NGHIEN CUU SLT DUNG KHANG SINH TRONG VIEM NOI TAM MAC NHIEM KHUAN CAY MAU AM TINH KHONG DAP UNG VOI BETA-LACTAM VA AMINOSID
TRONG QUA TRINH DIEU TR!
Ta Manh Cifdng(1), Nguyen Thj Thanh Nga(:
TOM TAT
Qua nghien cu'u nhung benh nhan viem noi tam mac nhiem khuan cay mau am tinh co bieu hien khong dap irng vdi khang sinh beta-lactam va aminosid trong qua trinh dieu tri chiing roi nhan thay neu benh nhan khong dap irng vdi trj lieu penicillin va aminosid nay thi cd the thay the bang mot phac do phoi hop penicillin khac va aminosid khac, neu benh nhan khong dap iitig vdi phac do cephalosporin the he 3 va aminosid thi nen thay bang phac do cephalosporin the he 3 khac va aminosid khac, neu khong dap irng vdi dieu tri bang imipenem/cilastatin + aminosid khi nhap vien thi van co the diing vancomycin hoac cephalosporin the he 3 phoi hop vdi clarythromycin de tiep tuc dieu trj cho ngudi benh.
ABSTRACT
Studying antibiotic in the bacterial endocarditis patients with negative blood cultures do not respond to beta-lactam and aminosid during
treatment
By studying the medical records of the patients with blood culture-negative endocarditis is manifested not respond to beta-lactam and aminosid antibiotics in the process of treatment we found that if patients do not respond to penicillin and aminosid therapy, we should be replacing it with a other penicillin and other aminosid, if patients treated by third-generation cephalosporin and aminosid, we should be replaced this treatment by other third-generation cephalosporin and other aminosid and if patients do not responding to treatment with imipenem/cilastatin and aminosid, we may still use vancomycin or third-generation cephalosporin with clarythromycin to coordinate treatment for patients.
(1): Viin Tim Mach Viet Nam;
(2): TrWdng Dai hgc DWdc Ha Ngi
I. OAT VAN OE~
Viem noi tam mac nhilm khuan (VNTMNK) la mot tinh trang nhilm triing mau va khu tru ciia tic nhan gay benh len mang trong tim binh thudng hoac benh ly. Benh co dien bien phUc tap, thudng nang, ty le tU vong cao dac biet la nhtfng trUdng hop VNTMNK cay mau khong tim thay tac nhan gay benh (VNTMNK cay mau am tinh). Cho den nay tri lieu khang sinh phoi hop beta-lactam va aminosid van la lira chon dau tay trong dieu trj viem npi tam mac nhilm khuan cay mau am tinh, tuy nhien ket qua khong phai bao gid cung nhu mong ddi: mot so benh nhan khong dap Ung vdi nhirng loai khang sinh kinh dien noi tren. Thirc te lam sang dat ra la ddi vdi nhUng benh nhan nay, chiing ta nen lira chon loai khang sinh nao de co the diet dUdc vi khuan gay benh, khi ma tien sd benh nhan, dudng vao ciia vi khuan hau nhu khdng the xac dinh dude.
Vi vay, chiing toi tien hanh nghien cu'u, tdng ket ho sd benh an ciia nhirng benh nhan viem npi tam mac nhilm khuan cay mau am tfnh khdng dap irng vdi khang sinh beta-lactam phoi hdp vdi aminosid trong qua trinh dieu tri nham muc tieu : Tim hieu each thirc tiep tuc sif dung khang sinh trong trddng hop that bai vdi tri lieu beta-lactam va aminosid d nhtTng benh nhan
viem ngi tam mac nhiem khuan cay mau am tinh.
II. 06l Tl/<?NG VA PH JONG PHAP NGHIEN CUu 2.1. Doi tirpng nghien ciru
Li nhirng benh an ciia benh nhan dude chan dean VNTMNK cay mau am tfnh dude dieu tri bang beta-lactam va amincsid nhung khong dap trhg vdi dieu tri, dau hieu nhilm khuan khong thuyen giam hoac thuyen giam rat it, sau 3-5 ngay dieu trj phai thay the bang mot tri lieu khang sinh phoi hdp khac (co the van la penicillin
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Y HOC VIET NAM THANG 7 - SO 1/2010 va aminosid nhi/ng la mot loai biet dude khac).
Theo doi ket qua ciia nhung tri lieu khang sinh noi tren cho den khi benh nhan khoi benh, xuat vien va rut ra ket luan. Thdi gian nghien ciru tir nam 2002 - 2007 tai Vien Tim Mach Viet Nam.
