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Fulltext Fluoroquinolones resistance in multidrug-resistant tuberculosis in Pakistan and suitability of guidelines recommended standardized regimen

Ahmad N, Khan AH, Syed Sulaiman SA, Javaid A

Int J Mycobacteriol, 2015 09;4(3):258-9.
PMID: 27649876 DOI: 10.1016/j.ijmyco.2015.05.012
Fulltext Applicability of the World Health Organization recommended new shorter regimen in a multidrug-resistant tuberculosis high burden country

Javaid A, Ahmad N, Khan AH, Shaheen Z

Eur Respir J, 2017 01;49(1).
PMID: 28049176 DOI: 10.1183/13993003.01967-2016
Risk factors for high death and loss-to-follow-up rates among patients with multidrug-resistant tuberculosis at a programmatic management unit

Javaid A, Shaheen Z, Shafqat M, Khan AH, Ahmad N

Am J Infect Control, 2017 Feb 01;45(2):190-193.
PMID: 27769706 DOI: 10.1016/j.ajic.2016.07.026

Among 186 retrospectively evaluated patients with multidrug-resistant tuberculosis, 33.9% were cured, 6.6% completed treatment, 25% died, 18.3% were lost to follow-up, 2.2% failed treatment, and 13.8% were still undergoing treatment by the end of the study period. Rural residence was a risk factor for loss to follow-up (odds ratio [OR], 3.315; P = .016), whereas baseline body weight <40 kg (OR, 2.175; P = .042) and resistance to ofloxacin (OR, 2.889; P = .025) were risk factors for death. Despite programmatic management, treatment outcomes of the current cohort were distressing.
Occurrence, Management, and Risk Factors for Adverse Drug Reactions in Multidrug Resistant Tuberculosis Patients

Ahmad N, Javaid A, Syed Sulaiman SA, Afridi AK, Zainab, Khan AH

Am J Ther, 2016 3 5;25(5):e533-e540.
PMID: 26938643 DOI: 10.1097/MJT.0000000000000421

Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about prevalence, management, and risk factors for adverse drug reactions (ADRs) in MDR-TB patients in Pakistan. To evaluate occurrence, management, and risk factors for ADRs in MDR-TB patients, and its impact on treatment outcomes, this observational cohort study was conducted at programmatic management unit for drug resistant TB of Lady Reading Hospital Peshawar, Pakistan. A total of 181 MDR-TB patients enrolled at the study site from January 1, 2012 to February 28, 2013 were included. Patients with drug resistant TB other than MDR-TB, transferred out patients and those who were still on treatment at the end of study duration (January 31, 2015) were excluded. Patients were followed until treatment outcomes were reported. ADRs were determined by laboratory data and/or clinical criteria. SPSS 16 was used for data analysis. A total of 131 patients (72.4%) experienced at least 1 ADR. Gastrointestinal disturbance was the most commonly observed adverse event (42%), followed by psychiatric disturbance (29.3%), arthralgia (24.3%), and ototoxicity (21%). Potentially life-threatening ADRs, such as nephrotoxicity (2.7%) and hypokalemia (2.8%) were relatively less prevalent. Owing to ADRs, treatment regimen was modified in 20 (11%) patients. On multivariate analysis, the only risk factor for ADRs was baseline body weight ≥ 40 kg (OR = 2.321, P-value = 0.013). ADRs neither led to permanent discontinuation of treatment nor adversely affected treatment outcomes. Adverse effects were prevalent in current cohort, but caused minimal modification of treatment regimen, and did not negatively impact treatment outcomes. Patient with baseline body weight ≥ 40 kg should be closely monitored.
Management and treatment outcomes of MDR-TB: results from a setting with high rates of drug resistance

Ahmad N, Javaid A, Basit A, Afridi AK, Khan MA, Ahmad I, et al.

Int J Tuberc Lung Dis, 2015 Sep;19(9):1109-14, i-ii.
PMID: 26260834 DOI: 10.5588/ijtld.15.0167

Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about the management and treatment outcomes of MDR-TB patients in Pakistan.
Fulltext Effects of Multidrug Resistant Tuberculosis Treatment on Patients' Health Related Quality of Life: Results from a Follow Up Study

Ahmad N, Javaid A, Syed Sulaiman SA, Basit A, Afridi AK, Jaber AA, et al.

PLoS One, 2016 Jul 28;11(7):e0159560.
PMID: 27467560 DOI: 10.1371/journal.pone.0159560

At present, within the management of multidrug resistant tuberculosis (MDR-TB) much attention is being paid to the traditional microbiological and clinical indicators. Evaluation of the impact of MDR-TB treatment on patients' Health Related Quality of Life (HRQoL) has remained a neglected area.
Fulltext Validity of Time to Sputum Culture Conversion to Predict Cure in Patients with Multidrug-Resistant Tuberculosis: A Retrospective Single-Center Study

Javaid A, Ahmad N, Afridi AK, Basit A, Khan AH, Ahmad I, et al.

