Case #1

Alexa Simon MSIVSeptember 19, 2007

UNC Infectious Disease

CC: Nausea vomiting, fever

HPI: 56 y/0 AAF with history significant for ovarian cancer stage IIIC with a complicated surgical history including debulking surgery in 2005, ileocecal resection, and recent repair of enterocutaneous fistula presented to Johnston Memorial with acute onset of nausea, vomiting, fever and abdominal pain.

HPI cont….

At JM she was found on CT scan to have fluid collection in the anterior subcutaneous tissue.

She was started on Zosyn

Patient was transferred to Gyn/Onc at UNC and started on Ceftazidine and Flagyl.

HPI cont….She progressively became more hypotension with

increasing 02 requirements:

Became obtunded and ID consult team was paged.

The Ob/gyn resident ended phone call to ID saying “I need to go intubate the patient.”

Tumor HistoryPrior to 2005 was healthy9/2005: Presents with abdominal pain

CT with massive ascites and 2 large adnexal masses CA-125>300

9/29/2005: Ex-laporatomy BSO with iliocecal resection, Re-anastomosis omentectomySuboptimal debulking massPE with attempted VIR for embolectomy of saddle

embolusMultiple MIsTPN dependence begins

12/2005: Chemotherapy began with Taxol7/2007: Repair enterocutaneous fistula

Infection History10/2006: Candida albicans and coagulase negative

staphylococcal infection at port site Rx: Fluconazole and daptomycin for 2 wks

11/2006: Candida parapsilosis fungemia Rx: Capsofungin with 8 wks

1/2007: Coagulase negative staphylococcal and ampicillin sensitive enterococcal bacteremia

Rx: Daptomycin

3/07: Coagulase negative staphylococcal bacteremia Rx: Daptomycin

7/2007 coag negative staph line infection and UTIs with enterococci and candida Rx: Linezolid and fluconazole

Additional HistorySH:

Patient denies alcohol, tobacco, drugs

Family History Mother had ovarian cancer Father had prostate cancer

ROS: unobtainable due to intubation and sedation

Additional HistoryMeds

Ceftazidine 2g IV q12 Flagyl 500mg q12 Linezolid 600mg q12 Micafungin 100 mg IV

QD Dopamine GGT Morphine PRN Benadryl PRN Phenergan PRN Zofran PRN

Allergies

Zosyn: Rash Ace Inhibitors: Rash Vancomycin: Rash PCN: Rash Zofran: Rash

Physical ExamVitals: Tmax 36.8/Tc: 35.9 BP:110/58 P:87 CVP:14-17

Vent: SIMV PS:10 PEEP:5 FIO2%:40 TV 600 Rate 16General: Intubated, withdraws from pain 6-7/THEENT: Icteric, PERRLA, no LADCV: RRR 2/6 holosystolic murmur, non radiating on left

sternal border; no rubs or gallopsLungs: Crackles Bilaterally at basesSkin: jaundiced, no rash or bruising notedAbdomen: tender throughout, no rebound, hypoactive

bowel sounds; multiple surgical scars, with palpable subcutaneous midline mass (not fluctuant)No hepatosplenomegaly appreciated

Extremities: 1+ pitting edema bilaterally

Labs:

Ca:7.4 Mg:1.9 Phos:4.6GGT:122Differential:

ANC: 18.0↑ALC:0.8AMC: 0.8AEC:0.2ABC: 0

20.7

27.5

9.2

51139

3.1

112

14

31

181

20.4

1.571

84 74

21.6

2.26.2

RadiologyRUQ US:

Lack visualized flow in portal veins/SMV, some echogenic material in portal veins concerning for clot

Hepatomegaly

New extrahepatic biliary ductal dilations

CT Adomen/ Pelvis

RadiologyCTA Abdomen:

Fluid collections contain focal area of gas with density within the soft tissues overlaying a anterior abdominal wall may represent abscess

Increase in the size of multiple high density lesions seen in the liver, which contain calcifications.

Low density fluid in pelvis collection with in abdomen c/w ascites

Stable Left pleural effusion

DISCUSSION………..

TTE:Left Ventricle: hyperdynamic EF: 65-70%Mitral Valve: thickened with mild prolapse, moderate regurgitationAortic Valve: trileaflet with mild thickeningRight Ventricle: normalTricupsid Valve: mild thickening with mobile echo from the atrial surface consistent with degenerative, disease and vegetation, with mild regurgitationPulmonary Valve: not well imagine

Microbiology:

Urine Culture: gram positive cocci in chains

Blood Culture (peripheral and central line):GPCs in chains and GPRs

Abdominal abscess: GPCs in chains

Infectious Disease DiagnosisBacteremia:

Enterococci (ampicillin sensitive, but gentamicin R) Bacillus cereus

Endocarditis of the tricuspid valveAntibiotics used: Imepenem/cilastin and

daptomycin used to treat for 12 weeks

B. cereus now…

Bacillus cereusCommonly found in soil, inanimate objects,

and mucus membranes healthy peopleGram positive motile rods with paracentral

sporesTaxonomy of 3 groups: large cell subgroup,

small cell, mixedLarge group is B. anthracis and cereusThey differ by fewer 9 nucleotides

Bacillus cereus cont’d…Grows on blood agar as large flat, granular,

ground glass, beta-hemolytic Grows aerobically and a facultative anaerobeContains catalase, hemolysins, beta-lactamases,

oxididaseFerments glucose, maltose, sucrose, trehalose

Does not ferment lactose, xylose, mannitolResistant to heatMotile

Bacillus cereus ToxinsEnterotoxin- can be necrotizingEmetic toxin- mitochondrial toxin

Inhibits mitochondrial fatty-acid oxidation Can cause liver failure

Phospholipases- release lysozyme enzymes (like alpha toxin c. perfringens)

