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Cystitis in Females Medication

  • Author: John L Brusch, MD, FACP; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Aug 19, 2015
 

Medication Summary

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.

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Sulfonamides

Class Summary

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 (Bactrim, Bactrim DS, Septra, Septra DS)

 

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.[1] General dosing recommendations include administering 1 tablet (160 mg/800 mg) twice a day for 3 days in patients with uncomplicated cystitis.

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Antibiotics, Other

Class Summary

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 (Furadantin, Macrobid, Macrodantin)

 

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.[1] 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 (Monurol)

 

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.[1] Fosfomycin can be administered at a dose of 3 g as a single dose with 3-4 oz of water for uncomplicated cystitis.

Trimethoprim (Primsol)

 

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.

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Fluoroquinolones

Class Summary

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.[38] 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.[1]

Ciprofloxacin (Cipro. Proquin XR)

 

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

 

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 (Levaquin)

 

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.

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Penicillins, Amino

Class Summary

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.

Amoxicillin-clavulanate (Augmentin, Augmentin XR)

 

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.[1]

Ampicillin

 

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.

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Cephalosporins, Second Generation

Class Summary

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.[1] Cephalosporin antibiotics are classified into “generations” that somewhat correspond to their spectrum of action.

Cefaclor

 

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 (Ceftin, Zinacef)

 

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.

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Cephalosporins, Third Generation

Class Summary

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.[1]

Cefpodoxime

 

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

 

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 (Fortaz, Tazicef)

 

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.

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Cephalosporins, Other

Class Summary

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 (Maxipime)

 

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.

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Penicillins, Extended-Spectrum

Class Summary

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 (Zosyn)

 

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.

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Aminoglycosides

Class Summary

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

 

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.

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Analgesics, Urinary

Class Summary

These agents relieve pain, discomfort, and spasms of the bladder.

Phenazopyridine (Azo Standard, Azo Standard Maximum Strength, Baridium, Pyridium, UTI Relief)

 

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.

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Carbapenems

Class Summary

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 (Doribax)

 

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/cilastatin (Primaxin)

 

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 (Merrem)

 

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.

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Contributor Information and Disclosures
Author

John L Brusch, MD, FACP Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance

John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Burke A Cunha, MD Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital

Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Jeffrey M Tessier, MD Assistant Professor, Division of Infectious Diseases, Department of Internal Medicine, Virginia Commonwealth University School of Medicine

Jeffrey M Tessier, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Mary F Bavaro, MD Fellowship Director, Division of Infectious Disease, Navy Medical Center, San Diego

Mary F Bavaro, MD is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Acknowledgements

Michael S Beeson, MD, MBA, FACEP Professor of Emergency Medicine, Northeastern Ohio Universities College of Medicine and Pharmacy; Attending Faculty, Akron General Medical Center

Michael S Beeson, MD, MBA, FACEP is a member of the following medical societies: American College of Emergency Physicians, Council of Emergency Medicine Residency Directors, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Pamela L Dyne, MD Professor of Clinical Medicine/Emergency Medicine, University of California, Los Angeles, David Geffen School of Medicine; Attending Physician, Department of Emergency Medicine, Olive View-UCLA Medical Center

Pamela L Dyne, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

David S Howes, MD Professor of Medicine and Pediatrics, Section Chief and Emergency Medicine Residency Program Director, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine

David S Howes, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Physicians-American Society of Internal Medicine, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Elicia S Kennedy, MD Clinical Assistant Professor, Department of Emergency Medicine, University of Arkansas for Medical Sciences

Elicia S Kennedy, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Klaus-Dieter Lessnau, MD, FCCP Clinical Associate Professor of Medicine, New York University School of Medicine; Medical Director, Pulmonary Physiology Laboratory; Director of Research in Pulmonary Medicine, Department of Medicine, Section of Pulmonary Medicine, Lenox Hill Hospital

Klaus-Dieter Lessnau, MD, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Medical Association, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Sepracor None None

Allison M Loynd, DO Resident Physician, Department of Emergency Medicine, Wayne State University School of Medicine, Detroit Receiving Hospital

Allison M Loynd, DO is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, and Emergency Medicine Residents Association

Disclosure: Nothing to disclose.

Mark Jeffrey Noble, MD Consulting Staff, Urologic Institute, Cleveland Clinic Foundation

Mark Jeffrey Noble, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, American Urological Association, Kansas Medical Society, Sigma Xi, Society of University Urologists, and Southwest Oncology Group

Disclosure: Nothing to disclose.

