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Objective: The purpose of this study was to determine the clinical value of triple antibiotic therapy consisting of doxycycline, compound sulfamethoxazole and rifampicin in the treatment of brucellosis spondylitis., Methods: A retrospective analysis was performed on 100 patients with brucellosis spondylitis admitted to the First Affiliated Hospital of Hebei North University from March 2016 to June 2019. Patients were divided into the following two groups: the control group (n = 50) treated with dual antibiotic therapy (rifampicin + compound sulfamethoxazole), and the observation group (n = 50) treated with triple antibiotic therapy (rifampicin + doxycycline + compound sulfamethoxazole). The treatment effect, low back pain relief, levels of erythrocyte sedimentation rate (ESR), procalcitonin (PCT) and C-reactive protein (CRP), as well as the adverse reactions were compared between the two groups., Results: The response rate of the observation group was significantly higher than that of the control group ( P < 0.05). Before treatment, there was no significant difference in the low back pain assessed by the visual analogue scale (VAS), or levels of ESR, PCT and CRP between the two groups ( P > 0.05). But after treatment, the VAS score and the levels of ESR, PCT and CRP in observation group were lower than those in the control group ( P < 0.05). No significant difference was found in the incidence of adverse reactions ( P > 0.05)., Conclusion: The triple antibiotic therapy of doxycycline, compound sulfamethoxazole and rifampicin is effective in the treatment of brucellosis spondylitis. It can significantly alleviate patients' back pain and inflammation with a high safety profile, which is worthy of clinical application., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Yang et al.)

Tuberculosis (TB) can manifest prolonged fever or fever of unknown origin, especially when it is located extrapulmonary. We report a case of disseminated TB complicated by iliac bone osteolysis and a gluteal abscess in a 75-year-old female patient with fever and bone marrow dysplasia. Diagnosis of TB was made despite transient false-positive high-titer agglutination tests and ELISA antibodies to Brucella. The case presented shows that in a highly suggestive case of TB, positive agglutination tests or ELISA antibodies to Brucella should be interpreted with caution, and repeated testing should be performed to assess their persistence and fluctuation over time.

Brucellosis is a zoonosis seen all over the world and is still endemic in certain parts of the world. Brucellosis is a systemic infection which involves multiple organs and tissues. Although musculoskeletal system involvement is frequent in brucellosis, bursal involvement is seen rarely. In this article, we present a case of subacromial and subdeltoid brucellar bursitis with positive serology and aspiration culture. Patient achieved complete recovery with rifampicin and doxycycline treatment, without any evidence of relapse. A high clinical suspicion is required for the diagnosis of brucellar bursitis.

Background: Brucellosis is one of the most important infection of diseases. Due to its large period of treatment and survival ability of bacteria inside the macrophages, relapse of this disease is the main challenge, especially, after the treatment., Objective: The current study was carried out to evaluate the antibacterial effect of solid lipid nanoparticles loaded with doxycycline on the Brucella melitensis in in vivo conditions., Methods: The double emulsion synthesized doxycycline-encapsulated solid lipid nanoparticles (DOX-SLN) was characterized using DLS and FE-SEM. The efficacy of the DOX-SLN on the acute and chronic Wistar rat infected brucellosis was investigated. The pathological assessments were made on the spleen and liver in the treated rates., Results: The in vivo experimental results demonstrated that the treated rats with DOX-SLN had significantly decreased the B. melitensis CFUs in their spleen and liver compared to that of the treated rates with free doxycycline and untreated ones. The pathologic results indicate that the improvement trend of spleen and liver tissues in rats treated by DOX-SLN was satisfactory., Conclusion: According to in vivo results, the DOX-SLN has better effects on the treatment of chronic brucellosis. Therefore, DOX-SLN is recommended to treat the brucellosis and avoid its relapse.

To explore how to diagnose and treat brucellosis accurately and timely in patients with fever of unkown origin in non-pastoral areas. The epidemiological history, clinical symptoms, complete blood counts, procalcitonin and treatment efficacy of 7 patients with brucellosis were analyzed retrospectively. Some characteristic manifestations should be differentiated from tuberculosis. The clinical symptoms were relieved after combination of doxycycline, rifampicin, levofloxacin and amikacin for 6 weeks, only one patient with bone destruction needed orthopedic surgery. The overall response rate was 6/7. No relapse occurred during half year follow-up.

Introduction: Because of its infrequent and the lack of clinical data and image finding, the management of acute infections with the hepatosplenic brucella abscesses is challenging., Methods: There were 10 serologically diagnosed cases with this brucella infection. All patients had fever, 50% patients had upper abdominal pain. Ninety percent patients lived in an urban environment. The localization of lesions included: 30% hepatosplenic, 30% liver, and 40% spleen., Results: Abdominal computed tomography (CT) scans and magnetic resonance imaging (MRI) demonstrated hepatosplenomegaly, with multiple small abscess lesions of various sizes in the acute stage of brucellosis, with the largest diameter of 1.5 cm in the liver. After contrast-enhanced CT and MRI findings, the arterial phase in which the enhancing area of lesions was thick, revealed multifocal hypodense or hypointense lesions of various sizes. These lesions manifested distinct boundary, which was intensified obviously in portal venous phase., Conclusion: Our results indicate that early CT or MRI dynamic contrast enhancement of suspected cases could improve rapid diagnosis. However, diagnostic criteria remain problematic and diagnosis is mostly based on a combination of clinical suspicion, serologic markers, and radiologic findings.

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, naïve 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 ± 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., (© 2018 John Wiley & Sons Ltd.)

