INVESTIGASI KASUS INFEKSI ALIRAN DARAH DI NICU

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INVESTIGASI KASUS

INFEKSI ALIRAN

DARAH DI NICU

Divisi Neonatologi

FKUI-RSCM

Dr Lily Rundjan SpA(K)

Dr Christopher Khorazon

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Pendahuluan

Tujuan utama investigasi kasus infeksi

aliran darah adalah menemukan

sumber infeksi secara efektif dan

terfokus sehingga tata laksana

tepat sasaran dan tepat guna

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Pembahasan

• _{Definisi IAD}

• _{Pembagian IAD}

• _{Kolonisasi VS Infeksi}

• _{Perkiraan organisme penyebab}

• _Investigasi

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INFEKSI ALIRAN DARAH (IAD)

Definisi IAD:

Infeksi akibat pemasangan kateter intravena, setelah > 48 jam terpasang kateter intravena

Positif IAD secara laboratorik

ü

Hasil kultur darah (+) dari 2 tempat berbeda dalam waktu bersamaan ditemukan

mikroorganisme yang sama

ü

Hasil kultur darah 2x berturut-turut pada waktu berbeda ditemukan mikroorganisme yang

sama

ü

Hasil kultur jalur sentral dan perifer ditemukan mikroorganisme yang sama

CRBSI (Catheter Related Blood Stream Infection)

• Pemasangan kateter perifer / sentral sebelum terjadinya IAD

CLABSI (Central Line Associated Blood Stream Infection)

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BSI

Primary BSI

Secondary BSI

Infeksi aliran darah (terbukti secara laboratorik) bukan berasal dari organ lain

Infeksi dari organ lain menyebar ke aliran darah

o VAP o SSI o ISK o Gastrointestinal o Skin infection o Conjunctivitis

PEMBAGIAN INFEKSI ALIRAN DARAH

Catheter related : peripheral / central line

VAP (Ventilator Associated Pneumonia) SSI (Surgical Site Infection)

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KOLONISASI VS INFEKSI

Kolonisasi

• Mikroorganisme ditemukan di tubuh bayi tanpa

gejala klinis

• Bayi sehat saat lahir terkolonisasi oleh mikroflora

endogen dari vagina dan flora usus ibu (transmisi vertikal)

• Bayi yang dirawat lama di RS mempunyai risiko tinggi

terkolonisasi oleh multidrug-resistant Gram-negative

bacteria (MDRGN) di tubuh atau usus bayi

Infeksi

• Gejala klinis sepsis (+), ditunjang oleh septic marker

dan kultur darah

• Concordant BSI : kolonisasi berat mikroorganisme

penyebab mendahului infeksi invasif

• Translokasi mikroorganisme dari saluran cerna ke

aliran darah melalui dinding usus yang cedera

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MODE OF TRANSMISSIONS

Patient to patient transmissions Droplet transmissions Airborne transmissions Contact transmissions

Horizontal transmissions via healthcare staff’s hands à most frequently reported Colonization Infection Risk factors Sources / Reservoirs of infections Transplacental / Vertical transmissions

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Extrinsic Intrinsic

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Transmisi

Infeksi

HORISONTAL Lingkungan Staph aureus (MRSA, MSSA) Staph epidermidis CONS Klebsiella Pseudomonas Proteus Enterobacter Serratia CMV Rotavirus Rhinovirus RSV Fungal VERTIKAL TORCHES Syphilis HIV Hepatitis Varicella Parvovirus TB Gonorrhea Malaria Lyme GBS E. Coli Listeria Anaerobes Enterococcus Chlamydia Gonorrhea Ureaplasma Mycoplasma Hepatitis HIV HSV HPV Adenovirus Coxsakie virus (Par)Echo/Enterovirus Polio virus Candida

Awitan dini (0-72 jam)

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Investigasi

• Investigasi dikerjakan berdasarkan faktor risiko bayi,

organ target yang terlibat dan peta pola kuman RS

• Metoda transmisi infeksi : transplasental / vertikal,

horisontal

• Mikroorganisme penyebab pikirkan bakteri/virus/jamur

• Investigasi : kultur darah, kultur urin, kultur LCS, USG

abdomen / ginjal, bone survey, ekokardiografi, X Ray, dll

• Investigasi tambahan : kultur rektal/kulit, kultur ujung

kateter, ujung ETT (kolonisasi), kultur cairan infus

Th is P h o tob y Un kn o wn Au th o r is licen sed u n d er C C B Y

o VAP o SSI o ISK o Gastrointestinal o Skin infection o Conjunctivitis

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Sepsis Awitan Dini VS Lambat

