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06/08/2018
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คณะแพทยศาสตรศิ์รริาชพยาบาล มหาวทิยาลยัมหดิล
รศ.ดร.พญ.ภญิโญ รตันาอมัพวลัยสาขาวิชาโรคติดเช้ือและอายุรศาสตรเขตรอน
คณะแพทยศาสตรศิริราชพยาบาล มหาวิทยาลัยมหิดล
Rational Antimicrobial Use in OPD Settings
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Outline of Presentation
Antimicrobial resistance and Thailand situation
Rational Antimicrobial Use in OPD Settings
Common cold
A di h Acute diarrhea
Fresh wound
UTIs
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
06/08/2018
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คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
World Burden of Bacterial Resistance
More than 140,000 episodes of infection caused by resistant bacteria per yearp y
More than 30,000/year patients die More than 2 billion loss in productivity /year
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คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Antimicrobial resistance
Prevent transmission
Susceptible host
Infection control
Key Prevention Strategies
Infection
Early Dx & RxAntimicrobial therapy
Rational Use
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Upper Respiratory Tract Infections
Causes: 80% virus 20% bacteria
Adults with URIs at Siriraj hospital: GAS infectionGAS infection
7.9% in patients with tonsillitis/pharyngitis
3.1% in patients with non-specific URI/common cold
J Med Assoc Thai. 2006 Aug;89(8):1178-86.
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Meta-analysis of antibiotics for common cold and acute purulent rhinitis
Cochrane Database Syst Rev. 2013 Jun 4;6
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Differential Diagnosis of upper respiratory tract conditions
SymptomsCommon
coldStreptococcal
pharyngitis
Acute bacterial sinusitis
Allergic rhinitis
Duration ͠ 7 d 7 d > 10 d variable
Sore throat - sometimes
Nasal discharge -
Discharge color White - Yellow/Green Clear
Sneezing - -
Cough - sometimes sometimes
Facial pressure sometimes - -
Fever sometimes -
Common cold: mild injected pharynx, no exudate
Exudative tonsillitis:Injected pharynx with yellowish exudate
Diphtheria:Dirty greyish patch
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CENTOR criteria
GAS AOM, Sinusitis
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Acute Bronchitis
Mostly viral Clues: dry cough with chest rhonchi Treatment: Supportive Rx
Antibiotics in high risk (elderly, COPD, low IR) Amoxycillin 500 mg tid or 1000 mg bid
Roxithromycin 150 mg PO bid
Amoxyclav 625 mg tid or 1000 mg bid
Levofloxcin 500 mg od
Duration = 5 days
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Acute Diarrhea
Acute diarrhea: ≥ 3 loose or watery stools per day
≥ 1 mucous bloody stools
Causes: Food poisoning (toxin) – watery diarrhea N/V Food poisoning (toxin) – watery diarrhea, N/V
Viral infection – loose stool, low-grade fever. Feel ill
Bacterial infection – high fever, bloody stools
Most are self-limited!!
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Food poisoning
Bacterial Preformed-Toxin Food Poisoning
Causes: Bacillus cereus
Staphylococcus aureus
Clostridium perfringens Clostridium perfringens
Clinical features: Short incubation period
Vomiting is the predominant presentation
Often no fever, mild diarrhea with abdominal cramp
Recovery occurring in 1-2 days
Romney MH. Clin microbiol Rev 2015: 28; 1‐31
06/08/2018
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คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Common Causes of Food poisoning
Causes IC(hr)
Food Toxin Clinical Syndrome
S. aureus 2-7 Improperly cooked or stored food
Heat-stable preformed-toxin
Vomiting
C.perfringens 8-14 Contaminated meat vegetables
Enterotoxin(Heat labile
Watery diarrhea S vomitingmeat, vegetables,
or poultry(Heat-labile toxin, heat-stable spore)
vomiting“Pig-bel” beta toxin– intestinal wall necrosis
B. cereus ½-6 Contaminated fried rice,vegetable sprouts
Emetic toxin(cereulide)
Similar to S. aureus enterotoxin(nausea/vomiting)
8-16 Pore-forming enterotoxin
Similar to C. perfringens(diarrhea)
Romney MH. Clin microbiol Rev 2015: 28; 1‐31
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Acute Infectious DiarrheaParameter Secretory