New therapies are needed to treat chronic bacterial diseases and intracellular pathogens, in particular, are very difficult to manage. The use of nanotherapeutics represents an approach to exploit size and charge of biological membranes to overcome barriers for treatment of intracellular pathogens including Brucella melitensis. In this work, polyanhydride nanoparticles comprised of copolymers of sebacic acid, 1,6-bis(p-carboxyphenoxy)hexane, and 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane were synthesized to encapsulate antimicrobial compounds doxycycline and rifampicin. The nanoparticles demonstrated sustained release of rifampicin for a week with the antimicrobial activity peaking at 72 h and lasting up to a week. Treatment of B. melitensis infected macrophages with rifampicin-containing nanoparticles rapidly eliminated viable intracellular bacteria following 48 h of treatment and pretreatment with the nano-formulations prevented intracellular infection in contrast to soluble drug controls. Treatment of infected BALB/c mice with a nanoparticle cocktail containing doxycycline and rifampicin for five days decreased bacterial burden by three log 10 in the liver. Extended release of antibiotics was demonstrated in vivo by treating B. melitensis infected mice with the standard therapy of daily 0.5 mg doxycycline dose or single 0.5 mg doxycycline-encapsulated nanoparticles delivered once a week. After 3 weeks, bacterial counts in spleen and liver were statistically equal between animals treated with the weekly nano-formulation and daily soluble drug, representing a seven-fold dose sparing. Altogether, these results demonstrated that the use of nanotherapeutics was successful at increasing antimicrobial efficacy and improving in vivo activity through a combination of intracellular delivery, dose sparing, and extended release in treating chronic bacterial infections. This platform technology can also provide benefits for drug delivery against other chronic intracellular bacterial pathogens, including Mycobacterium and Burkholderia species, including treatments against antibiotic-resistant infections., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Human brucellosis, one of the most common zoonoses worldwide, rarely occurs in Japan, and only a few chronic cases have been reported. We herein report the case of a 39-year-old Japanese woman with chronic human brucellosis, considered a Brucella canis infection, that persisted for 19 years. Her medical history and fever pattern suggested chronic brucellosis, and the diagnosis was made based on the results of a serum tube agglutination test (SAT). After undergoing combination therapy with streptomycin and doxycycline, she achieved symptomatic relief and showed negative SAT results. Even in non-endemic areas, chronic brucellosis is an important differential diagnosis in patients with long-term persistent fatigue or a fever.

Background: Brucellosis is one of the neglected zoonotic diseases in humans. The serological methods based on antibody detections are unable to detect the effectiveness of treatment in humans as antibodies persist for long time in humans even after therapy. Therefore, we developed qPCR technique to overcome such discrepancy and device a rapid and efficient test for both diagnosis and follow up of the brucellosis affected individuals., Methods: High risk suspected individuals with positive serology (RBPT, STAT and iELISA) and PCR were mainly analyzed for DNA quantification by qPCR assay. The bcsp-31 gene, a shared gene of Brucella species was amplified by genus specific primers and cloned to pGEMT™ easy vector and the cloned plasmid were used to construct a standard curve (R 2 =0.99, efficiency=1.98) over 7 orders of magnitude with sensitivity of ≈10 copy number. The assay was found 100% specific., Results: Overall 85 individuals were found positive out of 188. Out of them, 23 serological, PCR and qPCR positive individuals were recommended for 45days therapy according to WHO regimen (Doxycycline and Rifampin) and each case was further followed by qPCR. The mean threshold cycle (C q ) before treatment was 26.05±0.347 (3940.5copies/μl), which increased significantly to 32.7±0.66 (259.13copies/μl) on 4th week during treatment, 35.12±3.12 (38.52copies/μl) at 6th week on day of treatment completion, 35.6±0.66 (34.21copies/μl) on 21st day after treatment depicting a significant reduction in DNA load over the course of treatment. Serological follow up showed that only 3 individuals had decreased STAT titre but no change in RBPT results. Out of 17 symptomatic individuals under therapy, 10 improved clinically, 5 improved clinically with persistent weakness and 2 had no effect of therapy., Conclusion: The study suggests that qPCR is more useful and rapid test to follow treated individuals than serology., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brucellosis is associated with a high recurrence rate and requires more than one course of standard treatment; therefore, more research is required to find more effective treatments that lead to prompt recovery, and reduce the relapse of disease. This single-blind, randomized study was designed to evaluate the effect of the standard treatment for brucellosis in combination with hydroxychloroquine. A total of 177 patients with acute brucellosis were randomly assigned to one of two treatment groups: doxycycline-streptomycin (DS) and doxycycline-streptomycin-hydroxychloroquine (DSH). Clinical symptoms and signs, serological tests, and side effects of therapy were compared between the two groups during the treatment course and at three and six months after the end of drug therapy. Of the 177 patients, with a mean age of 40.5 ± 16.9 years, 66.1% were males. The mean duration of clinical signs prior to admission was 43.4 ± 41.1 days. Appropriate clinical responses, relapse, treatment failure, and adverse drug reactions were seen in 98.9%, 1.2%, 0.0%, and 12.6% of patients, respectively, in the DSH group vs. 86.7%, 11.6%, 2.3%, and 19.8% of patients, respectively, in the DS group. There were significant differences in clinical response and relapse rates between the two groups. The addition of hydroxychloroquine to a doxycycline-streptomycin regimen appears to increase the efficacy of treatment, accelerate improvement of clinical symptoms, and significantly reduce the rate of relapse of brucellosis., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background & Objectives: Brucellosis can lead to haematological abnormalities including cytopenia confusing with haematological malignancies. The aim of this study was to compare the main characteristics of brucellosis patients without cytopenia (Group 1) and with cytopenia (Group 2)., Methods: This five-year period study which was performed in two referral hospitals in Turkey, included all adult brucellosis patients. Abnormally, low counts of leucocyte or haemoglobin or platelets in a patient were considered as cytopenia. The demographics, clinical, laboratory, treatment and outcome data were analyzed., Results: A total of 484 brucellosis patients were enrolled. Among the cases, 162 (33.5%) of them had cytopenia. One hundred and four (21.5%) had anaemia, 88 (18.8%) had thrombocytopenia, 71 (14.6%) had leucopenia and 28 (5.8%) had pancytopenia. The mean age of group 2 was 35.01±16.05 yr and it was 33.31±14.39 yr in group 1. While there was no difference between the groups in terms of duration of treatment, the median length of hospital stay (LOS) was significantly longer in group 2 (9 vs 10 days; P<0.001). The most frequently applied combination therapy consisted of doxycycline plus rifampicin and doxycycline plus streptomycin regimens. No significant difference was observed in terms of duration of treatment, LOS and restoration time of cytopenia between the patients who received either of these combinations., Interpretation & Conclusions: Our findings suggested that the patients with cytopenia should be investigated for brucellosis, especially if living in, or with a history of travel to, endemic areas, in view of the increase in world travel., Competing Interests: None

