Management of Hospitalized

Community Acquired
Pneumonia

Tazocin - Slide RTD Reference 2018

Community-acquired pneumonia
(CAP)
• Major respiratory disease with a high prevalence in the
general population, clinical heterogeneity and variable
severity.
• Usually causes symptoms for 3–4 weeks, and daily
activities may be impaired for a further 3 weeks on
average.
• Reported incidence of pneumonia varies considerably
from country to country and study to study, with a
consistently higher incidence in very young children and
elderly adults.

ERS European Lung White Book, Chapter 18 - Acute lower respiratory infections. Accessed thru
http://www.erswhitebook.org/chapters/acute-lower-respiratory-infections/ on 26 August 2016.
 Definisi Pneumonia Berat
• Terdapat 2 kriteria minor atau 1 kriteria mayor.
• Perawatan ICU dibutuhkan untuk pasien dengan
syok septic yang membutuhkan vasopressor
atau dengan gagal napas yang membutuhkan
intubasi dan ventilasi mekanik (Rekomendasi
kuat; level II evidence)
• Perawatan ICU atau monitoring ketat
direkomendasikan untuk pasien dengan 3
kriteria minor untuk pneumonia berat
(Rekomendasi sedang; level II evidence)
Kriteria Pneumonia Komunitas Berat

Kriteria Minor
•Laju napas . 30kali/mnt
•Rasio PaO2/FiO2 < 250
•Infiltrat Multilobar
•Penurunan kesadaran/ disorientasi
•Uremia (BUN level > 20 mg/dl)
•Leukopenia (WBC count < 4000 cell/mm3)
•Trombositopenia (platelet count <100.000 cell/mm3)
•Hipotermia (core temperature)
•Hipotensi yang membutuhkan resusitasi cairan
Kriteria Minor
•Ventilasi mekanik invasive
•Syok septic yang membutuhkan vasopresor
 Most common etiologies

Mandell, LA. Postgrad Med 2015; 127(6): 607–615.

 CAP in Asia
• In Asia, CAP is estimated to cause almost one million adult deaths per
year.1,2
– Many of these deaths occur in the elderly, but a large number occur in those with
good life expectancy
• Systematic review of all adult CAP etiology studies publish in English from
Jan 1990- Mar 2012 (incl. China, India, Indonesia, Japan, Malaysia,
Philippines, Singapore, South Korea, Taiwan, Thailand and Vietnam) 2

• Streptococcus pneumoniae
was the most commonly
identified pathogen (13.3%). 2
• Overall rate of Haemophilus
influenzae for Asia was
6.9%; Legionella spp. was
low at 3.0%2
• Gram negative bacilli (GNB)
were identified in 13.0% of
hospitalised patients
(averaging all Asian studies) 2

1. World Health Organization. Global burden of disease (GBD). Geneva: World Health Organization; 2008.
http://www.who.int/healthinfo/ global_burden_disease/gbd/en/ [accessed 1 August 2012].
2. Peto, L., et al. Trans R Soc Trop Med Hyg 2014; 108: 326–337.
 Indonesia: Resistance in nosocomial
pathogens in an ICU – P. aeruginosa
Cross sectional retrospective study of bacterial pathogens isolated from ICU patients in
one tertiary hospital in Indonesia from 2009-2010 (N=722)

Antibiotic resistance pattern of

microorganisms isolated
from ICU patients (%)

P. aeruginosa isolated from ICU patients

(n=66)
Frequency of

Cephalexin 95.3
Cefotaxime 64.1
Ceftriaxone 60.9
Cefpirome 59.4
Ciprofloxacin 56.3

P. aeruginosa was the predominant pathogen in ICU isolates, and had high resistance
rates for cephalexin (95.3%), cefotaxime (64.1%) and ceftriaxone (60.9%)
Radji, et al. Asian Pac J Trop Biomed 2011;1:39-42
 British Thoracic Society :
CURB 65 severity score

1. Lim WA, et al. Thorax 2009;64 Suppl3:iii1-55.

 BTS : Hospital management of
CAP in the first 4 hours
Patient meets criteria for CAP: Treat according to clinical judgement
and CURB65 severity score

