Materiały źródłowe

• #1 Brucellosis Treatment & Management: Approach Considerations, Initial Supportive Care, Pharmacologic Therapy

  https://emedicine.medscape.com/article/213430-treatment

  The goal of medical therapy in brucellosis is to control symptoms as quickly as possible in order to prevent complications and relapses. […] Multidrug antimicrobial regimens are the mainstay of therapy because of high relapse rates reported with monotherapeutic approaches. […] Optimal antibiotic therapy for brucellosis has been studied to some degree; however, recommendations may differ. […] For acute brucellosis in adults and children older than 8 years, the World Health Organization (WHO) guidelines recommend the following: Doxycycline 100 mg PO twice daily plus rifampin 600-900 mg/day PO Both drugs are to be given for 6 weeks; this regimen is more convenient but probably increases the risk of relapse. […] Treatment of brucellosis in pregnant women is a challenging problem, and the available data are limited.

• #2 Treatment of brucellosis: a systematic review of studies in recent twenty years

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3755828/

  The treatment of human brucellosis is controversial. The purpose of this study was to search published clinical trial papers to provide a simple and effective treatment in brucellosis. […] The comparison of combined doxycycline and rifampicin (DR) with a doxycycline plus streptomycin (DS) favors the latter regimen. The combined doxycycline/cotrimoxazole (DCTM) showed similar effect with DR. The treatment with the combined regimen including quinolones was similar to DR but with higher relapse rates. Higher relapse rate was searched in monotherapy (13% vs. 4.8%) and in short-term (less than 4 weeks) treatment regimen (22% vs. 4.8%), respectively. Although in children, clinical trials were limited but showed cotrimoxazole plus rifampin for six weeks was the best treatment regimen. […] In uncomplicated brucellosis in adult patients, doxycycline-aminoglycoside combination is the first choice with doxycycline- rifampin and doxycycline-cotrimoxazole should be the alternative regimens. The other oral regimens including quinolones may be considered as alternatives. Cotrimoxazole plus rifampin for six weeks may be the regimen of choice for the treatment of patients younger than 8 years old. Gentamicin for 5 days plus cotrimoxazole for six weeks may be a suitable alternative regimen.

• #3

  https://www.who.int/news-room/fact-sheets/detail/brucellosis

  Brucellosis typically causes flu-like symptoms, including fever, weakness, malaise and weight loss. […] Treatment options include doxycycline 100 mg twice a day for 45 days, plus streptomycin 1 g daily for 15 days. The main alternative therapy is doxycycline at 100 mg, twice a day for 45 days, plus rifampicin at 15mg/kg/day (600-900mg) for 45 days. Experience suggests that streptomycin may be substituted with gentamicin 5mg/kg/daily for 710 days, but no study directly comparing the two regimes is currently available. The optimal treatment for pregnant women, neonates and children under 8 is not yet determined; for children, options include trimethoprim/sulfamethoxazole (co-trimoxazole) combined with an aminoglycoside (streptomycin, gentamycin) or rifampicin.

• #4 Clinical Profile of the Diagnosis and Treatment of Human Brucellosis in Ghindae Zonal Referral Hospital, Northern Red Sea Region, Eritrea

  https://clinmedjournals.org/articles/ijtd/international-journal-of-tropical-diseases-ijtd-5-064.php?jid=ijtd

  According to the World Health Organization, it is recommended that Gentamicin be administered in a dose of 5 mg/kg/day intravenously or intramuscularly for seven to ten days in combination with Doxycycline administered for six weeks. […] According to the Eritrean Standard Treatment Guideline, the treatment regimen for adult brucellosis in the absence to osteoarticular disease, neurobrucellosis, or endocarditis is Doxycycline 100 mg orally twice daily for 6 weeks plus streptomycin 1 gram intramuscularly once daily for the first 14 to 21 days (Gentamicin may be substituted for streptomycin). […] The commonly used regimen, in this case, is Cotrimoxazole plus Gentamicin. […] Relapse after treatment usually occurs within the first six months following completion of treatment, although it may occur up to 12 months following completion of treatment. […] Treating patients with uncomplicated brucellosis with Doxycycline as a background regimen for 40-45 days along with Gentamicin injections for 7-10 days was found to be effective, although a broader prospective study or clinical trial is recommended.

