1. VIEMPHOI-THACHTHUC-28-8

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KHNG KHNG SINH TRONG VIM PHI CNG NG V VIM PHI BNH VIN TI VIT NAM V CC NC CHU PGS.TS. Trn Vn Ngc

S PHN T THUC KHNG SINH MI NG K C FDA HOA K PH DUYT MI 5 NMTng s thuc khng sinh mi

IDSA CID 2011

TC NG CA S KHNG KHNG SINH LN T L T VONG, THI GIAN NM ViNNhim trng v vi khun gy bnh Tng nguy c t vong 1.9 3.4 2.1 1.8 - 5.4 5.0 Thi gian nm vin c th (ngy) 2.2 2.6 6.2 5.7 6.5 9.0 5 13 Tng 1.6

Vi khun huyt MRSA Nhim trng phu thut MRSA Nhim trng VRE Nhim trng P. aeruginosa khng thuc Nhim trng enterobacter khng thuc

Nhim trng acinetobacter khng 2.4 6.2 thuc Maragakis LL et al. Expert Rev Anti Infect Ther 2008; 6:751763. Nhim trng E. coli hay Klebsiella 3.6

DCH T HC :

T vong khng gim t khi Penicilline c s dng n nay.

T l t vong i vi bnh nhn ngai tr < 1% Bnh nhn ni tr khong 10%-14% Bnh nhn nhp ICU t 30%-40%.

Vit Nam: VPC nguyn nhn thng gp nht trong cc bnh nhim trng. S dng KS khng hp l VK khng thuc ngy cng tng .

VIM PHI NHIM KHUN HANG U GY T VONG CAC NC ANG PHAT TRINTRIU NGI

WHO 2006

Source: Mathers, C.D., A.D.Lopez, and C.J.L.Murray 2006.The Burden of Disease and Mortality by Condition: Data, Methods, and Results for 2001. In Global Burden of Disease and Risk Factor, ed.A.D.Lopez, C.D.Mathers, M.Ezzati, D.T.Jamison, and C.J.L.Murray, table 3.6 new York: Oxford University Press

Tnh hnh S.pneumoniae khng PNCThp (30%)Php Ty Ban Nha Cng ha Slovac Bungari Rumani Th Nh K

Bc PhiP- ru New Zealand

IsrealArp Saudi Kenia Nigeria

MM-hi-c Bc Phi Thi Lan

PhilippinesSingapore Australia

Nht bnHn Quc i Loan Hng Kng

Clinical Microbiology and Infection, Volume 7, Sup 4, 2001

Vit Nam

Pneumococci khng Macrolide ANSORP (20002001)100Erythromycin-resistant (MIC 1 mg/L) isolates as % of all S. pneumoniae

92

90 80

86

81

77

74

7060 50 40 30

2010 0

685 invasive isolates from 11 countries

Song et al. Antimicrob Agents Chemother 2004; 48:21012107

Pneumococci khng Fluoroquinolone chu 1212Ciprofloxacin-resistant (MIC 4 mg/L) isolates as % of all S. pneumoniae

685 invasive isolates from 11 Asian countries

10 8 6 4

20

Song et al. Antimicrob Agents Chemother 2004; 48:21012107

PD Fluoroquinolone140

(72-120)120 Ngn chn s khng ~AUC/MIC100

Free AUC/MIC

100 80 60 40

100

(41-69) (24-40)35

(13-21)20

Hiu qu ~AUC/MIC35

0Levofloxacin Levofloxacin Gemifloxacin Moxifloxacin 500 mg 750 mg 320 mg 400 mgMoran G. J Emerg Med. 2006;30:377-387.

KT HP KHNG PNC V KHNG CC KHNG SINH KHCCefotaxime Erythromycin TMP/SMX Tetracycline Levofloxacin Pen S 0 3.2% 6.6% 1.3% 0.1% Pen I 2.8% 35.1% 49.4% 19.1% 0.3% Pen R 42.4% 61.3% 92.3% 25.5% 0.7%

R > 3 thuc : 14%(Whitney, et al. NEJM 343:1917, 2000)

TiN TRIN KHNG QUINOLONES CA PH CU TI HONG KONG

khng Levofloxacin (MIC >4 g/ml)1995 1998 2000 < 0.5% 5.5% 13.3%

khng ca cc chng khng PNC : 27.3% Tt c chng khng FQ u khng PNC, cefotax, eryth

(Ho, et al, JAC 48:659, 2001)