Sepsis awitan dini

Faktor risiko ibu

q Korioamnionitis

q KPD > 18 jam

q Persalinan prematur

q Ibu demam, janin takikardi

q Ibu gejala gastroenteritis atau flu-like illness

q Serologi ibu, riwayat infeksi ibu

Gold standard : kultur darah

Pendukung (bila kultur darah negatif)

q Swab/kultur dan PA plasenta

q Kultur cairan OGT (kolonisasi)

q Swab kulit belakang telinga (kolonisasi)

Sepsis awitan lambat

Faktor risiko intrinsik (bayi)

o Kateter intravaskular: perifer dan sentral

o ETT

o Orogastric tube

o Kateter urin

o Chest drain, drain intraabdominal

o Post surgery

Faktor risiko ekstrinsik (lingkungan)

o Keluarga yang sakit – viral infection

o Infeksi dari bayi lain

o Gastrointestinal: diare

o Urine, ASI, transfusi darah – CMV

postnatal

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Rekomendasi jumlah darah untuk kultur darah

Blood cultures contaminated with skin flora during collec-tion are common, but contaminacollec-tion rates should not exceed 3%. Laboratories should have policies and procedures for ab-breviating the work-up and reporting of common blood culture contaminants (eg, coagulase-negative staphylococci, viridans group streptococci, diphtheroids, Bacillus species other than B. anthracis). These procedures may include abbreviated identifi-cation of the organism, absence of susceptibility testing, and a comment that instructs the clinician to contact the laboratory if the culture result is thought to be clinically significant and re-quires additional work-up and susceptibility results.

Physicians should expect to be called and notified by the lab-oratory every time a blood culture becomes positive because these specimens often represent life-threatening infections. If the physician wishes not to be notified during specific times, ar-rangements must be made by the physician for a delegated healthcare professional to receive the call and relay the report.

Key points for the laboratory diagnosis of bacteremia/funge-mia:

• Volume of blood collected, not timing, is most critical. • Disinfect the venipuncture site with chlorhexidine or 2% iodine tincture in adults and children >2 months old (chlorhex-idine NOT recommended for children <2 months old).

• Draw blood for culture before initiating antimicrobial therapy.

• Catheter-drawn blood cultures have a higher risk of con-tamination (false positives).

• Do not submit catheter tips for culture without an ac-companying blood culture obtained by venipuncture.

• Never refrigerate blood prior to incubation.

• Use a 2–3 bottle blood culture set for adults, at least one aerobic and one anaerobic; use 1–2 aerobic bottles for children.

• Streptococcus pneumoniae and some other gram-positive organisms may grow best in the anaerobic bottle.

B. Infections Associated With Vascular Catheters

The diagnosis of catheter-associated BSIs often is one of exclu-sion, and a microbiologic gold standard for diagnosis does not exist. Although a number of different microbiologic methods have been described, the available data do not allow ﬁrm con-clusions to be made about the relative merits of these various diagnostic techniques [8, 9]. Fundamental to the diagnosis of catheter-associated BSI is documentation of bacteremia. The clinical signiﬁcance of a positive culture from an indwelling catheter segment or tip in the absence of positive blood cultures is unknown. The next essential diagnostic component is dem-onstrating that the infection is caused by the catheter. This usually requires exclusion of other potential primary foci for the BSI.

Numerous diagnostic techniques for catheter cultures have been described and may provide adjunctive evidence of cathe-ter-associated BSI; however, all have potential pitfalls that make interpretation of results problematic. Routine culture of intrave-nous (IV) catheter tips at the time of catheter removal has no clinical value and should not be done [10]. Although not per-formed in most laboratories, the methods described include the following:

• Time to positivity (not performed routinely in most labo-ratories): Standard blood cultures (BCs) obtained at the same time, one from the catheter or port and one from peripheral ve-nipuncture, processed in a continuous-monitoring blood culture system. If both BCs grow the same organism and the BC drawn from the device becomes positive more than 2 hours before the BC drawn by venipuncture, there is a high probabili-ty of catheter-associated BSI [11].

• Quantitative BCs (not performed routinely in most labora-tories): one from catheter or port and one from peripheral veni-puncture obtained at the same time using lysis-centrifugation (Isolator) or pour plate method. If both BCs grow the same or-ganism and the BC drawn from the device has 5-fold more

Table I-1a. Recommended Volumes of Blood for Culture in Pediatric Patients (Blood Culture Set May Use Only 1 Bottle)

Weight of Patient (kg)

Total Patient Blood Volume (mL)

Recommended Volume of Blood for Culture (mL)

Total Volume for Culture (mL) % of Total Blood Volume Culture Set No. 1 Culture Set No. 2 ≤1 50–99 2 . . . 2 4 1.1–2 100–200 2 2 4 4 2.1–12.7 >200 4 2 6 3 12.8–36.3 >800 10 10 20 2.5 >36.3 >2200 20–30 20–30 40–60 1.8–2.7

When 10 mL of blood or less is collected, it should be inoculated into a single aerobic blood culture bottle.

