Treatment Guidelines for Community-acquired Pneumonia in Korea: An Evidence-based Approach to Appropriate Antimicrobial Therapy

Jae-Hoon Song; Ki-Suck Jung; Moon Won Kang; Do Jin Kim; Hyunjoo Pai; Gee Young Suh; Tae Sun Shim; Joong Hyun Ahn; Chul Min Ahn; Jun Hee Woo; Nam Yong Lee; Dong-Gun Lee; Mi Suk Lee; Sang Moo Lee; Yeong Seon Lee; Hyukmin Lee; Doo Ryeon Chung

doi:10.3947/ic.2009.41.3.133

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Song, Jung, Kang, Kim, Pai, Suh, Shim, Ahn, Ahn, Woo, Lee, Lee, Lee, Lee, Lee, Lee, Chung, and a Joint committee for CAP Treatment Gui: Treatment Guidelines for Community-acquired Pneumonia in Korea: An Evidence-based Approach to Appropriate Antimicrobial Therapy

Special Article

Infect Chemother 2009;41(3):133-153.

Published online: 30 June 2009

DOI: https://doi.org/10.3947/ic.2009.41.3.133

Treatment Guidelines for Community-acquired Pneumonia in Korea: An Evidence-based Approach to Appropriate Antimicrobial Therapy

Jae-Hoon Song¹, Ki-Suck Jung², Moon Won Kang³, Do Jin Kim⁴, Hyunjoo Pai⁵, Gee Young Suh¹, Tae Sun Shim⁶, Joong Hyun Ahn⁷, Chul Min Ahn⁸, Jun Hee Woo⁶, Nam Yong Lee¹, Dong-Gun Lee³

, Mi Suk Lee⁹, Sang Moo Lee¹⁰, Yeong Seon Lee¹¹, Hyukmin Lee¹², Doo Ryeon Chung¹; a Joint committee for CAP Treatment Gui

¹Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea

²Hallym University Sacred Heart Hospital, Korea

³Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Korea

⁴Soonchunhyang University Bucheon Hospital, Korea

⁵Hanyang University Hospital, Korea

⁶University of Ulsan College of Medicine, Asan Medical Cetner, Korea

⁷Incheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Korea

⁸Gangnam Severance Hospital, Yonsei University College of Medicine, Korea

⁹Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Korea

¹⁰Health Insurance Review & Assessment Service, Korea

¹¹Korea Centers for Disease Control and Prevention, Korea

¹²Kwandong University Myongji Hospita, Korea

Correspondence author : Jae-Hoon Song, M.D., Ph.D. Division of Infectious Diseases, Samsung Medical Center, Sungkyunkwan University School of Medicine, Asian-Pacific Research Foundation for Infectious Diseases (ARFID) 50 Il-won dong, Gangnam-gu, Seoul 135-710, Korea Tel : +82-2-3410-0320, Fax : +82-2-3410-0328 E-mail : songjh@skku.edu or jhsong@ansorp.org

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A successful therapy of community-acquired pneumonia requires appropriate empirical antimicrobial therapy. Etiology and antimicrobial susceptibility of major pathogens of pneumonia can differ by country. Therefore, an ideal treatment guideline of community-acquired pneumonia should be based on the studies performed in each country. We developed a treatment guideline for community-acquired pneumonia in immunocompetent adults in Korea. This guideline was developed by the joint committee of the Korean Society for Chemotherapy, the Korean Society of Infectious Diseases, and the Korean Academy of Tuberculosis and Respiratory diseases.

Keywords: Pneumonia, Community-acquired infections, Guideline

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Table 1.

Grading Levels of Evidence

Levels of evidence		Definition
Studies performed outside Korea	Studies performed in Korea	Definition
Level I	Level I	Well-performed, randomized, controlled trials
Level II	Level II	Well-designed, non-randomized, controlled trials
		Cohort study, case-control study
		Large-scale case series study with systematic analysis for etiology
Level III	Level III	Case series study or experts' opinion
Level III	Level III	Antimicrobial susceptibility data

Table 2.

