PNEMONI

KULIAH RESPIRASI II
SEMESTER 4
FK UKWM
2013
03/09/17 BENJAMIN MARGONO 1
 PNEUMONIA

03/09/17 BENJAMIN MARGONO 2

 PNEUMONIA
New infiltrates or progressively infiltrates
with two or more:
- increased cough,
- change in sputum characteristic,
- temperature 380C or history of fever

- sign of consolidation (bronchial

sound, crackles),
- leucocyte 10.000 or 4.500
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 CAP The Two Types of Presentations

Classical Atypical

Sudden onset of CAP Gradual & insidious onset

High fever, shaking chills
Pleuritic chest pain, SOB
Productive cough
Rusty sputum, blood tinge
Poor general condition
High mortality up to 20% in
patients with bacteremia
S.pneumoniae causative
Low grade fever
Dry cough, No blood tinge
Good GC Walking CAP
Low mortality 1-2%; except
in cases of Legionellosis
Mycoplasma, Chlamydiae,
Legionella, Ricketessiae,
Viruses are causative

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 PNEUMONIA CATEGORIES
CAP (Community Acquired Pneumonia):
Pneumonia in a community resident, w.o.risk factors
for HCAP
HAP ( Hospital Acquired Pneumonia)
Pulmonary infection occurring > 48 hrs after
hospitalization in patients with no previous infection.
Early onset= up to 96 hrs; late onset = > 96 hrs.
VAP ( Ventilator associated Pneumonia)
Pneumonia occurring > 48 hrs after endotracheal
intubation. Early onset = within 48-96 hrs, late onset >
96 hrs.
HCAP ( Health associated Pneumonia )
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 PNEUMONIA CATEGORIES
HCAP
Pulmonary infections in a patient meeting 1 or more
the following conditions:
Infection within 90 days of a 2-day hospitalization
Infection in a nursing home or longterm-care resident
Infection withon 30 days of receiving IV antimicrobials,
chemotherapy or wound care
Infection following a hospital or hemodialysis clinic unit
Contact with MDR pathogens
Different treatment from CAP, more similar treatment to
HAP / VAP
ALL HCAP patients are considered at risk for MDR
infections
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 Recommendations for
the Management of CAP

ATS guidelines 1993 revised in 2001

IDSA guidelines 1998 revised in 2000
updated 2003
Canadian guidelines 1993
BTS guidelines 1993 updated 2004
PDPI (PERHIMPUNAN DOKTER PARU
INDONESIA) 2003

7
BEFORE THX

ATS algorithm

assessment

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 ATS /IDSA GUIDELINE
HAP, VAP. HCAP :UPDATED 2004

4 MAJOR PRINCIPLES:
DONT DELAY ADEQUATE THX
OPTIMIZING
TAILOR THX to the RESULT of LRT
CULTURES DE-ESCALATION
SHORTENING THX to MINIMAL EFFECTIVE
PERIOD MINIMIZING RESISTANCE
PREVENTIVE STRATEGIES aimed at
MODIFIABLE RISK FACTORS
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 An updated of the IDSA 2003
guideline for management CAP
Discharge criteria during 24 hours to
discharge to home patients should not
have more than 1 of the following:
- elevated temp > 37,80 C
- pulse > 100/ minute
- respiratory rate > 24/ minute
- systolic blood pressure < 90 mmHg
- blood oxygen saturation < 90%
- inability to maintain oral intake 10
 The Indonesian Association of
Pulmonologists Guidelines CAP- Outpatient

Without modifying factors

-lactam or -lactam + -lactam inhibitor
With modifying factors
-lactam + -lactam inhibitor or respiratory
fluoroquinolone (levofloxacin, moxifloxacin,
gatifloxacin

Note : suspect atypical : + New macrolide

(roxithromycin,clarithromycin, azithromycin)

11
 The Indonesian Association of
Pulmonologists Guidelines CAP-Inpt (Ward)

Without modifying factors

-lactam + -lactam inhibitor iv or
2nd G, 3rd G Cephalosporin iv or
Respiratory fluoroquinolone iv
With modifying factors
2nd G, 3rd G Cephalosporin iv or
Respiratory fluoroquinolone iv

Note : suspect atypical : + New macrolide

(roxithromycin, clarithromycin, azithromycin)

12
 The Indonesian Association of
Pulmonologists Guidelines CAP - ICU

Non Pseudomonas
3 rd G Cephalosporin non pseudomonas iv + New
macrolide or respiratory fluoroquinolone iv
Pseudomonas
antipseudomonal Cephalosporin iv or carbapenem
+ antipseudomonal fluoroquinolone (ciprofloxacin)
iv or aminoglycoside iv
Suspect atypical : antipseudomonal Cephalosporin
iv or carbapenem + aminoglycoside iv + new
macrolide or respiratory fluoroquinolone iv