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

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1346783/

  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. […] Although several studies have been conducted over the past 2 decades, there is no conclusive evidence on the optimum antibiotic therapy for brucellosis. […] 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. […] 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.

• #6 Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials | The BMJ

  https://www.bmj.com/content/336/7646/701

  Objectives To determine and quantify differences in efficacy between treatment regimens for brucellosis. […] Results were consistent among patients with bacteraemia and complicated brucellosis. Doxycycline-streptomycin resulted in a significantly higher rate of failure than doxycycline-rifampicin-aminoglycoside (triple drug regimen) (2.50, 1.26 to 5.00; two trials). […] Monotherapy was associated with a higher risk of failure than combined treatment when administered for a similar duration (2.56, 1.55 to 4.23; five trials). Treatment for six weeks or more offered an advantage over shorter treatment durations. […] The preferred treatment should be with dual or triple regimens including an aminoglycoside. […] The combination of tetracycline-streptomycin was significantly superior to tetracycline-rifampicin, mainly with regard to rates of relapse.

• #7 Treatment of brucellosis: a systematic review of studies in recent twenty years

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3755828/

  In 1986, the World Health Organization (WHO) recommended antibiotic regimen of oral doxycycline 100 mg twice a day for 6 weeks plus oral rifampicin 600 to 900 mg daily for 6 weeks or streptomycin 1 g intramuscularly daily for 2-3 weeks for the treatment of brucellosis. This treatment is still accepted as the preferred treatment for most infectious diseases specialists. […] The combination of streptomycin or gentamicin plus doxycycline and rifampicin (SDR or GDR) should be considered as the first choice of triple therapy regimens. […] The present study showed that a combination of doxycycline and aminoglycoside as the most widely studied treatment regimen with overall relapse of 4.8% and treatment failure rate of 7.4% was the preferred treatment in acute or uncomplicated chronic brucellosis or complicated cases (except of endocarditis, spondylitis or arthritis). […] For the prevention of multi-drug resistant tuberculosis, prescription of rifampin in the treatment of brucellosis in TB high prevalence area should be limited. Monotherapy and short-term therapy are not suitable treatment regimens.

• #8 Brucellosis: Symptoms and Treatment

  https://www.webmd.com/a-to-z-guides/brucellosis-symptoms-treatment

  Brucellosis can be difficult to treat. If you have brucellosis, your doctor will prescribe antibiotics. Antibiotics commonly used to treat brucellosis include: doxycycline (Acticlate, Adoxa, Doryx, Monodox, Oracea, Vibra-Tabs, Vibramycin), streptomycin, ciprofloxacin (Cipro) or ofloxacin, rifampin (Rifadin), sulfamethoxazole/trimethoprim (Bactrim), tetracycline. […] You will generally be given doxycycline and rifampin a in combination for 6-8 weeks. […] You must take the antibiotics for many weeks to prevent the disease from returning. The rate of relapse following treatment is about 5-15% and usually occurs within the first six months after treatment. […] Recovery can take weeks, even months. Patients who receive treatment within one month of the start of symptoms can be cured of the disease.

• #9 Brucellosis – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/brucellosis/diagnosis-treatment/drc-20351744

  Treatment for brucellosis is to relieve symptoms, prevent the disease from coming back and prevent complications. Treatment involves taking antibiotics for at least six weeks. Symptoms may not go away completely for several months. The disease also may return and become long-term, called chronic.

• #10 About Brucellosis | Brucellosis | CDC

  https://www.cdc.gov/brucellosis/about/index.html

  Brucellosis can be treated with antibiotics. […] Once your healthcare provider has confirmed that you have brucellosis from test results, you can begin treatment with antibiotics. […] Your doctor will decide which antibiotics you’ll get for a minimum of 6-8 weeks. […] If you have with an infection from a strain of Brucella called RB51 from consuming infected animal products, you’ll need antibiotics other than rifampin. […] It’s important that you take all your medicines when being treated for brucellosis. […] If you’re not properly treated, the infection can become chronic and lead to long-term disease associated with arthritis, endocarditis, chronic fatigue, depression, and swelling of the liver or spleen. […] Depending on the timing of treatment and how sick you are, recovery may take a few weeks to several months.

