ahapproach to pti tp atients with fever · 2019-02-10 · 2.2...

A h t P ti t ith fApproach to Patients with fever

Pathogenesis

เชอไวรส

Pathogen

เดงกPathogen

สงแวดลอม

คน ยงลาย Host Environment

Pathogen

• Bacteriai• Virus – AFI : Dengue infection, Chigunkunya virus, acute HIVInfectio s monon cleosis EBV CMV HIV– Infectious mononucleosis : EBV, CMV, HIV

– Fever with rash : Measle, Rubella– Vesicular lesion : HSV Chicken pox HZV– Vesicular lesion : HSV, Chicken pox, HZV– Respiratory tract infection : Influenza virus, parainfluenza virus, RSV, adenovirusp , ,

– Hepatitis : HAV, HBV, HCV– Encephalitis : Enterovirus, HSV, JE

• Fungus : PJP, Candida, Cryptococcus• Parasite , Protozoa (Giardia lambia)

Host defense system : ระบบการตอตานเชอของรางกาย

1.กลไกตอตานเชอโดยกาเนด (Natural or innate defense) หรอกลไกตอตานเชอไมจาเพาะ (non‐specific defense) หรอกลไกตอตานเชอทมอยตลอดเวลา จาเพาะ (non specific defense) หรอกลไกตอตานเชอทมอยตลอดเวลา (constitutive defense)

2.กลไกตอตานเชอทเกดขนจากการปรบตว (Adaptive defense) หรอกลไกตอตานเชอชนดจาเพาะ (specific defense) หรอกลไกตอตานเชอทเกดจากการกระตน (induced defense)

Innate defense1.โครงสรางทางกายวภาคและสรรวทยา

1.1 ผวหนง1.2 เยอเมอกบผว เชน นาตา, mucociliary apparatus ในทางเดนหายใจ, กรดในกระเพาะอาหาร,

เชอประจาถนในลาไสใหญ

2. การตอบสนองตอภมคมกน2. การตอบสนองตอภมคมกน2.1 เซลลในระบบภมคมกน : phagocyte แบงเปน 2 ชนดคอ

neutrophil และ macrophage ( l ) ไ 2.2 ระบบคอมพลเมนต (complement system) ม 3 กลไกคอ

classical pathway, alternative pathway, lectin pathway2.3 ปฏกรยาการอกเสบ (inflammatory response )จะเกดฏ ( y p ) การหลง cytokine หลายชนด2.4 การสรางสารอน ๆ ทมบทบาทตอตานเชอ เชน ferritin

Adaptive defense

• เกดหลงจากไดรบเชอเขาสรางกายและเกดตามหลงกลไกการตอตานเชอโดยธรรมชาต เซลล • เกดหลงจากไดรบเชอเขาสรางกายและเกดตามหลงกลไกการตอตานเชอโดยธรรมชาต เซลล

phagocyte ทจบกนเชอแปลกปลอมจะทาการยอยสลายเชอภายในเซลลและนาสวนทมคณสมบตเปนแอนตเจนออกสผวเซลล จงเรยกเซลลเมดเลอดขาวกลมนวา antigen‐presenting cell ซงจะรวมตวในรปสารเชงซอนกบสาร major histocompatibility complex (MHC) ซงแบงเปน class I และ class II antigen presenting cell ไ 2 ไซง antigen presenting cell นจะกระตนระบบภมคมกนจาเพาะได 2 กลไก

Adaptive defense

1 Humoral‐mediated response :1.Humoral‐mediated response : – การสรางสารนา ไดแกแอนตบอดหรอ immunoglobulin: Ig ซงแบงเปน IgM,

IgG, IgA โดยท IgM และ IgG ทาหนาทในการตอตานการตดเชอในกระแสเลอดและ เนอเยอ ในขณะท IgA จะถกหลงออกสบรเวณเยอเมอกบผวและทาหนาทชวยปองกนการบก

รกของเชอแปลกปลอมจากภายนอก

– การกระตนระบบคอมพลเมนต classical pathwayการกระตนระบบคอมพลเมนต classical pathway

2. Cell‐mediated response : มกพบในการตดเชอกลม Intracellular pathogen

Approach to Patients with feverConfirm “Fever”

• Acute fever < 2 weeks

• Prolong fever > 2 weeks

• Verification of fever and fever patternp

Pattern of Fever

Malaria

Typhoid

Pattern of Fever

Pel‐Ebstein pattern

B li i ( l i f tt )

Fever patterns are neither sensitive nor specific enough for diagnosis of any disease

Borreliosis (relapsing fever pattern)

diagnosis of any disease. (possible exception of tertian and quartan malaria)

Cause of FeverCause of Fever• Infectious diseaseInfectious disease

• Non‐infectious diseaseCNS: SAH cerebral infarction hemorrhage– CNS: SAH, cerebral infarction/hemorrhage

– RS: lung atelectasis, PE

– GI: Pancreatitis, Ischemic bowel

– Crystal induced arthritis, DVT,Hematoma,Crystal induced arthritis, DVT,Hematoma, Phebitis

– Neoplastic fever Drug fever– Neoplastic fever, Drug fever

– Post transfusion, Postoperative fever (<48h)

Approach : 1 Sign and SymptomApproach : 1. Sign and Symptom

• Fever with specific organ involvement : Pneumonia UTIPneumonia, UTI

• Fever without specific organ involement– Undifferentiated fever– Undifferentiated fever – Multi‐organs involvement

Approach : 1 Sign and SymptomApproach : 1. Sign and Symptom

• Typicalmanifestation of a common disease

• Atypicalmanifestation of a common disease

• Typical manifestation of a uncommon diseaseyp

• Atypicalmanifestation of a uncommon disease

A h 2 HostApproach : 2. Host

• Infection in the Elderly (>65 year)

• Infection in NeutropeniaInfection in Neutropenia

• Infection in Cirrhosis

• Infection in Diabetes Mellitus

• Infection in Thalassemia patients• Infection in Thalassemia patients

• Infection in SLE, RA

• Infection in Transplant recipients

Approach : 2 HostApproach : 2. Host

• Fever in HIV infected patients

• Fever in ICUFever in ICU

• Fever in the returned traveler

• Postoperative fever

• Fever of unknown origin• Fever of unknown origin

Approach : 3 Epidemiology ExposureApproach : 3. Epidemiology, Exposure

• Race

• Domicile, RegionDomicile, Region

• Career

• Hobby

• Immunization• Immunization

• Travel

Approach : Fever from Infectious diseaseApproach : Fever from Infectious disease

1. Sign & Symptoms– Specific organ symptomp g y p

– Non specific organ symptoms : Undifferentiated / Multi‐organ involvementUndifferentiated / Multi organ involvement

2. Host3. Epidemiology, Exposure

Acute Undifferentiated FeverAcute Undifferentiated Fever

Case 1Case 1

• 30 year old healthy woman• 30 year old healthy woman

• CC: High fever with chill for 3 days

• PI: 3 days PTA, High fever with chill, headache, muscle pain diarrhea?(1‐2 times/d) nomuscle pain, diarrhea?(1 2 times/d), no dysuria, no cough, no abnormal bleeding

b• PE: BT 38.5C BP 120/80 mmHg, PR 100 bpm, RR 18 /min, no stiffness of neck, others: WNL

• Q&A:


