中华传染病杂志
中華傳染病雜誌
중화전염병잡지
CHINESE JOURNAL OF INFECTIOUS DISEASES
2014年
9期
522-527
,共6页
叶荣夏%季京淑%史可人%蒋琰%俞云松
葉榮夏%季京淑%史可人%蔣琰%俞雲鬆
협영하%계경숙%사가인%장염%유운송
磷霉素%替加环素%KPC%肺炎克雷伯菌%联合抗菌效应%fosA
燐黴素%替加環素%KPC%肺炎剋雷伯菌%聯閤抗菌效應%fosA
린매소%체가배소%KPC%폐염극뢰백균%연합항균효응%fosA
Fosfomycin%Tigecycline%KPC%Klebsiella pneumoniae%Combined antimicrobial activity%fosA
目的：评价磷霉素和替加环素对产肺炎克雷伯菌碳青霉烯酶（KPC 酶）肺炎克雷伯菌的体外联合抗菌效应并研究其对磷霉素的耐药机制。方法微量肉汤稀释法分别测定磷霉素和替加环素单药对42株肺炎克雷伯菌（20株产 KPC 酶，22株 KPC 酶阴性）的最低抑菌浓度（MIC）。采用棋盘法设计测定不同浓度组合的抗菌药物的联合药物敏感试验，计算分级抑菌浓度指数（FICI）并判定联合效应。FICI＝MIC磷霉素联合/MIC磷霉素单药＋MIC替加环素联合/MIC替加环素单药。相关判读标准：FICI≤0．5为协同作用，0．5＜FICI≤1．0为相加作用，1＜FICI≤2为无关作用，FICI＞2为拮抗作用。对磷霉素耐药的产 KPC酶肺炎克雷伯菌进行常见磷霉素耐药基因筛选。数据比较采用 t 检验。结果产 KPC 酶肺炎克雷伯菌对磷霉素的敏感率为35．0％（7/20），替加环素敏感率为70．0％（14/20）。联合用药后，敏感率分别增至50．0％（10/20）和95．0％（19/20），且各自 MIC 值均有所下降。替加环素在联合后 MIC 值下降明显，与单药 MIC 比较差异有统计学意义（t＝-2．596，P ＝0．013），而磷霉素联合前后 MIC 比较差异无统计学意义（t ＝-1．274，P ＝0．211）。FICI 显示，2种抗菌药物的协同、相加效应共计60％，无关效应占40％，未发现拮抗作用。22株 KPC 酶阴性菌株2种抗菌药物联合无关作用占54．5％，相加、协同效应分别为31．8％和13．6％，无拮抗作用。2株携带 fosA 耐药基因的菌株，其 fosA 与 KPC 酶基因均定位于同一质粒上，质粒分别为138．9 kb 与104．5 kb。结论产 KPC 酶肺炎克雷伯菌对替加环素敏感性较高。替加环素联合磷霉素以协同作用和相加作用为主，提示该联合用药方案对产 KPC 酶肺炎克雷伯菌具有一定的抑制效应。
目的：評價燐黴素和替加環素對產肺炎剋雷伯菌碳青黴烯酶（KPC 酶）肺炎剋雷伯菌的體外聯閤抗菌效應併研究其對燐黴素的耐藥機製。方法微量肉湯稀釋法分彆測定燐黴素和替加環素單藥對42株肺炎剋雷伯菌（20株產 KPC 酶，22株 KPC 酶陰性）的最低抑菌濃度（MIC）。採用棋盤法設計測定不同濃度組閤的抗菌藥物的聯閤藥物敏感試驗，計算分級抑菌濃度指數（FICI）併判定聯閤效應。FICI＝MIC燐黴素聯閤/MIC燐黴素單藥＋MIC替加環素聯閤/MIC替加環素單藥。相關判讀標準：FICI≤0．5為協同作用，0．5＜FICI≤1．0為相加作用，1＜FICI≤2為無關作用，FICI＞2為拮抗作用。對燐黴素耐藥的產 KPC酶肺炎剋雷伯菌進行常見燐黴素耐藥基因篩選。數據比較採用 t 檢驗。結果產 KPC 酶肺炎剋雷伯菌對燐黴素的敏感率為35．0％（7/20），替加環素敏感率為70．0％（14/20）。聯閤用藥後，敏感率分彆增至50．0％（10/20）和95．0％（19/20），且各自 MIC 值均有所下降。替加環素在聯閤後 MIC 值下降明顯，與單藥 MIC 比較差異有統計學意義（t＝-2．596，P ＝0．013），而燐黴素聯閤前後 MIC 比較差異無統計學意義（t ＝-1．274，P ＝0．211）。FICI 顯示，2種抗菌藥物的協同、相加效應共計60％，無關效應佔40％，未髮現拮抗作用。22株 KPC 酶陰性菌株2種抗菌藥物聯閤無關作用佔54．5％，相加、協同效應分彆為31．8％和13．6％，無拮抗作用。2株攜帶 fosA 耐藥基因的菌株，其 fosA 與 KPC 酶基因均定位于同一質粒上，質粒分彆為138．9 kb 與104．5 kb。結論產 KPC 酶肺炎剋雷伯菌對替加環素敏感性較高。替加環素聯閤燐黴素以協同作用和相加作用為主，提示該聯閤用藥方案對產 KPC 酶肺炎剋雷伯菌具有一定的抑製效應。
목적：평개린매소화체가배소대산폐염극뢰백균탄청매희매（KPC 매）폐염극뢰백균적체외연합항균효응병연구기대린매소적내약궤제。방법미량육탕희석법분별측정린매소화체가배소단약대42주폐염극뢰백균（20주산 KPC 매，22주 KPC 매음성）적최저억균농도（MIC）。채용기반법설계측정불동농도조합적항균약물적연합약물민감시험，계산분급억균농도지수（FICI）병판정연합효응。FICI＝MIC린매소연합/MIC린매소단약＋MIC체가배소연합/MIC체가배소단약。상관판독표준：FICI≤0．5위협동작용，0．5＜FICI≤1．0위상가작용，1＜FICI≤2위무관작용，FICI＞2위길항작용。대린매소내약적산 KPC매폐염극뢰백균진행상견린매소내약기인사선。수거비교채용 t 검험。결과산 KPC 매폐염극뢰백균대린매소적민감솔위35．0％（7/20），체가배소민감솔위70．0％（14/20）。연합용약후，민감솔분별증지50．0％（10/20）화95．0％（19/20），차각자 MIC 치균유소하강。체가배소재연합후 MIC 치하강명현，여단약 MIC 비교차이유통계학의의（t＝-2．596，P ＝0．013），이린매소연합전후 MIC 비교차이무통계학의의（t ＝-1．274，P ＝0．211）。FICI 현시，2충항균약물적협동、상가효응공계60％，무관효응점40％，미발현길항작용。22주 KPC 매음성균주2충항균약물연합무관작용점54．5％，상가、협동효응분별위31．8％화13．6％，무길항작용。2주휴대 fosA 내약기인적균주，기 fosA 여 KPC 매기인균정위우동일질립상，질립분별위138．9 kb 여104．5 kb。결론산 KPC 매폐염극뢰백균대체가배소민감성교고。체가배소연합린매소이협동작용화상가작용위주，제시해연합용약방안대산 KPC 매폐염극뢰백균구유일정적억제효응。
