Case Studies. A Complicated Case of Sepsis Involving a Rare Organism in a 46-Year-Old White Woman with Asplenia and a History of Drug Abuse.

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1 A Complicated Case of Sepsis Involving a Rare Organism in a 46-Year-Old White Woman with Asplenia and a History of Drug Abuse Mary Pollard, BS, MLS(ASCP) CM * Lab Med Fall 2015;46:e88-e92 DOI: /LMPWIPVWZLQY624S Patient history Patient: 46-year-old white woman. Chief Complaint: Bloody emesis. Presenting Symptoms: Blood in vomit, 8 to 10 occurrences of diarrhea within the past 24 hours, rash with purpura on extremities, and myalgia. Physical Examination Findings: Hypotension, temperature increased to 38.5 C. Medical History: Traumatic splenectomy in pedestrian-versus-motor vehicle accident (patient was the pedestrian) in 2012, history of cocaine and alcohol abuse. Main Laboratory Findings: Table 1, Table 2, Image 1, Image 2, Image 3. Additional Diagnostic Test Results: A fusiform Gram-negative rod was seen on the preliminary Gram stain from the blood culture bottles. Isolated colonies were oxidase positive. Contaminates were identified as Acinetobacter baumanii and Acinetobacter lwoffi. A specimen was sent to the Department of Health, Bureau of Public Health Laboratories Jacksonville, which definitively identified the oxidasepositive, fusiform Gram-negative rod as Capnocytophaga canimorsus via 16s ribosomal RNA (rrna) gene sequencing. Questions 1. What could have caused the patient s presenting symptoms? 2. Given the laboratory data, what is the patient s diagnosis? 3. What are the treatment options, given the patient s complications? Abbreviations: DIC, disseminated intravascular coagulation; BUN, blood urea nitrogen; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; CK-MB, creatine kinase myocardial band; PT, prothrombin time; PTT, partial thromboplastin time; rrna, ribosomal RNA; D50, 50% dextrose solution; CR, creatinine; GFR, glomerular filtration ratio; MCV, mean cell volume; MCHC, mean cell hemoglobin concentration; RDW, red blood cell distribution width; INR, international normalized ratio Medical Lab Sciences, Department of Biology, University of North Florida, Jacksonville, FL *To whom correspondence should be addressed. mkpoll1231@gmail.com 4. What is the pathogenesis of the infecting organism? Why did the patient s health deteriorate so quickly? 5. The patient died would she have survived with the treatment she was given, in the absence of the salient elements of her medical history? Possible Answers 1. Given the blood in her stool and emesis, the patient was likely experiencing gastrointestinal bleeding. The additional presentation of purpura on her extremities e88 Lab Medicine Fall 2015 Volume 46, Number 4