Acute systemic febrile illness, or

A t PUO S t i i f tiAcute PUO, or Systemic infection

Acute Fever ‐ No primary focus of infection‐Multi‐system involvement

Acute Undifferentiated Fever (Systemic Febrile Illness)

Primary Bacteremia

Dengue Infection

(Acute viral hepatitisMalaria:Pf Pv Po

Rickettsioses:S b t h(Acute viral hepatitis,

Chikungunya, Acute retroviral syndrome Infectious mononucleosis

Pf, Pv, Po, Pm, P.knowlesi

LeptospirosisScrub typhus,Typhus group, Spotted fever group

Infectious mononucleosis

Approach to Patients with feverApproach to Patients with fever

• Confirm “Fever”• S/S : Undifferentiated feverS/S : Undifferentiated fever

• Host: Healthy

• Epidemiology, Exposure : Race, Domicile, Career, Hobby, Immunization, Travel, , y, , ,Incubation period

• Investigation for diagnosis

Sign & Symptoms

Malaria‐ Sign & SymptomsMalaria‐ Sign & Symptoms

Asexual development se ua de e op e t(Schizogony)

• 30 mins

• Exoerythrocytic cycle (5‐16 days)y )

• Erythrocytic cycle (48‐72 h)

• Schizogony(merozoites)

• gametocytogenesis

)(gametocyte)Sexual development(Sporogony)(Sporogony)

Viral InfectionViral Infection

f f• Dengue infection: Dengue fever, Dengue Hemorrhagic fever

• Viral hemorrhagic fever: Hanta virus

• Chikungunya infectiong y

• Infectious mononucleosis : EBV, CMV

BacteremiaBacteremiaPathogenic Leptospira Pathogenic Leptospira sppspp

High feverH d hspp.spp.

O. tsutsugamushi, R. O. tsutsugamushi, R. typhityphi

HeadcheConjunctival injectionMyalgia etc.

MeningoencephalitisJaundice, Abnormal LFTAbnormal LFTHemoptysis, PneumonitisOliguria, renal failureMyocarditis etc.

Clinical presentations: Leptospirosis and Rickettsioses

• Latent or subclinical infection• Acute uncomplicated or flu‐like febrile illness • Acute fever plus

– hepatic dysfunction‐‐> acute acalculous cholecystitis– renal dysfunction‐‐> acute renal failure– interstitial pneumonitis ‐‐‐> lung hemorrhage‐‐> ARDS– aseptic meningoencephalitis– multiorgan dysfunctionh h i if t ti– hemorrhagic manifestations

Acute Undifferentiated Fever

1 663 d lt ti t ti ith A t f ith t• 1,663 adult patients presenting with Acute fever, without an obvious focus of infection, at 6 hospitals in Thailand

• between October 2000‐March 2003between October 2000 March 2003– Leptospirosis 463 (27.8%)– Scrub typhus 268 (16.1%)yp ( )– Murine typhus 28 (1.7%)– Leptospirosis and rickettsioses 82 (4.9%)– Spotted fever group rickettsioses 18 (1.1%)– Dengue infection 55 (3.3%)– Bacteremia 8 (0.5%) – Unknown 725 (43.6%)

Anicteric Leptospirosis Icteric LeptospirosisWeil’s Syndrome

ระยะแรก3-7 วน

Septicemic0-30 วนImmune

ระยะทสอง ระยะแรก 3-7 วน 10-30 วน

Septicemic Immune

ระยะทสอง

Septicemic Immune

อาการไข

Myalgia Meningitis Jaundice Headache Abdominal pain

gUveitis Rash Fever

Hemorrhage Renal failure Myocarditis

Vomiting Conjunctival suffusion

y

Fever Blood

CSFBlood

CSFCSF

Urin

e

CSF

Urin

e

CLINICAL PRESENTATIONS OF 540 PATIENTS WITHCLINICAL PRESENTATIONS OF 540 PATIENTS WITH

SUSPECTED SEVERE LEPTOSPIROSIS

Clinical Presentations N (%)

‐ Acute febrile illness

‐ Jaundice

127 (23.5)

154 (28.5)Jaundice

‐ Renal dysfunction

Lung involvement

154 (28.5)

182 (33.7)

111 (20 6)‐ Lung involvement

‐ Hypotension

l di li i

111 (20.6)

72 (13.3)

( )‐ Bleeding complication

‐ Thrombocytopenia (<100,000)

63 (11.7)

189 (35.0)

Clinical Infectious Diseases, Clinical Infectious Diseases, 20042004; ; 3939: : 14171417‐‐2424

CLINICAL PRESENTATIONS OF 540 PATIENTS WITH

SUSPECTED SEVERE LEPTOSPIROSIS : FINAL DIAGNOSISFINAL DIAGNOSIS

Di i N (%)Diagnosis N (%)

LeptospirosisOnlyPlus rickettsiosesPlus other bacteremia

256 (47.4)

62 (11.5)Plus other bacteremiaRickettsiosesOthers

( )

2 (0.04)

71 (13.1)OthersOther bacterial infectionViral infection

( )

22 (0.4)Unknown

22 (0.4)

19 (0.3)

88 (16.3)88 (16.3)

Clinical Infectious Diseases, 2004; 39: 1417‐24

Rickettsioses‐ Sign & SymptomsRickettsioses‐ Sign & Symptoms

d h kh h l• Sepsis study at Maharat Nakhon Ratchasima Hospital

• Between November 2001 to January 2002

• 18/51 (35.3%) of community‐acquired sepsis were caused by scrub typhus.y yp

• 3 (16.7%) patients died

Thap LC, et al. Southeast Asian J Trop Med Public Health 2002

Case 1 : AFICase 1 : AFI• อาชพ: พนกงานขายหางโลตส• อาชพ: พนกงานขายหางโลตส • ภมลาเนา :พกอยบานหลงโลตส รอบบานมสวนขนาดเลก ไมมสตวเลยงสตวเลยง

• โสด ปฏเสธประวตมเพศสมพนธ ประจาเดอนมาปกต LMP 20/09/54/ /

• เดนทาง : 3 อาทตยกอนเดนทางไปเชยงใหมอยแตในเมอง ไมไดเขาปา ไปเชาเยนกลบ ไมมคนละแวกบานเปนไขเลอดออก

• วคซน : ไมเคยฉดวคซนปองกนไขหวดใหญ• งานอดเรก : อานหนงสอ

Investigation

Case 1 : AFI‐ Initial investigationCase 1 : AFI‐ Initial investigation

• CBC• CBC

• Urinary analysis

• Hemoculture ?

• Bun/Cr LFT• Bun/Cr, LFT

• CXR ?