ProteasesHemolysins-causing cell lysis of leukocytes and

macrophagesBeta-lactamases thus resistant to most PCNs

Bacillus cereus Infections1: Local (burns, trauma, post op, fulminant eye

infections)2: Bacteremia/septicemia3: CNS4: Respiratory infection5: Endocarditis, pericarditis6: Food poisoning, toxin inducedIncrease in non-food poisoning in IVDU, neonates,

malignancy, AIDs, prosthetic partsMost common form is GI intoxication from spores by

enterotoxins

Food-PoisoningOccurs 6-8hrs after ingesting B. cereus

toxins Patients typically have significant

emesis and less frequently diarrheaEnterotoxins : hemolysin, non-

hemolytic enterotoxin, enterotoxin T, and cytotoxin K

Emetic toxinNo fevers because not systemic diseaseCommonly isolated from reheated

foods

Endophthalmitis5/10,000 hospital patients60% occur after intraocular surgery

Often due to transient bacterial contamination by conjuctival flora4-13% after penetrating traumaOnce inoculated bacillus spreads through out whole eye

If motile strain <12 hours to detect inflammatory reaction in the eye

Symptoms: pain “ache”, redness, blurry vision, ring corneal infiltrate Loss retinal function in 18hours if fully virulent (pclR gene and

motile) High morbidity with loss of vision in infected eye

Phospholipases toxins responsible for the destructionsTreatment is injection of antibiotics into the vitreous and vitrectomy,

along with systemic antibiotics.

5 year Review of Cleveland Hospitals

From: 1981-198638 patients with significant Bacillus infections:

78.9% bacteremia 1/3 IVDU or had indwelling catheters, 4 had

cancer30% IVDU7.9% endopthalmitis1.8% Endocarditis (only with IVDU)OsteomyelitisVisceral infection- significant morbidity1 pneumonia and1 necrotizing fasciitis after trauma

Medicine (Baltimore) 1987;66(3):218-23.

5 year Review continued…Intravascular device (pacemaker, central

line) is a cause of the nosocomial bacillus bacteremia

4/38 patients improved after removal intravascular catheter with out antibiotics

Endocarditis rare phenomenon with B. Cereus

Overall patients with primary bacteremia recovered quicker and had less morbidity then patient with a localized infection

Medicine (Baltimore) 1987;66(3):218-23.

Bacillus spp. Among hospitalized patients with Haematological malignancies3.4% bacteremic with bacillus spp.

Most only presented with feverFew cases of pneumonia, GI/Hepatic symptoms

Patients that are granulocytopenic are at risk for opportunistic infections with bacillus

Many species can effect neutropenic patients which in clude B. licheniformis, B. cereus, B. pumilus

All patient were bacteremic, only few had pneumonias, endocarditis, or localized infections

Journal of Hospital Infections 2006.;64(2):169-76.

Pseudo EpidemicsOutbreaks have been seen in dialysis units, ICUs,

neonatal ICUsBacillus spores are sticky

Non-sterile cotton wool Laundered linens including gowns, sheets Ventilation systems Dressings Hands Dairy plants- filling machines Korean dried red pepper

Contaminated TransfusionsPlatelet transfusions: contaminated 0.08-0.7 %

Stored at room temperatures, thus longer storage time increase risk of contamination

Possible contaminants: dipthroid rods, coagulase negative staph, B. cereus, E. cloacae, E. coli, P. aeruginosa

Most cases deteriorated with minutes of transfusionLeading to hospital outbreaks of infectionsMore common with patients with hematological malignancy

Second to transfusions or long term indwelling cathetersBlood transfusions no data seen

TreatmentB. Cereus inherently resistant to most beta-lactamsAntibiotics known to work:

ImipenemClindamycin

In vitro activities of antibiotics on Bacillus spp and SporesAminoglycosides: MIC 2-0.5Doxycycline: MIC 0.5Vancomycin: MIC 1Erythromycin: MIC>16Ciprofloxacin: MIC 0.25Daptomycin: MIC 1 Journal of Clinical Microbiology 2006;44(10):3814-18

References te Boekhorst PA, et al. Clinical significance of bacteriologic screening in platelet

concentrates. Transfusion 2005;45(4):514-19. Drobniewski FA. Bacillus cereus and related species. Clinical microbiology

reviews 1993;6(4):324-38. Sliman R, et al. Serious infections caused by bacillus species. Medicine

(Baltimore)1987;66(3):218-23. Rotman B, Cote MA. Application of real-time biosensor to detect bacteria in

platelet concentrates. Biochemical and biophysical research communications 2003;300(1):197-200.

Yomtovian R, et al. A prospective microbiologic surveillance program to detect and prevent the transfusion of bacterial contaminated platelets. Transfusion 1993;33(11):902-9.

Guinebretiere MK, et al. Enterotoxigenic profiles of food-poisoning and food-borne bacillus cereus strains. Journal of Clinical Microbiology 2002;40(8):3053-56.

References (cont’d.) Callegan M, et al. Bacillus endophthalmitis: Role of bacterial toxins and

motility during infections. Investigative Ophthalmology and Visual Science 2005;46(9):3233-8.

Citron DM, Appleman MD. In vitro activities of daptomycin, ciprofloxacin, and other antimicrobial agents against the cells and spores of clinical isolates of bacillus species. Journal of Clinical Microbiology 2006;44(10):3814-8.

Mahler H, et al. Fulminant liver failure in association with the emetic toxin of

bacillus cereus. NEJM 1997;336(16):1142-8. Ozkocaman V, et al. Bacillus spp. among hospitalized patients with

haematological malignancies: clinical features, epidemics and outcomes. Journal of Hospital Infections 2006;64(2):169-76.

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