Urinary Tract Infection - Complicated Xử trí

Đánh giá

Indications for Hospital Admission

The decision to hospitalize the patients should be individualized based on the severity of the illness. Factors that would necessitate hospital admission include:

• Patient is unable to maintain oral hydration or take oral medications
• Concerns regarding patient adherence to treatment
• Uncertainty of diagnosis
• Severe illness with high fever and pain
• Marked debility and signs of sepsis
• Suspected urinary tract obstruction

Outpatient Management

Patients who do not meet the above categories may be considered for treatment on an outpatient basis. 

Nguyên tắc điều trị

The successful treatment of a complicated UTI involves optimal antimicrobial therapy, appropriate management of underlying abnormalities or diseases, and adequate life-supporting measures. The selection of initial empiric therapy depends on the clinical presentation, known or suspected microorganism and its susceptibilities, local resistance data, patient’s tolerance or allergies, documented efficacy and, in some cases, cost.

In a recent update from the Infectious Diseases Society of America (IDSA), a 4-step process was suggested when selecting initial empiric therapy: Assessing the severity of illness, considering patient-specific risk factors for resistant uropathogens, evaluating other patient-specific considerations, and consulting the relevant local antibiogram, if available, in cases of sepsis.

A conditional IDSA recommendation was also made for the use of third- or fourth-generation cephalosporins, carbapenems, Piperacillin/tazobactam or quinolones in patients with complicated UTI with sepsis; if without sepsis, third- or fourth-generation cephalosporins, Piperacillin/tazobactam or quinolones are recommended. Initial parenteral therapy is preferred for individuals who have symptoms requiring hospitalization, including hemodynamic instability, nausea, vomiting, questionable absorption or an infection caused by suspected resistant organisms for which oral therapy is not available. Patients may be switched to appropriate oral therapy within 72 hours if with clinical improvement and if they can tolerate oral medications. Oral antibiotic therapy may be started in stable patients. Patients with complicated UTIs generally require 7-14 days of antimicrobial therapy, although treatment for 7 days may be considered if the patient is hemodynamically stable and afebrile for at least 48 hours. The IDSA recommends a shorter duration of 5-7 days in patients showing clinical improvement on appropriate therapy, as it has been shown to provide similar efficacy to longer courses, except in cases of men with febrile UTI with suspected bacterial prostatitis.

Pharmacological therapy

Empiric Therapy

Empiric therapy should be initiated without delay and subject to subsequent modification based on urine culture and susceptibility testing results. A broad-spectrum antimicrobial regimen is recommended in patients with complicated UTI who are critically ill, show worsening of condition despite therapy or are suspected of having obstruction. Agent selection depends on the prevalence of multidrug-resistant organisms, particularly ESBL-producing organisms. If prevalence is not known to be <10%, an antipseudomonal carbapenem in addition to Vancomycin is recommended; narrower-spectrum agents may be used if resistance is <10%. The choice of therapy for patients who are hospitalized but not critically ill and without suspicion of obstruction depends on the individual risk for infection with multidrug-resistant Gram-negative organisms.

Aminoglycosides

Aminoglycosides are one of the treatments of choice if parenteral therapy is needed. Depending on the suspected etiologic agent, they may be used as initial therapy or reserved as an alternative therapy. They may be given as monotherapy or combined with an aminopenicillin/beta-lactamase inhibitor with or without pseudomonal coverage (many times, an aminopenicillin is used as initial therapy) (eg Amoxicillin), or a second-generation cephalosporin. Aminoglycosides are effective against several resistant microorganisms. Plazomicin and Fosfomycin have some activity against some ESBL-producing enterobacterales and multidrug-resistant P aeruginosa isolates and may be used if cultures confirm susceptibility.

Aminopenicillin with Beta-lactamase Inhibitor

The synergistic action with a beta-lactamase inhibitor causes these agents to be more active than aminopenicillins alone. They are efficacious against Gram-positive microorganisms (eg group B streptococci and Enterococcus sp) and susceptible enterobacterales (eg E coli, K pneumoniae, P mirabilis). 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. Amoxicillin may be used as the agent of choice if susceptible Enterococcus is isolated. Aminopenicillins may also be given as an alternative to quinolones for outpatient treatment.

