ĐIỀU TRỊ VIÊM PHỔI BỆNH VIỆN - VIÊM PHỔI LIÊN QUAN THỞ MÁY DO VI KHUẨN ĐA KHÁNG THUỐC. PGS.TS. Trần Văn Ngọc
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1 ĐIỀU TRỊ VIÊM PHỔI BỆNH VIỆN - VIÊM PHỔI LIÊN QUAN THỞ MÁY DO VI KHUẨN ĐA KHÁNG THUỐC PGS.TS. Trần Văn Ngọc
2 VPBV VPBV Hospital-acquired pneumonia (HAP) VP 48 h Sau nhập viện VPTM- Ventilator-associated pneumonia (VAP) VP> h Sau đặt NKQ VPCSSK Healthcare-associated pneumonia (HCAP) (1) Nhập viện trong 1 cơ sở chăm sóc trong > 2 ngày trong vòng 90 ngày trƣớc (2) Cƣ trú trong nhà điều dƣỡng hay cơ sở chăm sóc lâu dài (3) Mới đƣợc điều trị KS, hóa trị hay chăm sóc vết thƣơng trong vòng 30 ngày qua (4) Mới lọc máu hay nhập viện ATS/IDSA HAP Guidelines. AJRCCM;2005:171:
3 Đê khańg KS tăng lên: vâń đê toaǹ câù! MRSA : MIC với vancomycin giảm hiệu quả lâm sàng Đề kháng KS của GNB tác động khó khăn trong trị liệu khi chọn lư a thay thế đúng KS ban đầu Sử dụng KS phổ rộng, lạm dụng KS, KS dư phòng tràn lan đa dâ n đến xuất hiện như ng GNB sinh ESBL và VK không lên men đa kháng thuô c Có nhu cầu lớn các kháng sinh phổ rộng mới, thay thế cho các KS phổ rộng hiện nay
4 Tổng số thuốc kháng sinh mới SỐ PHÂN TỬ THUỐC KHÁNG SINH MỚI ĐĂNG KÝ ĐƢỢC FDA HOA KỲ PHÊ DUYỆT MỖI 5 NĂM IDSA CID 2011
5 Tử vong do VPTM CHEST 2005; 128:
6 VAP in CR hospital-2010 HAP in Bạch mai Hospital Causes A. baumannii P. aeruginosa Klebsiella sp E. coli S. aureus Numb er % 61 11,7 10,4 5,2 11,7 Total % 6% 10% 14% 24% 42% Acinetobacter baumannii Pseudomonas aeruginosa Klebsiella pneumoniae Escherichia coli Staphylococcus aureus Khác Nguyễn hữu Ngoan Luận văn thạc sỹ 2010
7 Các đặc điểm về NKBV (1) Các NKBV và vi khuẩn gây bệnh thường gặp trên người bệnh nằm tại đơn vị ICU 40% 37% 35% 35% 30% 24% 25% 20% 15% 10% 5% 4% 2% 0% Viêm phổi thở máy Nhiễm trùng huyết Viêm phổi không thở máy Nhiễm trùng tiểu Nhiễm trùng vết mổ Các loại nhiễm khuẩn bệnh viện thường gặp là viêm phổi thở máy, nhiễm khuẩn huyết, viêm phổi không thở máy Đa số nhiễm khuẩn do vi khuẩn gram âm, trong đó 4 loại vi khuẩn thường gặp theo thứ tự là Acinetobacter spp, Klebsiella pneumonia, Pseudomonas aeruginosa, E. coli
8 A.BAUMANNII KHÁNG THUỐC Kháng sinh Kháng n =143 Nhạy n = 143 Cefoperazole/ Sulbactam n (%) 5 (3,5) 138 (96,5) Imipenem n (%) 84 (58,74) 59 (41,26) Meropenem n (%) 82 (57,34) 61 (42,66) Ceftazidime n (%) 126 (88,11) 17 (11,89) Ceftriaxone n (%) 126 (88,11) 17 (11,89) Ciproloxacine n (%) 121 (84,62) 22 (13,38) Levofloxacine n (%) 70 (48,9) 73 (51,1) Polymicine B n (%) 2 (1,4) 141 (98,6) Colistin n (%) 2 (1,4) 141 (98,6) ĐẶC ĐiỂM LÂM SÀNG - MỐI LIÊN QUAN KiỂU GIEN VÀ TÍNH KHÁNG THUỐC CỦA VI KHUẨN ACINETOBACTER BAUMANNII TRONG VPBV -BVCR 01 06/2008. Cao Xuân Minh Trần Văn Ngọc Phạm Hùng Vân
9 HAP and VAP in Asian Countries Epidemiology, Resistance, Treatment Outcomes Major bacterial pathogens Acinetobacter, P. aeruginosa, S. aureus, K. pneumoniae Resistance rates Imipenem MDR XDR PDR A. baumannii (479) 67.3% 82.0% 51.1% 0.2% P. aeruginosa (411) 30.1% 42.8% 4.9% 0.7% K. pneumoniae (275) 2.2% 44.7% (ESBL, 41.4%; No NDM- 1) Colistin-R in A. baumannii: all (0.8%), China (1.4%), Taiwan (9.5%) MRSA: 82.1% (No VISA or VRSA) All-cause mortality rate: 38.9% Discordant initial empirical antimicrobial therapy increased the likelihood of pneumonia-related mortality (O.R ) Chung DR, Hsueh PR, Song JH et al. Am J Respir Crit Care Med 2011;184:
