Poly-drug Resistance Research Articles

Drug susceptibility testing and line probe assay of first-line anti-tuberculosis drugs among presumptive tuberculosis patients attending a secondary care hospital in Bhubaneswar.

Pyrazinamide (PZA) is important for identification in multi-drug-resistant tuberculosis patients before starting therapy. PZA drug susceptibility testing (DST) is essential for the management of drug-resistant and susceptible TB patients. The degree of drug resistance among TB patients and discrepancy between DST results of the phenotype and genotype were assessed. Socio-demographic and clinical profiles of TB patients recruited in the study were documented. Sputum samples were processed for diagnosis using TrueNat Xpert MTB, TrueNat Xpert MTB Plus, and MGIT culture. Rifampicin (RIF) line probe assay (LPA) showed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100%, whereas isoniazid (INH) LPA testing showed a sensitivity of 85.7%, a specificity and PPV of 100%, and NPV of 94.8%. The gene mutation for RIF resistance was between the codon, 530-533 of rpoB gene, and that for INH resistance was at the codon, 315 of katG gene. Our findings demonstrated high prevalence of mono- and poly-drug resistance as well as pyrazinamide resistance.

Genotypic and phenotypic drug resistance patterns of Mycobacterium tuberculosis isolated from presumptive pulmonary tuberculosis patients in Ethiopia: A multicenter study.

The emergence of drug-resistant tuberculosis (DR-TB) has been a major obstacle to global tuberculosis control programs, especially in developing countries, including Ethiopia. This study investigated drug resistance patterns and associated mutations of Mycobacterium tuberculosis Complex (MTBC) isolates from the Amhara, Gambella, and Benishangul-Gumuz regions of Ethiopia. A cross-sectional study was conducted using 128 MTBC isolates obtained from patients with presumptive tuberculosis (TB). Phenotypic (BACTEC MGIT 960) and genotypic (MTBDRplus and MTBDRsl assays) methods were used for drug susceptibility testing. Data were entered into Epi-info and analyzed using SPSS version 25. Frequencies and proportions were determined to describe drug resistance levels and associated mutations. Of the 127 isolates recovered, 100 (78.7%) were susceptible to four first-line anti-TB drugs. Any drug resistance, polydrug resistance, and multi-drug resistance (MDR) were detected in 21.3% (27), 15.7% (20), and 15% (19) of the isolates, respectively, by phenotypic and/or genotypic methods. Mono-resistance was observed for Isoniazid (INH) (2, 1.6%) and Streptomycin (STR) (2, 1.6%). There were two genotypically discordant RIF-resistant cases and one INH-resistant case. One case of pre-extensively drug-resistant TB (pre-XDR-TB) and one case of extensively drug-resistant TB (XDR-TB) were identified. The most frequent gene mutations associated with INH and rifampicin (RIF) resistance were observed in the katG MUT1 (S315T1) (20, 76.9%) and rpoB (S531L) (10, 52.6%) genes, respectively. Two MDR-TB isolates were resistant to second-line drugs; one had a mutation in the gyrA MUT1 gene, and the other had missing gyrA WT1, gyrA WT3, and rrs WT1 genes without any mutation. The detection of a significant proportion of DR-TB cases in this study suggests that DR-TB is a major public health problem in Ethiopia. Thus, we recommend the early detection and treatment of DR-TB and universal full first-line drug-susceptibility testing in routine system.

Epidemiology of tuberculosis in Saudi Arabia following the implementation of end tuberculosis strategy: Analysis of the surveillance data 2015-2019.

To analyze the evolution of tuberculosis (TB) epidemiology in Saudi Arabia in the 5 years following the implementation of the end-TB Strategy. A retrospective analysis of surveillance data, reported by the national tuberculosis control program from 2015-2019, was carried out. The annual incidence and the percentage of yearly changes were calculated and compared to the World Health Organization (WHO) milestones, which anticipate a 4-5% annual decline. Additionally, various other epidemiological indicators of TB were examined. The national TB incidence declined from 10.55% per 100,000 in 2015 to 8.76% per 100,000 in 2019, aligning with the WHO's 2019 milestone estimated between 8.59-8.96% per 100,000. While Makkah Region (40.3%) and Riyadh (24.6%) accounted for the majority of cases, Jazan region consistently exhibited the highest incidence throughout the study period. Demographic features shifted towards a younger age category, male, and native dominance. There was a consistent decrease in resistance and intermediate sensitivity to all first-line anti-TB drugs, associated with a substantial decrease in both polydrug resistance (from 4.7-1.9%; p<0.001) and multidrug resistance (from 4.4-2.4%; p=0.008). The figures of TB incidence TB in Saudi Arabia between 2015-2019 has met the WHO end-TB milestones, predicting successful progress toward the 2035 goal.

