Pre-ICU training (Antibiotics)

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Pre-ICU training (Antibiotics)

• ??????
• ???
• ?????

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??????????10????????
3
?????????????????(2007?)
Incidence Rate ()
Incidence rate is the number of isolates reported
per 1000 patietn days
4
??????????????(2007?)
10.5
All infections 1,593
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???????????15????(2007?)
Total 1,717

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???????????15???????????(2007?)
PATHOGEN LRI SSI GISI EENTI BSI UTI SSTI Others TOTAL ISOLATE
E. coli 0.0 3.3 0.0 0.0 10.8 13.5 7.0 0.0 177 10.3
Yeast form fungi 0.0 2.2 0.0 0.0 6.7 16.6 0.0 0.0 173 10.1
A. baumannii 55.6 2.2 0.0 0.0 8.1 8.5 3.8 7.7 170 9.9
S. aureus 11.1 18.7 0.0 30.0 14.6 2.3 30.8 38.5 163 9.5
C. albicans 0.0 3.8 3.0 0.0 3.9 16.3 0.0 0.0 159 9.3
P. aeruginosa 8.9 12.1 7.0 20.0 3.9 11.7 11.5 7.7 153 8.9
K. pneumoniae 1.1 3.3 0.0 10.0 10.1 9.9 7.7 7.7 148 8.6
Enterococcus 1.1 9.9 0.0 0.0 7.0 8.9 7.7 0.0 132 7.7
Coagulase(-) Staphylococcus 0.0 5.5 0.0 0.0 9.1 1.1 3.8 7.7 74 4.3
E. cloacae 1.1 1.6 0.0 0.0 3.6 2.6 3.8 0.0 46 2.7
S. marscens 0.0 0.5 0.0 0.0 3.3 1.0 3.8 7.7 30 1.7
Other GNF bacteria 1.1 1.6 0.0 0.0 3.8 0.4 0.0 7.7 30 1.7
Other Streptococcus 0.0 6.6 0.0 0.0 1.2 0.9 0.0 0.0 26 1.5
Rotavirus 0.0 0.0 83.0 0.0 0.0 0.0 0.0 0.0 24 1.4
B. fragilis 0.0 6.6 0.0 0.0 1.4 0.0 0.0 7.7 21 1.2
All others 20.0 22.0 7.0 40.0 12.5 6.1 19.2 7.7 191 11.1
NUMBER OF ISOLATES 90 182 29 10 583 784 26 13 1,717 100.00
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????????UTI??????(2007?)
Total 784
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????????LRTI??????(2007?)
Total 90
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????????SSI??????(2007?)
Total 182
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????????BSI??????(2007?)
Total 583
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????????SSTI???15????(2007?)
Total 26
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What organisms are most likely???????????????????
??

• ???????
• ?????(Clinical syndrome)
• ????(Host factor)
• ??????(Epidemiological data)

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• If several antibiotics are available, which is
  best?
• (This question involves such factors as drugs of
  choice, pharmacokinetics, toxicology, cost,
  narrowness of spectrum, and bactericidal compared
  with bacteriostatic agents.)
• ???????????,?????????,????????????,????????????

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Staphylococcus aureus Antibiotics

• Methocillin-sensitive S. aureus (MSSA)
• ???? oxacillin
• ???????????
• ?? penicillin allergic - Erythromycin,
  Clindamycin, Glycopeptide (Vancomycin,
  Teicoplanin)
• Methocillin-resistant S. aureus (MRSA)
• ????Glycopeptide (Vancomycin, Teicoplanin)
• ???? Linezolid
• Fusidic acid
• Rifampicin

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Streptococcus pneumoniae

• Penicillin-sensitive??????(first choice)
  Penicillin G

Categories of Susceptibility of S. pneumoniae to
Penicillin
NCCLS 2001
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Treatment of S. pneumoniae Pneumonia