10 Tìm hiểu thư c trạng sử dụng kháng sinh trong nhiễm khuẩn bệnh viện tại các đơn vị điều trị tích cư c ở một sô cơ sở khám, chư a bệnh Tỉ lệ vi khuẩn E.coli & Klebsiella spp. được làm test ESBL E.coli hay Klebsiella (n=301) Tỉ lệ Có làm ESBL ESBL (+) 125 (77%) 55% ESBL (-) 38 (23%) Không làm ESBL % Lý Ngọc Kính, Ngô Thị Bích Hà-2010
11 Liên quan sử dụng 3 rd cephalosporin và E. coli và K. pneumoniae tiết ESBL Yếu tố nguy cơ Tr. hợp (n=33) Chứng (n=66) Nguy cơ ESBL O.R 95 % C.I P value Tổng số KS < Thời gian dùng kháng sinh 21.7 d 3.4 d < Ceftazidime 24.2 % 1.5 % FQs 21.2 % 0 Aminoglycosides 27.3 % 4.6 % TMP-SMX 39.4 % 9.1 % Vancomycin 45.5 % 7.6 % < Metronidazole 33.3 % 9.1 % Lautenbach et al. Clin Infect Dis. 32;1162, 2001
12 Tăng tử vong do VK sinh ESBL meta-analysis : Tăng tỉ lệ tư vong / BN nhiễm trùng huyết do Enterobacteriaceae sinh ESBL Schwaber MJ, et al. J Antimicrob Chemother. 2007;60:
13 Frequency ĐiỀU TRị THẤT BẠI CAO KHI MIC CỦA MRSA ĐỐI VỚI VANCOMYCIN CAO MIC (mg/l) Sakoulas, et. al., 2004 JCM 42:2398; Moise-Broder et al CID 38: ; Hidayat et al Arch Intern Med 166: ; Moise wt al AAC 51: MICs measured by Etest. 43 isolates from Bach Mai Hospital in Hanoi, 57 isolates from Chợ Rẫy Hospital in Ho Chi Minh City J. Clinical Medicine, Bach Mai hospital, No.35, Dec, 2008
14 Results of MIC Vancomycin High mortality in septicemia due to MRSA with MIC 2 mg/l ò empiric therapy with vancomycin OR (95% CI) P-value Mortality with MIC 1.0 Vancomycin MIC Vancomycin MIC ( ) 0.08 X ~ 3 Vancomycin MIC ( ) <0.001 X ~ 6 Inappropriate therapy 3.62 ( ) <0.001 X ~ 4 l Soriano A, Marco F, Martinez JA, et al. Clin Infect Dis 2008:46:
15 ĐIỀU TRỊ VIÊM PHỔI BỆNH VIỆN & VIÊM PHỔI LIÊN QUAN THỞ MÁY
16 Am J Respir Crit Care Med 2005;171: Masterton RG et al. J Antimicrob Chemother 2008;62:5-34. Asian HAP Working Group. Am J Infect Control 2008;36:S HCAP, HAP Guidelines VN guidelines for the management of lower respiratory infections -2013
17 ĐIỀU TRỊ VPBV-ATS/IDSA 2005 VPBV sớm /không YTNC VK đa kháng VPBV muộn /có YTNC VK đa kháng PRSP (-) Moxifloxacin hay Levofloxacin 750 mg qd hay Ceftriaxone hay Ertapenem hay Ampicillin / sulbactam PRSP (+) Moxifloxacin hay Levofloxacin 750 mg qd K. pneumoniae ESBL+ hay nghi ngờ Acinetobacter Carbapenem + Hoặc ciprofloxacin 400 mg q8h / levofloxacin 750 mg qd Hoặc aminoglycoside All doses mentioned are for intravenous routes MDR = Multidrug resistant PRSP = Penicillin-resistant Streptococcus pneumoniae MRSA = Methicillin-resistant Staphylococcus aureus ESBL = Extended-spectrum beta-lactamase Nghi ngờ MRSA Antipseudomonal ß- lactam / Carbapenem + Vancomycin / Linezolid + Hoặc ciprofloxacin 400 mg q8h / levofloxacin 750 mg qd Hoặc aminoglycoside Nghi ngờ Legionella Antipseudomonal ß- lactam / Carbapenem + Hoặc ciprofloxacin 400 mg q8h / levofloxacin 750 mg qd Hoặc combination of aminoglycoside and azithromycin Adapted from ATS/IDSA. Am J Respir Crit Care Med 2005;171:
