Local resistance impacts cost-effectiveness of antibiotics for UTI

Findings from a recent British study indicate that trimethoprim 200 mg BID for 3 or 7 days is the most effective antibiotic for uncomplicated urinary tract infection (UTI) when levels of local resistance to the drug are < 30%, but when it is ≥ 35%, a single dose of fosfomycin 3g or nitrofurantoin 100 mg BID for 7 days is more cost-effective. The results are similar to those from analyses of the effectiveness of trimethoprim-sulfamethoxazole (TMP-SMX) performed in the United States.          

Suspected, uncomplicated UTIs are one of the most common reasons for women to visit their doctors, and 14% of antibiotic prescriptions for community-acquired infections in 2011 in the UK were written for UTIs. Typically, these infections are treated empirically without ordering urine culture, which means that both the pathogen responsible for the infection and its susceptibility to a specific antibiotic remain unknown. However, good antibiotic stewardship requires that antibiotics be prescribed judiciously to eradicate pathogens while minimizing cost and spread of resistance.        

British researchers analyzed the efficacy and cost-effectiveness of four antibiotics-fosfomycin, nitrofurantoin, pivmecillinam, and trimethoprim-that are commonly recommended in England to treated uncomplicated UTIs. The study was the first ever to compare the relative cost-effectiveness of the four agents, and nine different treatment regimens involving different durations and doses of the four drugs were analyzed.

The investigators created a decision-tree economic model of treatment pathways with the four antimicrobials incorporating different levels of resistance to Escherichia coli to guide physicians in managing UTIs. Recovery and persistence of infection, as well as pyelonephritis and hospitalization, were selected as endpoints. Cost-effectiveness was evaluated in terms of cost to resolve per UTI, and included the cost of prescriptions, primary- and secondary-care treatments, and diagnostic testing.

The results indicated that trimethoprim 200 mg twice daily for 7 days had the highest clinical cure rate and was the most cost-effective agent for uncomplicated UTI when resistance was < 30%, followed by fosfomycin 3 g once. After those two agents, the agents and regimens were ranked in order of decreasing cost-effectiveness as follows:

• nitrofurantoin 100 mg BID for 7 days,
• pivmecillinam 200 mg BID for 7 days (not available in the United States),
• nitrofurantoin 50 mg QID for 7 days,
• pivmecillinam 200 mg TID for 7 days,
• pivmecillinam 400 mg BID for 3 days,
• trimethoprim 200 mg once, and
• nitrofurantoin 100 mg QID for 3 days.

The researchers noted that they only calculated results for resistance to E. coli in their base model. They stated that nitrofurantoin has 100% efficacy against E. coli, but is resistant to certain Klebsiella and Enterobacter strains and most strains of Proteus. Cost-effectiveness of all the agents-particularly nitrofurantoin-was reduced when reported estimates of resistance to the latter species were considered, but the ranking of treatments stayed the same.

Results comparable to US studies

In the United States, TMP-SMX is the most commonly recommended treatment for uncomplicated UTI in women, versus fluoroquinolones or nitrofurantoin. TMP-SMX was found to be the most cost-effective agent when resistance was < 30% in a US analysis performed in 2001.

The investigators for the UK study cautioned that there is evidence that resistance to trimethoprim is rapidly increasing and potentially varies by locale within the country, which “casts doubt on its cost-effectiveness in empirical treatment of uncomplicated UTI.” They suggested that studies to investigate both in vitro susceptibility and clinical response to individual antimicrobials would be helpful in further identifying the efficacy and cost-effectiveness of empiric antibiotic therapy for uncomplicated UTI.