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CASE Approach to patients with prolonged fever

Sirichai Wiwatrojanagul, M.D., M.Sc.

Division of Infectious Disease

Department of Medicine

Maharat Nakhon Ratchasima Hospital

Approach to fever

• History • Age

• Occupation

• Place of origin, Travel history

• Consumption of unpasteurized dairy products

• STI risk

• Family history

• Contact pulmonary tuberculosis

• Family members has an illness

• Drugs • Immunosuppressive drugs

• Previous antibiotics

• Host (underlying disease)• Immunodeficiency

• Post splenectomy

• Diabetes mellitus

• Cirrhosis

• CKD

• ...

How to differentiate the cause of prolonged fever in clinical practice

• Clinical Presentation

• Host

• Exposure / Epidemiology

Clinical Presentation

• Fever with specific organ/system involvement

• Fever with multi-organs/system involvement

• Fever without specific organ/system involvement

• Typical manifestation of a common disease

• Atypical manifestation of a common disease

• Typical manifestation of a uncommon disease

• Atypical manifestation of a uncommon disease

Host

• Infection in the Elderly (>65 year)

• Infection in Neutropenia

• Infection in Cirrhosis

• Infection in Diabetes Mellitus

• Infection in Thalassemia patients

• Infection in SLE, RA

• Infection in Transplant recipients

• Fever in the returned traveler

• Fever of unknown origin

Host

• Steroid: CMI deficiency and Phagocytic dysfunction• CMI deficiency -> Listeria monocytogenes, Nocardia spp, TB/NTM, Mould,

dimorphic fungi, C. neoforman, toxoplasma gondii

• Phagocytic dysfunction -> S. aureus, P. aeruginosa, zygomycetes

• DM: Phagocytic dysfunction • Phagocytic dysfunction -> S. aureus, P. aeruginosa, zygomycetes

• Iron overload : L. monocytogenes, e.coli, V. vulnificus, A. hydrophila, Y. enterocolitica, zygomycetes

• Splenomegaly: Encapsulated -> S. pneumonia, H. influenza, N. menigitidis, C. canimorsus, C.cynodegmi

Exposure / Epidemiology

• Race

• Domicile, Region

• Career

• Hobby

• Immunization

• Travel

No Localizing sign & symptoms

Prolonged FeverLocalizing symptoms▪ CNS ▪ GI ▪ CVS ▪ GU ▪ Skin ▪ LN▪ Respiratory ▪ Bone & joint ▪ Hemato

Laboratory▪ CBC ▪ LFT ▪ Bun/Cr ▪ UA ▪ Hemoculture▪ ESR/CRP

Review history ▪ Occupation/recreation ▪ Habitat ▪ Travel ▪ Animal contact ▪ Contact with ill person ▪ Medications

No diagnosis ! FUO

Prolonged Fever

Localized infections

• CNS -> Meningitis, Brain mass• CVS -> IE, Aortitis/Aneurism• Respi -> Pneumonia, Effusion• GI -> Intraabdominal infection• Bone&Joint -> Spodylodiscitis• Lymphadenopathy• Skin lesion• KUB• Hemato

Non- Localized infections

• Fever of unknown origin• Infection

• Autoimmune

• Tumor

Fever of unknown origin

Infection Tumor Miscellaneous

▪ CT chest

▪ CT Abdomen▪ Anti-HIV▪ PPD

▪ Occult abscess▪ Occult TB▪ Culture negative IE▪ HIV

▪ CT abdomen

▪ CT chest▪ Bone marrow Bx

▪ RE tumor: lymphoma, leukemia▪ Renal cell CA▪ Hepatic cancer▪ Hepatic metastasis

▪ TFT▪ ANA, RF, ESR▪ Venous doppler

▪ Drug fever▪ Temporal arteritis▪ Still’s syndrome▪ DVT/PE▪ Sarcoidosis▪ Vasculitis

