A Long-Term, Multicenter, Double-Blind Study of an Escherichia Coli Extract (OM-89) in Female Patients with Recurrent Urinary Tract Infections

Abstract

Objective:

To investigate the long-term preventive effect of the immunotherapeutic OM-89 versus placebo in uncomplicated recurrent UTI in a large cohort of female patients only.

Methods:

Adult female patients could enrol in this multicenter, double-blind study if they had acute UTI at the enrolment visit and positive results of urinalysis (≥10³ bacteria/ml). Patients received the immunotherapeutic OM-89 or a matching placebo; 1 capsule per day for 90 days, 3 months without treatment, then the first 10 days in Months 7, 8 and 9 and were followed up during 12 months. Primary efficacy criteria were UTI rates over 12 months, distribution of UTIs and proportion of patients with UTI.

Results:

A total of 453 patients were treated, 231 in the active group and 222 in the placebo group. Mean rate of post-baseline UTIs was significantly lower in the active group than in the placebo group (0.84 vs. 1.28; p < 0.003), corresponding to a 34% reduction of UTIs in patients treated with OM-89. In the active group, 93 patients (40.3%) had 185 post-baseline UTIs, compared to 276 UTIs in 122 patients (55.0%) in the placebo group (p = 0.001). The safety profile of OM-89 was good and consistent with that reported in previous studies.

Conclusions:

OM-89 significantly reduced the incidence of UTI during the 12 months of the study including 3 months of treatment and three 10-day booster courses. These results confirm that OM-89 is a valuable component of the management of recurrent UTI.

Introduction

Urinary tract infections (UTI) are commonly encountered in medical practice and range from asymptomatic bacteruria to debilitating acute pyelonephritis (for review see [1], [2]). They are especially problematic for women, up to one-third of whom will experience at least one UTI at some point during their lifetime, and are a major cause of morbidity in patients with neuropathic bladder dysfunction and catheterization [3], [4]. The predominant pathogen in both complicated and uncomplicated UTI is E. coli, although Klebsiella sp. and Proteus appear with increased frequency in complicated UTI, and the empiric use of antibiotics usually brings prompt positive results in the acute phase of infection [2], [5].

Recurrent UTI affect women of all ages [2], [6]. In a recent epidemiological study performed in the US, 10.8% percent of women aged 18 and older reported at least one presumed UTI during the past 12 months, with the majority of cases occurring among women with a history of two or more previous UTI episodes [7]. These episodes place a large burden on both the patient and healthcare resources; the annual cost of treating UTI in the US alone has been estimated to be $1.6 billion [7].

Low-dose antimicrobial regimens given daily or postcoitally can be effective in preventing recurrences in most women with a predisposition to frequent infection [8], but their use is limited by concerns of bacterial resistance, even for newer generation antibiotics [9], [10], and the potential for attenuation of host response [11]. An alternative approach is the oral administration of an immunotherapeutic agent that prevents recurrent UTI without the undesired effects of chronic antibiotic therapy.

OM-89 is a lyophilized extract of selected E. coli strains in a capsule formulation containing 6 mg of the bacterial extract. Experimental models have shown that it decreases mortality induced by E. coli, S. typhimurium, and P. aeruginosa [12] in animals, and has activity on macrophages and lymphocytes [13]. Clinical trials performed since 1980 have shown a statistically significant decrease of episodes of UTI in adult, pediatric, pregnant, postmenopausal, or paraplegic patients treated with OM-89 as compared to placebo or to previous reference period [14], [15], [16], [17], [18], [19], [20], [21].

The rationale for performing the present study was to investigate further the long-term preventive effect of this agent in uncomplicated recurrent UTI in a large cohort, comprising female patients only.