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CID

•

Baron et al

at IDSA member on July 11, 2013

http://cid.oxfordjournals.org/

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page 13

Mermel LA, et al. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection. Infectious Diseases Society of America. 2009

Methods for the diagnosis of acute fever for a suspected short-term CVC infection or arterial cathether infection.

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page 14

Mermel LA, et al. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection. Infectious Diseases Society of America. 2009

Approach to the management of patients with short-term CVC-related or arterial catheter-related bloodstream infection.

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page 15

Mermel LA, et al. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection. Infectious Diseases Society of America. 2009

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Mermel, et al 2009

Kultur darah untuk S. aureus,

Coagulase-negative Staphylococci,

atau Candida species + tidak ada sumber infeksi lain yang terdeteksià kecurigaan CRBSI meningkat

Perbaikan gejala dalam 24 jam setelah pencabutan kateter menandakan

(tetapi tidak memastikan) bahwa kateter merupakan sumber infeksi.

Coating antimicrobial dapat

memberikan hasil false negative

Organisme Penyebab Tersering CRBSI

Kateter percutaneous Kateter surgically

implanted & CVC perifer

Coagulase-negative

Staphylococci Coagulase-negative Staphylococci

S. aureus Enteric gram-negative

bacilli

Candida species S. aureus

Enteric gram-negative

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Catheter related BSI

• _{Pada kecurigaan CRBSI à kultur darah perifer dan akses sentral}

• Kultur ujung kateter tidak rutin dikerjakan – menunjukkan kolonisasi,

bermakna bila kultur darah positif dengan kuman yang sama

• _{Eksudat dari tempat insersi à swab, kultur dan gram}

• Setiap kali mengganti antibiotik harus kultur darah

• Pasien yang diobati tanpa pencabutan kateter harus dipantau dengan

evaluasi klinis dan kultur darah ulang. Apabila terjadi perburukan

klinis atau CRBSI persisten à harus segera cabut kateter

Mermel LA, et al. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection. Infectious Diseases Society of America. 2009

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Coagulase-negative Staphylococcus species

• Investigasi CONS à perhatikan ada kateter / benda asing lainnya

• Kultur darah ulang perlu diambil dari 2 tempat : kateter sentral dan perifer

sebelum pemberian antibiotik atau pencabutan kateter.

• Bila infeksi CONS persisten, investigasi ke arah :

• Septic emboli

à

angiogram, MRI

• Endocarditis à transesophageal echocardiograph (TEE) 5-7 hari setelah

onset bakteremia untuk meminimalisir kemungkinan hasil false-negative.

TEE ulang dilakukan apabila pasien memiliki demam atau IAD > 72 jam

setelah pencabutan kateter

• Abses à USG abdomen, kepala

• Management

• Cabut kateter à pemasangan kateter baru dapat dilakukan ketika kultur

darah berikutnya bersih

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MRSA

• MRSA (susah eradikasinya) - Staph aureus CRBSI mempunyai

risiko tinggi

hematogen

à

bila MRSA persisten investigasi ke

arah:

• Infective endocarditis, vegetation

• Bone scan – septic artritis

• Soft tissue

• Paru

Mermel LA, et al. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection. Infectious Diseases Society of America. 2009

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Enterococcus CRBSI

• Enterococcus CRBSI – investigasi ke arah:

• New murmur or embolic phenomena – endocarditis (low

risk)

• Septic pulmonary emboli

à

pulmonary angiography

• Bila bakteremia persisten (>72 jam setelah inisiasi terapi

antibiotik) à ulang kultur darah dan pencabutan kateter

Mermel LA, et al. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection. Infectious Diseases Society of America. 2009

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Gram negative CRBSI

• Enterobacter (saluran cerna): E.coli, Serratia sp, Klebsiella sp

• Non fermenter (host bukan manusia, ada di lingkungan): Acinetobacter,

Pseudomonas, Burkholderia cepacia, Stenotropomonas, Citrobacter freundii

• Pada pasien dengan CRBSI gram-negative yang menyangkut pemakaian

kateter jangka panjang dan bakteremia persisten atau sepsis berat à kateter

harus dicabut, investigasi endokarditis dan organ lain

• Bayi dengan short-gut syndrome lebih rentan terhadap CRBSI akibat bacilli

gram-negative.

