Old Antibiotic for Uncomplicated Urinary Tract Infection

Pam Harrison

April 08, 2014

CAPE TOWN, South Africa — In hospitalized patients with uncomplicated urinary tract infections (UTIs), cure rates with oral fosfomycin, an old antibiotic, are excellent, even in those colonized with resistant organisms, a new study shows.

"Results from this project showed an 83% cure rate. Even in patients who did not achieve a clinical cure, only about 3% overtly failed therapy," said investigator Shauna Jacobson, PharmD, from the Orlando Regional Medical Center in Florida.

"We recently restricted fluoroquinolones at our hospital, and then we went on to restrict meropenem," she told Medscape Medical News. Although "fosfomycin has been studied pretty well in community patients, especially in patients with uncomplicated cystitis, it hasn't been well studied in hospitalized patients," she said. "We wanted to see how our patients did on it."

The study results were presented here at the 16th International Congress on Infectious Diseases.

Retrospective Review

In their retrospective review, Dr. Jacobson and her colleagues evaluated 71 patients treated for a UTI in their hospital system from November 2012 to November 2013

Approximately 60% of the patients had acquired their infection outside of the hospital and had been hospitalized for other reasons. However, about 38% of the infections were nosocomial in nature.

The median age of the cohort was 75 years, 39% had diabetes, 21% had renal insufficiency, and 38% had undergone a recent urologic procedure.

Almost three quarters of the cohort received systemic antibiotics in the 2 weeks preceding the introduction of fosfomycin, and slightly more than half received antibiotics concurrent with fosfomycin, often for infections other than UTIs.

Of the urinary isolates treated, 40 were enteric Gram-negative rods, 9 of which were isolates that produce extended-spectrum beta-lactamases and 9 of which were Pseudomonas aeruginosa; some cultures were mixed. Of 24 susceptibility studies, 3 isolates were intermediate and another 3 were resistant.

Notably, almost half of the patients evaluated responded to a single dose of fosfomycin 3 g. A smaller proportion required fosfomycin 3 g administered every 72 hours for a total of 3 doses, and still a smaller proportion required fosfomycin 3 g administered every 48 hours for a total of 3 doses.

The group defined cure as a resolution of symptoms — including fever, elevated white blood count, and painful, frequent, or urgent urination — with no need for retreatment or reisolation for the same organism within 30 days.

"Patients may have failed our definition of cure, but they did not necessarily fail therapy," Dr. Jacobson explained. For example, of the 12 patients who did not achieve a clinical cure rate, only 2 failed therapy. Isolates treated in these 2 patients were Proteus mirabilis and Klebsiella pneumoniae.

Four patients had isolates that showed high levels of resistance to fosfomycin in vitro, and treatment was changed before efficacy could be evaluated, Dr. Jacobson reported.

Treatment was also changed in 1 patient to more aggressively address a P aeruginosa nephrostomy tube infection and in 2 patients to treat a concurrent non-UTI infection.

Three other patients were retreated for an UTI within 30 days, but on repeat culture, the organism was not the same, she pointed out.

"Fosfomycin also has good efficacy for organisms that are frequently treated with broad-spectrum agents," Dr. Jacobson noted. For example, for the 9 P aeruginosa isolates treated, the cure rate with fosfomycin was 78%.

In the cohort, a 100% cure rate was achieved for the 8 extended-spectrum beta-lactamase isolates and an 86% cure rate was achieved for the 14 Enterococcus bacteria.

In addition, treatment was extremely well tolerated, with very few patients reporting any adverse effects.

"Fosfomycin is a very attractive option for UTIs because it mostly stays in the urinary tract," Dr. Jacobson explained. This means that there is less potential for the drug to cause resistance to bacteria in other parts of the body, she added.

"It also has a great spectrum of activity against most of the organisms that cause UTIs, including bacteria that produce extended-spectrum beta-lactamases and P aeruginosa," she added. Because the drug is not absorbed systemically, it is far less likely to alter gut flora than other antibiotics, and to thereby set the stage for Clostridium difficile infection.

As investigators point out, the inpatient treatment of UTIs is becoming a major driver of antimicrobial resistance and C difficile infection.

In the cohort, only 7% of patients developed C difficile infection in the 30 days after exposure to fosfomycin, but all of them had been exposed to other broad-spectrum systemic antibiotics.

"We wouldn't use it if a patient has a more invasive infection involving the kidneys, but when a patient only has cystitis, I very frequently recommend it," Dr. Jacobson said.

"The only problem I see with fosfomycin is cost," she told Medscape Medical News. Fosfomycin costs about $50 a dose.

Fosfomycin is not used to treat more serious infections like pneumonia; fluoroquinolones can be preserved for use in such situations, said Douglas Slain, PharmD, associate professor of pharmacy and medicine at West Virginia University in Morgantown.

"But in lower-risk patients, fosfomycin can be given once or twice in those who do not require long courses of an antibiotic," he told Medscape Medical News.

"Bacteriuria is common in hospitalized patients, especially those with indwelling catheters, but it may not always require a course of antibiotics," Dr. Slain added.

This study was done independently. Dr. Jacobson and Dr. Slain have disclosed no relevant financial relationships.

16th International Congress on Infectious Diseases (ICID): Abstract 50.002. Presented April 4, 2014.

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