gastroenteritisInflammatory
gastroenteritisInvasive
gastroenteritis
Location Proximal small bowel Colon Distal small bowel
Type of illness Watery diarrhea Dysentery Enteric fever
Stoolexamination
No fecal PMN Fecal PMN Fecal PMN
Mechanism Enterotoxin or bacterial adherence/invasion cause a shift in water and electrolyte excretion/adsorption
Bacterial invasion or cytotoxins cause mucosal damage that leads to inflammation
Bacterial penetrate the mucosa and invade the reticuloendothelialsystem
Classic pathogens
Vibrio cholerae, ETEC, Clostridium perfringens, Bacillus cereus, Staphylococcus aureus
Shigella, STEC, Salmonella (not Salmonella Typhi/Paratyphi), Vibrio parahaemolyticus, Clostridium difficile, Campylobacter
SalmonellaTyphi/Paratyphi, Yersiniaenterocolitica
Principles and syndromes of enteric infection, 7th Ed Mandell 2010: 1335–1351
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Investigations for Acute Diarrhea
No need of investigations in most cases
Stool exam: if severe or persist ≥ 2 days
Stool culture: Inflammatory or Cholera-like diarrheay Diarrhea ≥ 1 week Traveler or immunocompromised host
Stool parasite: Diarrhea ≥ 2 weeks Outbreak setting Traveler or immunocompromised host
Mayo Clinic Infectious Diseases Board Review 2011
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Management
Adequate hydration and symptomatic treatment
Empirical antibiotic treatment in1. Febrile dysentery or elderly Norflox 400 mg bid x 3 d
2. Suspected V.cholera Norflox 400 mg bid x 3 d2. Suspected V.cholera Norflox 400 mg bid x 3 d
3. Severe traveler’s diarrhea Azithro 1000 mg stat
4. Antibiotic-associated diarrhea Metronidazole/vanco
5. Non-typhoidal salmonellosis with
Severe or bacteremia
High risk patients
Mayo Clinic Infectious Diseases Board Review 2011
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Fresh Wound
Bleeding-heart bird
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คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
WHO wound management guideline
Never close infected wound
Delayed primary closure for 48 hours in contaminated wounds and clean wounds > 6 hours old
A ibi i h l i i l d d i Antibiotic prophylaxis is only recommended in high-risk and contaminated wound
Topical antibiotics and washing wounds with antibiotic solutions are not recommended!!
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คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Upper UTI VS.
Lower UTI
Urinary Tract Infections
CA-UTIVS.
Nosocomial UTI
Complicated VS.
UncomplicatedUTI
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Diagnosis Clinical signs and symptoms
Pyuria: Centrifuged ≥ 10 WBC/HPF, Uncentrifuged ≥ 5 WBC/HPF Might be absent in neutropenic hostsg p
Significant bacteriuria:
Conditions MUC
Acute uncomplicated cystitis ≥105 CFU/ml
Acute uncomplicated pyelonephritis ≥104 CFU/ml
UTIs in Male ≥104 CFU/ml
Complicated UTIs ≥103 CFU/ml
Rubin RH, et al. CID 1992. 15; S216‐27
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Common UTIs
1. Asymptomatic bacteriuria (ASUB)
2. Uncomplicated UTI in female
• Cystitis
• Acute pyelonephritis
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Asymptomatic Bacteriuria Diagnosis:
Single cath (both sex): MUC > 102
Asymptomatic patient: MUC > 105 ( 1 time for male, 2 times for female)
Treatment is recommended in
Pregnancy
Plan to undergo TURP/Urosx with mucosal bleeding
Asymptomatic female with cath-bacteriuria that persists 48 h after indwelling catheter removal
IDSA Guidelines for Asymptomatic Bacteriuria • CID 2005:40
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คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Acute Cystitis 1st time – MUC and imaging not necessary
Treatment options:
Nitrofurantoin (Dual) 100 mg bid x 7 d
Fosfomycin 3 g single dose
Co-trimoxazole 800/160 mg bid x 3 d
IDSA guideline for acute uncomplicated cystitis and pyelonephritis in women: CID 2011
X CCr < 50X PregnancyX Early upper UTI
X Early upper UTI X High resistant ratei.e. > 20%
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Acute Cystitis Alternative treatment options:
Fluoroquinolones
Ofloxacin 200 mg bid x 3 dCiprofloxacin 250 mg bid x 3 d
β lactams
Amoxicillin/clavulanateCefdinir
IDSA guideline for acute uncomplicated cystitis and pyelonephritis in women: CID 2011
