycin has bactericidal activity against, and is used to treat infections caused by, E coli, Proteus species, Klebsiella species, Serratia species, Enterobacter species, and Citrobacter species. Tobramycin can be administered intravenously or intramuscularly. Dosage is based on weight and renal function.
Amikacin has bactericidal activity against gram-negative organisms. Clinical studies have shown that amikacin is clinically effective for serious complicated and recurrent cystitis. Amikacin can be administered intravenously or intramuscularly. Dosage is based on weight and renal function.
Glycopeptide antibiotics such as vancomycin have bactericidal activity and can be used as alternative therapy for patients with pyelonephritis.
Vancomycin is a potent antibiotic directed against gram-positive organisms and is active against Enterococcus species. Vancomycin is indicated for patients who cannot receive or did not respond to penicillins and cephalosporins or patients who have infections with resistant staphylococci.
Unlike the penicillins and cephalosporins, aztreonam is a monobactam. Monobactams such as aztreonam are bactericidal; however, they lack activity against gram-positive activity.
Aztreonam is approved for the treatment of complicated and uncomplicated cystitis. It is approved for the treatment of pyelonephritis caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter species, and Serratia marcescens. Aztreonam lacks cross-sensitivity with beta-lactam antibiotics and may be used in patients allergic to penicillins or cephalosporins. General dosing recommendations include administering 1 g IV every 8-12 hours.
Use of a urinary analgesic is indicated when a patient has dysuria to such an extent that it disrupts activities of daily living. These agents relieve pain, discomfort, and spasms of the bladder.
Phenazopyridine is an azo dye excreted in urine, where it exerts a topical analgesic effect on urinary tract mucosa. Its use is compatible with antibacterial therapy and can help relieve pain and discomfort before antibacterial therapy controls infection.
It is 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. Its analgesic action may reduce or eliminate the need for systemic analgesics or narcotics.
Gupta K, Hooton TM, Naber KG, Wullt B, Colgan R, Miller LG, 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. [Medline].
Czaja CA, Scholes D, Hooton TM, Stamm WE. Population-based epidemiologic analysis of acute pyelonephritis. Clin Infect Dis. 2007 Aug 1. 45(3):273-80. [Medline].
National Kidney & Urologic Diseases Information Clearinghouse (NKUDIC). Kidney and Urologic Diseases Statistics for the United States. Available at http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/#urologic. Accessed: October 31, 2011.
Mazaki-Tovi S, Vaisbuch E, Romero R, et al. Maternal plasma concentration of the pro-inflammatory adipokine pre-B-cell-enhancing factor (PBEF)/visfatin is elevated in pregnant patients with acute pyelonephritis. Am J Reprod Immunol. 2010 Mar 1. 63(3):252-62. [Medline].
Kofteridis DP, Papadimitraki E, Mantadakis E, et al. Effect of diabetes mellitus on the clinical and microbiological features of hospitalized elderly patients with acute pyelonephritis. J Am Geriatr Soc. 2009 Nov. 57(11):2125-8. [Medline].
Lumbiganon P, Laopaiboon M, Thinkhamrop J. Screening and treating asymptomatic bacteriuria in pregnancy. Curr Opin Obstet Gynecol. 2010 Apr. 22(2):95-9. [Medline].
Arambašić J, Mandić S, Debeljak Ž, Mandić D, Horvat V, Šerić V. Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL). Clin Chem Lab Med. 2015 Jun 6. [Medline].
Rafiei A, Mohammadjafari H, Bazi S, Mirabi AM. Urinary neutrophil gelatinase-associated lipocalin (NGAL) might be an independent marker for anticipating scar formation in children with acute pyelonephritis. J Renal Inj Prev. 2015. 4 (2):39-44. [Medline].
Abrahamian FM, Moran GJ, Talan DA. Urinary tract infections in the emergency department. Infect Dis Clin North Am. 2008 Mar. 22(1):73-87, vi. [Medline].
Martina MC, Campanino PP, Caraffo F, et al. Dynamic magnetic resonance imaging in acute pyelonephritis. Radiol Med. 2010 Mar. 115(2):287-300. [Medline].
Silverman SG, Leyendecker JR, Amis ES Jr. What is the current role of CT urography and MR urography in the evaluation of the urinary tract?. Radiology. 2009 Feb. 250(2):309-23. [Medline].
Talan DA, Stamm WE, Hooton TM, et al. Comparison of ciprofloxacin (7 days) and trimethoprim-sulfamethoxazole (14 days) for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial. JAMA. 2000 Mar 22-29. 283(12):1583-90. [Medline].