H. influenzae tit -lactamaseNghin cu a trung tm trn 248 chng ti VN70% 60% 7% 50% 40% 30% 20% 10% 0% 0% Ac 1% 0% Cu 0% 8% Am Az Bt BLM(+)Ac Cu Cr Am Az Bt BLM Amoxicillin-Clavulanic acid Cefuroxime 48% Cefaclor Ampicillin Azithromycin Sultamethoxazol-Trimethoprim Beta-lactamase

R

I 4% 60% 49%

8% 0% Cr

Y Hc TP. H Ch Minh. 11(suppl.3): 47-55:2007

T l khng ampicillin cc quc gia Tt TBDng do H. influenzae tit men betalactamaseQuc giaKorea Hong Kong Australia Singapore Malaysia Japan Vietnam

% khng ampicillin65% (Protekt 2000) 18 25% (Seto 2003) 20% (Turnidge 2003) 20% (Alexander Project 1999) 25% (Rohani 2000) 8.5% (Protekt 2000); BLNAR common 49% (P.H.Van, 2006)

MRSA TRONG CNG NG TI CHU % MRSA / NHIM TRNG DO S. aureus%

5040.5

40 30

38.8 30.1 28.2 20.5

20 10 0Taiw an Sri Lanka Philippines VietNam Korea

13.8 8.4 8.4 6.9 2.2India Hong Kong Hong Kong China Thailand

ANSORP Surveillance in Asia-2005-6

TINH HINH KHNG KHNG SINH CA CC VK GY VPBV

CC VI KHUN KHNG KS CHU YU TRONG BNH ViN

VK Gram dng:MRSA VRE

VK Gram m:

PA v Acinetobacter

Khng Quinolone Khng Cephalosporin v penicillin Khng Carbapenem Chromosomal beta-lactamases ESBLs Khng Quinolone Khng Carbapenem

Enterobacteriaceae

VI KHUN NGUY HiM, KHNG C THUC TR1

Nhm chuyn gia nh gi tnh kh dng ca khng sinh (Antimicrobial Availability Task Force) ca Hi Bnh Nhim Trng Hoa K (IDSA)1 nh danh cc vi khun gy bnh c bit kh gii quyt

A. baumannii v P. aeruginosa Enterobacteriaceae sinh ESBL MRSA Enterococcus khng vancomycin

Cc u t nghin cu pht trin ESBL gim dn 2 khng sinh: Extended spectrum beta lactamaseMRSA: Methicillin resistant Staphylococcus aureus

1. Infectious Diseases Society of America. Bad Bugs, No Drugs: As Antibiotic Discovery Stagnates, A Public Health Crisis Brews. http://www.idsociety.org/pa/IDSA_Paper4_final_web.pdf. July, 2004. Accessed March 17, 2007. 2. Talbot GH, et al. Clin Infect Dis. 2006;42:657-68.

TC NHN GY VIM PHI BNH VIN14% 6% 4% 42%

10% 24%

Acinetobacter baumannii Klebsiella pneumoniae Staphylococcus aureus

Pseudomonas aeruginosa Escherichia coli Khc2

Nguyn Th Hng Thy, KY cc cng trnh NCKH BV Bch Mai, 2008, tp

T L VPTM -2010Tc nhn gy bnh A. baumannii P. aeruginosa Klebsiella sp E. coli S. aureus TngNguyn hu Ngoan 2010

S lng 47 9 8 4 9 77

% 61 11,7 10,4 5,2 11,7 100

A. BAUMANNII KHNG KS (%)Khang sinh H.Lnh-2000 K.Tuyen-2001 T.Anh-2002 N.Thao-2003 NTBE.TVN2004

Cefepim

66.7%

66.6%

91%

83%

Ceftriaxone LevofloxacinCiprofloxacin Amikacin Piper /Tazo Ceftazidim

78.9%

27.5%

82%

100% 82%

82.6% 73.3%71.6% 69.6% 47.7% 38.3%

68.2% 66.7% 54.5% 76.2%

34.8% 13.6% 11.76% 26.6%

7.1% 38.5% 19% 82%

7.6% 76% 55% 100%

Ticar/clavuColistin Imipenem 6.7% 8%

33.3%8.7% 4.4%

SMART

Study

40 trung tm / 17 nc - 2002 76 trung tm / 32 nc - 2005 , 93 trung tm -2007

MYSTIC study Lagamayo et al. AJIC May 2008

Adapted from Chow JW, et al. Surg Infect (Larchmt). 2005;6(4):439448; Gallagher G, et al. Poster presented at: 17th European Congress of Clinical Microbiology and Infectious Diseases; 31 March3 April 2007; Munich, Germany. Poster #663.

