Pyelonephritis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Usama Talib, BSc, MD [2]

Overview

All patients with pyelonephritis should be treated empirically with antimicrobial therapy. Mild pyelonephritis may be managed with oral antimicrobial therapy, and an initial intravenous dose may be administered depending on local resistance patterns. Patients with dehydration, nausea, vomiting, or signs of sepsis should be admitted and should receive parenteral therapy. Medical therapies for pyelonephritis include fluoroquinolones, TMP-SMX, β-lactams, and aminoglycosides.

Medical Therapy

The medical therapy for pyelonephritis includes a few important aspects:

• All patients with pyelonephritis should be treated empirically with antimicrobial therapy.
• Before initiating antimicrobial treatment for suspected pyelonephritis, a urine culture and susceptibility test should always be performed.
• Mild pyelonephritis may be managed with oral antimicrobial therapy, and an initial intravenous dose may be administered depending on local resistance patterns. Patients with dehydration, nausea, vomiting, or signs of sepsis should be admitted and should receive parenteral therapy.
• Optimal management depends on the severity of illness at presentation, regional resistance data, and host factors.
• When local resistance patterns are unknown, an initial intravenous (IV) dose of a long-acting, broad-spectrum antimicrobial agent may be considered.
• Oral beta-lactams are less effective than either trimethoprim-sulfamethoxazole, fluoroquinolones, or aminoglycosides in eradicating uropathogens.
• Uncomplicated pyelonephritis due to MRSA is uncommon, and there is insufficient evidence to support empiric use of an MRSA-active agent.
• Pregnant women, patients who failed to respond to oral therapy, and patients with nausea, vomiting, high fever, marked leukocytosis, or dehydration should be hospitalized and managed with parenteral antibiotics.

Antimicrobial Therapy

As a broader rule, antibiotics are started only after the sample has been drawn for culture. Uncomplicated pyelonephritis is treated with specific and short duration (5 to 14 days) of antibiotics while complicated pyelonephritis is treated with broad spectrum and longer duration (at least 14-21 days) of antibiotics. In hospitalized cases, treatment with IV until patient is 24-48 hours afebrile is recommended; following this treatment, a 2 week course of PO regimen for uncomplicated pyelonephritis is also recommended.

• Pyelonephritis empiric therapy

• Outpatient treatment

• Preferred regimen, regional fluoroquinolone resistance < 10%: Ciprofloxacin 500 mg PO q12h x 7 days ± 400 mg IV in a single dose OR Ciprofloxacin XR 1000 mg PO q24h for 7 days OR Levofloxacin 750 mg PO q24h for 5 days OR Ofloxacin 400 mg Po bid OR Moxifloxacin 400 mg PO q24h
• Preferred regimen, regional fluoroquinolone resistance ≥ 10%: (Ciprofloxacin 500 mg PO q12h x 7 days ± 400 mg IV in a single dose OR Ciprofloxacin XR 1000 mg PO q24h for 7 days OR Levofloxacin 750 mg PO q24h for 5 days) AND (Ceftriaxone 1 g IV x 1 dose OR Gentamicin 7 mg/kg IV x 1 dose OR Tobramycin 7 mg/kg IV x 1 dose OR Amikacin 20 mg/kg IV x 1 dose)
• Alternative regimen (1): regional fluoroquinolone resistance < 10%: TMP-SMX 160/800 mg PO q12h x 14 days OR Amoxicillin-clavulanate 875/125 mg po q12h or 500/125 mg po tid or 1000 /125 mg po bid OR Cefdinir 300 mg po q12h or 600 mg po q24 OR Cefaclor 250-500 mg po q8h OR Cefpodoxime-proxetil 100-200 mg po q12h OR Cephalexin250-500 mg po q6h not studied well but effective.
• Alternative regimen (2): regional fluoroquinolone resistance ≥ 10%: TMP-SMX 160/800 mg PO q12h x 14 days AND (Ceftriaxone 1 g IV x 1 dose OR Gentamicin 7 mg/kg IV x 1 dose OR Tobramycin 7 mg/kg IV x 1 OR Amikacin 20 mg/kg IV x 1 dose
• Alternative regimen (3): (Amoxicillin–Clavulanate 500/125 mg PO q12h x 14 days OR Amoxicillin–Clavulanate 250/125 mg PO q8h x 5–7 days OR Cefaclor 500 mg PO q8h x 7 days) AND (Ceftriaxone 1 g IV in a single dose OR Gentamicin 7 mg/kg IV in a single dose OR Tobramycin 7 mg/kg IV in a single dose OR Amikacin 20 mg/kg IV in a single dose )
• Alternative regimen (4): TMP-SMX, 160mg and 800mg, twice daily for 3 days
• Alternative regimen (5): Fosfomycin, a single dose of 3g