Incidence and Patterns of Drug Resistance in Patients with Spinal Tuberculosis: a Prospective, Single-Center Study from a Tuberculosis-Endemic Country.

There is paucity of data on incidence and pattern of drug resistance in spinal TB. This prospective observational study was conducted to document the incidence and drug-resistance pattern among primary and presumptive resistant cases. 59 consecutive cases diagnosed clinico-radiologically (imaging) were grouped into Group A (n = 51, primary cases) and Group B (n = 8, presumptive resistant cases) based on pre-defined criteria (INDEX-TB guidelines). Tissue samples obtained percutaneously (37.29%, 22/59) and on surgery (62.71%, 37/59) were subjected to genotypic DST (CBNAAT, LPA) and phenotypic DST (BACTEC MGIT 960 culture and sensitivity using fixed critical concentration of drugs). Etiological diagnosis was ascertained in all. 13/51 (25.49%) in Group A, while 3/8 (37.5%) in Group B and 16/59 (27.12%) overall demonstrated drug resistance. 12/16 (75%) had no prior history of ATT intake. 4 demonstrated INH (Isoniazid) mono-resistance. 12 polydrug resistance demonstrated: 5MDR, 3pre-XDR, while RIF + FQ (fluoroquinolones), FQ + Lz (linezolid), only SLID (second-line injectable drugs), and only FQ resistance observed in 1 case each. Isolated RIF (Rifampicin) resistance and XDR pattern were not observed. Overall frequency of RIF resistance was 16.4% (9/55) and INH was 25% (12/48) with low-(n-2) and high-level INH resistance (n-10). Among second-line drugs, FQ resistance was more than SLID resistance and within FQ, levofloxacin resistance was more frequent than moxifloxacin. MGIT demonstrated positive growth in 16/59 samples, out of which 1 sample was positive for nontuberculous mycobacteria (M. chelonae) but on genotypic testing demonstrated MTB resistant to RIF and FQ. This is the first report on incidence and drug-resistant pattern in culture-positive/negative cases. High (25.49%) primary drug resistance is worrisome. This being the first study in spinal TB cases which document prevalent drug-resistant pattern as evaluated for consecutive culture-positive/negative cases. The tissue obtained must be submitted for AFB culture and molecular tests to ascertain drug resistance in culture-positive/negative cases. However, in the presence of insufficient tissue sample histology and CBNAAT can ascertain etiological diagnosis in 100% cases. INH resistance is more than RIF with isolated RIF resistance unreported.

Prevalence of Multidrug-Resistant TB Among Smear-Positive Pulmonary TB Patients in Banadir, Somalia: A Multicenter Study.

Tuberculosis (TB) is an infectious disease that is the second most common cause of death from a single infectious agent. TB infection affects anyone, regardless of age, gender, and ethnicity. Drug-resistant TB is a serious public health problem, which needs treatment with a second-line anti-TB drug and it includes poly-drug resistance (PDR), multi-drug resistance (MDR), and extensive drug resistance (XDR). The goal of this research is to find out the prevalence of MDR TB among pulmonary TB patients in Banadir, Somalia. This was a multicenter retrospective review of data involving 1732 smear-positive pulmonary TB patients visiting Banadir TB centers between July 1, 2019 and June 30, 2020. Demographic, clinical, and drug susceptibility data were retrieved from TB treatment cards. The data were analyzed using Statistical Package for Social Sciences (SPSS) software(IBM SPSS Statistics version 26). All 1732 pulmonary TB cases were previously diagnosed by the Gene Xpert MTB/RIF test. Among them, 70.4% (1219/1732) were males. The mean age was 31.77 years. Overall, the prevalence of drug resistance TB was 10.56% (183/1732). The MDR TB was 1.96%, poly-drug resistance (PDR) was 0.12%, and extensive drug resistance was 0.06%. This study showed a prevalence of MDR-TB among pulmonary TB patients, which is similar to some of the eastern African countries.

Mechanism and management of antibiotic drug resistance tuberculosis

Drug resistance in tuberculosis has been shown to result from spontaneous mutation in several chromosomal genes of M.Tuberculosis. Mutation may reduce the medications' capacity to bind to the target genes. In many patients polydrug resistance, multidrug resistance, rifampicin resistance (RR) and extensive drug resistance (XDR) were seen. The diagnosis of drug-resistant TB in HIV-positive persons is more difficult and may be confused with other pulmonary or systemic infections. Management of patients with mono- or poly-resistant TB will be done with standard first line chemotherapy. Treatment of latent infection for people suffering from multidrug resistant bacilli is problematic because the only cure by isoniazid and rifampicin. In the recent cases of severe hepatotoxicity associated with preventive treatment comprising either pyrazinamide and rifampicin or pyrazinamide and fluoroquinolone. The use of dilatory fluoroquinolones, such as moxifloxacin, remarkable improved treatment outcomes of XDR-TB.