2.2. Phifdng phap nghien cu'u
2.2.1. Tieu chuan chan doan viem noi tam mac nhiem khuan cay mau am tinh
- Benh nhan mac benh van tim (hd, hep van hai la va/hoac hd hep van dong mach chii, hd van ba la thue tdn dupe chan doan xac dinh tren lam sang va sieu am tim
- Sot keo dai tir 2 tuan trd len,
- NhOTig bieu hien khac ciia tinh trang nhilm triing: da xanh, niem mac nhdt, hemoglobin giam, bach cau tang, toe dp lang mau va CRP (C- Reactive Protein) tang,
- Cd ton thudng sui van tim, dirt day chang van tim hoac ap xe trong tim (vong van, cd tim...) dUdc phat hien tren sieu am tim qua
thanh ngue hoac sieu am tim qua third quan.
- Cay mau 3 lan, each nhau it nhat 2 gid giua cac lan cay mau khdng tim thay tac nhan •gay nhiem triing (cay mau am tinh).
2.1.2. Tieu chuan danh gia hieu qua cua khang sinh trong dieu tri
• Khang sinh khong hieu qua (khong dap Ling vdi dieu tri): sau 3 - 5 ngay dieu tri, benh nhan khdng het sot (than nhiet > 37 dp C), hoac sau khi het sot nhieu tuan (4 - 6 tuan) benh nhan cd bieu hien sot trd lai.
• Khang sinh co hieu qua (benh nhan dap dng vdi dieu tri): sau 3 - 5 ngay dieu tri bang khang sinh, nhiet dp giam ro ret hoac benh nhan het sot va khdng sot lai trong 4 - 6 tuan tiep theo, ve xet nghiem: hemoglobin tang, bach cau giam, tdc dp mau lang giam, nong dp CRP giam, chirc nang gan (SGOT, SGPT) va than (creatjnin) on dinh.
III. KET QUA NGHIEN CU'U - Dac diem mau nghien cu'u
Tir 1/2002 den 12/2008, chung tdi chon dUdc 85 benh an VNTMNK cay mau am rinh trcng do 55,3% la nam va 44,7% la nu'. Tudi trung binh la 43 ± 17 vdi thdi gian dieu tri trung binh la: 34,4 ± 16,3 ngay.
- Ki t qua dieu tri khang sinh
Phac do n Ty le %
Don doc:
(Hactam 30 35.3
• Vancomycin 1 1.2
Phoi hdp 2 khang sinh:
• B-lactam + aminosid 36 42.4
• B-lactam + quinolon 5 5.9
• B-lactam + imidazole 1 1.2
• B-lactam + cyclin 3 3.5
• Aminosid + vancomycin 4 4.7
• Quinolon + fosfomycin 1 1.2
• Vancomycin + quinolon 1 1.2
Phoi hdp 3 khang sinh:
• B-lactam + aminosid + vancomycin 2 2.4
• p-lactam + B-lactam + quinolon 1 1.2
Tong 85 100
Bieu do : Ty le benh nhan dung cac nhom khang sinh p-lactam ket hdp aminosid Tu bang va bieu do tren nhan thay, B-lactam ket hdp vdi aminosid chiem ty le cad nhat 42,4%
benh nhan trong do nhom penicillin va aminosid chiem 16,5%; cephalospdrin the he 3 va aminosid chiem 23,5%; c6n lai 2,4% la dung imipenem/cilastatin va aminosid.
Trong 36 benh nhan dUdc dieu tri bang B-lactam ket hdp vdi aminosid ngay tU khi vao vien co 26 benh nhan khong dap Ung vdi B-lactam va aminosid dUdc thay bang nhUng phac do phoi hdp khac.
Sau khi thay ddi khang sinh ddi vdi 26 benh nhan noi tren thi cd 24 benh nhan dap Ung tot va xuat vien sau 4 - 6 tuan dieu tri, 2 benh nhan khong dap Ung va phai dung them mot phac do dieu tri thU 3 mdi cd ket qua. Cach thuc dieu tri cu the dUdc the hien thee bang 2.