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

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1346783/

  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. […] 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. […] 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. […] Also, triple-antibiotic combinations were found to be of value in some case series of brucellar endocarditis, spondylitis, and meningitis. […] 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.

• #12 Brucellosis Medication: Antibiotics, Other, Corticosteroids

  https://emedicine.medscape.com/article/213430-medication

  Gentamicin is commonly used to treat brucellosis in combination with either TMP-SMZ or doxycycline. […] TMP-SMZ is used adjunctively in children younger than 8 years and is used either as monotherapy or in combination with rifampin or gentamicin to treat infection in pregnant women. […] Rifampin is used as a component of combination therapy for brucellosis. […] In patients with brucellosis, corticosteroids are indicated to reduce inflammation and improve neurologic outcome. […] The use of corticosteroids is reserved for symptomatic Brucella meningitis. Although these agents are generally recommended, scientific evidence supporting their use is lacking.

• #13 Pediatric brucellosis | Saudi Medical Journal

  https://smj.org.sa/content/39/4/336

  Brucellosis is one of the most common zoonotic bacterial infections and causes disease worldwide. […] The optimal antimicrobial treatment for brucellosis is frequently hampered by the requirement for prolonged antibiotic administration and the need to use combination therapy. […] Systematic review of the literature demonstrated that antibiotic treatment should be administered for 6 weeks or longer to reduce the risk of relapse, and the authors concluded that a dual or triple antimicrobial regimen with an aminoglycoside (either streptomycin or gentamicin) for the first 2-3 weeks is preferable. […] For the treatment of brucellosis in children, combination treatment regimens that include TMP-SMX, doxycycline, and rifampicin are recommended. […] Doxycycline is recommended only for children over 8 years old, as children younger than 8 years may be more sensitive to the side effects of doxycycline, especially tooth discoloration.

• #14 Pediatric brucellosis | Saudi Medical Journal

  https://smj.org.sa/content/39/4/336

  There are 2 effective treatment regimens for different age groups. For children over 8 years old, oral doxycycline (4 mg/kg/day) and rifampicin (20 mg/kg/day) are typically prescribed, and for children under 8 years old, oral trimethoprim TMP (6-8 mg/kg/day), sulphamethoxazole SMX (30-40 mg/kg/day), and rifampicin (20 mg/kg/day) are typically prescribed. […] Complications and relapse can be successfully treated with triple-drug regimens. […] Pediatricians involved in the management of children with brucellosis should encourage compliance with the prescribed antibiotic regimen through education of patients and their families and assess treatment results through rigorous long-term follow-ups. […] Several studies reported that combined treatment of childhood brucellosis lasting at least 4 weeks results with a wide range frequency of relapses (0-32%).

• #15 Brucellosis Treatment & Management: Approach Considerations, Initial Supportive Care, Pharmacologic Therapy

  https://emedicine.medscape.com/article/213430-treatment

  In patients with spondylitis or sacroiliitis, doxycycline and rifampin combined with an aminoglycoside (gentamicin) for the initial 2-3 weeks, followed by 6 weeks of rifampin and doxycycline, is usually recommended. […] Patients with nervous system infections typically require combination therapy. […] Chronic brucellosis is treated with triple-antibiotic therapy. The combination of rifampin, doxycycline, and streptomycin often is used. […] The use of corticosteroids is reserved for symptomatic Brucella meningitis. […] Ultimately, treatment for brucellosis in pregnant patients should be determined in consultation with their obstetrician to ensure the best outcomes for both mother and child. […] The main roles of surgery in patients with brucellosis lie in the treatment of endocarditis and in the drainage of pyogenic joint effusions or paraspinal abscesses. […] No special diet is required for the treatment of brucellosis. […] Outpatient care consists of completing the prescribed course of antibiotic therapy, treating any exposed patients, and avoiding contact with the initial source of infection.

