GARISPANDUAN

PELAKSANAAN PROSES NOTIFIKASI DAN PENGURUSAN

“CARBAPENEM RESISTANT ENTEROBACTERIACEAE” (CRE)

DI HOSPITAL-HOSPITAL KEMENTERIAN KESIHATAN

EDISI KETIGA

Disediakan oleh Bahagian Perkembangan Perubatan - Mei 2013

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 PELAKSANAAN PROSES NOTIFIKASI DAN PENGURUSAN

“CARBAPENEM RESISTANT ENTEROBACTERIACEAE” (CRE)

DI HOSPITAL-HOSPITAL KEMENTERIAN KESIHATAN

TUJUAN

1. Tujuan garispanduan ini dikeluarkan adalah untuk;

1.1 Memaklumkan mengenai pelaksanaan proses notifikasi CRE dan

langkah-langkah bagi memperkukuhkan pengendalian dan rawatan kes-
kes ini di hospital Kementerian Kesihatan.

1.2 Menggariskan tindakan yang perlu di ambil oleh semua jabatan dalam
pengendalian kes-kes CRE bagi memastikan usaha-usaha pencegahan
dan kawalan hospital dilaksanakan dengan segera dan berkesan.

PENGENALAN

2. Survelans epidemiologi global menunjukkan peningkatan kekebalan

antibiotik terhadap Enterobacteriaceae bacteria, seperti Escherichia coli dan
Klebsiella pneumoniae yang merupakan flora normal di usus.
Walaubagaimana pun,bakteria ini kerap mengakibatkan infeksi saluran
urinari, saluran darah dan jangkitan bawaan hospital. Carbapenems
(imipenem, meropenem, ertapenem dan doripenem) merupakan antibiotik
yang digunakan untuk rawatan jangkitan yang disebabkan oleh bakteria
gram-negatif yang telah rintang terhadap pelbagai jenis antibiotik. Jangkitan
yang disebabkan oleh bakteria yang rintang kepada carbapenem adalah sukar
untuk dirawat dan perlu dikawal daripada merebak.

3. Kerintangan carbapenem di kalangan bakteria Enterobacteriacea boleh

disebabkan oleh kombinasi ESBL atau AmpC, dengan kehilangan ‘porin’ di

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 permukaan bakteria yang menyebabkan ketaktelapan (impermeability).
Mekanisma kerintangan ini tidak stabil dan bakteria tersebut jarang merebak.
Yang menjadi kebimbangan sekarang ialah kerintangan carbepenem yang
berlaku apabila bakteria Enterobacteriaceae memperolehi gen-gen yang
rintang terhadap carbapenem seperti gen NDM, IMP, VIM, KPC dan OXA-48.
Bakteria yang memperolehi salah satu gen tersebut akan mengeluarkan
enzim ‘carbapenemase’ iaitu enzim yang memusnahkan antibiotik
carbapenems, cephalosporins dan hampir seluruh antibiotik beta-lactams.

4. Bakteria yang mengeluarkan enzim ‘carbapenemase’ ini dipanggil

‘carbapenemase-producing Enterobacteriaceae’ dan di dalam garispanduan
ini dirujuk sebagai carbapenem-resistant Enterobacteriaceae (CRE). Implikasi
serius bakteria yang mengeluarkan carbapenemase ini ialah keupayaan
menyebarkan gen rintang antibiotik dikalangan bakteria dari spesis lain.
Setakat ini gen NDM-1 merupakan penyebab utama dalam kes-kes CRE di
Malaysia. Oleh yang demikian, pengenalpastian bakteria dan kawalan infeksi
serta pengawalan penggunaan antibiotik sangat penting untuk menghalang
penyebaran bakteria tersebut.

5. Garispanduan ini dikeluarkan bagi menggariskan tindakan yang perlu

dimulakan dengan segera apabila kes CRE dikesan dan disahkan secara
mikrobiologikal. Pengesanan dan intervensi awal adalah penting untuk
mencegah kejadian wabak.

