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COMMMUNITY-ACQUIRED

RESPIRATORY TRACT
INFECTION :
PROBLEMA &
PENATALAKSANAANYA
Soedarsono
Lab-SMF Penyakit Paru
FK Unair- RSUD Dr. Soetomo
Surabaya
1

OUTLINE OF DISCUSSION
COMMUNITYACQUIRED
PNEUMONIA
(CAP)

ACUTE
EXACERBATION
CHRONIC
BRONCHITIS
(AECB)

ANTIMICROBIAL
THERAPEUTIC
2

Current important issue in


the management of RTI
Immune
status

IDENTIFICATION
IDENTIFICATION
RISK
RISKFACTORS
FACTORS

Comorbidity

MANAGEMENT
MANAGEMENT

NEW and
RESISTANT
PATHOGEN

OUTCOMES
OUTCOMES

COST
EFFECTIVE
CARE
3

BATASAN
COMMUNITY-ACQ. PNEUMONIA (CAP) :
INFEKSI AKUT PARENKIM PARU DI MASYARAKAT
INFILTRAT PADA FOTOTORAK DISERTAI 2 Gx :
- FEVER 380C
- LEKOSISITOSIS > 10.000 / mm3
- SPUTUM PURULEN
- BATUK, SESAK, NYERI DADA
- FISIS : TANDA KONSOLIDASI
RAWAT JALAN
DRAJAT SKOR
RISIKO

RAWAT INAP
4

CLASSIFICATION
CLASSIFICATION OF
OF PNEUMONIA
PNEUMONIA
By Source of
Infection

By Infectious
agent

By Site
Infection

Communiy-acquired

Bacterial pneum. Lobar pneumonia

Hospital-acquired

Atypical pneum.

Bronchopneumo.

Aspiration

Viral pneum.

Interstitial pneum

Immunocompr. host

Fungi & other


infective agent
5

Lobar
pneumonia
Bacterial
pneumonia

Atypical
pneumonia

CAP
Bronchopneumonia

Interstitial
pneumonia

CURRENT STRATEGY IN THE MANAGEMENT


OF PNEUMONIA
IDENTIFICATION OF RISK FACTORS
INITIAL EMPIRIC THERAPY EARLY
THE BEST CHOICE SPECIFIC DRUGS
SWITCH THERAPY

MORTALITY
COST- EFFECTIVE
PREVENTION OF OCCURANCE RESISTANCE OF PATHOGEN
7

Community-acquired pneumonia
EVALUASI SISTIM SKOR
FAKTOR DEMOGRAFI
PEMERIKSAAN FISIK
LABORATORIUM / RADIOLOGIK
TOTAL SKOR
RISK. I/II/III
(RENDAH)

RAWAT JALAN

RISK. IV
SEDANG

RAWAT INAP

RISK. V
BERAT
8

RAWAT INAP

INDIKATOR YANG DIPAKAI


UNTUK MENENTUKAN
PENDERITA RAWAT JALAN
ATAU RAWAT INAP
PENILAIAN TERHADAP
KEPARAHAN PENYAKIT MENURUT
SISTIM SKOR DARI PORT
(PNEUMONIA PATIENT OUTCOME
RESEARCH TEAM)
9

Patient with community-acquired pneumonia

Is the patient over 50 years of age ?

YES

NO
Does the patient have aof any of the following comorbid
conditions :

YES

. Neoplastic disease
. Congestive heart failure
. Cerebrovascular disease
. Renal
disease
. Liver disease

Assign patient to
risk class II-V based
on prediction model
scoring system

NO
Does the patient have any of the following abnormalities on
physical examination ?
- Altered mental status
- Pulse 125 / BPM
- Respiratory rate 30/min - Systolic BP < 90 mm Hg
- Temperature < 350C (950F) or 400C(
1040F)

YES

NO

Assign patient to risk class I

FIG.-PREDICTION MODEL FOR10CAP


PATIENT RISK ASSESMENT

SCORING SYSTEM

SISTIM
SKOR
pada
CAP
berdasarkan
PORT

PATIENT CHARACTERISTIC

POINTS ASSIGNED*

Demographic factors
Age: Males

Age (in years)