Patterns of Presentation of Drug-Resistant Tuberculosis in Nigeria: A Retrospective File Review

Background: An understanding of the patterns of drug-resistant tuberculosis (DR-TB) is needed to develop the best diagnostic tools and decide on optimal treatment combination therapies for the management of DR-TB in Nigeria. Objective: We aimed to investigate patterns of DR-TB for the five first-line anti-TB drugs over a period of seven years (2010–2016) and the associated clinical and socio-demographic factors. Methods: A retrospective study recruited 2555 DR-TB patients between 2010 and 2016 across the six geopolitical treatment zones in Nigeria. We determined DR-TB patterns based on standard case definition and their association with demographic and clinical information. Data were analyzed using Statistical Package for Social Sciences (SPSS) software. Independent predictors of DR-TB patterns/types were determined using bivariate and multivariate analyses with a statistical significance of p &lt; 0.05 and a 95% confidence interval. Results: The majority of the participants were males, 66.93% (1710), 31–40 years old, 35.19% (899), previously treated, 77.10% (1909), had received at least two treatments, 411 (49.94%) and were multi-drug resistant, 61.41% (1165). The Southwest zone had the highest number of DR-TB cases, 36.92%. We found an upward trend in the prevalence of DR-TB from 2010 to 2016. Participants who had received one previous treatment showed statistically significant higher rifampicin resistance (59.68%), those with two previous treatments reported a statistically significant higher polydrug resistance (78.57%), and those with three or more previous treatments had a statistically significant higher multidrug resistance (19.83%) (χ2 = 36.39; p = 0.001). Mono-drug resistance and rifampicin resistance were statistically significantly higher in the southwest zone (29.48% and 34.12% respectively), polydrug resistance in the northcentral (20.69%) and south-south zones (20.69%), and multidrug resistance in the southwest (30.03%) and northcentral zones (19.18%) (χ2 = 98.26; p = 0.001). Conclusions: We present patterns of DR-TB across the six geopolitical zones in Nigeria. Clinicians should weigh in on these patterns while deciding on the best first-line drug combinations to optimize treatment outcomes for DR-TB patients. A national scale-up plan for DST services should focus on patients with previous multiple exposures to anti-TB treatments and on those in the Northeastern zone of the country.

Community-Acquired Pneumonia of Bacterial Etiology and the Spectrum of Pathogen Sensitivity to Antibiotics in Corona-Positive and Corona-Negative Patients in Rostov-on-Don

Relevance. In the context of the ongoing pandemic of coronavirus infection, the course of viral pneumonia is often complicated by the addition of bacterial microflora due to a decrease in the body's immune status. The causative agents of such a co-infection can exhibit multiple drug resistance, which significantly reduces the effectiveness of etiotropic therapy. In this regard, it seems expedient to provide microbiological support to patients in order to select the most optimal treatment regimens. Aim. To study the composition of bacterial pathogens’ species, that cause community-acquired pneumonia (CAP) in corona-positive (COVID-19+) and corona-negative (COVID-19–) patients and to determine the spectrum of their sensitivity/resistance to antibacterial drugs. Material and methods. The species composition of microorganisms in sputum samples from 723 patients with CAP, who were admitted from the healthcare facility in Rostov-on-Don in August and December 2020 were studied. The isolated cultures were identified using bacteriological and mass spectrometric methods. The sensitivity of bacteria to antibiotics was determined by the disk diffusion method. Results. It was shown that in August pneumococci and staphylococci prevailed in the spectrum of CAP pathogens, while in December the percentage of excretions of Acinetobacter spp. and S. haemolyticus increased. Various types of p. Candida yeast were found with a high degree of isolation, COVID-19 + patients showed a tendency towards greater contamination (I104 mcl/ml). Some pathogens (A.baumannii, S.haemolyticus, P.aeruginosa, S.maltophilia) are characterized by polydrug resistance, and some strains of these species are pan-resistant to all groups of antibiotics. Conclusion. The data obtained demonstrate that severe forms of community-acquired pneumonia can be caused by viral-bacterial and viral-bacterial-yeast combinations of pathogens, including bacteria with a narrow spectrum of sensitivity to antibacterial drugs.