Introduction: Brucellosis is a zoonosis caused by Brucella spp. It may be acquired by consuming unpasteurized dairy products. Brucellosis has a low incidence in Chile, thus, we have a scarce data., Aim: To report and to characterize the first series of clinical cases of adult patients diagnosed with brucellosis in Chile., Methods: We describe a series of 13 clinical cases in patients diagnosed between 2000 and 2016 in three different centers in the Metropolitan Region, Chile. A retrospective analysis was performed on clinical presentation, laboratory, antibiotic treatment, morbidity and mortality., Results: The mean age was 50 years old. Eight cases had a record of consumption of unpasteurized dairy products. The most frequently reported complaints were fever. The most frequent focal point involved was the spine. Only one patient had a positive blood culture, while the diagnosis was made using serological techniques in the other part of the group. The most indicated antibiotic regimens were doxycycline-rifampicin and doxycycline-gentamicin. The hospital stay was 20 days approximately as an average. Clinical cure was achieved in all cases., Conclusions: Brucellosis is an infrequent zoonosis in Chile, and it produces a nonspecific clinical picture, so it is necessary to have high suspicion to make the diagnosis based in the antecedent of consumption of unpasteurized dairy or raw meat.

Background: This study aims to analyze the clinical characteristics and treatment outcomes of 590 patients with brucellosis in Xinjiang, China., Methodology and Principal Findings: The clinical characteristics, laboratory findings, complications and prognosis of 590 patients infected with brucellosis were retrospectively analyzed. These patients had a mean age of 44.24 ± 15.83 years with 60.5% having a history of close contacting with cattle and sheep. Of them, 53.6% (316 /590) were in acute phase and 21.5% were in chronic phase. Agglutination test showed 98.5% positive with 34% blood culture positive of Brucella. The major symptoms were fatigue (91%), hyperhidrosis(88.1%), fever(86.9%), and joint pain(81%) with 29.8% having enlarged liver, 26.1% having enlarged spleen and 23.2% having osteoarticular complications. Combination of doxycycline plus rifampicin for 12 weeks was an effective regimen for patients without complications. The 3-drug regimen (doxycycline+rifampicin+levofloxacin) for 12 weeks was recommended for these with complications. There were 6 patients died (1.02%) with overall relapse rate of 5.98%., Conclusions: Brucellosis is mostly associated with contacting with domestic animal production in Xinjiang, China. Clinical symptoms include fever, fatigue, hyperhidrosis, and joint pain with common complication of osteoarticular involvement. Three-drug-regimen of doxycycline+rifampicin+levofloxacin for 12 weeks was effective for these patients with complications.

Introduction: This study aimed to identify a follow-up modality that can be used to evaluate therapeutic responses in patients receiving treatment for brucellar sacroillitis and to determine whether antibiotherapy can be stopped., Methodology: A total of 32 patients with sacroiliac joint involvement demonstrated via magnetic resonance imaging or bone scintigraphy were followed up and treated. Patients received 200 mg/day of doxycycline and 600-900 mg/day of rifampicin for 3-21 months, and 1 g/day of streptomycin for 21 days., Results: The mean age of the 32 patients involved was 21.81±4.09. In total, 10/32 patients did not complete therapy, and the remaining 22 patients received combination antibiotic treatment for a mean of 8.95±4.34 months. Of the 22 patients, 15 underwent MRI, and 7 of them did not consent to MRI. Similarly, 17 patients were followed up by bone scintigraphy, and 5 patients did not have scintigraphy results. In 9/17 patients followed up with bone scintigraphy, sacroiliitis findings were found to reduce after a mean of 7.44±3.71 months, whereas in 12/15 patients on whom MRI was performed,  there were no active sacroiliitis findings for a mean of 6.95±2.83 months., Conclusions: While active involvement findings in bone scintigraphy were observed for a longer period in scintigraphy images, active sacroiliitis findings disappeared in a relatively shorter period of time with MRI. Therefore, we have demonstrated that high-resolution MRI is a very sensitive technique compared to scintigraphy.

A teenage woman migrating from Syria arrived in May 2015 in Germany. She gave birth to a healthy child in early 2016, but became febrile shortly after delivery. Blood cultures revealed Brucella melitensis. In retrospect, she reported contact with sheep in Syria and recurrent pain in the hip joints over about five months before diagnosis of brucellosis. We discuss consequences for adequate treatment of mother and child as well as for clinical and laboratory management., Competing Interests: Conflicts of Interest: None declared., (This article is copyright of The Authors, 2016.)

Aim: The aim of this study was to compare both the efficacy and safety profile of the WHO-recommended, dual therapy (doxycycline-rifampin) to a quinolone-based, triple therapy (doxycycline-rifampin-levofloxacin) for treating acute/subacute brucellosis., Patients and Methods: We studied 107 consecutive, naïve patients with acute/subacute brucellosis admitted to Assiut University Hospital. Patients were randomly allocated to receive the dual therapy of doxycycline-rifampin (group-A) or to receive the triple therapy of doxycycline-rifampin-levofloxacin (group-B). Acute/subacute brucellosis was diagnosed based on the presence of: (1) contact with animals or fresh animal products, (2) suggestive clinical manifestations of less than one-year duration, and (3) positive antibody titer (1:160) by standard tube agglutination test., Results: There was no significant difference between the two groups regarding their demographic data. Fever was the most frequent manifestation (96.3%). Epigastric pain was the most frequent adverse effect of treatment (12.1%). Group-A patients had a significantly higher relapse rate compared to group-B patients (22.6% versus 9.3%, p-value=0.01). The rate of treatment adverse effects was higher among group-B patients, although not reaching statistical significance (20.4% versus 11.3%, p-value=0.059)., Conclusions: Adding levofloxacin to the dual therapy for acute/subacute brucellosis (doxycycline-rifampin) may increase its efficacy in terms of lowering the relapse rate of the disease. Further, larger scale studies are needed before considering modifying the standard, dual therapy for brucellosis., (Copyright © 2016 Elsevier Editora Ltda. All rights reserved.)