Malaria‐ Investigation for DiagnosisMalaria‐ Investigation for Diagnosis

• Uncomplicated malaria• Uncomplicated malaria

‐ P. falciparum

P i‐ P. vivax

‐ P. ovale

‐ P. malariae

‐ P. knowlesi

• Complicated or severe malaria

P f l i‐ P. falciparum

‐ P. vivax

‐ P. knowlesi


• Microscopy : "gold standard”• Microscopy : gold standard

–Thick smears are used for screening purposes‐l it ilow parasitemia

–Thin smears are for morphological detail and species identification

• Rapid diagnostic tests (RDT)

• Molecular technique ; especially for differentiate• Molecular technique ; especially for differentiate betaween P.m. & P.knowlesi


Parameter Microscopy PCR Fluorescence Dipstick Dipstick HRP-2 pLDH,

Sensitivity parasites/µl)

5-10 5 50 >100 >100

P f P f only P f and P v Specificity All species All species

P. f good, others

difficult

P. f only P. f and P. vgood

Parasite density or parasitemia

Yes No No Crude estimation

Crude estimation

Ti f 30 60 i 24 h 30 60 i 20 i 20 iTime for result

30–60 min 24 h 30–60 min 20 min 20 min

Skill level High High Moderate Low Low Equipment Microscope PCR QBC Kit only Kit onlyEquipment Microscope PCR

apparatus QBC

apparatus or microscope

Kit only Kit only

Cost/test Low High Moderate/low Moderate Moderate

Diagnosis?Diagnosis?


P h k T OptiMAL Assay • detection of an intracellular

metabolic enzyme produced by

Paracheck Test• useful in detecting P.f.infection only metabolic enzyme produced by

malarial parasites in blood‐LDeHydrogenase (pLDH)

iff i i b l i l

y• It is based on antibody recognition of the HRP‐2 antigen of P f • Differentiation between malarial

species is based on antigenic differences between pLDH

antigen of P.f.

pisoforms

Malaria‐Clue for suspected diagnosis of P. knowlesiMalaria Clue for suspected diagnosis of P. knowlesi

*Parasite morphology from blood smear is similar to PParasite morphology from blood smear is similar to P. malariae and with

• high parasitemia• high parasitemia

• severe manifestation

i f S k M l i S h f Th il d• coming from Saravak, Malaysia, South of Thailand

*Confirmative diagnosis by PCR or RDT (Animalaria™ test)

Malaria‐Clue for suspected diagnosis of P. knowlesiMalaria Clue for suspected diagnosis of P. knowlesi

Dengue Infection Investigation for DiagnosisDengue Infection ‐ Investigation for Diagnosis

Direct evidenceDirect evidence

Viral isolation

PCR ( Fever day1‐3)PCR ( Fever day1‐3)

Indirect evidence: immunodiagnosis

Antibody detection :Antibody detection :

Haeagglutination inhibition test (HI test)

Antibody capture EIAAntibody capture EIA

Immunochromatographic test:

Rapid Antibody test: Dengue duo (IgM IgG Ag)Rapid Antibody test: Dengue duo (IgM, IgG, Ag)

(IgM; false positive & false negative 10‐20%)

A ti d t ti N St t l t i (NS1)Antigen detection : Non Structural protein (NS1)

Leptospirosis‐ Investigation for DiagnosisLeptospirosis‐ Investigation for Diagnosis

Direct evidence

Gram stain, AFB,

Dark field microscopypy

Culture DNA detection



Serogroup specific :Microscopic agglutination test (MAT,Gold standard)( , )

Genus specific : IFA , Lepto‐dipstick test

Antigen detection : Rapid Ag detection system (RDTS)Antigen detection : Rapid Ag detection system (RDTS)

autumnalis orpomona ortarassovi

autumnalis oricterohaemorrhagia

hardjo orpomona

Leptospira biflexa

Leptospira

pomona

Leptospira interrogans

25 serogroups

> 250 serovars

i lcanicola


Antibody detection : detectable by the 6th to 10th day ,peaks within 3‐4 weeks

Slack A, 2010

gradually decreases but may remain detectable for years

Leptospirosis : Diagnosis

WHO criteria

Leptospirosis : Diagnosis

WHO criteria

Symptom &signsRisk factorsLaboratory results

sensitivity 68%specificity 58% specificity 58%

+ve predictive value 64%–ve predictive value 59%

RickettsiosesRickettsioses

Orientia tsutsugamushi Scrub typhus

Typhus group (TG)

‐ R. typhi Murine typhus

‐ R prowazakii Epidemic typhus‐ R. prowazakii Epidemic typhus

Spotted fever group (SFG) rickettsia

‐ R. rickettsii Rocky Mountain spotted fever

‐ R. conorii Mediterranean spotted fever

‐ R. australis Queenland tick typhus

R akari rickettsial pox etc‐ R. akari rickettsial pox etc.

Rickettsioses‐ Investigation for DiagnosisRickettsioses‐ Investigation for Diagnosis

Direct evidence

Culture : extremely difficultCulture : extremely difficult


A tib d d t ti IFA IIPAntibody detection : IFA, IIP

Rapid O. tsutsugamushi Ab test

Antigen detection


• Indirect immunofluorescent antibody test (IFAT)

• Indirect immunoperoxidase test(IIP)Indirect immunoperoxidase test(IIP)

– Detection of both IgM and IgGg g– Standard diagnosis of rickettsial infection– High IFAT or IPP titer more than 1: 400– A four‐fold rising of more than 1 : 200

Ricketsiosis‐ Investigation for DiagnosisRicketsiosis‐ Investigation for Diagnosis

Primary Infection

Reinfection

IFA Profile: ID Lab Siriraj HospitalISO15189ISO15189

Leptospires Orientia R.typhi

Test

-ve control

C t l+veControlIgM IgG IgM IgG IgM IgG

[email protected] Phone: 02 [email protected] Phone: 02 4197203

O. tsutsugamushi Gilliam 11/46, 24%from Thai patients

(2000‐2009)

Kato 1/46, 2%

TA763 8/46,17%

Karp 23/46 50%Karp 23/46, 50%

Rickettsial infection : Weil-Felix testRickettsial infection : Weil Felix test

Proteus vulgaris OX - 19 murine or epidemic typhusProteus vulgaris OX- 2 spotted fever groupProteus mirabilis OX K scrub typhusProteus mirabilis OX - K scrub typhus

Tests usually become +ve first 1-2 weeks of infectionA four-fold rise in paired sera or suggestive of recent infectionA four fold rise in paired sera or >1 : 320

suggestive of recent infectionSensitivity and specificity < 50% have been abandoned in many

countriescountries

Case 1 : AFI‐Investigation for DiagnosisCase 1 : AFI‐Investigation for Diagnosis

• Malaria : Thick film, Thin film, Rapid test

• Dengue infection : Dengue PCR NS1 IgM IgG• Dengue infection : Dengue PCR, NS1, IgM, IgG

• Leptospirosis : MAT, IFA

• Ricketsia : IFA for Scrub typhus, Murine typhus, Spotted fever grouptyphus, Spotted fever group

• Primary bacteremia : Hemoculture

Treatment

20102010

Dengue Infection TreatmentDengue Infection ‐ Treatment

S ti t t t• Supportive treatment

Treatment : Leptospirosis RickettsiosesTreatment : Leptospirosis , Rickettsioses

• Antimicrobial therapy shortens the course of

th ill d it i t d t litthe illness and its associated mortality

• Doxycycline and azithromycin are effectiveDoxycycline and azithromycin are effective antimicrobial treatment in mild cases

Treatment – Severe LeptospirosisTreatment – Severe Leptospirosis

• There remains uncertainty regarding the optimumThere remains uncertainty regarding the optimum

antimicrobial therapy for severe leptospirosis

• Choices of antimicrobial therapy are• Choices of antimicrobial therapy are

– Penicillin G sodium

– Ceftriaxone or cefotaxime

– Doxycycline

• Neither high dose steroid nor desmopressin is effective as an

adjunctive treatment of pulmonary hemorrhage associatedadjunctive treatment of pulmonary hemorrhage associated

with leptospirosis

Fever with specific organ p ginvolvement

Fever with specific organ involvementFever with specific organ involvement

• CNS infection: Meningitis, Encephalitis, Brain abscess

• RS : URI, Tracheobronchitis, Pneumonia (CAP, HAP, VAP), Aspiration pneumonia,Infected bronchiectasis