Age: Females

Age (in years) 10

nursing-home resident

+ 10

COMORBID DISEASE
Neoplastic disease
Liver disease

+30
+ 20

Congestive heart failure

+ 10

Cerebrovascular disease

+ 10

Renal disease

+ 10

PHYSICAL EXAMINATION FINDINGS


Altered mental status

+ 20

Pulse 125/BPM

+ 10

Respiratory rate 30/min

+ 20

Systolic blood pressure < 90 mm/Hg


Temperature < 35C or 40C (104F)
LABORATORY FINDINGS
Hematocrit < 30%

+ 30

pH < 7.35

+ 30

Blood urea nitrogen > 10.7 mmol/L

+ 20

Sodium < 130 mEq/L

+ 20

Glucose > 13.9 mmol/L

+ 10

PO2< 60 mm Hg+

+ 10

Pleural effusion

+ 10

11

STRATIFICATION OF RISK
SCORE FOR CAP
Risk

Risk Class Based on

Recommendation
for site of care

Low

Algorithm

Outpatient

Low

II

70 total points

Outpatient

Low
III
Moderate IV

71-90 tot. points


91-130 tot.points

Inpatient
Inpatient

High

> 130 tot. points

Inpatient

Mortality : I (0,1%) ; II (0,6%); III (2,8%) ; IV ( 8,2%) ; V (29,2%)


12

ANTIMICROBIAL for CAP


IS EMPIRICSM STILL NEEDED ?
WHAT HAS CHANGED OVER THE PAST
SEVERAL YEARS ?
WHAT IS THE BEST WAY TO CHOOSE SPESIFIC
DRUG ?

13

Is Empiricsm still needed ?


The treatment can be DIRECTED or

EMPIRIC
Advantages w/ DIRECTED Tx :

Polypharmacy
Cost
Adverse drug reaction
14

Why would anyone ever use


empiric treatment ?
The disease itself
mortality

The Pathogens
difficulty in finding pathogen

Limitations of Diagnostic Testing


30-60 % no identifiable pathogen
15

Diagnostic Methods & Their Limitations


Clinical
Invasive

Sputum gram stain

& culture

Culture of blood &


pleural fluid

Serology

- too sensitive
- lacks specifity
- special skills
- adherence to protocol
- too costly
- patients cannot produce
sputum
- false negative on
antibiotic - cannot detect
atypical
- low sensitiity
- high specificity
- time delay
16

EMPIRICAL ANTIBIOTIC for CAP


WHAT HAS CHANGED OVER THE PAST
SEVERAL YEARS ?
WHAT IS THE BEST WAY TO CHOOSE
SPESIFIC DRUG ?

17

Key Bacterial Pathogens in


Community-Acquired Pneumonia :
A Global Meta-analysis
Other
11%
Legionella spp.
4%

Mycoplasma
pneumoniae
7%

S. pneumoniae
66%

Global meta-analysis of
English-language studies
Study cohorts: N=127
Total patients: N= 33,148
Total patients reporting
data: N=6,866

Haemophilus
influenzae
12%
Fine MJ et al. JAMA 1996; 275:134.

18

Etiology of CAP
(Persahabatan Hosp. 2000)

19

Pathogens in CAP :
Dr. Soetomo Hospital ( 1998 )

20

Review of the Decade on Pneumonia,


World Lung Congress di Florence 2000

S. PNEUMONIAE PENYEBAB
TERBANYAK

20-20% MERUPAKAN INFEKSI


CAMPURAN
30-60% PNEUMONIA PATOGEN
PENYEBAB TIDAK DIKETAHUI
21

PEDOMAN (GUIDELINE) PEMILIHAN


ANTIBIOTIK SECARA EMPIRIK
antara lain :
American Thoracic Society (ATS) 2001
Infectious Disease Society of America (IDSA)
2000
British Thoracic Society (BTS ) 2001

