The progressive increase of extended-spectrum
beta-lactamase (ESBL) -producing enteric bacteria in recent years has called for a re-evaluation of current
antibiotic therapy for these
infections. The activity and potential use of two old antimicrobials,
nitrofurantoin and
fosfomycin, and the new compound
tigecycline for treatment of
infections due to ESBL-producing Enterobacteriaceae, with special emphasis on E. coli, are reviewed.
Fosfomycin continues to be active against the most common uropathogens; in a recent survey from Spain, among the 428 ESBL-producing isolates, the resistance rate of E. coli to
fosfomycin was 0.3%, whereas the resistance rate of K. pneumoniae was 7.2%. Other recent surveys, from other parts of the world, confirm the activity of
fosfomycin against ESBL-producing E. coli. The rate of resistance to
nitrofurantoin in recent surveys in the USA and Canada was 1.1% among 1142 isolates of E. coli from outpatient urinary isolates. However, among 115 clinical isolates of E. coli ESBL producers, only 71.3% were sensitive to
nitrofurantoin. Also, E. coli resistance to
nitrofurantoin has been reported to be high in a recent survey in Latin American hospitals and in Italy.
Tigecycline is a
glycylcycline that circumvents efflux and ribosomal protection, the two most frequent genetic mechanisms of tetracycline resistance. The recent activity of
tigecycline against 285 nonclonally related isolates expressing well-characterised ESBLs from hospital settings and the community reveal susceptibility rates for
tigecycline of 97.5%. Because responses to
nitrofurantoin may be less satisfactory and may require longer courses of
therapy,
nitrofurantoin is considered to be an alternative, rather than a first-line, therapeutic agent for this clinical syndrome.
Fosfomycin trometamol is a safe and effective alternative for the treatment of
cystitis and asymptomatic UTI during pregnancy, and has become, in many countries, the first choice for treatment of any type of
cystitis. Finally, for treatment of systemic
infections in the hospital setting,
tigecycline could be an option that would reduce selection for ESBL-producing organisms.