CAGAYAN VALLEY MEDICAL CENTER

CASE
DEPARTMENT OF INTERNAL MEDICINE

PRESENTATION
PGI Cagayan, Klaire
PGI Cruz, Rhaiz
PGI Formoso, JC
PGI Iringan, Abby
PGI Luna, Dennis
PGI Mendoza, Kimberly
PGI Pagaddu, Gian
PGI Ranjo, Johana
PGI Valdez, Hazel Mae
General Data

Name: J.P.
Age: 34 y/o
Sex: Male
Citizenship: Filipino
Birthdate: October 21, 1986
Residence: Santiago, Isabela
Occupation: School Teacher

Date of Admission: September 2, 2019

Chief Complaint

Fever and Chills

 History
HISTORYof
OFPresent
PRESENTIllness
ILLNESS

• previously diagnosed • His induction chemotherapy regimen • Fever spike at

as a case of acute consists of 7 + 3 induction chemotherapy 38.8°C (101.8°F)
myeloid leukemia with cytarabine and daunorubicin. • Complained of chills
• He was advised to and nausea
undergo • He was placed on neutropenic • Denies cough,
chemotherapy. precautions, started on appropriate vomiting, abdominal
• No known exposure antimicrobial prophylaxis. pain, pain in the
to person with TB, catheter site &
pneumonia, & other diarrhea.
infectious disease
prior to
chemotherapy.

Ten days after the completion of his

1 month PTA Day 1 of admission induction chemotherapy
 Past Medical History

● The patient had the usual childhood diseases such as measles, mumps, and chickenpox during
childhood.
● He denies any history of trauma, as well as hypertension, diabetes, bronchial asthma, pulmonary
tuberculosis, heart, liver, lung, kidney, and thyroid diseases.
● Few days prior to diagnosis of AML, he went to a private physician due to the presence of small
ulcerative lesions on the lip, gingival, & buccal area in which he was diagnosed with HSV
infection. Home medications were given.

Surgical History
• Appendectomy (10 years ago)
Family History

● Father had AML and passed away 8 years ago;

● Mother has hypertension and epilepsy;
● No siblings
PERSONAL-SOCIAL HISTORY
● Married with twins (5 years old).
● Has never smoked and denies illicit drug use.
● Drinks alcohol socially. He is an elementary school teacher.
● One sexual partner (wife)

Allergies
Penicillin (reaction: rash)
Inpatient Medications

● Posaconazole delayed-release 300 mg PO BID x1 day

followed by 300 mg PO daily (day 1 start)

● Valacyclovir 500 mg PO BJD (day 1 start)

● Levofloxacin 500 mg PO daily (day 1 start)

 REVIEW OF
REVIEW OFSYSTEMS
SYSTEMS
● Constitutional: (-) Weight loss (+) Fever and chills, Nausea
(-)Vomiting
● Hematology: (+) Easy fatigability (-) Easy bruising
● CNS: (-) Headache (-) Seizure (-) Loss of consciousness
● HEENT: (-) Blurring of vision (-) Hearing loss (-) Tinnitus
● Respiratory: (-) Dyspnea, (-) Colds (-) Apnea
● CVS: (-) Orthopnea (-) Palpitation
● GIT: (-) Constipation, (-) Abdominal Pain
● GUT: (-) Dysuria (-) Oliguria (-) Frequency (-) Urgency
● NMS: (-) Malaise (-) Myalgia (-) Numbness
 PHYSICAL EXAMINATION
PHYSICAL EXAMINATION
● General Survey: conscious, coherent, not in distress

● Vital Signs:
BP: 110/70 HR: 105 bpm
RR: 18 cpm Temp: 38.8oC O2 sat: 98%

Ht. & Wt: 5’8 / 70kg

BMI: 23.5

● HEENT: Pale palpebral conjunctiva, white sclera, no nasoaural

discharge, no tonsillopharyngeal congestions

● Neck: Supple neck, no neck vein engorgement, no cervical

lymphadenopathies
● Chest and Lungs: Symmetrical chest expansion, no retractions,
normal lung sounds, no wheezes, no crackles or ronchi.