Bang 2: Phac dd khang sinh dieu tri cho benh nhan dap Ung
Ty le Ty le
Phac do dau tien n (%) Phac do cuoi cung n (%)
Quinolon+fosfomycinw 1 1.2
C2GW 1 1.2
C3G+aminosid(+) 1 1.2
Penicillin + aminosid'"' 12 46,2 C3G+quinolon+rifampicin'+) 1 1.2 Penicillin + aminosid'"' 12 46,2
Penicillin+aminosid khac'+) 5 5.9 Amoxitillin/clavulanat+aminosid(+> 1 1.2 Aminosid+vancomycin(+) 1 1.2 Aminosid+clarythromycin<+) 1 1.2 C3G khac +aminosid khac(+> 7 8.2 C3G+quinolon'+> 1 1.2 C3G + aminosid H 12 46,2 Imipenem/cilastatin(+) 1 1.2
C3G + aminosid H 12 46,2 Penicillin'*' 1 1.2
Penicillin+quinolon'"' 1 1.2 Aminosid+vancomycin'"' 1 1.2
Imipenem/cilastatin+ 2 7,6 vancomycin 1 1.2
Aminosid '"' 2 7,6 C3G+clarythromycin 1 1.2
Cpng: 26 100
(+): dap dng vdi dieu tri; (-): khong dap ting vdi dieu trj
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Y HOC VIET NAM THANG 7 - SO 1/2010 Kit qua nghien cu'u cho thay:
• 14,1% benh nhan dieu tri bang Penicillin va aminosid that bai, khi dUdc thay the bang phac do khac thi co 5 benh nhan dap Ung vdi mot Penicillin va aminosid khac, con lai cac phac do khac, moi phac do chi co 1 benh nhan dap Ung.
• 14,1% benh nhan dieu tri bang Cephalosporin the he 3 va aminosid that bai, khi dupe thay the bang phac do khac thi co 7 benh nhan dap Ung vdi mot cephalosporin the he 3 khac va mot aminosid khac; 1 benh nhan khong dap Ung vol penicillin va quinolon; 1 benh nhan khong dap Ung vol aminosid va vancomycin.
• 2,4% dung imipenem/cilastatin va aminosid that bai co 1 benh nhan dap Ung vdi vancomycin, 1 benh nhan dap Ung vdi cephalosporin the he 3 phoi hdp vdi clarythromycin.
IV. BAN LUAN
1. Phac do khang sinh dung cho benh nhan VNTMNK cay mau am tinh ngay khi nhap vien
Trong nghien cUu, chung toi nhan thay phan ldn benh nhan VNTMNK cay mau am tinh khi bat dau nhap vien deu dUdc dieu tri phac do L3- lactam ket hdp aminosid trong do dai dien chi'nh la Cephabsporin the he 3 phoi hdp aminosid va Penicillin ket hdp aminosid. Dieu nay hoan toan phu hdp vdi nhieu khuyen cad trong va ngoai nude [1,3].
Khuyen cio ciia My nhan manh nhUng benh nhan VNTMNK cay mau am tinh nen dieu tri bang phac do phoi hdp B-lactam va aminosid trUdc khi co ket qua phan tich dac biet [3]. Gan day, Brund Hden cung khuyen cac viec diing phac do B- lactam va aminosid cho benh nhan VNTMNK cay mau am tinh se dem lai hieu qua hdn han so vdi nhUng phac dd khac [5].
Nhu da biet, VNTMNK cay mau am tinh thudng gay ra bdi nhung vi khuan hiem gap: vi khuan Gr(-), lien cau cd nhu cau dinh dudng khac nhau, Brucella, Coxiella burnetii, Bartonella, Legionella, Tropheryma Whipple! hoac nhdm HACEK. NhUng tac nhan nay khd phat hien dUdc
luon am tinh [3,4]. Vi the viec vieu tri VNTMNK cay mau am tinh ludn gap nhieu khd khan.
Thed Harrison, da so lien cau bi Uc che bdi penicillin, diing penicillin ddn thuan trong 4 tuan cho ty le thanh cdng d 99% benh nhan, khi ket hdp them vdi gentamycin hoac streptomycin thu dUdc hieu qua diet khuan nhanh hdn va cho ty le chua khdi tUdng dUdng trdng 2 tuan. Vdi nhung benh nhan cd o ap xe di can hoac soc nhiem khuan nen diing penicillin 4 tuan ket hdp them aminosid trong 2 tuan dau, con vdi benh nhan cd tien sU di Ung vdi penicillin thi nen diing cephalosporin de thay the [4].