• GI : Diarrhea (Food poisoning, Infective diarrhea,GI : Diarrhea (Food poisoning, Infective diarrhea, Parasite infection, Toxin), Hepatobiliary tract infection, Peritonitis, hepatosplenic abscessec o , e o s, epa osp e c abscess

• GU : UTI (upper, lower) (Complicated/uncomplicared)

• SSTI : Furuncle cellulitis NF Abscess pyomyositis• SSTI : Furuncle, cellulitis, NF, Abscess, pyomyositis

Case 1 : Acute Fever with HeadacheCase 1 : Acute Fever with Headache

A 34 year old man looked distress

CC: Acute fever with headache for 2 daysCC: Acute fever with headache for 2 daysPE: Good conscious, BT 39 C, BP 130/90 mmHg,

PR 100 bpm, RR 22 /min

Stiffness of neck: positive Others : WNLStiffness of neck: positive, Others : WNL

Diagnosis : Acute meningitis Bacteria

Clinical of bacterial meningitis

Blood culture

Empirical ABO+/ steroid (Strep)

Blood culture

Empirical ABO+/- steroid (Strep)

Indication for emergency CT Yes

↓No↓ ↓

CT↓

↓Immediate LP

↓CS

No contraindiction↓

Contraindication↓

Continue empirical

CSF analysis↓

Adjust antibiotics Continue empirical Rx

Adjust antibiotics

Acute bacterial meningitisAcute bacterial meningitis

Host Usual pathogen Therapy

N l d lt S i C ft i 2 12 hNormal adult S. pneumoniae

N. meningitidis

Ceftriaxone 2 g q 12 h

+/- Vancomycin 1 g q 12 h

Elderly >50 y.

Pregnanc

S. pneumoniae

GNB

Ceftriaxone 2 g q 12 h +

Ampicillin 2 g q 4 h Pregnancy,

Alcoholism,

Steroid use

GNB

Listeria monocytogenes

Ampicillin 2 g q 4 h

+/- Vancomycin 1 g q 12 h

Steroid use

Case 2 : Fever with dysuriaCase 2 : Fever with dysuria

A 19 year old primigravida GA 29 weeksA 19 year old primigravida, GA 29 weeksCC: Fever and right flank pain for 2 daysPI : 2 mo PTA acute fever with dysuria visited privatePI : 2 mo PTA, acute fever with dysuria, visited private

clinic oral ATB for 7 days and clinically improved1 mo PTA, same symptoms, took same antibiotic and o , sa e sy p o s, oo sa e a b o c a dgot better

2 d PTA, high grade fever and Rt. flank PE: BP 120/80 mmHg, BT 38.5 0C ,RR 24 /min, HR 108 bpm

Abdomen: marked tenderness right flankIx : UA : WBC 10‐20/HPF, numerous RBC

D A l h i i li dDx: Acute pyelonephritis, complicated

Case Presentation : Ultrasound KUB (8 AUG 11)Case Presentation : Ultrasound KUB (8 AUG 11)• RK showed large low echo lesion with internal septation diameter 5.4x5 cm in midpart with mild hydronephrosis

•LK showed marked hydronephrosis with turbid

Case 2 : ManagementCase 2 : Management

• Complicated UTIComplicated UTI– Antibiotic (community onset): Ceftriaxone 2 g iv od– Drainage : Consulted Urologist Close drainageDrainage : Consulted Urologist Close drainage – Bilateral hydronephrosisPhysiologic change or Structural abnormalities ?Physiologic change or Structural abnormalities ? Consulted Urologist Plan to evaluate

abnormality after deliveryy y

• Preterm Labor :Preterm Labor :– Inhibited labor pain by medication success

Bacterial etiology of urinary tract infection% Uncomplicated %Complicateda

Gram-negative

% Uncomplicated %Complicateda

E.coliP mirabilisKlebsiella sp

70-951-21-2

21-541-102-17Klebsiella sp

Citrobacter spEnterobacter sp

1-2<1<1

2-175

2-10P aeruginosaOtherGram-positive

<1<1

2-196-20

Gram positiveCoagulase-negative staphylococciE t i

5-10b

1-21

1-41-231 4Enterococci

Group B streptococciS. aureus

<1<1<1

1-41-22

Other aData from Nicolle LE. A practical guide to the management of complicated urinaryTract infection. Drugs 1997;53”583-92.,also 2005

bS saprophyticus

: Acute Pyelonephitis

Case 4: Fever with sore throatCase 4: Fever with sore throat

• 30 year old healthy woman• 30 year old healthy woman

• CC: High fever with sore throat for 2 days

• PI: 2 days PTA, fever with sore throat, sneezing headache no coughsneezing, headache, no cough

• PE: BT 38.0C BP 120/80 mmHg, PR 84 bpm, RR ld d h l l16 /min, mild injected pharynx, lung clear,

others: WNL

Common cold

Acute Pharyngitis

Acute Laryngitis

Common Cold : Sign & SymptomCommon Cold : Sign & Symptom

• Sore throat, scratchy throat (resolve quickly )

followed closely by nasal obstruction and rhinorrheafollowed closely by nasal obstruction and rhinorrhea

• Cough 30% (begin after onset of nasal symptom)

Ch i l i d i th f• Change in color is common during the course of illness and not indicative bacterial superinfection or i itisinusitis

• Nasal cavity : swollen, erythematous nasal turbinate

Common Cold : Sign & SymptomCommon Cold : Sign & Symptom

• Cold persist about 1 week, 25% last 2 weeks

• Symptoms that persist > 10 days are more likely toSymptoms that persist > 10 days are more likely to be bacterial infection1,2

• Differential diagnosis : Allergic rhinitis

• Complication: Acute otitis media 30%, sinusitis 8%

Gwaltney, J Allergy Clin Immunol. 1992;90:457‐461;discuss 62.Gwaltney, J Allergy Clin Immunol. 1992;90:457 461;discuss 62.Wald ER,Pediatrics.1986;77:795‐800

SinusitisSinusitis

• Pathogenesis of sinusitis are similar to viral URI

• Acute community‐acquired bacterial sinusitis

– Persistent nasal discharge or cough>10 days– Persistent nasal discharge or cough>10 days

– Severe symptoms: fever, purulent nasal discharge

– Worsening symptoms: new fever, increasing nasal discharge, congestion or daytime cough

• Chronic sinusitis

Acute Pharyngitis : Sign & Symptom y g g y p

T i l T i d th t f d• Typical Triad : sore throat, fever and pharyngeal inflammation

Microbial Causes of Acute Pharyngitis

Suggestive of GASSuggestive of Viral etiology gg• Sudden onset

• Sore throat

gg gy

• Conjunctivitis

• Fever

• Headache

• Coryza

• Cough

• Neusea, vomitting, abdominal pain

• Inflammation of pharynx and

• Diarrhea• Discrete ulcerative lesions

p ytonsils

• Patchy discrete exudates

d l i i l• Tender, enlarge anterior cervical nodes

• Patients age 5‐15 yearsg y

• Presentation in winter or early springHi t f• History of exposure

CID 2002;35:113‐125

Streptococcal Pharyngitis : AntibioticsStreptococcal Pharyngitis : Antibiotics

• To prevent poststreptococal sequelae

– Acute rheumatic fever Rheumatic heartAcute rheumatic fever Rheumatic heart disease