• Penicillin
• MIC (?g/ml) primary alternative
• ?1 penicillin 1st cephalosporins
• (S) ampicillin or amoxicillin
• 2 penicillin (high dose) 3rd or 4th
  cephalosporins
• (I) ampicillin or amoxicillin
• ?4 3rd or 4th cephalosporins
  vancomycin or teicoplanin
• (R) vancomycin or teicoplanin rifampin or
  newer fluoroquinolones
• The infectious diseases society R.O.C. 2000

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Treatment of Pneumococcal Meningitis

• MIC (?g/ml) dosage
• PCN CTX therapy adults
  children (/kg)
• lt0.12 ?0.5 penicillin 300,000 u/kg/d
  3-400,000 u q4-6h
• ?0.12 ?0.5 Cefotaxime or 2 g q6h
  200-225 mg q6-8h
• Ceftriaxone 2 g q12h 100 mg
  q12-24h
• 1.0 Cefotaxime or 300 mg/kg/d (m.24g)
  300 mg q6-8h
• Ceftriaxone 2 g q12h 100
  mg q12-24h
• Vancomycin 60 mg/kg/d (M.2g)
  60 mg q6h
• ?2.0 Same as 1.0
• Rifampin 300 mg q12h 20 mg
  q12h
• Kaplan SL and mason EO jr. Clin
  microbiol rev 1998

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Streptococcus pneumoniae

• ?CNS Infection?Non- CNS Infection (Pneumonia,
  bacteremia) ??????,??MIC????????
• Invasive Pneumococcal disease ????
• Non- CNS Infection (Pneumonia, bacteremia) high
  dose penicillin G, or other cephalosporins
  (ceftriaxonecefotaxime),or newer
  fluoroquinolones. Not vancomycin?
• CNS Infection (Meningitis) Not Penicillin,
  vancomycin ceftriaxone (cefotaxime, Cefepime,
  Cefpirome, Meropenem)

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Enterococci sp.

• E. faecalis, E. faecium
• Habitat commensal of human and animal gut
• Lancefield group D, bile resistant
• Infections
• - Urinary tract infection
• - Intra-abdominal sepsis
• - Biliary tract infection
• - Endocarditis

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Enterococci sp.

• ???? Ampicillin
• ??????gentamicin?????(synergistic effect)
• Never use cephalosporins or aminoglycosides alone
  or Clindamycin, TMP/SMX for Enterococci
• ?ampicillin??? Glycopeptide
• Vancomycin-resistant Enterococci(VRE) -
• Quinupristin/dalfopristin
• Linezoid
• Chloramphenicol

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????(Linezolid)

• 1.???MRSA(methicillin-resistant staphylococcus
  aureus)??,????vancomycin???????vancomycin?teicopla
  nin???????vancomycin?teicoplanin????????
• 2.???VER(vancomycin-resistant enterococci)??,?????
  ???????
• 3 ???(osteomyelitis)?????(endocarditis)????????
• 4 ?????????????,?????,?????????????????(??????????
  ??????????)?

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Klebsiella pneumoniae

• ????(first choice) cephalosporins
• ?????? cefazolin aminoglycosides
• ????????????? third generation
  cephalosporins?????
• ?????penicillins???
• (Unasyn, augmentin,
• Timentin, tazocin??????)

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Escherichia coli

• Most common possible etiologies
• Cystitis pyelonephritis
• Emphysematous pyelonephritis.(DM)
• Acute bacterial prostatitis
• ????(first choice)
• ?-lactam antibiotics aminoglycosides?
• ?????????cefazolin, 80 ?ampicillin ????