Clinical Evaluation of Fever of unknown origin

• History :Comprehensive History is cornerstone

• Physical Examination : Repeated PE

• Laboratory Investigation : Noninvasive test ; CBC, UA, chemistry, culture, serology, BM study

• Imaging Studies : U/S, CT scanning

• Invasive Diagnostic Procedures : Histopathology ; excisional biopsy, needle biopsy or laparotomy

• Therapeutic Trials

FUO : Therapeutic Trials

• Limitations and risks of empirical therapeutic trials are obvious

• Underlying disease may remit spontaneously

• Naproxen test to differentiate malignant from nonmalignant remains invalidated

• Reserved for very few patients in whom all other approaches have failed or so seriously ill

• In practice, most often in suspected TB

Classic Nosocomial Neutropenic HIV-related

Definition >38°C 3 wk., > 3 visits or 3 d in hospital (Durack & street 1991)

>38°C, 3 d, not present or incubating on admission

>38oC, 3 days, negative cultures after 48 hrs. with ANC

>38°C,< 3 d for inpatients, outpatient > 4 wk. HIV infection confirmed

Patient location

Community, clinic or hospital

Acute care hospital Hospital or clinic Community, clinic or hospital

Leading causes

Infections, inflammatory conditions, cancer, undiagnosed, habitual hyperthermia

Nosocomial infections, postoperative complications, drug fever C. difficileinfection, thrombophlebitis

Majority due to infections, but cause documented in only 40–60% (Aspergillus spp., Candida spp.)

(HIV primary infection), typical & atypical mycobacteria, CMV, lymphoma, toxoplasmosis, cryptococcosis

History emphasis

Travel, contacts, animal and insect exposure, medications, immunizations, family history, cardiac valve disorder

Operations and procedures, devices, anatomic considerations, drug treatment

Stage of chemotherapy, drugs administered, immunosuppressive disorder, Skin folds, IV sites, lungs, perianal area

Drugs, exposures, risk factors, travel contacts, stage of infection Mouth, sinuses, skin, lymph nodes, eyes, lungs perianal area

Classification of the four subtypes of FUO

CASE1: ชายไทยค อาย 47ป อาชพคร ภมล าเนาจ.นครราชสมา

• CC: กอนโตขนตามตว มา 3 เดอน

4 เดอนกอน สงเกตวามไขต าๆ โดยเฉพาะชวงค า ไมมอาการผดปตอยางอนรวมดวย

3 เดอนกอน ยงมไข รวมกบสงเกตวามกอนทคอ 2 ขางโตมากขน กอนแขง ไมมอาการปวด มเบออาหารและน าหนกลดลง (จาก 86 เหลอ66 กโลกรมในชวง3 เดอน)ไมมไอเรอรง ไมมอาการอนผดปกต

2 เดอนกอน ยงคงมไข รวมกบกอนโตเพมขนทบรเวณขาหนบทงสองขาง แขง ไมเจบ กอนทบรเวณคอยงมขนาดเทาๆ เดม ผปวยซอยาหมอมาตมกนอย 1 เดอน สงเกตวากอนยบลงแตไมหมด

1 เดอนกอน ไขสงขนหลงหยดยาหมอ รวมกบกอนโตมากขน จงไปพบทรพช. และสงตวตอมารกษาตอ รพ.มหาราช นครราชสมา


Physical examination

• T 38.6 c, BP 116/75 mmHg, HR 120/min, RR 16/min

• GA: Good consciousness, moderately pale, no jaundice, no dyspnea & tachypnea

• HEENT: no thyroid gland enlargement

• CVS & RS: unremarkable

• Abdomen: soft, no distension, no tenderness, no hepatosplenomegaly, no ascites, normal bowel sound

• Nervous system: no neurological deficit

Lymphatic system :

• Cervical-> Bilateral matted LN, the largest node was 10 cm in diameter firm consistency, not tender, movable

• Axillar -> Bilateral multiple matted LN, 3 cm in diameter of 4-5 nodes each side firm consistency, not tender, movable