• #16 Brucellosis: A perspective from physical therapy and rehabilitation specialist | 2021, Volume 7 – Issue 3 | Demiroglu Science University Florence Nightingale Journal of Medicine

  https://journalmeddbu.com/full-text/270

  The World Health Organization recommends doxycycline 200 mg/day and rifampicin 600-900 mg/day for the treatment of brucellosis; in oral/parenteral therapy, streptomycin 15 mg/kg/day (first 2-3 weeks) in combination with rifampicin for at least six weeks. […] Streptomycin 10.75-1 g intramuscular (IM) and doxycycline 2100 mg for 2-3 weeks is the standard treatment for osteoarticular brucellosis, followed by a combination of rifampicin 1600 mg and doxycycline 2100 mg. […] In complicated brucellosis, 12 weeks of triple therapy was associated with a lower relapse rate than a four-week combination of streptomycin or gentamicin + rifampicin/ doxycycline. […] The duration of treatment in patients with spondylodiscitis, paravertebral abscess, epidural abscess, or psoas abscess may need to be extended with clinical, laboratory, and radiological follow-up (3-9 months).

• #17 Brucellosis Medication: Antibiotics, Other, Corticosteroids

  https://emedicine.medscape.com/article/213430-medication

  Although many antibiotics display in vitro activity against Brucella species, clinical response has been demonstrated with only a few of them. Drugs that display clinical activity with low relapse rates include doxycycline, gentamicin, streptomycin, rifampin, and trimethoprim-sulfamethoxazole (TMP-SMZ). […] Corticosteroids are indicated to reduce inflammation and improve neurologic outcome in patients with neurobrucellosis. […] Trials have established the efficacy of doxycycline as treatment for brucellosis. Because of concerns regarding treatment failures, combination therapy with rifampin or an aminoglycoside now is recommended, although doxycycline remains approved for use as monotherapy. […] Streptomycin is indicated as a cotherapeutic agent to augment the antibacterial actions of other agents used to treat brucellosis.

• #18 Brucellosis Medication: Antibiotics, Other, Corticosteroids

  https://emedicine.medscape.com/article/213430-medication

  Gentamicin is commonly used to treat brucellosis in combination with either TMP-SMZ or doxycycline. […] TMP-SMZ is used adjunctively in children younger than 8 years and is used either as monotherapy or in combination with rifampin or gentamicin to treat infection in pregnant women. […] Rifampin is used as a component of combination therapy for brucellosis. […] In patients with brucellosis, corticosteroids are indicated to reduce inflammation and improve neurologic outcome. […] The use of corticosteroids is reserved for symptomatic Brucella meningitis. Although these agents are generally recommended, scientific evidence supporting their use is lacking.

• #19 Brucellosis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/gram-negative-bacilli/brucellosis

  Optimal treatment usually requires 2 antibiotics: doxycycline plus an aminoglycoside, rifampin, or a fluoroquinolone and, in children, trimethoprim/sulfamethoxazole plus rifampin. […] If antibiotics are given, combination therapy is preferred because relapse rates with monotherapy are high. Doxycycline for 6 weeks plus streptomycin (or gentamicin) for 14 days lowers the rate of relapse. For uncomplicated cases, rifampin for 6 weeks can be used instead of an aminoglycoside. Regimens using fluoroquinolones for 14 to 42 days plus rifampin or doxycycline instead of an aminoglycoside have been shown in small studies to be equally effective, but these regimens are not preferred. […] In children 8 years, TMP/SMX and rifampin for 4 to 6 weeks have been used. […] Neurobrucellosis and endocarditis require prolonged treatment, and 3 antibiotics are commonly given. […] Even with antibiotic treatment, about 5 to 15% of patients relapse overall, so all patients should be followed clinically and with repeat serologic titers for 1 year.