● Heart: Adynamic precordium, tachycardic but regular rhythm, (-)

murmurs

● Abdomen: Flat, normoactive bowel sounds, soft, dull on

percussion; nontender; no hepatosplenomegaly

● Genitourinary: Normal male genitalia, no complaints of dysuria

or hematuria, prostate exam not performed; no perirectal lesions

● Extremities: No gross deformities, warm and dry, no rashes, no

erythema or induration around the catheter site, CRT <2 sec, no
edema

● Neurology: Alert and oriented to 3 spheres. GCS 15

● 39 y/o, Male
● Diagnosed with AML
● Induction chemotherapy
● Presence of central venous catheter
● Fever
● Chills
● Tachycardia
● Mild to moderate distress
● Nausea
● Fatigue
DIFFERENTIAL DIAGNOSES
 FEVER
FEVER

INFECTION INFLAMMATION IMMUNE

HSV REACTIVATION DRUG-INDUCED

CANDIDIASIS

PNEUMONIA

NOSOCOMIAL SEPSIS

CATHETER-RELATED
INFECTION * RISK FACTORS
 DRUG-INDUCED IMMUNE REACTION

RULE IN RULE OUT

Allergy to penicillin Within 7 days of exposure to the drug

Fever Skin lesion or eruptions

Chills
Tachycardia
Nausea
Fatigue
 HSV REACTIVATION

RULE IN RULE OUT

Immunocompromised Herpes labialis
Fever
Chills
Tachycardia
Nausea
Fatigue
 DISSEMINATED CANDIDIASIS

RULE IN RULE OUT

Immunocompromised No signs of organ involvement
Presence of intravenous catheter
Use of antibiotics
Fever
Chills
Tachycardia
Nausea
Fatigue
 PNEUMONIA
RULE IN RULE OUT
Immunocompromised Cough
Fever Adventitious breath sounds
Chills
Tachycardia
Nausea
Fatigue
 NOSOCOMIAL SEPSIS
RULE IN RULE OUT
Immunocompromised Tachypnea
Presence of intravenous catheter Hypotension
Use of antibiotics Oliguria
Fever Altered mental status
Chills
Tachycardia
Nausea
Fatigue
 HOSPITAL-ACQUIRED INFECTION
(Catheter-related bloodstream infection)

RULE IN RULE OUT

Immunocompromised *Cannot totally rule out
Presence of central venous catheter
Fever
Chills
Nausea
Tachycardia
Fatigue
 WORKING IMPRESSION

HOSPITAL-ACQUIRED INFECTION, PROBABLY

CATHETER-RELATED;
R/O HOSPITAL-ACQUIRED PNEUMONIA;
CYTARABINE & DAUNORUBICIN INDUCTION
CHEMOTHERAPY, COMPLETED
PLAN
Admit patient to medical ward
Secure consent for management
TPR q shift and record
Diet: DAT
IVF: PNSS 1 L X q 12h
Diagnostics and Imaging work-up:
CBC UA
Serum N, K, Cl Blood CS x 2 sites
BUN Viral serology
Creatinine CXR PA
AST/ALT Bilirubin
PLAN
Medications

○ D/C Levofloxacin, start Cefepime 2g/ IV every 8 hrs

○ G-CSF 5 μg/kg/day SC
○ Posaconazole 300 mg PO BID
○ Valacyclovir 500 mg PO BID

● Monitor VS q shift and record

● Monitor I and O q shift and record
● Watch out for untoward signs and symptoms
● Refer accordingly
Laboratory Findings (day 17)

Na =135 mEq/L Hgb = 7.8 g/dL ↓ AST= 18IU/L ↑

K=4.0mEq/L Hct= 23.4% ↓ ALT= 22IU/L ↑

Cl= 97mEq/L Plt=23 x 103 /mm3 ↓ T Bili = 0.8 mg/dL

C02 = 25 mEq/L WBC = 0.1 cells/mm3 ↓

BUN = 14 mg/dL PMNs= 14% HSV IgG = positive(day 1lab)

SCr = 0.8 mg/dL Bands= 5% CMVIgG = negative(day1lab)

