GOOD MORNING!

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• GOOD MORNING!

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MEDICAL GRANDROUNDS

• Antonio A. Carlos, Jr., MD
• First Year Resident
• 12 June 2008

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THE GREAT IMITATOR
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OBJECTIVES

• To present a case of liver abscess with an
  unusual cause
• To give an overview on the etiology and
  management of liver abscess
• To discuss melioidosis, its diagnosis and
  management.

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• Santiago City, Isabela

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• Santiago City, Isabela

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IDENTIFYING DATA

• E. B.
• 58 year-old female
• Married
• Farmer
• Non-diabetic
• Non-hypertensive

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CHIEF COMPLAINT

• Abdominal pain

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HISTORY OF PRESENT ILLNESS

• 8 months prior to admission,
• crampy left upper quadrant abdominal pain
• occur intermittently
• no fever, vomiting, and diarrhea

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• consulted at a local hospital
• abdominal ultrasound showed the presence of three
  hepatic nodules
• no treatment was done due to financial
  constraints
• lost to follow-up

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• 2 months prior to admission,
• intermittent abdominal pain
• consulted in another local hospital
• abdominal CT scan showed the presence of five
  hepatic nodules
• advised biopsy of the nodules
• opted to seek second opinion

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• 2 weeks prior to admission,
• consulted a gastroenterologist in Manila
• EGD was done
• showed gastric ulcer
• biopsy of the ulcer showed positive for
  Helicobacter pylori
• started on H. pylori regimen

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• advised admission for the work-up of the hepatic
  nodules

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PAST MEDICAL HISTORY

• (-) Hypertension
• (-) Diabetes
• (-) Bronchial asthma
• (-) Tuberculosis

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FAMILY MEDICAL HISTORY

• () Hepatitis A
• () Bronchial asthma
• (-) Hypertension
• (-) Diabetes
• (-) Tuberculosis

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PERSONAL/SOCIAL HISTORY

• Farmer
• Non-smoker
• Non-alcoholic beverage drinker
• No known allergies

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REVIEW OF SYSTEMS

• (-) weight loss
• (-) fever
• (-) cough and colds
• (-) loss of appetite
• (-) easy fatigability
• (-) chest pain
• (-) palpitations

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PHYSICAL EXAMINATION

• GS conscious, coherent, ambulatory,
• not in respiratory distress
• VS BP 100/70 HR 82 RR 18 T 36.9
• HEENT anicteric sclerae, pale palpebral
• conjunctivae, no nasoaural
  discharge,
• no CLAD
• CL symmetric chest expansion,
• clear breath sounds

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• CVS adynamic precordium, normal rate,
• regular rhythm, distinct S1 and S2
• ABD flat, normoactive bowel sounds, soft,
• () direct tenderness on LUQ,
• no guarding, no organomegaly
• EXT no edema, no cyanosis,
• full and equal pulses

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SALIENT FEATURES

• 58 year-old female
• farmer
• left upper quadrant abdominal pain
• abdominal CT scan finding of hepatic nodules

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What is the nature of the hepatic nodules?
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DAY OF ADMISSION

• Primary Impression
• Hepatocellular carcinoma
• Differential Diagnosis
• Liver Abscess

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EB
Abdominal Pain
Hepatic Nodules
Hepatocellular CA
Liver Abscess
Primary
Metastatic
Etiology??
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• CBC

• CT Guided Liver Biopsy

Gram Stain
Culture and Sensitivity
AFB Smear and Culture
Cell Block
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1st HOSPITAL DAY

• Patient had febrile episodes, maximum temperature
  of 39.4C
• Blood culture was done
• Started on Metronidazole 50mg/IV q8
  Ciprofloxacin 500mg/tab, 1 tablet 2x a day
  Paracetamol 500mg/tab, 1 tablet every 4 hours

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2nd HOSPITAL DAY

• Patient still had febrile episodes
• CBC done
• Referred to Infectious Disease Service

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What is the focus of the fever?
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• Patient was seen by the Infectious Disease
  Service

