Urinary%20tract%20infection%20in%20women%20-%20complicated Treatment

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

Aminoglycosides

• 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

Aztreonam

• 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

Carbapenems

• 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

Cephalosporins

• 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

Quinolones

• 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