磷霉素钠体外联合药敏研究
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摘要
目的评价磷霉素钠体外单药及联合其他抗菌药物对我国临床分离金黄色葡萄球菌、肺炎克雷伯菌和铜绿假单胞菌的抗菌作用。方法联合药敏测定采用棋盘法,最低抑菌浓度(MIC)测定采用琼脂二倍稀释法,对来自全国18所医院近3年临床分离的金黄色葡萄球菌(113株)、肺炎克雷伯菌(108株)和铜绿假单胞菌(110株)进行单药及联合药敏测定。结果对所测菌株,不论其对其他抗菌药物是否耐药,磷霉素钠单药的MIC_(50)值均≤32 mg/L。与左氧氟沙星、米诺环素、苯唑西林、克林霉素联合均对耐甲氧西林金黄色葡萄球菌(MRSA)有较好协同作用,协同率>43%。对于亚胺培南不敏感铜绿假单胞菌,磷霉素钠与左氧氟沙星、亚胺培南的协同率>35%,对于亚胺培南敏感铜绿假单胞菌,磷霉素钠与所测药物协同率均>35%。结论磷霉素钠对临床常见耐药菌,如MRSA、产超广谱β-内酰胺酶肺炎克雷伯菌等仍有较好的抗菌作用,与多种其他类抗菌药物可产生协同作用,提示针对耐药菌所致感染,在有限的治疗手段中,含磷霉素的联合用药不失为一种选择。
Objective To evaluate in vitro antimicrobial effect of fosfomycin sodium single use and combination with other antimicrobial agents on clinically isolated Staphylococcus aureus(S.aureus),Klebsiella pneumoniae(K.pneumoniae)and Pseudomonas aeruginosa(P.aeruginosa)in China.Methods Combined antimicrobial susceptibility testing was performed with checkerboard method,minimal inhibitory concentrations(MICs)were detected by two-fold agar dilution method,susceptibility of S.aureus(n=113 strains),K.pneumoniae(n=108 strains),and P.aeruginosa(n=110 strains)isolated from 18 hospitals in China in recent three years was determined by single and combined antimicrobial susceptibility testing.Results MIC_(50) value of fosfomycin sodium single use were all≤32 mg/L against all tested strains,regardless of whether strains were resistant to other antimicrobial agents or not.The synergistic rate of fosfomycin sodium with levofloxacin,minocycline,oxacillin,and clindamycin against methicillin-resistant S.aureus(MRSA)was>43%.Synergistic rate of fosfomycin sodium with levofloxacin and imipenem against imipenem-nonsusceptible P.aeruginosa was>35%,synergistic rates of fosfomycin sodium with tested antimicrobial agents against imipenem-susceptible P.aeruginosa were all>35%.Conclusion Fosfomycin sodium still has good antimicrobial activity against common clinical drug-resistant bacteria,such as MRSA,extended-spectrumβ-lactamase-producing K.pneumoniae and so on,it has synergistic effect with many other kinds of antimicrobial agents,suggesting that in the limited treatment of infection caused by drug-resistant bacteria,fosfomycin in combination with other antimicrobial agents may be a useful choice.
Objective To evaluate in vitro antimicrobial effect of fosfomycin sodium single use and combination with other antimicrobial agents on clinically isolated Staphylococcus aureus(S.aureus),Klebsiella pneumoniae(K.pneumoniae)and Pseudomonas aeruginosa(P.aeruginosa)in China.Methods Combined antimicrobial susceptibility testing was performed with checkerboard method,minimal inhibitory concentrations(MICs)were detected by two-fold agar dilution method,susceptibility of S.aureus(n=113 strains),K.pneumoniae(n=108 strains),and P.aeruginosa(n=110 strains)isolated from 18 hospitals in China in recent three years was determined by single and combined antimicrobial susceptibility testing.Results MIC_(50) value of fosfomycin sodium single use were all≤32 mg/L against all tested strains,regardless of whether strains were resistant to other antimicrobial agents or not.The synergistic rate of fosfomycin sodium with levofloxacin,minocycline,oxacillin,and clindamycin against methicillin-resistant S.aureus(MRSA)was>43%.Synergistic rate of fosfomycin sodium with levofloxacin and imipenem against imipenem-nonsusceptible P.aeruginosa was>35%,synergistic rates of fosfomycin sodium with tested antimicrobial agents against imipenem-susceptible P.aeruginosa were all>35%.Conclusion Fosfomycin sodium still has good antimicrobial activity against common clinical drug-resistant bacteria,such as MRSA,extended-spectrumβ-lactamase-producing K.pneumoniae and so on,it has synergistic effect with many other kinds of antimicrobial agents,suggesting that in the limited treatment of infection caused by drug-resistant bacteria,fosfomycin in combination with other antimicrobial agents may be a useful choice.
引文
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[5]权菊香,赖蓓.磷霉素临床应用的研究现状[J].中国临床药理学杂志,2015,31(20);2067-2069.
[6]Kastoris AC,Rafailidis PI,Vouloumanou EK,et al.Synergy of fosfomycin with other antibiotics for Gram-positive and Gram-negative bacteria[J].Eur J Clin Pharmacol,2010,66(2):359-386.