13
 G.DRUSANO 2002
MODIFYI IDSA ATS PDPI ERS SPILF JAPAN
NG
FACTORS (FRANCE)

NO M M B-
LACTAM
AMOX AMOX PEN+
CLAV
DOXY DOXY B-LACT TETRA, M M/
CEPH,
+CLAV RESP.Q, M
TETRA

RESP. M (SUSP STREPTO RESP.Q

Q ATYPICAL GRAMIN

YES RESP. CEPH. B-LACT+ AMOX+ AMOX+ CARBA

AMOX, CLAV
Q CLAV CLAV +M
AMOX+CLA

RESP.Q RESP.Q CEPH 3rdCEPH+

(LEVO- PN.C CLINDA+
MOKSI-GATI) M

RESP.Q CLINDA/
INNITIAL EMPIRIC ANTIBIOTIC THX PN.C. VANCO+
FOR ADULT OUTPATIENT CAP AMINOG
L+Q
 EMPIRIC THERAPY has
become ACCEPTED PRACTICE
LARGE NUMBER OF ORGANISMS
THAT MAY CAUSE PULMONARY
DISEASE
THE IN-EXACTNESS OF COMMONLY
USED DIAGNOSTIC TECHNIQUES
SERIOUS CONSEQUENCES OF
INAPPROPRIATE THERAPY

03/09/17 BENJAMIN MARGONO 15

 MICROBIOLIC ETIOLOGICAL
IDENTIFICATION DIFFICULTY

CONTROVERSIES :
COLONIZATION vs- INFECTION
CONTAMINATION of SPECIMEN:
Only resp.tract below larynx is normally sterile
MONO or MIXED INFECTION
QUANTITATIVE CULTURES for DEFINING
PNEUMONIA
FALSE NEGATIVE due to PREVIOUS
ANTIBIOTIC EXPOSURE
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 Invasive Strategy for
Diagnosing HAP
Quantitative culture approach:
bronchoscopic protected specimen brush (103
CFU/ml)
~67% sensitive, 95% specific
bronchoalveolar lavage (104 CFU/ml)
~73% sensitive, 82% specific
quantitative endotracheal aspirate (105 CFU/ml)
38-100% sensitive, 14-100% specific
Antibiotic use more appropriate and accurate
Claim of improved survival at 28 days
(Fagon JY, Chastre J, Wolff M, et al. Ann Intern Med 2000;132:621-630)
(Craven DE, and Steger KA, et al. Infect Cont Hosp Epidemiol 1997;18:783-795)

03/09/17 (Grossman RF and Fein A. Chest 2000;117:177S-181S)

BENJAMIN MARGONO 17
 CAP The Pathogens Involved
40-60% - No causative agent identified; 2-5% - Two are more agents identified

18
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 CAP Grams Stain of Sputum
Good sputum samples is obtained only from 39%
83% show only one predominant organism

19
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 Pathogens Retrieved from Blood Culture

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 USUAL RTI PATHOGENS( Cunha 2004)
CAP
STREP. PNEUMONIAE MOST COMMON
PATHOGEN IN HOSP.ADULTS
H.INFLUENZAE
M.CATARRHALIS COPD
M.PNEUMONIAE AMBULATORY
Chl.PNEUMONIAE YOUNG ADULTS
LEGIONELLA species ELDERLY
COMPROMISED HOST

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 CURB-65
Assessment of pneumonia severity
C onfusion of new onset (< 8 )
U rea > 7 mmol ( BUN > 19)
R esp. rate > 30 / min
B lood Pressure :
Syst < 90 mmHg
Diast < 60 mmHg
> 65 yrs
( Recommended by British Thoracic Society )

03/09/17 BENJAMIN MARGONO 22

 Assessment of severity of pneumonia with the CURB-65 scoring system. Reproduced and
adapted with permission1

Hoare, Z. et al. BMJ 2006;332:1077-1079

03/09/17 BENJAMIN MARGONO 23

Copyright 2006 BMJ Publishing Group Ltd.
 THE ROLE OF PRIMARY CARE
PHYSICIANS
Play critical roles in the management
of CAP
Makes initial treatment decisions
INITIAL EMPIRIC TREATMENT choice is
one of the most important clinical
decisions
Inadequate initial treatment
associated with
Increased mortality
Expert Rev .Anti Infect. Ther. 2010;
Increased risk 8(11)
of clinical failure
24
03/09/17
Greater frequency of drug resistant
BENJAMIN MARGONO
pathogens
 CAP Complications
Hypotension and septic shock
3-5% Pleural effusion; Clear fluid + pus cells
1% Empyema thoracis pus in the pleural space
Lung abscess destruction of lung - CSLD
Single (aspiration) anaerobes, Pseudomonas
Multiple (metastatic) Staphylococcus aureus
Septicemia Brain abscess, Liver Abscess
Multiple Pyemic Abscesses