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Klebsiella sp. Escherichia coli

• In vitro resistant to any of the third generation
  cephalosporins
• Strain produced an extended-spectrum ?-lactamases
  (ESBL)
• Resistance to all penicillins, cephalosporins
  aztreonam
• ????(first choice)
• Carbapenem
• Cephamycins (AmpC ?-lactamases)
• Piperacillin-tazobactam(Tazocin) ( AmpC
  ?-lactamases)
• Ciprofloxacin
• Aminoglycosides

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Citrobacter, Enterobacter, Acinetobacter,
Serratia, Providencia Species

• Hospital acquired pathogens UTI, ventilator
  associated pneumonia, septicaemia
• Antibiotic susceptibility unpredictable since
  often multiply antibiotic resistant need
  susceptibility test guidance of treatment
• Inducible ß- lactamase(Amp C)
• 4th cephalosporin(Maxipime, Cefrom),
  Imipenem-cilastatin, Meropenem

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Pseudomonas aeruginosa

• Habitat
• GIT of humans animals, environment
• Water survives in hospitals (In antiseptics)
• Obligate aerobe, gram-negative rods, polar
  flagella, oxidase positive (in contrast to
  Enterobacteriaceae)
• Infections
• Hospital acquired infections UTI with urinary
  catheter, pneumonia (cystic fibrosis, ventilator
  associated), burns infection, septicaemia in
  immunocompromised (transplantation, oncology,
  ICU)
• Chronic otitis media externa
• Eye infection secondary to trauma

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Pseudomonas aeruginosa

• Antipseudomonal Antibiotics
• Ceftazidime(Fortum)
• Cefepime(Maxipime), Cefpirome(Cefrom)
• Aztreonam
• Imipenem-cilastatin / Meropenem
• Piperacillin, Piperacillin-tazobactam(Tazocin)
• Ticarcillin, Ticarcillin-clavulanate(Timentin)
• Ciprofloxacin, Levofloxacin
• Aminoglycosides

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Acinetobacter baumannii

• ???????????????????
• ????(first choice) Imipenem/Cilastatin (Tienam)
  / Meropenem
• ???? Ampicillin/sulbactam (Unasyn ) or
  sulbactam, Colistin, Tigecycline (Tygacil )

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????(Tigecycline)

• ??????????????????????????????????????????????,??t
  igecycline?????(sensitivity)??????????????????????
  ????
• ??????????????????????,??????????,???????
• ?????????????????????

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Stenotrophomonas maltophilia

• ???????????????????
• ????(first choice) TMP/SMX Co-trimoxazole
• ????
• Moxalactam
• Timentin (Ticarcillin-clavulanate)
• Ciprofloxacin, Levofloxacin

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Is an antibiotic combination appropriate?????????
??????????

• Febrile leukopenic patient
• In infections in which multiple organisms are
  likely or proved
• Synergism
• Serial inhibition of microbial growth
• One antibiotic enhances the penetration of
  another
• Limiting or preventing the emergence of
  resistance

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Combination Therapy

• Tuberculosis
• Disseminated Mycobacterium avium complex
• Helicobacter pylori
• Endocarditis(alpha haemolytic streptococcus,
  enterococcal )
• Vancomycin-resistant enterococcal disease
• Life-threatening infection caused by P.
  aeruginosa
• Empiric treatment ( pneumococcal meningitis
  febrile, severely neutropenic host polymicrobic
  infection life-threatening infection with
  inapparent source)

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Gentamicin

• ??Gentamicin????? (Synergistic effect)
• Enterococci endocarditis(????) or bacteremia
  Gentamicin Ampicillin or penicillin G
• Viridans streptococci endocarditis
• Gentamicin penicillin G
• MRSA or S. epidermidis prosthetic valve
  endocarditis Vancomycin Gentamicin
• Listeria mononcytogenes Ampicillin Gentamicin
• Serious Pseudomonas aeruginosa infection
  Aminoglycosides Anti-Pseudomonal agents

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Pseudomonas aeruginosa

• The use of monotherapy with antipseudomonal
  penicillins or cephalopsorins for patient with
  severe P. aeruginosa infections can lead to the
  emergency of antimicrobial-resistant strain.
• Combination of 2 antipseudomonal ß - lactam
  antibiotics lacks synergy in animal models in
  human
• Combination of an aminoglycosides
  antipseudomonal ß - lactam antibiotics works
  synergistically against P. aeruginosa improved
  clinical outcome.

