Transcript Persistent Fever by Rona Marie Leonor 111209

To present a case of a patient with persistent
fever.
 To discuss the approach and management in
patient with persistence of fever.

R.B, 58-year-old male,
 married, Filipino
 Farmer from Tuguegarao, admitted
5,2009

on July

3 WEEKS PTA
› fever, undocumented
› right upper quadrant pain
› No change in bowel movement
› local Institution in Tuguegarao.
› A> enteric fever
› Cotrimoxazole and Metronidazole.
› A> Malaria
› Chloroquine started as an empiric treatment.
› opted to go home , and was lost to follow up

2 WEEKS PTA
› Fever and Right upper quadrant pain
› Dyspnea
› No cough, chest pain

local institution Tuguegarao.
Abdominal Ultrasound: Cholesterolosis
 Chest xray and Chest Ultrasound : pleural
effusion on the right.
 Thoracentesis 1 liter

Empirically
treated
with
Ceftriaxone,
Ciprofloxacin and eventually Anti koch’s
medication
 Opted to go home
 Pleural fluid Culture and histopath results
unknown to patient


consult in MMC for further management
generalized weakness
 weight loss
 Loss of appetite
 no headache
 no palpitations
 No signs of bleeding
 no dysuria/ frequency/ hematuria
 no joint stiffness/ weakness

No Diabetes Mellitus
 No hypertension
 No Asthma
 No Pulmonary Tuberculosis
 No history of accidents or injuries
 No history of blood transfusion
 No history of hepatitis
 No previous surgeries

Non smoker
 Non alcoholic beverage drinker
 No illicit drug use
 Denies exposure to a PTB patient






No Hypertension
No Cancer
No Diabetes Mellitus
No asthma
No PTB

Conscious, coherent, ambulatory, Not in cardio
respiratory distress
› weight: 61 Kg Height: 165 .4 cm
BMI 22.5
› 100/70 HR : 92/min RR 20 cycles/min Temp 38.0 C

Skin: no jaundice, good turgor, no lesions.
Pink palpebral conjunctivae, anicteric sclerae, no neck
mass, no cervical lymphadenopathy, no oral mass or
ulcers


Adynamic precordium, no heaves, no thrills, Normal
rate, regular rhythm, no murmurs
Asymmetrical chest expansion (Right chest
lag), no rib retractions,
decreased tactile fremitus, dull on percussion
and decreased breath sounds - mid to lower
right lung field, no crackles, no wheezes
Left lung field: resonant, clear breath sounds
 Flat abdomen, normoactive bowel sound, soft,
direct tenderness, RUQ, no masses
 Full & equal peripheral pulses. No cyanosis. no
edema








58 year old male

FEVER x 3 weeks
right lower quadrant pain 
Dyspnea
UTZ: Cholesterolosis

CXR & Chest UTZ: Pleural
Effusion


Febrile ( 38C), RR- 20
R chest lag
decreased tactile fremitus, dull
on percussion,mid-lower right
lung field
decreased breath sounds- mid to
lower right lung field
no crackles, no wheezes
Flat abdomen, normoactive
bowel sound, soft, direct
tenderness, RUQ
Fever secondary to Pulmonary Tuberculosis vs.
Pneumonia r/o malignancy
 Pleural effusion, right
 Cholesterolosis

CBC
 Chest radiograph
 Serum electrolytes
 sputum smear for acid fast bacilli
 Paracetamol 500mg
 Tramadol 50mg

febrile Tmax 39.3 ; abdominal pain
 Patient referred to IDS
 Impression: Hepatic abcess.
Parapneumonic Effusion, right.
 CT scan of the chest and abdomen
 Chest tube thoracostomy, right (300ml of serous
fluid)


repeat Chest radiograph

Acid fast bacilli sputum smear

Ampicillin-Sulbactam 1.5g, q6
•
•
Pleural fluid gram staining
Ampicillin-Sulbactam was shifted to Cefepime
1g, every 12 hrs.
4th Hospital day
D1 CEFEPIME
Febrile Tmax 39.1
 CBC
 Blood culture
 Acid fast bacilli smear of pleural fluid
 Acid fast bacilli culture
 HRZE (Myrin P forte) 4 tablets, once a day.

