Cystitis in Females Medication
- Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD more...
The goals of pharmacotherapy are to eradicate the infection, prevent complications, and provide symptomatic relief to patients. Early treatment is recommended to reduce the risk of progression to pyelonephritis.
It is important to identify antimicrobial resistance patterns when considering empirical antimicrobial selection. Oral therapy with an empirically chosen antibiotic that is effective against gram-negative aerobic coliform bacteria, such as Escherichia coli, is the principal treatment intervention in patients with lower urinary tract infections. Appropriate antimicrobials for the treatment of cystitis include trimethoprim-sulfamethoxazole (TMP-SMX), nitrofurantoin, fluoroquinolones, or cephalosporins. Some patients may require a urinary analgesic such as oral phenazopyridine, which is useful to relieve discomfort due to severe dysuria.
Sulfonamides inhibit bacterial dihydropteroate synthase by competing with para-aminobenzoic acid (PABA). This action interferes with the uptake of PABA into folic acid, an essential component of bacterial development.
Trimethoprim-sulfamethoxazole (TMP-SMX) is designed to take advantage of the synergy between trimethoprim and sulfonamides. TMP-SMX activity includes common urinary tract pathogens, both aerobic gram-positive and gram-negative bacteria, except Pseudomonas aeruginosa. Empiric therapy with TMP-SMX should be avoided if the prevalence of resistance is greater than 20%. This agent has been given an A-I rating in the 2010 Infectious Disease Society of America (IDSA) guidelines for treating cystitis. General dosing recommendations include administering 1 tablet (160 mg/800 mg) twice a day for 3 days in patients with uncomplicated cystitis.
Empiric antimicrobial therapy should cover all likely pathogens in the context of this clinical setting. Antibiotics that have been used include nitrofurantoin, fosfomycin, or trimethoprim.
Nitrofurantoin is bacteriocidal in urine at therapeutic doses. It is indicated for the treatment of cystitis when caused by susceptible strains of E coli, enterococci, Staphylococcus aureus, and certain strains of Klebsiella and Enterobacter species. It is a good treatment option because of minimal resistance and propensity for collateral damage.
This agent has been given an A-I rating in the 2010 Infectious Disease Society of America (IDSA) guidelines for treating cystitis. Nitrofurantoin should be avoided if there is suspicion for early pyelonephritis, and it is contraindicated when creatinine clearance is less than 60 mL/min.
Nitrofurantoin is manufactured in different forms to facilitate durable concentrations in the urine: macrocrystals (Macrodantin) and microcrystal suspension (Furadantin). A combined preparation of monohydrate/monocrystals (Macrobid) is indicated only for the treatment of acute cystitis caused by susceptible strains of E coli or S saprophyticus in patients 12 years of age and older.
General dosing recommendations for patients with uncomplicated cystitis include nitrofurantoin monohydrate/macrocrystals, 100 mg twice a day for 5-7 days, or
nitrofurantoin macrocrystals, 50-100 mg 4 times a day for 7 days.
Fosfomycin is a bactericidal agent that is used for the treatment of uncomplicated cystitis in susceptible strains of E coli and Enterococcus faecalis. Little cross-resistance between fosfomycin and other antibacterial agents exists. It is primarily excreted unchanged in the urine, and concentrations remain high for 24-48 hours after a single dose. This agent has been given an A-I rating in the 2010 IDSA guidelines for treating cystitis. Fosfomycin can be administered at a dose of 3 g as a single dose with 3-4 oz of water for uncomplicated cystitis.
Trimethoprim inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. It is active in vitro against a broad range of gram-positive and gram-negative bacteria, including uropathogens, such as Enterobacteriaceae and S saprophyticus. Resistance usually is mediated by decreased cell permeability or alterations in the amount or structure of dihydrofolate reductase. It demonstrates synergy with the sulfonamides, potentiating the inhibition of bacterial tetrahydrofolate production.
Fluoroquinolones 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. For that reason, these agents should be reserved as alternative therapies for acute cystitis. Fluoroquinolones are effective in 3-day regimens. In the 2010 IDSA guidelines, quinolones have an A-III rating for treating cystitis.
Ciprofloxacin is used to treat cystitis that is caused by E coli or S saprophyticus. For acute uncomplicated cystitis, the recommended dosage is 250 mg twice daily for 3 days. As the severity of the condition worsens, the duration of therapy is extended.
