Complicated urinary tract infection (UTI) is associated with a condition [eg structural or functional abnormalities of the genitourinary tract (GUT)] or the presence of an underlying disease that interferes with host defense mechanisms, which increases the risks of acquiring infection, failing therapy or having recurrent infections. The successful treatment of a complicated UTI considers effective antimicrobial therapy, optimal management of the underlying abnormalities or other diseases and adequate life-supporting measures.

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Principles of Therapy

General Therapy Principles

  • The successful treatment of a complicated UTI considers effective antimicrobial therapy, optimal management of the underlying abnormalities or other diseases and adequate life-supporting measures
  • Patients with complicated UTIs generally require 7-14 days of antimicrobial therapy

Oral versus Parenteral Therapy

  • Oral antibiotic therapy may be started in stable patients
  • Initial parenteral therapy is preferred only for individuals who have: Hemodynamic instability, nausea and vomiting, questionable absorption or an infection by suspected resistant organisms for which oral therapy is not available
    • Patients may be switched to appropriate oral therapy within 72 hours if showing clinical improvement and if they can tolerate oral medications

Empiric Treatment

  • The selection of a specific antimicrobial agent is based upon clinical presentation, the known or suspected microorganism in the community and its susceptibilities, patient tolerance, documented efficacy and in some cases, cost
    • Use a broad-spectrum antimicrobial regimen with ESBL coverage
  • Should immediately be replaced with specific treatment once pathogen is detected in urine culture since intense use of any antimicrobial will lead to the emergence of resistant microorganisms



  • One of the treatments of choice if parenteral therapy is needed
  • Depending on suspected etiologic agent, may be used as initial therapy or reserved as an alternative therapy
    • May be combined with beta-lactam with or without pseudomonal coverage (many times an aminopenicillin is used as initial therapy)
  •  Effective against several resistant microorganisms

Aminopenicillin with Beta-lactamase Inhibitor

  • Synergistic action with beta-lactamase inhibitor causes these agents to be more active than aminopenicillins alone
    • Efficacious in Gram-positive microorganisms (eg group B streptococci and Enterococcus sp)
  • Aminopenicillins alone are no longer sufficiently active against E coli and therefore should not be used as empiric therapy
    • Depending on local antimicrobial resistance patterns, aminopenicillins in combination with aminoglycosides may be used for empiric therapy

Antipseudomonal Penicillin with Beta-lactamase Inhibitor

  • May be used in case of failure of initial empiric therapy or for severe cases


  • Appropriate empiric parenteral therapy in hospitalized patients who fail to respond to initial antibiotic therapy or in patients in whom the bacteria is known to be resistant to other agents


  • Appropriate empiric parenteral therapy in hospitalized patients who fail to respond to initial antibiotic therapy, patients with urinary tract obstruction, or in patients with risk factors for a multidrug-resistant Gram-negative infection (eg Ertapenem) 
  • Antipseudomonal carbapenems include Doripenem, Imipenem and Meropenem


  • Oral 1st, 2nd or 3rd generation cephalosporins may be appropriate for patients with mild-moderate complicated UTI 
  • IV 2nd or 3rd generation cephalosporins may be used as initial empiric therapy in hospitalized patients
  • IV 3rd or 4th generation cephalosporins may be used in case of initial empiric therapy failure
    • Ensure that 3rd generation cephalosporin to be used was not previously administered and has antipseudomonal coverage (eg Ceftazidime and Cefoperazone)
  • Can still be given to patients with penicillin hypersensitivity provided there had been no previous systemic anaphylaxis

Co-trimoxazole [Sulfamethoxazole (SMZ) and Trimethoprim (TM)]

  • May be used in the outpatient treatment of patients with low risk of multidrug-resistant infection who have contraindications or concerns regarding fluoroquinolone use 
  • Though most countries have high rates of E coli resistance to Co-trimoxazole, its use can be considered if susceptibility is known


  • Due to high levels of resistance, fluoroquinolones can only be used as empiric treatment if it has not been used in the last 6 months, if the patient is not severely ill and can safely take oral therapy, or if the patient has had a previous beta-lactam anaphylactic reaction 
    • Oral quinolones are appropriate as initial empiric therapy in patients with mild-moderate complicated UTIs
    • IV quinolones may be used for severe cases
  • Consider empiric treatment with Ciprofloxacin in women with complicated pyelonephritis if fluoroquinolone resistance is <10% and patient has contraindications for an aminoglycoside or a 3rd generation cephalosporin