• Inguinal -> Bilateral multiple matted LN, 4 cm in diameter of 4-5 nodes each sidefirm consistency, not tender, movable


Problem List

• Prolonged fever with Generalized lymphadenopathy for 4 months

• Significant weight loss (20 kg in 3 months)

• Anemia

Investigation

• CBC: Hb7.4 g/dL, Hct24.2%, MCV 82 fL, WBC 7,480/mm3(N 75.4%, L 14.3%, M 7.2%, Eo2.8%, B 0.3%), plt424,000/mm3

• Blood chemistry : BUN 12.1mg/dL, Cr 1.0mg/dL,Na 137 mmol/L, K 2.9 mmol/L, Cl95 mmol/L, HCO328 mmol/L

• LFT: TB 0.3 mg/dL, DB 0.16 mg/dL, AST 18 U/L, ALT 12 U/L, ALP 240U/L, Albumin 2.5 g/dL, Globulin 6.1 g/dL

Prolonged fever with Generalized lymphadenopathy

Key Factors in Evaluation• Age of patient • Location of lymphadenopathy • Systemic signs/symptoms • Presence/absence of

splenomegaly • Size, consistency, tenderness,

and fixation of LN• History of exposures • Drug history

•Aspirate LN: AFB, mAFB, G/S, Wright, culture

•LN Aspiration, biopsy and culture

Specific treatment

• HIV: -> TB/NTM, Dimorphic fungi, Crypto• Exposure-> Cat->CSD• Systemic or Autoimmune -> Kikuchi Fujimoto disease• Rash/Arthritis-> Still's disease• IgG4-related disease

Case1: ชายไทยค อาย 47ป อาชพคร ภมล าเนาจ.นครราชสมา

• FNA: AFB+

• PCR: Positive for NTM

• Tissue C/S: M. abscessus

• H/C for mycobacterium : M. abscessus

• Anti-HIV – nonreactive

• Anti IFN Gamma Ab– positive

Adult-onset immunodeficiency with disseminated M. abscessus infection

Mycobacteria

Mycobacterium tuberculosis complex

(MTBC)Non-tuberculous mycobacteria (NTM)

M.tuberculosisM.africanumM.bovisM.canettiM.capraeM.microtiM.pinnipedii

RGMSGMNon-

culturable

M.fortuitum complexM.chelonae-abscessuscomplexM.smegmatis complex

M.leprae

Photochrom

ogen

Scotochrom

ogen

Non-chrom

ogen

M.MarinumM.kansasiiM.simiae

M.scrofulaceumM.gordonaeM.szulgai

MACM.haemophilumM.ulcerans

Baldwin SL et al. PLoS Negl Trop Dis. 2019;13(2): e0007083 Retrieved form Facebook : oneslide ID

Haworth CS, et al. Thorax 2017;72:ii1–ii64

Anti IFN-gamma autoantibody associated with adult-onset immunodeficiency

IL-12, IFN-Y, TNF-a Pathway

CASE2: หญงอาย 68ป อาชพท านา ภมล าเนานครราชสมา

• CC: ไขมา 2 เดอน• PI: 2 เดอน มไขสงๆต าๆ ทานพาราเชตแลวดขน

1เดอน เรมปวดบรเวณกนกบปวดตอๆ เปนมากเวลานอนหงายและขยบตว

วนนไมดขนยงมไข และปวดกนกบมากขน และน าหนกลด 5กโลกรม (56->51)

-No Hx contact TB-ไมไดเลยงสตว

Physical examination

• T 38.5 c, BP 140/86 mmHg, HR 100/min, RR 16/min

• GA: Good consciousness, no pale, no jaundice, no dyspnea & tachypnea

• HEENT: no thyroid gland enlargement

• CVS & RS: unremarkable

• Abdomen: soft, no distension, no tenderness, no hepatosplenomegaly, no ascites, normal bowel sound