Glc = 84mg/dL Lymphs= 81%

 Day 1 2 3 4 7 9 12 17

WBC 4.5 4.1 3.7 3.2 1.4 0.7 0.2 0.1

ANC 3240 2665 2109 1568 476 189 44 19

(PMN) 50% 45% 41% 36% 26% 21% 17% 14%

(band) 22% 20% 16% 13% 8% 6% 5% 5%

Daunorubicin - Daunorubicin Nausea Cytarabine Nausea Nausea Fever, chills,

and cytarabine completed; completed; nausea
started nausea nausea

Posaconazole G-CSF Levofloxacin

Valacyclovir started shifted to
Levofloxacin Cefepime
started
Blood Cultures:
○ Periphery X2 (positive);
○ port catheter (positive)

Urinalysis
○ 0 WBC,
○ leukocyte esterase negative,
○ nitrite negative; urine
○ culture not performed

Chest X-ray
○ Lungs are clear
 FINAL DIAGNOSIS
FINAL DIAGNOSIS

HOSPITAL-ACQUIRED INFECTION,
CATHETER RELATED
FEBRILE NEUTROPENIA, SECONDARY
CYTARABINE & DAUNORUBICIN
INDUCTION CHEMOTHERAPY,
COMPLETE
 Case
Discussion
Febrile NEUTROPENIA
FEBRILE neutropenia

 defined as an oral temperature of >38.3°C or

two consecutive readings of >38.0°C for 2 h and
an absolute neutrophil count (ANC) of <0.5 ×
109/l, or expected to fall below 0.5 × 109/l.

Management of febrile neutropaenia: ESMO ClinicalPractice Guidelines

Incidence
• FN remains one of the most frequent and serious complications of cancer
chemotherapy (ChT).
• It is major cause of morbidity, healthcare resource use and compromised
treatment efficacy resulting from delays and dose reductions of ChT
• FN is observed in ∼8 cases per 1000 patients receiving cancer ChT

Mortality
o < 5% if the MASCC score is ≥21
o possibly as high as 40% if the MASCC score is <15

Management of febrile neutropaenia: ESMO ClinicalPractice Guidelines

Management of febrile neutropaenia: ESMO ClinicalPractice Guidelines
Journal of Cancer Preventhttps://medcraveonline.com/JCPCR/febrile-neutropenia-in-cancer-patient-
epidemiology-microbiology-pathophysiology-and-management.htmion & Current Research
Risk factors

• age of 65 years or older,

• presence of chronic comorbidities,
• underweight and malnutrition;
• proxies for poor performance status (use of hospice
care, skilled nursing facility, hospital bed, supplemental
oxygen, walking aid, or wheel chair),
• use of immunosuppressive drugs,
• history of selected blood-related disorders, infection,
surgery (recent), and radiation or chemotherapy

https://jnccn.org/view/journals/jnccn/13/8/article-p979.xml
Diagnostics &
Assessment
Tools
PGI MENDOZA, KIMBERLY MAE
Laboratory & Imaging

• CBC
• Urinalysis
• Blood Cultures
• Throat Cultures
• Fecalysis
• Renal Function Test
• Liver Function Test
• Chest X-ray
Assessment Tools

Multinational Association for Supportive Care in Cancer

(MASCC)
Talcott’s Rules
 for identifying low-risk cancer patients with febrile neutropenia

The Clinical Index of the Stable Febrile Neutropenia (CISCNE)

 for predicting major complications in patients with seemingly
stable FN
Multinational Association for Supportive
Care in Cancer (MASCC)
The Clinical Index of the Stable Febrile
Neutropenia (CISCNE)
MANAGEMEN
T
INITIAL ASSESSMENT & INVESTIGATIONS
OUTCOME RISK ASSESSMENT
LOW-RISK PATIENTS
• ORAL THERAPY
 are haemodynamically stable
 do not have acute leukaemia or
evidence of organ failure
 do not have pneumonia, an
indwelling venous catheter
 severe soft tissue infection
 LOW-RISK PATIENTS

• Single-agent quinolones were not inferior to combinations.