0-1 2 3-5
Low severity Moderate severity High severity

Other reasons for  Hospital  Hospital

admission (unstable  Supportive care  Supportive care
comorbidity, social)  Microbiological  Microbiological
investigations investigations
 Antibiotics given  Antibiotics given
 Urgent senior review
Ye No  Decision regarding
s transfer to critical
care unit (especially
• Home • Hospital if CURB65 = 4 or 5)
• Antibiotics • Antibiotics

1. Lim WA, et al. Thorax 2009;64 Suppl3:iii1-55.

 Table 2. Initial Empiric Antibiotic Therapy For Hospital-Acquired
Pneumonia or Ventilator-Associated Pneumonia in Patients with
No Known Risk Factors for Multidrug-Resistant Pathogens, Early
Onset, and Any Diseases Severity

Potential Pathogen Recommended Antibiotics

Streptococcus pneumoniae Ceftriaxone

Haemophilus influenzae or
Methicillin-sensitive Staphylococcus Levofloxacin,moxifloxacin,or
aureus ciprofloxacin
Antibiotic-sensitive enteric gram- or
negative bacilli Ampicillin/sulbactam
Escherichia coli or
Klebsiella pneumoniae Ertapenem
Enterobacter species
Proteus species
Serratia marcescens

Am J Respir Crit Care Med vol 171, pp 388-416, 2005

 Table3.Initial Empiric Therapy for HAP, VAP and HCAP in Patients with Late-
onset Disease or Risk Factors for Multidrug-Resistant Pathogens and All
Disease Severity
Potential Pathogens Combination Antibiotic Therapy
Pathogens listed in table 2 and MDR Antipseudomonal cephalosporin
pathogens (cefepime, ceftazidime)
Pseudomonas aeruginosa or
Klebsiella pneumoniae (ESBL) Antipseudomonal carbapenem
Acinetobacter species (imipenem or meropenem)
or
-lactam/-lactamase inhibitor
(piperacillin-tazobactam)
plus
Antispeudomonal fluoroquinolone
(ciprofloxacin or levofloxacin)
or
Aminoglycoside
(amikacin,gentamicin,or tobramycin)
plus
Methicillin-resistant Spthylococcus Linezolid or vancomycin
aureus (MRSA)

Legionella pneumophila
Table 4.Initial Intravenous,Adult Doses of Antibiotics for Empiric Therapy of
HAP, including VAP and HCAP In Patients with Late-Onset Disease or Risk
Factors for Multidrug-Resistant Pathogens

Antibiotic Dosage
Antipseudomonal cephalosporin
Cefepime 1-2g every 8-12h
Ceftazidime 2g every 8h
Carbapenems
Imipenem 500mg every 6h or 1g every 8h
Meropenem 1g every 8h
-lactam/-lactamase inhibitor
Piperacillin-tazobactam 4.5g every 6h
Aminoglycosides
Gentamicin 7mg/kg per d
Tobramycin 7mg/kg per d
Amikacin 20mg/kg per d
Antipseudomonal quinolones
Levofloxacin 750mg every d
Ciprofloxacin 400mg every 8h
Vancomycin 15mg/kg every 12h
Linezolid 600mg every 12h

Am J Respir Crit Care Med vol 171, pp 388-416, 2005

 Clinical Efficacy of
Piperacillin/Tazobactam in HAP

An Evidence-based Review of Randomized

Control Studies

Piperacillin vs Imipenem
Jaccard C, Troillet N, Harbarth S, et al. Antimicrob Agents Chemother 1998 Nov;42(11):2966-2972.

