CARBAPENEM TRONG NHIỄM KHUẨN NẶNG Ở TRẺ EM KHÁNG SINH TRONG NHIỄM KHUẨN HUYẾT TRẺ EM PGS TS BS PHÙNG NGUYỄN THẾ NGUYÊN BỘ MÔN NHI – ĐHYD TPHCM KHOA COVID 19, BV NĐ1

CARBAPENEM TRONG NHIỄM KHUẨN NẶNG Ở TRẺ EM KHÁNG SINH TRONG NHIỄM KHUẨN HUYẾT TRẺ EM PGS TS BS PHÙNG NGUYỄN THẾ NGUYÊN BỘ MÔN NHI – ĐHYD TPHCM KHOA COVID 19, BV NĐ1 NỘI DUNG Các nguyên tắc dùng KS tro.

NỘI DUNG

Các nguyên tắc dùng KS trong sepsis Các yếu tố ảnh hưởng chọn KS ban đầu Các hướng dẫn cụ thể

Ở các nước phát triển, tử vong do

sốc nhiễm khuẩn < 20%.

Ở các nước đang phát triển: tử

vong do sốc nhiễm khuẩn 50%

Nguyên nhân tử vong:

1 Sốc kéo dài

2 Suy cơ quan

Updates on pediatric sepsis, JACEP Open 2020;1:981–993

Sử dụng kháng sinh

6 nguyên tắc

•Zhou, Xiang; Su, Long-Xiang; Zhang, Jia-Hui; Liu, Da-Wei; Long, Yun Rules of anti-infection therapy for sepsis and septic shock, Chinese Medical Journal: March 5, 2019 - Volume 132 - Issue 5 - p 589-596 doi: 10.1097/CM9.0000000000000101

TÁC NHÂN

4 Các hướng dẫn điều trị hiện nay

5 Theo dõi nồng độ vancomycin trong điều trị Phân loại vi khuẩn

Vi khuẩn

Dạng chuổi

Sreptococci

MSSA, MRSA

Staphylococcuc coagulase negative

Cầu khuẩn

Neisseria Moraxella

Trực khuẩn

Trực khuẩn hô hấp

Hemophillus Bordetella

Trực khuẩn tiêu hóa

E coli

K Pneumonia Enterobacter Pseudomonas Shigella Proteus Serratia

Cầu trực khuẩn

Acinetobacter

Clostridium Bacteroides Peptostreptococci

Mycoplasma Chlamydia Legionella

Tác nhân theo cơ địa

Cắt lách S pneumoniae, Haemophilus influenzae, N meningitidis

Giảm BCĐNTT Gr (-), Gr (+) và nấm nhất là Candida spp

Giảm Gammaglobulin S pneumoniae, E Coli

Bỏng S aureus, P aeruginosa, Gr (-) đa kháng

HIV S aureus, P aeruginosa, Pneumocystis carinii.

Dụng cụ nội mạch S aureus, S epidermidis

NTBV S aureus, Enteroccocus spp, E coli, Gr (-) đa kháng,

Candida spp

Tác nhân theo vị trí

Phổi S pneumoniae, Haemophilus influenzae, Legionella spp,

Chlamydia pneumoniae

Trực khuẩn Gr (-) hiếu khí

Bụng E coli, Bacteroides Fragilis Trực khuẩn Gr (-) hiếu khí, vi khuẩn kỵ khí,

candida spp

khuẩn Gr (-) hiếu khí, P aeruginosa, vi khuẩn kỵ khí, Staphylococcus spp.

Staphylococcus aureus, trực khuẩn Gr (-) hiếu khí

S aureus

P aeruginosae Aspergillus

Giảm kháng thể

Bẩm sinh

Đa u tủy

Phế cầu HI

Giảm lympho T

HIV Ghép tạng

Lao, P carinii, C Neoformans, legionella, CMV

Dùng thuốc hóa trị, steroids

Lupus Viêm đa khớp HCTH

Tỷ lệ nhiễm vi khuẩn gram âm 2016-2021 BV NĐ1

VI KHUẨN GRAM ÂM

Acinetobacter spp Escherichia coli Haemophilus influenzae Klebsiella pneumoniae Pseudomonas aeruginosa

NHIỄM KHUẨN HUYẾT

Tỷ lệ tạo ESBL của E coli là 55,3% của Klebsiella spp là 57%

Tỷ lệ nhạy kháng sinh của một số vi khuẩn gram

âm tại BVND1 năm 2018

NGUYÊN TẮC CHỌN KHÁNG SINH

1 Sau khi cấy

Kháng sinh cho sớm

2 Sớm: trong vòng 1 giờ đầu tiên

Crit Care Clin 2011;27:53-76 Crit Care Med 2014 November ; 42(11): 2409–2417

Thời gian khởi đầu KS theo SSC

1 giờ

Sốc Giảm neutrophile SGMD

Cắt lách Viêm màng não

In children with sepsis-associated organ dysfunction but without shock, we suggest starting

antimicrobial therapy as soon as possible after appropriate evaluation, within 3 h of