Criteria for Admission: Pneumonia Severity Index (PSI) Score

Factor	Score
Patient age
Male (age in years)	Age
Female (age in years)	Age-10
Nursing home resident	+10
Coexisting illness^*
Neoplastic disease	+30
Liver disease	+20
Congestive cardiac failure	+10
Cerebrovascular disease	+10
Chronic renal disease	+10
Signs on examination
Acutely altered mental state^†	+20
Respiratory rate ≥30/min	+20
Systolic blood pressure <90 mmHg	+15
Temperature <35°C or ≥40℃	+15
Pulse rate ≥125/min	+10
Results of investigations
Arterial pH <7.35	+30
BUN ≥30 mg/dL	+20
Serum sodium <130 mEq/L	+20
Serum glucose >250 mg/dL	+10
Hb <9 g/dL (Hematocrit <30%)	+10
PaO₂ <60 mmHg (SaO₂ <90%) at room air	+10
Pleural effusion on chest X-ray	+10

^* Coexisting illness

- Neoplastic disease: within one year, excluding cutaneous basal cell carcinoma or cutaneous squamous cell carcinoma)

- Liver disease: clinical or histological liver cirrhosis or chronic active hepatitis

- Congestive cardiac failure: diagnosed by history, physical examination or laboratory findings

- Cerebrovascular disease: clinical stroke or confirmed cases by CT or MRI

^† Altered mental state: disorientation to person, place and time; or recently decreased level of consciousness

Table 3.

Expected Mortality, Risk, and Recommended Place for Treatment according to PSI

Class	PSI score	Expected mortality (%)	Risk	Recommendation
Class I	aged less than 50 yrs old, no underlying disorder/no severe clinical signs	0.1-0.4	Low	Home
Class II	1-70	0.6-0.7		Home
Class III	71-90	0.9-2.8		Home or admission^*
Class IV	91-130	8.2-9.3	Moderate	Hospitalization
Class V	>130	27.0-31.1	High	Intensive care unit

^* Hospitalization for a short term or treatment at observation unit

Table 4.

CURB-65, Mortality, Risk, and Recommended Place for Treatment

Clinical factor	points
C (Confusion)	1
U (Blood urea): >19 mg/dL	1
R (Respiratory rate): ≥30/min	1
B (Blood pressure): Systolic pressure <90 mmHg or diastolic pressure ≤60 mmHg	1
65: ≥65 years	1

CURB-65 score	Mortality	Risk	Recommendation
0	0.7%	Low	Home
1	2.1	Low	Home
2	9.2	Moderate	Hospitalization
3	14.5	High	Intensive care unit
4	40
5	57

Table 5.

Criteria for Severe Pneumonia

Major criteria (2)

Invasive mechanical ventilation

Requiring vasopressors due to septic shock

Minor criteria (9)

Respiratory rate ≥30/min

PaO₂/FiO₂ ratio ≤250

Multilobar pneumonia in chest X-ray

Decreased level of consciousness/disorientation

BUN ≥20 mg/dL

WBC <4,000/mm³

Platelet <100,000/mm³

Core temperature <36℃

Hypotension requiring aggressive fluid therapy

Criteria for admission to intensive care unit

One major or more

Three minor or more

Table 6.

Checklist for Decision of Discharge

Clinically stable state

Body temperature ≤37.8℃

Pulse rate ≤100 per minute

Respiratory rate ≤24 per minute

Systolic pressure ≥90 mmHg

SaO₂ ≥90% at room air or PaO₂ ≥60 mmHg

Possible oral intake

Normal level of consciousness

Need for treatment of other underlying diseases

Need for other diagnostic tests

Social circumstances for patient care

Table 7.

Major Pathogens of Community-acquired Pneumonia in Korea

Pathogen	No. (%)
Pathogen	Woo JH (53) (N=219)	Chung MH (54) (N=54)	Yoo CW (55) (N=81)	Sohn JW (56) (N=39)	Song JH (57) (N=108)
Gram-positive
S. pneumoniae	59 (26.9)	19 (35.2)	27 (33.3)	17 (43.6)	38 (35.2)
S. aureus	25 (11.4)	5 (9.3)	13 (16.0)	1 (2.6)	12 (11.1)
Viridans group streptococci	12 (5.5)	1 (1.9)			4 (3.7)
β-hemolytic streptococci	1 (0.5)	3 (5.6)		4 (10.3)	5 (4.6)
Others	2 (0.9)				2 (0.9)
Gram-negative
Klebsiella spp.	44 (20.0)	8 (14.8)	12 (14.8)	4 (10.3)	12 (11.1)
Pseudomonas spp.	28 (12.8)	1 (1.9)	5 (6.2)	4 (10.3)	7 (6.5)
Enterobacter	14 (6.4)	1 (1.9)		2 (5.1)	5 (4.6)
Haemophilus	11 (5.0)	12 (22.2)	11 (13.6)	1 (2.6)	3 (2.8)
Acinetobacter spp.	7 (3.2)	1 (1.9)		4 (10.3)	1 (0.9)
E. coli	6 (2.7)	2 (3.7)		2 (5.1)	4 (3.7)
Others	10 (4.6)	1 (1.9)	13 (16.0)		9 (8.3)
Anaerobes					3 (2.8)

Table 8.

