의료관련감염관리역학의활용울산의대서울아산병원진단검사의학과

김미나

HAI 역학의활용

• Endemic vs. Epidemic HAI의역학

• HAI 문제규명을위한역학조사

• 언제, 어떻게(systematic approach)

Endemic vs. Epidemic HAI 정의

• Endemic HAI 정의

• 의료기관에서기저감염률을이루는산발적인감염(sporadic infection)

• 기저감염율은시기적변동을보이지만, 통계적으로유의하지않다.

• 대부분의 HAI는 endemic & 감염관리활동의상시목표

• 주요 HAI 병원균과감염부위에공통점이많지만기관의환자특성별,의료행위별, 그외다양한요인에따라차이

• Endemic HAI의특성• Breaks in aseptic technique

• Person-to-person transmission

• Failure of hand washing

• General infection control recommendation에으로감염예방

Endemic vs. Epidemic HAI 정의

• Epidemic infection의정의

• 기저감염율보다통계적으로유의하게감염률이높을때

• Numerator data(분자) 만을이용한유행감시

• 드문균이나특정내성균에의한유행감지에효과적

• 특정시기특정장소에서 S. aureus 혈류감염의유행을감지할수없다.

• Denominator data (분모) 필요

• Risk에영향을주는인자들을조절한정의사용

• Pre-epidemic period의기저감염율자료필요– active prospective surveillance (감시)를해야유행을조기에감지. Numerator자료만수집해서군집이의심되면retrospective surveillance 실시해야유행인지아닌지감별할수있다.

Endemic과 Epidemic HAI 의감지

• Surveillance(감시): 기본

• Surveillance 방법: Endemic과 epidemic 구분하려면 numerator, denominator 를수집한방법을명확히해야한다.• Surveillance artifact: numerator, denominator 둘다에영향 –감염률분석전에영향요인에대해충분한평가가필수. 시간이걸리는작업

• Validation of numerator & denominator: 여러명이각증례를각각독립적으로검토

Endemic vs. Epidemic HAI 정의

• Disease frequency 측정

• Denominator: 조사기간이시작될때감염이없고, 위험에노출된집단

• Numerator : denominator 중감염된환자

• Prevalence(유병율): the frequency of existing cases of the infection in a population, %

• Incidence와 disease duration에비례, disease burden 산정. Population 이역동적이면어느시점에서조사하는지에따라영향

감염된환자수조사시점에위험이노출된총환자수

유병율 =

Disease frequency• Incidence(빈도): the number of new cases of the infection that develop in a

population of individuals at risk, during a specified time period, %

*누적빈도는조사시작시점의위험에노출된집단을반영. 조사기간동안 denominator 모두동일한기간추적해야하는데환자들의입원기간이다르기때문에불가능. 감염빈도로비교하기어렵다. HAI frequency는 incidence 를사용한다.

조사기간중새로발생한감염환자수조사시작시감염이없고위험이있는총환자수

누적빈도 =

(Cumulative incidence, risk)

조사기간중새로발생한감염환자수조사기간중위험이있는총환자-일수

빈도 =

(Incidence, Incidence rate)

발병률과유병률의계산

• 조사기간발생률=

• 조사시점유병률=

유병률조사

UTI

UTI

PNEU

PNEU

PNEU

UTI

UTI

11.1 11.306건의감염발생

조사기간위험에노출된환자수

2건의감염

조사시점전체환자수

• 분모를감염발생감시기간동안위험에노출된환자의환자일수(조사기간중대상병동에입원한모든환자의재원일수를더한것)나연삽입기구일(device-days)로계산하는것. 보통 1개월단위로사용

• Patient-days infection rate =No. of Nosocomial Infections(at all sites)

No. patient-days

Device-days infection rate = No. of device-associated infections for a site

No. of device-days

HAI frequency by incidence

x 1,000

x 1,000

Surveillance artifact

• Introduction of new infection definitions

• New Infection control practitioner

• Initiation of surveillance in new areas or population of patients

• Introduction of new laboratory tests

• Introduction of new population of patients

• Increased or decreased frequency of culturing/testing of patients

• Introduction of new medical procedure (e.g. endoscopy, cardiac surgery)

Updated CDC/NHSN definitions of UTI

Definition of nosocomial infection• Urinary tract infections

Press MJ et al. ICHE

2013; 34

Impact of the Change in Surveillance Definitions on the

Rates of Urinary Tract Infection in Intensive Care Units: 1988

versus 2009 Definitions (Choi et al. IHCE 2012)

When we applied the revised NHSN definitions of UTI, the rates of UTI in the ICU

decreased 55.1%. Removal of ASB was responsible for this change. No patient

had ABUTI, suggesting that ABUTI is not useful for UTI surveillance.

혈액종양병동 invasive aspergillosis

• Proven & probable IA by EORTC criteria: Clinical & radiological criteria + 1개이상의 mycological criteria• Mycological criteria

• Direct: 병리또는배양양성

• Indirect: Galactomannan Ag ( No PCR)

• 배양결과 – 2007년 vs. 2008년 IA 율차이없음

• 2008년 12개월동안mycological evidence

• Aspergillus 배양양성 4명, 모두객담 – 2명만EORTC기준만족, 민감도, 특이도낮다.

• Aspergillus Ag 양성: 혈액, 35명 101검체 – 배양양성자 3명포함(이중 2명이EORTC기준만족한 case)

• Aspergillus Ag 양성을EORTC 기준으로했을때proven & probable IA 훨씬증가

0

1

2

3

4

5

6

7

1 2 3 4 5 6 7 8 9 10 11 12

Month

No. of cases

(Aspergillus Ag

positive)

Outbreak?

