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 To present a case of a patient with persistent fever.  To discuss the approach and management in patient with persistence of fever.

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Presentation on theme: " To present a case of a patient with persistent fever.  To discuss the approach and management in patient with persistence of fever."— Presentation transcript:

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2  To present a case of a patient with persistent fever.  To discuss the approach and management in patient with persistence of fever.

3  R.B, 58-year-old male,  married, Filipino  Farmer from Tuguegarao, admitted on July 5,2009

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5  3 WEEKS PTA › fever, undocumented › right upper quadrant pain › No change in bowel movement

6 › 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

7  2 WEEKS PTA › Fever and Right upper quadrant pain › Dyspnea › No cough, chest pain

8  local institution Tuguegarao.  Abdominal Ultrasound: Cholesterolosis  Chest xray and Chest Ultrasound : pleural effusion on the right.  Thoracentesis 1 liter

9  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

10  generalized weakness  weight loss  Loss of appetite  no headache  no palpitations  No signs of bleeding  no dysuria/ frequency/ hematuria  no joint stiffness/ weakness

11  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

12  Non smoker  Non alcoholic beverage drinker  No illicit drug use  Denies exposure to a PTB patient

13  No Hypertension  No Cancer  No Diabetes Mellitus  No asthma  No PTB

14  Conscious, coherent, ambulatory, Not in cardio respiratory distress › weight: 61 Kg Height: 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

15  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

16  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

17  Fever secondary to Pulmonary Tuberculosis vs. Pneumonia r/o malignancy  Pleural effusion, right  Cholesterolosis

18  CBC CBC  Chest radiograph Chest radiograph  Serum electrolytes Serum electrolytes  sputum smear for acid fast bacilli sputum smear for acid fast bacilli  Paracetamol 500mg  Tramadol 50mg

19  febrile Tmax 39.3 ; abdominal pain  Patient referred to IDS  Impression: Hepatic abcess. Parapneumonic Effusion, right.  CT scan of the chest and abdomen CT scan of the chest and abdomen  Chest tube thoracostomy, right (300ml of serous fluid)

20  repeat Chest radiograph repeat Chest radiograph  Acid fast bacilli sputum smear Acid fast bacilli sputum smear  Ampicillin-Sulbactam 1.5g, q6

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22 Pleural fluid gram staining Pleural fluid gram staining Ampicillin-Sulbactam was shifted to Cefepime 1g, every 12 hrs.

23 4 th Hospital day D1 CEFEPIME 4 th Hospital day D1 CEFEPIME

24  Febrile Tmax 39.1  CBC CBC  Blood culture Blood culture  Acid fast bacilli smear of pleural fluid Acid fast bacilli smear of pleural fluid  Acid fast bacilli culture Acid fast bacilli culture  HRZE (Myrin P forte) 4 tablets, once a day.

25 6 th hospital day D1 ANTI KOCH’S 6 th hospital day D1 ANTI KOCH’S

26 › febrile Tmax 39C › loss of appetite › Dizziness › loose bowel movement › Pleural fluid cytology Pleural fluid cytology › Myrin P Forte discontinued

27  INH 300mg,1 tab, before breakfast  Rifampicin 600mg,1 tab, before breakfast;  Ethambutol 400mg,3 tabs, after breakfast  PZA 500mg,4 tablets, after lunch

28  Febrile Tmax 38.9  Headache, vomiting, dizziness and tinnitus  Impresssion: Drug induced vs central cause R/O Connective tissue disease

29 Lupus Panel Lupus Panel Plan: Cranial CT scan & Lumbar Tap Anti Koch’s, Tramadol were discontinued Betahistine was started

30 10th hospital day ANTI KOCH’S 10th hospital day ANTI KOCH’S 4 th Hospital day D1 CEFEPIME 4 th Hospital day D1 CEFEPIME

31  Fever secondary to Infection vs. Malignancy  Naproxen 375mg, BID and later decreased to 275mg, BID  Cefepime discontinued

32 12 th hospital day CEFEPIME 12 th hospital day CEFEPIME

33 12 th hospital day NAPROXEN

34  Fever  Pleural fluid cytology CYTOSPIN Pleural fluid cytology CYTOSPIN  Chest tube thoracostomy drainage (24ml for 24 hrs)  Contrast chest CT scan done. Contrast chest CT scan done.  Chest tube removed.  Video- assisted Thoracoscopic surgery.

35 18 th hospital day 24ml x 24hrs 18 th hospital day 24ml x 24hrs

36  Post MINI thoracostomy, Decortication with pleural and lung biopsy 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

37 25 th hospital day S/P VATS 25 th hospital day S/P VATS

38  Afebrile Chest x-ray no recurrence of fever noted

39 DAY RE CHALLENGE ANTI KOCH’S DAY RE CHALLENGE ANTI KOCH’S

40  PLEURAL EFFUSION, RIGHT SECONDARY TO PULMONARY TUBERCULOSIS  S/P CHEST TUBE INSERTION, RIGHT  S/P MINI THORACOSTOMY, DECORTICATION WITH PLEURAL AND LUNG BIOPSY

41  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)

42 FEVER OF UNKOWN ORIGIN (FUO) CLASSICNOSOCOMIALNEUTROPENICHIV

43 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

44 Temp of >38.3 on several occasions X >3 weeks; Failure to reach a diagnosis despite 1 week of inpatient investigation 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 PHYSICAL EXAM & HISTORY