Todd FH et al CID 2000 311349-56
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Antifungal agents

• Fluconazole (Diflucan)
• Itraconazole (Sporanox)
• Caspofungin (Cancidas)
• Micafungin
• Voriconazole (Vfend)
• Amphotericin-B

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????(itraconazole)

• 1.??????????amphotericin-B????????????????????????
  ??????????????????,?14????
• 2.?????????????????????????????????????(????????)?
  ??,??14????
• 3.??????????????,?????,?????????????????(?????????
  ???????????)?

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????(caspofungin)

• 1.????????????????????????????????????????????
• 2.??????????????????????????,?????????????fluconaz
  ole???????????

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????(micafungin)

• ??16??????????????
• ????????????????????

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????(voriconazole)

• ?

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AMERICAN THORACIC SOCIETY DOCUMENTS
Guidelines for the Management of Adults with
Hospital-acquired, Ventilator-associated, and
Healthcare-associated Pneumonia Am. J. Respir.
Crit. Care Med. 2005 171 388-416
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Contents

• Executive Summary
• Introduction
• Methodology Used to Prepare the Guideline
• Epidemiology
• Incidence
• Etiology
• Major Epidemiologic Points
• Pathogenesis
• Major Points for Pathogenesis
• Modifiable Risk Factors
• Intubation and Mechanical Ventilation
• Aspiration, Body Position, and Enteral Feeding
• Modulation of Colonization Oral Antiseptics
  and Antibiotics
• Stress Bleeding Prophylaxis, Transfusion, and
  Glucose Control
• Major Points and Recommendations for
  Modifiable Risk Factors
• Diagnostic Testing
• Major Points and Recommendations for Diagnosis
• Diagnostic Strategies and Approaches
• Clinical Strategy

• Recommended Diagnostic Strategy
• Major Points and Recommendations for Comparing
  Diagnostic Strategies
• Antibiotic Treatment of Hospital-acquired
  Pneumonia
• General Approach
• Initial Empiric Antibiotic Therapy
• Appropriate Antibiotic Selection and Adequate
  Dosing
• Local Instillation and Aerosolized Antibiotics
• Combination versus Monotherapy
• Duration of Therapy
• Major Points and Recommendations for Optimal
• Antibiotic Therapy
• Specific Antibiotic Regimens
• Antibiotic Heterogeneity and Antibiotic
  Cycling
• Response to Therapy
• Modification of Empiric Antibiotic Regimens
• Defining the Normal Pattern of Resolution
• Reasons for Deterioration or Nonresolution
• Evaluation of the Nonresponding Patient
• Major Points and Recommendations for
  Assessing Response to Therapy

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Executive Summary(1)

• Official statement of ATS/IDSA, evidence-based
• HCAP included in the spectrum of HAP/VAP, need
  therapy of MDR pathogen
• Lower resp. tract cultures (LRTCs) quantitative
  (?specificity of diagnosis) or semi-quantitative
  non- or bronchoscopical collection for all cases
• Negative LRTCs may stop ABx without ABx changes
  in the past 72 hrs

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Executive Summary(2)

• Early, appropriate, broad-spectrum, antibiotic
  therapy with adequate doses to optimize
  antimicrobial efficacy
• Empiric regimen should include with a different
  antibiotic class agents than those recently
  received
• Combination therapy for a specific pathogen
• Consideration of short-duration (5 days)
  aminoglycoside, when used in combination with a
  ß-lactam to treat P. aeruginosa pneumonia

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Executive Summary(3)

• Linezolid an alternative to vancomycin may have
  an advantage for proven VAP due to MRSA
  (unconfirmed, preliminary data)
• Colistin considered in VAP due to a
  carbapenem-resistant Acinetobacter species
• Aerosolized antibiotics may have value as
  adjunctive therapy in VAP due to some MDR
  pathogens
• De-escalation of ABx should be considered once
  according to the results of LRTCs and the
  patients clinical response