Adam J Rosh, MD Assistant Professor, Department of Emergency Medicine, Detroit Receiving Hospital, Wayne State University School of Medicine

Adam J Rosh, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Joseph A Salomone III, MD Associate Professor and Attending Staff, Truman Medical Centers, University of Missouri-Kansas City School of Medicine; EMS Medical Director, Kansas City, Missouri

Joseph A Salomone III, MD is a member of the following medical societies: American Academy of Emergency Medicine, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Richard H Sinert, DO Associate Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center

Richard H Sinert, DO is a member of the following medical societies: American College of Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mark Zwanger, MD, MBA Assistant Professor, Department of Emergency Medicine, Jefferson Medical College of Thomas Jefferson University

Mark Zwanger, MD, MBA is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and American Medical Association

Disclosure: Nothing to disclose.

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Nonobstructing distal left ureteral calculus 2 X 1 X 2 cm.
Multiple abscesses, upper pole of left kidney.
Bilateral hydronephrosis.
Plain radiograph in a 63-year-old patient with poorly controlled type 2 diabetes mellitus shows emphysematous cystitis.
Lactobacilli and a squamous epithelial cell are evident on this vaginal smear. The presence of squamous cells and lactobacilli on urinalysis suggests contamination or colonization. Source: Centers for Disease Control and Prevention, Dr. Mike Miller
Table 1. Treatment Regimens for Uncomplicated Cystitis in Nonpregnant Women [1]
First-line therapy
  • trimethoprim/sulfamethoxazole * 160 mg/800 mg (Bactrim DS, Septra DS) 1 tablet PO BID for 3d (use when bacterial resistance is < 20% and patient has no allergy) or
  • nitrofurantoin monohydrate/macrocrystals (Macrobid) 100 mg PO BID for 5-7d or
  • nitrofurantoin macrocrystals (Macrodantin) 50-100 mg PO QID for 7d or
  • fosfomycin (Monurol) 3 g PO as a single dose with 3-4 oz of water
Second-line therapy
  • ciprofloxacin (Cipro) 250 mg PO BID for 3d or
  • ciprofloxacin extended release (Cipro XR) 500 mg PO daily for 3d or
  • levofloxacin (Levaquin) 250 mg PO q24h for 3d or
  • ofloxacin 200 mg PO q12h for 3d
Alternative therapy
  • amoxicillin-clavulanate (Augmentin) 500 mg/125 mg PO BID for 3-7d or
  • amoxicillin-clavulanate (Augmentin) 250 mg/125 mg PO TID for 3-7d or
  • cefdinir 300 mg PO BID for 7d or
  • cefaclor 500 mg PO TID for 7d or
  • cefpodoxime 100 mg PO BID for 7d or
  • cefuroxime 250 mg PO BID for 7-10d
*Should generally be avoided in elderly patients because of the risk of affecting renal function.
Table 2. Treatment Regimens for Complicated Cystitis in Nonpregnant Women [15]
First-line therapy
Oral:



Patients with complicated cystitis who can tolerate oral therapy may be treated with the following options:



  • ciprofloxacin (Cipro) 500 mg PO BID for 7-14d or
  • ciprofloxacin extended release (Cipro XR) 1 g PO daily for 7-14d or
  • levofloxacin (Levaquin) 750 mg PO daily for 5d
Parenteral:



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:



  • ciprofloxacin (Cipro) 400 mg IV q12h for 7-14d or
  • levofloxacin (Levaquin) 750 mg IV daily for 5d or
  • ampicillin 1-2 g IV q6h plus gentamicin 2 mg/kg/dose q8h for 7-14d or
  • piperacillin-tazobactam (Zosyn) 3.375 g IV q6h or
  • doripenem 500 mg (Doribax) IV q8h for 10d or
  • imipenem-cilastatin (Primaxin) 500 mg IV q6h for 7-14d or
  • meropenem (Merrem) 1 g IV q8h for 7-14d
Duration of therapy: shorter courses (7d) are reasonable if patient improves rapidly; longer courses (10-14d) are reasonable if patient has a delayed response or is hospitalized.



Parenteral therapy can be switched to oral therapy once clinical improvement is observed.



Second-line therapy
  • cefepime (Maxipime) 2 g IV q12h for 10d or
  • ceftazidime (Fortaz, Tazicef) 500 mg IV or IM q8-12h for 7-14d
Duration of therapy: shorter courses (7d) are reasonable if patient improves rapidly; longer courses (10-14d) are reasonable if patient has a delayed response or is hospitalized.



Parenteral therapy can be switched to oral therapy once clinical improvement is observed.



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