Acute Pyelonephritis or Complicated Urinary Tract Infection

• See investigation and treatment guidelines in Hospital HealthPathways.
• A urinary tract infection is complicated if the following apply:
  • Pregnant (see Uncomplicated Acute Lower Urinary Tract Infections in Women for empiric treatment options for cystitis in pregnancy)
  • Male (cystitis in men is treated as for women but for a longer course of 7 days. See Uncomplicated Acute Lower Urinary Tract Infections in Women)
  • Recurrent UTIs (≥ 3 in one year, or 2 in 6 months)
  • Failed antibiotic treatment (UTI symptom recurrence within 1 week or persistent symptoms)
  • Recent urological or gynaecological instrumentation including intermittent self-catheterisation
  • Presence of an indwelling urinary foreign body, e.g. catheter, stent, nephrostomy tube
  • Risk for multidrug-resistant Gram-negative bacilli (MDR-GNB)
    • recent admission to overseas healthcare facility
    • multidrug-resistant Gram-negative bacilli positive
    • travel to developing country in previous six months
    • household contact with MDR-GNB
    • residence or admission to any facility with high prevalence of MDR-GNB
    • broad spectrum antimicrobial treatment

  • Impaired immunity, e.g. diabetes
  • Spinal cord impairment
• If upper urinary tract obstruction is present, an urgent Urology referral and drainage is required.
• For a post-op or post-procedure UTI – see Urinary Tract Infection / Pyelonephritis (Post-operative).
• Pregnant women and patients with severe renal failure require special consideration – see separate sections below.

Pathogens

• Common: E. coli
• Uncommon: Coliforms, P. aeruginosa, Enterococcus
• Consider risk factors for multidrug-resistant Gram-negative bacilli (MDR-GNB), such as extended spectrum beta-lactamase (ESBL) producers. If risk factors, ensure urine is sent for culture and susceptibility testing before initiating antimicrobial therapy. Meropenem is the preferred option for suspected ESBL-producing organisms.
  • recent admission to overseas healthcare facility
  • multidrug-resistant Gram-negative bacilli positive
  • travel to developing country in previous six months
  • household contact with MDR-GNB
  • residence or admission to any facility with high prevalence of MDR-GNB
  • broad spectrum antimicrobial treatment

Drug Treatment

• Consider early switch from IV to oral antimicrobials.
• A single IV dose of antimicrobial followed by oral therapy is usually sufficient. However, IV therapy may be continued until patient can take oral fluids.
• The empiric oral agents below are listed in order of preference.
• Susceptibilities from urine samples to guide oral treatment are usually available within 24 hours.
• For mild infection, duration of treatment is usually 10 days for a beta-lactam-based regimen, or 7 days for a ciprofloxacin-based regimen. Longer courses may be considered for patients slow to respond (maximum of 14 days for a beta-lactam-based regimen, and 10 days for a ciprofloxacin-based regimen).

Empiric

Non-pregnant Patients

gentamicin HMLSchedNZFPMLnoids Gentamicin F: n/a Half life: 3 hours Elimination: renal fe: 0.9 Additional points: TDM.

Single dose of IV 5 mg/kg ideal body weight. Round dose to the nearest half vial (40 mg)

• fe = 0.9, adjust dose if CrCl reduced.

AND one of the following three agents (listed in order of preference):

amoxicillin+ clavulanic acid HMLSchedNZFPMLnoids Amoxicillin+Clavulanic Acid F: 0.9 / 0.5 Half life: 2 hours / 1 hour Elimination: renal fe: 0.9 / 0.5

PO 500 mg/125 mg three times a day

• fe (amoxicillin) = 0.9, fe (clavulanic acid) = 0.5, dose is not normally reduced in patients with reduced CrCl for UTI treatment because urinary concentrations are important.

OR

cefalexin HMLSchedNZFPML Cefalexin F: 0.9 Half life: 1 hour Elimination: renal fe: 0.9

PO 1000 mg four times a day

• Locals experts recommend a high dose is used based on local studies to ensure adequate concentrations against E. coli in the blood stream and kidney as well as in the bladder.
• fe = 0.9, dose is not normally reduced in patients with reduced CrCl for UTI treatment because urinary concentrations are important.

OR

ciprofloxacin HMLSchedNZFPMLnoids Ciprofloxacin F: 0.7 Half life: 4 hours Elimination: renal fe: 0.5 Additional points: Inhibits CYP1A2 and 3A. Antacids, milk, and enteral feeds ↓ absorption.

