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Brucellosis Medication

  • Author: Wafa Al-Nassir, MBBS; Chief Editor: Michael Stuart Bronze, MD  more...
 
Updated: Mar 15, 2016
 

Medication Summary

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). Other agents with potential roles are chloramphenicol, imipenem-cilastatin, and various fluoroquinolones. When relapse occurs, the development of antibiotic resistance does not appear to be the underlying cause.

Corticosteroids are indicated to reduce inflammation and improve neurologic outcome in patients with neurobrucellosis.

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Antibiotics, Other

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Doxycycline (Doryx, Vibramycin, Adoxa)

 

Doxycycline is a synthetic broad-spectrum antibiotic derived from oxytetracycline. It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Its activity, like that of other tetracyclines, is essentially bacteriostatic. Doxycycline is readily absorbed and is eliminated by biliofecal and urinary excretion. Dosage must be adjusted in patients with impaired renal function.

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

 

Streptomycin is an aminoglycoside antibiotic that exerts a bacteriostatic effect by inhibiting protein synthesis through binding to 30S ribosomal subunits. It typically achieves peak serum concentration within 1 hour of being injected intramuscularly (IM). It achieves good penetration of all organ systems except the central nervous system (CNS), and it readily passes through placental membrane barriers. Streptomycin is excreted by renal glomerular filtration; dosage adjustment is necessary in patients with diminished renal function.

Streptomycin is indicated as a cotherapeutic agent to augment the antibacterial actions of other agents used to treat brucellosis.

Gentamicin

 

Gentamicin is an aminoglycoside antibiotic that exerts a bacteriostatic effect by inhibiting protein synthesis through binding to 30S ribosomal subunits. It is commonly used to treat brucellosis in combination with either TMP-SMZ or doxycycline. Dosing regimens are numerous. Either a single daily dose or multiple daily doses may be used for adults. The dose should be adjusted on the basis of creatinine clearance and changes in volume of distribution and may be administered either intravenously (IV) or IM.

Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra DS)

 

TMP-SMZ (also referred to as cotrimoxazole) inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. It 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 (Rifadin)

 

Rifampin inhibits DNA-dependent bacterial (but not mammalian) RNA polymerase activity in susceptible cells. No known cross-resistance of microbes occurs, except when other rifamycins are involved. Rifampin is readily absorbed after oral dosing. Renal and hepatobiliary routes of elimination are active. Rifampin is used as a component of combination therapy for brucellosis. It may exhibit bacteriostatic or bactericidal activity, depending on its concentration at the site of infection.

Tetracycline

 

Tetracycline is a readily absorbed antibiotic with bacteriostatic effects produced by inhibition of microbial protein synthesis. It is concentrated by the liver in bile and is excreted in feces and urine. Dosage must be adjusted for patients with renal impairment; excessive systemic accumulation may occur, which can result in possible hepatic toxicity or worsening of azotemia, hyperphosphatemia, and acidemia. In patients with significantly abnormal renal function, monitoring of serum concentrations may be warranted.

Ciprofloxacin (Cipro)

 

Ciprofloxacin is a synthetic broad-spectrum antimicrobial agent of the fluoroquinolone class. It exerts bactericidal activity by interfering with microbial DNA gyrase activity. It is well absorbed orally and is largely cleared unchanged in urine.

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Corticosteroids

Class Summary

In patients with brucellosis, corticosteroids are indicated to reduce inflammation and improve neurologic outcome. The addition of anti-inflammatory therapy with methylprednisolone or another corticosteroid may be beneficial in patients with severe or diffuse CNS involvement, cranial neuropathies, optic neuritis, or arachnoiditis.

Dexamethasone (Baycadron)

 

The use of corticosteroids is reserved for symptomatic Brucella meningitis. Although these agents are generally recommended, scientific evidence supporting their use is lacking. No consensus exists on optimal dosing, frequency, or duration of therapy.