22

Guideline ATS 2001

APPROACH

Evaluate prognostic factors and sosial factors


Treat as out patient
G. I
No CPD, no
modifiers

G. IIIA
CPD and / or
modifiers

Hospitalize patient

G. II
CPD and/or
modifiers

G. IIIB
No CPD, no
modifiers

Mild to moderate
infection
(general ward)
G. IVA
No risk of
P. aeruginosa

Severe
infection
(ICU)
G. IVB
No risk of
23
P. aeruginosa

MODIFYING FACTORS
RISK OF INFECTION WITH
SPESIFIC PATHOGENS

Penicillin-resistant & resistant pneumococci

Enteric gram-negatives
Pseudomonas aeruginosa
24

MODIFYING FACTORS
Penicillin resistant &
drug resistant pneumococci
Age > 65 year
Betalaktam therapy within the past 3
months Alcoholsm
Immune-suppressive illness
Multiple medical comorbdities
25
Exposure to a child in a day

MODIFYING FACTORS
Enteric gram-negatives

Residence in a nursing home


Underlying cardiopulmonary disease
Multiple medical comorbidities
Recent antibiotic therapy
26

MODIFYING FACTORS
Pseudomonas aeruginosa

Structural lung disease (bronchiectasis)


Corticosteroid therapy (>10 mg of prednison/day)
Broad-spectr. antibiotic tx for >7 d in the past
month
Malnutriton
27

KRITERIA MINOR :

KRITERIA MAYOR :

- Frekuensi napas > 30 x/m


- PaO2/FiO2 < 250 mmHg
- Ro : bilateral
- Ro : 2 lobus
- Tekanan sistolik < 90
mmHg - Tekanan diastolik <
60 mmHg

- Ventilasi mekanik
- Serum kreatinin - Infiltrat
> 50%
- Septik syok
> 2 mg/dl
atau pean > 2 md/dl

Minimal
Minimal ::22 dari
dari33MINOR
MINORtertentu
tertentu
11 dari
dari22MAYOR
MAYORtertentu
tertentu

ICU

28

Group I :
-S. pneumoniae
-M. pneumoniae
-C . pneumoniae

Group 3A :
=
group 2 plus
H. influenzae
mixed infection

Group 4A :
= group 3 plus
- Legionella
spp

Enteric gram neg

Group 2. :
-S. pneumoniae
( DRSP)
M.
pneumoniae
C. pneumoniae

PATHOGEN

Group 3B :
= group 2 plus
H. influenzae
mixed infection

Group 4B :
=group 4A plus
- P.
aeruginosa
29

.Group I :
- Azithromicin
Clarithromicin
- Doxicycline

Group 3A :
- IV BL plus
IV/oral Macrolide /
Doxicycline OR
- IV New FQ
(monotherapy)

Group 2. :
-- BL plus Macrolide /
Doxicycline OR
- New FQ ( monotherapy)

ANTIMICROBIAL

Group 4A :
-IV BL plus
IV Azithromicin
OR
-IV New
FQ

Group 3B :
= group
3A

Group 4B :
- IV BL antipseudomonal
plus
- IV FQ

30

Empiric Therapy in CAP : Outpatient


IDSA 2000

ATS 2001

BTS 2001

Group I:
Minimal Risk:
Generally Preferred:
No CP disease
< 65 yrs, Stable VS
No Modifying Factors
No Co-morbidity
Macrolide
Adv. Gen. Macrolide
Amoxycillin OR
OR
(Azithromycin/Clarithromycin) Extended Macrolide OR
Doxycycline
Cotrimoxazole
OR
OR
Fluoroquinolone (FQ) Doxycycline
Older Patients or w/
underlying disease:
Fluoroquinolone

Low Risk:
Group II: w/ CP disease
< 65 yrs., Stable VS
& /or Modifying Factors
Stable Co-morbidity
B-Lactam
Cotrimoxazole OR
+
Sultamicillin OR
Macrolide or Doxycycline Co-Amoxyclav OR
OR
2nd Gen Oral Ceph OR
31
Antipneumococcal FQ
Extended Macrolide
alone

Empiric Therapy in CAP : Hospital- Ward


IDSA 2000
Generally Preferred:
Ext. Cephalosporins
+
Macrolide
OR
BL/BLI + Macrolide
OR
Fluoroquinolone
(alone)

