Study On In Vitro Antibacterial Activities And Respiratory Ward Rationality Of Four Medication Of Complex Preparation Containing β-lactamase Inhibitor

Objective:1To investigate the enzyme productions and phenotype of clinicalisolates of Gram-negative bacteria, Determine of antibacterial activity in vitrocomposed of inhibitors β-lactamase inhibitor with different proportions of β-lactamantimicrobial compound inculding: Piperacillin Sodium and Sulbactam Sodium forInjection/Piperacillin Sodium and Tazobactam Sodium for Injection/CefoperazoneSodium and Sulbactam Sodium for Injection/Cefoperazone Sodium and TazobactamSodium for Injection. Combined with the rational evaluation of current clinicalapplication of antibiotics in the treatment of respiratory infection cases, put forwardsuggestions of rational use of antibiotics of clinical treatment,and try to promote therational use of medical resources.Method:1Nitrocefin paper assay was used to detect the situation of producingβ-lactamases Gram-negative bacteria, the disk diffusion method and disk diffusionconfirmatory screening test assay was used to detect the situation of producingextended-spectrum β-lactamases (ESBLs), cefoxitin three-dimensional test wasadopted to detect the emergence of cephalosporin enzyme (AmpC), double-disksynergy test and the efficiency test assay was used to detect metalloenzymes (MBL)in order to determine enzyme phenotype.2By broth dilution method to determine minimum inhibitory concentration (MIC)and Plate method to determine minimum bactericidal concentration (MBC) of sevendifferent manufacturers β-lactam antimicrobial agents against clinical isolates ofGram-negative bacteria.3Guiding principles for clinical application of Antibacterials, estimate the rationalityof clinical application composed of inhibitors β-lactamase inhibitor including：Cefoperazone Sodium and Tazobactam Sodium for Injection/Piperacillin Sodiumand Tazobactam Sodium for Injection/Piperacillin Sodium and Sulbactam Sodium forInjection.Results:1. Among258gram-negative bacilli,there were103strains Acinetobacter baumannii (39.92%),60strains Escherichia coli(23.26%),49strains Klebsiellapneumonia(18.99%),46strains Pseudomonas aeruginosa, Among258gram-negativebacilli, there were202strains producingβ-lactamase (78.29%),38strains producingESBLs (14.73%),58strains producing AmpC(22.48%),9strains producingMBL(3.48%).and10strains producing ESBLs and AmpC enzyme(3.88%),1strainsproducing ESBLs and MBL enzyme(0.33%),1strains producing ESBLs and MBLenzyme(0.33%),2strains(0.66%) producing ESBLs, AmpC and MBL enzyme at thesame time. The most common detection of ESBLs is the Escherichia coli andKlebsiella pneumoniae, ESBLs total respectively detection rate was41.67%(25/60),and28.57%(14/49), AmpC highest detection rate is Acinetobacter baumannii, was38.83%.2CPZ/SBT (2:1), PIP/SBT (2:1), CPZ/TAZ (4:1), PIP/TAZ (8:1) MIC90andMBC90for Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosaAeromonas, value Acinetobacter baumannii is CPZ, PIP preparations1/4to1/2.For Escherichia coli, Pseudomonas aeruginosa, CPZ/SBT (2:1), PIP/SBT (2:1)MIC90and MBC90is CPZ/TAZ (4:1), is PIP/TAZ (8:1)1/2. For Klebsiellapneumoniae, Acinetobacter baumannii, to four antimicrobial MIC90and MBC90theβ-lactamase inhibitor is basically the same.Acinetobacter baumannii is not sensitive to various antimicrobial agents, highresistance rates, resistance rates prescribed preparations which close to100%.Resistance to the compound preparation also more than80%. Pseudomonasaeruginosa to piperacillin sulbactam and cefoperazone sulbactam higher sensitivity,resistance rates of single preparations at around80%. For Klebsiella pneumoniaestrains resistant rate is greater than the sensitivity rate for compound preparationresistance rates below80%, the rate of resistance to unilateral formulations above80%. Escherichia coli strains higher sensitivity, more than30%. However, resistancerates of single preparations at around80%.3The β-lactamase producing Escherichia coli resistance to each antimicrobial agentsresistance were CPZ/SBT27.66%, CPZ/TAZ34.04%, PIP/SBT10.64%, PIP/TAZ38.30%. The β-lactamase producing Klebsiella pneumoniae resistance to each antimicrobial agents resistance were CPZ/SBT73.33%, CPZ/TAZ76.67%, PIP/SBT46.67%, PIP/TAZ76.67%. The β-lactamase producing Pseudomonasaeruginosa resistance to each antimicrobial agents resistance were CPZ/SBT44.44%,CPZ/TAZ70.37%, PIP/SBT29.63%, PIP/TAZ62.96%.. The β-lactamaseproducing Acinetobacter baumannii resistance to each antimicrobial agents resistancewere CPZ/SBT94.85%, CPZ/TAZ100.00%, PIP/SBT50.52%, PIP/TAZ97.94%.The β-lactamase producing Pseudomonas aeruginosa and the β-lactamase producingAcinetobacter baumannii