6th hospital day
D1
ANTI KOCH’S
› febrile Tmax 39C
› loss of appetite
› Dizziness
› loose bowel movement
› Pleural fluid cytology
› Myrin P Forte discontinued
INH 300mg,1 tab, before breakfast
 Rifampicin 600mg,1 tab, before breakfast;
 Ethambutol 400mg,3 tabs, after breakfast
 PZA 500mg,4 tablets, after lunch

Febrile Tmax 38.9
 Headache, vomiting, dizziness and tinnitus
 Impresssion: Drug induced vs central cause
R/O Connective tissue disease

•
Lupus Panel
•
Plan: Cranial CT scan & Lumbar Tap
•
Anti Koch’s, Tramadol were discontinued
•
Betahistine was started
4th Hospital day
D1 CEFEPIME
10th hospital day
ANTI KOCH’S
Fever secondary to Infection vs. Malignancy
 Naproxen 375mg, BID and later decreased to
275mg, BID
 Cefepime discontinued

12th hospital day
CEFEPIME
12th hospital day
NAPROXEN
Fever
 Pleural fluid cytology CYTOSPIN
 Chest tube thoracostomy drainage (24ml for 24
hrs)
 Contrast chest CT scan done.
 Chest tube removed.
 Video- assisted Thoracoscopic surgery.

18th hospital day
24ml x 24hrs

Post MINI thoracostomy, Decortication with
pleural and lung biopsy
Isoniazid 300mg,1 tab, after dinner (Aug 1)
 Rifampicin 600mg,1 tab,before dinner (Aug 2)
 Ethambutol,400mg,3 tabs,after dinner (Aug 4

25th hospital day
S/P VATS
 Afebrile
Chest x-ray
no recurrence of fever noted
DAY 28-30
RE CHALLENGE
ANTI KOCH’S
PLEURAL EFFUSION, RIGHT SECONDARY TO
PULMONARY TUBERCULOSIS
 S/P CHEST TUBE INSERTION, RIGHT
 S/P
MINI THORACOSTOMY, DECORTICATION
WITH PLEURAL AND LUNG BIOPSY

Temp of >38.3 on several occasions
 >3 weeks
 Failure to reach a diagnosis despite 1 week of
inpatient investigation

Approach to the adult with fever of Unknown Origin
UpToDate®www.uptodate.com
AuthorDavid H Bor, MDSection EditorPeter F Weller, MD, FACPDeputy
EditorAnna R Thorner, MD Last literature review version 17.2: May 2009
T| his topic last updated: September 22, 200(8M ore)
CLASSIC
NOSOCOMIAL
FEVER OF UNKOWN ORIGIN
(FUO)
NEUTROPENIC
HIV
58 year old male
FEVER x 3 wks
RUQ pain
Dyspnea
Decreased
tactile fremitus
dull on
percussion
decreased
breath soundsmid to lower
right lung field
no crackles
no wheezes
INFECTIONS
NEOPLASMS
COLLAGEN VASCULAR DISEASES
MISCELLANEOUS CONDITION
Temp of >38.3 on several
occasions X >3 weeks; Failure
to reach a diagnosis despite 1
week of inpatient investigation
PHYSICAL EXAM
& HISTORY
CBC, DIFF SMEAR, ESR,CRP, URINALYSIS, LFT, MUSCLE
ENZYMES,VDRL,HIV,CMV,EBV,ANA,RF,SPEP,PPD,CONTROL
SKIN TESTS, CREATININE,ELECTROLYTES, Ca, Fe,
TRANSFERRIN, TIBC, VIT B12, BLOOD CULTURE, URINE,
SPUTUM,FLUIDS
CBC, DIFF SMEAR, ESR,CRP, URINALYSIS, LFT,
MUSCLE ENZYMES, VDRL, HIV, CMV, EBV,
ANA, RF, SPEP, PPD, CONTROL SKIN TESTS,
CREATININE,ELECTROLYTES, Ca, Fe,
TRANSFERRIN, TIBC, VIT B12, BLOOD CULTURE,
URINE, SPUTUM,FLUIDS
Diagnostic clues
Directed exam
Positive
Negative
No diagnostic clues
Chest CT,
abdomen, pelvis.
Colonoscopy
Negative
Positive
leading diagnosable cause of FUO
 6th leading cause of morbidity and mortality

Diagnosis, Treatment, Prevention and Control of Tuberculosis: 2006 Update
CLINICAL PRACTICE GUIDELINES