ATS 2001

BTS 2001

Group III a : w/ CP disease


&/or Modifying Factors
IV -lactam
+
IV or Oral Macrolide OR

Moderate Risk:
> 65 yrs, Unstable VS ,
Complicated CXR,
Aspiration, Extrapulmo.
evidence of sepsis,
Unstable Co-morbidity

Doxycycline
OR
IV Antipneumo-FQ alone
Group III b : No CP disease
No Modifying Factors
IV Azithromycin alone
If macrolide intolerant:
Doxycycline + B-Lactam
OR
Antipneumo- FQ alone

IV -lactam
with or without
anerobic coverage
+/IV Macrolide
(or alternatives)
OR
Fluoroquinolone alone
32

Empiric Therapy in CAP : ICU


IDSA 2000
Generally Preferred:
Ext. Ceph. or BL/BLI
+
Macrolide or FQ
Structural Lung Dis:
Antipseudo. Agent
+
Fluoroquinolone
B-Lactam Allergy:
Fluoroquinolone
+/Clindamycin
Suspected Apiration:
Fluoroquinolone
+/BL/BLI or Clindamycin

ATS 2001
Group IV a :
No Risks for P. aeruginosa
IV -lactam
+
IV Macrolide(azithromycin)
OR
IV Fluoroquinolone
Group IV b :
Risks for P. aeruginosa
IV Antipseudo. -lactam
+
IV Fluoroquinolone
OR
IV Antipseudo. -Lactam
+ IV Aminoglycoside
+ IV Macrolide
or IV Non-pseudo FQ

BTS 2001
High Risk:
Shock or signs of
hypoperfusion or
Respiratory failure
IV Antipseudo. -lactam
+/IV Aminoglycoside
OR
IV Fluoroquinolone
+
IV Macrolide

33

Recommended Initial Antimicrobial Treatment for Adults


With Suspected Pneumococcal CAP in the Era of Drug
Resistance to Streptococcus pneumoniae
OUTPATIENTS :

Oral -lactam ( high dosages 8 to 10 days )


Amoxicillin 3 x 1 gr
Amoxicillin plus clavulanic acid ( 3 x 875 mg )
Ampicillin plus sulbactam ( 3 x 750 mg)

or

Macrolide ( e.g., azithromycin 1 x 500 mg for 5 days or


clarithromycin 2 x 500 mg for 8 to 10 days )

Doxycycline ( 2 x 100 mg 8 to 10 days )

or

34
alternative

Recommended Initial Antimicrobial Treatment for Adults


With Suspected Pneumococcal CAP in the Era of Drug
Resistance to Streptococcus pneumoniae
HOSPITALIZED PATIENTS :

Intravenous -lactam
Ampicilin plus sulbactam (3 x 1,5-3 g)
Cefotaxim ( 3 x 2g ) or ceftriaxone ( 2 x 1g)
4th-generation cephalosporine (Cefepime 3 x 2g)
Consider combination with IV or oral macrolide
( azithromycin or clarithromycin)

or

New oral or IV fluroquinolones ( levo, gati or moxifloxacin)


35

Carbapenem and Vancomycin in selected patients with defined

Documented infection with


highly resistant pneumococcal
strain

Recommended of
New oral/IV fluoroquinolone
(e.g. GATIFLOXACIN)
GATIFLOXACIN

Treatment failure to one of


--lactam, macrolide or
doxycycline

Alergy to one of
lactam, macrolide or
doxycycline
36

Acute Exacerbation of
Chronic Bronchitis
(AECB)

DEFINITIONS

AECB is the sudden onset of :


sputum production
sputum purulence
dyspnea

Chronic bronchitis is a subset of COPD :


Productive cough of 3 month per year for at
least 2 consecutive years
37

ACUTE EXACERBATION CHRONIC


BRONCHITIS (AECB)

Host
Microbial
load

Inflammatory
Response
Fig. Test tube model
of bacterial
bronchial infection

Cough
Purulent sputum
38

PREVALENCE OF MAJOR
RESPIRATORY PATHOGENS IN AECB

39

Antibiotics in AECB
INDICATIO
N
AT LEAST 2 OF 3
FOLLOWING SYMPTOMS :