– Acute poststreptococcal glomerulonephritis (PSGN)(PSGN)

Streptococcal Pharyngitis : AntibioticsStreptococcal Pharyngitis : Antibiotics

• To prevent suppurative complication

– Peritonsillar abscess : adolescent, young adult

– Retropharyngeal abscess : common in first few years

– Sinusitis : very rareSinusitis : very rare

• To reduce symptoms

• To prevent transmission : pediatrics

Modified Centor Score

Upper Respiratory tract infectionUpper Respiratory tract infection

• Acute epiglottitis : sore throat with odynophagia

• Acute Laryngitis: Horseness, Dry cough

• Acute laryngotracheobronchitis : Croup

• Acute Bronchiolitis• Acute Bronchiolitis

TB

LaryngotracheobronchitisLaryngotracheobronchitis

COPD with exacerbate

Bronchiectasis

COPD with exacerbate

Acute Bronchitis

Acute Pneumonia

Lower respiratory tract infectionLower respiratory tract infection

• Acute Bronchitis : cough predominate– Productive cough> 2 weeks R/O TB

– Prolong cough> 4 weeks + poroxysmal vomitting– Prolong cough> 4 weeks + poroxysmal vomitting suggest Bordetella pertussis

• Asthmatic attack

• COPD with exacerbate

AECOPDAECOPD

Lower respiratory tract infectionLower respiratory tract infection

• Bronchiectasis : Infected bronchiectasis

• Acute PneumoniaAcute Pneumonia – Symptoms: Fever,cough, dyspnea, pleuritis pain

Si C i i– Sign: Crepitation

– CXR : Pulmonary infiltrate

• Tuberculosis• Tuberculosis

Most common etiologies of CAP (2007 IDSA/ATS Consensus)Most common etiologies of CAP (2007 IDSA/ATS Consensus)

Fever of Unknown OriginFever of Unknown Origin

• 40 year old helthy woman• CC: fever with chill 3 weeks, wt loss 6 kg/2CC: fever with chill 3 weeks, wt loss 6 kg/2 wks, no organ specific symptomsPE BT 38 5 BP 130 80 H PR 98 b RR• PE: BT 38.5 c,BP 130/80 mmHg, PR 98 bpm, RR 16 /min

• Mildly pale, no jaudice, Others: WNL• Initial investigation: CBC UA LFT BUN/Cr Anti• Initial investigation: CBC, UA, LFT, BUN/Cr, Anti HIV, CXR

Approach : Fever of unknown originApproach : Fever of unknown origin

• Classical FUOClassical FUO• Infants and Children

• Elderly Persons• Elderly Persons

• Returned Travelers

• Health Care Associated FUO• Health Care‐Associated FUO• Postoperative patients

ICU ti t• ICU patients

• Stroke patients

• Immune Deficient FUO• Neutropenic FUO

• HIV related FUO

Subtle Physical Finding Having Special Significance in Patients with FUOSignificance in Patients with FUO

Rare Miscellaneous Causes of Fever

Clinical Evaluation of Fever of unknown origin

• History :Comprehensive History is cornerstoney p y

• Physical Examination : Repeated PE

• Laboratory Investigation : Noninvasive test ; CBC• Laboratory Investigation : Noninvasive test ; CBC, UA, chemistry, culture, serology, BM examI i St di CT U S S i ith l b l d• Imaging Studies : CT, U/S, Scanning with labeled autologous leukocytes, Ga scan

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

• Therapeutic Trialsp

FUO : Therapeutic TrialsFUO : Therapeutic Trials

Li it ti d i k f i i l th ti• Limitations and risks of empirical therapeutic trials are obvious

• Underlying disease may remit spontaneously

• Naproxen test to differentiate malignant from• Naproxen test to differentiate malignant from nonmalignant remains unvalidated

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

• In practice, most often in suspected TB

Case 4 :FUOCase 4 :FUO

• Classic FUO– Infection : IE, Hepatosplenic abscess, TB, , p p , ,Melioidosis

– Malignancy :Malignancy : • Hematologic: Lymphoma

• Solid tumor: Renal cell CA HCC or Liver metastasis• Solid tumor: Renal cell CA, HCC or Liver metastasis

– Autoimmune : SLE

• CXR: Hilar adenopathyCXR: Hilar adenopathy

Melioidosis ‐ Sign & SymptomsMelioidosis ‐ Sign & Symptoms

Thai : 686 pateintsOrgan %

Australian : 252 pateints in 10 years

Organ %• Septicemia 57.4• Pulmonary 44.9• Skin & soft tissue 16.2

Organ %

• Bacteremia 117 (46)

• Pneumonia 27 (50)• liver + spleen(7+2.3) 9.3• UTI 7.4• Bone and joint 5.2

• Skin/soft tissue 42 (17)

• Genitourinary infection 37 (15)

O li i / i h i i 9(4)j

• CNS 2.7• Pericardium 2.4• LN 2 1

• Osteomyelitis/septic arthritis 9(4)

• Neurological 10 (4)

• Other 27 (11)LN 2.1• Parotid gland 1.9

Other 27 (11)

Punyagupta S Melioidosis 1989:217‐29 Currie BJ CID 2000;31:981‐6Punyagupta S. Melioidosis 1989:217‐29 Currie BJ. CID 2000;31:981 6


• Acute infection:

– Direct inoculation during work

– Inhalation during monsoon

– Drowning– Drowning

• Reactivation :

– Dormant intracellular after exposure

– Relapse by the same strain

Direct IF Direct IF stain

Melioidosis – Risk FactorsMelioidosis Risk Factors

• Age 42 yr peak 40 60 yr• Age 42 yr. peak 40‐60 yr.

• Seasonal Variation: Rainy

• Risk factors OR (95%CI)• Risk factors OR (95%CI)

Preexisting renal dz. 2.6 (1.5‐5.6)

Th l i 11 8 (2 5 54 5)Thalassemia 11.8 (2.5‐54.5)

Malignancy 0.4 (0.1‐0.9)

DM 4 8 (3 0 7 7)DM 4.8 (3.0‐7.7)

Soil & water exposure 1.8 (0.6‐5.4)

il & ( )DM + Soil & water exposure 6.3 (3.8‐10.4)

• Exposure to soil and water

Suputtamongkol Y. Intern J Epidemio 1994;23:1082‐90Suputtamongkol Y.CID 1999;29:408‐13


• Lung involvement

– Rapidly progressive community acquired pneumonia

– Chronic pneumonia mimics TB

– Mass lesion mimics malignancy

• Intra‐abdominal abscess (Single > Multiple organs)– Single Abscess: Splenic > Liver > Kidney

M lti l b– Multiple abscesses

– Small abscesses < 3cm

– Cart‐wheel or Swiss cheeseCart wheel or Swiss cheese– Prostatic abscess

Melioidosis ‐ Investigation for DiagnosisMelioidosis ‐ Investigation for Diagnosis

Direct evidence

Gram stain

Culture: (1‐4 days)Gold standardGold standard

Ashdown’s agarDirect IF Ashdown s agarDirect IF stain

Melioidosis ‐ Investigation for DiagnosisMelioidosis ‐ Investigation for Diagnosis

Indirect evidence: immunodiagnosis limited valueIndirect evidence: immunodiagnosis limited valueAntibody detection : Melioid titer

In endemic areas : High background Ab in healthy– In endemic areas : High background Ab in healthy

– Cross reaction with other Gram negative infections

t ff 1 160 iti it 80% ifi it 80%– cut off 1: 160 sensitivity 80%, specificity 80%

– 4‐ 4 rising of IHA titer???

