Predictors of therapeutic failure among patients with acute brucellosis treated by dual therapy with doxycycline-rifampin Ahmad Farooq Alsayed Hasanain 1 , Muhammad Abbas El-Masry 2 , Ali Abdel-Azeem Hasan Zayed 3 , Amany Mohamed Adawi Nafee 4 , Rasha Abdel-Monem Hassan Attia 5 and Sherif Mohamed Abdel-Aal 6 1 Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Assiut University, Assiut, Egypt 2 Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt 3 Department of Chest Diseases, Faculty of Medicine, Assiut University, Assiut, Egypt 4 Department of Microbiology and Immunology, Faculty of Medicine, Assiut University, Assiut, Egypt 5 Department of Parasitology, Faculty of Medicine, Assiut University, Assiut, Egypt 6 Department of Diagnostic Radiology, Faculty of Medicine, Assiut University, Assiut, Egypt Abstract objective To determine the frequency of therapeutic failure among patients with acute and subacute brucellosis and to explore the predictors of failure. methods The study included 213 consecutive, na € ıve patients with acute and subacute brucellosis. All participants underwent clinical evaluation, chest radiography, stool microscopic examination and interferon-gamma release assay. Patients received the WHO-recommended therapy of doxycycline 200 mg/day and rifampin 900 mg/day, for 6 weeks. results Mean age of the study population was 39.8 Æ 12.2 years; 64.8% of them were males. The therapeutic failure rate was 16.4%. Adverse effects were reported by 13.1%. Multivariate analysis of factors associated with therapeutic failure revealed latent tuberculosis infection (LTBI) (OR 3.1, 95% CI, 1.9–24.6, P: 0.009), ascariasis (OR 2.6, 95% CI 1.5–17.9, P: 0.012), and the use of acid suppressive therapy (OR 2.1, 95% CI 1.2–19.5, P: 0.037) as the predictors of therapeutic failure. conclusions The prevalence of therapeutic failure among the Egyptian patients with acute/subacute brucellosis is increasing. Predictors of therapeutic failure are LTBI, ascariasis, and the use of acid suppressive therapy. keywords brucellosis, therapeutic failure, latent tuberculosis, ascariasis, doxycycline Introduction Brucellosis is the most common zoonotic infection. Glob- ally, more than 500 000 new cases occur annually [1]. The prevalence is highest in the countries of the Mediter- ranean Sea basin, hence it is also known as Mediter- ranean fever [2]. In Egypt, a seroprevalence rate of approximately 1.3% exists in Assiut governorate [3]. The control program for brucellosis in Egypt includes vaccina- tion of animals and slaughter of those infected (with posi- tive serologic results). Egypt has mixed populations of cattle, sheep, and goats. The most frequent Brucella spe- cies is Brucella abortus followed by Brucella melitensis [4, 5]. Infected domestic animals – mainly cattle, sheep, goats and swine – are the source of infection in humans. Infection can be acquired by humans through direct con- tact with diseased animals or by consumption of contam- inated animal products [6]. The presentation includes subclinical, acute and subacute, localised, relapsing and chronic forms [7]. The diagnosis of brucellosis is confirmed when compatible clinical manifestations are associated with at least a four-fold rise of Brucella anti- body titre between acute and convalescent sera obtained at least 14 days apart measured by standard agglutina- tion test (SAT). The diagnosis is probable when compati- ble clinical manifestations are associated with a single SAT antibody titre of at least 1:160 [8]. Monotherapies are characterised by high rates of relapse; therefore a combination therapy of two drugs is used. Doxycycline (200 mg daily) plus rifampin (600– 900 mg daily) for 6 weeks is the standard-of-care therapy [9], which has a rate of 11–17% of therapeutic failure [10]. Doxycycline is absorbed in the proximal duodenum after being solubilised by gastric acidity [11]. Brucella isolates are considered susceptible to the WHO-recom- mended therapy which includes doxycycline and rifam- pin; only sporadic cases of antibiotic resistance were reported [12, 13]. After infection with Brucella, the first line of defense is phagocytosis by cells (neutrophils, macrophages and © 2018 John Wiley & Sons Ltd 185 Tropical Medicine and International Health doi:10.1111/tmi.13179 volume 24 no 2 pp 185–191 february 2019