We present a 51-year-old male patient with Brucella abortus septic arthritis in the right knee following arthroscopic meniscus surgery. He had eaten a traditional dish of raw minced cattle conceptus (bovine fetus) that was prepared after the cow was slaughtered. Despite treatment with empirical antibiotics and debridement of the postoperative surgical wound, the infection persisted without improvement. Polymerase chain reaction sequencing identified Brucella abortus from tissue samples obtained from the patient. After confirmation of the diagnosis of brucellar infection, antibiotics were replaced with doxycycline and rifampin, which were used for 4 months. In patients with a non-specific arthralgia who eat raw meat or live close to animals, it is important to consider the possibility of septic arthritis due to infection with Brucella spp.

Brucellosis is a common zoonotic disease with worldwide distribution and protean clinical manifestations. Therefore, its prompt and timely diagnosis is still challenging. Among several complications of brucellosis, spontaneous bacterial peritonitis (SBP) in previously healthy participants is rarely recognised, although this condition can be fatal if misdiagnosed and untreated. We present a case of a 69-year-old previously healthy stockbreeder who suffered from back pain along with abdominal pain and distension because of ascites of 6-8 weeks duration. Cultures of ascitic fluid and peripheral blood specimens revealed Brucella spp as the causative agent of ascites and spondylodiscitis, which was then confirmed by MRI findings. After appropriate treatment for 4.5 months (streptomycin 1 g/day for 3 weeks intramuscularly, doxycycline 100 mg twice a day orally and rifampicin 900 mg/day orally), the patient fully recovered. Conclusively, in the appropriate epidemiological and clinical setting, the consideration of brucellosis in the differential diagnosis of SBP could be rational as well as life-saving., (2015 BMJ Publishing Group Ltd.)

Infection of total knee or hip arthroplasty by Brucella species is a rare complication. We describe the case of a failed hip replacement secondary to infection by Brucella abortus, as well as presentation, treatment course, and 2-year follow-up. In addition, we review the literature for features of periprosthetic Brucella species infections, and we describe the common exposures, clinical presentations, preoperative evaluation, and treatments used in the reported cases. Furthermore, we discuss the risk of transmission to operating room personnel and the appropriate preventative measures to avoid transmission.

Isolated case reports of peritonitis due to Brucella spp. during peritoneal dialysis (PD) continue to surface in the medical literature. However, the optimal treatment regimen for these patients, in particular with regards to the fate of PD catheter, is still largely unknown. We report a case of brucella peritonitis successfully treated with intraperitoneal administration of amikacin, along with oral rifampicin and doxycycline but without catheter removal. Furthermore, we have reviewed the literature up until present day.

We evaluated the efficacy and tolerability of antibiotic regimens and optimal duration of therapy in complicated and uncomplicated forms of spinal brucellosis. This is a multicentre, retrospective and comparative study involving a total of 293 patients with spinal brucellosis from 19 health institutions. Comparison of complicated and uncomplicated spinal brucellosis was statistically analysed. Complicated spinal brucellosis was diagnosed in 78 (26.6%) of our patients. Clinical presentation was found to be significantly more acute, with fever and weight loss, in patients in the complicated group. They had significantly higher leukocyte and platelet counts, erythrocyte sedimentation rates and C-reactive protein levels, and lower haemoglobulin levels. The involvement of the thoracic spine was significantly more frequent in complicated cases. Spondylodiscitis was complicated, with paravertebral abscess in 38 (13.0%), prevertebral abscess in 13 (4.4%), epidural abscess in 30 (10.2%), psoas abscess in 10 (3.4%) and radiculitis in 8 (2.7%) patients. The five major combination regimens were: doxycycline 200 mg/day, rifampicin 600 mg/day and streptomycin 1 g/day; doxycycline 200 mg/day, rifampicin 600 mg/day and gentamicin 5 mg/kg; doxycycline 200 mg/day and rifampicin 600 mg/day; doxycycline 200 mg/day and streptomycin 1 g/day; and doxycycline 200 mg/day, rifampicin 600 mg/day and ciprofloxacin 1 g/day. There were no significant therapeutic differences between these antibiotic groups; the results were similar regarding the complicated and uncomplicated groups. Patients were mostly treated with doxycycline and rifampicin with or without an aminoglycoside. In the former subgroup, complicated cases received antibiotics for a longer duration than uncomplicated cases. Early recognition of complicated cases is critical in preventing devastating complications. Antimicrobial treatment should be prolonged in complicated spinal brucellosis in particular., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Brucellosis is a zoonotic disease caused by a Gram-negative coccobacillus from the Brucella genus. The disease has a broad spectrum of clinical manifestations. The musculoskeletal system involvement is frequent and, rarely, arthritis can be the only clinical feature of the disease. We report a case of monoarthritis caused by Brucella melitensis.

We present a 23-year-old woman who was admitted due to fever, palpitation, musculoskeletal pain and a transient bout of sudden-onset left-sided hemiparesis. She had also myopericarditis according to echocardiography findings. After comprehensive diagnostic work-up for infectious and immunologic disorders, brucellosis was confirmed by bone marrow aspiration culture. She received doxycycline, rifampin and trimethoprim-sulfamethoxazole for 3 months. The treatment was continued with doxycycline and rifampin for another 6 months. By the end of treatment, she recovered completely with no evidence of persistent neurological or cardiac complications.

