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GOOD MORNING! MEDICAL GRANDROUNDS Antonio A. Carlos, Jr., MD First Year Resident 12 June 2008 THE GREAT IMITATOR OBJECTIVES 1. To present a case of liver abscess with an unusual cause; 2. To give an overview on the etiology and management of liver abscess; 3. To discuss melioidosis, its diagnosis and management. Santiago City, Isabela Santiago City, Isabela IDENTIFYING DATA E. B. 58 year-old female Married Farmer Non-diabetic Non-hypertensive CHIEF COMPLAINT Abdominal pain HISTORY OF PRESENT ILLNESS 8 months prior to admission, crampy left upper quadrant abdominal pain occur intermittently no fever, vomiting, and diarrhea 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 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 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 advised admission for the work-up of the hepatic nodules PAST MEDICAL HISTORY (-) Hypertension (-) Diabetes (-) Bronchial asthma (-) Tuberculosis FAMILY MEDICAL HISTORY (+) Hepatitis A (+) Bronchial asthma (-) Hypertension (-) Diabetes (-) Tuberculosis PERSONAL/SOCIAL HISTORY Farmer Non-smoker Non-alcoholic beverage drinker No known allergies REVIEW OF SYSTEMS (-) weight loss (-) fever (-) cough and colds (-) loss of appetite (-) easy fatigability (-) chest pain (-) palpitations 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 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 SALIENT FEATURES 58 year-old female farmer left upper quadrant abdominal pain abdominal CT scan finding of hepatic nodules “What is the nature of the hepatic nodules?” DAY OF ADMISSION Primary Impression Hepatocellular carcinoma Differential Diagnosis Liver Abscess EB Abdominal Pain Hepatic Nodules Hepatocellular CA Primary Metastatic Liver Abscess Etiology?? CBC CT Guided Liver Biopsy Gram Stain Culture and Sensitivity AFB Smear and Culture Cell Block 1st HOSPITAL DAY Patient had febrile episodes, maximum temperature of 39.4°C 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 2nd HOSPITAL DAY Patient still had febrile episodes CBC done Referred to Infectious Disease Service “What is the focus of the fever?” Patient was seen by the Infectious Disease Service Transfer IV site Urinalysis Chest x-ray EB Hepatocellular CA Primary Metastatic Liver Abscess Phlebitis UTI Etiology?? PTB 3rd HOSPITAL DAY Patient was still febrile Liver aspirate culture grew gram negative rods, T/C Pseudomonas Ciprofloxacin was discontinued Piperacillin-Tazobactam 4.5g/IV every 8 hours was started 4th HOSPITAL DAY Liver biopsy showed negative for malignant cells Cytomorphologic features consistent with an acute suppurative infection Liver aspirate culture grew Burkholderia pseudomallei Piperacillin-Tazobactam was shifted to Ceftazidime 1g/IV every 8 hours EB Hepatocellular CA Primary Metastatic Liver Abscess Burkholderia pseudomallei PTB 5th HOSPITAL DAY Blood culture and sensitivity showed no growth after 5 days Day 1 afebrile 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 FINAL DIAGNOSIS Melioidosis Cannot totally rule out Pulmonary Tuberculosis Peptic ulcer disease RECOMMENDATION PTB work-up should be done MELIOIDOSIS 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 100 cases identified during the French occupation of Vietnam in 1948-1954 300 cases identified during the American occupation in the 1970’s, popularly known as the “Vietnamese Time Bomb” EPIDEMIOLOGY Regarded as endemic to Southeast Asia and Northern Australia Corresponds approximately to latitudes o o between 20 N and 20 S Fig. 1 Worldwide distribution of melioidosis 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 ETIOLOGIC AGENT Burkholderia pseudomallei gram negative bacillus bipolar staining safety pin appearance saprophytic considered a Category 3 pathogen by the CDC Resilient organism capable of surviving hostile environmental conditions Produces several virulence factors: exopolysaccharides and lipase phospholipase C hemolysin protease Often called the Great Imitator RISK FACTORS Exposure to aquatic environments and agricultural lands Diabetes mellitus Chronic obstructive pulmonary disease Use of steroids CLINICAL SYNDROMES Sepsis Pneumonia Liver abscess Splenic abscess Skin and soft tissue abscess 4 DISEASE CATEGORIES (CDC, 2000) 1. Acute localized infection ▪ localized as a nodule ▪ results from inoculation through a break in the skin 2. Acute pulmonary infection ▪ produce a clinical picture ranging from mild bronchitis to severe pneumonia ▪ radiologic findings include nodule, upper lobe consolidation, cavitary lesions 3. Acute bloodstream infection ▪ patients with underlying illness such as diabetes, renal failure are affected by this type of disease ▪ usually results in septic shock 4. Chronic suppurative infection ▪ involves the liver, lung, spleen, lymph nodes ▪ may become dormant with exacerbation occurring after primary infection MODES OF ACQUISITION 1. 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 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 3. Ingestion ▪ contamination of potable water in two outbreaks in Northern Australia INCUBATION PERIOD Incubation period of melioidosis is not clearly defined In the Darwin Series, an incubation period of 121 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) DIAGNOSIS Isolation of B. pseudomallei remains the gold standard in diagnosis A modified Ashdown medium with colistin is commonly used Monoclonal antibody latex agglutination test Shown to agglutinate blood culture fluid positive to B. pseudomallei Sensitivity of 95% Specificity of 99.7% TREATMENT Characteristics of Antimicrobial: It should have a bactericidal effect; Should be able to penetrate phagocytic cells; Eliminate or inhibit glycocalyx Treatment of Melioidosis is divided into two stages: 1. an intravenous high intensity stage 2. an oral maintenance stage to prevent recurrence Intravenous Intensive Phase Intravenous ceftazidime is the current drug of choice for melioidosis Meropenem, imipenem, cefoperazonesulbactam are also active Amoxicillim-clavulanate may be used if none of the above are available 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 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 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 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 THANK YOU! CBC Hemoglobin April 23, 2008 9.3 Hematocrit WBC Neutrophils Lymphocytes Eosinophils Monocytes Basophils Platelet 30.9 9.91 84 10 1 5 0 263,000 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 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 Consider calcified granuloma in the left apex. The rest of the lungs are clear. Heart and other chest structures are within normal limits Site of Collection: Post Liver Biopsy April 23, 2008 Results: Identified Organism/s: Burkholderia pseudomallei Light growth Sensitivities: Amikacin Ticarcillin/Clavulanic acid Piperacillin/Tazobactam Cotrimoxazole Ceftazidime Cefepime Ciprofloxacin 6R 28 S 29 S 32 S 25 S 18 S 24 S