MUST INCLUDE
COVERAGE :
- H. influenzae
- S.
pneumoniae
- Moraxella
catarrhalis

SPUTUM PRODUCTION
SPUTUM PURULENCE
DYSPNEA

40

Classification of aacute bronchial infection


and recommendation for treatment
Class

Baseline
clinical status
Acute

tracheobronchitis

II

Simple cronic
bronchitis

III

Complicated
chronic bronchitis

IV

Chronic bronchial
suppuration

Defenition & risk


factors for assesment
of severity

Recommended
first-line
tharapy

Acute cough & sputum

None

Exacerbation in

Amoxicillin or
tetracycline

established : dyspnea /
sputum / sputum
= Classpurulence
II plus 1 :

Fluoroquinolone

- exacerbation > 4 / year


comorbidity
- age > 65 years
history of chronic
bronchitis > 10 years

or
-lactam/
-lactamase
inhibitor
combination

= class III, plus continuous


year-round production of
purulent sputum

Ciprofloxacin
(oral)
41

GUIDELINE TERAPI UNTUK


CAP / AECB
BETALAKTAM
MAKROLID /
TETRACYCLINE
FLUOROKUINOLON
42

Beta-lactams
They are virtually all inactives againts the
atypical pathogens : M. pneumoniae, C.
pneumoniae, Legionella sp.
Current problems with beta-lactams:
Trend Penecillin-Resistant S. pneumoniae
H. influenzae (>40%)
,
produce betalactamase
M. catarrhalis (>95%)
S. aureus (>90%)
43

BETA LACTAMs
MAIN LIABILITY as EMPIRIC
THERAPY in PNEUMONIA
NOT EFFECTIVE AGAINST INTRACELLULAR
PATHOGEN e.g. ATYPICAL PATHOGEN :
M. PNEU & CHL. PNEU
RISING RESISTANCE TO STR.PNEU , WITH IS
ASSOCIATED TO MACROLIDE RESISTANCE

44

Prevalence of Penicillin
Non-Susceptible* Pneumococci:
Asia/Pacific and the Americas

The SENTRY Database, 1997-1998.


Song et al. Clin Infect Dis 1999;28:1206.
Turnidge et al. Med J. Aust 1999;170:152.
Fung et al. J Antimicrob Chemother 2000;45:49.

* Including penicillin-intermediate and penicillin-resistant strains.


45

Macrolides

ERYTHROMYCIN : original macrolide


Two newer additional class : CLARITHROMYCIN &
AZITHROMICIN
All : effective againts atypical pneumonia
( M. pneumoniae, C. pneumoniae & Legionella sp)
Less effective to H. influenzae
Azithromysin : the most active againts Leigonella,
H. influenzae, M. pneumoniae
Cross- resistance of S. pneumoniae to macrolide
46

ADVANTAGES
HIGH TISSUE PENETRATION
EFFECTIVE against ATYPICALS
NO CROSS HYPERS. With PEN.

MACROLIDEs
LOW/NEGLIGIBLE SERUM CONC.
=> NOT SUITABLE FOR SEVERE
INFECTION / SEPSIS
INEFFECTIVE against H.INFLUEN.
NO ANAEROB ACTIVITY
47

DISADVANTAGES

TETRACYCLINE
2 groups :
naturally molecule (TETRACYCLINE) &
semisynthetic molecule ( DOXYCYCLINE &
MINOCYCLINE)
TETRACYCLINE : poor activity ~ H. influenzae
DOXYCYCLINE : especially active ~ M. catarrhalis
MINOCYCLINE : > active ~ H. influenzae & S.
pneumoniae
The most important imitation use of this class :
increasing emergence of microbial resistance
48

Quinolone

49

The Evolution of Quinolones


Limited gram
negatives

Nalidixic Acid

Expanded
gram negatives

Ciprofloxacin, Norfloxacin,
Ofloxacin

Grampositives

Levofloxacin, Sparfloxacin

Expanded grampositives &


atypical

GATIFLOXACIN, Gemifloxacin,
Moxifloxacin

Anaerobes

Trovafloxacin, Clinafloxacin
50

51

Structure of Gatifloxacin
O
F

COOH

[1-1/2 H2O]

OCH3

HN
CH3

Domagala JM. J Antimicrob Chemother 1994;33(4):685-706.