Piperacillin/Tazobactam vs Ceftazadime
Joshi M, Bernstein J, Solomkin J, et al. J Antimicrob Chemother 1999;43:389-397.
Alvarez-Lerma F, Insausti-Ordenana J, Jorda-Marcos R, et al. Intensive Care Med 2001;27:493-502.
Brun-Buisson C, Sollet JP, Schweich H, et al. Clin Infect Dis 1998 Feb;26:346-354.
Fowler RA, Flavin KE, Barr J, et al. Chest 2003 Mar;123(3):835-844.
 Piperacillin/Tazobactam vs. Imipenem
in HAP
• Prospective, randomized, multicenter (Switzerland)
• Adult (≥72 h in hospital)
– Piperacillin/tazobactam – 4.5 g q8h IV
OR
– Imipenem/cilastatin – 500 mg/500 mg q6h IV

• HAP episodes: clinical and bacteriologic response

• Evaluable patients
– 75 in piperacillin/tazobactam group
– 79 in imipenem/cilastatin group

Jaccard C, Troillet N, Harbarth S, et al. Antimicrob Agents Chemother 1998 Nov;42(11):2966-2972.

 Success Rates in Evaluable †

Patients
Piperacillin/ Imipenem/ P value
tazobactam cilastatin
Clinical 83% 71% 0.09
response (62/75) (56/79)
P. aeruginosa 91% 50% 0.004
response (19/21) (12/24)
†
Cure was defined as the resolution of symptoms of pneumonia and an improved chest radiograph.

• Pseudomonas pneumonia failure

Pip/tazo - 2/21 (10%)
Imipenem - 12/24 (50%); P = 0.004
• Resistance developed during therapy
Pip/tazo - 1 patient
Imipenem - 6 patients

Jaccard C, Troillet N, Harbarth S, et al. Antimicrob Agents Chemother 1998 Nov;42(11):2966-2972.

 Piperacillin/Tazobactam + Amikacin vs.
Ceftazidime + Amikacin
• Prospective, randomized, open, multicenter (Spain)
• Adult
– Piperacillin/tazobactam – 4.5 g q6h IV PLUS
OR
Amikacin
– Ceftazidime – 2 g q8h IV
15 mg/kg/day,
divided
• HAP episodes
– Clinical response
• Cured, improved, relapse, or failure
– Bacteriologic response
• Eradication, presumed eradication, superinfection, relapse,
or failure

Alvarez-Lerma F, Insausti-Ordeñana J, Jordá-Marcos R, et al. Intensive Care Med 2001;27:493-502.

 Piperacillin/Tazobactam + Amikacin vs.
Ceftazidime + Amikacin

Pip/tazo Ceftazidime
+ Amikacin + Amikacin
Eligible 88 36
episodes

Evaluable 83 26
episodes

Alvarez-Lerma F, Insausti-Ordeñana J, Jordá-Marcos R, et al. Intensive Care Med 2001;27:493-502.

 Success Rates in Evaluable †

Patients
Pip/tazo Ceftazidime P-
+ Amikacin + Amikacin value
Clinical 63.9% 61.5% 0.831
response (53/83) (16/26)
Microbiologic 68.9% 65.0% 0.757
response (31/45) (13/20)
†
Successful outcomes included a cured or improved clinical response, and an eradication
or presumed eradication of the baseline pathogen.

Alvarez-Lerma F, Insausti-Ordeñana J, Jordá-Marcos R, et al. Intensive Care Med 2001;27:493-502.

 Piperacillin/Tazobactam
Combination Therapy

Compared with ceftazidime + amikacin:

• Equivalent treatment efficacy
• Similar eradication rates of baseline pathogen
• Attributable mortality rate
– Not statistically significant

Alvarez-Lerma F, Insausti-Ordeñana J, Jordá-Marcos R, et al. Intensive Care Med 2001;27:493-502.