• Tender at LS area

• Nervous system: no neurological deficit

CASE2: หญงอาย 68ป อาชพท านา ภมล าเนานครราชสมา

Investigation

• CBC: Hct30 WBC5700 Plt331000

• BUN/Cr LFT:normal

• ESR100

Problem list

• –> Prolonged fever with inflammatory back pain for 2 months

• Spondylodiscis• Etiology – TB/NTM, Pyogenic,

Brucellosis

• Investigation • MRI spine

MRI finding: spondylodiscitis

1. Decrease signal intensity from disc and adjacent vertebral body on T1-weight image and loss of vertebral endplate

2. Increase signal intensity on T2-weight images ( due to edema)

3. Gadolinium enhancement of disc, vertebrae and surrounding soft tissue

Sign on MRI Sensitivity

1. Inflammation of soft tissue ( high T2

signal intensitiy and contrast uptake )98%

2. Disc enhancement ( contrast uptake ) 95%

3. High T2 signal intensity from the disc

or fluid-like signal93%

4. Loss of intradiscal space 84%

1+2, 2+3, 3+4, 1+3 หรอ 1+ destruction

of the vertebral endplates100%

Variable Pyogenic Tuberculous Brucellar

Commonly involved region Lumbar spine Thoracic spine Lumbosacral spine

Involvement of vertebral bodies

Involvement ≤2 vertebral bodies

Multiple body involvement or Skip lesion

Involvement ≤2 vertebral bodies

Degree of disc preservation Moderate to complete disc destruction

Normal to mild disc destruction (Late)

Moderate to complete disc destruction

Endplate destruction Anterior Anterior and posterior Anterior and superior“ Parrot-beak osteophyte”

Bony destruction more than half

Infrequent and mild to moderate

Frequent and more severe Infrequent and mild to moderate

Vertebral body enhancement pattern

Homogeneous Heterogeneous and focal Homogeneous

Epidural abscess Presence Presence , More common Presence

Paraspinal abscess and abscess wall

<2cm, Thick and irregular >2cm, Thin and smooth <2cm, Thick and irregular

Postcontrast paraspinalabnormal signal margin

Ill-defined Well defined Ill-defined

Abscess with postcontrastrim enhancement

Disc abscess Vertebral intraosseousabscess

Disc abscess

Dx: Brucellosis

• H/C : Brucella melitensis x II specimen

• Rx :

Non localized Doxycycline (6wks) + Gentamicin (7D)Doxycycline (6wks) + Rifampin (6wks)

Osteoarticular Doxycycline (3mo) + Gentamicin (7D) or Ciprofloxacin (3mo) + Rifampin (3mo)

Neurobrucellosis Doxycycline + Rifampin + CeftriaxoneUntil CSF become normal

Pregnant Woman TMP/SMX + Rifampin

B. melitensis -> GoatB. abortus -> CattleB. canis -> DogB. suis -> Pig

Diagnosis• Culture: Blood, BM• Non Culture- PCR- Serology

- Rose Bengal- Serum agglutination test (titer >1:160)- ELISA

CASE3: ชายไทยค อาย 54ป อาชพขบรถรบจาง ภมล าเนาจ.นครราชสมา

• CC: ไข 1 เดอน

• 1 เดอนมไขต าๆ ตลอดทงวน กนยาลดไขแลวอาการดขน กนไดลดลงอมเรวขน รสกแนนทองหลงกนอาหาร ไมมคลนไส/อาเจยน ถายอจจาระปกต ไมเคยเขาปา/ลยน า ไมได ทองเทยงตางจงหวด ไมเคยมประวตคนในครอบครว/คนใกลตวเปนวณโรค

• 1 สปดาหปวดทองดานขวาบน ไมมราวไปต าแหนงอน ไขเรมสงขนหนาวสน สงเกตวาตวและตาเหลองมากขนจงมาโรงพยาบาล