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03/09/17 BENJAMIN MARGONO
CAP: Empiric Therapy Principles
TREAT EARLY consensus in guidelines
TREAT MOST LIKELY PATHOGENS
Consider :
Local antibiotic resistance patterns
Infection incidence data
Patient demographic features
We cannot differentiate the etiology reliably
based only on clinical findings
ATS. Am J Respir Crit Care Med. 2001;163:1730-1754; Bartlett
26
JG, et al. CID. 2000;31:347-382; Heffelfinger JD, et al. Arch Intern
Med. 2000;160:1399-1408.
 QUINOLONE
11.0% MACROLIDEs
CIPROFL. ERYTHRO
OFLOXAC. 17.4% SPIRA
ANTIBIOTIC
RESP.Q

LEVOFLOX. OPTIONS ROXITHRO

CAP :
MOXIFLOX. ATS 01, IDSA 98, CLARITHRO
ERS 98 AZITHRO

BETA LACTAMs 54.4 %

PENICILLIN / CEPHALOSP. + B-LACT.INHIB.
03/09/17CARBAPENEM ; BENJAMIN
MONOBACTAM
MARGONO ; FOSMYCIN 27
 EMPIRICAL ANTIBIOTICs
in SEVERE INFECTION
ALL INITIAL THX IS EMPIRIC
APPROPRIATE & ADEQUATE:
COVERING > 90 % OF PROBABLE PATH
+ CONSIDER RESISTANCE PATTERN.
IMMEDIATE :
DELAY > 8 h MORTALITY SIGNIFICANT
CHANGING WILL
E SATISFACTORY NOT ALTER
M MORTALITY
P
CLIN. MICROB. DATA & Facilitate
I THX
RESP. SENSITIVITY De-escalation
R
I
C
03/09/17
UNSATISFACTORY
BENJAMIN MARGONO
CHANGE
28
Evaluation : 48 72 hrs
 EVALUATION : 48 - 72 hrs
DEFERVESCENCE RHONCHI (-)
day 7 ( 60-80%)
day 2 - 4

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

Do NOT
03/09/17
CHANGE Tx < 72BENJAMIN
hrs, w.o. CLINICAL DETERORIATION
MARGONO 29
SYMPTOMS CYTOKINE RELEASE : TNF & Il-1.
ASSESSMENT of NON-
RESPONDERS

D
iagnosis
Atelectasis, emboli,
ARDS, Ca

O
rganism
Drug resistant pathogen
FUNGAL infection

C
omplication
Empyema, abscess
Drug fever
03/09/17 BENJAMIN MARGONO 30
 NOT ALL PATHOGEN BACTERIA

Candida Species the 4th most common

bloodstream pathogen in U.S.
nosocomial bloodstream infections
Candida Species highest mortality
(40%) of all bloodstream pathogens

CANDIDA ALBICANS
03/09/17 BENJAMIN MARGONO 31
In BLOODSMEAR
 DE-ESCALATION THERAPY
SWITCH from
INNITIAL
BROADSPECTRUM
HIGH DOSE
EMPIRIC COVERAGE
RE ASSESS WHEN
MICROBIOLOGICAL
DATA AVAILABLE

TARGETED OPTIMIZING OUTCOME

MINIMIZING:
(NARROW / DEDICATED) RESISTANCE
SPECTRUM TOXICITY
03/09/17 BENJAMIN MARGONO COST 32
 DO NOT save your BEST
ANTIBIOTIC for
POSTMORTEM

The use of empirical therapy with

the most effective broad-spectrum
agents available is justified in
severely ill patients who may not
survive until the causative pathogens
are identified.
D.J. Bihari FRCP, RC Spencer FRCP, 1995.
Bacterial infections in Intensive Care. Medicom (UK)

DE-ESCALATION NOT ESCALATION

03/09/17 BENJAMIN MARGONO 33
 HIT RIGHT
HIT HARD

STOP EARLY
PATIENT

03/09/17 3 SAFE Ps
BENJAMIN MARGONO
POCKET
PLANET34
 Mortality Associated With Initial
Inadequate Therapy In Critically Ill Patients
With Serious Infections in the ICU