Brucellosis, a zoonotic infection caused by the genus Brucellae, is an ancient condition linked to the consumption of milk and milk products. The disease has global importance due to its impact. Therapeutic options for brucellosis rely mostly on uncontrolled, nonrandomized, non-blinded studies. The choice and duration of therapy are related to patient characteristics and the presence of a focal disease. The usual therapy of acute brucellosis is a combination of doxycycline plus rifampicin for 6 weeks. An aminoglycoside could be substituted for rifampin for the initial week of combination therapy. Other alternatives include a combination of doxycycline plus trimethoprim-sulfamethoxazole, or a fluoroquinolone plus rifampicin. The presence of spondylitis or endocarditis usually indicates that the required treatment will be of a longer duration or a combination of therapy. The article has the discussion of some recent patents related to antibiotic susceptibility and Brucellosis.

On February 10, 2012, the Maine Center for Disease Control and Prevention (Maine CDC) was notified of a positive Brucella culture from a harbor porpoise (Phocoena phocoena) found on the coast of southern Maine. Maine CDC, in consultation with CDC, initiated an investigation of potential occupational exposures of staff members at university A and at diagnostic laboratories known to have handled samples from the porpoise. This report describes the results of that investigation. In humans, brucellosis can cause fever, sweats, headaches, back pains, physical weakness, and sometimes severe infections of the brain, bone, heart, liver, or spleen. Because staff members at university A did not use respiratory protection while handling the porpoise or its specimens, the four exposed staff members were advised to begin immediately a 3-week regimen of rifampicin and doxycycline for antimicrobial prophylaxis, conduct daily fever checks, be monitored for symptoms of acute febrile illness weekly, and have their serum tested for Brucella antibodies immediately and at regular intervals for 24 weeks after the last known exposure. As of June 26, none of the four persons had seroconverted or become ill. The potential for human infection and illness as well as the intensity, duration, and expense of the follow-up recommended for Brucella exposure highlights the need for facilities to develop standard protocols for preventing exposures during the handling of marine mammals, particularly during aerosol-generating procedures.

No data on whether brucellar meningitis or meningoencephalitis can be treated with oral antibiotics or whether an intravenous extended-spectrum cephalosporin, namely, ceftriaxone, which does not accumulate in phagocytes, should be added to the regimen exist in the literature. The aim of a study conducted in Istanbul, Turkey, was to compare the efficacy and tolerability of ceftriaxone-based antibiotic treatment regimens with those of an oral treatment protocol in patients with these conditions. This retrospective study enrolled 215 adult patients in 28 health care institutions from four different countries. The first protocol (P1) comprised ceftriaxone, rifampin, and doxycycline. The second protocol (P2) consisted of trimethoprim-sulfamethoxazole, rifampin, and doxycycline. In the third protocol (P3), the patients started with P1 and transferred to P2 when ceftriaxone was stopped. The treatment period was shorter with the regimens which included ceftriaxone (4.40 ± 2.47 months in P1, 6.52 ± 4.15 months in P2, and 5.18 ± 2.27 months in P3) (P = 0.002). In seven patients, therapy was modified due to antibiotic side effects. When these cases were excluded, therapeutic failure did not differ significantly between ceftriaxone-based regimens (n = 5/166, 3.0%) and the oral therapy (n = 4/42, 9.5%) (P = 0.084). The efficacy of the ceftriaxone-based regimens was found to be better (n = 6/166 [3.6%] versus n = 6/42 [14.3%]; P = 0.017) when a composite negative outcome (CNO; relapse plus therapeutic failure) was considered. Accordingly, CNO was greatest in P2 (14.3%, n = 6/42) compared to P1 (2.6%, n = 3/117) and P3 (6.1%, n = 3/49) (P = 0.020). Seemingly, ceftriaxone-based regimens are more successful and require shorter therapy than the oral treatment protocol.

A male patient of 32 years was referred for surgical drainage and orchidectomy of the right testis following a cycling injury. A Venereal Disease Research Laboratory (VDRL) test was requested by the surgery department to rule out secondary syphilis. Although serum samples gave a negative result in the VDRL test, qualitative screening was performed for Brucella antibodies, as per hospital policy, since brucellosis is endemic in this region. Following a positive reaction, a quantitative standard tube agglutination test was carried out yielding titres that were exceptionally high (STAT = 40 960 IU ml(-1); 2-ME = 1 : 5120). This finding correlated with the patient's history which included a number of predisposing factors for contracting brucellosis including exposure to cattle, consumption of raw milk and assisting in the parturition of cattle. Consequently, surgery was postponed and treatment was changed from injections of ceftriaxone to the WHO regimen for the treatment of brucellosis: 1 g streptomycin once daily, administered intra-muscularly, plus 100 mg doxycycline twice daily, taken orally. Following 3 days of this treatment, the testicular swelling reduced considerably and orchidectomy was not required. Indeed, after a week, swelling was completely resolved and the patient was discharged. To our knowledge, this is the first case of such high titres in a patient as a result of epididymo-orchitis without the typical clinical presentation of fever and joint pain that is normally associated with brucellosis.

A 49-year-old man was admitted to the hospital with complaints of fatigue, epistaxis and a skin rash. The whole blood count revealed isolated thrombocytopenia (4,000/mL), and the patient was admitted to the hematology department with a diagnosis of immune thrombocytopenia. He did not respond to steroid treatment for 15 days, and a subfebrile fever developed during this period. A diagnosis of acute brucellosis was considered due to positive serological tests and a blood culture positive for Brucella spp. After starting doxycycline and rifampicin therapy, the patient's thrombocyte count increased to 15,000/mL on the third day, to 41,000/mL on the sixth day and was normal on the 21st day of treatment. A diagnosis of brucellosis must be considered in patients presenting with severe and isolated thrombocytopenia in countries where brucellosis is endemic.