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Complicated UTI Associated with an Indwelling Catheter

Symptomatic complicated UTIs occurring in patients with a short-term indwelling catheter should be treated by removing the catheter and administering a narrow-spectrum antibiotic based on culture and sensitivity results. The recommended duration of treatment is 7-14 days, but a 5-day regimen of Levofloxacin may be considered in patients who are not severely ill. The catheter should be replaced or removed before starting antibiotics if it has been in place for >7 days. Asymptomatic bacteriuria should not be treated regardless of whether the patient has a short-term or long-term catheter, except in certain situations (eg prior to traumatic urinary tract procedures). Antibiotic prophylaxis is not recommended for preventing CA-UTI.

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 who 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, whether anatomic or physiologic, predisposes this group of patients to UTI. Symptomatic episodes of infection should be treated with antimicrobials. There is no superiority of one agent or class of antimicrobials over another. Asymptomatic bacteriuria should not be treated.

Complicated UTI Associated with DM

Failure to respond to treatment within 48-72 hours requires further evaluation (eg 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 whether to start antibiotic treatment for diabetics with asymptomatic bacteriuria.

Complicated UTI in Renal Transplant Patients

Effective antibiotic therapy requires the use of antibiotics that achieve therapeutic concentrations in the urine and are appropriately dose-adjusted for the level of renal failure. Initially, patients should be treated with parenteral broad-spectrum antibiotics until the urine culture becomes negative. Antibiotic treatment for 10-14 days is required in most cases. Patients may be shifted to oral agents guided by culture and sensitivity results to complete 4-6 weeks of therapy. Monitoring for asymptomatic bacteriuria should be limited to the first 2 months post-transplant. Detection of asymptomatic bacteriuria should be confirmed by a second urine culture. Two consecutive cultures with >10⁵ cfu/mL of the same pathogen may be treated based on its susceptibility pattern.

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 the first prenatal visit, ideally at 16 weeks of gestation. Both symptomatic and asymptomatic bacteriuria should be treated with antibiotics, and a specimen for urine culture should be obtained before starting treatment.

Urine culture is repeated 7 days after completing antibiotic treatment. Urine culture is also repeated at each prenatal visit until delivery. However, if the urine culture during the first prenatal visit is negative, it is unnecessary to repeat urine culture during subsequent prenatal visits. For cystitis, penicillins, cephalosporins, Fosfomycin and Nitrofurantoin (except during the end of pregnancy), Trimethoprim (not during the first trimester) and sulphonamides (not in the third trimester) are recommended. For pyelonephritis, aminopenicillins with or without a beta-lactamase inhibitor and cephalosporins are mainstays; aminoglycosides may be used with caution. Lastly, it must be noted that most pregnant women will need hospitalization and parenteral antibiotics.

Complicated UTI in Men

An underlying urologic abnormality is usually present, commonly an enlarged prostate. A specimen for urine culture should be obtained in all men with symptoms of UTI, and a positive result is a colony count of ≥10³ cfu/mL. Antibiotics must adequately penetrate prostatic tissue, and quinolones that penetrate the prostatic tissue well or Co-trimoxazole may be used in accordance with sensitivity testing results. A persisting focus in the prostate (eg prostatic abscess or chronic bacterial prostatitis) may result in repeated seeding of the urinary tract. Evaluation of the urinary tract must be performed in all men with febrile UTI, pyelonephritis, recurrent UTI or whenever a complicating factor is considered.

Recurrent UTI

Recurrent UTI is defined as ≥2 UTI episodes in 6 months or ≥3 UTI episodes in 12 months and may result from persistent bacterial infection or reinfection. Antibiotic prophylaxis may be considered in women in whom behavioral or other preventive measures have been ineffective or inappropriate. It may be administered continuously at a low dose for 3-12 months or post-coitally. Post-coital prophylaxis should be considered in pregnant women with a history of frequent UTIs prior to pregnancy. Agents may include Fosfomycin, Nitrofurantoin, Trimethoprim and, during pregnancy, Cefaclor or Cefalexin. Recurrent UTIs may also be prevented with immunoactive prophylaxis in all age groups, Methenamine hippurate in women without urinary tract abnormalities and vaginal Estrogen in postmenopausal women. Other agents to consider for reducing recurrent UTIs include cranberry products and oral or local probiotics for vaginal flora regeneration.