Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-negative bacteria are a growing concern due to limited therapeutic options. Gram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospital acquired UTIs. These organisms can acquire genes that encode for multiple antibiotic resistance mechanisms, including extended-spectrum-lactamases (ESBLs), AmpC- β -lactamase, and carbapenemases. The assessment of suspected UTI includes identification of characteristic symptoms or signs, urinalysis, dipstick or microscopic tests, and urine culture if indicated. UTIs are categorized according to location (upper versus lower urinary tract) and severity (uncomplicated versus complicated). Increasing rates of antibiotic resistance necessitate judicious use of antibiotics through the application of antimicrobial stewardship principles. Knowledge of the common causative pathogens of UTIs including local susceptibility patterns are essential in determining appropriate empiric therapy. The recommended first-line empiric therapies for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females is a 5-day course of nitrofurantion or a 3-g single dose of fosfomycin tromethamine. Second-line options include fluoroquinolones and β-lactams, such as amoxicillin-clavulanate. Current treatment options for UTIs due to AmpC- β -lactamase-producing organisms include fosfomycin, nitrofurantion, fluoroquinolones, cefepime, piperacillin-tazobactam and carbapenems. In addition, treatment options for UTIs due to ESBLs-producing Enterobacteriaceae include nitrofurantion, fosfomycin, fluoroquinolones, cefoxitin, piperacillin-tazobactam, carbapenems, ceftazidime-avibactam, ceftolozane-tazobactam, and aminoglycosides. Based on identification and susceptibility results, alternatives to carbapenems may be used to treat mild-moderate UTIs caused by ESBL-producing Enterobacteriaceae. Ceftazidime-avibactam, colistin, polymixin B, fosfomycin, aztreonam, aminoglycosides, and tigecycline are treatment options for UTIs caused by carbapenem-resistant Enterobacteriaceae (CRE). Treatment options for UTIs caused by multidrug resistant (MDR)-Pseudomonas spp. include fluoroquinolones, ceftazidime, cefepime, piperacillin-tazobactam, carbapenems, aminoglycosides, colistin, ceftazidime-avibactam, and ceftolozane-tazobactam. The use of fluoroquinolones for empiric treatment of UTIs should be restricted due to increased rates of resistance. Aminoglycosides, colistin, and tigecycline are considered alternatives in the setting of MDR Gram-negative infections in patients with limited therapeutic options.

Complicated urinary tract infections (cUTIs) are a major cause of hospital admissions and are associated with significant morbidity and health care costs. Patients presenting with a suspected UTI should be screened for the presence of complicating factors, such as anatomic and functional abnormalities of the genitourinary tract. In the setting of cUTIs, the etiology and susceptibility of the causative organism is not predictable; therefore, when infection is suspected, patients should undergo a urinalysis in addition to culture and sensitivity testing. Although not warranted in all cases of complicated pyelonephritis, blood cultures are appropriate in some clinical settings. With the increased prevalence of antimicrobial resistance, and the lack of well-designed clinical trials, treatment of cUTIs can be challenging for clinicians. Although resistant organisms are not always implicated as the causative agent, all patients with cUTIs should be assessed for predisposing risk factors. Consideration of an optimal antimicrobial agent should be based on local resistance patterns, patient-specific factors, including anatomic site of infection and severity of disease, pharmacokinetic and pharmacodynamic principles, and cost. Resistance to first-line antimicrobial agents, including fluoroquinolones, has become increasingly common in Escherichia coli. Fluoroquinolones should not be used as a first-line option for empiric treatment of serious cUTIs, especially when patients exhibit risk factors for harboring a resistant organism, such as previous or recent use of fluoroquinolones. Fluoroquinolones, trimethoprim-sulfamethoxazole, and nitrofurantoin are still appropriate empiric options for mild lower cUTIs. However, empiric treatment for serious cUTIs, where risk factors for resistant organisms exist, should include broad-spectrum antibiotics such as carbapenems or piperacillin-tazobactam. Once organisms and susceptibilities are identified, treatment should be targeted accordingly. Nitrofurantoin and fosfomycin have limited utility in the setting of cUTIs and should be reserved as alternative treatment options for lower cUTIs following confirmation of the causative organism. Aminoglycosides, tigecycline, and polymyxins can be used for the treatment of serious cUTIs when first-line options are deemed to be inappropriate or patients fail therapy. The duration of treatment for cUTIs has not been well established; however, treatment durations can range from 1 to 4 weeks based on the clinical situation.

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