PELAKSANAAN PROSES NOTIFIKASI DAN PENGURUSAN KES CRE

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6. Secara keseluruhannya, proses notifikasi dan pengurusan CRE melibatkan
tiga langkah utama;

6.1 Pengesanan Kes

Makmal di setiap hospital akan menjalankan ujian saringan CRE pada setiap isolat
yang diterima. Tatacara pemilihan ujian dan pengesahan oleh makmal adalah
mengikut carta alir pada Laboratory Detection of Carbapenem Resistant
Enterobacteriaceae seperti di Lampiran I.

6.2 Pengurusan Kes yang disyaki

Pengurusan kes yang disyaki adalah mengikut carta alir Carbapenem Resistant
Enterobactericeae (CRE) Management seperti di Lampiran II. Jika terdapat kes
CRE yang disyaki oleh makmal, Pakar Klinikal Mikrobiologi atau pegawai sains
(mikrobiologi) perlu memaklumkannya kepada Pakar Klinikal yang merawat
pesakit dan Pengerusi Kawalan Infeksi Hospital dengan segera agar langkah
pencegahan dan kawalan infeksi dapat dimulakan.

Seterusnya, Pakar yang merawat pesakit bertanggungjawab untuk melengkapkan

Carbapenem Resistant Enterobacteriaceae Investigation Form
(CRE/MOH/2013) seperti di Lampiran III. Pengerusi Jawatankuasa Kawalan
Infeksi Hospital perlu memastikan borang penyiasatan tersebut dilengkapkan.

Borang Penyiasatan CRE yang telah lengkap perlu di hantar melalui Pengerusi
Kawalan Infeksi Hospital atau Pengarah Hospital kepada Unit Kawalan Infeksi,
Cawangan Kualiti Penjagaan Perubatan, Bahagian Perkembangan Perubatan, dan
salinan perlu dihantar kepada Pengerusi Kawalan Infeksi Negeri. Borang
Penyiasatan CRE hendaklah dihantar dalam masa sebulan selepas kes CRE
dikesan.

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 6.3 Strategi Kawalan Infeksi

Pada masa yang sama langkah-langkah pencegahan dan kawalan infeksi yang
dikhususkan bagi pesakit dan kontak perlu dijalankan oleh anggota kesihatan di
wad mengikut Infection Control Strategies to Reduce CRE Transmission
seperti di Lampiran IV.
Proses dan prosedur bagi penyaringan kontak perlulah mengikut carta alir
Protocol for Screening of Close Contacts of CRE Patients yang di tunjukkan di
Lampiran V.

KESIMPULAN

7. Perlaksanaan pekeliling ini memerlukan kerjasama dan sokongan yang

mantap dari semua anggota kesihatan di hospital bermula dengan
komunikasi segera dari Pakar Mikrobiologi Klinikal atau pegawai sains
mikrobiologi yang mengesyaki kes, menjalankan langkah-langkah
pencegahan dan kawalan di wad oleh Pakar Klinikal dan unit kawalan infeksi
sehingga perawatan pesakit selesai.

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8. SENARAI LAMPIRAN

Lampiran I Laboratory Detection of Carbapenem Resistant

Enterobacteriaceae
Lampiran II Carbapenem Resistant Enterobacteriaceae (CRE) Management
Lampiran III Carbapenem Resistant Enterobacteriaceae Investigation Form
(CRE/MOH/2013)

Lampiran IV Infection Control Strategies to Reduce CRE Transmission

Lampiran V Protocol for Screening of Close Contacts of CRE Patients

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 Lampiran I

Laboratory Detection of Carbapenem Resistant Enterobacteriaceae

Enterobacteriaceae Detection

Enterobacteriaceae

Nonsusceptibility (I/R) to one of the

following carbapenems: imipenem,
meropenem, ertapenem
(refer exclusion*)
AND
Resistant to all ceftriaxone,
cefotaxime, ceftazidime
(by disc diffusion)**
1. Immediately inform treating
specialist and infection control
Probable CRE chairman for local control and
investigation
2. Send isolate (s) to IMR for
antibiotic resistance verification
and molecular detection of
carbapenemase genes including
NDM

Modified Hodge Test MIC of carbapenem

(E-Test)

Negative Positive

Non-carbapenemase producers - Carbapenemase producing

resistance most commonly due to Enterobacteriaceae (referred to as
combinations of ESBL or AmpC and CRE in this guideline)
porin loss

Notify MOH
(CRE/MOH/2013 Form)
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*Exclusion:
1. Proteae (e.g Proteus/Providencia/Morganella) which showed resistance to imipenem
only; these species have inherently low susceptibility to imipenem. This is not considered
CRE. Do not send such isolates to IMR.

