Brucella

Background

  • Brucella are gram negative coccobacilli
  • Zoonosis that causes brucellosis (also known as undulant fever, mediterranean fever, or malta fever)
  • Facultative intracellular pathogens, live in monocytes and macrophages in lymph nodes, bone marrow, liver and spleen.
  • Several species, including Brucella melitensis (most patholgenic in humans, main hosts are goats/sheep), Brucella abortus, Brucella suis, Brucella canis, Brucella ceti, and Brucella pinnipediae
    • Brucella melitensis eradicated in the US since 1970s, but cases still occur, mainly secondary to unpasteurized dairy products from outside the US
    • Brucella abortus' main host is cattle, cases occur from wild bison/elk
    • Brucella Suis' main host is swine
    • Brucella canis' main host is dogs
    • Brucella ceti and pinnipediae find hosts in marine species, cause neurobrucellosis
  • Death from brucellosis occurs in only 2% of cases (CDC).

Transmission

  1. Consumption of poorly cooked meat or unpasteurized dairy products (most common mode of transmission).
  2. Inhalation of bacteria. Increased in those that work in laboratories that work with the bacteria and slaughterhouse workers.
  3. Directly via open skin wounds.
  4. Rare modes of transmission include via breastmilk, sexual transmission, tissue transplant, blood transfusion.

Clinical Symptoms

  • Typical syndrome includes acute to sub-acute febrile illness, associated with fatigue, myalgias,joint pain, and headaches. Patients may also experience hepatomegaly and/or splenomegaly. Fever may "undulate" over days, which is why some describe the disease as "undulant fever." Patients may find symptoms are best in the morning and progressively worsen over the day. The acute illness can progress to a chronic illness. Incubation is 2-3 weeks but may also be insidious in onset.
  • Fever
  • Diaphoresis
  • Myalgias
  • Headache
  • Fatigue
  • Joint/bone pain - occurs in 40% of cases, represented by arthritis, ostemyelitis, bursitis, etc.
  • Nausea/vomiting
  • Abdominal pain

Complications

  1. Cardiac: Endocarditis (2% of cases per W.H.O.) with aortic valve>mitral valve involvement.
  2. Pulmonary: Hilar lymphadenopathy, pneumonitis, pneumonia, effusions.
  3. GI: nausea/vomiting, abdominal pain.
  4. Liver: liver granulomas, hepatitis, hepatocellular necrosis
  5. Gallbladder: cholecystitis
  6. Neuro: "Neurobrucellosis"causing meningitis/encephalitis, neuro abscess, GBS, peripheral neuroapthy.
  7. Bone/joint: tenosynovitis, arthritis, osteomyelitis.
  8. Skin: Rashes, abscess. Rash is nonspecific and can range from erythema nodosum to nodules and petechiae.
  9. ophtho: Uveitis, optic neuritis.
  10. GU: Epididymitis, orchitis, salpingitis.
  11. Reproductive: spontaneous abortion

Chronic brucellosis

  • >12 months of symptoms
  • Divided into 3 categories:
  1. relapse: relapsing symptoms after treatment.
  2. chronic localized infection
  3. Delayed convalescence

Differential Diagnosis

Lower Respiratory Zoonotic Infections

Evaluation

  • Culture is often negative
  • Serology is most useful in diagnosis.

Management

  • Relapse is associated with use of beta-lactams, cephalosporins, macroides.

Adults (>8 years old)

Combination therapy to decrease the incidence of relapse and duration recommended at a minimum of 6 weeks[1]

  • Oral doxycycline (2–4 mg/kg per day, maximum 200 mg/day, in 2 divided doses) or oral

tetracycline (30–40 mg/kg per day, maximum 2 g/day, in 4 divided doses) -and-

  • Rifampin (15–20 mg/kg per day, maximum 600–900 mg/day, in 1 or 2 divided doses).
  • Combination therapy with trimethoprim-sulfamethoxazole (TMP-SMZ) can be used if

tetracyclines are contraindicated.