45 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 PositiveNegative No diagnostic clues Chest CT, abdomen, pelvis. Colonoscopy NegativePositive

46  leading diagnosable cause of FUO  6th leading cause of morbidity and mortality Diagnosis, Treatment, Prevention and Control of Tuberculosis: 2006 Update CLINICAL PRACTICE GUIDELINES

47  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

48 CATEGORIESDEFINITION NEWA patient who has never had treatment for TB or, if with previous anti TB medications, taken for less than 4 weeks. RELAPSEDeclared 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 (+)

49 CATEGORIESDEFINITION FAILUREWhile 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 2 nd month TRANSFER –INManagement was started from another area and now transferred to a new clinic CHRONIC CASEBecame or remained smear (+) after completing fully a supervised re- treatment regimen

50  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

51  INTERPRETATION OF RESULTS: › SMEAR POSITIVE: If at least two sputum specimens are AFB (+) › SMEAR NEGATIVE: If none of the specimens are AFB (+)

52  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

53  What additional tests should be done after a TB symptomatic has been found to be SMEAR POSITIVE? › No further tests are required

54  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

55  Blood/serum tests maybe taken when specific risks for possible adverse events during treatment are present

56  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)

57  What tests are recommended for TB symtomatics who are smear negative? › TB culture with Drug susceptibilty › Chest Radiograph

58  RECOMMENDED TREATMENT FOR NEWLY DIAGNOSED SMEAR POSITIVE › Short course chemotherapy (SCC) regimen  2 months isonoazid, rifampicin, pyrazinamide and ethambutol

59  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

60  The recommended dosages for daily and thrice – weekly administration in mg/kg body weight are as follows: DRUGSDAILY (RANGE)THRICE-WEEKLY (RANGE) ISONIAZID RIFAMPICIN PYRAZINAMIDE ETHAMBUTOL STREPTOMYCIN

61  RECOMMENDED TREATMENT FOR NEWLY DIAGNOSED SMEAR NEGATIVE  2HRZE/4HR (WITHOUT HIV OR WITH AN UNKNOWN HIV)

62  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

63  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)

64  TUBERCULOUS PLEURAL EFFUSION  Microscopic examination detecs acid fast bacilli in about 5-10% of cases

65  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

66 ADVERSE REACTIONS DRUGMANAGEMENT MINOR Gastro intestinal intolerance Rifampicin/INH Meds at bedtime/ small meals Mild skin reactionAny kind of drugsAnti histamine Orange/ red colored urine RifampicinReassure patients Pain at the Injection site streptomycinWarm compress

67 ADVERSE REACTIONS DRUGMANAGEMENT Peripheral neuropathy IsoniazidPyridoxine ng, daily (Treatment) 100mg prevention Arthralgia due to Hyperurecemia PyrazinamideNSAID Flu-like symptomsRifampicinAnti pyretics

68 ADVERSE REACTIONS DRUGSMANAGEMENT MAJOR Severe skin rashAny 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 EthambutolDiscontinue anti TB drugs, refer to DOTS

69 ADVERSE REACTIONSDRUGSMANAGEMENT PsychosisIsoniazidDiscontinue anti TB drugs, refer to DOTS Hearing impairmentStreptomycinDiscontinue anti TB drugs, refer to DOTS Thrombocytopenia, anemia, shock RifampicinDiscontinue anti TB drugs, refer to DOTS OliguriaStreptomycin/Rifam picin Discontinue anti TB drugs, refer to DOTS

70  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

71 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 months. Ann Acad Med Singapore 2002;31: (CLINICAL PRACTICE GUIDELINES)

72  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 months. Ann Acad Med Singapore 2002;31:

73 “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: (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.

74  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

75 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 )

76  Restart each anti koch’s one by one.  To determine which the drug that the patient had allergic reaction

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79  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

80  Pleural Fluid culture (July 8): no growth  Pleural Fluid Cytology: negative for malignant cells  Cytospin: Chronic Inflammatory process

81  Pleural Tissue and Lung Biopsy › CHRONIC GRANULOMATOUS INFLAMMATION, CONSISTENT WITH TUBERCULOSIS, RIGHT PLEURAL BIOPSY › Congestion and atelectasis, adjacent lung tissue

82  Lupus panel : negative

83  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

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86 JULY 6,09

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90 JULY 8.09

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92 JULY29,09

93  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

94  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.

95 POSITIVE DIRECTED EXAM Needle biopsy, invasive testing NO DIAGNOSIS EMPIRICAL THERAPY Anti TB therapy Colchicine/ NSAID Steroids WATCHFUL WAITING DIAGNOSIS Specific therapy

96 NEGATIVE DIRECTED EXAM GA Scan, PMN scan, PET scan NEGATIVE POSITIVE Needle biopsy, invasive testing NO DIAGNOSIS EMPIRICAL THERAPY Anti TB therapy Colchicine/ NSAID Steroids WATCHFUL WAITING

97 NEGATIVE CT chest, abdomen, pelvis and colonoscopy GA Scan, PMN scan, PET scan NEGATIVE POSITIVE Needle biopsy, invasive testing No diagnosis Empirical therapy Anti TB therapy Colchicine/ NSAID Steroids Watchful waiting

98 POSITIVE CT chest, abdomen, pelvis and colonoscopy Needle biopsy, invasive testing NO DIAGNOSIS Empirical therapy Anti TB therapy Colchicine/ NSAID Steroids Watchful waiting DIAGNOSIS Specific therapy

99  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

100 Thank you!!!


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