Methylprednisolone (A-Methapred, Medrol, Depo-Medrol, Solu-Medrol)

 

Methylprednisolone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

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Contributor Information and Disclosures
Author

Wafa Al-Nassir, MBBS Infectious Diseases Consultant, National Guard Health Affairs, Saudi Arabia

Wafa Al-Nassir, MBBS is a member of the following medical societies: American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Salata, MD Chief and Clinical Program Director of Division of Infectious Diseases, Vice Chair for International Affairs, Professor, Department of Medicine, Case Western Reserve University School of Medicine

Robert A Salata, MD is a member of the following medical societies: American Association of Immunologists, American Federation for Medical Research, American Medical Association, Central Society for Clinical and Translational Research, Infectious Diseases Society of America, Ohio State Medical Association, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Michelle V Lisgaris, MD Assistant Professor of Medicine, Case Western Reserve University School of Medicine

Michelle V Lisgaris, MD is a member of the following medical societies: American College of Physicians, American Medical Association, Infectious Diseases Society of America, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP Assistant Professor of Pediatrics, Co-Director of Antimicrobial Stewardship, Medical Director, Division of Pediatric Infectious Diseases and Immunology, Connecticut Children's Medical Center

Nicholas John Bennett, MBBCh, PhD, MA(Cantab), FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics

Disclosure: Received research grant from: Cubist Pharmaceuticals, Durata Therapeutics, and Biota Pharmaceutical<br/>Received income in an amount equal to or greater than $250 from: HealthyCT insurance<br/>Medico legal consulting for: Various.

Chief Editor

Michael Stuart Bronze, MD David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Michael Stuart Bronze, MD is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, Oklahoma State Medical Association, Southern Society for Clinical Investigation, Association of Professors of Medicine, American College of Physicians, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Acknowledgements

Walid Abuhammour, MD, FAAP Professor of Pediatrics, Michigan State University College of Medicine; Director of Pediatric Infectious Disease, Department of Pediatrics, Hurley Medical Center

Walid Abuhammour, MD, FAAP is a member of the following medical societies: American Medical Association, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society

Disclosure: Nothing to disclose.

Jeffrey D Band, MD Professor of Medicine, Oakland University William Beaumont School of Medicine; Director, Division of Infectious Diseases and International Medicine, Corporate Epidemiologist, William Beaumont Hospital; Clinical Professor of Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Nicholas John Bennett, MB, BCh, PhD Fellow in Pediatric Infectious Disease, Department of Pediatrics, State University of New York Upstate Medical University

Nicholas John Bennett, MB, BCh, PhD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Pediatrics

Disclosure: Nothing to disclose.

Itzhak Brook, MD, MSc Professor, Department of Pediatrics, Georgetown University School of Medicine

Itzhak Brook, MD, MSc is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians-American Society of Internal Medicine, American Federation for Clinical Research, American Medical Association, American Society for Microbiology, Armed Forces Infectious Diseases Society, Association of Military Surgeons of the US, Infectious Diseases Society of America, International Immunocompromised Host Society, International Society for Infectious Diseases,Medical Society of the District of Columbia, New York Academy of Sciences, Pediatric Infectious Diseases Society, Society for Ear, Nose and Throat Advances in Children, Society for Experimental Biology and Medicine, Society for Pediatric Research, Southern Medical Association, and Surgical Infection Society

Disclosure: Nothing to disclose.

Robert G Darling, MD, FACEP Adjunct Clinical Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Director, Center for Disaster and Humanitarian Assistance Medicine

Robert G Darling, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, American Telemedicine Association, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Joseph Domachowske, MD Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University

Joseph Domachowske, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Society for Microbiology, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Ronald A Greenfield, MD Professor, Department of Internal Medicine, University of Oklahoma College of Medicine

Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist Honoraria Speaking and teaching; Forest Pharmaceuticals Speaking and teaching

Gerald E Maloney Jr, DO, FAAEM Senior Instructor, Department of Emergency Medicine, Case Western Reserve University School of Medicine; Director of Medical Toxicology, Department of Emergency Medicine; Associate Medical Director, MetroLifeFlight, MetroHealth Medical Center, Cleveland, OH

Gerald E Maloney Jr, DO, FAAEM is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, American College of Osteopathic Emergency Physicians, American Osteopathic Association, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Jerry L Mothershead, MD Medical Readiness Consultant, Medical Readiness and Response Group, Battelle Memorial Institute; Advisor, Technical Advisory Committee, Emergency Management Strategic Healthcare Group, Veteran's Health Administration; Adjunct Associate Professor, Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences

Jerry L Mothershead, MD is a member of the following medical societies: American College of Emergency Physicians and National Association of EMS Physicians

Disclosure: Nothing to disclose.

Khaled Nashar, MD Instructor of Clinical Internal Medicine, Section of Hospitalist Medicine, Division of General Internal Medicine, Department of Medicine, University of Pittsburgh Medical Center

Khaled Nashar, MD is a member of the following medical societies: American College of Physicians, American Medical Association, and American Society of Hypertension

Disclosure: Nothing to disclose.