Children (<8 years old)

  • Oral TMP-SMZ (trimethoprim, 10 mg/kg per day, maximum 480 mg/day; and sulfamethoxazole,

50 mg/kg per day, maximum 2.4 g/day) divided in 2 doses for 4 to 6 weeks.

  • Consider adding rifampin.
  • Tetracyclines (such as doxycycline) should be avoided in children less than 8 years of age.

Post-exposure prophylaxis

  • Doxycycline x 6 weeks.

Antibiotic Sensitivities[2]

Category Antibiotic Sensitivity
Penicillins Penicillin G X1
Penicillin V X1
Anti-Staphylocccal Penicillins Methicillin X1
Nafcillin/Oxacillin X1
Cloxacillin/Diclox. X1
Amino-Penicillins AMP/Amox X1
Amox-Clav X1
AMP-Sulb X1
Anti-Pseudomonal Penicillins Ticarcillin X1
Ticar-Clav X1
Pip-Tazo X1
Piperacillin X1
Carbapenems Doripenem X1
Ertapenem X1
Imipenem X1
Meropenem X1
Aztreonam X1
Fluroquinolones Ciprofloxacin X1
Ofloxacin X1
Pefloxacin X1
Levofloxacin X1
Moxifloxacin X1
Gemifloxacin X1
Gatifloxacin X1
1st G Cephalo Cefazolin X1
2nd G. Cephalo Cefotetan X1
Cefoxitin X1
Cefuroxime X1
3rd/4th G. Cephalo Cefotaxime X1
Cefizoxime X1
CefTRIAXone X1
Ceftaroline X1
CefTAZidime X1
Cefepime X1
Oral 1st G. Cephalo Cefadroxil X1
Cephalexin X1
Oral 2nd G. Cephalo Cefaclor/Loracarbef X1
Cefproxil X1
Cefuroxime axetil X1
Oral 3rd G. Cephalo Cefixime X1
Ceftibuten X1
Cefpodox/Cefdinir/Cefditoren X1
Aminoglycosides Gentamicin S+
Tobramycin S+
Amikacin S+
Chloramphenicol S
Clindamycin R
Macrolides Erythromycin R
Azithromycin R
Clarithromycin R
Ketolide Telithromycin R
Tetracyclines Doxycycline S
Minocycline S
Glycylcycline Tigecycline X1
Daptomycin R
Glyco/Lipoclycopeptides Vancomycin R
Teicoplanin R
Telavancin R
Fusidic Acid X1
Trimethoprim X2
TMP-SMX X2
Urinary Agents Nitrofurantoin X1
Fosfomycin X1
Other Rifampin S+
Metronidazole R
Quinupristin dalfoppristin X1
Linezolid R
Colistimethate X1

Key

  • S susceptible/sensitive (usually)
  • I intermediate (variably susceptible/resistant)
  • R resistant (or not effective clinically)
  • S+ synergistic with cell wall antibiotics
  • U sensitive for UTI only (non systemic infection)
  • X1 no data
  • X2 active in vitro, but not used clinically
  • X3 active in vitro, but not clinically effective for Group A strep pharyngitis or infections due to E. faecalis
  • X4 active in vitro, but not clinically effective for strep pneumonia

Table Overview

See Also

References

  1. http://www.cdc.gov/brucellosis/
  2. WHO Library Cataloguing-in-Publication Data

Brucellosis in humans and animals. Produced by the World Health Organization in collaboration with the Food and Agriculture Organization of the United Nations and World Organisation for Animal Health Principal author: M.J. Corbel. 1.Brucellosis - prevention and control. 2.Brucellosis - epidemiology. 3.Brucellosis - complications. 4.Guidelines. I.Corbel, M.J. II.World Health Organization. III.Food and Agriculture Organization of the United Nations. IV.World Organisation for Animal Health.

  1. CDC Brucellosis Reference Guide https://www.cdc.gov/brucellosis/pdf/brucellosi-reference-guide.pdf
  2. Sanford Guide to Antimicrobial Therapy 2014