 Piperacillin/Tazobactam + Amikacin vs.
Ceftazidime + Amikacin

• Prospective, randomized, open, multicenter (France)

• Adult (≥72 h hosp, ≥48 h MV)
– Piperacillin/tazobactam – 4.5 g qid IV PLUS
OR Amikacin
– Ceftazidime – 1 g qid IV
7.5 mg/kg bid
• HAP episodes
– Evaluable
• 51 piperacillin/tazobactam cohort
• 64 ceftazidime cohort
– Microbiologically documented ventilator-associated pneumonia
evaluated
– Clinical response
– Bacteriologic response

Brun-Buisson C, Sollet JP, Schweich H, et al. Clin Infect Dis. 1998 Feb;26:346-354.
 Outcomes of Evaluable Patients †

Pip/tazo Ceftazidime P-
+ Amikacin + Amikacin value
Clinical 51% 36% NS
response (26/51) (23/64)
Microbiological 33% 51% NS
failures (17/51) (33/64)
†
Cure was defined as complete or partial resolution of clinical signs and symptoms of
pneumonia. Failure was defined as the need for a change in therapy during treatment or
followup.

Brun-Buisson C, Sollet JP, Schweich H, et al. Clin Infect Dis. 1998 Feb;26:346-354.
 Piperacillin/Tazobactam + Amikacin vs.
Ceftazidime + Amikacin

Compared with ceftazidime + amikacin:

• Equivalent treatment efficacy
– P > 0.05
• Trend toward better eradication of baseline
pathogens
• Overall mortality rate
– Not statistically significant

Brun-Buisson C, Sollet JP, Schweich H, et al. Clin Infect Dis. 1998 Feb;26:346-354.
 IDSA 2007: CAP Empiric Antimicrobial
Therapy

Recommendations on empiric antibiotics

Outpatients Macrolide (azithromycin, Doxycycline
Previously clarithromycin, or
healthy erythyromycin)
Presence of Respiratory ẞ-lactam plus a macrolide
comorbidities fluoroquinolone
Inpatient, non A respiratory A ẞ-lactam plus a macrolide
ICU treatment fluoroquinolone A respiratory fluoroquinolone
for penicillin-allergic patients

Mandell, LA, et al. Clinical Infectious Diseases 2007; 44:S27–72.

 IDSA 2007: CAP Empiric antibiotics
in inpatient ICU
 Routinely cover the 3 most common severe CAP pathogens, all the atypical
pathogens, and most of the relevant Enterobacteriaceae spp.

Recommendations on empiric antibiotics

ICU patients A β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam)
+
Azithromycin; OR
A respiratory fluoroquinolone
If Pseudomonas An antipneumococcal, antipseudomonal β-lactam (piperacillin-
suspected tazobactam, cefepime, imipenem or meropenem)
+
Ciprofloxacin or levofloxacin; OR
An aminoglycoside and azithromycin; OR
An aminoglycoside and an antipneumococcal fluoroquinolone
If community-acquired Add vancomycin or linezolid
MRSA suspected

Mandell LA, et al. Clin Infect Dis 2007;44 Suppl2:S27-72.