Molecular Detection of Drug-Resistant Mycobacterium tuberculosis in Sputum Specimens from the New and Previously Treated Tuberculosis Cases at the National Reference Chest Diseases Laboratory in Lusaka, Zambia

Background: Drug-Resistant Tuberculosis (DR-TB) is one of the major public health issues globally. Zambia is highly burdened by TB and multi-drug resistant TB. In this study, sputum samples obtained from the new and previously treated cases of TB were examined for drug-resistant Mycobacterium tuberculosis (MTB). Methods: Sputum specimens were processed using the N-acetyl-L-cysteine-sodium hydroxide method, stained and examined using fluorescent technique and microscopy respectively. Mycobacterial DNA was extracted using the Genolyse kit, then subjected to multiplex polymerase chain reaction amplification and reverse hybridization. Drug-resistance and mutations in MTB genes were detected using the Genotype MTBDRplus VER 2.0 and MTBDRsl VER 2.0 assays. Results: A total of 329 MTB-positive sputum specimens, 102 from the new TB cases and 227 from previously treated TB cases, were analysed for drug-resistance. Among the new TB cases, 3.9% had Rifampicin (RIF) mono-resistance, 12.8% Isoniazid (INH) mono-resistance, and 17.7% had Multi-Drug Resistance (MDR). For the previously treated TB cases, 10.1% had RIF mono-resistance, 6.6% INH mono-resistance, 33.0% MDR, 1.8% poly-drug resistance, and 0.8% had pre-Extensively Drug-Resistance (pre-XDR). Mutations identified were rpoB (Ser531Leu, His526Asp, Asp516Val, His526Tyr, and Glu510His), katG (Ser315Thr 1 and Ser315Thr 2), InhA (Cys15Thr), gyrA (Ala90Val and Asp94Gly), and eis (Cys14Thr), each with a varying frequency. Conclusion: DR-TB is prevalent, especially MDR-TB, which is currently the most worrisome form of DR-TB and an emerging threat hampering efforts in the control of TB in Zambia. The early detection and effective treatment of TB cases are key in the control of DR-TB.

Magnitude of Phenotypic and MTBDRplus Line Probe Assay First-Line Anti-Tuberculosis Drug Resistance Among Tuberculosis Patients; Northwest Ethiopia.

BackgroundMycobacterium tuberculosis (Mtb) drug resistance is a key challenge in ending TB.ObjectiveThe study aimed to determine anti-TB drug resistance and compare the discordance between phenotypic and genotypic drug-susceptibility testing (DST).MethodsProspective enrollment and sputum collection from patients suspected of active pulmonary TB from May 2018 to December 2019 at the University of Gondar Hospital. Phenotypic DST study for streptomycin, isoniazid, rifampin, and ethambutol was done by MGIT 360 SIRE Kit. Genotypic resistance for isoniazid and rifampin was performed by MTBDRplus v2 line probe assay (LPA) and compared to phenotypic drug resistance.ResultsA total of 376 patients, median age 32 years, and 53.7% male were enrolled. Mtb was isolated from 126 patients. 106/126 (84%) patients were newly diagnosed with TB and 20 patients with prior TB treatment. Seventy (66.0%) were susceptible to all anti‐TB drugs tested. Twenty-five (19.8%) of the isolates were resistant to isoniazid, 12 (9.5%) to rifampicin and six (5%) were multidrug resistant. Among previously treated TB patients, 4 (20.0%) and 5 (25.0%) were mono-resistant and poly-resistant, respectively. The sensitivity and specificity of LPA resistance for isoniazid were 94.4% and 100%, and for rifampin was 75.0% and 100%, respectively.ConclusionThe frequency of mono- and poly-drug resistance among both newly diagnosed and previously treated TB patients was high to the rest of the nation. MTBDRplus showed excellent concordance for isoniazid and rifampin. We concluded that DST should be performed for all patients to improve management and decrease spread of drug-resistant Mtb strains in the community.

Resistance Patterns of Mycobacterium tuberculosis to First-Line Anti-TB Drugs in Kaduna State, North-Western Nigeria

The problem of tuberculosis (TB) in Nigeria has been made worse by the issues of drug resistant Mycobacterium tuberculosis. Resistance associated with treatment failures has become a common occurrence worldwide. Of particular concern is the increasing prevalence of multi drug resistant M. tuberculosis; organisms resistant to isoniazid and rifampicin, the two drugs that form the backbone of modern short-course therapy. Susceptibility of forty (40) M. tuberculosis isolates to isoniazid (INH), rifampicin (RIF), streptomycin (SM) and ethambutol (EMB) was determined by the proportion method on Lowenstein Jensen egg based slopes containing critical concentrations of INH, RIF, SM and EMB (0.2 μg/ml, 40 μg/ml, 4.0 μg/ml and 2.0 μg/ml respectively). Overall drug resistance was found in 21 (52.5%) isolates. Mono-drug resistance was seen in 9 (22.5%) of the isolates tested and was against streptomycin. Two (5.0%) isolates were found to be MDR. Five (12.5%) were poly-drug resistant. One isolate showed poly-drug resistance to SM and INH, 2 (5%) were poly-drug resistant to SM and EMB, 1 (2.5%) was resistant to INH and EMB. Poly resistance to SM, INH and EMB was found in only 1 isolate. No poly-resistance to RIF and EMB, RIF and SM or RIF/SM/EMB was observed.&#x0D;