Robert Stanley Rust Jr, MD, MA Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia School of Medicine; Chair-Elect, Child Neurology Section, American Academy of Neurology

Robert Stanley Rust Jr, MD, MA is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International Child Neurology Association, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mark R Schleiss, MD American Legion Chair of Pediatrics, Professor of Pediatrics, Division Director, Division of Infectious Diseases and Immunology, Department of Pediatrics, University of Minnesota Medical School

Mark R Schleiss, MD is a member of the following medical societies: American Pediatric Society, Infectious Diseases Society of America, Pediatric Infectious Diseases Society, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Aashit K Shah, MD Professor of Neurology, Director, Comprehensive Epilepsy Program, Program Director, Clinical Neurophysiology Fellowship, Detroit Medical Center, Wayne State University School of Medicine

Aashit K Shah, MD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Epilepsy Society, and American Neurological Association

Disclosure: UCB pharma Consulting fee Speaking and teaching

Russell W Steele, MD Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine

Russell W Steele, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, Infectious Diseases Society of America, Louisiana State Medical Society, Pediatric Infectious Diseases Society, Society for Pediatric Research, and Southern Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Florian P Thomas, MD, MA, PhD, Drmed Director, Regional MS Center of Excellence, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Director, Neuropathy Association Center of Excellence, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, St Louis University School of Medicine

Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Neurological Association, American Paraplegia Society, Consortium of Multiple Sclerosis Centers, National Multiple Sclerosis Society, and Sigma Xi

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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Well-formed hepatic granuloma from patient with brucellosis.
Brucella species are poorly staining, small gram-negative coccobacilli (0.5-0.7 × 0.6-1.5 µm) and are seen mostly as single cells with an appearance resembling "fine sand."
Table 1. Currently Recognized Brucella Species
Organism Animal Reservoir Geographic Distribution
Brucella melitensis Goats, sheep, camels Mediterranean, Asia, Latin America, parts of Africa and some southern European countries
Brucella abortus Cows, buffalo, camels, yaks Worldwide
Brucella suis Pigs (biotype 1-3) South America, Southeast Asia, United States
Brucella canis Canines Cosmopolitan
Brucella ovis Sheep No known human cases
Brucella neotomae Rodents Not known to cause human disease
Brucella pinnipediae and Brucella cetaceae Marine animals, minke whales, dolphins, seals Case reports describing some human cases (mainly neurobrucellosis)
Table 2. Symptoms and Signs of Brucellosis
Study No. of Patients Fever or Chills Arthralgia or Arthritis Sweating Constitutional symptoms* Hepatomegaly Splenomegaly
Memish et al (2000)[13] 160 146 (91.3%) 105 (65.6%) 30 (18.8%) 70 (43.8%) 9 (5.6%) 11 (6.9%)
Kokoglu et al (2006)[14] 138 108 (78.3%) 107 (77.5%) 100 (72.5%) 98 (71%) 37 (26.8%) 50 (36.2%)
Mantur et al (2006)[15] 495 417 (84.2%) 117 (23.6%) 19 (3.8%) 6 (1.2%) 56 (11.3%) 95 (19.2%)
Ruiz-Mesa et al (2005)[16] 711 702 (98.7%) 353 (49.6%) 597 (84%) 533 (75%) 250 (35.2%) 148 (20.8%)
Barroso Garcia et al (2002)[17] 565 441 (78.1%) 248 (43.9%) 483 (85.5%) 472 (83.5%) 422 (74.7%) 152 (26.9%)
Hasanjani Roushan et al (2004)[18] 469 314 (67%) 252 (53.7%) 357 (76.1%) ... ... 27 (5.8%)
Pappas et al (2005)[19] 100 91 (91%) 44 (44%) .. 26 (26%) 7 (7%) 16 (16%)
Troy et al (2005)[20] 28 25 (89%) 15 (54%) .. 13 (46%) 8 (29%) 5 (18%)
Andriopoulos et al (2007)[21] 144 144 (100%) 125 (86.8%) 138 (95.8%) 140 (97.2%) ... 74 (51.4%)
Giannakopoulos et al (2006)[22] 52 42 (81%) 43 (83%) 8 (15%) 7 (13%) ... ...
Mantur et al (2004)[23] 93 49 (53%) 19 (20%) ... ... ... ...
Tsolia et al (2002)[24] 39 27 (69%) 27 (69%) 8 (21%) 13 (33%) 11 (28%) 15 (38%)
* Anorexia, asthenia, fatigue, weakness, malaise.
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