IDSA 2007: Pathogen-directed therapy for
CAP in ICU inpatients
 Employ pathogen-directed antimicrobial therapy once etiology identified
Organism Preferred antimicrobial(s) Alternative antimicrobial(s)
Streptococcus pneumoniae
Penicillin nonresistant; Penicillin G, amoxicillin Macrolide, cephalosporins (oral or
MIC <2 μg/mL parenteral), clindamycin, doxycycline,
respiratory fluoroquinolone
Penicillin resistant; Choice based on susceptibility, including Vancomycin, linezolid, high-dose amoxicillin
MIC ≥2 μg/mL cefotaxime, ceftriaxone, fluoroquinolone (3 g/day with penicillin MIC ≤4 μg/mL)
Staphylococcus aureus
Methicillin susceptible Anti-staphylococcal penicillin Cefazolin, clindamycin
Methicillin resistant Vancomycin or linezolid TMP-SMX*
Haemophilus influenzae
Non-β-lactamase Amoxicillin Fluoroquinolone, doxycycline, azithromycin,
producing clarithromycin
β-lactamase producing 2nd- or 3rd-gen. cephalosporin, amoxi-clav
Enterobacteriaceae 3rd-gen. cephalosporin, carbapenem (drug β-lactam/β-lactamase inhibitor,
of choice if ESBL producer) fluoroquinolone
Legionella species Fluoroquinolone, azithromycin Doxycycline
* Suggest to refer to local susceptibility results or advice from local specialists
Mandell LA, et al. Clin Infect Dis 2007;44 Suppl2:S27-72.
 Time to first antibiotic dose
• In a UK study, time to first antibiotic (TFA) was ≤4 h in 63%1
– Adjusted 30-day inpatient (IP) mortality was lower for adults with TFA
≤4h vs. TFA >4h (adjusted OR 0.84, 95% CI 0.74 to 0.94; p=0.003).
– Increasing TFA was associated with greater OR of 30-day IP mortality
(p value for trend=0.001), but no TFA threshold was evident.
– Although association between TFA and mortality, not adequate to
conclude that this is causal or whether TFA might just be a quality
measure for overall or other processes of care.
• For patients admitted through the emergency department, the first antibiotic
dose should be administered while still in the ED. (Moderate
recommendation; level III evidence)2
• Rather than designating a specific window in which to initiate treatment, the
committee felt that hospitalized patients with CAP should receive the first
antibiotic dose in the ED.2
1. Daniel P, et al. Thorax 2016;71:568–570. doi:10.1136/thoraxjnl-2015-207513.
2. Mandell, LA, et al. Clinical Infectious Diseases 2007; 44:S27–72.
 Switch from intravenous to oral and
duration of antibiotic therapy
• Consider switch from intravenous to oral therapy when hemodynamically stable and
clinically improving, able to ingest medications, have a normally functioning
gastrointestinal tract (Strong recommendation; level II evidence)
• Patients should be discharged as soon as clinically stable, have no other active
medical problems, and have a safe environment for continued care. Inpatient
observation while receiving oral therapy is not necessary. (Moderate
recommendation; level II evidence)
• Patients with CAP should be treated for a minimum of 5 days (level I evidence),
afebrile for 48–72 h, and should have no more than 1 CAP-associated sign of Clinical
instability before discontinuation of therapy (level II evidence). (Moderate
recommendation)
• Longer duration of therapy may be needed if initial therapy was not active against
the identified pathogen or if it was complicated by extrapulmonary infection (Weak
recommendation; level III evidence)

Mandell, LA, et al. Clinical Infectious Diseases 2007; 44:S27–72.

 Conclusion
• CAP is major respiratory disease with a high prevalence in the general population, clinical
heterogeneity and variable severity 1
• In Asia CAP estimated to cause almost one million adult deaths per year with Streptococcus
pneumoniae was the most commonly identified pathogen (13.3%) 2 while in Indonesia ICU P.
aeruginosa was the predominant pathogen 3
• Hospitalized patients with CAP should receive the first antibiotic dose in the ED. 4
– Non ICU patient:
• Beta-lactams + macrolide or
• Respiratory fluoroquinolone
– ICU Patient routinely need antibiotic cover the 3 most common severe CAP pathogens, all the
atypical pathogens, and most of the relevant Enterobacteriaceae spp includes the following:
• Beta-lactam + macrolide or respiratory fluoroquinolone
– If Pseudomonas is suspected, therapy is as follows:
• Anti-pneumococcal and anti-pseudomonal beta-lactam (piperacillin/tazobactam,
cefepime, carbapenem [imipenem, meropenem, or doripenem]) + ciprofloxacin or
levofloxacin or
• Beta-lactam (as above) + aminoglycoside and azithromycin or aminoglycoside and
fluoroquinolone
• Patients with CAP should be treated for a minimum of 5 days (level I evidence), afebrile for 48–72
h, and should have no more than 1 CAP-associated sign of Clinical instability before
discontinuation of therapy. 4

1. ERS European Lung White Book, Chapter 18 - Acute lower respiratory infections. Accessed thru http://www.erswhitebook.org/chapters/acute-lower-respiratory-infections/ on 26 August 2016
2. Peto, L., et al. Trans R Soc Trop Med Hyg 2014; 108: 326–337.
3. Radji, et al. Asian Pac J Trop Biomed 2011;1:39-42
4. Mandell, LA, et al. Clinical Infectious Diseases 2007; 44:S27–72.