Brucellosis

brucellosis

1. Brucellosis: By: Somayyeh Nasiripour , pharm.D Assistant professor of clinical pharmacy

2. is a zoonotic infection transmitted to humans by contact with fluids from infected animals (sheep, cattle, goats, pigs, or other animals) or derived food products such as unpasteurized milk and cheese. one of the most widespread zoonoses worldwide Brucellosis has high morbidity both for humans and animals; it is an important cause of economic loss and a public health problem in many developing countries

3. CLINICAL MANIFESTATIONS incubation period : 1-4 weeks it may be as long as several months Brucella melitensis causes more severe infection than Brucella abortus Brucella canis is infrequently associated with human disease, and reported cases have usually been mild

4. is a systemic infection with a broad clinical spectrum, ranging from asymptomatic disease to severe and/or fatal illness Clinical and laboratory features vary widely ( table 1 and table 2 ) The main presentations are acute febrile illness, with or without signs of localization, and chronic infection. Infection among children is generally more benign than in adults with respect to likelihood and severity of complications and response to treatment Brucellosis in pregnancy is associated with risk of spontaneous abortion, premature delivery, miscarriage, and intrauterine infection with fetal death

5. Acute brucellosis  Acute illness usually consists of the insidious onset of fever, night sweats (with a strong, peculiar, moldy odor), arthralgia, myalgia, low back pain, and weight loss as well as weakness, fatigue, malaise, headache, dizziness, depression, and anorexia A significant percentage of patients may have dyspepsia, abdominal pain, and cough. Physical findings are variable and nonspecific. Hepatomegaly , splenomegaly , and/or lymphadenopathy may be observed. brucellosis can affect any organ system

6. Osteoarticular involvement is the most common presentation The sacroiliac joints and large joints of the lower limbs are most frequently involved [ Spondylitis is a serious complication of brucellosis; it is more prevalent in older patients and patients with prolonged illness prior to treatment

7. Osteoarticular involvement is the most common presentation The sacroiliac joints and large joints of the lower limbs are most frequently involved Spondylitis is a serious complication of brucellosis; it is more prevalent in older patients and patients with prolonged illness prior to treatment

8. Genitourinary involvement occurs in 2 to 20 percent of cases; orchitis and/or epididymitis are the most common manifestations Pulmonary involvement occurs in up to 7 percent of patients with Gastrointestinal involvement can present with clinical hepatitis (3 to 6 percent of cases) Hematological abnormalities, including anemia, leukopenia , thrombocytopenia, pancytopenia ,… ●Neurological involvement occurs in 2 to 7 percent of cases. Manifestations include meningitis (acute or chronic), encephalitis, .. ●Cardiac involvement is relatively rare ●Ocular involvement ●Dermatologic manifestations .

9. Relapse The rate of relapse following treatment is about 5 to 15 percent Relapse usually occurs within the first six months following completion of treatment, although it may occur up to 12 months following completion of treatment Causes of relapse include inadequate choice of antibiotics, shortened treatment duration, lack of adherence, or localized foci of infection relapse due to antibiotic resistance is rare

10. Chronic brucellosis  Chronic brucellosis refers to patients with clinical manifestations for more than one year after the diagnosis of brucellosis is established Chronic brucellosis is characterized by localized infection (generally spondylitis, osteomyelitis, tissue abscesses, or uveitis) and/or relapse

11. DIAGNOSIS laboratory findings should be interpreted together with clinical manifestations, exposure history, occupation, and history of past infection Laboratory tools for diagnosis of brucellosis include culture, serology, and polymerase chain reaction (PCR)

12. Ideally, the diagnosis is made by culture of the organism from blood or other sites such as bone marrow or liver biopsy specimens. The sensitivity of culture is limited if standard blood cultures are negative and brucellosis remains a consideration, Serologic testi ng should also be performed; serum agglutination and ( ELISA) are the most common serologic tests.

13. Serologic tests  rising titers of specific serum antibodies The interpretation of serological tests can be difficult, particularly in the setting of chronic infection, reinfection , relapse, and in endemic areas where a high proportion of the population has antibodies against brucellosis Positive serological test results can persist long after recovery in treated individuals, so it is not always possible to distinguish serologically between active and past infection

14. White blood cell counts are usually normal to low; pancytopenia can occur. Minor abnormalities in hepatic enzymes are relatively common

15. Radiographs, bone scans, ( CT), ( MRI), and echocardiography may be helpful in evaluating focal disease but do not provide a definitive diagnosis.

16. TREATMENT TREATMENTThe goal of brucellosis therapy is to control the illness and prevent complications, relapses, and sequelae [ use of antibiotics with activity in the acidic intracellular environment ( doxycycline , rifampin ), use of combination regimens, and prolonged duration of treatment

17. Major regimens  two major regimens for the treatment of adults with uncomplicated brucellosis ( eg , not having spondylitis , neurobrucellosis , or endocarditis ) Monotherapy and regimens shorter than six weeks are not accepted treatment strategies for brucellosis

18. Doxycycline 100 mg orally twice daily for six weeks, plus streptomycin 1 g intramuscularly once daily for the first 14 to 21 days. It has been suggested that gentamicin (5 mg/kg) may be substituted for streptomycin; equal efficacy has been demonstrated The optimal duration of gentamicin is uncertain; 5 days to 14 days is acceptable ● Doxycycline 100 mg orally twice daily plus rifampin 600 to 900 mg (15 mg/kg) orally once daily. Both drugs are administered for six weeks.

19. Alternative agents  Fluoroquinolones ( ciprofloxacin 500 mg twice daily or ofloxacin 200 mg twice daily) have good in vitro activity against Brucella can be used in combination with doxycycline or rifampin but are not appropriate first-line agents They may be useful in the setting of drug resistance, antimicrobial toxicity, and some cases of relapse doxycycline and trimethoprim-sulfamethoxazole (TMP-SMX; one double-strength tablet twice a day), since the strain is resistant to rifampin

20. In general, longer courses of therapy (at least 12 weeks) are warranted for treatment of spondylitis , neurobrucellosis , endocarditis , or localized suppurative lesions at least three drugs are generally warranted in the setting of neurobrucellosis , endocarditis , and localized suppurative lesions

21. Spondylitis two antibiotic agents for at least 12 weeks Patients with Brucella spondylitis appear to respond better to doxycycline (100 mg orally twice daily for 12 weeks) plus streptomycin (1 g intramuscularly once daily for the first 14 to 21 days) than to doxycycline-rifampin

22. Neurobrucellosis two or three drugs that cross the blood-brain–cerebrospinal fluid (CSF) barrier for treatment of neurobrucellosis . Reasonable regimens include doxycycline , rifampin , and either ceftriaxone Ceftriaxone -based regimens may be more successful and allow shorter duration of

23. Pregnant women  Regimens include rifampin (900 mg once daily), with or without TMP-SMX (one double-strength tablet twice a day) for six weeks ceftriaxone is also a reasonable regimen Use of TMP-SMX during the last week prior to delivery is associated with kernicterus and should be avoided if possible

24. Children with a tetracycline (for children ≥8 years) or TMP-SMX (for children <8 years) and at least one other agent ( rifampin , gentamicin , or streptomycin ,