When should one suspect that patient may have
PTB?
› Cough of two weeks or more
› Cough with or without the ff: night sweats,
weight loss, anorexia, unexplained fever and
chills, chest pain, fatigue and body malaise
› Cough x 2 weeks or more with or without
accompanying symptoms TB SYMPTOMATIC
CATEGORIES
NEW
RELAPSE
RETURN TO TREATMENT
AFTER DEFAULT
DEFINITION
A patient
who has never had
treatment for TB or, if with previous
anti TB medications, taken for less
than 4 weeks.
Declared cured of any form of TB in
the past by a physician after one full
course of anti TB medications, & now
has become sputum smear (+)
Stops medications for 2 months or
more and comes back to the clinic
smear (+)
CATEGORIES
FAILURE
TRANSFER –IN
CHRONIC CASE
DEFINITION
While on treatment, remained or
become smear (+) again at the fifth
month of anti TB treatment or later; or a
patient who was smear (-) at the start of
treatment and becomes smear (+) at the
2nd month
Management was started from another
area and now transferred to a new clinic
Became or remained smear (+) after
completing fully a supervised retreatment regimen

What is the initial work up for a TB
symptomatic?
› Sputum microscopy (preferably 3 should be
sent)
› Collected first thing in the morning for 3
consecutive days

INTERPRETATION OF RESULTS:
› SMEAR POSITIVE: If at least two sputum
specimens are AFB (+)
› SMEAR NEGATIVE: If none of the specimens
are AFB (+)

DOUBTFUL: When only one of the 3 sputum
specimens is (+)
› When results are doubtful, a second set of the
three must be collected
› One of the second three is (+): SMEAR
POSITIVE
› All of the second three are (-): SMEAR
NEGATIVE

What additional tests should be done after a TB
symptomatic has been found to be SMEAR
POSITIVE?
› No further tests are required
Chest radiographs are not routinely necessary
in the management of a TB symptomatic patient
who is smear positive
 PPD (Purified Protein derivative) testing will not
add additional information


Blood/serum tests maybe taken when specific
risks for possible adverse events during
treatment are present
All adults suspected to have PTB should have
TB culture
 Drug susceptibility testing is recommended:
› Retreatment
› Treatment failure
› Smear positive patients suspected to have one
or multi-drug resistant TB (MDR-TB)


What tests are recommended
symtomatics who are smear negative?
› TB culture with Drug susceptibilty
› Chest Radiograph
for
TB

RECOMMENDED TREATMENT
DIAGNOSED SMEAR POSITIVE
FOR
NEWLY
› Short course chemotherapy (SCC) regimen
2
months
isonoazid,
rifampicin,
pyrazinamide and ethambutol
 4 moths isoniazid and rifampicin
 Given daily as initial phase followed by
daily or thrice weekly administration of
isoniazid and rifampicin during the
continuation phase

The recommended dosages for daily and thrice –
weekly administration in mg/kg body weight are
as follows:
DRUGS
DAILY (RANGE)
ISONIAZID
RIFAMPICIN
PYRAZINAMIDE
ETHAMBUTOL
STREPTOMYCIN
10
10
25
15
15
THRICE-WEEKLY
(RANGE)
10
35
30
15

RECOMMENDED TREATMENT FOR NEWLY
DIAGNOSED SMEAR NEGATIVE
 2HRZE/4HR (WITHOUT HIV OR WITH AN
UNKNOWN HIV)

How can one reliably diagnose extrapulmonary
tuberculosis (EPTB)?
› High degree of suspicion in a patient at risk
› Appropriate specimen should be processed for
microbiologic, both microscopy, culture and
histopathologic examinations

What is the effective treatment regimen for
EXTRAPULMONARY TUBERCULOSIS?
› 6-9 month regimen consisting of 2 months
Isoniazid, Rifampicin, Pyrazinamide and
Ethambutol (Initial Phase)
› 4-7 months Isoniazid and Rifampicin
(Continuation Phase)

TUBERCULOUS PLEURAL EFFUSION
 Microscopic examination detecs acid fast
bacilli in about 5-10% of cases