2. Enterobacter spp., with cephalosporin and low level ertapenem but susceptible to
imipenem and meropenem – these generally have combinations of AmpC beta-lactamase
and impermeability and not due to carbapenemase production. Do not send such isolates to
IMR.

3. However, if the above strains show resistance to all tested carbapenem (imipenem/
meropenem/ ertapenem) they must be sent to IMR.

** Oxa-48-type carbapenemasehydrolysepenicillins at a high level and carbapenems at a low level,

sparing broad-spectrum cephalosporins and are not susceptible to β-lactamase inhibitors (Ref:
Poirel L et al Journal of Antimicrobial Chemotherapy 2012).

Table 1: The zone diameters and MIC interpretive criteria for cephlosporins and carbepenem
Antibiotic Zone of inhibition (mm) MIC (ug/mL)
Disk Diffusion method
S I R S I R
Cephalosporins
Ceftriaxone, 30 µg 23 20-22 19 1 2 4
Cefotaxime, 30 µg 26 23-25 22 1 2 4
Ceftazidime, 30 µg 21 18-20 17 4 8 16
Carbapenems
Ertapenem 10 µg 22 19-21 18 0.5 1 2
Meropenem 10 µg 23 20-22 19 1 2 4
Imipenem 10 µg 23 20-22 19 1 2 4
Reference: CLSI 2013, page 44-61.
These zone diameters and MIC interpretive criteria are subject to change; please refer to the
latest edition of CLSI for future references.

CRE is suspected when there is nonsusceptibility (intermediate or resistant) to either of the

carbapenems by disc diffusion test (CLSI). The laboratory shall use ertapenem, meropenem and
imipenem discs for the above test for all Enterobacteriaceae.

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The laboratory shall carry out the following steps:

1. The Clinical microbiologist/ Microbiologist/ Scientific officer shall inform the Clinical Specialist
and HOSPITAL Infection Control CHAIRMAN of a suspected CRE IMMEDIATELY. They should
also inform State Infection Control Chairman through SMS.

2. Hospital should send all pure isolates with resistant/intermediate to any one of the
carbapenem by disc diffusion/MIC on blood agar or nutrient slant agar to IMR for antibiotic
resistance verification and detection of carbapenemase genes by PCR. The accompanying
laboratory request form shall indicate “Carbapenemase gene detection” and to indicate
whether clinical case specimen or screening for contact specimen.

3. IMR shall notify all positive isolates to Clinical Microbiologist/ Microbiologist/ Scientific officer
by phone, followed by hard copy of the results (Lab TAT 1-2 working days).

4. The Clinical Microbiologist/ Microbiologist/ Scientific officer will inform the final result to the
treating specialist and the Hospital Infection Control Chairman immediately.

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 Lampiran II

Carbapenem Resistant Enterobactericeae (CRE) Management

SUSPECTED CRE

Clinical
Microbiologist/
Science Officer

Laboratory diagnosis Inform Treating Specialist and

Hospital Infection Control
(Refer Appendix I)
Chairman

Send specimen to IMR Implementation of Treating specialist to complete

for verification & Infection Control and submit the CRE Investigation
molecular detection Precautions Form (CRE/MOH/2013) to
of carbapenemase Hospital Infection Control
(Refer Appendix IV)
genes including NDM Chairman upon confirmation

Hospital Infection Control

negative positive
Chairman to forward CRE
Investigation Form to
Infection Control Unit,
Medical Development
Division within 1 month

Data Management

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 Lampiran III

Carbapenem Resistant Enterobacteriaceae Investigation Form

(CRE/MOH/2013)

case
contact screening

A. CASE IDENTIFICATION DATA

Name :_____________________________ I/C or Passport No: ______________________

RN : _______________________________ Age: _____

Gender : Male/ Female Status: In-patient /out- patient

Hospital/Clinic : ____________________________ Department : ______________________

Ward:________________________

Date of admission /consultation: ________________ Date of discharge : __________________