• Past Hx: DM type2

• Personal Hx: กนเหลาขาว 1-2 แบน/วน สบบหร 20 pack-year

CASE3: ชายไทยค อาย 54ป อาชพขบรถรบจาง ภมล าเนาจ.นครราชสมา

• PE V/S BP 120/70 mmHg PR 80/min RR15 T 37.8˚c

• Thai man, good consciousness, pale, no jaundice

• HEENT: moderately plae conjunctivae, anicteric sclerae

• Heart : no murmur

• Lung : clear, no adventitious sound

• Abdomen : soft, mild tender at RUQ, no guarding, no rebound tenderness, liver 3 FB BRCM, liver span 12 cm, splenic dullness – positive, Fist test -positive

• Ext : no rash, no petechiae or ecchymosis, no pitting edema

Case3: ชายไทยค อาย 54ป อาชพขบรถรบจาง ภมล าเนาจ.นครราชสมา

Problem list

• Prolonged fever with RUQ pain with Hepatosplenomegaly and tender

Investigation

• CBC: Hb 12 g/dL, Hct 38.5%, WBC 13,300 /mm

3 (N 83.1%, L

7.4%,band9.5%) Platelet 145,000 /mm

3

• BUN 20 mg/dL, Cr 1.1 mg/dL, Na 133, K 3.5, Cl 97, HCO3 22 mmol/L

• LFT: Alb 2.8, Glob 3.9 g/dl, TB 0.46, DB 0.27 mg/dL, AST 58, ALT 130, ALP210 U/L

Gram stain:

- Many WBC (PMN predominate)

- Numerous gram negative rod

(bipolar stain)

Pus C/S : Burkholderia pseudomallei

Dx: Melioidosis

• Safety pin/Bipolar staining• Burkholderia pseudomallei• Pseudomonas aeruginosa• Klebseilla pneumoniae• Yersinia pestis• Pasturella multocida• Klebsiella granulomatis• Francisella tularensis

Melioidosis

• Gram-negative bacteria

• Burkholderia pseudomallei

• Mean incubation period 3-7

days in acute infection & 2-3

weeks to months or years in

chronic infection

Risk factor OR (95% CI )

Thalassemic disease 10.2 (3.5-30.8)

DM 5.9 (4.0-8.9)

Preexisting Renal disease 2.9(1.7-2.5)

DM with high soil & water exposure

8.5(5.5-13.1)

DM with Moderate soil & water exposure

5.6(1.7-18.6)

High soil & water exposure 3.3(1.8-6.3)

Moderate soil & water exposure

2.1(0.8-5.6)

Excessive alcohol consumption

Less prevalence in Thailand

Suputtamongkoletal B, et al, Risk factor for melioidosis. CID 1999;29.

W. Joost Wiersinga, Melioidosis, NEJM,2012, 367;11

Transmission of infection• Percutaneous inoculation.• Inhalation.• Aspiration and ingestion.

Signs and symptoms of liver abscess

Clinical practice in gastroenterology. 2555; 278

Amoebic Pyogenic Melioidosis

Symptoms

- Fever 51-48 42-86 100

- Abdominal pain 86-100 52-58 44

- RUQ pain 47-60 45-48 24

- Dysentery 10-42 0-11 -

Signs

- Hepatomegaly 62-87 52-85 76

- Abdominal tenderness 33-77 35-62 47

- Jaundice 14-27 21-48 26

- Ascitis 9 10 -

- Peritonitis 11 10 -

Sonographic appearance of liver abscesses

Amoebic Pyogenic Melioidosis

Number

- Single 71-96 52-80 18

- Multiple 4-29 20-48 82

Site

- Right lobe 86-96 50-63 74

- Left lobe 4-9 8-31 6

- Both lobes 2-9 6-41 26

Characteristic

Hypoechoic round or oval, no septum

Hypo-,or isoechoic, multiloculated or

multiseptated

Multiloculated or multiseptated, cart-wheel or

swiss-cheese

Spleenic abscess - 6 56Clinical practice in gastroenterology. 2555; 278

Visceral organ involvement in melioidosis

Organs PatientsOne organ 57 (71%)

- Spleen 37

- Liver 16

- Kidney 4

Multi-organ 23 (29%)

- Liver and spleen 17

- Liver, spleen and kidney 3

- Spleen and kidney 2

- Liver and kidney 1

Wibulpolprasert B, et al, Visceral organ abscesses in melioidosis. J clin Ultrasound 1999; 29-34.