TREATMENT ADMINISTRATION
› FIXED DOSE COMBINATION
 Recommended for newly diagnosed TB
patients:
 Minimize the risk of monotherapy
 Minimize drug resistance
 Improve adherence with lesser number of
pills to swallow
 Reduce prescription errors
ADVERSE
REACTIONS
DRUG
MANAGEMENT
MINOR
Gastro intestinal
intolerance
Rifampicin/INH
Meds at bedtime/ small
meals
Mild skin reaction
Any kind of drugs
Anti histamine
Orange/ red
colored urine
Pain at the
Injection site
Rifampicin
Reassure patients
streptomycin
Warm compress
ADVERSE
REACTIONS
DRUG
MANAGEMENT
Peripheral
neuropathy
Isoniazid
Pyridoxine 100-200ng,
daily (Treatment)
100mg prevention
Arthralgia due to
Hyperurecemia
Flu-like symptoms
Pyrazinamide
NSAID
Rifampicin
Anti pyretics
ADVERSE
REACTIONS
DRUGS
MANAGEMENT
Severe skin rash
Any kinds of drugs
(Streptomycin)
Discontinue anti TB drugs, refer to DOTS
Jaundice
(Isoniazid,
Rifampicin,
Pyrazinamide)
Discontinue anti TB drugs, refer to DOTS;
If symptoms subside, resume treatment &
monitor clinically
Impaired visual
acuity
Ethambutol
Discontinue anti TB drugs, refer to DOTS
MAJOR
ADVERSE REACTIONS
DRUGS
MANAGEMENT
Psychosis
Isoniazid
Discontinue anti TB drugs, refer
to DOTS
Hearing impairment
Streptomycin
Discontinue anti TB drugs, refer
to DOTS
Thrombocytopenia,
anemia, shock
Rifampicin
Discontinue anti TB drugs, refer
to DOTS
Oliguria
Streptomycin/Rifam Discontinue anti TB drugs, refer
picin
to DOTS

SINGLE DOSE PREPARATION
› Adverse reactions
› Co morbid conditions requiring dose
adjustments
› Disease conditions where treatment is
expected to have significant drug interactions
with Anti TB drugs
› At risk for adverse reactions
The 2000 Philippine TB Consensus found
no studies correlating the resolution of
clinical signs and symptoms with
bacterial response to treatment
Teo SK. Four month chemotherapy in the treatment of smear negative PTB:
results at 30-60 months. Ann Acad Med Singapore 2002;31: 175-81
(CLINICAL PRACTICE GUIDELINES)

MONITORING OF OUTCOMES AND RESPONSE
DURING TREATMENT
› Defervesence occurred within 2 weeks in
78% of patients with drug susceptible
organisms while only 9% of patients with multi
drug resistance became afebrile
› Teo SK. Four month chemotherapy in the treatment of smear negative
PTB: results at 30-60 months. Ann Acad Med Singapore 2002;31: 175-81
“Possible causes of persistent fever in pulmonary
tuberculosis (once non-compliance and supraadded infections have been excluded) include
cytokine release, drug induced fever, drug
resistance, and drug malabsorption.”
BMJ 1996;313:1543-1545 (14 December)
Education and debate
Grand Rounds--Hammersmith Hospital: Persistent fever in pulmonary
tuberculosis Hammersmith Hospital, London W12 0HS Case presented by: Maha
T Barakat, senior house officer in respiratory medicine Chairman: J Scott, director
of medicine.





Patients with cancer in a study conducted at the
Oncology Unit of the Good Samaritan Hospital in
Dayton, Ohio.
Patients with FUO and suspected or diagnosed
malignancy
Naproxen 250 mg twice a day orally at 12-hourly
intervals for at least 3 days
Validity was not established because of the lack of an
independent, blind comparison with a reference
standard
Correlation of the final diagnoses of FUO in all patients
with their response to antibiotics and naproxen
Recommendation:
More appropriate reference standard would be the
absence of infection after extensive and thorough
laboratory work-up coupled with the absence of any
clinical deterioration without administration of any
antibiotics on continued follow-up for at least a
period of 2 weeks.
Utility of Naproxen in the Differential Diagnosis of Fever of Undetermined
Origin in Patients with Cancer: A Commentary
Marissa M. Alejandria, M.D.*
(*Infectious Disease Fellow, UP-PGH, Taft Avenue, Manila)
(Phil J Microbiol Infect Dis 1999; 28(2):73-74)
Restart each anti koch’s one by one.
 To determine which the drug that the patient
had allergic reaction

CBC
JULY 5
JULY 10
JULY 27
HEMOGLOBIN
11.6
12.0
12
HEMATOCRIT
33
34.4
36
WBC
3.94
6.79
11.7
SEGMENTER
69
66
76
LYMPHOCYTE
18
17
13
MONOCYTE
9
11
9
PLATELETS
493,00
401,000
349,000
Sodium
Potassium
Creatinine
BUN
Glucose
Calcium
albumin
Alkaline phosphatase
AST
ALT
7/5
139
7/6
137
3.8
0.90
4.3
1.0
75.9
7/15
137
8.3
2.7
152
28
21
42
34
7/23
7/30
0.9
1.0
8/4

