Management of Urinary Tract Infections From Multidrug-Resistant Organisms

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Key points

  • Antimicrobial resistance to a broad spectrum of agents is encountered with increasing frequency among uropathogens, even in the community setting.

  • An understanding of resistance mechanisms and determinants can help optimize empiric therapy.

  • Treatment of urinary tract infections from multidrug-resistant organisms is complicated by limited oral options and may require a return to older antibiotics, combination therapy, or intravenous agents.

Epidemiology

Antimicrobial resistance among uropathogens has been widely documented. Resistance to commonly used antimicrobials, even in community-associated uncomplicated cystitis, has been described for more than a decade.7 However, the prevalence of multidrug-resistant organisms in the outpatient setting is increasing, and the problem of uncomplicated UTIs requiring intravenous therapy because of the lack of oral options is a new challenge for clinicians, complicating a once simple-to-treat infection.

The

Determinants of resistance

Microbial resistance can be a result of sporadic chromosomal mutations that offer selective advantage and allow organisms to either change the drug target site, increase drug efflux, or limit drug entry. Resistance can also be carried on foreign DNA through transposons and plasmids, which can be transferred between organisms of the same species or across species. Plasmids may also concurrently carry genes for resistance to multiple antibiotics. Hence, multiclass resistance is not uncommon, even

Clinical implications

At initial presentation, patients should be evaluated for known risk factors for multidrug-resistant bacterial infections in general. These factors include age older than 60 years, prior UTI history or chronic medical conditions, recent hospitalizations or antibiotic treatment, and recent travel.21 Aside from selection pressure from antimicrobial use, particularly with β-lactam antibiotics and fluoroquinolones, transmission risk factors for ESBL UTIs are not well understood.5, 29, 30

Identifying

New therapies in the pipeline

Several new approaches are being evaluated to address the dearth of active agents against carbapenemases. In particular, several novel β-lactamase inhibitors with activity against carbapenemases show promise when used in combination with β-lactam agents.51 Although these agents may have limited activity alone, they potentiate the effect of other β-lactams, extended-spectrum cephalosporins, and aztreonam. Some promising regimens are presented in Table 2.51, 52, 53, 54, 55, 56, 57 Ceftolozane

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    Funding: None.

    Conflict of Interest: Dr K. Gupta has served as a consultant to Paratek Pharmaceuticals and holds equity in Aegis Women’s Health Technologies; Dr N. Bhadelia: None.

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