p gLevofloxacin 250-500 mg od x 3 d
X Pregnancy & childrenX Avoid if FQ resistance > 10%Reserved for future use
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Recommended antimicrobials for acute pyelonephritis in Female
IV: Ciprofloxacin 400 mg IV q 12 h Ceftriaxone 1-2 g IV od Once daily aminoglycoside Ertapenem 1 g IV od if ESBL is suspectedp g p
PO: Ciprofloxacin 500 mg bid (if susceptible) Levofloxacin 750 mg od (if susceptible) Cotrimoxazole DS 1 tab bid (IV to PO) Oral 3rd Ceph (IV to PO)** Avoid empirical FQ Rx if FQ resistance >10%**
IDSA guideline for acute uncomplicated cystitis and pyelonephritis in women: CID 2011
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Risk factors for ESBL+ Pathogens
Risk factors OR 95% CI Ref.Prior hospitalization 4.52 1.6-13.1 (1)ICU admission 35.7 6.0-214.1 (1)Previous antibiotic exposure
1.10 1.03-1.18 (2)
Ceftazidime use 13.40 1.21-148.85 (3) Fluoroquinolone use 7.1 2.3-22.4 (4) NG tube insertion 3.1 1.5-6.3 (4) Tracheostomy 5.13 1.24-21.1 (3)
(1) Antimicrob Agents Chemother 2002;46:1481-91(2) CID2001;32:1162-71
(3) J Hosp Infect 2003;53: 39-45(4) SIRIRAJ data
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Meta-analysis of short (≤7d) vs. long (>7d) duration of antibiotic in ac. pyelonephritis
Clinical failure at the end of follow up; RR = 0.79 [0.56 – 1.12]
J Antimicrob Chemother. 2013 Oct;68(10):2183-91
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
CPG for the Treatment of Acute Uncomplicated Cystitis & Pyelonephritis in Women 2010
• Recommended duration of antibiotic for acute uncomplicated pyelonephritis• FQs for 7 days• Cotrimoxazole 14 days• Beta-lactam 10-14 daysBeta-lactam 10-14 days
Clinical Infectious Diseases 2011;52(5):561–564
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คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Indications for Radiologic Studies
1. Acute pyelonephritis, who did not respond to appropriate ATB within the first 72 hrs.
2. Poor controlled DM
3. Immunocompromised hosts
4 P KT4. Post-KT
5. Recurrent UTIs
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
IV to PO conversions• Types of IV to PO conversions:
1. Sequential therapy: same drug2. Switch therapy: different drug, same spectrum3. Step-down therapy: different drug, narrower
spectrumspectrum
• Can’t be used in some conditions:• CNS infections• Infective endocarditis
• Bacteremia is not a contraindication
Kris M kuper. Health-system pharmacies fourth edition (chapter 39)
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
IV to PO conversions (cont.)• Selection of patients:1. Intact and functioning GI tract2. Improving clinical status3. Effective antibiotic with good bioavailability is
availableavailable4. Still need antibiotic therapy!!
*** IV to PO conversions may lead to unnecessary (prolonged) antibiotic use ***
Kris M kuper. Health-system pharmacies fourth edition (chapter 39)
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Antibiotics commonly used for sequential therapy
Antibiotics IV dose PO doseCiprofloxacin 400 mg q 12 h 500 mg q 12 h
Levofloxacin 500-750 mg q 24 h 500-750 mg q 24 h
Moxifloxacin 400 mg q 24 h 400 mg q 24 hg q g qCotrimoxazole 800/80 q 12 h 800/80 q 12 hMetronidazole 500 mg q 8 h 400 mg q 8 h
Linezolid 600 mg q 12 h 600 mg q 12 h
Azithromycin 500 mg q 24 h 500 mg q 24 h
Cefuroxime 750-1500 mg q 8 h 250-500 mg q 12 h
Clindamycin 300-600 mg q 8 h 300-450 mg q 6 h
คณะแพทยศาสตรศิ์ริราชพยาบาล มหาวิทยาลยัมหดิล
Antibiotics commonly used for switch therapy
IV antibiotics PO antibioticsAmpicillin 1-2 g q 4-6 h Amoxycillin 500 mg tid or 1000 mg bid pc
Cefazolin 1-2 g q 8 h Cephalexin 250-1000 mg qid pc
Ceftriaxone 1-2 g q 24 hCefotaxime 1-2 g q 8 h
Cefdinir 100 mg tid or 200 mg bid pcCefixime 400 mg od pcCefditoren 100 mg tid or 200 mg bid pcCeftibuten 400 mg od pc
Cloxacillin 2 g q 4 h Dicloxacillin 250-500 mg qid ac
17 May 2019 (Friday) Workshop on Antimicrobial Stewardship Program
18‐20 May 2019 (Sat‐Mon)f f
SAVE THE DATE
Siriraj Infectious Disease Conference 2019
@ Siriraj Hospital, Bangkok
Organized by Division of Infectious Diseases and Tropical Medicine, Faculty of Medicine Siriraj Hospital
Contact: [email protected] page: Siriraj Infectious Disease Conference