• #20 Better efficacy of triple antibiotics therapy for human brucellosis: A systematic review and meta-analysis | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0011590

  Better efficacy of triple antibiotics therapy for human brucellosis: A systematic review and meta-analysis […] The treatment of brucellosis suffers from a high recurrence rate and drug resistance. Our study researched the differences in efficacy and side effects between triple antibiotics therapy and dual antibiotics therapy in the treatment of brucellosis through a systematic review and meta-analysis. […] The meta-analysis included 15 studies consisting of 11 randomized controlled trials and 4 cohort studies. Triple antibiotics showed better efficacy than dual antibiotics in a comparison of 3 overall outcome indicators (therapeutic failure rate (RR 0.42; 95% CI 0.30 to 0.59), relapse rate (RR 0.29; 95% CI 0.18 to 0.45), and overall therapeutic failure rate (RR 0.37; 95% CI 0.28 to 0.48)). […] In the treatment of brucellosis, triple antibiotics have better efficacy than dual antibiotics and do not increase the incidence of side effects.

• #21 Brucellosis – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/brucellosis/symptoms-causes/syc-20351738

  Symptoms of brucellosis may include fever, joint pain and being very tired. The infection can often be treated with antibiotics. However, treatment takes several weeks to months. And the infection can come back. […] Long-term, called chronic, brucellosis may cause complications in just one organ or through the body. Possible complications include: […] This is one of the most serious complications of brucellosis. Untreated endocarditis can damage or destroy the heart valves. This is the main cause of death from brucellosis. […] Brucellosis can also affect the spleen and liver, causing them to get larger than usual.

• #22 Brucellosis Treatment, Cause, Diagnosis, Symptoms

  https://www.emedicinehealth.com/brucellosis/article_em.htm

  A multidrug antibiotic regimen is the cornerstone of treatment for brucellosis. […] The cornerstone of treatment for brucellosis is antibiotics. Because of the high relapse rate associated with the disease, the use of a multidrug (two or more) antibiotic regimen is recommended. The antimicrobials most commonly used include doxycycline (Vibramycin), streptomycin, rifampin (Rifadin), gentamicin (Garamycin), and trimethoprim-sulfamethoxazole (Bactrim, Septra). The combination of antibiotics used will vary based on disease severity, age, and pregnancy. […] In general, a full 6-week course of antibiotics is recommended, and prompt treatment can lead to an improvement in symptoms and may also prevent the complications associated with brucellosis. However, relapse rates of the disease are still about 5%-10%, even with treatment. Depending on the severity of the illness, the associated complications (if any), and the timing of treatment, recovery may take from a few weeks to a few months. […] Rarely, surgical intervention may be needed for certain complications associated with brucelloses, such as abscess formation or heart-valve infection. Your healthcare professional may need to consult other physicians, including surgeons, infectious disease specialists, or a neurologist.

• #23 Brucellosis: Causes, Symptoms, Treatment & Prevention

  https://my.clevelandclinic.org/health/diseases/17886-brucellosis

  Brucellosis is treated with antibiotics. […] Your healthcare provider will treat brucellosis with a combination of at least two types of antibiotics. You’ll need to take them for at least six to eight weeks. Depending on your specific case, you may need other therapies (like draining infected areas or managing complications). […] Antibiotics healthcare providers prescribe to treat brucellosis include: Streptomycin or gentamicin, Rifampin, Doxycycline, Trimethoprim/sulfamethoxazole (TMP/SMX), Ciprofloxacin. […] In addition to taking prescribed antibiotics to get rid of the bacteria, you may be able to manage some symptoms of brucellosis, like joint pain and fever, at home. Ask your healthcare provider if there are over-the-counter (OTC) medications or other therapies that are safe for treating your symptoms.