• MDR gram negative bacili yang memproduksi biofilm: A.baumannii,

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Bayi UG 38 minggu, BL 3740 g

Usia 5 hari:

• Suhu 39o_{C, distensi abdomen, letargis}

• Abdominal + Chest X-ray: normal

• Hasil lab: Leukosit 13,5 x 109_/L (86%

segmenter)

• Antibiotik: IV Amoksisilin + seftazidim

Usia 9 hari:

• Perburukan kondisi dan kultur darah

negatif

• Eritromisin dan asiklovir diberikan untuk

patogen atipikal dan HSV

Usia 10 hari:

• Masuk ke NICU à intubasi karena gagal

nafas

• Paru: terdengar krepitasi bilateral; x-ray

menunjukkan infiltrat bilateral dan efusi pleura

• CRP 91 mg/L, leukosit normal

• Nasofaringeal swab à Adenovirus type 7

• Kultur darah dan aspirasi bronkial tetap

negatif

• Diagnosis: severe Adenovirus pneumonia

• Terapi: gamma-globulin single dose (300

mg/kg); terapi antibiotik dihentikan

Usia 14 hari: Perbaikan gejala

Usia 29 hari: Ekstubasi

Usia 58 hari : Pasien dipulangkan

Persalinan per vaginam, Nilai Apgar 9/9, pulang ke rumah hari ke2

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Bayi UG 38 minggu, BL 3740 g

• Sampel feses dari kakak pasien (usia 2 tahun) terdapat adenovirus 7

à

kemungkinan terjadi cross-infection

• Titer antibodi bayi

• Usia 10 hari= 1:128

• Usia 17 hari= 1:1024

• Titer antibodi ibu

• Saat bayi usia 16 hari= 1:2048

Kemungkinan ibu terinfeksi adenovirus saat persalinan, karena apabila ibu terinfeksi lebih awal, antibodi titer

bayi saat awal akan lebih tinggi.

PENTING

Adenovirus tipe 7 penyebab pneumonia berat, metoda transmisi aerosol, inhalasi dari jalan lahir atau transplasenta. Tanyakan riwayat infeksi saluran napas pada ibu/keluarga menjelang persalinan

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Bayi dengan infeksi Enterovirus

• Bayi dengan infeksi enterovirus (EV)

• Semua bayi menunjukkan letargis dan poor feeding pada usia 5-10 hari

• Riwayat ibu sakit menjelang persalinan, transmisi fecal-oral, respiratory

• Gejala seperti acute sepsis like syndrome, meningitis/meningoensefalitis dan

hepatitis, koagulopati, trombositopenia

• Komplikasi : PVL, miokarditis, hepatitis

• Miokarditis diterapi dengan IVIG 3-5 g/kg.

• _{Kesimpulan: bayi yang tampak septik tanpa penyebab infeksi bakteri à}

cek LCS PCR. Bayi dengan infeksi EV harus diinvestigasi lebih lanjut untuk

mencari tanda PVL atau miokarditis

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Parechovirus

• Mayoritas infeksi dari Human parechovirus (HPeV) à

pada anak / dewasa : influenza like illness, diare (viral)

• Gejala yang lebih khas pada bayi : demam, irritable dan

terkadang terdapat ruam merah (“red, hot and angry”)

• Gejala berat: sepsis berat (syok), meningoensefalitis

(10%), trombositopenia, neutropenia

• 77% butuh ventilasi mekanik, 40% butuh inotropik,

kejang, apnu sentral (meningoensefalitis), acute

abdomen, perforasi, gagal hati

• Tes LCS dan feses PCR (sangat sensitif) pada kecurigaan

dengan gejala di atas

• Saat ini terapi masih hanya berupa suportif, contact

precaution

Britton PN, et al. Parechovirus: an important emerging infection in young infants. MJA 208(8). 2018

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SIMPULAN

Investigasi infeksi aliran darah dikerjakan berdasarkan perkiraan

target organ/faktor risiko / jenis kuman penyebab :

o Selalu pikirkan penyebab virus/bakteri/jamur

o Bayi terpasang jalur intravena perifer / sentral à kultur darah

perifer dan sentral

o Kultur ujung PICC/umbilikal/CVC - kolonisasi

o Full septic work up: kultur darah/urin/LCS, Rontgen toraks /

abdomen

o Pasca bedah GI : USG abdomen, FNAB, pungsi cairan

o Terintubasi – VAP à kultur ujung ETT, kultur cairan aspirat

bronkial

o Chest drain – kultur cairan pleura

o Bila kultur darah negatif à Viral panel (respiratory, LCS PCR)

o Bila trombositopeni à CMV

o Bila antibiotik lama, pemasangan kater à kultur darah jamur

o VAP o SSI o ISK o Gastrointestinal o Skin infection o Conjunctivitis Jenis kuman penyebab :

CONS MRSA Enterococcus Gram negative

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