Sizes and sonographic appearance of abscesses in melioidosis


Characteristic Melioiodosis Other bacterias

Number

- Multiple 28 (82) 5 (31)

- Single 6 (18) 11 (69)

Site

- Right lobe 25 (74) 10 (63)

- Left lobe 2 (6) 5 (31)

- Both lobe 7 (20) 1 (6)

- With spleen 19 (56) 1 (6)

Sizes and sonographic appearance of abscesses in melioidosis


Site and size Appearance of lesion ( No. Patients)

Cystic Target-like Bull's eye Multiloculated

Splenic abscess

< 2cm. ( 54 Pts.) 1 37 3 15

>=2cm. ( 13 Pts.) 2 3 3 6

Liver abscess

<2cm. (21 Pts.) 0 13 4 5

>=2cm. (23 pts.) 0 0 1 21

Chest x-ray characteristic

Acute with bacteremian=55 (%)

Acute without bacteremian=50 (%)

Subacute/chronic bacteremian=31 (%)

Subacute/chronic

n=47 (%)

Infiltrations

Nodular 46 (84) 11 (22) 17 (55) 13 (28)

Alveolar 4 (7) 26 (52) 4 (13) 8 (17)

Mixed 2 (3.5) 9 (18) 8 (26) 23 (49)

Miscellaneous 3 (3.5) 4 (8) 2(6) 3 (6)

Distribution

One lobe 9 (17) 19 (38) 9 (29) 17 (36)

Multiple lobe 44 (80 ) 31 (62) 22 (71) 30(64)

Apical lesion 5 (9) 6 (12) 6 (19) 10 (21)

Treatment of melioidosisAntimicrobial drug Dose

Initial intensive therapy (at least 14 days)

Ceftazidime (120mg/kg/day) 2 gm iv q 8hr

Imipenem (50mg/kg/day) 1 gm iv q 8hr

Meropenem (75mg/kg/day) 1 gm iv q 8 hr

Amoxy/clav (160mg/kg/day of amoxy) 2.4 gm iv loading then 1.2gm iv q 4hr

Cefoperazone/sulbactam + Co-trimoxazone 25mg/kg/day(cefoperazone)+ 8mg/kg/day (TMP)

Eradication therapy (20 wks)

Co-trimoxazole (80TMP/400SMX)

BW > 60 kg 4tab oral q 12hr

BW 40-60 kg 3tab oral q 12hr

BW < 40 kg 2tab oral q 12hr

Co-trimoxazole+doxycycline : relapse 4% Add doxycycline(100) 1 tab oral q 12hr

Amoxy/clav : relapse 16% ( recommend in pregnancy) 60mg/kg/day(amoxy) + 15mg/kg/day(clavulanic)

Ciprofloxacin+azithromycin : relapse 22% Ciprofloxacin 500mg bid + azithromycin 500 mg oral od

CASE4: หญงไทยค อาย 74ป ไมไดประกอบอาชพ ภมล าเนาจ.นครราชสมา

CC: เหนอยมากขน 1วน• 1เดอนกอน รสกมไขต าๆ เปนตลอดทงวน รวมกบมอาการไอแหงๆ เลกนอย ไมมอาการผดปกต

• 2สปดาหกอน ยงมไขตลอด ไอเรมมเสมหะ ไปตรวจท รพช แพทยใหนอนโรงพยาบาลไดยาเปน Ceftriaxone และ Azithromycin