B. CLINICAL DATA
i. Current working diagnosis

ii. Is it epidemiologically linked (contact) to confirmed case of CRE : Yes/No

iii. Previous contact with healthcare facilities in Malaysia (last 30 days) : Yes/No (If Yes fill in table below)

Date of visit / Healthcare facilities Reason for visit /hospitalization

admission & discharge

CRE – Carbapenem Resistant Enterobacteriaceae ( inclusive of NDM )

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iv. General predisposing risk factors [ √ where appropriate ]

1. Underlying disease
(Diabetes Mellitus/ Malignancy/ ESRF)

2. Immunosuppressive therapy

3. Prolonged hospitalization > 2/52

4. Prematurity / Low Birth Weight

5. Others

(Specify : ……………….………………………………)

v. Type of devices present in the last 30 days prior to CRE isolation [ √ where appropriate ]

1. Indwelling urinary
catheter

2. Mechanical
ventilator

3.
Tracheostomy

4. Central venous catheter

5. Arterial
Lines

6. Peripheral venous
line

7. Other drainage catheters

iv. Antibiotic exposure in the last 30 days prior to CRE isolation

Duration ( √ where appropriate )

No Name and Group of Antibiotic
. Less than 3 days 3 to 7 days More than 7 days

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C. MICROBIOLOGICAL DATA (attach copy of result)

Date of specimen Organism with positive CRE NDM (Yes/No) Type of specimen
collection

D. OUTCOME DATA

Clinical outcome data at 1 month

Status: Clinically significant - proceed to (a) & (b)

Colonization

(a) Infection diagnosis

UTI Pneumonia SSI SSTI BSI

Intra-abdominal infection Others _________________________

(b) Clinical Outcome: Alive

Died Cause of death : ______________________________

Death related to CRE? : Yes No

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 Reported by: Verified by:

Signature of Reporting Specialist: Signature of HIACC chairman:

Name and Designation: Name and designation:

Date: Date:

Lampiran IV

Infection Control Strategies to Reduce CRE Transmission

Suspected
CRE

Microbiologist/scientific
officer to inform
treating/ward specialist and
Infection Control Chairman
immediately

CRE Patient Hospital Contact (other patients)

1. Isolate patient with strict contact precautions
2. Reinforce infection control practices within the
unit
3. Treatment is required only if clinically significant
4. Chlorhexidine 2% bath to all affected patients
5. Preferably continue contact precautions until
discharged.
6. Effective enhanced and terminal cleaning
including of high contact and sanitary areas
7. Currently there is no recommended
decolonization strategy for affected patients.
8. Affected patients must be tagged in BHT and
follow up card so that contact precautions are
instituted during revisits/readmissions.
9. All follow ups must be in pre determined health
care facility.
1. Screen close contacts (within the same
cubicle or ward*) once
2. Screening protocol: Rectal swab, wound
swabs (if open wounds), urine (if on CBD),
tracheal aspirate (for ventilated patients)
3. Institute contact precautions for the contacts
until screened negative.
4. If possible, restrict the movement of the
close contacts, until the contacts are screened
negative. If not possible, keep track of contacts’
movements.
* Decision to screen only the cubicle or the
whole ward has to be taken at the local level
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There is no indication for screening health care
workers and house hold contacts
 Lampiran V

Protocol for Screening of Close Contacts of CRE Patients

Index Patient

NO
Discharge Screen all patients in the
d? cubicle/ ward*

YES

Identify high risk contacts# during exposure

period (from date of positive sampling to
date of discharge)

Screening Protocol:

NO - Rectal Swab
Contacts - Wound Swab
- Urine C &S If On CBD
Discharge
- Tracheal Aspirate (For
d??d?
Ventilated Patients)
YES

If they are readmitted, isolate To trace high risk patients

them until they are screened for screening with help
negative@. 14 from JKA/PKD
Notes:

* Decision to screen only the cubicle or the whole ward has to be taken at the local level
depending on the risk of transmission.

# High risk contacts will include patients with open wounds or on CBD, or having
tracheostomy.

@ In order not to miss these patients at the time of readmission, a name list of these high
risk contacts has to be distributed to the Emergency Department and clinics. Also where
feasible, these patients’ note has to be tagged either electronically or manually.

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