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.
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.
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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Well-formed hepatic granuloma from patient with brucellosis.
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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."
Tables
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) |
| Brucella inopinata | unknown | Case report of human infection of a breast implant |
| Brucella microti | Voles | South Moravia, Czech Republic |
| Brucella papionis | Baboons | Tanzania |
| Brucella vulpis | Foxes | Austria |
Study |
No. of Patients |
Fever or Chills |
Arthralgia or Arthritis |
Sweating |
Constitutional symptoms* |
Hepatomegaly |
Splenomegaly |
Memish et al (2000) [16] |
160 |
146 (91.3%) |
105 (65.6%) |
30 (18.8%) |
70 (43.8%) |
9 (5.6%) |
11 (6.9%) |
Kokoglu et al (2006) [17] |
138 |
108 (78.3%) |
107 (77.5%) |
100 (72.5%) |
98 (71%) |
37 (26.8%) |
50 (36.2%) |
Mantur et al (2006) [18] |
495 |
417 (84.2%) |
117 (23.6%) |
19 (3.8%) |
6 (1.2%) |
56 (11.3%) |
95 (19.2%) |
Ruiz-Mesa et al (2005) [19] |
711 |
702 (98.7%) |
353 (49.6%) |
597 (84%) |
533 (75%) |
250 (35.2%) |
148 (20.8%) |
Barroso Garcia et al (2002) [20] |
565 |
441 (78.1%) |
248 (43.9%) |
483 (85.5%) |
472 (83.5%) |
422 (74.7%) |
152 (26.9%) |
Hasanjani Roushan et al (2004) [21] |
469 |
314 (67%) |
252 (53.7%) |
357 (76.1%) |
... |
... |
27 (5.8%) |
Pappas et al (2005) [22] |
100 |
91 (91%) |
44 (44%) |
.. |
26 (26%) |
7 (7%) |
16 (16%) |
Troy et al (2005) [23] |
28 |
25 (89%) |
15 (54%) |
.. |
13 (46%) |
8 (29%) |
5 (18%) |
Andriopoulos et al (2007) [24] |
144 |
144 (100%) |
125 (86.8%) |
138 (95.8%) |
140 (97.2%) |
... |
74 (51.4%) |
Giannakopoulos et al (2006) [25] |
52 |
42 (81%) |
43 (83%) |
8 (15%) |
7 (13%) |
... |
... |
Mantur et al (2004) [26] |
93 |
49 (53%) |
19 (20%) |
... |
... |
... |
... |
Tsolia et al (2002) [27] |
39 |
27 (69%) |
27 (69%) |
8 (21%) |
13 (33%) |
11 (28%) |
15 (38%) |
* Anorexia, asthenia, fatigue, weakness, malaise. |
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