A ti d t tiAntigen detection

– IF staining of clinical specimens

– Latex agglutination for colony identification

– PCR specific for B pseudomallei Di t IF t i– PCR specific for B. pseudomallei Direct IF stain

Melioidosis ‐ TreatmentMelioidosis ‐ Treatment

I i i l h I d i h• Initial phase or Induction phase– Severe cases to decrease mortality – Parenteral antimicrobial– ~ 2 week of treatment or defervescence

• Maintenance phase– To prevent relapseo p e e e apse– Oral antimicrobial– 12‐20 weeks of treatment12‐20 weeks of treatment

Direct IF Direct IF stain

RCT studies in acute phase treatment of melioidosis

Authors Regimen, dose No.patientsper arm

Treatmentfailure

Mortalityrate

White et al Ceftazidime (120) vs TMP/SMX (10/50)+

Doxycycline (4) + chloramphenicol (100)34 vs 31 37 vs 74*

มนตเดช และ

คณะ

Ceftazidime (120)+ TMP/SMX (8/40) vs

TMP/SMX (8/40) + Doxycycline (4) +

chloramphenicol (100)

27 vs 34 18.5 vs 47*

p ( )

ยพนและคณะ Ceftazidime (120) vs co-amoxyclav (120/40) 106 vs105 39 vs 51* 47 vs 47

Simpson et al Ceftazidime (120) vs imipenem (50) 106 vs 108 41 vs 20* 38 vs 36

เพลนจนทร และ

คณะ

Ceftazidime (100) TMP/SMX (8/40) vs

Cefoperazone – sulbactam (25/25)+

/S ( / )

51 vs 51 14 vs 18

TMP/SMX (8/40)

วรงครองและคณะ Ceftazidime (120) vs Ceftazidime (120)

TMP/SMX (10/50)118 vs 123 26 vs 19 22 vs 20

* Significant different

Melioidosis – Induction TreatmentMelioidosis Induction Treatment

( )• Ceftazidime 120 MKD (2g IV 8 hourly)

• Amoxycillin‐clavulanic acid 160 MKD (2.4g IV stat then 1.2gm IV 4 h)

I i 60 /k /d (1 IV 8 h l )• Imipenem 60mg/kg/day (1g IV 8 hourly)

• Cefoperazone/sulbactam 25mg/kg/day (1 g IV 8 h) + Trimethoprim‐sulfamethoxazolesulfamethoxazole

• Mean fever clearance (days)( y )

– Imipenem 7.751

– Ceftazidime 9‐111,2

– Sulperazone 102

1. Simpson AH. Clin Infect Dis 1999;29:381‐7 2. Chetchotisakd P. Clin Infect Dis 2001;33:29‐34

RCT studies in maintenance phase treatment of melioidosisRCT studies in maintenance phase treatment of melioidosis

A th R i d /k D ti No RelapseAuthors Regimen, dose mg/kg Durationweeks

No.patents

Relapserate(%)

อดลย Amoxicillin-clavulanate (60/15) vs 20 vs 20 49 vs 52 16 vs 4*

[TRSTMH

1995]

chloramphenicol (40), doxycycline (4),

and TMP-SMX (10/50)

วภาดา

[CID 1999]

Doxycycline (4) vs chloramphenicl (40),

doxycycline (4) and TMP-SMX (10/50)

20 vs 20 58 vs 58 26 vs 1*

เพลนจนทร Azithromycin (8) and ciprofloxacin (8) vs 12 vs 20 36 vs 29 22 vs 3*เพลนจนทร

[AJTMH 2001]

Azithromycin (8) and ciprofloxacin (8) vs

doxycycline (4) TMP-SMX (10/50)

12 vs 20 36 vs 29 22 vs 3*

วภาดา Doxycycline (4) and TMP-SMX (10/50) vs 12-20 vs 89 vs 91 8 vs 10

[AAC2005]

y y ( ) ( )

chloramphenicol (40), doxycycline (4),

and TMP-SMX

12-20

* Significant different

Melioidosis ‐Maintenance phase for 12‐20 weeksp

• Bactrim (TMP/SMX): 8‐10mg/kg/d of TMP ( / ) g/ g/GFR > 30 mL/min GFR < 30 mL/min

– BW >60 kg: 4 tab bid 3 tab bid BW 40 60 kg: 3 tab bid 2 tab bid– BW 40‐60 kg: 3 tab bid 2 tab bid

– BW <40 kg: 2 tab bid 1 tab bid

• Coamoxyclav:30 MKD of amoxy (Cheng AC.Am J Trop Med Hyg 2008;78:208‐9)

– BW < 60 kg• Coamoxyclav (375mg) 2 tab tid + amoxy 500mg tid orCoamoxyclav (375mg) 2 tab tid amoxy 500mg tid or• Coamoxyclav (625mg) 2 tab tid x 20 wks

– BW > 60 kgC l 1500/375 TID• Coamoxyclav 1500/375 TID

• Coamoxycalv (625) 3 tab TID

11 Feb 2009 16 Feb 200911 Feb 2009 16 Feb 2009

Case 3: A 52‐year‐old manCase 3: A 52‐year‐old man

CC Hi h f 4 d• CC: High fever 4 days

• Underlying: DM type2, NPDR last HbA1c 7.3% y g yp 1HT, dyslipidemia, CAD s/p PCI, BUN/Cr 27 6/1 727.6/1.7

• PI: 4days PTA, High fever with chill, severe h d h d hheadache, no nausea, vomiting, no diarrhea, no cough, no dysuria

• Q&A:

Case 3: Physical ExaminationCase 3: Physical Examination

• BT 37.5ºC, HR 80/min, RR 20/min BP 120/80 mmHg

• HEENT: No icteric sclera no pallor• HEENT: No icteric sclera, no pallor

• CVS: High JVP, PMI at 5th ICS mid clavicular line, no h i th illheaving, no thrill, no murmur

• Lung :clear

• Abdomen : Liver 2 cm below right costal margin, span 12 cm, no splenic dullness, no signs of chronic liver disease

Lab results on admissionLab results on admission

A B

C DC

Diagnosis?Diagnosis?

mycoplasma Legionellamycoplasma Legionella

Case : A 25‐year‐old man, BKKCase : A 25 year old man, BKK

• High fever with chill for 3 days• High fever with chill for 3 days• He has productive cough with yellowish

sputum, severe muscle pain at both thighs, nausea vomiting, watery diarrhea g , g, y4-5 time/day for 1 day.