• 1วน ขณะทยงนอนโรงพยาบาล มไขสงขนและหอบเหนอยมากขน จงreferมา

• ไมมโรคประจ าตว


mass at right chest wall 2x3 cm with tender, redness , fluctuation

Vital sign : BP 95/60 mmHg PR 75 bpm BT 38.5 RRGA: A Thai middle-aged woman ,AlertHEENT: not conjuctivae, anicteric sclerae, LN can’t palpableHeart: apex at 5th ICS , impalpable apex , JVP notengorge, no heaving, no thrill, normal s1 s2, no MurmurLung: trachea in midline normal breath sound, equally both lung , secretion sound both lung, Fine crepitation both lungAbdomen: normal distension, no superficial vein dilatation, normoactive bowel sound, soft , not tender , fluid thrill negative, liver span 10 cmExtremites: no pitting edema, no petechiae , no ecchymosisNeuro: grossly intact

CASE4: หญงไทยค อาย 74ป ไมไดประกอบอาชพ ภมล าเนาจ.นครราชสมาProblem list

• Progressive dyspnea for 3 day

• Multiple mass at chest wall

• Hx of pneumonia

• Hx of breast mass

• mAFB:Positve• A cluster of beaded

branching filamentous

Dx: Nocardiosis

Nocardiosis

• Nocardia spp.

Clinical presentation

• Pulmonary nocardiosis

• Lymphocutaneous

• Disseminated nocardiosis

Risk factorUsually Immunosuppressive condition

• HIV (esp. CD4 < 100 cell/mm3)

• Solid organ/hematopoietic stem cell transplant

• Glucocorticoid / CMT therapy

• Chronic lung disease

• DM

Up to 1/3 of patient are immunocompetent

Non-severe infection

Isolated cutaneous infection TMP-SMX OR Minocycline (alternative regimen)

Non-severe mycetoma TMP-SMX +/- Dapsone

Mild or moderate pulmonary disease in immunocompetent hosts

TMP-SMX

Mild or moderate pulmonary disease in immunocompromised hosts

TMP-SMX

Severe infection

Severe mycetoma Imipenem +/- Amikacin

Severe pulmonary or disseminated disease (without CNS involvement)

TMP-SMX PLUS Amikacin (first-line regimen)ORImipenem PLUS Amikacin (alternative regimen)

Involvement of ≥2 sites in immunocompromisedhosts (without CNS involvement)

TMP-SMX PLUS Amikacin (first-line regimen)ORImipenem PLUS Amikacin (alternative regimen)

Isolated CNS disease TMP-SMX PLUS Imipenem

CNS disease with multiorgan involvement (ie, at least one other site)

TMP-SMX PLUS Imipenem PLUS Amikacin

Life-threatening disease TMP-SMX PLUS Imipenem PLUS Amikacin

Rx: Nocardiosis

Switch to oral therapy

• Start after induction phase (usually 3rd -6th week)

• Based upon a susceptibility result

CNS not involvement

• monotherapy

CNS involvement/multiorganinvolvement/immunocompromised

• 2 drug regimen(based upon susceptibility)

• TMX-SMX(10mg/kg/day)

• Minocycline (100mg twice daily)

• Amoxicillin-clavulanate (875 mg twice daily)

Duration

Immunocompetent

• Isolated cutaneous infection : 3-6 month

• Pulmonary involvement : 6-12 month

• CNS involvement : at least 1 year

Immunocompromised

• Isolated cutaneous infection : 6-12 month

• Other :at least 1 year

CASE5: หญงไทยค อาย 70ป ไมไดประกอบอาชพ ภมล าเนาจ.นครราชสมา• CC: ไข 4 เดอนกอนมารพ.• 4เดอนกอน ไขต าๆ โดยเฉพาะชวงค า ไมมอาการผดปกตอยางอน• 3เดอนกอน ไขยงคงมอยตลอด ไปรกษาคลนก ไดยามาทาน แตไมดขน• 2เดอนยงคงมไข ไปตรวจทรพช ไดนอน รพ. ใหยาฆาเชอ นอนนาน1เดอน มไขทกวน อาการเทาๆเดม จงขอแพทยกลบบาน

• วนนไขยงมเหมอนๆเดม แตรสกเหนอยเพลย น าหนกลด 58->45Kg/4เดอน จงมารพ.