2 Table 1. Critical Laboratory Findings for the Patient, a 46-Year-Old White Woman Analyte Result Normal Range Interpretation Sodium 138 mmol/l mmol/l Normal Potassium 4.8 mmol/l mmol/l High Chloride 91 mmol/l mmol/l Low CO 2 15 mmol/l mmol/l Low Glucose 33 mg/dl mg/dl Critically low BUN 44 mg/dl 6-22 mg/dl High CR 3.84 mg/dl mg/dl High Anion gap High BUN/CR ratio Normal Calculated osmolality 283 milliosmole/kg milliosmole/kg Normal Estimated GFR 14 ml/min/1.73 cm 3 >60 ml/min/1.73 cm 3 Low Albumin 3.6 g/dl g/dl Low Total protein 6.6 g/dl g/dl Normal Total bilirubin 1.7 mg/dl mg/dl High Direct bilirubin 0.8 mg/dl mg/dl High Alkaline phosphatase 119 U/L U/L High ALT 150 U/L U/L High AST 476 U/L U/L High Indirect bilirubin 0.9 mg/dl mg/dl Normal ph Low Lipase 30 U/L 0-60 U/L Normal Lactic acid High Troponin I < Normal CK 16.6 <5 High CK-MB High Hematology White blood cell /mm /mm 3 High Red blood cell /mm /mm 3 Normal Hemoglobin 15.2 g/dl g/dl Normal Hematocrit 45.1% 37%-47% Normal MCV 90.7 fl fl Normal MCHC 30.6 g/dl g/dl Normal RDW 17.9% 12.0%-16.1% High Platelet /L /L Critically low D-dimer >20 FEU/mL FEU/mL High PT 53.8 sec sec High INR High PTT 199 sec sec High Fibrinogen 94 mg/dl mg/dl Low BUN, blood urea nitrogen; CR, creatinine; GFR, glomerular filtration ratio; ALT, alamine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; CK-MB, creatine kinase myocardial band; MCV, mean cell volume; MCHC, mean cell hemoglobin concentration; RDW, red blood cell distribution width; PT, prothrombin time; INR, international normalized ratio; PTT, partial thromboplastin time. suggests that she had a noncongenital coagulopathy: potentially, disseminated intravascular coagulation (DIC). DIC commonly occurs as a secondary complication to infections, pregnancy, tissue injury, vascular injury, snakebites, and heat stroke. 1 The patient s elevated temperature suggested that these complications were secondary to sepsis. 2. The chemistry results for our patient (Table 1) suggest that she had kidney injury (elevated blood urea nitrogen [BUN] and creatinine levels), liver injury (elevated alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), and hemolysis (elevated bilirubin level). She also had acidosis (low blood ph), which was probably caused by muscle breakdown (elevated lactic acid and creatine kinase [CK] levels, along with CK myocardial band [CK-MB]) and is consistent with her muscle pain. Her hematology results (Table 1 and Table 2) show a high white blood cell count with an increase in immature granulocytes, toxic granulation, and vacuoles (Image 1), Downloaded from Fall 2015 Volume 46, Number 4 Lab Medicine e89

3 Image 1 Intra- and extracellular organisms, toxic granulation, and vacuoles observed in a Wright stain of the peripheral blood smear (original magnification 1000 of the patient, a 46-year-old white woman. Table 2. Hematology Differential for our Patient, a 46-Year-Old White Woman Cell Type Percentage Normal Range, % Interpretation Neutrophil Low Band 21 0 High Lymphocyte Low Variant lymphocyte 2 0 High Monocyte Low Eosinophil Low Basophil Normal Metamyelocyte 29 0 High Myelocyte 13 0 High Promyelocyte 0 0 Normal Poikilocyte Moderate None High Schistocyte Occasional None High Other notes Toxic granulation and vacuoles present Intra-/extracellular organisms present consistent with infection. The coagulation assays are consistent with disseminated intravascular coagulation (DIC), showing prolonged prothrombin time (PT) and partial thromboplastin time (PTT), elevated D-dimer level, and low fibrinogen level. Her bloody feces at presentation was caused by her critically low platelet count due to the DIC. I observed an organism in the peripheral blood smear of the patient (Image 1), which provides an explanation of why all these conditions manifested. This patient was experiencing an extensive case of sepsis. In most cases, intra- and extracellular organisms can only be observed when a slide is made with the buffy coat of a centrifuged specimen; however, this case involved copious neutrophils showing ingested organisms in an uncentrifuged specimen (Image 1). 3. In cases of sepsis such as that of the patient, which involve multiple complications, the goal is to treat the primary condition. Initially, multiple antibiotics are used to cover a broad spectrum of potential pathogens. Once the organism is identified, more-specific antibiotics can be used if the organism shows increased drug resistance. Treatment of disseminated intravascular coagulation (DIC) includes replacing the coagulation factors and platelets that are being consumed. Cryoprecipitate or fresh frozen plasma and platelets should be administered; however, platelets are contraindicated if the patient has a fever. 1 Currently, there are no direct treatment options for secondary liver or kidney injury. 2,3 Given this patient s critically low glucose level, she should receive glucose concentrate; also, she should receive bicarbonate concentrate to compensate for her acidosis. e90 Lab Medicine Fall 2015 Volume 46, Number 4