• Heavy alcoholic drink for 4-5 yrsS k f 8• Smoker for 8 year

• No previous antibioticsp

Case : Physical ExaminationCase : Physical Examination

• T 39ºC, HR 128/min, RR 32/min BP 131/63 mmHg• Mild icteric sclera no pallor no signs of chronic liverMild icteric sclera, no pallor, no signs of chronic liver

disease• High JVP, PMI at 6th ICS 2cm. lateral to mid clavicularHigh JVP, PMI at 6 ICS 2cm. lateral to mid clavicular

line, no heaving, no thrill, systolic murmur grIII maximum at left parasternal bordery g p

• Fine crepitation at right lung• Liver 4 cm below right costal margin, span 18 cm.g g , p• No splenomegaly

Initial LaboratoryInitial Laboratory Investigationsg

5.33 13.19061114107723.80.81 037Urine Sp gr 1.0374+0-1

Urine Sp. gr.ProteinWBC

Wh t i di i ?What is your diagnosis?

1. Severe community‐ acquired pneumonia 2 Severe leptospirosis2. Severe leptospirosis3. Severe scrub typhus4 Comm nit acq ired sepsis4. Community‐acquired sepsis5. Severe pneumonia with alcoholic hepatitis

and cardiac beriberi

Clinical Co rseClinical Course

• Sputum Gram stain: normal oropharyngeal floras• Blood culture : S. pneumoniae x II specimenp p

Penicillin MIC 0.012 μg/mlCefotaxime MIC 0 016 μg/mlCefotaxime MIC 0.016 μg/ml

• Echocardiogram: - Poor LV contraction, EF 28.7%

generalized wall hypokinesiag yp- Moderate to severe PR, mild MR

• IFA for leptospirosis: IgG <1:50 IgM <1:50• IFA for leptospirosis: IgG <1:50, IgM <1:50

Clinical Co rseClinical Course

• IFA for Orientia tsutsugamushi: IgG IgM

9 Feb 2009 1:400 1:10012 Feb 2009 1:1600 1:100

• 11 Feb 2009: +ve PCR for O.tsutsugamushi

71 year old Thai female Nakhon Pratom71‐ year old Thai female, Nakhon‐Pratom

• CC: Dyspnea 1 day• CC: Dyspnea 1 day

• High fever and chill 5 days, generalized abdominal pain no vomiting no diarrheapain, no vomiting, no diarrhea

• Oliguria and dyspnea 1 day

• PE: Temp 39.30 C,P 114/min,

R 22/min, BP86/53 mmHg./ , / g

fine crepitation both lungs

No rash no lymphadenopathyNo rash, no lymphadenopathy

Problem list

Eschar at lower abdomen‐ Fever 5 days.‐ History of abdominal

pain‐ Eschar‐ Bilateral pneumonitis, hypoxemiahypoxemia

‐ Hypotension‐> sepsis

Chest X-ray AP: on Admission

Admission LabAdmission Lab

CBC

Clinical CourseC ca Cou se

IFA for Scrub typhus 7/2/2008 12/2/2008IgG 1:50 1:400gIgM 1: 400 1:3200

ชาย อาย 41 ป อาชพ ขายประกน

CC: ไขสง ตวเหลอง 6 วน กอนมารพ.

PI: 4 วน จกใตชายโครงขวา ทองอดมากขน ปสสาวะออกนอยลง PI: 4 วน จกใตชายโครงขวา ทองอดมากขน ปสสาวะออกนอยลง

- 1 วนกอน เรมมเหนอยมากขน นอนราบไมได ขาบวม ไมเจบ

ไป ไ หนาอกไปรพ. เอกชน ไดรบการวนจฉยวา Fulminant hepatic failure with

hepato-renal syndrome ไดรบการฟอกไต 1 ครงรวมกบยาปฏชวนะเขาเสน

แลวสงตวผปวยมา

PE: Temp 38.50C, P 100/min, R 28/min, BP 130/80 mmHgp g

mildly pale , mod jaundice, pitting edema 2+, ascites +ve

fine basal crepitation both lungsfine basal crepitation both lungs,

JVP 6 cm above sternal angle, PMI at 5th ICS,

no murmur

CBC: Hct 26.6%, WBC 16,700, P84%,Plt 167,000

U/A: sp.gr 1.020, alb 4+BUN 119, Cr 7.5, Na 139, K 4.2, HCO3 22, , , ,Direct Bili 28.2, AST 152, ALT 105, Alp 259A/G 2.6/2.1Blood Gas: pH 7 49 pCO2 34 8Blood Gas: pH 7.49, pCO2 34.8

pO2 59.1O2 sat. 92.4

On admission and 1 week after admissionIFA for - Leptospira spp. : negative

- O. tsutsugamushi : negative- R. typhi : IgM 1:100 1: 6400

I G 1 100 1 3200IgG 1:100 1:3200


Acute systemic febrile illness, or

A t PUO S t i i f tiAcute PUO, or Systemic infection

Acute Fever ‐ No primary focus of infection‐Multi‐system involvement

Acute Undifferentiated Fever (Systemic Febrile Illness)

Primary Bacteremia

Dengue Infection

(Acute viral hepatitisMalaria:Pf Pv Po

Rickettsioses:S b t h(Acute viral hepatitis,

Chikungunya, Acute retroviral syndrome Infectious mononucleosis

Pf, Pv, Po, Pm, P.knowlesi

LeptospirosisScrub typhus,Typhus group, Spotted fever group

Infectious mononucleosis

Clinical presentations: Leptospirosis and Rickettsioses

• Latent or subclinical infection• Acute uncomplicated or flu‐like febrile illness • Acute fever plus

– hepatic dysfunction‐‐> acute acalculous cholecystitis– renal dysfunction‐‐> acute renal failure– interstitial pneumonitis ‐‐‐> lung hemorrhage‐‐> ARDS– aseptic meningoencephalitis– multiorgan dysfunctionh h i if t ti– hemorrhagic manifestations

Leptospirosis ‐ Pulmonary InvolvementLeptospirosis ‐ Pulmonary Involvement

• Pulmonary involvement is more common in patients• Pulmonary involvement is more common in patients presented with other complications such as jaundice, renal failure, or thrombocytopenia.renal failure, or thrombocytopenia.

• Diffuse pulmonary lesions and cardiomegaly are commoncommon

• Severe pulmonary involvement (ARDS or pulmonary hemorrhage) occurs in 1‐ 5%.hemorrhage) occurs in 1 5%.

• Pulmonary hemorrhage and multiorgan failure are• Pulmonary hemorrhage and multiorgan failure are main causes of death in severe form of leptospirosis.

Rickettsioses‐ Pulmonary InvolvementRickettsioses‐ Pulmonary Involvement

Ab l h di h i 59% 72%• Abnormal chest radiography in 59% to 72%.

• Bilateral reticulonodular infiltration, hilar LN enlargement, and septal line are common findingsand septal line are common findings.

• Air‐space nodules is relatively uncommon

I t t d i t titi l iti ( ith ith t• In an autopsy study; interstitial pneumonitis (with or without vasculitis) has been found in almost all patients.

