12. 万古霉素耐药性1997 日本首次报道 VISA
2002年美国首次报道 VRSAMMWR July 2002
1st 例 – Michigan
导管及糖尿病溃疡培养
2nd 例 – Pennsylvania Tenover et al 2004
足根溃疡
先前无万古霉素暴露Whitener et al 2004
20. 奎奴普丁/达福普汀疗效Design: 2 randomized, open-label, controlled clinical trials in cSSSI
Study 1: Q/D (7.5 mg/kg q12h IV) vs oxacillin (2 g q6h IV)*
Study 2: Q/D (7.5 mg/kg q12h IV) vs cefazolin (1 g q8h IV)*Q/D (n=450)Comparator (n=443)Study 1 (US)49.5%51.9%Study 2 (International)66.4%64.2%Postoperative infections‡14/38 (36.8%)24/42 (57.1%)Traumatic wound infections‡33/55 (60.0%)33/55 (60.0%)*vancomycin 1 g q12h IV could be substituted if the pathogen was suspected or confirmed MRSA or the patient was allergic to penicillin, cephalosporins, or carbapenems. †Patients cured or improved. ‡Results are combined from the 2 clinical trials. Statistical conclusions could not be reached due to the small number of patients in the subsets.
CE=clinically evaluable; cSSSI=complicated SSSI.Efficacy in the CE Population†Synercid® IV (quinupristin/dalfopristin for injection) [package insert]. Bristol, Tenn: Monarch Pharmaceuticals, Inc; 2002.
21. 奎奴普丁/达福普汀疗效Design: 2 randomized, open-label, controlled clinical trials in cSSSISummary of Clinical and Microbiologic Results*Q/D (n=450)Comparator(n=443)Clinical efficacy†68.2%70.7%Microbiologic eradication‡66.6%77.7% MSSA64.3% 76.6% MRSA77.8%50.0% Gram-positive cocci only56.3%69.7%*Results are combined from the 2 clinical trials. †Patients cured or improved in the CE population. ‡Overall and by-pathogen bacteriologic eradication rates in the microbiologically evaluable population.
Nichols RL et al. J Antimicrob Chemother. 1999;44:263-273.
28. Dalbavancin (Zeven)新一代糖肽类
每周一次,静脉给药
Dalbavancin vs 利奈唑胺治疗 CSSSI
Dalba 首剂1 gm, 7日后再用 500 mg
利奈唑胺600mg q12h IV 或 po ×14 d
两组疗效均 >90%
Jauregui, CID Nov 15, 2005
29. Clinical Efficacy of Weekly Dalbavancin vs Standard-of-Care Antimicrobials for SSSIsStandard-of-care antibiotics included cefazolin, vancomycin, clindamycin, ceftriaxone, and piperacillin/tazobactam.Seltzer E et al. Clin Infect Dis. 2003;37:1298-1303.
30. Dalbavancin (Zeven)与万古霉素比较??
治疗GPC所致导管相关性BSI 临床有效率:
Dalbavancin = 87%
万古霉素 = 50%
Raad et al, CID Feb 2005
31. Telavancin新一代糖肽类
治疗 CSSSI 细菌清除率:
Telavancin = 92%
万古霉素 = 68%
Stryjewski et al, AAC Mar 2006
32. Telavancin新一代糖肽类
对GPC呈浓度依赖性快速杀菌作用
MRSA, MRSE, VRE, VISA, VRSA
随即对照双盲 III 期临床试验 (n=167)
Telavancin QD vs 耐酶青霉素 QID 或万古霉素 BID
Stryjewski ME et al. Clin Infect Dis. 2005;40:1601-1607.nTelavancin Comparator*S aureus10280%77%MRSA – clin cure4882%69%MRSA – micro cure4884%74%
45. Arbekacina derivative of dibekacin, is an aminoglycoside
developed and used in Japan for the treatment MRSA infections
46. Nationwide investigation in Japan on the efficacy of arbekacin in MRSA infections A clinical investigation of MRSA infections to study the efficacy of arbekacin was carried in 115 institutions in Japan
348 patients were evaluated. 74 patients were treated with ABK alone and 274 with ABK in combination with other compounds
Bacteriological clinical efficacy was 75.6%/67.9% in pure infection and 63.6%/71.3% in polymicrobial infection
Adverse effects were seen in 4.76%/5.7%, but no case was serious. Abnormal laboratory findings were noted in 15.4% of casesDrugs Exp Clin Res. 1994;20(6):225-32.
51. Carbapenemase-Producing Klebsiella pneumoniae Organisms that produce KPC have similar resistance profiles to most ESBLs, but with the addition of carbapenem resistance.
Treatment options
Tigecycline
Polymyxins
Other tetracyclines (at times)
Aminoglycosides (at times)Pharmacotherapy. 2008;28(2):235-249
63. Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the treatment of multidrug resistant Acinetobacter baumannii ventilator-associated pneumonia METHODS
A prospective cohort study in adult critically ill patients with VAP
Amp/Sulb (9 g every 8h) or COL (3 MIU every 8h) intravenously
RESULTS
A total of 28 patients were enrolled (15 COL, 13 Amp/Sulb).
Resolution of symptoms and signs occurred in 60% (9/15) of the COL group and 61.5% (9/13) of the Amp/Sulb group, improvement in 13.3% (2/15) vs. 15.3% (1/13) and failure in 26.6% (4/15) vs. 23% (3/13
Bacteriologic success was achieved in 66.6% (10/15) vs. 61.5% (8/13) in the COL and Amp/Sulb groups
Mortality rates (14 days and 28 days) were 15.3% and 30% for the Amp/Sulb and 20% and 33% for the COL group
Adverse events were 39.6% (including 33% nephrotoxicity) for the COL group and 30.7% (15.3% nephrotoxicity) for the Amp/Sulb group (p=NS)
CONCLUSION
Colistin and high-dose AM/SB were comparably safe and effective treatments for critically ill patients with MDR A. baumannii VAP J Infect. 2008 Jun;56(6):432-6
64. Management of MDR PathogensIf P aeruginosa, combination therapy is recommended
If Acinetobacter spp, the most active agents are the carbapenems, sulbactam, colistin, and polymyxin
Avoid monotherapy with a third-generation cephalosporin for ESBL+ Enterobacteriaceae
Consider adjunctive inhaled aminoglycoside for MDR Gram-negative pneumonia in patients not improving with systemic therapy
Linezolid is an alternative to vancomycin for treatment of MRSA VAP
Linezolid may be preferred (but more data are needed) in patients:
Who have renal insufficiency
Receiving other nephrotoxic agentsATS/IDSA. Am J Respir Crit Care Med. 2005;171:388-416.