Ofloxacin is indicated for the treatment of both uncomplicated and complicated cystitis. Like other fluoroquinolones, it is most effective against gram-negative organisms such as E coli, Citrobacter diversus, C freundii, Enterobacter cloacae, Klebsiella species, Proteus species, and Shigella species. The usual regimen for uncomplicated cystitis is 200 mg given twice daily for 3 days. Complicated cystitis can be treated for 10 days.
Levofloxacin is indicated for the treatment of uncomplicated and complicated cystitis. It is used to treat cystitis caused by E coli, S saprophyticus, or Klebsiella species. Levofloxacin can be given for uncomplicated cystitis at a dose of 250 mg every 24 hours for 3 days. It can also be given for complicated cystitis at a dose of 750 mg daily for 5 days or a dose of 250 mg daily for 10 days.
Penicillins such as amoxicillin and ampicillin are not recommended as empiric therapy for uncomplicated cystitis. However, amoxicillin-clavulanate may be used in uncomplicated cystitis as an alternative therapy.
A beta-lactam antibiotic such as amoxicillin-clavulanate in 3-7 day regimens is recommended for the treatment of uncomplicated cystitis when other agents are not appropriate. In the 2010 IDSA guidelines, amoxicillin-clavulanate has a B-I rating for treating cystitis.
Ampicillin has activity against anaerobes and gram-negative aerobes. Ampicillin can be given intravenously or intramuscularly and is generally used in combination with an aminoglycoside (gentamicin) for empiric or directed activity against E faecalis in patients with complicated cystitis who cannot tolerate oral therapy or in patients in whom infection with resistant organisms is suspected.
Cephalosporins, Second Generation
Cephalosporins represent the majority of antibiotics known as beta-lactam antibiotics. The 2010 IDSA guidelines for treating cystitis give beta-lactams, in general, a B-I rating, listing them as second-line agents. Cephalosporin antibiotics are classified into “generations” that somewhat correspond to their spectrum of action.
Cefaclor is indicated for the treatment of cystitis and pyelonephritis that is caused by E coli, Proteus mirabilis, Klebsiella species, and coagulase-negative staphylococci. Cefaclor has been used at a dose of 500 mg 3 times a day for 7 days in patients with uncomplicated cystitis.
Cefuroxime is indicated for the treatment of uncomplicated cystitis that is caused by E coli or Klebsiella pneumoniae. The general dosing recommendation is 250 mg given twice daily for 7-10 days.
Cephalosporins, Third Generation
Third-generation cephalosporins are broad-spectrum and have bactericidal activity. These drugs are the most active against serious gram-negative pathogens but have some activity against gram-positive pathogens. The 2010 IDSA guidelines for treating cystitis give beta-lactams, in general, a B-I rating, listing them as second-line agents.
Cefpodoxime is approved for the treatment of uncomplicated cystitis. It is an extended-spectrum oral cephalosporin with bactericidal activity against a wide spectrum of gram-positive and gram-negative bacteria, including E coli, S saprophyticus, and K pneumoniae. Patients with uncomplicated cystitis can be treated with cefpodoxime, 100 mg twice a day for 7 days.
Cefdinir has been used an alternative therapy for uncomplicated cystitis when other therapies cannot be used. Dosing recommendations include 300 mg twice daily given for 7 days.
Ceftazidime has broad-spectrum gram-negative activity and lower efficacy against gram-positive organisms. It is approved for both complicated and uncomplicated cystitis caused by Pseudomonas aeruginosa; Enterobacter species; Proteus species, including P mirabilis and indole-positive Proteus; Klebsiella species; and E coli. Ceftazidime, 500 mg IV or IM every 8-12 hours for 7-14 days, can be administered to patients with complicated cystitis. For patients with uncomplicated cystitis, a dose of 250 mg IV or IM can be given every 12 hours.
Cefepime is a fourth-generation drug that has the gram-negative activity of the third-generation agents and the gram-positive activity of the first-generation drugs.
Cefepime is a zwitterion; this property is thought to enhance the ability of this agent to penetrate porin channels in the cell walls of gram-negative bacteria. Cefepime is ideal for intramuscular administration.
Cefepime is indicated for the treatment of complicated and uncomplicated cystitis caused by E coli or K pneumoniae when the infection is severe or caused by E coli, K pneumoniae, or P mirabilis when the infection is mild to moderate, including cases associated with concurrent bacteremia with these microorganisms. Cefepime can be administered at a dose of 2 g IV every 12 hours for 10 days for patients with severe complicated cystitis.
Extended-spectrum penicillins have a broad spectrum of bactericidal activity. They are used mainly in the treatment of infections suspected or known to be caused by gram-negative aerobes.