• #24

  https://continentalhospitals.com/diseases/brucellosis/

  Treatment of brucellosis typically involves a combination of antibiotics to effectively eradicate the bacteria. […] The primary treatment involves a prolonged course (typically 6 weeks to several months) of antibiotics such as doxycycline and rifampin. Alternatives include trimethoprim-sulfamethoxazole or fluoroquinolones. […] Two or more antibiotics are often used simultaneously to prevent relapse and reduce the risk of developing antibiotic resistance. […] Regular follow-up visits and laboratory tests are crucial to monitor treatment response and detect any complications. […] Medications for pain, fever, and other symptoms may be prescribed to alleviate discomfort. […] Adequate rest and hydration are important to support recovery and reduce symptoms. […] Patients should avoid consuming raw dairy products to prevent further exposure. […] In endemic areas, preventive measures include vaccination of animals and proper food hygiene practices.

• #25 Brucellosis: Definition, transmission, and treatment

  https://www.medicalnewstoday.com/articles/brucellosis

• #26 SciELO Brazil – Guidelines for the management of human brucellosis in the State of Paraná, Brazil Guidelines for the management of human brucellosis in the State of Paraná, Brazil

  https://www.scielo.br/j/rsbmt/a/t9kY3TjkwRCQHfpT5fBZsSG/

  For patients with brucellosis, clinical and laboratory follow up is required for 2 years. […] Failure was defined as the presence of signs and symptoms after 4 weeks of treatment and relapse was the return of signs and symptoms of brucellosis. […] Patients were defined as cured if they did not meet the definitions of failure or relapse.

• #27 Brucellosis – Infections – MSD Manual Consumer Version

  https://www.msdmanuals.com/home/infections/bacterial-infections-gram-negative-bacteria/brucellosis

  Two antibiotics are given at the same time to increase the chance of a cure. […] Doctors give 2 antibiotics at the same time to increase the chance of a cure. Which antibiotics are given depends on the person’s age. […] For people over 8 years of age, usually 1 of the antibiotics is doxycycline, given by mouth. The second antibiotic can be either streptomycin or gentamicin, injected daily, or rifampin or a fluoroquinolone, given by mouth. […] Children under 8 years of age may be given the combination antibiotic trimethoprim/sulfamethoxazole (TMP/SMX) and also rifampin by mouth. […] After being treated, some people develop symptoms again, so people are periodically examined and tested for a year after treatment.

• #28 A systematic review and meta-analysis of comparative clinical studies on antibiotic treatment of brucellosis | Scientific Reports

  https://www.nature.com/articles/s41598-024-69669-w

  Brucellosis is a difficult to treat infection that requires antibiotic combinations administered over several weeks for clearance of infection and relapse prevention. […] Standard dual therapy with doxycycline+rifampicin had a higher risk of treatment failure compared to triple therapy which added streptomycin (RR: 1.98, 95% CI 1.173.35, p=0.01) or levofloxacin (RR: 2.98, 95% CI 1.675.32, p=0.0002), but a similar or lower risk compared to alternative dual antibiotic combinations (p0.05). […] Triple antibiotic therapy is more effective than standard dual therapy with rifampicin and doxycycline. However, the latter is also efficacious and suitable for uncomplicated disease. […] Treatment of brucellosis requires combinations of antibiotics administered over an extended period. […] Given the risk of complications and poor quality of life associated with ongoing infections, it is important to avoid treatment failure and relapses with efficacious combinations of antibiotics based on current evidence.

• #29 Treatment of human brucellosis: systematic review and meta-analysis of randomised controlled trials | The BMJ

  https://www.bmj.com/content/336/7646/701

  The main difference was in primary failure of the regimen with an NNT of 10 patients (6 to 33) with triple combination therapy to prevent one therapeutic failure with dual therapy. […] Treatment should be administered for six weeks or longer as treatment for 30 days or less results in an increased relapse rate, even with the more potent doxycycline-streptomycin regimen. […] According to results of two trials, the optimal treatment regimen for brucellosis is doxycycline-aminoglycoside-rifampicin, with the aminoglycoside administered for the first seven to 14 days and doxycycline-rifampicin continued for six to eight weeks. […] Quinolones cannot currently be recommended, either as monotherapy or in combination therapy, as the available evidence shows them to be less effective than the traditional regimens.