18 Viêm phổi bệnh viện Asean (2008) Am J Infect Control May;36(4 Suppl):S83-92.
19 BN VPBV nhe TB, không có YTN MDRA, không bệnh căn bản đi ke m Cephalosporins thế hệ 3 ( ceftriaxone, ceftazidim ), thế hệ 4 ( cefepim ) Quinolones hô hâ p ( moxifloxacin, levofloxacin ) betalactam / ức chế beta lactamase ( ampicillin /sulbactam ) Ertapenem Cephalosporin thế hệ 3 + macrolide Monobactam + clindamycin Hướng dẫn xư trí nhiễm trùng hô hâ p không do lao- Hội Lao&Bệnh phổi VN- 2013
20 BN VPBV khởi phát muộn, mư c độ nặng, nguy cơ nhiễm MDRA Chọn lư a một trong các phối hợp sau tùy ti nh hi nh đê kháng tại chô, thuốc să n co va chi phí [67] Ciprofloxacin / levofloxacin / amikacin phối hợp carbapenem / cefoperazone-sulbactam/ampicillin sulbactam/piperacillintazobactam Carbapenem ( imipenem, meropenem, doripenem ) phối hợp ampicillin hay cefoperazone - sulbactam / piperacillintazobactam / colistin Colistin phối hợp carbapenem / Cefoperazone sulbactam/ampicillin sulbactam/piperacillin-tazobactam. Hướng dẫn xử trí nhiễm trùng hô hấp không do lao- Hội Lao&Bệnh phổi VN-2013
21 5 sai lầm thông thƣờng Điều trị thích hợp trễ Liều không đủ Không biết KS có vào tổ chư c và huyết động học Không biết sư thay đổi phổ VK tại chỗ Dùng KS kéo dài
22 Không có kháng sinh mới Cần cách tiếp cận mới
23 % mortality Sư quan troṇg cuả choṇ lư a khańg sinh khởi đâù theo kinh nghiêṃ Adequate init. antibiotic Inadequate init. antibiotic Alvarez- Lerma * 41.5 (Alvarez-Lerma F. Intensive Care Med 1996;22:387-94) Rello* Luna * Kollef * Clec'h * (Rello J, Gallego M, Mariscal D, et al. Am J Respir Crit Care Med 1997;156: ) (Luna CM, Vujacich P, Niederman MS et al. Chest 1997;111: ) (Kollef MH and Ward S. Chest 1998;113:412-20) p <.05 (Clec h C, Timsit J-F, De Lassence A et al. Intensive Care Med 2004;30: )
24 Điều trị KS thích hợp và kết quả lâm sàng Thất bại Khỏi bệnh 63% 60% 40% 37% Thích hợp Không thích hợp Thích hợp Không thích hợp -Tỉ lệ thất bại ở nhóm điều trị KS thích hợp thấp hơn nhóm điều tri KS không thích hợp (40% so với 63%)
25 ĐIỀU TRỊ KHÁNG SINH 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% KS không thích hợp KS thích hợp 84% 74% 67% 33% 26% 16% Tổng cộng E.coli hay Klebsiella Acinetobacter hay Pseudomonas Nghiên cứu của Cục QLKCB năm tại 19 bệnh viện của HN, HCM, HP
26 Thuốc chọn lựa cho Enterobacteriacae sinh ESBL Klebsiella pneumoniae, Escherichia coli Carbapenem Ertapenem Imipenem Meropenem Doripenem Beta / betalactamase inhibitor. MIC of ceftriaxone = 1-4 µg/ml = NSB-MIC
27 Kháng sinh nhoḿ Carbapenem Ưu tiên carbapenem nhóm 1 trong những trường hợp nhiễm trùng không nghi ngờ do Pseudomonas để giảm nguy cơ gây đề kháng
28 Thuốc chọn lựa điều trị P. aeruginosa Monotherapy with any first-line antimicrobial is inadequate Core antimicrobial Ceftazidime Cefepime Piperacillin-tazobactam Meropenem Doripenem Imipenem In MDR era Colistin Amikacin Combined with only one agent Amikacin Ciprofloxacin Levofloxacin Colistin Fosfomycin Amorn Leelarasamee, MD.Faculty of Medicine Siriraj Hospital, Mahidol University.Bangkok, Thailand Meropenem, doripenem Imipenem