Alvarez-Lerma,1996 Initial appropriate

therapy
Rello, 1997
Kollef, 1999 Initial inadequate
therapy
Kollef, 1998
Ibrahim, 2000
Luna, 1997
HIT
0% 20%
Mortality*
40% 60% 80% RIGHT
100%

*Mortality refers to crude or infection-related mortality

Alvarez-Lerma F et al. Intensive Care Med 1996;22:387-394.
Ibrahim EH et al. Chest 2000;118L146-155.
Kollef MH et al. Chest 1999; 115:462-474
03/09/17
Kollef MH et al. Chest 1998;113:412-420. BENJAMIN MARGONO 35
Luna CM et al. Chest 1997;111:676-685.
Rello J et al. Am J Resp Crit Care Med 1997;156:196-200.
 INADEQUATE THERAPY
CHOICE of ANTIBIOTIC :
ANTI MICROBIAL ACTIVITY
BACTERIAL RESISTANCE PROFILE
PHARMACOKINETIC
PHARMACODINAMIC
DOSE
METHOD OF ADMINISTRATION
DE-ESCALATION
03/09/17 BENJAMIN MARGONO 36
 What is Appropriate
Antimicrobial Therapy?
The chosen antimicrobial agent is:
on the formulary
in the treatment guideline or clinical pathway
The pathogen is:
susceptible to the antimicrobial agent
The patient:
patient
is not allergic to the prescribed antimicrobial agent
has not had a previous adverse event to the
prescribed agent
Paladino, 2004 37
 HIT HARD & RIGHT
GET THE JOB DONE RIGHT
THE FIRST TIME
UNEQUIVOCALLY DESTROY
MICROBES DEFEATING
RESISTANCE BEFORE IT STARTS
DEAD BUGS
DO NOT MUTATE !!!
03/09/17 BENJAMIN MARGONO 38
 STOP EARLY
THE SHORTEST, SAFE DURATION
THAT WILL KILL THE PATHOGEN
QUICKLY MINIMIZING RESISTANCE
DEVELOPMENT
THE ANTIBIOTIC SHOULD BE:
THE MOST APPROPRIATE
THE MOST PHARMACODYNAMICALLY ACTIVE

03/09/17 BENJAMIN MARGONO 39

 PATIENT:
ADVERSE EFFECTS
THE 3 SAFE Ps
RARE

PLANET :
HIGHLY BACTERICIDAL DEAD BUGS
DO NOT
RESISTENCE RARE MUTATE

POCKET :
EFFECTIVENESS : HIGH
THE MOST EXPENSIVE THERAPY

FAILED THERAPY
03/09/17 BENJAMIN MARGONO 40
 Take home
messages
The decision to use an
antimicrobial agent is not only
relied onwhat is
recommended in the
guidelines but consideration in
the LOCAL SUSCEPTIBLE
PATTERN OF THE PATHOGEN
of interest is also important.
03/09/17 BENJAMIN MARGONO 41
 A WORD of CAUTION
(lancet infect dis: jan 20, 2011- publ.online)
(Kett D.H.)
Study of 4 US Academic Medical Centers:
Incl.criteria : HAP in ICU, MDR risk factors (+),
ATS / IDSA GDLN:
TRIPLE DRUG within 1 d of PNEU DX
CEPHALOSP./ CARBAPENEM / BL+BLI
AMINOGLICOSIDE or FLUOROQUINOLONE
LINEZOLID or VANCOMYCIN
compliant to ATS/IDSA guideline: mortality: 34 %
NON compliant : mortality 20 % (28 days) p=-0042)
PROBABLE CAUSE: ANTIBIOTIC SPECIFIC TOXICITY eg
AMINOGLYCOSIDE ( colistin) : ACUTE RENAL FAILURE,
POLYNEURO-MYOPATHY
QUINOLONES : NEUROTOXICITY, QT INTERV.PROLONGATION-
LEADING TO VENTRIC.ARRYTHMIAS
03/09/17 BENJAMIN MARGONO 42
 SUMMARY
1. THE ANTIMICROBIAL REGIMEN :
early-appropriate-adequate-empirical thx reduce
mortality by 50%
re-assess after 48 - 72 h based on microbiological
& clinical data
2. .The decision to use an antimicrobial agent is not only relied on
what being recommended in the guidelines but consideration in
the local susceptible pattern of the pathogen of interest is also
important
3. ONCE A CAUSATIVE PATHOGEN is identified:
MONOTHERAPY : NO evidence that combination
therapy is more effective
4 DE-ESCALATION THERAPY
to prevent the development of resistance,
to reduce toxicity & costs.
5. DURATION OF THERAPY :
7 to 10 days and guided by clinical response.
.
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