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

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1346783/

  However, there is only one brief review focusing on the issue, published in 1992. […] Monotherapy with ciprofloxacin results in an unacceptably high probability of relapse, as shown by Lang et al. […] The finding of lower toxicity in the quinolone treatment arm, described by Akova et al., although statistically significant, referred to less gastrointestinal discomfort, which did not necessitate discontinuation of therapy and thus could not represent a serious criterion in favor of quinolone use per se. […] Despite the above observations, quinolones may have some role in the management of brucellosis. […] Fluoroquinolones should not be used as monotherapy for the treatment of brucellosis. […] Fluoroquinolones can be used in combination with rifampin or doxycycline for the treatment of acute uncomplicated brucellosis as an alternative to the doxycycline-rifampin combination, if needed.

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

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1346783/

  Fluoroquinolones may be used in combination with rifampin or doxycycline for the treatment of brucellar spondylitis, but further studies are needed to evaluate the appropriate duration of therapy. […] Fluoroquinolones in combination with rifampin or doxycycline were not shown to be superior to the traditional doxycycline-rifampin combination; thus, there is no reason to recommend these as a first-line therapy for the treatment of acute uncomplicated brucellosis or brucellar spondylitis. […] Fluoroquinolones in combination with rifampin or doxycycline can be used in cases of patients who exhibit toxicity with other combination regimens. […] Fluoroquinolones in combination with rifampin or doxycycline can be used in cases of patients who do not respond to other combination regimens or relapse after treatment with them.

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

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1346783/

  In cases of complicated brucellosis that are expected or shown to be unresponsive to conventional combination therapy, a fluoroquinolone may be added to the regimen (triple-antibiotic therapy). […] In conclusion, a critical review of the available literature from laboratory and clinical studies regarding quinolone use in the treatment of human brucellosis suggests that there is a lack of evidence supporting the inclusion of quinolones in the initial therapeutic regimen.

• #33 Updated therapeutic options for human brucellosis: A systematic review and network meta-analysis of randomized controlled trials | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0012405

  Updated therapeutic options for human brucellosis: A systematic review and network meta-analysis of randomized controlled trials […] In clinical practice guidelines, there is no consensus about the medications that should be initially offered to patients with brucellosis. To provide informative evidence, we compared and ranked brucellosis medications based on their efficacy and safety. […] Brucellosis medications differ in efficacy and safety. Doxycycline + Gentamicin, Triple, and Doxycycline + Streptomycin have superior efficacy and safety. Treatment of brucellosis should strike a balance between efficacy, safety, and cost. […] Our systematic review and network meta-analysis not only updates the relevant evidence but also has broader conclusions. We found that Doxycycline + Gentamicin is the best in terms of efficacy, which was also recommended in a previous systematic review. The second-ranked treatment is triple therapy. […] Based on the evidence in the current review, we recommend 6 weeks of doxycycline plus 1 to 2 weeks of gentamicin or plus 2 to 3 weeks of streptomycin treatment. As Rifampicin + Quinolones has a high safety profile and good efficacy, we recommend 6 weeks of treatment as an alternative therapy. If finances allow, consider triple therapy. […] Monotherapy, Streptomycin + TMP/SMX, and Rifampicin + TMP/SMX also cannot currently be recommended.

• #34 Better efficacy of triple antibiotics therapy for human brucellosis: A systematic review and meta-analysis | PLOS Neglected Tropical Diseases

  https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0011590

  The current treatment for brucellosis is the dual antibiotics regime recommended by the WHO in 1986 (doxycycline combined with streptomycin or rifampicin). However, classical therapy has a high recurrence rate and increasing rates of drug resistance. […] Our study compared the efficacy and safety between the 2 therapies in the treatment of brucellosis, founding that triple antibiotics had better efficacy compared to dual antibiotics and there was no increase in the rate of side effects. […] In conclusion, the choice of a treatment plan for brucellosis requires consideration of a variety of factors, such as the dose and course of the drugs, the socioeconomic situation, the availability of drugs, and even the traditional treatment protocols of medical institutions and the clinical experience of physicians. Therefore, the choice of treatment options for brucellosis should be diverse. Finally, our study aims to provide evidence-based medicine for the treatment of brucellosis.

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