Background: Brucellosis is a persistent health problem in many developing countries throughout the world, and the search for simple and effective treatment continues to be of great importance., Methods and Findings: A search was conducted in MEDLINE and in the Cochrane Central Register of Controlled Trials (CENTRAL). Clinical trials published from 1985 to present that assess different antimicrobial regimens in cases of documented acute uncomplicated human brucellosis were included. The primary outcomes were relapse, therapeutic failure, combined variable of relapse and therapeutic failure, and adverse effect rates. A meta-analysis with a fixed effect model was performed and odds ratio with 95% confidence intervals were calculated. A random effect model was used when significant heterogeneity between studies was verified. Comparison of combined doxycycline and rifampicin with a combination of doxycycline and streptomycin favors the latter regimen (OR = 3.17; CI95% = 2.05-4.91). There were no significant differences between combined doxycycline-streptomycin and combined doxycycline-gentamicin (OR = 1.89; CI95% = 0.81-4.39). Treatment with rifampicin and quinolones was similar to combined doxycycline-rifampicin (OR = 1.23; CI95% = 0.63-2.40). Only one study assessed triple therapy with aminoglycoside-doxycycline-rifampicin and only included patients with uncomplicated brucellosis. Thus this approach cannot be considered the therapy of choice until further studies have been performed. Combined doxycycline/co-trimoxazole or doxycycline monotherapy could represent a cost-effective alternative in certain patient groups, and further studies are needed in the future., Conclusions: Although the preferred treatment in uncomplicated human brucellosis is doxycycline-aminoglycoside combination, other treatments based on oral regimens or monotherapy should not be rejected until they are better studied. Triple therapy should not be considered the current treatment of choice.

Background: We investigated the seroprevalence of human brucellosis and risk factors in a village in Eastern Anatolia, Turkey, where a brucellosis outbreak among cattle had recently occurred., Patients and Methods: All 501 inhabitants enrolled were screened with the Rose Bengal Test and were asked to fill out a questionnaire to determine the signs and symptoms of brucellosis and the risk factors. Patients' laboratory findings and clinical responses were also evaluated., Results: The Rose Bengal Test was positive in 44 persons. In comparison of age groups, fever (20.2%), arthralgia (19.2%) and weight loss (8.4%) were frequently seen in children (p<0.05). Hepatomegaly (17.9%) was also prevalent in the age group of 0 to 14 years (p<0.05). The consumption of dairy products, a family history of brucellosis, and raising livestock were significantly related to seropositivity (p<0.05). Rifampicin plus doxycyline was the most common regimen administered in these cases (54.5%) and also had the highest relapse rate (p<0.05)., Conclusion: Brucellosis remains an important public-health problem in the rural areas of Turkey. Appropriate public health measures and education must be pursued to eradicate human brucellosis.

We present the case of a 42-year-old male patient who applied to the emergency department of our hospital with clinical nephritis, orchitis, acute renal failure without endocarditis, and a low-grade fever. Brucella agglutinin titers were 1:160, Rose Bengal test was positive and Brucella melitensis was isolated from urine and blood cultures.. A combination of oral rifampin (600 mg/day) and doxycycline (200 mg/day) was administered along with supportive treatment leading to resolution of his clinical status by eight weeks. This was a rare complication of severe renal involvement due to brucellosis which resolved with antibiotic treatment.

Brucellosis is a worldwide zoonosis with a huge economic impact on animal husbandry and public health. The diagnosis of human brucellosis can be protracted because the disease primarily presents as fever of unknown origin with unspecific clinical signs and symptoms. The isolation rate of the fastidious etiologic agent from blood cultures is low, and therefore laboratory diagnosis is mainly based on serologic and molecular testing. However, seronegative brucellosis patients have been described, and antibody titers of diagnostic significance are difficult to define. Whether the molecular detection of Brucella DNA in clinical samples should be followed by long-term antibiotic treatment or not is also a matter of debate. The aim of this article is to review and discuss the implications of laboratory test results in the diagnosis of human brucellosis on disease therapy.

Objectives: To compare the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks with streptomycin for 2 weeks plus doxycycline for 45 days in the treatment of human brucellosis., Methods: In each arm of the study, 82 patients older than 10 years randomly received 5 mg/kg gentamicin once daily for 5 days plus 100 mg of doxycycline twice daily for 8 weeks or 1 g of streptomycin intramuscularly for 2 weeks plus the same dose of doxycycline for 45 days. Therapeutic failure and relapse in these two treatment groups were compared. This study was registered in the Iranian Registry of Clinical Trials (www.irct.ir) with registration number ID: IRCT138708191441N1., Results: The clinical manifestations in these two groups were similar. Therapeutic failure was seen in two (2.4%) patients in the gentamicin/doxycycline group and in four (4.9%) patients in the streptomycin/doxycycline group [relative risk (RR) = 0.5, 95% confidence interval (CI) 0.09-2.66, P = 0.68]. Relapse was seen in two (2.4%) cases in the gentamicin/doxycycline group and in five (6.1%) cases in the streptomycin/doxycycline group (RR = 0.4, 95% CI 0.08-2, P = 0.44). The efficacy with the gentamicin/doxycycline regimen was 95.12% and that with the streptomycin/doxycycline regimen was 89% (RR = 1.07, 95% CI 0.98-1.17, P = 0.25). Cox regression analyses showed no differences among the two treatment groups for patients who had relapse or therapeutic failure and those who had not regarding baseline covariates such as sex, duration of disease before diagnosis, positive blood culture and focal disease., Conclusions: The results show that the efficacy of gentamicin for 5 days plus doxycycline for 8 weeks is not superior to that of streptomycin for 2 weeks plus doxycycline for 45 days.