Other Agents

  • Alternative agents that may be used for multidrug-resistant organisms or select cases of highly resistant infections include Ceftolozane/tazobactam, Ceftazidime/avibactam, Cefiderocol, Imipenem/cilastatin with Relebactam, Plazomicin, Meropenem/vaborbactam, and parenteral Fosfomycin

Specific Therapy

Complicated UTI Associated with Indwelling Catheter

  • Symptomatic complicated UTIs occurring in patients with a short-term indwelling catheter should be treated by removing the catheter and with administration of a narrow-spectrum antibiotic based on culture and sensitivity results
  • Replace or remove indwelling catheter before starting antibiotics if indwelling catheter has been in place >7 days
  • Asymptomatic bacteriuria should not be treated regardless whether or not the patient has short-term or long-term catheter, except in certain situations eg prior to traumatic urinary tract procedures
  • Antibiotic prophylaxis is not recommended for preventing catheter-related UTI
  • Topical antiseptics should not be applied to the catheter, urethra or meatus 

Complicated UTI Associated with Urinary Stones

  • Urinary obstruction without evidence of infection may be treated expectantly
  • Empiric broad-spectrum antimicrobials should be started immediately in patients that have clinical signs of infection
  • Efforts to remove the stone should only be considered once the infection has cleared but early intervention to relieve the obstruction using a stent or nephrostomy tube is frequently necessary
  • If complete removal of the stone cannot be accomplished, long-term antibiotic therapy may be considered

Complicated UTI in Spinal Cord-Injured Patients

  • The presence of residual urine and bladder outlet obstruction (anatomic or physiologic) predisposes this group of patients to UTI
  • Symptomatic episodes of infection should be treated with antimicrobials
    • There is no superiority of 1 agent or class of antimicrobials over another
  •  Asymptomatic bacteriuria should not be treated

Complicated UTI Associated with Diabetes Mellitus

  • 7-14 days of antimicrobial therapy is recommended
  • DM patients who present with UTI and signs and symptoms of sepsis should be hospitalized
    • Failure to respond within 48-72 hours requires plain abdominal radiograph and renal ultrasound
  • Asymptomatic bacteriuria in diabetics should not be treated routinely with antibiotics
    • A history of febrile UTI and other concomitant conditions are factors to be considered when deciding on starting antibiotic treatment for diabetics with asymptomatic bacteriuria

Complicated UTI in Renal Transplant Patients

  • Effective antibiotic therapy requires the use of antibiotics that achieve therapeutic concentration in the urine and are appropriately dose-adjusted for the level of renal failure
  • Initially, treat with parenteral broad-spectrum antibiotics until urine culture becomes negative
  • May be shifted to oral agents guided by culture and sensitivity results to complete 4-6 weeks
  • 10-14 days of antibiotic treatment is required in most cases
  • Asymptomatic bacteriuria that occurs during the first 6 months after transplantation may often need to be treated with antibiotics
    • Low-dose Co-trimoxazole antibiotic prophylaxis has been recommended for 6 months posttransplant

UTI in Pregnant Women

  • Progression of cystitis and asymptomatic bacteriuria to pyelonephritis is significantly increased in pregnant women
  • Pregnant women should be screened for asymptomatic bacteriuria through a quantitative urine culture at first prenatal visit, ideally at 16 weeks of gestation 
    • Obtain specimen for urine culture before starting treatment
    • If positive, confirm through a 2nd culture
    • Treat both symptomatic and asymptomatic bacteriuria with antibiotics
  • Repeat urine culture 7-14 days after completing antibiotic treatment
    • Repeat urine culture at each prenatal visit until delivery
  • If urine culture during 1st prenatal visit is negative, it is unnecessary to repeat urine culture during subsequent prenatal visits
  • For cystitis, penicillins, cephalosporins and Nitrofurantoin are recommended
  • For pyelonephritis, aminopenicillins with or without a beta-lactamase inhibitor and cephalosporins are mainstays; aminoglycosides may be used with caution
    • Most pregnant women will need hospitalization and parenteral antibiotics
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