PO 500 mg twice a day

• Inhibits CYP1A2 (strong) and 3A.
• Subject to OAT and OATP (transporter) inhibition.
• Avoid in pregnancy and breastfeeding.

If severe renal failure, i.e. CrCl or eGFR < 20 mL/min

ceftriaxone HMLSchedNZFPMLnoids Ceftriaxone F: n/a Half life: 8 hours Elimination: 50% renal and 50% biliary excretion fe: 0.5

IV 2 g every 24 hours

followed, if sensitive, by

OR

• Inhibits CYP1A2 (strong) and 3A.
• Subject to OAT and OATP (transporter) inhibition.
• Avoid in pregnancy and breastfeeding.

Pregnant Patients

• Refer all pregnant patients with pyelonephritis to Obstetrics.
• Treatment duration is usually 10 – 14 days.

• fe = 0.5, dose is not normally reduced in patients with reduced CrCl for UTI treatment because urinary concentrations are important.

followed, if sensitive, by

• Locals experts recommend a high dose is used based on local studies to ensure adequate concentrations against E. coli in the blood stream and kidney as well as in the bladder.
• fe = 0.9, dose is not normally reduced in patients with reduced CrCl for UTI treatment because urinary concentrations are important.

OR, after 14 weeks’ gestation (not in the first trimester - folate antagonist):

trimethoprim+ sulfamethoxazole HMLSchedNZFPMLnoids Trimethoprim+Sulfamethoxazole F: 0.8 Half life: 9 hours / 12 hours Elimination: CYP2C8/9 acetylated fe: 0.3 / 0.7

PO 160 mg/800 mg twice a day

• fe (trimethoprim) = 0.7, fe (sulfamethoxazole) = 0.3, dose is not normally reduced in patients with reduced CrCl for UTI treatment because urinary concentrations are important.
• Sulfamethoxazole is metabolised by CYP2C8/9 and conjugation.

Pathogens Known

E. coli

• fe = 0.9, adjust dose if CrCl reduced.
• Avoid in pregnancy.

OR, in severe renal failure (CrCl or eGFR < 20 mL/min) or pregnancy:

followed, if sensitive, by (in order of preference):

• Locals experts recommend a high dose is used based on local studies to ensure adequate concentrations against E. coli in the blood stream and kidney as well as in the bladder.
• Reduce dose to 500 mg twice daily in severe renal failure (CrCl or eGFR < 20 mL/min)

OR

• fe (trimethoprim) = 0.7, fe (sulfamethoxazole) = 0.3, dose is not normally reduced in patients with reduced CrCl for UTI treatment because urinary concentrations are important.
• Sulfamethoxazole is metabolised by CYP2C8/9 and conjugation.
• Avoid in first trimester of pregnancy.

Enterococci

amoxicillin HMLSchedNZFPMLnoids Amoxicillin F: 0.9 Half life: 2 hours Elimination: renal fe: 0.9

IV 1 g every eight hours or PO 500 mg three times a day

• fe = 0.7, dose is not normally reduced in patients with reduced CrCl for UTI treatment because urinary concentrations are important.

Penicillin allergy

Consult Infectious Diseases/Clinical Microbiology

Pseudomonas aeruginosa

• fe = 0.9, adjust dose if CrCl reduced.
• Avoid in pregnancy.

followed by

• fe = 0.7, consider dose reduction if CrCl reduced.
• Inhibits CYP1A2 (strong) and 3A.
• Subject to OAT and OATP (transporter) inhibition.
• Avoid in pregnancy and breastfeeding.

Extended-spectrum beta-lactamase (ESBL) producing coliforms – consult Infectious Diseases/Clinical Microbiology, inform Infection Prevention, and give:

meropenem HMLNZFPMLnoids Meropenem F: n/a Half life: 1 hour Elimination: renal; hydrolysis fe: 0.7

IV 1 g every eight hours

• Ertapenem IV 1 g every 24 hours may be considered for patients needing ongoing treatment on discharge. Discuss with Infectious Diseases.
• Meropenem rapidly and significantly reduces sodium valproate concentrations. Concomitant administration may precipitate seizures in patients with a pre-existing seizure disorder. Discuss alternative antibiotic options with Infectious Diseases/Clinical Microbiology.
• If still on meropenem beyond 48 hours, consider measuring a trough concentration. Consult Infectious Diseases for interpretation.
• fe = 0.7, start with full dose initially then consider extending dose interval and/or decreasing dose for subsequent doses if CrCl is reduced (< 30 mL/min). Consult pharmacist.

Topic Code: 99243

must be prescribed or recommended by a consultant.