Etiologies according to severity

Place for treatment	Etiology^*
Outpatient	S. pneumoniae, M. pneumoniae, H. influenzae, C. pneumoniae, respiratory viruses
Hospitalization	S. pneumoniae, M. pneumoniae, C. pneumoniae, H. influenzae, Legionella spp., respiratory viruses
Intensive care unit	S. pneumoniae, S. aureus, K. pneumoniae, E. coli, P. aeruginosa, Enterobacter, H. influenzae, Legionella spp.,

^* Others:M. tuberculosis, Orientia tsutsugamushi, Leptospira

Table 9.

Etiologies according to the risk factors

Risk factors	Common etiology
Heavy alcohol drinking	S. pneumoniae, oral anaerobes, Gram-negatives including K. pneumoniae, M. tuberculosis
COPD±smoking	H. influenzae, P. aeruginosa, Legionella spp. S. pneumoniae, M. catarrhalis, C. pneumoniae
Structural lung diseases such as bronchiectasis	P. aeruginosa, B. cepacia, S. aureus
Aspiration	Enterobacteriaceae, Anaerobes
Bronchial obstruction	Anaerobes, S. pneumoniae, H. influenzae, S. aureus
Influenza season	S. pneumoniae, S. aureus, H. influenzae
Occurring in autumn, rash with eschar	Orientia tsutsugamushi
Intravenous drug abuser	S. aureus, Anaerobes, M. tuberculosis, S. pneumoniae
Exposure to air conditioning of building for last 2 weeks	Legionella spp.
Exposure to birds	C. pneumoniae

Table 10.

Pathogen distribution of atypical pneumonia in Korea

Etiology	No. (%)
Etiology	Sohn JW (56) (N=126)	Lee DD (58) (N=38)	Lee SJ (62) (N=81)	Joo CH (59) (N=250)	Kim MJ (60) (N=431)
Mycoplasma pneumoniae	8 (6.3)	ND	7 (8.6)	23 (9.2)	ND
Chlamydia pneumoniae	9 (7.1)	ND	10 (12.3)	33 (13.2)	ND
Legionella spp.	3 (2.4)	2 (5.3)	0 (0)	ND	10 (2.3)

ND: not done

Table 11.

Etiology of Viral Pneumonia in Korea

Virus^*	No. (%)
Virus^*	N=317
Influenza A	16 (5.0)
Parainfluenza	10 (3.2)
Adenovirus	4 (1.3)
RSV^✝	3 (0.95)

^* Virus was isolated in 10.1% of community-acquired pneumonia

^✝ Respiratory syncitial virus

Table 12.

Recommended Antimicrobial Therapy according to Etiologic Microorganism

Pathogen		Preferred Antibiotics	Alternative Antibiotics
Streptococcus pneumoniae		penicillin G, high dose amoxicillin	3rd generation cephalosporin (cefotaxime, ceftriaxone), respiratory FQ, glycopeptides
Haemophilus influenzae
	β-lactamase non-producing	amoxicillin	respiratory FQ
	β-lactamase producing	2nd or 3rd generation cephalosporin, β-lactam/β-lactamase inhibitor	respiratory FQ
Staphylococcus aureus
	methicillin-susceptible	anti-staphylococcal penicillin or 1st generation cephalosporin	clindamycin
	methicillin-resistant	glycopeptide	linezolid
Enterobacteriaceae		3rd generation cephalosporin, β-lactam/β-lactamase inhibitor	carbapenem (except ertapenem), FQ
Pseudomonas aeruginosa		antipseudomonal β-lactam ± aminoglycoside or FQ	carbapenem, ciprofloxacin or levofloxacin
Mycoplasma pneumoniae		macrolides	respiratory FQ, doxycycline
Chlamydophila spp.		macrolides	respiratory FQ, doxycycline
Legionella spp.		respiratory FQ, macrolides	doxycycline
Coxiella burnetii		doxycycline	macrolide, FQ
Anaerobes		β-lactam/β-lactamase inhibitor, clindamycin	carbapenem
Influenza virus		oseltamivir

FQ: fluoroquinolone

Table 13.