Zhao X et al. Proc Natl Acad Sci USA 1997;94:13991-6.
Fukuda H et al. Antimicrob Agents Chemother 1998;42(8):1917-22.

Methoxy Group at C8:


Targets both DNA gyrase and
topoisomerase IV
May decrease emergence of
quinolone resistance
Increases bactericidal activity
Lack of halide at C8 eliminates
potential for phototoxicity
52

Pharmacokinetic/Pharmacodynamic
Relationships: Surrogate Markers

Concentration (mg/L)

Cmax = Peak serum


concentration

AUC = Area under curve

MIC = Minimal inhibitory


concentration

T>MIC

Cmin = Trough
Time (h)

53

Concentration (mg/L)

Pharmacodynamic Relationships:
AUC : MIC Ratio
Proposed Target Ratios
AUC:MIC >125 Gram-negative organisms
AUC:MIC ~ 30 Gram-positive organisms
AUC = Area under the
curve
MIC = Minimal inhibitory
concentration

Time (h)

Forrest A et al. Antimicrob Agents Chemother 1993;37:1073.


Thomas JK et al. Antimicrob Agents Chemother 1998 42:521.

54

Bioequivalence of Oral and Intravenous of


Gatifloxacin

Lacreta FP et al. 39th ICAAC 1999; Abstract #A-192.

55

SPEKTRUM KUINOLON
terhadap RESP.PATOGEN
STR.
PNE
OFLO

STA.
AUR

H.
INFL

M.
CATA

M.PNE CHL.
PNE

ENTE
RO B.

KL.
PNE

CIPRO

LEVO

GATI

56

PHARMACODYNAMIC
PROFILE OF THE
FLUOROQUINOLONES
Drug

Cmax
(mg/L)

AUC
(mg/L)

MIC90

AUC/MIC

S. pneumoniae

90

Cmax/
MIC90

Moxifloxacin

4.5

48

0.25

192

18

Gatifloxacin

4.2

34.4

0.5

68.8

8.4

Levofloxacin

5.7

47.5

1.0

47.5

5.7

57

AUC : MIC Ratios of Selected


Quinolones :
S. pneumoniae
Unit Oral
Dose (mg)

AUC
(mgh/L)

MIC90
(mg/L)

AUC:MIC90

Moxifloxacin

400

48

0.25

192

Gatifloxacin

400

51.3

0.5 *

103

Levofloxacin

500

72.5

2.0 *

36

Ciprofloxacin

750

20.2

1.0 *

20

Multiple-dose pharmacokinetic data from published U.S. prescribing information.


* Pfaller MA et al. Antimicrob Agents Chemother 1998;42:1762.
Nightingale CH. Pharmacother 2000;20:245.

58

RESISTENSI
LEVOFLOX
RESIST.
MECH.

FAKTA DI
LAPANGAN

MOXIFLOX

GATIFLOX

1 STEP
MUTATION

2 STEP
MUTATION

2 STEP
MUTATION

DOSIS
MAKIN

TIDAK/
BELUM ADA

TIDAK/
BELUM ADA

59

Antibotic used for CAP, AECB


ANTIMICROBIAL

ADVANTAGES

DiSADVANTAGES

Aminopenicillins & -lactam / -lactam inhibitors


eg. Amoxiccilin

Inexpensie, safe,
widely used

PRP, BL +, inactive
againts atypical

Amox/clavulanate

Broadspectrum. Actie
agains H. influenzae,
safe & well tolerated

PRP. Inactive
againts atypical ,
GI sideeffects

Broad spectrum,
active againts H.
influenzae

PRP, inactive
againts atypical

Cephalosporins
eg. Cefaclor,
cefdinir, cefixime

60

Antibotic used for CAP, AECB


ANTIMICROBIAL

ADVANTAGES

DiSADVANTAGES

Inexpensie, active
againts atypical
Dose od., active
againts atypical

PRP, inactive againts

Short-cource therapy,
active againts atypical

Low serum leel, PRP,


limited act. againts H.
influenzae

Macrolides
Erythromycin
Clarithromycin
Azithromycin

H. influenzae, GI side ef

PRP. Limited activity


againts H. influenzae

Fluoroquinolone
Ciprofloxacin
Newfluoroquinolone
( gatiflox., moxiflox.)

