Antibiotic therapy for acute uncomplicated pyelonephritis in women. Take resistance into account

Abstract

Acute uncomplicated pyelonephritis is a bacterial infection of the renal parenchyma, common in women. The bacterium responsible is usually Escherichia coli. Empirical antibiotic therapy should be initiated promptly to prevent serious complications. As of 2014, which empirical antibiotic regimen should be offered to non-pregnant adult women with acute uncomplicated pyelonephritis, while awaiting the results of antimicrobial susceptibility testing? We reviewed the available evidence using the standard Prescrire methodology. Certain oral fluoroquinolones were effective in a few clinical trials in the 2000s and 2010s: ciprofloxacin and levofloxacin, an isomer of ofloxacin. Symptoms resolved within 5 to 7 days in about 96% of the women. In France, in 2011, about 10% of E. coli isolated in community laboratories from outpatients with urinary tract infections were resistant to ciprofloxacin. Resistance is mainly a problem in patients treated with a quinolone during the preceding months and in recently hospitalised patients. In hospital laboratories, the fluoroquinolone resistance rate was about 18% in 2012 in France, and even higher in some other European countries. The main harms of fluoroquinolones are neuropsychiatric disorders, photosensitivity, tendon disorders, arrhythmia and cardiac conduction disorders, and Clostridium difficile infection. Injectable "third-generation" cephalosporins, such as ceftriaxone, are often effective against enterobacteria, in particular E. coli, and have good kidney penetration. The prevalence of E. coli resistance to third-generation cephalosporins is rising rapidly in France, particularly in hospitals: 1% in 2005 versus 10% in 2012. The main harms of cephalosporins are hypersensitivity reactions and C. difficile infection. Monotherapy with an aminoglycoside is an alternative that has not been evaluated in this clinical situation. Due to the serious irreversible adverse effects of aminoglycosides (nephrotoxicity, ototoxicity), they should only be used when the other options are unacceptable. In practice, as of 2014, the first-choice empirical antibiotic treatment for acute uncomplicated pyelonephritis remains an oral fluoroquinolone (ciprofloxacin or ofloxacin) or, in certain cases, the injectable third-generation cephalosporin ceftriaxone. Given the rapid development of bacterial resistance, broader-spectrum antibiotics should not be used as empirical therapy, to preserve their efficacy in serious infections. The empirical treatment should be adjusted as soon as the results of antimicrobial susceptibility testing are known. Whenever possible, it is preferable to avoid the use of fluoroquinolones and third-generation cephalosporins in non-serious infections such as cystitis.