Study On The Relationship Between Pyrazinamide-Resistant And Therapeutic Effect Of Pulmonary Tuberculosis

BackgroundTuberculosis is an ancient disease.Mycobacterium tuberculosis (human or cattle type) isthe pathogen of this disease,which had a coevolution with humans of tens thousands ofyears.It is also one of the most challenging public health problems worldwide. Contain in theDirectly Observed Treatment Short-course program recommended by World HealthOrganization（WHO）,pyrazinamide is an important antituberculosis drug.The main cause oftuberculosis treatment failure is drug resistance. Drug resistance can increase TB patients’fatality rate and reduce cure rate.Pyrazinamide(PZA) is an important first-line antituberculosis (anti-TB) drug, which canshorten the course of TB treatment from the9to12months to the6months due to its uniquerole, at the same time, PZA is also one of the cornerstone drugs retained in the treatment ofmultidrug-resistant tuberculosis (MDR-TB). WHO issued a MDR tuberculosis treatmentguidelines,PZA was recommended to be included in MDR-TB treatment regimens during theentire duration of treatment. Since the PZA was widely used in short-course chemotherapyregimen,there was a growing tendency of the resistant to PZA. According to the report ofAmerican Centers for Disease Contro(CDC),pyrazinamide resistance increased from2.0%to3.3%per year during1999-2009nationwide. There is no relevant epidemiological data in ourcountry. Some foreign researchers found that patients with PZA monoresistance TB hadsignificantly worse clinical outcomes than patients with fully susceptible strains. To ourknowledge,there is no report about how much effect pyrazinamide-resistance would on the short-term efficacy of TB patients. In the recent studies,the rate of resistance to PZA wasabout50%in MDR M.tuberculosis strains. Some studies showed that MDR-TB cases thatresistant to PZA were more likely to have an unfavourable outcome than other MDR-TBcases.Treatment of MDR-TB is challenging because of the high toxicity of second-line drugsand the longer treatment duration required compared with drug-susceptible TB. Therefore,todetect the condition of pyrazinamide resistance during the early stage of treatment, tounderstand pyrazinamide resistance whether influence the therapeutic effect of TB becomeseven more important.ObjectivesStudy on the prevalence condition of pyrazinamide-resistance in PTB patients. Thenanalyse the influence of pyrazinamide resistance on the treatment of PTB patients.Anddiscuss the impact of PZA-resistant on the the intensive phase treatment of MDR-TB.PartⅠ The prevalence condition of pyrazinamide-resistance in PTBPatients and methodsSelect the sputum-positive PTB inpatients from Guangzhou chest hospital from2011to2013.,the total number is814, age between12-89years old (mean42.7years);517cases weremale,297cases were female (M/F=1.74);630cases were fisrt-treatment patients(77.4%),184cases were re-treatment patients(22.6%).All sputum specimens were collected from the deep sputum specimens in the earlymorning,which must be qualified that determined by laboratory personnelvisualization.Detect all the first-line antituberculosis drug(contains HRZES) resistant byBACTEC MGIT960method based on liqued medium.Results1. Among the sputum-positive PTB inpatients, the prevalence of pyrazinamide resistantwas25.81%, and prevalence of pyrazinamide monoresistance was10.2%;2. Among the PTB inpatients,the prevalence of pyrazinamide resistant in first-treated andre-treated patients was18.41%、48.37%,respectively,P=0.000; The prevalence ofpyrazinamide resistant in sputum acid fast bacilli(AFB)-positive and AFB-negative patientswas30.53%、20.82%、29.29%,respectively,P=0.001;3. Among the MDR-TB inpatients, the prevalence of pyrazinamide resistant was63.43%. PartⅡ The influence of pyrazinamide resistance on the therapeutic effect of PTBPatients and methods1. Cases Selection: The sputum culture-positive and AFB-positive pulmonary tuberculosisinpatients whom had been a treated in Gungzhou chest hospital from2011to2013during thehospitalization and194cases accorded with the condition. Divided into two groups,pyrazinamide susceptibility(PZA-S) group and pyrazinamide resistance(PZA-R) group. Thetotal number of PZA-S group is148, age between15-82years old (mean38.1years old),100cases were male,48cases were female,113cases were fisrt-treatment patients,35cases werere-treatment patients; The total number of PZA-R group is46, age between16-77years old(mean38.1years old),24cases were male,22cases were female,36cases were fisrt-treatmentpatients,10cases were re-treatment patients.2.Clinical observation method:The deep sputum specimens were collected from all theabove patients in the morning at the beginning、after2months and after6monthstreatment,detect first-line antituberculosis drug susceptibility tes（tDST） by BACTEC MGIT960method based on liqued medium if the culture was positive.At the same time, the sputumspecimens were dyed with the Ziehl-Neelsen anti-acid dyeing method three times. Examinechest X-ray(CT) at the beginning and after2months treatment.Results1. After two months treatment, the sputum negative conversion rate of PZA-S group andPZA-R group was86.49%、78.26%, respectively（χ2=1.816,P=0.178）;2. After two months treatment, the lesions absorption rate of PZA-S group and PZA-Rgroup was78.38%、76.08%, respectively（χ2=0.279,P=0.597）;3. After two months treatment, the tumor shrinking rate of PZA-S group and PZA-R groupwas75.4%、48.65%, respectively（χ2=9.623,P=0.002）;4. After six months treatment, the sputum conversion rate of PZA-S group and PZA-Rgroup was95.95%、86.96%, respectively（χ2=3.461,P=0.063）. PartⅢ The influence of pyrazinamide resistance on the treatment of MDR-TB intensivephasePatients and method1.Cases Selection: The MDR tuberculosis inpatients whom had been received a MDRregimen treatment(contain4-5kinds of anty-TB drugs) in Gungzhou chest hospital from2011to2013during the hospitalization.The patient continued to have follow-up examinations inour out-patient clinic during six months after discharge.According to treatmentregimen,divided into PZA treatment group(PZA was contain in regimen) and controlgroup(PZA was not contain in regimen). The total number of PZA treatment group is81,52cases were male,29cases were female,according to their condition of PZA susceptibilitydivided into pyrazinamide susceptibility(PZA-S) group,in total31cases,23cases weremale,8cases were female;and pyrazinamide resistance(PZA-R) group, in total50cases,29cases were male,21cases were female. The total number of control group is36,21caseswere male,15cases were female.2. The deep sputum specimens were collected from all the above patients in the morningat the beginning and after6months treatment,detect first-line antituberculosis drugsusceptibility test（DST）by BACTEC MGIT960method based on liqued medium.At thesame time, the sputum specimens were dyed with the Ziehl-Neelsen anti-acid dyeing methodthree times. Examine chest X-ray(CT) at the beginning and after6months treatment.Results1. After six months treatment, the sputum conversion rate of control group and PZAtreatment group was65.43%、44.44%, respectively（χ2=4.537,P=0.033）.Among the PZAtreatment group, the sputum conversion rate of PZA-S group and PZA-R group was67.74%、64.0%, respectively（χ2=0.118,P=0.732）;2. After six months treatment, the lesions absorption rate of control group and PZAtreatment group was74.07%、55.56%, respectively （χ2=3.953,P=0.047）.The lesionsabsorption rate of PZA-S group and PZA-R group was83.87%、68.0%, respectively（χ2=2.51,P=0.113）;3. After six months treatment, the tumor shrinking rate of control group and PZA treatment group was42.03%、21.21%, respectively（χ2=4.236,P=0.04）. The tumor shrinking rate ofPZA-S group and PZA-R group was64.0%、21.21%, respectively（χ2=7.767,P=0.005）.Conclusions1.The prevalence of pyrazinamide resistance was high in the re-treatment patients andAFB-positive PTB patients;2. The prevalence of pyrazinamide resistance was63.43%in the MDR-TB patients;3.The sputum conversion and lesions absorption rate of pyrazinamide resistant patientsafter2and6months treatment was lower than pyrazinamide susceptible patients,but therewas no significant difference;4. Pyrazinamide resistant patients would have a lower tumor shrinking rate after treatmentthan pyrazinamide susceptible patients;5.Multidrug-resistant tuberculosis patients can achieve higher sputum conversion andlesions absorption rate if they treated with pyrazinamide;6. Pyrazinamide resistance can decrease the tumor shrinking rate of MDR-TB patients aftertreatment;.