In children with septic shock, we recommend starting

antimicrobial therapy as soon as possible, within 1 h of

evidence )

Chỉ định kháng sinh sớm

Kumar 2006, 2154 BN

1.04 per hour; 95% CI, 1.03–1.06; P<0.001)

ED arrival to the first dose of antibiotics was associated with a 10% (95% CI, 5–14%; P<0.001)

Increased patient’s length of stay (32,42), acute lung injury (43), acute kidney injury (44), and worsening organ dysfunction due to an exacerbated inflammatory

response are worrisome

33% in mortality when comparing immediate (within 1 hour) and delayed (>1 hour) antibiotic administration [OR, 0.67 (95% CI, 0.59–0.75)]

Martínez et al An approach to antibiotic treatment in patients with sepsis, 2020

2 Assess Airway/Breathing <5 min

Apply oxygen if required to keep SaO2 ≥9 2%

Attach cardiorespiratory monitoring Senior operator if intubation required

3 Vascular Access <15 min

Perform IO after 2 failed IV attempts Send bloods: blood gas (lactate, BSL), FBE, blood cultures, UEC/LFTs, CRP, sterile site PCR, +/- coags, +/- procalcitonin

4 Empiric Antibiotics +/- Antivirals <30 min

See Page 7 for empiric antimicrobial guidelines

If no IV/IO access, consider IM antibiotics

5 Cautious Fluid Resuscitation

6 Consider Early Inotropic Support

<30 min

<60 min

Careful fluid resuscitation: Senior clinician to decide on need for fluid bolus (10-20 ml / k g 0 9 % Na Cl )

Each time assess response

o Aim: improved HR, mentation, perfusion

o Overload: hepatomegaly, crepitations,

oedema Decide need for early inotropic/vasopressor support for persisting circulatory failure See Page 2 for

1 Repeated Medical Review Every hour

2 Repeat Observations Every 30 mins

3 Consider Differential Diagnoses

Anaphylaxis Cardiac causes Toxins/Ingestion Metabolic conditions (incl DKA)

Tr a u ma / NAI Surgical causes (incl intussusception) Paediatric Multisystem Inflammatory Syndrome

≥ ANY Purple Zone observation on RDR chart

Child UNWELL? Concerned with observations?

≥ Chronic disease or congenital disorder

≥ Recent trauma, surgery, invasive procedure or

≥ Altered conscious state

≥ Marked or persistent tachycardia

≥ Lactate 2-4 mmol/L concerning, >4 mmol/L high risk

≥ Unexplained generalised pain

Purpose and Scope of PCPG

The Sepsis in Children Paediatric Clinical Practice Guideline (PCPG) is primarily aimed at medical staff working in any of the primary care, local, regional, general or tertiary hospitals It may however assist the care provided by other clinicians such as nurses

The information is current at the time of publication and provides a minimum standard for the assessment (including investigations) and management sepsis; it does not replace or remove clinical judgement or the professional care and duty necessary for each specific case

Important points

> Sepsis is a syndrome of life-threatening organ dysfunction caused by a

dysregulated host response to infection (Sepsis-3 International Consensus Definition) These features distinguish it from an uncomplicated infection

> Sepsis in the paediatric population can be particularly difficult to recognise given the large

number of mimics and the fact that children will often appear very unwell, including significantly abnormal physiology, when febrile

> Sepsis is the primary cause of long-term morbidity and mortality from infection

> Clinician judgement is currently the best tool we have for early recognition of

sepsis

> Recognition of sepsis therefore mandates urgent attention

> There are presently no clinical criteria, laboratory features or diagnostic tests that uniquely

identify a septic patient

> Initial management includes urgent vascular access, early empiric antibiotics, careful fluid

resuscitation with early progression to inotropic or vasopressor support where required

> In an unwell child, procedures such as urinalysis and lumbar puncture should not delay

resuscitation and empiric antibiotics

Common Pathogens

< 3 months of age: Escherichia Coli, Group B Streptococcus, Listeria

monocytogenes

> 3 months of age: Neisseria meningitidis, Streptococcus pneumoniae, Group A

Streptococcus, Staphylococcus aureus, Methicillin Resistant Staphylococcus aureus

