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Is nitrofurantoin relevant for urinary tract infections: an instructive experience from France

In February 2011, the French Agency for the Safety of Medicines and Health Products (ANSM) issued a warning that prolonged use of nitrofurantoin could cause severe liver and lung toxicity.

Consequently, the use of nitrofurantoin for the prevention of urinary tract infections was not strictly recommended. A year later, the ANSM issued updated recommendations stating that nitrofurantoin seriously damages the liver and lungs and should be used to treat documented cases of cystitis caused by strains of susceptible microorganisms in case it is not possible to use another antibacterial drug inside with the best (compared to nitrofurantoin) benefit / risk ratio.

The recommendations indicate that nitrofurantoin may be considered a drug for empiric antibiotic therapy in emergency situations or when there is anamnestic evidence of an episode of UTI caused by a multidrug-resistant agent, but nitrofurantoin should not be used for prevent urinary tract infections.

The initial recommendations for an almost total ban on the use of nitrofurantoin were considered to be wrong - this type of information was published in the August issue of the Journal of Antimicrobial Chemotherapy.

According to the authors of the publication, the expression used in vain in the new French recommendations has practically left no niche for nitrofurantoin in the treatment of urinary tract infections, taking into account the fact that a cultural study, in general, is not routinely performed and, therefore, documented confirmation of infection is a rare occurrence in women with symptoms of UTI.

The researchers evaluated the impact of the ANSM recommendations on the prescription of antibiotics for urinary tract infections from May 2007 to August 2012. A warning publication on the toxicity of nitrofurantoin led to a rapid and significant decrease ( p less than 0.001) of its use (-49.3% after 16 months after the warning was issued). It should be noted that most (75%) of the nitrofurantoin prescriptions are short-term in an episode of acute cystitis. It is very likely that this 2-fold decrease in the frequency of use of nitrofurantoin is associated not only with the prohibition of its long-term use for the prevention of urinary tract infections, but also influenced the administration of the usual short cycles of this antibiotic. Later, antibiotic prescribers began to prefer fluoroquinolones for urinary tract infections over nitrofurantoins.

A warning regarding the toxicity of nitrofurantoin has been issued by reports of serious adverse events, mainly of the liver and lungs, with a frequency of 12.7 per year (1 case per 20,551 appointments). This indicator increased with prolonged treatment: from 1 case for 24,800 short-term appointments (less than a month) to 1 case for 7,666 appointments with prolonged use of the drug (more than one month).

The authors of the publication noted that no other European country has issued this type of warning, although in most of them nitrofurantoin is prescribed more often than in France, including its use for an indication prohibited (prevention of urinary tract infections).

According to the opinion of most European experts, there is no clear scientific evidence which would confirm the advisability of restricting the use of nitrofurantoin to short-term courses in the treatment of urinary tract infections, and his appointment is currently recommended by many practical guides around the world.

In conclusion, the authors of the publication conclude that, although long-term prophylactic use of nitrofurantoin should be limited, short periods of use of this nitrofuran for the treatment of urinary tract infections occur, particularly at one time. of increasing resistance of microorganisms of the Enterobacteriaceae family to a wide range of antimicrobial agents. The huge effect of increased fluoroquinolone intake on antibiotic resistance is well documented. Given the increasing resistance of uropathogens to antibiotics and the lack of new therapeutic options for the treatment of urinary tract infections, there is an urgent need to objectively assess the drugs available in the arsenal of physicians, and medical experts should avoid categorical formulations and consider the long-term prospects for the use of antibacterial drugs.