Active againts P.
aeruginosa
Broad spectrum, active
againts PRP, H. influenzae,
atypical, anerobes, dose od

Isolated report of
failure in PP
Limited activity
againts P.
61
aeruginosa

CHARACTERISTICS OF THE DIFFERENT


GROUPS OF ANTIBIOTICS
ANTIBIOTICS

Pcn

Cep

ACTIVITY
IN AECB

RISK
PROFILE
(GROUP)

RESISTANCE

RESPIRATORY
PENETRATION

DOSING

AMOXICILLIN

ADEQUATE

HIGH (MOST)

LOW

tid / qid

AMOXICILLIN /
CLAVULANATE

GOOD/
EXCELENT

3&4

LOW

LOW

bid / tid

CEPHALEXIN /
CEFACLOR

POOR

NR

RELATIVELY
HIGH

VERY LOW

tid / qid

ADEQUATE

MODERATE

LOW

qd / bid

TETRACYCLINE

POOR

NR

HIGH

LOW

qid

DOXYCLINE

GOOD

MODERATE-HIGH

LOW

bid

POOR

NR

HIGH

MODERATE

qid

CEFUROXIME /
LORACARBEF
CEFIXIME /
CEFPODOXIME

Tetr

MINOCYCLINE

Mac

ERYTHROMYCIN
AZITHROMYCIN /
DIRITHROMYCIN

qd
GOOD

MODERATE

VERY HIGH

CLARITHROMYCIN

Quinol

bid

CIPROFLOXACIN

GOOD

3&4

LOW

VERY HIGH

LEVOFLOXACIN

GOOD

3&4

LOW

VERY HIGH

GATIFLOXACIN

GOOD

3&4

LOW

VERY HIGH

bid

62

qd
qd

HEALTH ECONOMICS
STREAMLINING
PARENTERAL

ORAL

COMBINATION
BROAD

MONO-TX
NARROW SPECTR.
DOSE REDUCTION

63

SWITCH THERAPY
atau
TERAPI SULIH

PERALIHAN DARI TERAPI PARENTERAL


( SUNTIK) KE TERAPI ORAL

64

Community-Acquired Pneumonia
High risk
High Risk Pneumonia
- IV antibiotic treatment
- Hospital admission
Complicated pneumonia
- Prolonged IV antibiotic
treatment
Continued instability
Strategies for early discharge
of the hospitalized patient

Low risk
Low Risk Pneumonia
- Oral antibiotic treatment
- Out patient therapy
Unstable Pneumonia
- IV antibiotic
treatment
Observation
24 - 72 hours
Clinical Stability
- Rapid switch to oral antibiotic
- Hospital discharge65

1. patient comfort & risk of complications


2. mobility
3. risk of nosocomial infection
4. Earlier hospital discharge
advantages

Clinical aspects of Antibiotic Switch


Therapy
disadvantages
1. Risk of therapeutic failure
2. Concomitant use of other medicine
3. Microbial resistance

66

1. Lower acquistion cost


2. Shorterned hospitalization
3. Earlier return to
normal life & work
advantages

Economic aspects of Antibiotic Switch


Therapy
disadvantages

Patient unable to afford


outpatient treatment
67

GOAL

DAY 7-10

SWITCH day 3
DISCHARGE day 4

I.V.
to
ORAL
SWITCH

DAY 3

EASY

SWITCH OVER DIFFERENT DRUG EQUI -POTENT>


SEQUENTIAL
EQUI-POTENT>
SAME DRUG
STEP DOWN SAME / DIFF. DRUG NON-EQUI-POTENT
68

CRITERIA: IV to ORAL
RAMIREZ J.A.: 21 st IUATLD, MANILA, 2001

STABLE CLINICAL
CONDITION
IMPROVING COUGH & S.O.B.
AFEBRILE > 8 hrs
NORMALIZING WBC
ORAL INTAKE & G.I. ABSORPTION :
ADEQUATE
69