Objective: Due to its high morbidity rates brucellosis, a systemic inflammatory disease, is still an important health problem, particularly in Mediterranean regions. One-third of the patients are characterized with musculoskeletal involvement. Principally in chronic cases, there are difficulties in the follow-up of therapy success. Radiological imaging methods are used in musculoskeletal brucellosis in addition to standard serological tests. Two macrophage products, namely neopterin (NPT) and chitotriosidase (ChT), are used as novel markers in order to reflect the status of inflammatory diseases. In this study, we aimed to test the validity of these markers in follow-up of patients with brucellosis., Patients and Methods: A total of 40 brucellosis cases were included in the study and 27 healthy individuals were used as controls. Twenty of the brucellosis patients were presented with sacroiliac joint involvement. A 6-week treatment of doxycycline combined with rifampicin or streptomycin was used to treat brucellosis. Clinical observations and serological outcome were used to determine whether treatment was successful or not., Results: All of the 20 brucellosis patients without musculoskeletal involvement healed with the first cure of treatment, but all of the brucella-sacroiliitis patients had to be retreated. In addition to routine testing, serum NPT and ChT levels were evaluated after each treatment. The results presented a clear fall in both NPT and ChT levels in parallel with the serological data of the patients., Conclusion: In conclusion, NPT as well as ChT seems to be a useful marker in the follow-up of brucellosis patients and for evaluating the success of therapy.

Serum lipid changes during infection may be associated with atherogenesis. No data are available on the effect of Brucellosis on lipids. Lipid parameters were determined in 28 patients with Brucellosis on admission and 4 months following treatment and were compared with 24 matched controls. Fasting levels of total cholesterol (TC), HDL-cholesterol (HDL-C), triglycerides, apolipoproteins (Apo) A, B, E CII, and CIII, and oxidized LDL (oxLDL) were measured. Activities of serum cholesterol ester transfer protein (CETP), paraoxonase 1 (PON1), and lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and levels of cytokines [interleukins (IL)-1beta, IL-6, and tumor necrosis factor (TNFa)] were also determined. On admission, patients compared with controls had 1) lower levels of TC, HDL-C, LDL-cholesterol (LDL-C), ApoB, ApoAI, and ApoCIII and higher LDL-C/HDL-C and ApoB/ApoAI ratios; 2) higher levels of IL-1b, IL-6, and TNFa; 3) similar ApoCII and oxLDL levels and Lp-PLA(2) activity, lower PON1, and higher CETP activity; and 4) higher small dense LDL-C concentration. Four months later, increases in TC, HDL-C, LDL-C, ApoB, ApoAI, and ApoCIII levels, ApoB/ApoAI ratio, and PON1 activity were noticed compared with baseline, whereas CETP activity decreased. LDL-C/HDL-C ratio, ApoCII, and oxLDL levels, Lp-PLA(2) activity, and small dense LDL-C concentration were not altered. Brucella infection is associated with an atherogenic lipid profile that is not fully restored 4 months following treatment.

Splenic abscess due to Brucella spp. is extremely rare. We report a case of a splenic abscess due to Brucella spp. in a 61-year-old male patient. Brucella slide and tube agglutination tests (Wright) were positive while blood culture and culture from splenic tissue yielded negative results. The abdominal ultrasonography revealed a hypoechoic intrasplenic mass 15x12 mm in diameter at the middle portion of the spleen. The splenic lesions disappeared after prolonged treatment for 7 months with a combination of doxycycline, and rifampicin, followed by TMP-SXT. Brucella spp. should be considered in the differential diagnosis of splenic abscess in countries where brucellosis is endemic. The results of this case and literature review shows that a conservative approach using optimum antibiotics alone without surgical intervention can be successful in the treatment of patients with splenic brucellosis.

Objective: The central nervous system involvement of Brucellosis causes a hard to treat infection with multiple sequelae. The aim of this paper is to discuss the course of neurobrucellosis in response to therapy., Patients and Methods: Patients with neurobrucellosis were evaluated. The diagnosis was established by the isolation of bacteria, abnormal CSF findings and positive serology. Ceftriaxone, rifampicin, doxycycline and trimethoprim sulfamethoxazole were the antibiotic choices for these cases., Results: We present 11 cases with neurobrucellosis. None of our patients died, albeit one case has a critical situation due to subarachnoid hemorrhage and its' concordant sequelae. Only one of four patients with walking difficulty and two with hearing loss were normalized with therapy. Imaging techniques did not provide any specific contribution regarding the Brucella infection., Conclusions: Parenteral ceftriaxone should be used as an initial alternative in the management of neurobrucellosis. Although the therapy should be individualized, the duration of therapy should be a minimum of six months with suitable antibiotics.

Brucellosis continues to be an important cause of fever in underdeveloped countries and in rural areas of developed world. It is a multisystemic disease, associated with wide variety of symptoms. A wide variety of symptoms, including haematological abnormalities, such as anaemia, thrombocytopenia, pancytopenia, dissemine intravascular coagulation and leucopoenia could be seen, all of which are more common than usually thought. In this short study, we present a relatively uncommon haematological manifestation that of isolated thrombocytopenia mimicking idiopathic thrombocytopenic purpura, which we observed in seven of 114 patients who were diagnosed with brucellosis in our hospital over a 2-year period. Having given brucellosis treatment with rifampicin and doxycycline, complete remission was achieved and thrombocyte count returned to normal in all cases.

Brucellosis is a common zoonosis which still remains a major health problem in certain parts of the world. Osteoarticular involvement is the most frequent complication of brucellosis, in which the diagnosis of brucellar spondylodiscitis is often difficult since the clinical presentation may be obscured by many other conditions. Herein, we report an uncommon case of spondylodiscitis due to Brucella in a male who presented with abdominal pain. The diagnosis was established by positron emission tomography combined with computed tomography (PET/CT scan) and magnetic resonance followed by a confirmation on Brucella-agglutination test and positive culture of computed tomography (CT) guided punction fluid. This case report illustrates an atypical presentation of spondylitis and points out the difficulties in diagnosing the aetiological agens Brucella and differentiating its specific features from tuberculosis.

Treatment failure and relapse are major problems in the management of brucellosis. In developing countries, treatment with the oral combination doxycycline/rifampicin is preferred because of its convenience. However, its efficacy is lower than that of the doxycycline/streptomycin regimen and is likely further reduced when compliance is poor. Alternative regimens should be investigated in well designed clinical trials to determine whether treatment can be improved. Use of DNA detection as a marker for treatment success and for the prediction of relapse requires confirmation. In the absence of simple and effective treatment regimens, patient education to promote compliance is essential.