resistance rates of CPZ/SBT is below CPZ/TAZ, asignificant difference was statistically significant (P <0.01). The strains on PIP/SBTresistance rates lower than PIP/TAZ, a significant difference was statisticallysignificant (P <0.01).4. In2012Hospital respiratory ward use all total47kinds of antibacterial. Sortantimicrobial drugs DDDs value of four major applications β-lactam/β-lactamaseinhibitors are arranged in the previous18. in47kinds of antibacterial drugs In thetotal420clinical cases with drug use,345ones meet the standard, male-to-femaleratio of1.92:1,,286ones were fair treated,accounting for82.90%,59ones wereunfair treated,accounting for17.10%, and32’s treatments were either too long or tooshort,20recieved overdose,50had antibiotic associated with irrational,4underwenttreatments without clinical indications. There are12cases had adverse reactions,with a rate of3.74%.Conclusions:1collected within Gram-negative bacteria strains producing β-lactamase enzyme production rate is higher, especially Acinetobacter baumannii hasbecome infected with one of the most important nosocomial pathogens in currently.Within Gram-negative bacteria strains producing β-lactamase enzyme which yieldsESBLs and AmpC enzyme production yields are higher than yields in the mostcommon Escherichia coli and Klebsiella pneumoniae, AmpC enzyme productionyields are highest in Acinetobacter Acinetobacter. In clinical isolates ofGram-negative bacilli, ESBLs and AmpC enzyme production already at a certain level,it may be one of the main factors leading to such bacterial resistance, the bacteria canbe further study β-lactamase resistant detection of gene analysis. The enzyme productions and phenotype of clinical isolates of Gram-negative bacteria should becaused hospital infection management attention, The management of respiratory andintensive care (ICU) wards of hospitals to strengthen the management ofantimicrobial drug use need to strengthen.2. β-lactam/β-lactamase inhibitor combination can effectively improve effect forclinical Gram-negative bacilli antibacterial. Escherichia coli and Pseudomonasaeruginosa, compound preparations containing sulbactam better antibacterial activitythan the compound preparations containing tazobactam. With the β-lactam/β-lactamase inhibitor and a large number of antimicrobial agents in a wideapplications,the clinical resistant rate of Gram-negative bacilli to the drugs areimproved.. Klebsiella pneumoniae, Pseudomonas aeruginosa resistance tocefoperazone and sulbactam or piperacillin and tazobactam were over40%, Warninginformation shall timely inform clinical staff and let them carefully Experiencemedication. Acinetobacter baumannii cefoperazone sulbactam to variousantimicrobial agents resistance were50%, to various other antimicrobial resistancerates above90%., Selecte drugs according to the results of susceptibility testing.Gram-negative bacilli resistant to compound preparations containing β-lactamaseinhibitors in hospital tend to serious, especially Acinetobacter baumannii, showingmultidrug-resistant, extensively drug-resistant. Hospitals should focus on bacterialresistance monitoring, clinicians should rational use of antimicrobial drugs based onbacteriological examination and susceptibility results. Non-producing strains resistantis lower then producing strains.3.Drugs containing β-lactamase inhibitor antimicrobial is a major disease medicinesin clinical treatment of respiratory infections has high frequency of administration.Most cases select drugs can be referred to bacteriological examination, antimicrobialsusceptibility test results etc. Drug dose/drug interval/route of administration, drugincompatibility ect reasonable; There are antimicrobial drug combination therapy isnot appropriate, inadequate medication treatment, for special populations unable to doindividual dose, too frequent replacement drugs etc in some cases Hospitalmanagement departments should strengthen the management of antimicrobial drug use, drug-resistant bacteria in hospitals should be timely informed, clinicians useantimicrobial drugs should refer to the bacteriological examination, susceptibility testresults, the patient signs, symptoms, and other individual differences in rational drugselection and dosage, according to the standard medication treatment, to ensure thatthe treatment effect; combination therapy and medication replace should according toindications, and recorded in the medical record, avoid no indication combination andreplace, lead to the degree of bacterial resistance increasing, reduced effect. Clinicalpharmacists should work closely with clinicians to provide technical support for therational use of antimicrobial drugs for clinical use.