29 Điều trị nhiễm trùng nặng do MDR (Carbapenem-resistant) Acinetobacter baumannii Definite Therapy Colistin dành cho : carbapenemase-producing Enterobacteriaceae Ampicillin-sulbactam, : liều tới 6 g sulbactam IV/ ngày Tigecycline 100-mg IV loading dose 50 mg IV q 12 h Possible alternatives Truyền kéo dài carbapenem Imipenem 1 g IV infusion over a 3-hr period q 8 h Meropenem 1-2 g IV infusion over a 3-hr period every 8 hr Doripenem 500 mg- 1 g IV infusion over a 4-hr period q 8 hr Điều trị phối hợp với KS không kinh điển Rifampin Minocycline Azithromycin Doxycycline Use of these antibiotics is based on in vitro data and animal models and on clinical case reports and studies of small series of patients. Peleg AY, Hooper DC. Hospital-Acquired Infections Due to Gram-Negative Bacteria. N Engl J Med 2010;362:
30 Concentration (mg/l) Tô i ƣu hóa điều trị -lactam tô i đa hóa %T>MIC Tăng thời gian truyền Prolonged infusion 32 Same dose and dosing interval, ml, however, change duration of infusion (0.5 hr 3-4hr) T/MIC > 40% MIC Time Since Start of Infusion (h)
31 J Med Assoc Thai Vol. 93 No
32 MRSA ĐƠN HAY PHỐI HỢP KHÁNG SINH Low MIC High or NSB-MIC ESBL-p E. coli, Klebsiella spp. Low MIC High or NSB-MIC Vancomycin Vancomycin (trough level = 20 µg/ml) Or fosfomycin, daptomycin Ertapenem Ertapenem + amikacin or fosfomycin Imipenem or meropenem or doripenem KPC-p NDM-1 p Colistin or a carbapenem + fosfomycin Colistin (or amikacin) + a carbapenem Colistin (or amikacin) + a carbapenem A carbapenem + fosfomycin MDR P. aeruginosa Colistin + meropenem (LD+PI) Colistin + Pip-tazobactam (LD+PI) MDR A. baumannii Colistin + imipenem (LD+PI) LD: loading dose; PI: prolonged infusion (3 or 4 h intravenous infusion)
33 Liệu pháp kết hợp dư a trên Carbapenem trong điều trị nhiễm khuẩn với MDR Acinetobacter baumannii Kết hợp giữa imipenem và colistin đối với MDR A. baumannii cho thâ y Vượt trội hơn các liệu pháp đơn của từng loại Bổ sung sulbactam vào meropenem và colistin Co thể cải thiện điều trị. Thư nghiệm lâm sàng về các biện pháp kết hợp Đặc biệt cần thiết Pongpech P, Amornnopparattanakul S, Panapakdee S, Fungwithaya S, Nannha P, Dhiraputra C, Leelarasamee A. Antibacterial activity of carbapenem-based combinations against multidrug-resistant Acinetobacter baumannii. J Med Assoc Thai 2010;93(2):
34 Therapeutic Management of MRSA VAP 2 main risk factors for MRSA ( 5 days in hospital + prior antibiotics)? or documented MRSA colonisation YES EMPIRIC THERAPY for MRSA NO VANCO/TEICO Renal impairment or nephrotoxics use Severe sepsis or age > 65 years YES LINEZOLID MSSA CULTURES MRSA OXACILLIN (if not β-lactam allergy) Culture negative: Stop Rx Discontinue VANCO / Use LINEZOLID NO If VANCO -> switch to LINEZOLID If LINEZOLID -> add RIFA? Tygacil? add VANCO continuous infusion? Modified from Niederman. J Hosp Infect 2012 CLINICAL RESPONSE OK Continue
35 KẾT LUẬN Kháng thuốc ngày càng trầm trọng trên hầu hết các vi khuẩn Nguồn kháng sinh ngày càng cạn kiệt, kho trị, Tăng tư vong Tăng thời gian nằm viện Tăng chi phí điều trị CẦN CÓ MỘT KẾ HOẠCH HÀNH ĐỘNG CẦN SỬ DỤNG KS HỢP LÝ VÀ KHÔN NGOAN
36 CHÂN THÀNH CẢM ƠN!
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