Transfer IV site
Urinalysis
Chest x-ray
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EB
Liver Abscess
UTI
PTB
Phlebitis
Hepatocellular CA
Etiology??
Primary
Metastatic
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3rd HOSPITAL DAY

• Patient was still febrile
• Liver aspirate culture grew gram negative rods,
  T/C Pseudomonas

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• Ciprofloxacin was discontinued
• Piperacillin-Tazobactam 4.5g/IV every
• 8 hours was started

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4th HOSPITAL DAY

• Liver biopsy showed negative for malignant cells
• Cytomorphologic features consistent with an acute
  suppurative infection

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• Liver aspirate culture grew Burkholderia
  pseudomallei
• Piperacillin-Tazobactam was shifted to
  Ceftazidime 1g/IV every 8 hours

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EB
Liver Abscess
PTB
Hepatocellular CA
Burkholderia pseudomallei
Primary
Metastatic
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5th HOSPITAL DAY

• Blood culture and sensitivity showed no growth
  after 5 days
• Day 1 afebrile

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6th HOSPITAL DAY

• Day 2 afebrile
• Patient decided that blood transfusion
• would be done in Isabela
• Patient was discharged with follow-up
• after 2 months

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FINAL DIAGNOSIS

• Melioidosis
• Cannot totally rule out
• Pulmonary Tuberculosis
• Peptic ulcer disease

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RECOMMENDATION

• PTB work-up should be done

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MELIOIDOSIS
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HISTORICAL BACKGROUND

• Named from the Greek melis (distemper of asses)
  and eidos (resemblance)
• First described by pathologist Alfred Whitmore
  among morphia addicts in Burma in 1911
• In 1917, Stanton and Fletcher identified the
  bacteria that cause the disease

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• 100 cases identified during the French occupation
  of Vietnam in 1948-1954
• 300 cases identified during the American
  occupation in the 1970s, popularly known as the
  Vietnamese Time Bomb

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EPIDEMIOLOGY

• Regarded as endemic to Southeast Asia and
  Northern Australia
• Corresponds approximately to latitudes between
  20oN and 20oS

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• Fig. 1 Worldwide distribution of melioidosis

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REPORTED CASES

• In Australia, 40 cases per 100,000 in 2002
• In Thailand, 1,100 cases between 2004-2005
• In Malaysia, 50 cases in 2002
• In Singapore, 57 cases in 2004
• In Taiwan, 43 cases in 2004
• In Philippines, not reported in the world
  literature

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ETIOLOGIC AGENT

• Burkholderia pseudomallei
• gram negative bacillus
• bipolar staining
• safety pin appearance
• saprophytic
• considered a Category 3 pathogen by the CDC

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• Resilient organism capable of surviving hostile
  environmental conditions
• Produces several virulence factors
• exopolysaccharides and lipase
• phospholipase C
• hemolysin
• protease
• Often called the Great Imitator

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RISK FACTORS

• Exposure to aquatic environments and agricultural
  lands
• Diabetes mellitus
• Chronic obstructive pulmonary disease
• Use of steroids

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CLINICAL SYNDROMES

• Sepsis
• Pneumonia
• Liver abscess
• Splenic abscess
• Skin and soft tissue abscess

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4 DISEASE CATEGORIES (CDC, 2000)

• Acute localized infection
• ? localized as a nodule
• ? results from inoculation through a break in
  the skin
• Acute pulmonary infection
• ? produce a clinical picture ranging from mild
• bronchitis to severe pneumonia
• ? radiologic findings include nodule, upper lobe
  
• consolidation, cavitary lesions

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• Acute bloodstream infection
• ? patients with underlying illness such as
  diabetes,
• renal failure are affected by this type
  of disease
• ? usually results in septic shock
• Chronic suppurative infection
• ? involves the liver, lung, spleen, lymph nodes
• ? may become dormant with exacerbation occurring
  
• after primary infection

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MODES OF ACQUISITION

• Inoculation
• ? major mode of acquisition
• ? wounds to the feet of rice farmers are
• common sites of inoculation
• ? 25 in the Darwin study gave a history of
• an inoculation injury prior to
  presentation

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• 2. Inhalation
• ? based on studies of US soldier helicopter crew
  