1347. Tuberculosis Caused by Mycobacterium bovis in Children: A Retrospective Review of Cases From 2010 to 2019 in a Pediatric Tertiary-care Center in Mexico

BackgroundTuberculosis (Tb) is a leading cause of death worldwide. The most common cause of Tb is due to M. tuberculosis, however, M. bovis is considered a public health issue and an often-undetected cause of Tb. Information regarding Tb by M. bovis in children is scarce.MethodsRetrospective analysis of culture-proven cases of Tb by M. bovis from 2010 to 2019 in a pediatric tertiary-care center in Mexico. Clinical and paraclinical characteristics were compared.ResultsWe included 22 cases of Tb by M. bovis in children younger than 18 years of age. 64 percent were men, mean age was 3.8 years. All subjects had a positive history of BCG immunization. Eight subjects (36.4%) consumed unpasteurized dairy products, 3 (13.6%) referred contact with Tb-infected people, and none had contact with cattle. Twelve patients (54.5%) had an immunodeficiency (ID). The most common ID was defects in the IL-12/IFN-γ axis (36.3%), followed by severe-combined ID (9%). All of the subjects presented any form of extrapulmonary Tb, and 8 (36.4%) had disseminated Tb. The most common extrapulmonary presentations were lymph-node (40.9%), abdominal (18.2%), and skeletal Tb (13.6%). Fever was present in 21.3% of the cases, weight-loss in 12%, and diaphoresis in 9.3%. Hepatomegaly was present in 83% of patients with abdominal Tb (P = 0.001). We found a negative association between lymph-node enlargement and skeletal Tb by M. bovis (P = 0.01). Five cases (22.7%) were identified as M. bovis BCG strain. Infection by BCG strain was associated with a shorter time of presentation (< 4 months) (P = 0.005). Polydrug resistance (resistance to ≥2 drugs, excluding those classified as MDR) was observed in five strains (22.7%). We detected 3 RIF-resistant strains (19%), 2 INH-resistant strains (9.1%), and 1 EMB-resistant strain (4.5%). No MDR strains were detected. We report an 86% cure rate, and 5% mortality. Nine percent are still in treatment.ConclusionWe report 22 cases of culture-proven cases of Tb by M. bovis, from 2010 to 2019 in a pediatric tertiary-care center in Mexico. Disseminated presentation was common, as well as extrapulmonary involvement. Infection by M. bovis BCG strain was associated with a shorter time of presentation. Further studies are required in order to expand our knowledge on M. bovis infection in children.Disclosures All authors: No reported disclosures.

Ambient air pollution exposures and risk of drug-resistant tuberculosis

BackgroundFew epidemiological studies have explored the effects of air pollution on the risk of drug-resistant tuberculosis (DR-TB). ObjectiveTo investigate the short and long term residential concentrations of ambient air pollutants (particulate matter <10 μm in diameter (PM10) and particulate matter≤2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO)) in relation to the risk of DR-TB in a typical air pollution city, Jinan city, China. MethodsA total of 752 new culture-confirmed TB cases reported in TB prevention and control institutions of Jinan from January 1, 2014 to December 31, 2015 were included. Average individual-level concentrations of air pollution for 5 different exposure windows, vary from 90 days to 720 days to diagnosis were estimated using measurements from monitor closest to the patient home addresses. Logistic regression model adjusted for potential confounders was employed to evaluate correlation between air pollution and DR-TB risk at different five exposure windows individually. ResultsThere were substantially increased mono-drug resistance and poly-drug resistance risks for ambient PM2.5, PM10, O3, and CO exposures. High exposure to PM2.5, PM10, and CO was also significantly associated with increased incidence of multi-drug resistance (MDR) both in the single- and multi-pollutants regression models. The dominant positive associations for PM2.5was observed at 540 days exposure, for O3 was observed at 180 days exposure, and for PM10 and CO was observed from 90 days to 540 days exposures. ConclusionsOur finding suggest that exposure to ambient air pollution (PM2.5, PM10, O3, and CO) are associated with increased risk of DR-TB. We provided epidemiological evidence of association between pollution exposure and mono-, poly- and multi-drug resistance.