• No. U/D• ไมไดเลยงสตว

CASE5: หญงไทยค อาย 70ป ไมไดประกอบอาชพ ภมล าเนาจ.นครราชสมา• Vital sign : BP 120/70 mmHg PR 90 bpm BT 38.5 RR

• GA: A Thai woman ,Alert

• HEENT: mild conjuctivae, anicteric sclerae, LN can’t palpable

• Heart: apex at 5th ICS , impalpable apex , JVP not

• engorge, no heaving, no thrill, normal s1 s2, no Murmur

• Lung: trachea in midline normal breath sound, equally both lung , secretion sound both lung, Fine crepitation both lung

• Abdomen: normal distension, no superficial vein dilatation, normoactivebowel sound, soft , not tender , fluid thrill negative, liver span 10 cm

• Extremites: no pitting edema, no petechiae , no ecchymosis

• Neuro: grossly intact


• CBC: Hb9.6 g/dL, Hct29.2%, MCV 82 fL, WBC 4,780/mm3(N 75.4%, L 14.3%, M 7.2%, Eo2.8%, B 0.3%), plt424,000/mm3, MCV77, RDW17.5

• Blood chemistry : BUN 12.1mg/dL, Cr 1.0mg/dL,Na 137 mmol/L, K 2.9 mmol/L, Cl95 mmol/L, HCO328 mmol/L

• LFT: TB 0.3 mg/dL, DB 0.16 mg/dL, AST 118 U/L, ALT 12 U/L, ALP 112U/L, Albumin 3.1 g/dL, Globulin 5.4 g/dL

• TIBC 258, Serum iron 13

Investigation

• CXR -> Normal

• U/S whole abdomen-> Normal

• H/C for bacteria, fungus, mycobacteria -> NG

• BM study -> Negative

• BM C/S for Bacteria, MycoBacteria, Fungus -> Negative

• EGD and Colonoscopy -> Negative

• CT chest and abdomen -> Negative

• TTE/TEE -> No evident IE

• Anti-HiV : Non-reactive

• ANA : Negative

• CRP 85

• C3/C4- >nomal

• Urine Protein 24 Hr -> normal

• TFT ->normal

• LDH 680

Dx : Intravascular lymphoma

Clinical Presentation• Constitutional B symptoms

• Central nervous system (27 to 76 percent)

• Skin (15 to 39 percent)

• Laboratory studies• Elevated ESR, CRP, LDH

• Anemia

• Altered hepatic, renal, or thyroid function

•Diagnosis : Pathology

No Localizing sign & symptoms

Prolonged FeverLocalizing symptoms▪ CNS ▪ GI ▪ CVS ▪ GU ▪ Skin ▪ LN▪ Respiratory ▪ Bone & joint ▪ Hemato

Laboratory▪ CBC ▪ LFT ▪ Bun/Cr ▪ UA ▪ Hemoculture▪ ESR/CRP

Review history ▪ Occupation/recreation ▪ Habitat ▪ Travel ▪ Animal contact ▪ Contact with ill person ▪ Medications

No diagnosis ! FUO

Fever of unknown origin

Infection Tumor Miscellaneous

▪ CT chest

▪ CT Abdomen▪ Anti-HIV▪ PPD

▪ Occult abscess▪ Occult TB▪ Culture negative IE▪ HIV

▪ CT abdomen▪ Bone marrow Bx

▪ RE tumor: lymphoma, leukemia▪ Renal cell CA▪ Hepatic cancer▪ Hepatic metastasis

▪ TFT▪ ANA, RF, ESR▪ Venous doppler

▪ Drug fever▪ Temporal arteritis▪ Still’s syndrome▪ DVT/PE▪ Sarcoidosis▪ Vasculitis

case approach to patients with prolonged feverreviews.berlinpharm.com › 20191019 ›...

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