혈액종양병동 invasive aspergillosis

Endemic을 Epidemic 과감별

• Endemic과 Epidemic 을감별할수있는하나의기준은없다. • Quick and dirty analysis: numerator, denominator data 를정확히정의할수없을때 epidemic이있는지와역학조사를시작할것인지결정하기위해실시• Numerator data 는믿을만한데 denominator data 가불분명할때 –환자수나환자일수등을사용

• Prospective surveillance with specified threshold – low sensitivity, unreliable, but useful to initiate investigation

• Comparison with benchmark HAI rate – NNIS, KONIS data• 감염율이너무높지않은지비교 – high endemic rate or epidemic• Benchmark 없는 population 이너무많아서제한점

• Benchmark가모든 risk factor를조절하기어려워서자체기저율감시자료없이비교하는데제한점

역학조사를실시할시점

• 역학조사를할것인가? > 역학조사의수준과범위

• Cluster가 epidemic성격인가?• Rare pathogen의군집이라면유행이명확예) MERS

• Morbidity와 mortality는? • Ebola vs. MERS• MERS vs. 건국대원인불명폐렴

• 인력적인문제 –동원할수있는수와능력• 병원내인력을비상동원

• 병원내가용인력이없는경우아웃소싱 : 1,2차의료기관, 요양병원• 공공보건기구의지원: 시도보건환경연구원, 질병관리본부 – public health에미치는영향에따라예) MERS

• 민간 NGO의지원: 대한의료관련감염관리학회중소병원자문기구

• 사설기구: 국내에는없다.

• 역학조사의범위와수준을감당할수있는지조사전에반드시파악 –역학조사와검사실적조사병행하는경우

역학조사의수행

• 조사할대상을확보: 언제나첫번째해야할일

• Source, pathogen, host, mode of transmission 을규명

• 초기 case review• Line listing

• Case definition

• Case ascertainment

• Epidemic curve 작성

• 지형적인분포분석

• 숙주요인

• Case definition 재조정, 심층조사로이행할지재평가

역학조사의수준과범위

• 재평가단계에서감염원과전파경로를어느정도규명해서중재를할수있는지, 시간, 인력, 비용등고려해서다음단계결정

• Comprehensive Investigation

• Comparative epidemiologic study

• Observational study

• Culture survey

• Typing of the outbreak strain

Line listing

Fig. Summary of

epidemiologic

characteristics of

patients with MERS at

Pyeongtaek St. Mary’s

Hospital, Korea.

(Kim KM et al. Epidemiol

Health 2015; 37:

e2015041.)

Epicurve of 2015 MERS-CoV outbreak in

P hospital

Kim KM et al. Epidemiol Health 2015; 37: e2015041.

Layout of the ward where the index case patient with severe acute respiratory syndrome (SARS)

was hospitalized, showing the location of beds, air supply diffusers, and exhaust grilles.

Ignatius T. S. Yu et al. Clin Infect Dis. 2005;40:1237-1243

© 2005 by the Infectious Diseases Society of America

The temporal-

spatial spread of

SARS in the ward

was consistent with

airborne

transmission, as

modeled by use of

computational fluid

dynamics. Infected

health care workers

likely acted as

secondary sources

in the latter phase

of the outbreak.

Non-comparative epidemiologic studies

• Case report/case series• Function to generate hyopthesis

• No comparison group: 조사대상감염환자의 unique 특성모름

• Ecological study• 지역또는시간에따른위험인자변화비교

예) 카바페넴사용량변화 vs. 카바페넴내성대장균

• Quick and easy, 초기가설검증에이용, 여러가설검증못함.

• 환자자료는포함하지않음; 카바페넴치료받은환자에서카바페넴내성대장균감염발생은파악못함.

• Cross sectional study• 한시점에서위험요인이있는환자와감염자파악

예) 일시점에서모든입원환자대상으로카바페넴사용여부와

카바페넴내성대장균감염여부파악

• 시간개념이없어서위험요인노출과감염의전후관계모름

Comparative epidemiologic studies

• Case-control study• 감염유무에따라선정

• 후향적• 드문감염에선호• 빈도, RR계산못함

• Cohort studies• 위험노출유무로대상선정• 후향적/전향적• 한요인에여러가지

outcome분석가능• 추적중 drop out

• Experimental-

randomized

controlled trial• 노출무작위배정• Causality규명에최선

• Ethical issue: Quasi-

experimental design

To investigate association between a risk

factor (or exposure) and an infection

Measurement of effect

Measures of strength of association

• P value

• <0.05: 연구결과가우연히일어날확률이매우희박하다.

• 샘플사이즈크면임상적으로유의하지않은차이도통게적으로유의하게나올수있고반대의경우도.

• 95% confidence interval (95% 신뢰구간)

• P value 보완

• RR, OR의 95% CI

• 1을포함하면 p value<0.05 이기는거의불가능

Bias

• Bias• Systematic error: nondifferential or differential

예) nondifferential: bias가 null hypothesis 지향하면비교그룹간차

이가없어보인다.• Information bias/selection bias

예) recall bias –감염자가항균제사용기억력강하다.

• Confounding • Confounder: variable associated with both exposure and outcome

• 감염이심각할때카바페넴쓸가능성높다. 카바페넴내성균의치명률이높게나온다.

• 연구자가조절할수있다.

Quasi experimental study design

• Before-after = pre-post intervention study

• Randomization 하지않고 intervention 효과판정

• 감염관리연구에많이사용