Piperacillin-tazobactam is useful because of its broad spectrum of bactericidal activity against gram-positive and gram-negative aerobic and anaerobic organisms. Piperacillin is a beta-lactam antibiotic and is mainly bactericidal. Tazobactam is an irreversible inhibitor of bacterial beta-lactamases.
Aminoglycosides are bactericidal antibiotics used primarily in the treatment of gram-negative infections. They irreversibly bind to the 30S subunit of bacterial ribosomes, blocking the recognition step in protein synthesis and causing misreading of the genetic code. The ribosomes separate from the messenger RNA; cell death ensues.
Gentamicin has activity against various aerobic gram-negative bacteria, as well as E faecalis and staphylococcal species. It is the only aminoglycoside with appreciable activity against gram-positive organisms. Gentamicin is used with ampicillin to treat patients with complicated cystitis who cannot tolerate oral therapy or patients in whom infection with resistant organisms is suspected.
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. It is compatible with antibacterial therapy and can help relieve pain and discomfort before antibacterial therapy controls infection. Its analgesic action may reduce or eliminate the need for systemic analgesics or narcotics.
Carbapenem antibiotics are broad-spectrum antibiotics that are structurally related to beta-lactam antibiotics. The bactericidal activity of carbapenems results from the inhibition of cell wall synthesis and is mediated through the binding to penicillin-binding proteins (PBPs). Parenteral therapy may be warranted for treatment of patients with complicated cystitis who cannot tolerate oral therapy. Parenteral regimens that can be used include carbapenem antibiotics.
Doripenem is indicated as a single agent for the treatment of complicated cystitis and pyelonephritis caused by E coli (including cases with concurrent bacteremia), K pneumoniae, P mirabilis, P aeruginosa, and Acinetobacter baumannii. The general dosing recommendation is 500 mg IV every 8 hours for 10 days.
Imipenem is a carbapenem antimicrobial agent. It is mainly bactericidal, and it inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBPs that are located inside the bacterial cell wall.
Cilastatin is a reversible, competitive inhibitor of dehydropeptidase-1 (DHP-1), an enzyme found in the brush border of the proximal tubular cells of the kidneys that breaks down imipenem to inactive metabolites. Cilastatin prevents the renal metabolism of imipenem, which results in an increase in urinary concentrations of imipenem and minimizes the nephrotoxicity observed when imipenem is administered alone. Imipenem can be administered at a dose of 500 mg IV every 6 hours for 7-14 days.
Meropenem is indicated for the treatment of bacterial meningitis, complicated skin and skin-structure infections, and intra-abdominal infections. However, it can also be used for the treatment of complicated cystitis. It inhibits cell wall formation, facilitates bacterial cell lysis, and is primarily a bactericidal agent. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific PBPs that are located inside the bacterial cell wall.
[Guideline] Gupta K, Hooton TM, Naber KG, 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. 52(5):e103-20. [Medline]. [Full Text].
[Guideline] Wagenlehner FM, Schmiemann G, Hoyme U, Fünfstück R, Hummers-Pradier E, Kaase M, et al. [National S3 guideline on uncomplicated urinary tract infection: recommendations for treatment and management of uncomplicated community-acquired bacterial urinary tract infections in adult patients]. Urologe A. 2011 Feb. 50(2):153-69. [Medline]. [Full Text].
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].
Little P, Turner S, Rumsby K, Warner G, Moore M, Lowes JA, et al. Dipsticks and diagnostic algorithms in urinary tract infection: development and validation, randomised trial, economic analysis, observational cohort and qualitative study. Health Technol Assess. 2009 Mar. 13(19):iii-iv, ix-xi, 1-73. [Medline].
Lane DR, Takhar SS. Diagnosis and management of urinary tract infection and pyelonephritis. Emerg Med Clin North Am. 2011 Aug. 29(3):539-52. [Medline].
Czaja CA, Stamm WE, Stapleton AE, et al. Prospective cohort study of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection in women. J Infect Dis. 2009 Aug 15. 200(4):528-36. [Medline].
Kanj SS, Kanafani ZA. Current concepts in antimicrobial therapy against resistant gram-negative organisms: extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, and multidrug-resistant Pseudomonas aeruginosa. Mayo Clin Proc. 2011 Mar. 86(3):250-9. [Medline]. [Full Text].
[Guideline] Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 2010 Mar 1. 50(5):625-63. [Medline]. [Full Text].
Tiemstra JD, Chico PD, Pela E. Genitourinary infections after a routine pelvic exam. J Am Board Fam Med. 2011 May-Jun. 24(3):296-303. [Medline].