4 Image 2 Organism (from specimen from the patient, a 46-year-old white woman) isolated on sheep s blood agar. Note scant growth when incubated at 37 C in CO 2 at 5 days. Image 3 Gram stain of growth (from specimen from the patient, a 46-yearold white woman) observed on blood agar (original magnification The Department of Health Bureau of Public Health Laboratories Jacksonville definitively identified the pathogen as Capnocytophaga canimorsus via 16s ribosomal RNA (rrna) sequencing. This bacterium colloquially has been known to feed off exposed glycoproteins, allowing it to evade cellular immune response. Sialidase on the bacterial surface contributes to the bacterium s persistence and virulence. Sialidase removes terminal sialic acid from macrophage and epithelial cell surfaces, reducing its ability to bind microbes and to suppress the immune response. Sialidase is used to expose masked sugars on glycoproteins, on which the bacterium feeds. In the work of Mally et al, 4 C. canimorsus was shown to be highly selective for sugar utilization. When supplemented with glucose or galactose, there was poor growth, and successful colonies were observed when supplemented with N-acetyl-glucosamine and N-acetylgalactosaminyl. 4 Most isolates thrive on blood agar, but this strain did not. This sugar specificity could relate to the organism s poor growth on plated media and lack of initial identification in many cases. 5. The patient received 8 units of fresh frozen plasma, 1 unit of platelets, and 1 unit of leukoreduced red blood cells to treat her symptoms caused by disseminated intravascular coagulation (DIC). She was also given pantoprazole for gastrointestinal bleeding, norepinephrine bitartrate for low blood pressure, 50% dextrose solution (D50) for low glucose, and bicarbonate for acidosis. Capnocytophaga canimorsus has shown resistance to gentamycin, aztreonam, trimethoprim-sulfamethoxazole, and aminoglycosides. 5 The patient was given vancomycin, ciprofloxacin, cefepime hydrochloride, metronidazole, and azithromycin. Although the identity of the organism was unknown at the time of administration, the antibiotics given would have worked to treat the patient. However, C. canimorsus septicemia presents a more life-threatening disease in patients whose spleens have been removed and in immunocompromised patients. This patient had asplenia, and her history of drug and alcohol use had reduced her immune response to the infection. The mortality rate observed in cases of sepsis with C. canimorsus is roughly 30%; however, because the patient developed secondary complications (DIC, acute renal injury, and liver injury), she had a severely reduced likelihood of survival. 6-8 Chronic use of controlled substances may have hindered the patient s perception of her symptoms, delaying her presentation to the hospital. In some cases of cocaine use, DIC, renal injury, and hypotension have been observed, which may predispose the patient toward these complications. 9 LM Downloaded from Fall 2015 Volume 46, Number 4 Lab Medicine e91

5 References 1. McKenzie, S; Williams, J Aquired disorders of hemostasis associated with bleeding. Clinical laboratory hematology, second edition Zarjou, A; Agrawal, A Sepsis and acute kidney injury. Journal of American society of nephrology, 22 (6): asnjournals.org/content/22/6/999.full 3.. Furutani, M; Monden K; Adachi, Y; Funaki, N; Higashtsuji; Fujita, S; Mise, M; Ishiguro, S; Kitao, T Immunologic activation of hepatic macrophages in septic rats: a possible mechanism of sepsisassociated liver injury. Journal of laboratory and clinical medicine, 123 (3): Mally M, Shin H, Paroz C, Landmann R, Cornelis G. Capnocytophaga canimorsus: a human pathogen feeding at the surface of epithelial cells and phagocytes. PLoS Pathog. 2008;4(10). doi: / annotation/8d781d6d-5d4e-46ea-afd9-bb3ede03fcb4. 5. Low SC-M; Greenwood JE. Capnocytophaga canimorsus: infection, septicaemia, recovery, and reconstruction. J Med Microbiol. 2008;57(7): Janda, M; Graves, M; Lindquist, D; Probert, W Diagnosing Capnoctyophaga canimorsus infections. Emerging infectious disease, center of disease control, 12 (2): cdc.gov/eid/article/12/2/pdfs/ pdf 7. Jolivet-Gougeon A. Antimicrobe: Capnocytophaga species. Antimicrobe (journal) Web site. Available at: org/b92.asp. Accessed on: September 24, Lion C, Escande F, Burdin JC. Capnoctyophaga canimorsus infection in human: review of the literature and cases report. Eur J Epidemiol. 1996;12(5): Marcelo, S; Roth, D; Reddy, K; Fernandez, J; Albores-Saavedra, J; Schiff, E Hepatic dysfunction accompanying acute cocaine intoxication. Journal of hepatology, 12 (3): journal-of-hepatology.eu/article/ (91)90832-v/abstrac e92 Lab Medicine Fall 2015 Volume 46, Number 4