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
CASE1: ชายไทยค อาย 47ป อาชพคร ภมล าเนาจ.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
CASE1: ชายไทยค อาย 47ป อาชพคร ภมล าเนาจ.นครราชสมา
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
Wibulpolprasert B, et al, Visceral organ abscesses in melioidosis. J clin Ultrasound 1999; 29-34.
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
Wibulpolprasert B, et al, Visceral organ abscesses in melioidosis. J clin Ultrasound 1999; 29-34.
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
CASE4: หญงไทยค อาย 74ป ไมไดประกอบอาชพ ภมล าเนาจ.นครราชสมา
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
CASE5: หญงไทยค อาย 70ป ไมไดประกอบอาชพ ภมล าเนาจ.นครราชสมา
• 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