Hsiao CJ, Cherry DK, Beatty PC, Rechtsteiner EA. National Ambulatory Medical Care Survey: 2007 summary. Natl Health Stat Report. 2010 Nov 3. 1-32. [Medline].
Naber KG, Schito G, Botto H, Palou J, Mazzei T. Surveillance study in Europe and Brazil on clinical aspects and Antimicrobial Resistance Epidemiology in Females with Cystitis (ARESC): implications for empiric therapy. Eur Urol. 2008 Nov. 54(5):1164-75. [Medline].
Little P, Merriman R, Turner S, Rumsby K, Warner G, Lowes JA, et al. Presentation, pattern, and natural course of severe symptoms, and role of antibiotics and antibiotic resistance among patients presenting with suspected uncomplicated urinary tract infection in primary care: observational study. BMJ. 2010 Feb 5. 340:b5633. [Medline]. [Full Text].
Molander U, Arvidsson L, Milsom I, Sandberg T. A longitudinal cohort study of elderly women with urinary tract infections. Maturitas. 2000 Feb 15. 34(2):127-31. [Medline].
Johnson L, Sabel A, Burman WJ, Everhart RM, Rome M, MacKenzie TD, et al. Emergence of fluoroquinolone resistance in outpatient urinary Escherichia coli isolates. Am J Med. 2008 Oct. 121(10):876-84. [Medline].
[Guideline] American College of Obstetricians and Gynecologists (ACOG). 2008. Treatment of urinary tract infections in nonpregnant women. Available at http://guideline.gov/content.aspx?id=12628. Accessed: September 22, 2010.
Barclay L. Urinary Tract Infection: 3 Questions Aid Diagnosis in Women. Medscape Medical News. Available at http://www.medscape.com/viewarticle/810667. Accessed: September 16, 2013.
Knottnerus BJ, Geerlings SE, Moll van Charante EP, Ter Riet G. Toward a simple diagnostic index for acute uncomplicated urinary tract infections. Ann Fam Med. 2013 Sep-Oct. 11(5):442-51. [Medline]. [Full Text].
Schaeffer AJ, Schaeffer EM. Infections of the Urinary Tract. In: McDougal WS, Wein AJ, Kavoussi LR, et al, eds. Campbell-Walsh Urology. 10th Ed. Philadelphia, PA: Elsevier Saunders; 2012. 46-55.
Lifshitz E, Kramer L. Outpatient urine culture: does collection technique matter?. Arch Intern Med. 2000 Sep 11. 160(16):2537-40. [Medline].
Propp DA, Weber D, Ciesla ML. Reliability of a urine dipstick in emergency department patients. Ann Emerg Med. 1989 May. 18(5):560-3. [Medline].
Mehnert-Kay SA. Diagnosis and Management of Uncomplicated Urinary Tract Infections. American Family Physician. August 1, 2005. 27/No.3:1-9. [Full Text].
[Guideline] Gould CV, Umscheid CA, Agarwal RK, Kuntz G, Pegues DA. Guideline for prevention of catheter-associated urinary tract infections 2009. Infect Control Hosp Epidemiol. 2010 Apr. 31(4):319-26. [Medline]. [Full Text].
Kauffman CA, Fisher JF, Sobel JD, Newman CA. Candida urinary tract infections--diagnosis. Clin Infect Dis. 2011 May. 52 Suppl 6:S452-6. [Medline].
Falagas ME, Kotsantis IK, Vouloumanou EK, Rafailidis PI. Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a meta-analysis of randomized controlled trials. J Infect. 2009 Feb. 58(2):91-102. [Medline].
Foxman B. The epidemiology of urinary tract infection. Nat Rev Urol. 2010 Dec. 7(12):653-60. [Medline].
Little P, Moore MV, Turner S, Rumsby K, Warner G, Lowes JA, et al. Effectiveness of five different approaches in management of urinary tract infection: randomised controlled trial. BMJ. 2010 Feb 5. 340:c199. [Medline]. [Full Text].
Christiaens TC, De Meyere M, Verschraegen G, Peersman W, Heytens S, De Maeseneer JM. Randomised controlled trial of nitrofurantoin versus placebo in the treatment of uncomplicated urinary tract infection in adult women. Br J Gen Pract. 2002 Sep. 52(482):729-34. [Medline]. [Full Text].
Bleidorn J, Gágyor I, Kochen MM, Wegscheider K, Hummers-Pradier E. Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection?--results of a randomized controlled pilot trial. BMC Med. 2010 May 26. 8:30. [Medline]. [Full Text].