2. Sir dung khang sinh hieu qua trong dieu tr]
Ket qua nghien cUu cho thay 14,1% benh nhan dieu tri bang Penicillin va aminosid that bai, khi dUdc thay the bang phac de khac thi co 5 benh nhan dap Ung vdi Penicillin va aminosid khac. 14,1% benh nhan dieu tri bang Cephalosporin the he 3 va aminosid that bai, khi dUdc thay the bang phac dd khac thi cd 7 benh nhan dap Ung vdi Cephalosporin the he 3 khac va aminosid khac. NhU vay, trong qua trinh dieu tri, khi diing mot khang sinh trong nhdm phoi hdp vdi mot khang sinh nhdm khac that bai thi van nen tiep tuc chuyen sang dung nhung khang sinh khac ciing nhdm, chua nen doi hoan toan sang mot phac do phoi hdp mdi.
Nghien cUu ciia Adrian C mot fan nua khang dinh phac do phoi hdp khang sinh nhdm B- lactam vdi aminosid mang lai ty le thanh cdng chd 82,4% benh nhan [2]. Pesanti cung nhan manh phac do phoi hdp nay khong chi dUdc sU dung nhieu trong nghien cUu ma ccn dem lai ty le thanh cdng cad trong qua trinh dieu tri: khi ket hdp B-lactam vdi amincsid tac gia nhan thay phac do nay lam giam den 92% so benh nhan cd bieu hien sdt dudi 7 ngay va 50% sd benh nhan cd bieu hien sot hdn mot tuan. Hai tac gia khang dinh phac do phoi hdp nay dem lai mot ty le thanh cdng dang ke trong dieu tri. Vi vay viec tiep tuc chuyen diing nhung khang sinh cung nhdm trUdc khi chuyen sang mot phac do phoi
cephalosporin the he 1, vancomycin va cac thuoc khac lam thuan ldi hdn cho tinh trang suy than tien trien tren benh nhan: thudc ldi tieu, thuoc ut che men chuyen Angiotensin 2, khang aldosterol, ma nhOtig thuoc nay lai rat hay dUdc sit dung trong tim mach, nhat la khi benh nhan cd trieu chirng suy tim. Vi vay theo doi nhurig trieu chung lam sang va cac ket qua xet nghiem nhat la khi benh nhan mdi nhap vien rat quan trcng de phat hien sdm va xir tri kip thdi benh nhan cc bieu hien suy than khi sir dung thuoc tren. Tuy nhien trong dieu kien can phai diing nhurig nhom thuoc nay thi nen chon loai thudc cc dp dpc tinh thap nhat doi vdi than, chi dung vdi lieu dii cd hieu lut, giff dung khdang each giua cac lan dung va chi dung trong mdt thdi gian nhat dinh, khdng nen lam dung trong mot thdi gian dai de tranh dpc tinh cao gay tdn thudng nhirng cd quan nay.
V. KET LUAN
Qua nghien cu'u chung tdi nhan thay ddi vdi benh nhan viem npi tam mac nhiem khuan cay mau am tinh:
1. Neu khdng dap utig vdi trj lieu Penicillin va aminosid nay thi cd the thay the bang mot phac do phoi hdp Penicillin khac va amindsid khac vdi loai dang dung,
2. Neu khdng dap dng vdi phac do Cephalosporin the he 3 va amindsid thi nen thay bang phac dd Cephalospdrin the he 3 khac va aminosid khac.
3. Neu khdng dap dng vdi dieu tri bang Imipenem/cilastatin+Amindsid khi nhap vien thi van cd the dung Vancdmycin hoac cephalosporin the he 3 phoi hdp vdi clarythromycin.
TAI LIEU THAM KHAO
1. Ta Manh Cudng (2002), "Viem noi tam mac nhiem khuan", tap chi Tim Mach hoc Viet Nam, so 29 - thang 3, tr.55-60.
2. Andrian C, Aurilyn C, Jennifer A, Yolanda S (2000), "Blood culture negative endocarditis: Profile and Treatment outcome", Phil J Mcrobiol Infect Dis, 29(2), pp 14-17.
3. Baddour LM, Wilson WR, Bayer AS, et al (2005),
"Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America", Orcvlation, 111, ppe394-434.
4. Hoen B (2006), "Epidemiology and antibiotic treatment of infective endocarditis: an update".
Heart, 92, pp 1694-1700.
5. Hoen B, Selton-Suty C, Lacassin F, et al (1995), "Infective endocarditis in patients with negative blood cultures: analysis of 88 cases from a one-year nationwide survey in France", Clin Infect Dis, 20, pp 501-506.
6. Houpikian P, Raoult D (2005), "Blood culture- negative endocarditis in a reference center:
etiologic diagnosis of 348 cases", Medicine (Baltimore), 84, pp 162-173.
7. Pesanti EL, Smith IM (1979), "Infective endocarditis with negative blood cultures. An analysis of 52 cases", Am J Med, 66(1), pp 43-50.
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