• Oral quinolone therapy should not be used in patients who have taken a
quinolone antibacterial as prophylaxis.
• Early change to oral combinations in afebrile patients after 48 h on i.v. therapy is
supported
• Low-risk patients may be treated with outpatient parenteral regimens.
OUT-PATIENT & EARLY DISCHARGE

CRITERIA:
 clinically stable
 symptomatically better
 evidence of fever lysis after a minimum of 24 h in hospital
 understanding of the risks
 patient surveillance is available
HIGH-RISK PATIENTS

● Patients with FN who are at high risk

as assessed by the MASCC criteria
(<21), or have high-risk features as
judged by the admit_x0002_ting
doctor, should be admitted and
commenced on broad_x0002_spectrum
i.v. antibiotics, since the risk of
bacterial sepsis is very high.
SPECIFIC INDICATIONS FOR ALTERNATIVE THERAPY

● central i.v. catheters

● pneumonia
● vesicular lesions/suspected viral infection
● suspected meningitis or encephalitis
● cellulitis
● intra-abdominal or pelvic sepsis
● diarrhea
● candidiasis
FOLLOW-UP & ASSESSMENT OF RESPONSE
 DURATION OF THERAPY
CONDITION
• ANC is ≥0.5 × 109/L
• asymptomatic
• afebrile for 48 h
• blood cultures are negative
• ANC is ≤0.5 × 109/L
• no complications
• afebrile for 5–7 days
DURATION
• antibacterials can be discontinued
• antibacterials can be discontinued
• antibacterials up to 10 days or until
the ANC is ≥0.5 × 109/L
• high-risk cases with acute
leukaemia
• following high-dose
chemotherapy
PROPHYLAXIS
PROPHYLAXIS
● Antimicrobials have been used for a long time for the prevention of
episodes of FN in ChT-treated patients.
● Fluoroquinolones have been used extensively for chemoprophylaxis
● Emergence of resistant strains
● Guidelines from the EORTC (European Organisation for Research
and Treatment of Cancer) and American Society of Clinical Oncology
(ASCO)
○ Limit the use of antibacterial prophylaxis to patients at high risk for FN
● Cochrane meta-analysis
○ Use of ciprofloxacin or levofloxacin in cancer patients undergoing intensive ChT.
PROPHYLAXIS WITH GRANULOCYTE
COLONY STIMULATING FACTOR (G-CSF)
PROPHYLAXIS WITH GRANULOCYTE
COLONY STIMULATING FACTOR (G-CSF)
● Meta-analysis of randomised, controlled trials and experience in real-
world settings confirm the outstanding (>50% success) of primary
prophylaxis with filgrastim or pegfilgrastim.
● Secondary prophylaxis is indicated if dose reduction below threshold
or delay of ChT is not desirable.
● The most common adverse effect is minor or moderate bone pain
PROPHYLAXIS WITH GRANULOCYTE
COLONY STIMULATING FACTOR (G-CSF)

● Use of G-CSF in high-risk situations

○ The incidence of FN in high-risk situations is as follows
■ Common during autologous and allogeneic peripheral blood
stem-cell (PBSC) TPLs and bone marrow TPL, during graft
failure,
■ 35%–48% of acute myeloid leukaemia (AML) cases at
diagnosis
■ 13%–30% during acute lymphoblastic leukaemia (ALL) in-
duction ChT.
 PROPHYLAXIS WITH GRANULOCYTE
COLONY STIMULATING FACTOR (G-CSF)

● Dose schedule and route of application

○ 5 μg/kg/day of G-CSF subcutaneously (s.c.) 24–72 h
after the last day of ChT until sufficient/stable post-
nadir ANC recovery
○ Pegfilgrastim, injected s.c. as a single dose of either
100 μg/kg (individualised) or of a total dose of 6 mg
(general approach).
○ Filgrastim is 5 μg/kg/day for 10 days
References
● MASCC FN Risk Index Score. (n.d.). MASCC.
https://www.mascc.org/mascc-fn-risk-index-score

● Freifeld AG, Bow EJ, Sepkowitz KA, et al; Infectious Diseases Society of America.
Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with
cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis.
2011;52(4):e56-e93. doi: 10.1093/cid/cir073

● NCCN Clinical Practice Guidelines in Oncology. Prevention and Treatment of Cancer-

Related Infections, version 2. 2017. National Cancer Comprehensive Network website.
www.nccn.org/professionals/physician_gls/PDF/infections.pdf. Published February 21,
2017
● Management of febrile neutropaenia: ESMO ClinicalPractice Guidelines
● Journal of Cancer Preventhttps://medcraveonline.com/JCPCR/febrile-neutropenia-in-
cancer-patient-epidemiology-microbiology-pathophysiology-and-management.htmion &
Current Research
● https://jnccn.org/view/journals/jnccn/13/8/article-p979.xml