Chang, J.L., Pearson, J.C & Rhee, C Early Empirical Use of Broad-Spectrum

Antibiotics in Sepsis Curr Infect Dis

Rep 24, 77–87 (2022)

00777-2

https://doi.org/10.1007/s11908-022-Chang, J.L., Pearson, J.C & Rhee, C Early Empirical Use of Broad-Spectrum

Antibiotics in Sepsis Curr Infect Dis

Rep 24, 77–87 (2022)

00777-2

https://doi.org/10.1007/s11908-022-3 Lựa chọn KS thích hợp:

v Đảm bảo nguyên tắc 4D

Nguyên tắc 4D:

3 Lựa chọn KS thích hợp:

• Dùng loading dose

• BN không suy cơ quan, cho liều cao nhất của

hướng dẫn

• BN suy cơ quan:

liều bình thường 24-48 giờ

– Suy gan cấp nhưng không có tiền sử: cho liều

bình thường và theo dõi

Nguyên tắc 4D:

4 Phối hợp kháng sinh

2 KS có 2 cơ chế khác nhau cùng tác dụng lên 1 loại hay nhóm VK giống nhau.

Bất lợi của phối hợp:

• Tạo thuận lợi cho kháng

thuốc

• Tăng độc tính

• Tăng chi phí

• Tăng nguy cơ nhiễm nấm…

Phổ hẹp KS là tốt nhất vì giá thành, an toàn, và tính kháng thuốc

AHRQ Safety Program for Improving Antibiotic Use – Acute Care

Slide Title and Commentary Slide Number and Slide

Combination Therapy: Original Data

survived in the monotherapy group and 71%

survived in the combination therapy group)

However, 30 percent of the agents that were considered monotherapy were very narrow and

not agents that we would routinely use as monotherapy for empiric treatment of sepsis such

as vancomycin, macrolides, clindamycin, staphylococcal penicillins and first- and second-

anti-generation cephalosporins In contrast, combination therapy regimens primarily consisted

of a beta-lactam agent plus a second agent with broad Gram negative coverage such as an

aminoglycoside (40%) or a quinolone (38%)

Slide 14

Combination Therapy: Original Data

SAY:

In taking a closer look at the results when stratified

by agents, you can see that there was no difference in mortality in patients who received

combination therapy vs monotherapy when one of the agents in both arms was a beta-lactam/beta-

lactamase combination, an anti-pseudomonal third- or fourth-generation cephalosporin, or a

carbapenem, agents that are commonly used to treat patients with septic shock.

Slide 15

11

11 Sepsis

AHRQ Safety Program for Improving Antibiotic Use – Acute Care

Combination Antibiograms To Assess the

Potential Benefit of Combination Therapy

SAY:

Before making recommendations about possible

combination treatment regimens, it is helpful to

develop combination antibiograms to determine if

the addition of a second agent is likely to enhance

coverage This figure shows the susceptibility

profiles of cefepime, meropenem, and

piperacillin-tazobactam as monotherapy to a hypothetical

Gram-negative organism Then, for each potential

combination agent, an antibiogram is developed

that shows the additional proportion of Gram-

negative isolates that would be covered by the

combination agents, but not the monotherapy

agents Thus, the addition of tobramycin to

cefepime captures 11 percent more organisms that

were resistant to cefepime but susceptible to

tobramycin

In this example, an 11 percent increase in

susceptibility, such as would be assumed by adding

tobramycin to cefepime, may make a clinical

difference for patients and justify combination

therapy when patients are ill However, in the

same example, the addition of ciprofloxacin offers

little additional coverage and would not be a

suitable agent to add It is important to ensure that

a second agent adds coverage before exposing a

patient to additional antibiotics and their

associated side effects.

Slide 13

Phối hợp kháng sinh

Meropenem + AG

Cisneros et al Critical Care (2019) 23:383 https://doi.org/10.1186/s13054-019-2627-y

Meropenem & Colistin

Ef e k tivita s Me rope ne m- Le vof l oxa cin de ng a n Me rope ne

m-A mik a sin terha da p LOS & Le uk osit Pa sien Pneumonia

Komuniti Stra tif i k a si III RA SPRO ( Ef f ctive ne ss of Me rope ne m- Le vof l ox a cin w ith Me rope ne m-

A mik a sin Tow a rds LOS & Le uk ocytes to RA SPRO III

Stra tif i ca tion Community Pne umonia Pa tie nts)

