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 on July

5,2009

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 dayD1 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 dayD1

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

10th hospital day ANTI KOCH’S

4th Hospital dayD1 CEFEPIME

Fever secondary to Infection vs. Malignancy Naproxen 375mg, BID and later decreased to

275mg, BID Cefepime discontinued

12th hospital dayCEFEPIME

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

AfebrileChest x-ray

no recurrence of fever noted

DAY 28-30RE CHALLENGEANTI 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)

58 year old male FEVER x 3 wks

RUQ pain Dyspnea Decreased

tactile fremitus dull on

percussion decreased

breath sounds- mid to lower

right lung field no crackles

no wheezes

INFECTIONS

NEOPLASMS

COLLAGEN VASCULAR DISEASES

MISCELLANEOUS CONDITION

leading diagnosable cause of FUO 6th leading cause of morbidity and mortality

Diagnosis, Treatment, Prevention and Control of Tuberculosis: 2006 UpdateCLINICAL 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 DEFINITIONNEW A patient who has never had

treatment for TB or, if with previous anti TB medications, taken for less than 4 weeks.

RELAPSE 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 (+)

RETURN TO TREATMENT AFTER DEFAULT

Stops medications for 2 months or more and comes back to the clinic smear (+)

CATEGORIES DEFINITIONFAILURE 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

TRANSFER –IN Management was started from another area and now transferred to a new clinic

CHRONIC CASE Became or remained smear (+) after completing fully a supervised re-treatment 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 for TB symtomatics who are smear negative?› TB culture with Drug susceptibilty› Chest Radiograph

RECOMMENDED TREATMENT FOR NEWLY DIAGNOSED SMEAR POSITIVE

› 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) THRICE-WEEKLY (RANGE)

ISONIAZIDRIFAMPICIN

PYRAZINAMIDEETHAMBUTOL

STREPTOMYCIN

1010251515

10353015

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

MINORGastro intestinal

intoleranceRifampicin/INH Meds at bedtime/ small

meals

Mild skin reaction Any kind of drugs Anti histamine

Orange/ red colored urine

Rifampicin Reassure patients

Pain at the Injection site

streptomycin Warm compress

ADVERSE REACTIONS

DRUG MANAGEMENT

Peripheral neuropathy

Isoniazid Pyridoxine 100-200ng, daily (Treatment)100mg prevention

Arthralgia due to Hyperurecemia

Pyrazinamide NSAID

Flu-like symptoms Rifampicin Anti pyretics

ADVERSE REACTIONS

DRUGS MANAGEMENT

MAJOR

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

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/Rifampicin

Discontinue anti TB drugs, refer 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 supra-added 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 CommentaryMarissa 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

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

JULY 6,09

JULY 6,09

JULY 6,09

JULY 8.09

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.

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!!!