Recommended Dosage, Merits and Demerits^*

Antimicrobial agents		Dosage	Merits	Demerits
Penicillin
	Ampicillin	500 mg 4-6 times (po)		High dose is required for S. pneumoniae with high MIC
	Ampicillin	0.5-2 g q4-12h (iv)
	Amoxicillin	500 mg tid (po)
	Amoxicillin	(high dose, 1 g tid)
	Penicillin G	3-6 million unit 4-6 times (iv)
	Piperacillin	3 g q4-6h (max. 24 g/d) (iv)
Cephalosporin
	Cefpodoxime proxetil	100-200 mg bid (po)
	Cefditoren pivoxil	100 mg tid (po)
	Ceftriaxone	1-2 g q24h (iv)
	Cefotaxime	1-2 g q8h (iv)
	Cefepime	1-2 g q8h, q12h (iv)	Effective against P. aeruginosa
	Cefpirome	1-2 g q12h (iv)	Effective against P. aeruginosa
β-lactam/β-lactamase inhibitor
	Amoxicillin/clavulanate	(2:1) 750 mg tid (po)
		(4:1) 625 mg tid (po)
		(7:1) 1 g bid (po)
		(5:1) 1.2 g q8h, q6h (iv)
		(dose for combination)
	Ampicillin/sulbactam	1.5-3 g q8h, q6h (iv)
	Piperacillin/tazobactam	4.5 g q8h, q6h (iv)	Effective against P. aeruginosa
Carbapenem			Effective against most bacteria except MRSA	Increase of carbapenem-resistant P. aeruginosa
	Imipenem	0.5-1 g q8h, q6h (iv)		Increase of carbapenem-resistant P. aeruginosa
	Meropenem	0.5-1 g q8h (iv)		Seizure can be induced
Fluoroquinolone			Can be used for penicillin-allergic patients	Prolongation of QT interval, Seizure can be induced when used with NSAIDs
	Ciprofloxacin	500-750 mg bid (po)		Not belonging to respiratory FQ, less effective against S. pneumoniae and atypical pathogens
	Ciprofloxacin	400-800 mg q12h (iv)	Respiratory FQ, effective against penicillin-resistant, macrolide-resistant S. pneumoniae
	Levofloxacin	500-750 mg qd (po)
	Levofloxacin	500-750 mg q24h (iv)
	Gemifloxacin	320 mg qd (po)
	Gemifloxacin	400 mg qd (po)
	Moxifloxacin	400 mg q24h (iv)	Effective against anaerobes
Macrolide			Effective against atypical pathogens, high intracellular concentration	High resistant rate of S. pneumoniae
	Erythromycin	15-20 mg/kg/d,
		max. 4 g/d (iv)		Oral bioavailability 50%, abdominal pain or cramp, nausea, vomiting (>10%)
		250-500 mg qid (po)
	Roxithromycin	300 mg qd, 150 mg bid (po)
	Clarithromycin	250-500 mg bid (po)		Increase of serum concentration of other drugs due to interaction
	Clarithromycin	500 mg q12h (iv)
	Azithromycin	500 mg qd or q24h (X1) and	Little drug interaction due to less effect on cytochrome P450	Increase of theophylline serum concentration
	Azithromycin	then 250 mg qd or q24h (po/iv)		Increase of theophylline serum concentration

^* Antimicrobial agents recommended in empirical therapy were described. In general, dosages were based on the guidelines of Korea Food & Drug Administration.

Table 14.

Causes of Pneumonia with no Response to Antimicrobial Therapy

Misdiagnosis		Congestive heart failure, pulmonary embolism, myocardial infarction, malignant neoplasm, sarcoidosis, vasculitis (Wegener granulomatosis, etc), renal failure, pulmonary hemorrhage, bronchiolitis obliterans organizing pneumonia, drug-induced lung diseases, eosinophilic pneumonia, hypersensitivity pneumonia
Correct diagnosis
	Problem in patients	Focal site: obstruction, foreign body
		Immune suppression
		Complication of pneumonia: pleural empyema, parapneumonic effusion
	Problem in drugs	Errors in selection of drugs, dosage, or route of administration
		Adverse reactions such as drug fever or drug interaction
	Problem in microorganisms	Resistant bacteria, superinfection, uncommon organisms (Mycobacterium, Nocardia, fungus, virus, anaerobes, etc.)
	Metastatic infection	Endocarditis, meningitis, arthritis, pericarditis, peritonitis, etc

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