H A DISUMA RSONO1*,DIA N RATIH LA KSMITAW ATI2,RONA LD IRW A NTO1

1RSPI-Puri Indah,Puri Indah RayaS-2,Kembangan,JakartaBarat

2Fakultas Farmasi,Universitas PancasilaSrengsengSaw ah,JakartaSelatan

Diterima10Juli 2019,Disetujui 22 Oktober 2020

Vol.18,No.2JURNA L ILMU KEFA RMA SIA N INDONESIA ,Oktober2020,hlm.246-251

ISSN:1693-1831,E-ISSN:2614-6495

* Pe nulis k or e sponde nsi

e - ma il: hdi_suma rsono89 @y a oo co id

A bstract: A dministration ofantibiotics in theprivateospital "X"adopted aconcept called Ronald

Iw anto A ntimicrobial Stew eardship Program (RA SPRO).Thesuggestion ofan empirical antibiotic combination in typeII stratification community pneumoniapatients w as meropenem-levofloxacin

ormeropenem-amikasin.Theaim ofthestudyw as to determinetheefct ofmpirical antibiotic combination meropenem-levofloxacin w ithmeropenem-amikacin to RA SPRO typeI stratification communitypneumoniapatients tow ards theLOS and decreased leukocytes.Thetest samplecalculated usingdiffrencebetw een tw o population proportions formulaand analysed usingChi-squaremethod.Diabetes mellitus,immobilisation and geriatrics as confoundingvariables w erecontrolled bylogistic

regretion multivariateanalysis.Theresults show ed that meropenem-levofloxacin had atendency1.81times to eperienceLOS < 5 days and 0.92 times to experiencedecreased leukocytes ≥ 10% compared

to meropenem-amikacin,but bothw erenot significant (p 0.161and p 0.835).Theresult control ofconfoundingvariables w erefound that geriatrics as ameaningful confoundingvariablefct ofLOS

and no confoundingvariables w ereconsidered to afct thedecreased leukocytes.In conclusion,there

is no efct ofmpirical antibiotic combination meropenem-levofloxacin w ithmeropenem-amikacin tow ards theLOS and decreased leukocytes to RA SPRO typeIIIstratification communitypneumonia

patients usingstatistics aftercontrollingtheconfoundingvariables

Keyw ords:Communitypneumonia,meropenem,levofloxacin,amikasin,LOS,decreased leukocytes

A bstrak: Pemberian antibiotika di rumah sakit sw asta “X” menerapkan konsep bernama Ronald

Irwanto Antimicrobial Steweardship Program (RA SPRO).Saran kombinasi antibiotikampiris pada

pasien pneumoniakomuniti dengan stratifikasi tipeIantaralain menggunakan kombinasi meropenem

- levofloxacin atau meropenem - amikasin Tujuan penelitian adalah untuk mengetahui pengaruh

kombinasi antibiotikampiris meropenem -levofloxacin dengan meropenem -amikasin padapasien pneumonia komuniti stratifikasi tipe II RA SPRO terhadap LOS dan penurunan leukosit Sampel

uji dihitungmenggunakan rumus perbedaan duaproporsi dan dianalisamenggunakan metodeChi square.Variabel perancu diabetes mellitus,imobilisasi dan geriatri dikontrol berdasarkan uji analisamultivariat regresi logistik H asil penelitian menunjukkan kombinasi meropenem - levofloxacin

memiliki kecenderungan 1,81kali untukmengalami LOS < 5 hari dan 0,92 kali untukmengalami

penurunan leukosit ≥10% dibandingkan meropenem -amikasin,namun keduanyatidaksignifikan (p

0,161dan p 0,835).H asil kontrol variabel perancu ditemukan bahw ageriatri sebagi variabel perancu

yang bermakna dalam mempengaruhi LOS dan tidak ada variabel perancu yang dianggp dapat

mempengaruhi penurunan leukosit.Sebagi esimpulan,tidakterdapat pengaruhkombinasi antibiotika

empiris meropenem -levofloxacin dengan meropenem -amikasin terhadap LOS & penurunan leukosit

padapasien pneumoniakomuniti stratifikasi tipeIII RA SPRO dengan menggunakan statistiksetelah

mengontrol variabel perancu

Katakunci:Pneumoniakomuniti,meropenem,levofloxacin,amikasin,LOS,penurunan leukosit

5 Phải sử dụng kháng sinh đúng thời gian qui định:

Các yếu tố kéo dài thời gian dùng KS

Xuống thang

Giảm số lượng KS

Ngưng

KS MRSA

Ngưng KS khi không nhiễm trùng

Phổ hẹp KS

6 KS chiến lược xuống thang:

v Phổ rộng ban đầu

v Phổ hẹp hay ngưng khi có kết quả vi

sinh và cải thiện lâm sàng

• Kết quả vi sinh và tính nhạy của thuốc

• Phổ hẹp có thể dựa trên đáp ứng LS

v Phổ hẹp nhất có thể