Our study highlighted the myriad presentations and various manifestations of brucellosis, upon which treatment regimens might differ. Among patients with acute or sub-acute brucellosis, the combination of DOX-RIF was significantly associated with a favorable evolution of the disease, a lower risk of complications and side effects. Among sub-acute brucellosis cases, the combination of DOX-RIF-cotrimoxazole was significantly associated with a lower risk of death, while the combination of DOX-RIF-ciprofloxacin was significantly associated with a higher risk of relapse.

Brucellosis is a multisystem disease that might affect any organ. The revealing symptoms included fever (87%), fatigue (63%), arthralgia (62%) sweats (55%) and vomiting (26%) [1], which was similar to our results. The absence of fever might be explained by the undulant type of fever or the administration of non-steroidal anti-inflammatory drugs or antipyretics. In front of clinical suspicion of brucellosis, laboratory investigations should be ordered. Bacterial isolation is the gold standard. The sensitivity of blood cultures is high during the acute phase of brucellosis, while it is usually low during the sub-acute phase. Blood cultures offer the benefit of confirming the diagnosis even at en early stage of the disease when the infection is not clinically suspected, since brucellosis is known as the « great imitator » [6]. In the absence of a positive culture, the diagnosis relies on serological tests [7]. Although it does not provide direct evidence of the presence of the microorganism, serological tests remain an indispensable diagnostic tool for human brucellosis, especially in countries of endemicity [6].

The main goal of treatment is to shorten the duration of symptoms and to prevent complications, relapse, chronicity and mortality [8]. It is based on the administration of effective antibiotics, which have activity in vitro against Brucella species, for an adequate length of time. Complicated cases might require the addition of surgical treatment or/and corticosteroids [4]. Treatment of acute cases of brucellosis is based on a dual therapy due to the high relapse rate with monotherapy. The World Health Organization recommended the association of oral DOX (100 mg twice a day) and oral RIF (600 to 900 mg daily) for 6 weeks since 1986 [9]. This regimen is still prescribed by the most infectious diseases specialists not only because DOX-RIF is an all-oral regimen, but also because of the low price and the availability of rifampicin in all countries including the developing ones [10]. Several regimens were proposed including the association of DOX for 6 weeks and aminoglycosides : gentamicin for 7 to 10 days or streptomycin for 2 or 3 weeks (48), the combination of quinolones and RIF for 6 weeks and the combination of cotrimaxazole and RIF (especially for children and pregnant women) for 6 weeks [11]. A previous systematic review and meta-analysis concluded that the regimen combining DOX and streptomycin were superior to combined DOX-RIF in terms of both relapse rate and treatment failure. Also, no significant difference was noted with combined DOX-gentamicin and combined DOX-streptomycin [12]. An other study reported that the combination of cotrimoxazole-RIF among children with brucellosis showed failure and relapse rate that was not significantly different from the combination of DOX-RIF [9]. To conclude, among patients with acute brucellosis, the association of DOX and aminoglycosides was the preferred treatment with the lower rate of relapse and treatment failure. In our study, none of our patients received this combination and 94.3% of patients with acute brucellosis received DOX-RIF with a favourable evolution of the disease in 99.1% of the cases.

Regimens prescribed for sub-acute brucellosis cases varies according to the associated complications. As for osteoarticular brucellosis, the combination of DOX-RIF or DOX-streptomycin were the most prescribed regimens. The DOX-streptomycin combination was more effective but less tolerated because of the intramuscular injections [13, 14]. Due to its high bone penetration, ciprofloxacin was prescribed in association with RIF, and compared to DOX-streptomycin. No significant difference concerning clinical response was noted, but the cost of ciprofloxacin plus RIF therapy was higher [15]. In our study, DOX-RIF-ciprofloxacin was significantly associated with a higher risk of relapse.

The treatment of neurobrucellosis is not yet consensual. However, recent studies have recommended a therapeutic regimen based on the combination of 3 or even 4 antibiotics which have good central nervous system penetration [16, 17].  Erdem et al studied the efficacy and tolerance of a triple therapy containing ceftriaxone. Three groups including the combination of DOX-RIF-ceftriaxone, DOX-RIF- cotrimoxazole and DOX-RIF-Ceftriaxone relayed by DOX-RIF-cotrimoxazole on discontinuation of ceftriaxone. This study had shown that treatment regimens containing ceftriaxone were more effective with less treatment failure and fewer relapses compared to the DOX-RIF-cotrimoxazole regimen [18]. None of our patients received ceftriaxone for neurobrucellosis. However, the disease evolution was favorable in 91.6% of the cases of sub-acute brucellosis. According to the European Society of Cardiology guidelines, treatment of brucellar endocarditis is based on a combination of DOX-RIF-cotrimaxazole for ≥3-6 months [19]. However, other regimens were prescribed such as DOX-RIF-ceftriaxone, DOX-RIF-streptomycin, DOX-RIF- cotrimoxazole et DOX-streptomycin-ceftriaxone. The mortality rate was lower in patients receiving streptomycin [20].