High mortality during tuberculosis retreatment at a Ghanaian tertiary center: a retrospective cohort study.

IntroductionHigh mortality among individuals receiving retreatment for tuberculosis (RT-TB) persists, although reasons for these poor outcomes remain unclear.MethodsWe retrospectively reviewed 394 RT-TB patients diagnosed between January 2010 and June 2016 in Accra, Ghana.ResultsOf RT-TB patients, 161 (40.9%) were treated empirically (negative/absent smear, culture or Xpert), of whom 30.4% (49/161) had only extrapulmonary TB signs or symptoms. Mortality during treatment was 19.4%; 15-day mortality was 10.8%. In multivariable proportional hazards regression, living with HIV (aHR=2.69 [95 CI: 1.51, 4.80], p<0.01) and previous loss-to-follow up (aHR=8.27 (95 CI: 1.10, 62.25), p=0.04) were associated with mortality, while drug susceptibility testing (DST, aHR=0.36 (95 CI: 0.13, 1.01), p=0.052) was protective. Isoniazid resistance was observed in 40% (23/58 tested) and rifampin resistance in 19.1% (12/63 tested).ConclusionHigh rates of extrapulmonary TB and smear/culture negative disease highlight the barriers to achieving DST-driven RT-TB regimens and the need for improved diagnostics. Our finding of poly-drug resistance in rifampin-susceptible cases supports access to comprehensive first line DST. Additionally, interventions to reduce mortality, especially in HIV co-infected RT-TB patients, are urgently needed.

Antituberculosis Drugs Resistance and Treatment Outcomes Among Retreatment Patients in Guinea: A Five-Year Retrospective Cohort Study

Tuberculosis (TB) is a global outbreak whose drug resistance is a constant threat. This study aimed at describing anti-TB drugs resistance and treatment outcomes among retreatment TB patients in Guinea between 2008 and 2012. We conducted a retrospective cohort study with a sample of 558 patients aged of at least 10, who were admitted for TB retreatment and who were tested for anti-TB drugs susceptibility during the study period. Overall, 3187 retreatment TB patients were recorded from January 1, 2008 to December 31, 2012 in Guinea, of which 558 (17.5%) performed susceptibility testing to anti-TB drugs. We found overall resistance in 417 cases (74.7%) including 356 (85.4%) of multidrug resistance (MDR), 29 (6.9%) of monoresistance (isoniazid 2.9%, streptomycin 2.9%, rifampicin 0.9%, ethambutol 0.2%) and 32 (7.7% of polydrug resistance (isoniazid + streptomycin 4.3%, rifampicin + streptomycin 1.4%, isoniazid + ethambutol + streptomycin 1.0%, rifampicin + ethambutol + streptomycin 1.0%). Most of the patients (84.6%) with anti-TB drugs resistance were under 45 and labourers were mostly represented (27.8%) including drivers in majority (37.9%). MDR-TB incidence rate increased by 12.2% between 2008 (65.6%) and 2012 (77.8%), and the annual cure rate decreased gradually from 60.0% in 2009 to 45.7% in 2012. Among MDR-TB patients (n= 356), only 112 (31.5%) benefited from second-line treatment regimen, of which, 51.7% were cured, 6.3% completed treatment, 24.1% died, 6.3% were lost to follow-up and 11.6% were not evaluated. The cure rate was higher in HIV-negative patients (55.3%) than in those who were HIV-positive (35.3%) and the death rate was the highest (41.2%) in HIV-positive patients. Overall, treatment success rate was 58.0%. This study revealed a low rate of performing drug susceptibility testing, the gradual increase of the incidence of MDR-TB each year and the gradual decrease of cure rate from year to year. Besides, anti-TB drugs resistance concerned mostly drivers in our context. Prospective studies are needed for a deep understanding of the factors associated with these persistent challenges.

The effectiveness of individualized treatment regimen on smear-positive retreatment pulmonary tuberculosis with mono- and poly-drug resistance