• Inpatient treatment

• Preferred regimen (1): Ciprofloxacin 400 mg IV q12h for 10-14 days OR Levofloxacin 750 mg IV q24h for 10-14 days OR Gatifloxacin 400 mg IV q24h
• Preferred regimen (2): Ampicillin+gentamicin 150–200 mg/kg IV/day-MDD: 2 mg per kg load, then 1.7 mg per kg q8h or OD: 5.1 (7 if critically ill) mg/kg q24h
• Preferred regimen (3): Ceftriaxone 1-2 gm IV q24h
• Preferred regimen (4): Piperacillin-tazobactam 3.375 gm IV q4-6h
• Alternative regimen (1): Gentamicin 7 mg/kg IV q24h for 10-14 days ± Ampicillin 500 mg IV q6h for 10-14 days
• Alternative regimen (2): Tobramycin 7 mg/kg IV q24h for 10-14 days ± Ampicillin 500 mg IV q6h for 10-14 days
• Alternative regimen (3): Amikacin 20 mg/kg IV q24h for 10-14 days ± Ampicillin 500 mg IV q6h for 10-14 days
• Alternative regimen (4): Cefotaxime 1-2 g IV q8h for 10-14 days ± (Gentamicin 7 mg/kg IV q24h for 10-14 days OR Tobramycin 7 mg/kg IV q24h for 10-14 days OR Amikacin 20 mg/kg IV q24h for 10-14 days)
• Alternative regimen (5): Ceftriaxone 1 g IV q24h ± (Gentamicin 7 mg/kg IV q24h for 10-14 days OR Tobramycin 7 mg/kg IV q24h for 10-14 days OR Amikacin 20 mg/kg IV q24h for 10-14 days)
• Alternative regimen (6): Ceftazidime 12 g IV q8h ± (Gentamicin 7 mg/kg IV q24h for 10-14 days OR Tobramycin 7 mg/kg IV q24h for 10-14 days OR Amikacin 20 mg/kg IV q24h for 10-14 days)
• Alternative regimen (7): Ampicillin-Sulbactam 1.5 g IV q6h ± (Gentamicin 7 mg/kg IV q24h for 10-14 days OR Tobramycin 7 mg/kg IV q24h for 10-14 days OR Amikacin 20 mg/kg IV q24h for 10-14 days)
• Alternative regimen (8): Piperacillin-Tazobactam 3.375 g IV q4-6h ± (Gentamicin 7 mg/kg IV q24h for 10-14 days OR Tobramycin 7 mg/kg IV q24h for 10-14 days OR Amikacin 20 mg/kg IV q24h for 10-14 days)
• Alternative regimen (9): Ticarcillin-Clavulanate 3.1 g IV q4-6h ± (Gentamicin 7 mg/kg IV q24h for 10-14 days OR Tobramycin 7 mg/kg IV q24h for 10-14 days OR Amikacin 20 mg/kg IV q24h for 10-14 days)
• Alternative regimen (10): Meropenem 500 mg IV q8h for 10-14 days
• Alternative regimen (11): Ertapenem 1 g IV q24h for 10-14 days
• Alternative regimen (12): Doripenem 500 mg IV q8h for 10-14 days
• Alternative regimen (13): Aztreonam 1 g IV q8-12h for 10-14 days

• Pathogen-directed therapy

• Gram positive cocci

• Preferred regimen:ampicillin-sulbactam with or without an aminoglycoside if a gram positive cocci is the casitive organism.

• Enterococcus spp.

• Preferred regimen: Ampicillin 2 g IV q6h for 10-14 days AND Gentamicin 3-5 mg/kg/day IV q8h for 10-14 days

• Specific considerations

• Pregnancy and other cases of complicated pyelonephritis

In event of a pregnancy the treatment of pyelonephritis ha stop be done in an in patient setting due to higher and severe complications risks. Intravenous antibiotics should be given for the initial 1-2 days at least until the patient is not febrile and then continued on oral therapy for 10-14 days.

• Pyelonephritis empiric therapy

• Preferred regimen (1): Ceftriaxone 1-2 g IM q24h or IV cefazolin for 24-48hrs followed by oral cephalexin therapy for 10-14 days
• Preferred regimen (2): Aztreonam 1 g IV q8-12h for 10-14 days
• Preferred regimen (3): Piperacillin-Tazobactam 3.375-4.5 g IV q6h for 10-14 days OR Ticarcillin-clavulanate 3.1 gm IV q6h
• Preferred regimen (4): Meropenem or Ertapenem or Doripenem 500 mg IV q6h for 10-14 days
• Note: Fluoroquinolones and aminoglycosides should be avoided in pregnant patients
• Alternative regimen (2-3 weeks)
• Alternative regimen (1): Ciprofloxacin 400 mg IV q12h Template:OR Levofloxacin 750 mg IV/po x 5 days OR Gatifloxacin 400 mg IV q24h
• Alternative regimen (2): Ceftazidime 2 gm IV q8h OR Cefepime 2 gm IV q12h
• Note: Switch to oral fluoroquinolone or TMP-SMX when possible.

• Catheter Associated UTIs

• Urinary infections in catheterized patients tend to be polymicrobial with more resistant uropathogens.
• Urine culture: should be taken before initiation the antimicrobial therapy. For infected patients with indwelling catheters more than 2 weeks, the catheter should be replaced, and urine culture should be sampled from the new catheter to improve the out come of treatment with less complications.

• Regimen : TMP-SMX DS 1 tab bid x 3 days

• Duration of treatment

• Depends on the response to treatment regardless of the catheter is still placed or not. For quick resolution, a 7 days regimen is recommended. While delayed clinical improvement needs extended regimen (10-14 days).
• For mild catheter associated UTI, levofloxacin for 5 days is recommended. While 3 days regimen of antimicrobials is recommended for women≤65 with lower urinary symptoms only after catheter removal.

Followup Urinalysis

• Pregnant women are followed up with urinalysis and urine cultures every month to rule out bacteriuria which can trigger another episode of pyelonephritis.