Olson RP, Harrell LJ, Kaye KS. Antibiotic resistance in urinary isolates of Escherichia coli from college women with urinary tract infections. Antimicrob Agents Chemother. 2009 Mar. 53(3):1285-6. [Medline]. [Full Text].
McKinnell JA, Stollenwerk NS, Jung CW, Miller LG. Nitrofurantoin compares favorably to recommended agents as empirical treatment of uncomplicated urinary tract infections in a decision and cost analysis. Mayo Clin Proc. 2011 Jun. 86(6):480-8. [Medline]. [Full Text].
Falagas ME, Vouloumanou EK, Togias AG, Karadima M, Kapaskelis AM, Rafailidis PI, et al. Fosfomycin versus other antibiotics for the treatment of cystitis: a meta-analysis of randomized controlled trials. J Antimicrob Chemother. 2010 Sep. 65(9):1862-77. [Medline]. [Full Text].
[Guideline] Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005 Mar 1. 40(5):643-54. [Medline]. [Full Text].
Dalal S, Nicolle L, Marrs CF, Zhang L, Harding G, Foxman B. Long-term Escherichia coli asymptomatic bacteriuria among women with diabetes mellitus. Clin Infect Dis. 2009 Aug 15. 49(4):491-7. [Medline]. [Full Text].
Beerepoot MA, ter Riet G, Nys S, et al. Cranberries vs antibiotics to prevent urinary tract infections: a randomized double-blind noninferiority trial in premenopausal women. Arch Intern Med. 2011 Jul 25. 171(14):1270-8. [Medline].
Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev. 2008 Jan 23. CD001321. [Medline].
Tempera G, Corsello S, Genovese C, Caruso FE, Nicolosi D. Inhibitory activity of cranberry extract on the bacterial adhesiveness in the urine of women: an ex-vivo study. Int J Immunopathol Pharmacol. 2010 Apr-Jun. 23(2):611-8. [Medline].
De Vita D, Giordano S. Effectiveness of intravesical hyaluronic acid/chondroitin sulfate in recurrent bacterial cystitis: a randomized study. Int Urogynecol J. 2012 Dec. 23(12):1707-13. [Medline].
van der Starre WE, van Nieuwkoop C, Paltansing S, et al. Risk factors for fluoroquinolone-resistant Escherichia coli in adults with community-onset febrile urinary tract infection. J Antimicrob Chemother. 2011 Mar. 66(3):650-6. [Medline].
Cunha BA. Prophylaxis for recurrent urinary tract infections: nitrofurantoin, not trimethoprim-sulfamethoxazole or cranberry juice. Arch Intern Med. 2012 Jan 9. 172(1):82; author reply 82-3. [Medline].
Cunha BA, Schoch PE, Hage JR. Nitrofurantoin: preferred empiric therapy for community-acquired lower urinary tract infections. Mayo Clin Proc. 2011 Dec. 86(12):1243-4; author reply 1244. [Medline]. [Full Text].
Fischer HD, Juurlink DN, Mamdani MM, Kopp A, Laupacis A. Hemorrhage during warfarin therapy associated with cotrimoxazole and other urinary tract anti-infective agents: a population-based study. Arch Intern Med. 2010 Apr 12. 170(7):617-21. [Medline].
Hand L. Urinary Infections: Report Offers Long-Needed Clarity. Medscape [serial online]. Available at http://www.medscape.com/viewarticle/814305. Accessed: November 18, 2013.
Hooton TM, Roberts PL, Cox ME, Stapleton AE. Voided midstream urine culture and acute cystitis in premenopausal women. N Engl J Med. 2013 Nov 14. 369(20):1883-91. [Medline].
Pinson AG, Philbrick JT, Lindbeck GH, Schorling JB. ED management of acute pyelonephritis in women: a cohort study. Am J Emerg Med. 1994 May. 12(3):271-8. [Medline].
Turner D, Little P, Raftery J, Turner S, Smith H, Rumsby K, et al. Cost effectiveness of management strategies for urinary tract infections: results from randomised controlled trial. BMJ. 2010 Feb 5. 340:c346. [Medline]. [Full Text].
Patients with complicated cystitis who can tolerate oral therapy may be treated with the following options:
Patients who cannot tolerate oral therapy as outlined above or patients with infection that is suspected to be due to resistant organisms should be treated with parenteral therapy, as follows:
Parenteral therapy can be switched to oral therapy once clinical improvement is observed.
Parenteral therapy can be switched to oral therapy once clinical improvement is observed.