Quinolones for Treatment of Human Brucellosis: Critical Review of the Evidence from Microbiological and Clinical Studies

Brucellosis is a zoonotic disease with worldwide distribution that is endemic in the Mediterranean region, the Middle East, Central Asia, and parts of Africa and Latin America. Worldwide, brucellosis remains a major cause of morbidity in humans and domesticated animals. In animals, bovine brucellosis, caused mainly by Brucella abortus, is still the most widespread form. In humans, ovine/caprine brucellosis caused by Brucella melitensis is by far the most common type of disease. The disease has a wide spectrum of clinical manifestations and can affect a variety of organs and systems. Localized and complicated forms of brucellosis cause important morbidity and require prolonged medical treatment. Fortunately, mortality is relatively low and is related mainly to cardiovascular and central nervous system complications of the disease. Although several studies have been conducted over the past 2 decades, there is no conclusive evidence on the optimum antibiotic therapy for brucellosis. Disease relapse still represents one of the most important therapeutic problems. The last recommendation by the World Health Organization (WHO) for the treatment of acute brucellosis in adults was published in 1986 and suggested 600 to 900 mg rifampin and 200 mg doxycycline daily for a minimum of 6 weeks (8). Alternatively, the WHO suggested that rifampin could be replaced with 15 mg/kg of streptomycin, administered intramuscularly for only 2 weeks. However, a meta-analysis, as well as a prospective randomized trial, both performed by Solera et al., showed that the “good old” combination regimen of streptomycin with an oral tetracycline results in fewer relapses than the doxycycline-rifampin combination (57, 58). Controlled clinical trials with other antibiotics, including trimethoprim-sulfomethoxazole, new macrolides, and β-lactams, have shown inferior results or involved too few patients for a proper evaluation. Thus, the most widely used regimens are the two aforementioned combinations that were recommended by the WHO. In addition, rifampin monotherapy is the main option for brucellosis during pregnancy, whereas its combination with trimethoprim-sulfomethoxazole is the suggested treatment for childhood brucellosis (5, 34). Certain focal forms of brucellosis are difficult to treat, and surgery should be considered for patients with endocarditis or cerebral, epidural, splenic, or other abscesses (20, 41). Regarding medical treatment, although the antibiotics used are essentially the same, prolonged therapy, up to six or more months, may be needed for patients with osteoarticular forms of the disease, and especially spondylitis (18, 56, 65). Also, triple-antibiotic combinations were found to be of value in some case series of brucellar endocarditis, spondylitis, and meningitis (2, 41, 65). Relapse of the disease also represents a major therapeutic problem for its focal forms. Since the mid 1980s, laboratory researchers and clinicians have performed several microbiological and clinical studies of the possible use of quinolones in the treatment of human brucellosis. The activity against intracellular bacteria (23), reduced risk of nephrotoxicity, good pharmacokinetic characteristics, and lack of a requirement for drug level monitoring represent the main advantages of using quinolones in this setting. Moreover, the need for a regimen that would eliminate disease relapse further necessitated the use of quinolones. However, there is only one brief review focusing on the issue, published in 1992 (38). This study reviewed the available in vitro and clinical data at the time and examines the rationale, as well as the outcomes, of quinolone use for brucellosis.