An update on the management of urinary tract infections in the era of antimicrobial resistance

Abstract

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.

Cell-wall recycling and synthesis in Escherichia coli and Pseudomonas aeruginosa – their role in the development of resistance

“…Due to their effectiveness against both Gram-positive and Gram-negative bacteria, extensive use of fluoroquinolones has led to a rapid rise in resistance [229][230][231]. Development of resistance to quinolones entails multiple mechanisms [232,233].…”

Treatment of acute uncomplicated cystitis - A clinical review

“…Studies reporting in vitro susceptibility of E. coli causing uncomplicated UTI in North America and Europe demonstrated considerable geographic variability in susceptibility and a general trend toward increasing resistance [1][2][3]9,10,15]. These studies also revealed that, among the antimicrobials in common use for treatment of uncomplicated UTI, nitrofurantoin, fosfomycin and pivmecillinam (the latter not licensed in Sapin) have preserved their in vitro activity in all the countries investigated [1,9,10,15].…”

“…These studies also revealed that, among the antimicrobials in common use for treatment of uncomplicated UTI, nitrofurantoin, fosfomycin and pivmecillinam (the latter not licensed in Sapin) have preserved their in vitro activity in all the countries investigated [1,9,10,15]. Thus, these 3 antimicrobials were considered in the IDSA guidelines appropriate antimicrobials for empirical therapy in most regions [1].…”

“…Nitrofurantoin could also be a further option for oral antimicrobial treatment of acute uncomplicated cystitis produced by ESBL-producing bacteria [30]. However, there is a growing concern of increasing resistance of ESBLproducing organisms against nitrofurantoin, particularly in hospitalacquired infections [15].…”

Community‐onset Pseudomonas aeruginosa urinary sepsis in elderly people: Predictive factors, adequacy of empirical therapy and outcomes

“…Furthermore, the rate of PA resistant to antipseudomonal antibiotics was higher than 10% for every one of them, reaching 22.4% to carbapenems. This situation might be different in other settings, but it raises the possibility of prescribing, at least in the most severe cases, combined antibiotics or new antipseudomonal antibiotics, such as ceftolozane‐tazobactam or ceftazidime‐avibactam . On the other hand, in those cases without risk factors for PA, the use of antibiotics with anti‐PA activity could be limited.…”