Outlines. Introduction Prevalence Resistance Clinical presentation Diagnosis Management Prevention Case presentation Achievements

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1 Amal Meas Al-Anizi, PharmD Candidate KSU, Infectious Disease Rotation 2014

2 Outlines Introduction Prevalence Resistance Clinical presentation Diagnosis Management Prevention Case presentation Achievements

3 Brucellosis (Malta fever) is a zoonotic infection caused by the bacterial genus Brucella. The bacteria are transmitted from animals to humans by: Ingestion through infected products Direct contact with an infected animal Inhalation of aerosols Brucellosis continues to be a major public health concern worldwide and is the most common zoonotic infection.

4 Brucella organisms, which are small aerobic intracellular cocco-bacilli, localize in the reproductive organs of host animals They are presented in large numbers in the animal s urine, milk, placental fluid, and other fluids The following 4 species have moderate-tosignificant human pathogenicity: Brucella melitensis (from sheep; highest pathogenicity) Brucella suis (from pigs; high pathogenicity) Brucella abortus (from cattle; moderate pathogenicity) Brucella canis (from dogs; moderate pathogenicity)

5 The infection causes more than 500,000 infections per year worldwide. The annual number of reported cases in United States (now about 100) has dropped significantly because of aggressive animal vaccination programs and milk pasteurization.

6 In Saudi Arabia, human infection with B. melitensis is commonly encountered (80%-100%) The infection is highly contagious in the natural animal host, and it spreads rapidly within the herd.

7 Prevalence of brucellosis in Saudi Arabia Makkah Asir Goat 0.8% Sheep 0.5% Camels 2.8% Cows 3.6% Goats18.2% Sheep12.3% Camels 22.6% Cows15.5% Prevalence of brucellosis in Saudi Arabia. Ann Saudi Med 1986;6(Suppl):

8 Symptoms of Brucellosis: non-specific Fever, sweats, malaise, anorexia, headache, back-pain. Onset: acute, beginning within 2 to 4 weeks after inoculation. Depression common and often out of proportion to severity of symptoms. Mild lymphadenopathy reported in 10 to 20% of cases.

9 Complete history should be obtained for individual with unexplained fever and nonspecific complaints who has a possible source of exposure (contact with animal tissues, ingestion of unpasteurized milk or cheese). The diagnosis of brucellosis is established when Brucella are isolated from blood, bone marrow, or other body fluids or tissues

10 The percentage of cases with positive blood cultures ranges from 15 to 70% The majority of blood cultures are positive between the 7th and 21st day The presence of Brucella can be detected by the third day of incubation

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12 Endocarditis Arthritis Hepato-spleeno-megaly CNS infection (neurobrucellosis)

13 Complete blood count Leukocytosis is rare in brucellosis, Anemia is reported in 75% of patients. Liver enzymes A slight elevation in liver enzyme levels is a very common finding. These elevated levels may reflect the severity of hepatic involvement and correlate clinically with hepatomegaly.

14 Arthrocentesis Although significant joint effusion is uncommon, arthrocentesis may occasionally be needed to exclude septic arthritis. Chest radiograph Should be obtained if respiratory symptoms are present or if a source of infection is not apparent Serologic tests Include tube agglutination and enzyme-linked immunosorbent assay (ELISA)

15 Doxycycline 100 mg orally twice daily for six weeks streptomycin Rifampin 1 Gentamicin 600 g IM to once 900 daily mg (15 (5 mg/kg) for the mg/kg) first orally 5-14 once days to 21 days daily Both drugs are administered for six weeks

16 Alternative agents : Fluoroquinolones (Ciprofloxacin 500 mg twice daily or Ofloxacin 200 mg twice daily)in combination with doxycycline or rifampin, but are not appropriate first line agents They may be useful in the setting of drug resistance.

17 Brucellosis may be prevented via vaccination, which is effective for cattle, sheep, and goats Pasteurization of milk is important for the prevention of transmission to humans.

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19 Patient demographics AA is 17 years old Saudi female, medically free

20 Chief Complain Patient came to the ER complaining of fever, back pain abdominal pain, and vomiting

21 History of present illness 17 years old female complaining of one month history of documented high fever on daily basis 2-3 times associated chills and rigors. Associated with vomiting and nauseated most of the time and she has history of back pain, generalized body pain and myalgia

22 History of present illness Patient has history of animal contact (goat and sheep) but no history of ingestion of row milk Patient came to ER with same symptoms and blood sample was taken at first presentation and was incubated for 66 hours and showed Brucella spp. With positive IgM and IgG against Brucella and patient called

23 Past medical history None Past medication history None

24 Family History: Father has IHD post CABG and mother has no chronic disease Social History: Student at Intermediate school lives with family Allergies: NKA Surgical History: None

25 Physical Examination Hight 150 cm Wight 48.1 Kg Vital Signs T BP RR HR O sat 39.1 C 90/57 mmhg bpm 100 % CNS : Conscious, alert, oriented x 3 CVS: S1+ S2 +query ejection systolic murmur Chest: Bilaterally Clear Abd: Soft and lax none tender and not distended

26 Laboratory findings Chemistry Urea 3.7 Na 137 SCr 62 CrCl 100 K 4.1 CL 101 CRP 5.97 Liver enzymes ALT 74 ALP 189 AST 59 CBC WBC 4.17 RBC 5.37 HBG 9.7 PLT 255 ESR 84

27 Laboratory findings Neck CT Result: Enlarged left lymphnode, no other lymphadenopathy documented Chest CT Result: Bilateral benign appearing axillary lymph node with no evidence of lymphadenopathy

28 Day 1: Initial Assessment: 17 years old female, diagnosed with brucellosis and query infective endocarditis Plan: Recommended - Blood Culture Sensitivity Rifampin dose is mg once - Paracetamol 1 g IV STAT daily - Urgent Echo to R/O infective endocarditis - Start Doxycycline 100 mg Q12hr - & Rifampin 300 mg Q24hr

29 Day 2: S: patient is clinically stable, not nauseated or vomiting O: T max BP RR HR O sat 36.7 C 98/77 mmhg bpm 98% WBC HB K Na Cl AST ALT ALP Scr Urea

30 Day 2: A/P: Corrected by Antimicrobial stewardship team 1- Increase Rifmpin to 600 mg Q24hr 2- Add Gentamicin 240 mg IV Daily for 14 days

31 Day 3 S: patient is clinically stable, no new issues O: Labs: No change Blood culture grows Brucella which has intermediate sensitivity to Rifampin Echo : Is Normal no vegetation and infective endocarditis is ruled out

32 Day 3 A/P: 1- D/C Rifampin 2- Start Ciprofloxacin 500 mg PO Q12hr

33 Day 6 Day 14 A/P Patient completed Gentamicin course and for discharge

34 Day 4-14 S: patient is clinically stable, no new issues O: Labs: No change A/P: patient stay until Gentamicin course complete

35 Discharge medication Medication Ciprofloxacin Doxycycline Rifampicin Strength and frequency 500 mg Q12hr. 100 mg Q12hr 600 mg daily

36 Follow up monitoring Continue on : Ciprofloxacin 500 mg Q12hr for 4 weeks Doxycycline 100 mg Q12hr for 4 weeks Next appointment after 4 weeks Plan : 1- CRP and ESR 2- Brucella Serology

37 Follow up Monitoring Monitor for relapse and check antibiotic adherence. At a minimum Patients with uncomplicated disease should be seen in the third and sixth weeks of treatment. Follow-up at 3, 6, and 12 months is usually advised. The indicators of successful treatment include weight gain, absence of fever, disappearance of positive signs, and general wellbeing.

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