Acinetobacter spp.Khng sinh Amp/sulbacta m Amikacin Ceftazidime Ciprofloxacin Imipenem Pip/tazo %khng KS 2002 72% %khng KS 2007 71%

74%77% 79% 8% 55%

73%81% 81% 53% 74%

Pseudomonas aeruginosaKhng sinh Amikacin Ceftazidime Ciprofloxacin % khng 2002 23% 25% 36% % khng 2007 17% 35% 31%

Imipenem Pip-tazo

19% 18%

30% 20%

VI KHUN SINH -LACTAMASES-lactamases

Serine enzymes Class A enzymes Class C enzymes Class D enzymes

Metallo-enzymes Class B enzymes

(Plasmid)

(Chromosomal)

(Equivalent to Class C but plasmid)

(Chromosomal)

ESBLTEM,CTX-M,SHV

Amp CCMY,FOX,MOX,DHA

OXAOXA-48,-181..

MbLNDM,IMP,VIM

Pen-Cephs-Inh-R KPC

Cephs-Inh-R

Pens, esp Oxa Inhib-R

Carbapenems Inh-R

Bush. Rev Inf Dis 1987;10:681; Bush et al. Antimicrob Agents Chemother 1995;39:12111233 Bush. Curr Opin Investig Drugs 2002;3:12841290

VK sinh ESBL ti Chu -TBD

Adapted from Hawser SP., et al. Emergence of high levels of ESBL-producing gram-negative bacilli in the Asia-Pacific region: data from the SMART program 2007. Antimicrobial Agents and Chemotherapy 2009, 53(8): 3280-3284

T l vi khun sinh ESBL gia tng ti Vit NamBNH VINASTS program - MOH (2004) Ch Ry Hospital (2005) Vit c Hospital (2005) Bnh nh Hospital (2005) Vit Tip Hospital (2005) Bch Mai Hospital (2005) Bch mai Hospital (2006) Klebsiella spp. 23.7 (n = 485) 61.7 (87/141) 39.3 (55/140) 19.6 (29/148) 25.7 (09/35) 20.1 (37/184) 28.7 (99/347) E. coli 7.7 (n = 548) 51.6 (145/281) 34.2 (66/193) 36.2 (51/141) 36.1 (22/61) 18.5 (28/151) 21.5 (77/359)

Bch mai Hospital (2007)Bch mai Hospital (2008)

32.5 (105/323)33.7 (85/253)

41.2 (136/330)42.2 (97/231)

* Chng trnh ASTS 2002-2006 t 10 n v thnh vin Bc ,Trung, Nam; * D liu 6 thng u nm 2006

Hn 60% chng vi khun E.coli, Klebsiella sinh ESBL225 200 175 150 125 88 (36.2%) 100 75 50 16 (45.7%) 25 0 EnterobacterAnh L.T.K.3, Hai V.T.C4

ESBL [+] ESBL [-] 155 (63.8%)

202 (66.4%)

102 (33.6%)

19 (54.3%)

E. coli

Klebsiella

Nghien cu a trung tam khao sat tnh hnh e khang cac khang sinh cua cac trc khuan Gram [-] de moc gay nhiem khuan benh vien phan lap t 1/2007 en 5/2008 Van P.H.1,2,*, Bnh P.T.1,2, Y Hc TP. H Ch Minh; Tp 13; Ph bn S 2; Trang 138-148; 2009

NDM-1

Yu t di truyn 180-kb d dng c chuyn sang cho cc Enterobacteriaceae khc v cha : metallo--lactamase mi d dng thy phn penicillins, cephalosporins, v carbapenems Cc genes bt hot erythromycin, ciprofloxacin, rifampicin, v chloramphenicol. Bm khng sinh ra ngoi c kh nng gy khng thm vi khng sinh

VK Gram m a khng

Klebsiella Pneumoniae Carbapenemase (KPC)

KPC : nhm A -lactamase

Khng tt c -lactams k c extendedspectrum cephalosporins and carbapenems

Ch yu t EnterobacteriaceaeThng nht l Klebsiella pneumoniae K. oxytoca, Citrobacter freundii, Enterobacter spp., Escherichia coli, Salmonella spp., Serratia spp., t nht 1 bo co t Pseudomonas aeruginosa

iU TR THT BI CAO KHI MIC CA MRSA I VI VANCOMYCIN CAO

Sakoulas, et. al., 2004 JCM 42:2398; Moise-Broder et al. 2004 CID 38: 1700-5; Hiday