5. Low
acquisition cost

1. Coverage
= intravenous agent

4. No adverse
side effect

The ideal oral


antibiotic for
switch therapy

3. High
Bioavailability

2. OD or
BID dosing
to improve
compliance
70

EVALUATION : 48 - 72 hrs
DEFERVESCENCE
day 2 - 4

RHONCHI (-)
day 7 ( 60-80%)

CLINICAL
IMPROVEMENT
NORMALIZING WBC
day 4

X- RAY RESOLV.
2 wks ( 50.6 %)
4 wks ( 66.7 %)

71
Do NOT CHANGE Tx < 72 hrs, w.o. CLINICAL DETERORIATION

BILA TIDAK RESPONS TERHADAP TERAPI


EMPIRIK

DIAGNOSIS
SALAH
- Gagal
jantung
- Emboli
Keganasan
Sarkoidosis
- Reaksi
Obat
Perdarahan

DIAGNOSIS
BENAR
FAKTOR
PENDERITA

FAKTOR
OBAT

- Kelainan
lokal
- Respon yg

tidak
adekuat
Komplikasi

- Salah
pilih
obat
- Salah
dosis/cara
pemberia

FAKTO
R
KUMA
N
Resiste
nKuman
patoge
n
72
lain
-

5 - 14 days
DURATION of TREATMENT
SHORT TREATMENT
CLINICAL CURE

BACTERIAL
ERADICATION ?
RESISTANCE
(dead bugs do not mutate)

73

PILIHAN EMPIRIK
ANTIBIOTIKA
KONSENSUS
ASIA-PASIFIK:
#MENGATASI > 90 %
PATOGEN
#POLA RESISTENSI

POLA KUMAN
> 80 %
1. H. INFL.
2. M. CATARRH.
3. S.. PNEU
4 ATYPICAL

RESISTENSI > 20 %
GANTI PILIHAN EMPIRIK

74

COMBINED
ONLY INDICATION:
IF NO SINGLE AGENT
COVERS ALL PROBABLE
PATHOGENS

MONO IS PREFERED :
LESS DRUG INTERACTION
LESS ADVERSE EFFECTS
LESS EXPENSIVE
LESS CHANCE OF FORGETTING

MONO TX
CAP
(ATS-guideline)
BETA LACT.
+
MACROL

COVERED by
MONO

RESPIR.QUIN !!
75

ANTIBIOTIK YANG IDEAL


UNTUK INFEKSI PARU
KARAKTERISTIK

F. KUINOLON
-LAKTAM MAKROLID

LEVO

GATI

AKTIVITAS TINGGI GRAM +

AKTIVITAS TINGGI GRAM -

AKTIVITAS TINGGI PATOGEN


ATIPIK

PENETRASI JARINGAN BAIK

NILAI BAKTERISIDAL TINGGI

KECENDERUNGAN RESISTENSI
RENDAH

DOSIS SEKALI SEHARI

76

KESIMPULAN
80 %
KUMAN
AECB/CAP
H.INFL
M.CATARR
S.PNEU
ATYPICAL

RESISTENSI TINGGI
terhdp BETA LAKTAM
+
RESISTENSI SILANG
terhdp MAKROLID

GATIFLOX.
PILIHAN
EMPIRIK
1 DD 400 mg
7 - 1477hr

Summary :
Moxifloxacin in Patients with CommunityAcquired Pneumonia /AECB
Sebagai obat empirik CAP kelompok II / IIIa/IIIb & AECB, dapat
mencover semua patogen penyebabnya
Monoterapi
Kemampuan eradikasi kuman yang tinggi
Cara bekerjanya pada 2 tempat ( DNA gyrase & topoisomerase IV )
kemungkinan resistensi rendah
Memungkinkan sequential terapi ~ cost effective
Memenuhi

safe for the 3 Ps

78

EMPIRICAL CHOICE:
PNEUMONIA : ALL GR.
A(b)ECB : ALL CLASSES

BACTERICIDAL+++
ACQ.RESIST. LOW
(dead bugs do not mutate)

RESUME
GATIFLOXACIN

COST of Tx
SEQUENTIAL
EASY
I.V.= ORAL

HOSPITALIZATION
MEDICINE
ROUTE of ADM.
79

Thank You for


your attention

80

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