Pleural fluid analysis:
› MICROSCOPY:
 RBC 1219 U/L
 WBC 115 U/L
 SEGMENTER 0.05
 LYMPHOCYTE 0.95
› Fungal elements: negative
› AFB smear: negative
› Gram stain: pus cell 0-2

Pleural Fluid culture (July 8): no growth

Pleural Fluid Cytology: negative for malignant
cells

Cytospin: Chronic Inflammatory process

Pleural Tissue and Lung Biopsy
› CHRONIC GRANULOMATOUS INFLAMMATION,
CONSISTENT WITH TUBERCULOSIS, RIGHT
PLEURAL BIOPSY
› Congestion and atelectasis, adjacent lung
tissue

Lupus panel : negative
AFB Sputum x 3 days (July 5-7, 2009): Negative
 AFB sputum culture July 8,2009: no growth
 Blood Culture July 6,09: No growth after 5 days

Chest x-ray
July 6, 2009
Decreased in the pleural density at the right
mid-lower outer lung with blunting of the
costophrenic sulcus.
No layering seen in the right lateral decubitus
view. Loculated pleural effusion and /or
thickening considered.
Underlying parenchymal pathology not ruled
out. The heart is not enlarged.
JUNE 27,09
JULY 6,09
JULY
6,09
JULY 6,09
July 8. 2009
There is decreased in the pleural fluid seen in
the right Hemithorax. Right Chest tube is
noted
July 29, 2009
There is partial evacuation of the pleural
effusion in the right. The visualized lung
appear clear
JULY 8.09
July 8. 2009
There is decreased in the pleural fluid seen in
the right Hemithorax. Right Chest tube is
noted
July 29, 2009
There is partial evacuation of the pleural
effusion in the right. The visualized lung
appear clear
JULY29,09

CT SCAN OF THE CHEST July 7,2009:
› Consider Pneumonia vs PTB, right upper lobe.
› Moderate pleural effusion, right
› passive atelectasis of the posterior basal segment
of the right lower lobe prominent paratracheal
lymph nodes, not enlarged by CT criteria
› Subcentimeter cyst, right kidney, Bosniak I
Category
› Normal contrast enhanced CT scan of the rest of
the abdominal organs

CT SCAN OF THE CHEST July 23,2009:
› Interval placement of the right thoracostomy
tube with residual pleural effusion
› Possibilty of loculation is entertained
› No interval change in the right pulmonary
infiltrates since the previous examination
› Present note of focal atelectasis in the right lower
lobe seen
› Prominent pretracheal and precarinal lymph
node, relatively unchanged.
POSITIVE
DIRECTED
EXAM
Needle biopsy,
invasive testing
NO
DIAGNOSIS
EMPIRICAL
THERAPY
Anti TB
therapy
WATCHFUL
WAITING
Colchicine/
NSAID
Steroids
DIAGNOSIS
Specific
therapy
NEGATIVE
DIRECTED EXAM
GA Scan, PMN
scan, PET scan
NEGATIVE
POSITIVE
Needle biopsy,
invasive testing
NO
DIAGNOSIS
EMPIRICAL
THERAPY
Anti TB
therapy
WATCHFUL
WAITING
Colchicine/
NSAID
Steroids
NEGATIVE CT chest, abdomen, pelvis
and colonoscopy
GA Scan, PMN scan,
PET scan
POSITIVE
NEGATIVE
Needle biopsy,
invasive testing
No
diagnosis
Empirical
therapy
Anti TB
therapy
Watchful
waiting
Colchicine/
NSAID
Steroids
POSITIVE CT chest,
abdomen, pelvis and
colonoscopy
Needle biopsy,
invasive testing
NO
DIAGNOSIS
Empirical
therapy
Anti TB
therapy
Watchful
waiting
Colchicine/
NSAID
Steroids
DIAGNOSIS
Specific
therapy
 PTB leading diagnosable cause of FUO
 Defervesence
occurred within 2 weeks in
78% of patients with drug susceptible
organisms while only 9% of patients with
multi drug resistance became afebrile
 Validty is not established in Naproxen test
 Should be treated accordingly
Thank you!!!