抗菌药物用量与铜绿假单胞菌耐药相关性研究

Association between anti-bacterial agents use and drug resistance in Pseudomonas aeruginosa

目的分析抗菌药物用量与铜绿假单胞菌耐药的关系，帮助临床合理使用抗菌药。方法回顾性分析我院2001-2007年铜绿假单胞菌耐药率和具有抗假单胞菌活性抗菌药物的使用量，用药频度（DDDs）表示为每日每1000例患者中消耗的限定日剂量数。结果2001-2007年每年检出铜绿假单胞菌菌株数依次为150、208、165、205、264、271和262株。铜绿假单胞菌对多数抗菌药物的耐药率均较高，2005～2007年除头孢哌酮／舒巴坦的耐药率逐年下降外，其他抗菌药物耐药率均呈现增高趋势。2007年抗菌药物耐药率由低到高分别为：头孢哌酮／舒巴坦16．0％，头孢他啶33．1％，哌拉西林／三唑巴坦34．3％，头孢吡肟35．2％，左氧氟沙星37．7％，美罗培南39．3％，阿米卡星41．0％，亚胺培南44．7％。铜绿假单胞菌对哌拉西林／三唑巴坦的耐药率不仅与该药本身的DDDs显著相关（r=0．900，P=0．037），同时还与莫西沙星DDDs呈正相关（r=0．900，P=0．037），而与环丙沙星（r=-0．940，P=0．017）和阿米卡星（r=-0．900，P=0．037）的DDDs呈负相关；亚胺培南的耐药率与环丙沙星DDDs（r=-0．905，P=0．005）呈负相关；头孢他啶的耐药率与美罗培南（r=1.000，P=0．000）、哌拉西林／三唑巴坦（r=1．000，P=0．000）、莫西沙星（r=1．000，P=0．000）的DDDs呈正相关，而与环丙沙星（r=-0．968，P=0．032）、阿米卡星（r=-1．000，P=0．000）和奈替米星（r=-1．000，P=0．000）的DDDs呈负相关；左氧氟沙星的耐药率与亚胺培南／西司他丁的DDDs呈负相关（r=-0．988，P=0．012）；阿米卡星的耐药率与环丙沙星的DDDs呈负相关（r=-0．964，P=0．000）。结论铜绿假单胞菌对某种抗菌药的耐药率主要与该药本身以及同类药物的使用量有关。尽量减少抗假单胞菌药物的使用，才能从根本上减轻细菌耐药。

Objective To investigate the association between anti-bacterial agents use and drug resistance in Pseudomonas aeruginosa,and guide rational use of anti-bacterial agents. Methods The drugresistant rates of Pseudomonas aeruginosa to commonly used anti-bacterial agents and the use of antibacterial agents with activity against Pseudomonas strains from 2001 to 2007 were retrospectively analyzed. Anti-bacterial agents use data were expressed as the number of defined daily doses （DDDs） per 1000 patients. Results The number of strains of Pseudomonas aeruginosa from 2001 to 2007 were 150,208,165, 205,264,271 and 262 respectively. From 2005 to 2007, the drug-resistant rates of Pseudomonas aeruginosa to almost all anti-bacterial agents showed a trend of increase, except cefoperazone-sulbaetam. In 2007, cefoperazone-sulbactam had the lowest drug-resistant rate which was 16.0%, followed by ceftazidime 33.1%, piperacillin-tazobactam 34.3 %, cefepime 35.2 %, levofloxacin 37.7 %, meropenem 39.3 %, amikacin 41.0% and imipenem 44.7 %. The drug-resistant rate of Pseudomonas aeruginosa to piperaeillin-tazobactam was positively correlated with not only DDDs of piperacillin-tazobactam （ r =0. 900, P = 0. 037）, but also that of moxifloxacin（ r = 0. 900, P = 0. 037）, and negatively correlated with DDDs of ciprofloxcin（ r =0.940, P =0.017） and amikacin （r =-0.900, P =0.037）. Drug-resistant rate to imipenem was negatively correlated with DDDs of ciprofloxacin （r =-0.905, P = 0.005）. Drug-resistant rate to ceftazidime was positively correlated with DDDs of meropenem （r = 1. 000, P = 0. 000）, piperacillintazobactam（ r = 1. 000, P =0. 000） and moxicillin（ r = 1. 000, P =0. 000） ,while negatively correlated with DDDs of ciprofloxacin（ r = -0. 968, P =0. 032） ,amikacin（ r =-1. 000, P =0. 000） and netilmicin （ r = -1. 000, P = 0. 000）. Drug-resistant rate to levofloxacin was negatively correlated with DDDs of imipenemcilastatin（ r =-0. 988, P =0. 012）. Drug-resistant rate to amikacin was negatively correlated with DDDs of ciprofloxacin（ r =-0. 964, P = 0. 000）. Conclusions The drug resistance of Pseudomonas aeruginosa to anti-bacterial agent was mainly caused by the use of this agent itself and the same kind of anti-bacterial agents. In order to prevent bacterial resistance, the use of anti-bacterial agents with activity against Pseudomonas strains must be limited as far as possible.