Brucellosis, an "anthropophitic" disease of worldwide distribution can involve several organs and tissues but the osteoarticular disease is the most common complication. It can occur as sacroiliitis, bursitis, tenosynovitis or osteomyelitis. Prosthetic joint infection is a serious complication of total joint arthroplasty, with coagulase negative staphylococci and Staphylococcus aureus accounting for 50% of cases. Treatment of prosthetic infections remains complex. Prosthetic infections caused by Brucella spp are rarely described in the literature. We report a patient with a prosthetic joint infection due to Brucella spp, documented by a polymerase chain reaction. The patient has been cured after two-stage exchange of the prosthesis and long-term antimicrobial therapy.

Background: Combination drug therapy of brucellosis leads to recovery of symptoms, shortening of symptomatic interval, and decrease in morbidity rate, but single drug therapy is associated with more relapse episodes and a higher rate of drug resistance. Different drug combinations have been evaluated in the treatment of brucellosis. Considering the failure of treatment and relatively high rate of relapse of the disease with the World Health Organization's (WHO) recommended therapeutic regimen, we evaluated a new regimen that we assumed would increase the success of treatment and decrease the rate of relapse. In this study we compare the standard regimen of the WHO, doxycycline-rifampin (DR), to triple therapy with doxycycline-rifampin-amikacin (ADR)., Methods: Two hundred and twenty-eight consecutive patients with brucellosis, who attended Hamedan Sina Hospital between 1999 and 2001, whether seen as outpatients or as inpatients, were enrolled in the study. The participants were randomly allocated to the DR group (receiving doxycycline 100 mg twice a day and rifampin 10 mg/kg body weight/day every morning, both taken orally for eight weeks) or the ADR group (receiving doxycycline 100 mg twice a day and rifampin 10 mg/kg body weight/day every morning, both taken orally for eight weeks, plus 7.5 mg/kg amikacin intramuscularly twice a day for seven days). The patients were checked for the relief of symptoms, drug side-effects, and relapse of disease during the treatment and follow-up., Results: Of the 228 patients enrolled, eight were withdrawn - four patients from the DR group and four from the ADR group. Of the remaining 220 participants (110 in the ADR group and 110 in the DR group), 107 were male (48.6%) and 113 were female (51.4%). Mean age was 35.7+/-17 years in the ADR group and 37+/-18.4 years in the DR group (p=0.5). In the DR group, 97 (88.2%) and in the ADR group, 106 (96.4%) of the patients had relief of symptoms (a significant difference by Chi-square test (p=0.04)). After completion of treatment, and at the sixth month follow-up, nine (9.3%) patients in the DR group and six (5.7%) in the ADR group experienced a relapse of the disease, with no significant difference (p=0.4). Mild side-effects were found in only 10 patients, and none required discontinuation of the therapeutic regimen. Of these patients, four were from DR group and six from ADR group; no significant difference was observed (p=0.7)., Conclusions: Given the fact that the ADR regimen had a higher efficacy and more rapid action in terms of relief of symptoms compared to the DR regimen, and that no significant difference in drug side-effects and disease relapse existed in the patients of either group, adding amikacin to the DR standard treatment regimen seems beneficial.

We reviewed a case of Brucella spondylodiscitis admitted to a referral, university hospital, in Ankara, Turkey. A 75-year-old female was referred to our hospital with low back pain. Previous magnetic resonance imaging yielded cortical destruction of T9-10 and T12-L2 vertebral bodies, focal infectious foci at discs within this range, significant microabscesses at paravertebral areas, which lead to the diagnosis of spondylodiscitis. History of consumption of unpasteurized dairy products led us to first suspect brucellosis yet, the serum agglutination test and blood culture were negative and did mislead us to several other, sometimes invasive, diagnostic tests. The final diagnosis was reached by culturing the specimen obtained through fine-needle aspiration from the paravertebral microabscesses. The exhausting diagnostic journey that started with the suspicion of tuberculosis or malignancy ended with a diagnosis of brucellosis. Brucellosis should be considered in all patients with osteoarthritic complaints in endemic regions, and the "prozone phenomenon" should be kept in mind, before proceeding to high-tech lab tests, imaging, or invasive procedures.

Background: The optimal treatment regimen and duration of the therapy is still controversial in spinal brucellosis. The aim of this study is to compare the efficacy, adverse drug reactions, complications and cost of ciprofloxacin plus rifampicin versus doxycycline plus streptomycin in the treatment of spinal brucellosis., Methods: The patients diagnosed as spinal brucellosis between January 2002 to December 2004 were enrolled into the study. Patients were enrolled into the two antimicrobial therapy groups (doxycycline plus streptomycin vs. ciprofloxacin plus rifampicin) consecutively. For the cost analysis of the two regimens, only the cost of antibiotic therapy was analysed for each patient., Results: During the study period, 31 patients with spinal brucellosis were enrolled into the two antimicrobial therapy groups. Fifteen patients were included in doxycycline plus streptomycin group and 16 patients were included in ciprofloxacin plus rifampicin group. Forty-two levels of spinal column were involved in 31 patients. The most common affected site was lumbar spine (n = 32, 76%) and involvement level was not different in two groups. Despite the disadvantages (older age, more prevalent operation and abscess formation before the therapy) of the patients in the ciprofloxacin plus rifampicin group, the duration of the therapy (median 12 weeks in both groups) and clinical response were not different from the doxycycline plus streptomycin. The cost of ciprofloxacin plus rifampicin therapy was 1.2 fold higher than the cost of doxycycline plus streptomycin therapy., Conclusion: Classical regimen (doxycycline plus streptomycin), with the appropriate duration (at least 12 weeks), is still the first line antibiotics and alternative therapies should be considered when adverse drug reactions were observed.