Drugs Not Equal Against Bladder Infection

By | January 7, 2017

By medpagetoday.com

For uncomplicated bladder infections, cefpodoxime (Vantin) may not be a viable antibiotic alternative to fluoroquinolone ciprofloxacin (Cipro, Proquin), a randomized trial suggested.

More women needed further treatment after a short course of the cephalosporin than after the same duration of ciprofloxacin (clinical cure rate 82% versus 93%), Thomas M. Hooton, MD, of the University of Miami, and colleagues found.

The difference didn’t meet criteria for noninferiority (P=0.57), the researchers reported in the February 8 issue of the Journal of the American Medical Association.

Fluoroquinolones are considered the most reliable for treating urinary infections, but the search has been on for other, effective antimicrobials in this setting because of rising resistance to fluoroquinolones, the group explained.

“These findings, along with concerns about possible adverse ecological effects associated with other broad-spectrum beta-lactams, do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis,” Hooton and colleagues concluded.

Use of broad-spectrum cephalosporins has been seen to promote resistance across the beta-lactamase class, with one study linking parenteral use to gram-negative extended-spectrum beta-lactamase antibiotic resistance, they explained.

And largely citing concerns for resistance to lead to more serious and difficult-to-treat infections outside the urinary tract, the Infectious Diseases Society of America has recommended that fluoroquinolones be reserved for important uses other than acute cystitis.

The bottom line is that clinicians should look to other antibiotics before fluoroquinolones and beta-lacams like cefpodoxime, the researchers emphasized. Other recommended options are:

  • Nitrofurantoin
  • Trimethoprim-sulfamethoxazole, except in areas of known high the resistance prevalence
  • Fosfomycin (Monurol)
  • Pivmecillinam (Selexid, not available in the U.S.)

The trial randomized 300 women, ages 18 to 55, with acute uncomplicated cystitis to double-blind treatment with a three-day course of either ciprofloxacin orally (250 mg twice daily) or oral cefpodoxime (100 mg twice daily).

For the primary endpoint, ciprofloxacin gave a statistically significant 11% higher overall clinical cure rate, defined as no requirement for antimicrobial treatment during 30 days of follow up.

That difference exceeded the predetermined 10-percentage point margin for noninferiority of cefpodoxime that the researchers suggested would have been clinically acceptable.

Changing the assumption that women lost to follow up had been cured of their infection to one in which they were considered to have not responded to treatment didn’t change the results. Cefpodoxime still came out significantly worse with a clinical cure rate of 71% compared with ciprofloxacin’s 83%.

The difference between efficacy of the drugs was greatest among women who reported not having a urinary tract infection within the prior year, while ciprofloxacin barely came out ahead of cefpodoxime among women who had at least one recent urinary tract infection (84% for ciprofloxacin versus 80% for cefpodoxime).

Microbiological cure rates came in at 96% with ciprofloxacin compared with 81% with cefpodoxime, a statistically significant difference of 15% (95% CI 8% to 23%).

More than 80% of the women in both groups had vaginal colonization with Escherichia coli at baseline, which cefpodoxime was not effective at clearing.

By the first follow up at around five days, 16% of women in the ciprofloxacin group versus 40% on cefpodoxime still had vaginal E. coli colonization. At 30 days, the rate was still 29% versus 40%.

Those findings suggest one reason why beta-lactam antibiotics like cefpodoxime yield lower clinical response than other first-line antimicrobials, the researchers pointed out.

They noted that the highly compliant, largely white student population in the study might limit generalizability.

Source: https://www.medpagetoday.com/urology/urology/31084