Objective: To analyze and evaluate the effectiveness of individualized treatment regimen in the therapy of smear-positive retreatment pulmonary tuberculosis with mono-and poly-drug resistance, and therefor to provide information on how to develop rational individualized regimen for retreatment tuberculosis cases with drug resistance. Methods: This was a multi-centered, prospective cohort study. Totally 254 cases of sputum positive tuberculosis with previous treatment history during the period from July 1, 2009 to August 30, 2016 were included in the analysis. All the cases were randomly divided into 3 groups and received therapy after randomization into treatment groups. After 3 months, cases with multidrug resistant tuberculosis, extensively drug-resistant tuberculosis, non-tuberculosis mycobacterial infection and those with smear-positive but culture-negative tuberculosis were excluded according to result of sputum culture and drug susceptibility test (DST). In treatment group A (individualized treatment group), 86 cases with an average age of (42.1±13.7) years for men and (38.5±12.8) years for women, were treated with individualized regimen, which allowed drug replacement on the basis of standard regimen (2SHRZE/6HRE) according to DST result. Treatment duration was recalculated after drug replacement and the total length should be 12 months or more. If the DST result did not show drug resistance, the patients would continue the 8 months' standard treatment. In treatment group B (intensified retreatment regimen group), 86 cases with an average age of (43.2±14.2) years for man and (37.9±14.1) years for women, received intensified retreatment regimen (2HL(2)EZS/2HL(2)EZS(3)/4HL(2)E). The dose for H was 0.3 g/d for patients with body weight <50 kg, and 0.4~0.5 g/d for higher body weight (≥50 kg); The doses for L(2,)E and Z were 0.6 g, 2/w; 0.75, 1/d and 0.5g, 3/d. In treatment group C (standard treatment group), 82 cases with an average of (42.5±11.9) years for man and (38.6±12.8) years for women, were treated with standardized regimen recommended by national tuberculosis program (2HREZS/6HRE). In both group B and C, the total treatment duration was 8 months and the drugs were not replaced for mono-and poly-drug resistance. Treatment outcomes of the 3 groups were analyzed, the status of drug replacement in group A was analyzed, and the adjustment of dose of H and R according to patients' body weight was observed. SPSS 19.0 was used for data analysis. Results: The treatment cure rates for group A, B and C were 73.3%(63/86), 76.7%(66/86) and 50%(41/82), and the treatment success rates were 80.2%(69/86), 84.9%(73/86) and 62.2%(51/82) respectively. Treatment failure was 8.1%(7/86), 4.7%(4/86) and 19.5%(16/82) in 3 groups. There were significant differences in the above indicators for group A and B in comparison with group C(χ(2)=13.127, P=0.001). However, there was no difference observed between group A and B(χ(2)=0.646, P=0.422). In group A, tuberculosis specialized hospitals using regular doses for R was only 38.7%(12/31). After 3 years' follow-up, no-relapse-success for group A was 66.7% (10/15). Conclusions: Inappropriate individualized treatment would increase treatment failure for retreatment tuberculosis. Higher doses of H and R and prolonged extensive therapy phase could contribute to increased treatment success.

DRUG RESISTANCE PATTERN AMONG AFB SMEAR POSI-TIVE RETREATMENT COMPLETED CASES

Abstract Background: Worldwide, multidrug resistance (MDR TB) is a serious issue. It has increased over the last decade. Re-treatment completed sputum smear posi-tive cases have much higher incidence of MDR-TB as compared to primary MDR - TB. Objective: To estimate the incidence of drug resis-tance pattern among AFB smear positive re-treatment completed cases. Study Design: Evidence based prospective study. Study Setting: Institute of Chest Medicine, Mayo Khalid M. Ch. 1 Associate Professor, Department of Chest Medicine KEMU / Mayo Hospital, Lahore Hassan S. 2 Registrar, Department of Chest Medicine Mayo Hospital, Lahore Saeed M.S. 3 Chairman, Department of Chest Medicine KEMU / Mayo Hospital, Lahore Younus M. 4 Senior Registrar, Dept of Chest Medicine Mayo Hospital, Lahore Iqbal R. 5 Senior Research Officer Pakistan Medical Research Council Hospital Lahore, Tertiary care hospital affiliated with King Edward Medical University, Lahore, Pakistan. Methodology: A total 50 (Male 22, Female 28) pul-monary TB patients who had completed Re- treatment regimen in the past and are still sputum smear positive for acid fast Bacilli were included in the study. Three consecutive sputum specimens were collected at Aga Khan University collection center at Lahore. The spe-cimen were sent to Agha Khan University Lab Karachi for AFB smear, culture and drug sensitivity both for essential and reserve drugs. Reports for AFB smear were received within a week, while culture and drug sensitivity reports after 6 weeks. Reports data was analyzed for essential and reserve anti tuberculous drug sensitivity for mycobacterium tuberculosis. Results: Data Analysis revealed MDR TB in 31(62%) patients which include 11 males and 23 females. Indi-vidual drug resistance to essential drugs was INH - 62%, Rifampicin - 68%, Ethambutol - 24%, PZA - 25% and Streptomycin - 21%. Poly drug resistance was determined in 38% cases. Individual drug resis-tance to reserve drugs - kanamycin, Amikacin, ofloxa-cin, Ethionamide and PAS was 4%, 4%, 36%, 10% and 2% respectively. Conclusion: There is a very high proportion of MDR TB in sputum smear AFB positive retreatment cases. Suggestion: Comprehensive measures including DO-TS PLUS are needed to control MDR TB in Pakistan. Key words: MDR TB, XDR TB, Re-treatment regi-men, Essential drugs, Reserve drugs, AFB - acid fast bacilli.