[7]CLSI.Performance standards for antimicrobial susceptibility testing,27th edition.CLSI supplement M100[S].Wayne,PA:Clinical and Laboratory Standards Institute,2017.
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[9]Odd FC.Synergy,antagonism,and what chequerboard puts between them[J].J Antimicrob Chermother,2003,52(1):1.
[10]Falagas ME,Vouloumanou EK,Samonis G,et al.Fosfomycin[J].Clin Microbiol Rev,2016,29(2):321-347.
[11]Ferrara A,Dos Santos C,Cimbro M,et al.Effect of different combinations of sparfloxacin,oxacillin,and fosfomycin against methicillin-resistant Staphylococci[J].Eur J Clin Microbiol Infect Dis,1997,16(7):535-537.
[12]Evren E,Azap OK,Colakoglu S,et al.In vitro activity of fosfomycin in combination with imipenem,meropenem,colistin and tigecycline against OXA48-positive Klebsiella pneumoniae strains[J].Diagn Microbiol Infect Dis,2013,76(3):335-338.
[13]Liao Y,Hu GH,Xu YF,et al.Retrospective analysis of fosfomycin combinational therapy for sepsis caused by carbapenem-resistant Klebsiella pneumoniae[J].Exp Ther Med,2017,13(3):1003-1010.
[14]Grabein B,Graninger W,Rodríguez Ba1o J,et al.Intravenous fosfomycin-back to the future.Systematic review and meta-analysis of the clinical literature[J].Clin Microbiol Infect,2017,23(6):363-372.
[15]Bowers DR,Huang V.Emerging issues and treatment strategies in carbapenem-resistant Enterobacteriaceae(CRE)[J].Curr Infect Dis Rep,2016,18(12):48.
[16]Brennan-Krohn T,Truelson KA,Smith KP,et al.Screening for synergistic activity of antimicrobial combinations against carbapenem-resistant Enterobacteriaceae using inkjet printerbased technology[J].J Antimicrob Chemother,2017,72(10):2775-2781.
[2]Hendlin D,Stapley EO,Jackson M,et al.Phosphonomycin,a new antibiotic produced by strains of streptomyces[J].Science,1969,166(3901):122-123.
[3]Woodyer RD,Shao Z,Thomas PM,et al.Heterologous production of fosfomycin and identification of the minimal biosynthetic gene cluster[J].Chem Biol,2006,13(11):1171-1182.
[4]Michalopoulos AS,Livaditis IG,Gougoutas V.The revival of fosfomycin[J].Int J Infect Dis,2011,15(11):e732-e739.
[5]权菊香,赖蓓.磷霉素临床应用的研究现状[J].中国临床药理学杂志,2015,31(20);2067-2069.
[6]Kastoris AC,Rafailidis PI,Vouloumanou EK,et al.Synergy of fosfomycin with other antibiotics for Gram-positive and Gram-negative bacteria[J].Eur J Clin Pharmacol,2010,66(2):359-386.
[7]CLSI.Performance standards for antimicrobial susceptibility testing,27th edition.CLSI supplement M100[S].Wayne,PA:Clinical and Laboratory Standards Institute,2017.
[8]Eliopoulos GM,Moellering RC.Antibiotic combinations[M]//Lorian V.Antibiotics in laboratory medicine,3rd ed.Baltimore:Williams and Wilkins,1991:432-492.
[9]Odd FC.Synergy,antagonism,and what chequerboard puts between them[J].J Antimicrob Chermother,2003,52(1):1.
[10]Falagas ME,Vouloumanou EK,Samonis G,et al.Fosfomycin[J].Clin Microbiol Rev,2016,29(2):321-347.
[11]Ferrara A,Dos Santos C,Cimbro M,et al.Effect of different combinations of sparfloxacin,oxacillin,and fosfomycin against methicillin-resistant Staphylococci[J].Eur J Clin Microbiol Infect Dis,1997,16(7):535-537.
[12]Evren E,Azap OK,Colakoglu S,et al.In vitro activity of fosfomycin in combination with imipenem,meropenem,colistin and tigecycline against OXA48-positive Klebsiella pneumoniae strains[J].Diagn Microbiol Infect Dis,2013,76(3):335-338.
[13]Liao Y,Hu GH,Xu YF,et al.Retrospective analysis of fosfomycin combinational therapy for sepsis caused by carbapenem-resistant Klebsiella pneumoniae[J].Exp Ther Med,2017,13(3):1003-1010.
[14]Grabein B,Graninger W,Rodríguez Ba1o J,et al.Intravenous fosfomycin-back to the future.Systematic review and meta-analysis of the clinical literature[J].Clin Microbiol Infect,2017,23(6):363-372.
[15]Bowers DR,Huang V.Emerging issues and treatment strategies in carbapenem-resistant Enterobacteriaceae(CRE)[J].Curr Infect Dis Rep,2016,18(12):48.
[16]Brennan-Krohn T,Truelson KA,Smith KP,et al.Screening for synergistic activity of antimicrobial combinations against carbapenem-resistant Enterobacteriaceae using inkjet printerbased technology[J].J Antimicrob Chemother,2017,72(10):2775-2781.