Objective To evaluate antimicrobial activity of fosfomycin combined with tigecycline against Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae and study the mechanism of drug resistance to fosfomycin. Methods Broth microdilution method was used to independently determine the minimum inhibitory concentrations (MIC)of fosfomycin and tigecycline against 42 Klebsiella pneumoniae isolates (including 20 KPC-producing and 22 KPC non-producing isolates).Checkerboard design method was applied to evaluate combined effect of different concentrations on antimicrobial susceptibility and calculate the fractional inhibitory concentration index (FICI).FICI=MICfosfomycin joint/MICfosfomycin monotherapy +MICtigecycline joint/MICtigecycline monotherapy .Related interpretation criteria were as following:FICI≤0.5 means synergy;0.5 <FICI≤1 .0 means additive;1 <FICI≤2 means indifference;FICI> 2 means antagonism.The fosfomycin resistant genes in KPC-producing Klebsiella pneumoniae isolates were screened.The data were analyzed by t test.Results Antimicrobial susceptibility testing results indicated the fosfomycin and tigecycline susceptibility rates in KPC-producing isolates were 35 .0%(7/20)and 70.0% (14/20 ),respectively.The susceptibility rates of drug combination increased to 50.0% (10/20 )and 95 .0% (19/20 ),respectively,with both MIC decreased.MIC of tigecycline decreased significantly after combination therapy and showed a statistical significance compared with the MIC of monotherapy (t = - 2.596,P = 0.013 ),whereas there was no significant difference between single and combined therapy of fosfomycin (t=-1 .274,P =0.211).FICI indicated that a total of 60.0%isolates showed synergy and additive effects between two antimicrobial agents,followed by indifference (40.0%),but there was no antagonism effect.Among 22 KPC non-producing isolates,there were 54.5 %showing indifference effects,followed by additive (31 .8%)and synergy (13.6%)effects.No antagonism effect was found.The study also identified two isolates with fosA resistant gene which located on the same plasmid as well as the bla KPC gene.The plasmid sizes in the two isolates were 138.9 kb and 104.5 kb, respectively.Conclusions KPC-producing Klebsiella pneumoniae are more susceptible to tigecycline. Combined use of two antimicrobial agents mainly exerts synergy and additive effect rather than antagonism,which may suggest the combination therapy strategy could inhibit the activity of KPC-producing Klebsiella pneumoniae .