Current pattern of drug resistance in new cases of pulmonary tuberculosis at a tertiary care centre in India

Background: Drug resistant tuberculosis is a major obstacle in the effective control of tuberculosis. Early diagnosis of drug resistance using drug susceptibility testing can help treat the patient effectively. Drug resistance can be monodrug resistance, polydrug resistance or multidrug resistance. The aim of the study was to determine the current pattern of drug resistance in new cases of pulmonary tuberculosis. Methods: A prospective observational study was carried out from November 2012 to October 2014 in the Department of Pulmonary Medicine, Era’s Lucknow Medical College and Hospital, Lucknow. The study consisted of 221 new cases of pulmonary tuberculosis which were sputum smear positive for AFB (Acid fast bacilli). One sputum sample from each patient was sent for culture and Drug Susceptibility Testing (DST) to first line anti-tuberculosis drugs on Lowenstein-Jensen medium. Statistical analysis was done with chi-square test. Results: A total of 221 new sputum positive cases of pulmonary tuberculosis were diagnosed during the study period, of which 189 were culture positive for Mycobacterium tuberculosis. Drug resistance to first line anti-tuberculosis drugs among new cases of pulmonary tuberculosis was observed in 15.3% cases in our study. Multidrug resistant tuberculosis was observed to be 4.2% in these new cases. Conclusions: Multidrug resistance seems to be on a rise in the new cases of pulmonary tuberculosis in our country.

Drug Resistant Mycobacterium tuberculosis in Tertiary Hospital South East, Nigeria

Objective: Drug resistant Mycobacterium tuberculosis is a public health threat globally. We described the drug resistance pattern of M. tuberculosis to first line anti-TB drugs and the prevalence of Multidrug resistant TB among TB patients at tertiary hospital Nnewi, Nigeria. Methods: Sputum specimens from 550 suspected TB patients were analyzed for AFB. The smear positive samples were subjected to culture and drug susceptibility testing to first line anti-TB drugs on Lowenstein-Jensen medium. Result: Out of 180 (32.7%) culture positive samples subjected to DST, 97 (53.8%) were susceptible to all first line anti-TB drugs while 83 (46.1%) were resistant to one or two anti- TB drugs. The level of resistance was significant at p<0.05 identifying three patterns, Mono-drug resistance in 34(18.8%) patients, Multi-drug resistance in 14 (7.7%) and Poly drug resistance in 35 (19.4%) patients. The proportion of TB cases with resistance to single drugs ranged from 5 (2.7%) for rifampicin to 12 (6.6%) for isoniazid and previously treated TB 8 (4.4%) patients was a significant factor (P<0.000) to development of MDR-TB compared to new TB patients 6(3.3%) within the age range of 21-40 years. Other factors such as age, gender and HIV positive status were not significantly associated with the development of any resistance. Conclusion: The investigation highlights the presence of drug resistant TB with high prevalence of MDR-TB in the studied community. Larger studies are urgently recommended to improve TB clinical management and control efforts.

Multidrug‐resistant TB in Zambia: review of national data from 2000 to 2011

Multidrug-resistant tuberculosis (MDR-TB) is posing a great threat to global TB control. The burden in Zambia is not well defined because routine surveillance data are scarce. We reviewed national MDR-TB data for the last decade to inform future public health policy with respect to MDR-TB in Zambia. Retrospective review of national surveillance of MDR-TB data, TB programme and laboratory reports between 2000 and 2011. The total number of DSTs performed during this 11-year period was 2,038 and accounted for 2.6% (2,038/78,639) of all the retreatment cases notified. The total number of diagnosed MDR-TB cases for this period was 446, of which 56.3% (251/446) were male and 41.7% (186/446) female. Only one child was found to have MDR-TB. Poly-drug resistance accounted for 18.9% (172/911) of the DR-TB cases and 8.4% of the total DSTs. 8.8% (80/911) of the DR-TB cases showed either rifampicin mono- or poly-resistance other than MDR-TB. No XDR-TB was reported. There were no data available on DR-TB and HIV co-infection. Only 65 MDR-TB patients were notified and put on second-line treatment according to WHO guidelines. Multidrug-resistant tuberculosis may be an emerging challenge in Zambia. There is a need to invest in improving the capacity of the TB programme to detect and manage MDR-TB.