Am J Trop Med Hyg, 2018 06;98(6):1629-1636.
PMID: 29611497 DOI: 10.4269/ajtmh.17-0936

To evaluate the predictive value of time to sputum culture conversion (SCC) in predicting cure and factors associated with time to SCC and cure in multidrug-resistant tuberculosis (MDR-TB) patients, a retrospective study was conducted at programmatic management unit of drug resistant tuberculosis (TB), Peshawar. A total of 428 pulmonary MDR-TB patients enrolled at the study site from January 1, 2012 to August 31, 2014 were followed until treatment outcome was recorded. Survival analysis using Cox proportional hazards model and multivariate binary logistic regression were, respectively, used to identify factors associated with time to SCC and cure. A P value < 0.05 was considered statistically significant. Overall, 90.9% patients achieved SCC, and 76.9% were cured. Previous use of second-line drugs (SLDs) (hazard ratio [HR] = 0.637; 95% confidence interval [CI] = 0.429-0.947), ofloxacin resistance (HR = 0.656; 95% CI = 0.522-0.825) and lung cavitation (HR = 0.744; 95% CI = 0.595-0.931) were significantly associated with time to SCC. In predicting cure, sensitivities of SCC at 2, 4, and 6 months were 64.1% (95% CI = 58.69-69.32), 93.0% (95% CI = 89.69-95.52), and 97.6% (95% CI = 95.27-98.94), respectively, whereas specificities were 67.7% (95% CI = 57.53-76.73), 51.5% (95% CI = 41.25-61.68), and 44.4% (95% CI = 34.45-54.78), respectively. Furthermore, patients' age of 41-60 (odds ratio [OR] = 0.202; 95% CI = 0.067-0.605) and > 60 years (OR = 0.051; 95% CI = 0.011-0.224), body weight > 40 kg (OR = 2.950; 95% CI = 1.462-5.952), previous SLD use (OR = 0.277; 95% CI = 0.097-0.789), lung cavitation (OR = 0.196; 95% CI = 0.103-0.371) and ofloxacin resistance (OR = 0.386; 95% CI = 0.198-0.749) were significantly associated with cure. Association of SCC with cure was substantially stronger at 6 months (OR = 32.10; 95% CI = 14.34-71.85) than at 4 months (OR = 14.13; 95% CI = 7.92-25.21). However in predicting treatment outcomes, the combined sensitivity and specificity of SCC at 4 months was comparable to SCC at 6 months. Patients with risk factors for delayed SCC were also at high risk of unsuccessful outcomes.
Fulltext Resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients

Ahmad N, Javaid A, Sulaiman SA, Ming LC, Ahmad I, Khan AH

Braz J Infect Dis, 2016;20(1):41-7.
PMID: 26626164 DOI: 10.1016/j.bjid.2015.09.011

BACKGROUND: Fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. Despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from Pakistan.
OBJECTIVE: To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients.
METHODS: This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients' socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis.
RESULTS: High degree of drug resistance (median 5 drugs, range 2-8) was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%), and more than half were resistant to second line drugs (55.1%). The majority of the patients were ofloxacin resistant (52.7%). Upon multivariate analysis previous tuberculosis treatment at private (OR=1.953, p=0.034) and public private mix (OR=2.824, p=0.046) sectors were predictors of ofloxacin resistance.
CONCLUSION: The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public-private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.
Comparative molecular docking analysis for analyzing the inhibitory effect of Anakinra and Ustekinumab against IL17F

Nisar H, Attique SA, Javaid A, Ain QU, Butt F, Zaid M, et al.

J Biomol Struct Dyn, 2023;41(22):13302-13313.
PMID: 36715128 DOI: 10.1080/07391102.2023.2173299

Interleukin 17 F is a member of IL-17 cytokine family with a 50% structural homology to IL-17A and plays a significant role either alone or in combination with IL-17A towards inflammation in Rheumatoid arthritis (RA). A growing number of drugs targeting IL-17 pathway are being tested against population specific disease markers. The major objective of this research was to investigate the anti-inflammatory effect of Anakinra (an IL-1 R1 inhibitor) and Ustekinumab (an IL-12 and IL-23 inhibitor) by targeting IL17F. The three dimensional structures of IL17F was taken from PDB while structures of drugs were taken from PubChem database. Docking was performed using MOE and Schrodinger ligand docking software and binding energies, including s-score using London-dG fitness function and glide score using glide internal energy function, between drug and targets were compared. Furthermore, Protein-Drug complex were subjected to 150 ns Molecular Dynamics (MD) Simulations using Schrodinger's Desmond Module. Docking and MD simulation results suggest anakinra as a more potent IL17F inhibitor and forming a more structurally stable complex.Communicated by Ramaswamy H. Sarma.
Fulltext Predictors of two months culture conversion in multidrug-resistant tuberculosis: findings from a retrospective cohort study

Basit A, Ahmad N, Khan AH, Javaid A, Syed Sulaiman SA, Afridi AK, et al.

PLoS One, 2014;9(4):e93206.
PMID: 24705411 DOI: 10.1371/journal.pone.0093206

Various studies have reported culture conversion at two months as a predictor of successful treatment outcome in multidrug-resistant tuberculosis (MDR-TB).
Pattern of first- and second-line drug resistance among pulmonary tuberculosis retreatment cases in Pakistan

Javaid A, Hasan R, Zafar A, Chaudry MA, Qayyum S, Qadeer E, et al.

Int J Tuberc Lung Dis, 2017 03 01;21(3):303-308.
PMID: 28225340 DOI: 10.5588/ijtld.16.0444

BACKGROUND: Drug resistance in general, and multidrug-resistant tuberculosis (MDR-TB) in particular, threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Pakistan.
OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Pakistan.
METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in all provinces of Pakistan. We performed culture and drug susceptibility testing on M. tuberculosis isolates from patients with a prior history of anti-tuberculosis treatment (retreatment cases) from all over the country.
RESULTS: Of 544 isolates from previously treated cases, 289 (53.1%) were susceptible to all first-line drugs, 255 (46.9%) were resistant to at least one anti-tuberculosis drug and 132 (24.3%) were MDR-TB. Among MDR-TB isolates, 47.0% were ofloxacin (OFX) resistant. Extensively drug-resistant TB was found in two (0.4%) isolates.
CONCLUSION: Prevalence of drug resistance in retreatment isolates was high. The alarmingly high prevalence of OFX resistance among MDR-TB isolates may threaten the success of efforts to control and treat MDR-TB.