• in Vietnam
• ? non-ambulant patients in Singapore acquired
• the disease without exposure to soil or water

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• 3. Ingestion
• ? contamination of potable water in two
• outbreaks in Northern Australia

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INCUBATION PERIOD

• Incubation period of melioidosis is not clearly
  defined
• In the Darwin Series, an incubation period of
  1-21 days has been defined
• Incubation periods of as long as 24 to 29 years
  in ex-servicemen who were in Papua New Guinea and
  Vietnam have been described (hence the Vietnamese
  time bomb)

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DIAGNOSIS

• Isolation of B. pseudomallei remains the gold
  standard in diagnosis
• A modified Ashdown medium with colistin is
  commonly used

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• Monoclonal antibody latex agglutination test
• Shown to agglutinate blood culture fluid positive
  to B. pseudomallei
• Sensitivity of 95 Specificity of 99.7

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TREATMENT

• Characteristics of Antimicrobial
• It should have a bactericidal effect
• Should be able to penetrate phagocytic cells
• Eliminate or inhibit glycocalyx

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• Treatment of Melioidosis is divided into two
  stages
• 1. an intravenous high intensity stage
• 2. an oral maintenance stage to prevent
  recurrence

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• Intravenous Intensive Phase
• Intravenous ceftazidime is the current drug of
  choice for melioidosis
• Meropenem, imipenem, cefoperazone-sulbactam are
  also active
• Amoxicillim-clavulanate may be used if none of
  the above are available

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• Maintenance Phase
• Treatment with cotrimoxazole and doxycycline be
  used for 12 to 20 weeks to reduce the rate of
  recurrence
• Co-amoxiclav is an alternative for those who are
  unable to take cotrimoxazole or doxycycline

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PROGNOSIS

• Without access to antibiotics, the septicemic
  form of melioidosis has a mortality that exceeds
  90
• With appropriate antibiotics, mortality rate is
  about 10 for uncomplicated cases
• Relapse rate occurs in 10 to 20 of patients

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BIOLOGIC WEAPONS AGENT

• CDC classified melioidosis as Category B
  biological weapons agent
• Good candidate as a bioweapon because it is
  easily available in the tropics, easy to
  cultivate, sturdy, high potential to become
  bacteremic
• Countries studying melioidosis as a bioweapon are
  USA, Russia, and Egypt

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ACKNOWLEDGMENT

• Dr. Miguel Fores
• Dr. Tarcela Gler
• Dr. Jodor Lim
• Dr. Mabel Aloc
• Dr. Sasa Samson
• Dr. Ronnie Benitez
• Dr. John Jarin
• Dr. JC Sevilla

• Arianne
• Ivy
• Abbey
• Mara
• Gelo
• Ed B.
• MM

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• THANK YOU!

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CBC April 23, 2008
Hemoglobin 9.3
Hematocrit 30.9
WBC 9.91
Neutrophils 84
Lymphocytes 10
Eosinophils 1
Monocytes 5
Basophils 0
Platelet 263,000
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CBC April 25, 2008
Hemoglobin 8.6
Hematocrit 28.6
WBC 5.91
Neutrophils 65
Lymphocytes 19
Eosinophils 4
Monocytes 12
Basophils 0
Platelet 220,000
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Urinalysis
Color Yellow
Transparency Clear
pH Acidic
Specific Gravity 1.025
Sugar Negative
Proteins Negative
Ketones Negative
Nitrites Negative
Leukocyte Esterase Negative
Blood 0
RBC 0
WBC 0 1
Epithelial Cells 2
Bacteria 3
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• Consider calcified
• granuloma in the left
• apex.
• The rest of the lungs are
• clear.
• Heart and other chest
• structures are within
• normal limits

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Site of Collection Post Liver Biopsy April 23, 2008
Results Identified Organism/s Burkholderia pseudomallei Light growth
Sensitivities Amikacin 6 R Ticarcillin/Clavulanic acid 28 S Piperacillin/Tazobactam 29 S Cotrimoxazole 32 S Ceftazidime 25 S Cefepime 18 S Ciprofloxacin 24 S
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