Pivmecillinam--therapy of Choice for Lower Urinary Tract Infection

Pivmecillinam is the pro-drug of mecillinam, a beta-lactam antibiotic with a novel site of action and with specific and high activity against Gram-negative organisms such as Escherichia coli and other Enterobacteriaceae. Since its introduction, it has been widely used for the treatment of acute lower urinary tract infections (UTI), primarily in the Nordic countries. In contrast to the increasing resistance of urinary pathogens to other beta-lactams particularly ampicillin/amoxycillin and to other UTI antibiotics such as trimethoprim and trimethoprim/sulphamethoxazole (TMP/SMX), the level of resistance has remained on a low level. Less than 2% of E. coli community isolates are resistant to mecillinam. This paper reviews the clinical data on pivmecillinam with a special focus on the safety aspects. A large number of studies from the 70s to 80s have proven the clinical efficacy and safety of pivmecillinam for empirical treatment of acute cystitis. More recent studies confirm short-term treatment with pivmecillinam results in clinical and bacteriological cure rates similar to those obtained with other UTI agents. Both clinical studies in pregnant women with UTI and large epidemiological studies have confirmed the safety of pivmecillinam used in pregnancy. In the Nordic countries pivmecillinam has been the most widely used agent for treatment of UTI in pregnancy for many years. Ecological aspects of antibiotic treatment are important both with regard to adverse effects and development of resistance due to disturbance of the normal micro flora. Studies have shown that pivmecillinam has a very minor impact on the normal oropharyngeal, intestinal and skin microflora. The clinical implications of this are a low frequency of diarrhoea and Candida vaginitis as confirmed in the clinical studies. The high and increasing level of resistance among E. coli to currently recommended first-line agents for acute cystitis requires a re-evaluation of treatment guidelines. With the low resistance, its proven efficacy and favourable safety profile, pivmecillinam is a suitable first-line agent for empirical treatment of acute cystitis.