Sandberg T, Skoog G, Hermansson AB, Kahlmeter G, Kuylenstierna N, Lannergård A, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012 Aug 4. 380(9840):484-90. [Medline].
Pohl A. Modes of administration of antibiotics for symptomatic severe urinary tract infections (Review) [database online]. www.thecochranelibrary.com: The Cochrane Collaboration. 2008, Issue 3.
van Nieuwkoop C, van't Wout JW, Spelt IC, et al. Prospective cohort study of acute pyelonephritis in adults: safety of triage towards home based oral antimicrobial treatment. J Infect. 2010 Feb. 60(2):114-21. [Medline].
Nicolle L, Duckworth H, Sitar D, Bryski L, Harding G, Zhanel G. Pharmacokinetics/pharmacodynamics of levofloxacin 750 mg once daily in young women with acute uncomplicated pyelonephritis. Int J Antimicrob Agents. 2008 Mar. 31(3):287-9. [Medline].
Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. A double-blind, randomized comparison of levofloxacin 750 mg once-daily for five days with ciprofloxacin 400/500 mg twice-daily for 10 days for the treatment of complicated urinary tract infections and acute pyelonephritis. Urology. 2008 Jan. 71(1):17-22. [Medline].
Vouloumanou EK, Rafailidis PI, Kazantzi MS, Athanasiou S, Falagas ME. Early switch to oral versus intravenous antimicrobial treatment for hospitalized patients with acute pyelonephritis: a systematic review of randomized controlled trials. Curr Med Res Opin. 2008 Dec. 24(12):3423-34. [Medline].
Harwood-Nuss AL, Etheredge W, McKenna I. Urological Emergencies. Harwood-Nuss A, Wolfson AB, eds. The Clinical Practice of Emergency Medicine. 3rd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001. 2227-61.
Hansson S, Martinell J, Stokland E, Jodal U. The natural history of bacteriuria in childhood. Infect Dis Clin North Am. 1997 Sep. 11(3):499-512. [Medline].
Juliano TM, Stephany HA, Clayton DB, Thomas JC, Pope JC 4th, Adams MC, et al. Incidence of Abnormal Imaging and Recurrent Pyelonephritis After First Febrile Urinary Tract Infection in Children 2-24 Months. J Urol. 2013 Jan 22. [Medline].
|Bacteria||% Uncomplicated||% Complicated|
|Citrobacter spp||< 1||5|
|Enterobacter spp||< 1||2-10|
|Pseudomonas aeruginosa||< 1||2-19|
|Group B streptococci||< 1||1-4|
|Staphylococcus aureus||< 1||1-23|
|Adapted from Hooton TM. The current management strategies for community-acquired urinary tract infection. Infect Dis Clin North Am. Jun 2003;17(2):303-32. [Medline].
* S saprophyticus
|Extended-spectrum cephalosporins or penicillins:
|Aminoglycosides (because of their potential nephrotoxicity, aminoglycoside antibiotics should be reserved for patients with serious and potentially life-threatening infections, and their dosage and blood levels should be carefully monitored to minimize the risk of nephrotoxicity):
|Mild to moderate pyelonephritis|
|If patient is immunocompromised and/or has incomplete urinary drainage:
|Neonates||Infants 6 weeks to 3 years of age||Children 3-6 years of age||Children 6-11 years of age|
|UTI frequency (%)||1||1.5-3||1.5-3||1.2|
|Route of infection||Blood||Ascending||Ascending||Ascending|
|Signs and symptoms||Failure to thrive, fever, hypothermia, irritability, jaundice, poor feeding, sepsis, vomiting||Diarrhea, failure to thrive, fever, irritability, poor feeding, strong-smelling urine, vomiting||Abdominal pain, dysuria, enuresis, fever, gross hematuria, meningismus, strong-smelling urine, urinary urgency, urinary frequency, vomiting||Dysuria, enuresis, fever, flank pain or tenderness, urinary urgency, urinary frequency|
|Predominant organism||Klebsiella species||E coli||E coli, Proteus species in older boys||E coli|
|Management||Admit for intravenous ampicillin and gentamicin and further evaluation||Admit for intravenous ampicillin and gentamicin and further evaluation||Follow adult guidelines, but avoid fluoroquinolones, which are theoretically contraindicated due to potential effects on the musculoskeletal system||Follow adult guidelines, but avoid fluoroquinolones, which are theoretically contraindicated due to potential effects on the musculoskeletal system|