PERDANA UNIVERSITY RCSI CASE BASED LEARNINGCASE NO: 6 Monday 7th April 2014 - Thursday 10st April 2014

Clinical Discussants Microbiologist: Dr. Sufi HannanPathology:Prof ShiranModerator:Prof Anthony Cunningham

Presenting ComplaintFeeling cold and shivery on Day 11 following a first cycle of chemotherapy

History of Present IllnessThe patient, CL, was an 26-year-old Malay man who was diagnosed with acute myelogenous leukaemia 3 weeks previously. He was commenced on the first cycle of Remission Induction chemotherapy 11 days prior to the current presenting complaint. He tolerated the chemotherapy well. On Day 7 (the final day of the first Remission Induction cycle), he was found to be neutropenic (White cell count 1.5 x109/l (4.0-11.0 x109/L), neutrophil count 0.7 x109/l (2.0-7.5 x109/L).

Now on Day 11 following the chemotherapy, he is complaining of feeling cold and shivery. Further questioning reveals that he feels tired, weak and unwell, he has no appetite and feels nauseated.

Past Medical and Surgical HistoryAppendicectomy at age 7 years, no other medical or surgical history

Family History His father, aged 58 years, has hypertension and Type 2 Diabetes Mellitus. His mother, aged 52 years, suffers from recurrent urinary tract infection but is otherwise well and on no medications. Three siblings are alive and well with no medical complaints

Social History CL works in a Bank. Prior to this hospital admission, he smoked 15 cigarettes a day. He does not drink alcohol or use recreational drugs. He is a keen keep fit follower, and normally goes to the gym 4 times a week.

MedicationsAciclovir Fluconazole Anti-nausea mediations

AllergiesNo known drug allergies

Review of SystemsHe is alert, and orientated in time and place. He has no cough, shortness of breath or chest pain. He has no dysuria. He has no diarrhoea.

Physical Examination Vital Signs: Temperature: 38.8oC, Heart rate: 118 beats per minuteBlood Pressure: 110/50Respiratory Rate: 32 breaths per minute

General InspectionFlushed, no evidence of rash, Hickman line site dry and clean

Cardiovascular System, Respiratory System and Abdominal Examination: No abnormality detected:

InvestigationsBloods are taken for full blood count and differential,Chest X ray was performedTwo sets of blood cultures are taken, one set from the from the central line and one set from the right forearm.A swab was taken from the Hickman site

Working Diagnosis and ManagementA diagnosis of probable neutropenic sepsis was made, and treatment was commenced with intravenous piperacillin-tazobactam.

Results of Laboratory InvestigationsWhite cell count 0.7 x 109/L, neutrophils 0.2 x 109/LUrinalysis: no abnormality detected on dipstick, white cell count 1/cmm, sterile on culture after 18 hours incubationBlood cultures sterile after 18 hours incubation

RadiologyPA chest x-ray (Image 1):

Image 1

Clinical Course24 hours after the initial complaint, CL complained of feeling very unwell and had a temperature spike to 39.5oC. Blood pressure was 95/50mmHg, his heart rate was 124 beats per minute. Physical examination was unremarkable. Because of his clinical deterioration, the septic screen was repeated (Central line, and peripheral blood cultures, Urine, and chest X ray). Gentamicin 5 mg/Kg once daily iv was added to the antibiotic regimen. CL continued to spike a pyrexia. Six hours later he complained of pain at the Hickman line insertion site. On examination, there was erythema around the site with and scanty discharge from the site.

A phoned report was received from the Clinical Microbiology Laboratory: Gram positive cocci seen on Gram stain from blood culture bottle (central line cultures) (Image 2)

Image 2: Gram stain of aliquot from blood culture bottle

Treatment with piperacillin-tazobactam plus gentamicin was continued, and intravenous vancomycin was added to the regimen.

Within 48 hours of the initial blood cultures, the laboratory confirmed that the blood culture isolate was Staphylococcus epidermidis, susceptible to vancomycin; the peripheral line cultures remained sterile.

The central and peripheral line blood cultures were repeated on that day and each of the following 3 days.

Cl showed clinical improvement; his blood pressure returned to normal and the pyrexia settled but remained elevated between 37.80C and 380C. He continued to complain of pain at the Hickman line exit site and the erythema became more extensive. The central line blood cultures continued to remain culture positive for Staphylococcus epidermidis. The Hickman line was removed and the tip was sent for culture and sensitivity and a new line was inserted at another site. Central and peripheral blood cultures were repeated 24 hours after removal of the infected line.

Within 18 hours of line removal, his temperature had returned to normal and CL felt well. The repeat blood cultures were sterile.

On Day 24 after commencement of the first treatment cycle, CLs white cell ount had not recovered, and he continued to be neutropenic with a neutrophil count of 0.7 x 109/L. On Day 26, he complained of dry cough and shortness of breath.

Chest X Ray (Image 3) was performed followed by CT Thorax (Image 4)

Image 3

Image 4

Broncho-alveolar lavage was performed and the specimen was sent for culture and sensitivity; a lung biopsy specimen was sent for histology. An organism was isolated after 3 days incubation on Sabouraud dextrose agar (Image 5) . Microscopy was performed (Image 6).

Image 5

Image 6

Histology of the lung biopsy (Image 7)

Image 7

Treatment was commenced with an appropriate agent. CL responded well to treatment, and became asymptomatic after 3 weeks treatment. Treatment continued for a total of 5 weeks. During this time, the cough and shortness of breath resolved and the chest X ray appearance returned to normal.

His white cell count continued to improve during this time, and returned to normal following completion of this treatment. The second Remission Induction cycle of chemotherapy was administered without any infective complications.

QuestionsStudent 1 What is the definition of neutropenia? What are the causes of neutropenia? Explain why neutropenic patients are at increased risk of infection.Student 2 What infections may be encountered in neutropenic patients? What measures would be appropriate to reduce the risk of development of opportunistic infection in CL? Interpret and compare Images 1 and 3.Student 3 What abnormality is seen on the CT scan? What is the differential diagnosis? What investigations would be appropriate to confirm a diagnosis in this setting?Student 4 Describe what is seen in Images 5, 6 and 7. What is the diagnosis? What are the possible complications of this condition? What is the most appropriate treatmentStudent 5 Describe the different types of single room isolation What sort of isolation is appropriate for a patient with AML? What precautions would you take on entering the room and how do these precautions differ from those that you would take on entering the room of a patient with MRSA infection, or a patient with open pulmonary tuberculosisStudent 6 What is a Hickman line? What are the advantages of this type of line in comparison with a peripheral line? What measures are recommended to reduce the risks of infection in association with this type of iv access line?