• Pulmonary involvement is a marker of disease severity• Pulmonary involvement is a marker of disease severity

Anicteric Leptospirosis Icteric LeptospirosisWeil’s Syndrome

ระยะแรก3-7 วน

Septicemic0-30 วนImmune

ระยะทสอง ระยะแรก 3-7 วน 10-30 วน

Septicemic Immune

ระยะทสอง

Septicemic Immune

อาการไข

Myalgia Meningitis Jaundice Headache Abdominal pain

gUveitis Rash Fever

Hemorrhage Renal failure Myocarditis

Vomiting Conjunctival suffusion

y

Fever Blood

CSFBlood

CSFCSF

Urin

e

CSF

Urin

e


Direct evidence

Gram stain, AFB,

Dark field microscopypy

Culture DNA detection



Serogroup specific :Microscopic agglutination test (MAT,Gold standard)( , )

Genus specific : IFA , Lepto‐dipstick test

Antigen detection : Rapid Ag detection system (RDTS)Antigen detection : Rapid Ag detection system (RDTS)

autumnalis orpomona ortarassovi

autumnalis oricterohaemorrhagia

hardjo orpomona

Leptospira biflexa

Leptospira

pomona

Leptospira interrogans

25 serogroups

> 250 serovars

i lcanicola


Antibody detection : detectable by the 6th to 10th day ,peaks within 3‐4 weeks

Slack A, 2010

gradually decreases but may remain detectable for years

Rickettsioses‐ Sign & SymptomsRickettsioses‐ Sign & Symptoms

d h kh h l• Sepsis study at Maharat Nakhon Ratchasima Hospital

• Between November 2001 to January 2002

• 18/51 (35.3%) of community‐acquired sepsis were caused by scrub typhus.y yp

• 3 (16.7%) patients died

Thap LC, et al. Southeast Asian J Trop Med Public Health 2002


Direct evidence

Culture : extremely difficultCulture : extremely difficult


A tib d d t ti IFA IIPAntibody detection : IFA, IIP

Rapid O. tsutsugamushi Ab test

Antigen detection


• Indirect immunofluorescent antibody test (IFAT)

• Indirect immunoperoxidase test(IIP)Indirect immunoperoxidase test(IIP)

– Detection of both IgM and IgGg g– Standard diagnosis of rickettsial infection– High IFAT or IPP titer more than 1: 400– A four‐fold rising of more than 1 : 200

Rickettsial Diseases TreatmentRickettsial Diseases: Treatment

• Antimicrobial therapy shortens the course

of the illness and its associated mortality

• Chloramphenicol, Doxycycline, p y y

Azithromycin, Levofloxacin are effective

i i bi lantimicrobial treatment

Doxycycline & AzithromycinDoxycycline & Azithromycin

Scrub typhus and Murine typhusScrub typhus and Murine typhus

• Early recognition and appropriate treatment reduceEarly recognition and appropriate treatment reduce morbidity and mortality

• Rational antimicrobial therapy would be doxycycline in• Rational antimicrobial therapy would be doxycycline in mild cases and a combination of either cefotaxime or ceftriaxone and doxycycline in severe cases.y y

• Azithromycin could be considered as an alternative treatment when ever doxycycline allergy is suspected.treatment when ever doxycycline allergy is suspected.

• Failure to improve or defervesce within the next 48 hours would indicate the need to a thoroughhours would indicate the need to a thorough reevaluation of clinical findings and initial laboratory investigation results and a need to change antibiotic. g g

Hospital Acquire Pneumonia

DefinitionsDefinitions

H it l i d i (HAP)• Hospital‐acquired pneumonia (HAP)– Pneumonia occurs ≥ 48 hrs after admission

– Not incubating at the time of admission

V il i d i (VAP)• Ventilator‐associated pneumonia (VAP)– Pneumonia occurs ≥ 48‐72 hrs after endotracheal intubation

Not incubating at the time of intubation– Not incubating at the time of intubation

• Early v.s. Late onset (before or after 4 days of admission)

MicrobiologyMicrobiology

• HAP VAP in patients with no known risk• HAP, VAP in patients with no known risk factors for MDR‐pathogens, early onset– Streptococcus pneumoniae

Haemophilus influenzae– Haemophilus influenzae

– Methicillin‐sensitive Staphylococcus aureus

– Antibiotic‐sensitive enteric GNB• Escherichia coliEscherichia coli

• Klebsiella pneumoniae

• Enterobacter spp• Enterobacter spp.

• Proteus spp.Am J Respir Crit Care Med 2005; 171: 388–416.Rotstein C, et al. Can J Infect Dis Med Microbiol 2008; 19: 19-53.Song JH, et al.Am J Infect Control 2008; 36: S83-92.

Risk factors for MDR pathogensRisk factors for MDR‐pathogens

• Antimicrobial therapy in preceding 90 days

• Current hospitalization of 5 days or more• Current hospitalization of 5 days or more

• High frequency of resistance in the community or specific hospital unit

P f i k f t f HCAP• Presence of risk factors for HCAP

• Immunocompromised disease and/ or therapyp / py

Am J Respir Crit Care Med 2005; 171: 388–416.

MicrobiologyMicrobiology

• HAP, VAP, and HCAP, late onset, or risk factors for MDR‐pathogensfor MDR pathogens– Pathogens listed previously and MDR‐pathogens i l diincluding

– Pseudomonas aeruginosa

– Klebsiella pneumoniae

Acinetobacter spp– Acinetobacter spp.

– MRSAAm J Respir Crit Care Med 2005; 171: 388–416.Rotstein C, et al. Can J Infect Dis Med Microbiol 2008; 19: 19-53.Song JH, et al.Am J Infect Control 2008; 36: S83-92.

Potential pathogensPotential pathogens

American Thoracic Society‐ 2005American Thoracic Society‐ 2005

Treatment GuidelinesTreatment Guidelines

Am J Respir Crit Care Med 2005; 171:388-416

Treatment GuidelinesTreatment GuidelinesEarly-onset, AND

i k f MDR thRecommended Regimens

• S. pneumoniae 1. Non‐pseudomonal 3rd

generation cephalosporin

no risk of MDR-pathogens

• H. influenzae

• MSSA

A tibi ti iti t i

generation cephalosporin (cefotaxime, ceftriaxone) OR

• Antibiotic‐sensitive enteric gram‐negative bacilli e.g.

– E.coli,

2. ß‐lactam/ ß‐lactamase inhibitor

(amoxicillin/ clavulanic acidE.coli,

– K. pneumoniae, – Enterobacter spp.

(amoxicillin/ clavulanic acid, ampicillin/ sulbactam) OR

pp

– Proteus spp.– Serratia spp.

3. Carbapenems (ertapenem) OR

4 Fl oroq inolones4. Fluoroquinolones (Levofloxacin/ moxifloxacin)

Treatment GuidelinesTreatment Guidelineslate-onset, OR

i k f MDR thRecommended Regimens

• MDR‐pathogens

P i

1. Antipseudomonal cephalosporin (ceftazidime, cefoperazone/

no risk of MDR-pathogens

– P. aeruginosa

– K. pneumoniae

– Acinetobacter spp.

(ceftazidime, cefoperazone/ sulbactam, cefepime) OR

2. Antipseudomonal penicillin (piperacilllin/ tazobactam) ORAcinetobacter spp. (piperacilllin/ tazobactam) OR

3. Antipseudomonal carbapenems (imipenem, meropenem) PLUS

1. Aminoglycosides (amikacin, netilmycin) OR

2. Fluoroquinolones (Ciprofloxacin/ levofloxacin) PLUS

– MRSA 1. Vancomycin or Linezolid

Asian Guidelines ‐ 2008Asian Guidelines ‐ 2008

DosageDosage

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