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Drug resistance to anti-tuberculosis drugs: a cross-sectional study from Makkah, Saudi Arabia


Tuberculosis (TB) continues to be a chief healthcare predicament worldwide and a prominent cause of mortality from a solitary infectious disease agent. Universally, more than 10 million new cases of TB and 1.5 million mortalities have been documented in 2018. The World Health Organization (WHO) aspires to accomplish a dramatic decline in the frequency of TB and its mortality by 90% and 95%, respectively, by the end of year 2035. Despite TB can be successfully cured in the vast majority of patients, however, some individuals develop resistance to first line anti-TB therapy, comprising isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin [4]. Polydrug-resistant TB (PDR-TB) occurs when the patient develops treatment resistance to two or more first line anti-TB agents other than isoniazid and rifampicin. On the other hand, multidrug-resistant TB (MDR-TB) occurs when the patient develops treatment resistance to both isoniazid and rifampicin with or without the other first line agents [5, 6]. It is approximated that close to half million of the TB cases are diagnosed as MDR-TB [2]. Unfortunately, MDR-TB is associated with costly treatment expenses, lower rates of treatment success, and higher burdens of morbidity and mortality.


The study protocol was approved by the institutional review board at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. A retrospective, cross-sectional, and cohort study was conducted on all TB-confirmed patients, irrespective of age, who were referred to the Central TB Laboratory in Makkah city, Saudi Arabia, between January 2016 and September 2020. TB diagnosis was confirmed by various means including chest x-ray, sputum culture, microscopy, or molecular assays. TB resistance was established through drug susceptibility testing (DST). For isolation and identification of mycobacterium agent, Ziehl-Neelsen (ZN) staining was performed to examine for acid fast bacilli. Culture and DST were done using the mycobacteria growth indicator tube (MGIT) medium and BACTEC MGIT 960 instrument (Becton, Dickinson and Company, Maryland, United States of America), as reported previously [14]. The final drug concentrations utilized for DST included 5 ?g/ml for ethambutol, 0.1 ?g/mL for streptomycin, 1 ?g/mL for rifampin, 0.1 ?g/mL for isoniazid, and 25 ?g/mL for pyrazinamide. Moreover, for selected samples, GenXpert MTB/RIF assay (Cepheid, California, United States of America) was used to screen for Mycobacterium tuberculosis complex and resistance to rifampin.


A total of 472 records of TB-confirmed cases was included in the analysis. Table 1 summarizes the sociodemographics of the patients. The mean ± standard deviation of age was 38.5 ± 17.7 years (range: 2-101 years). The prevalence of TB was equally divided between Saudi and non-Saudi nationals (50.4% and 49.6%, respectively). The vast majority of patients were males (62.7%) and had pulmonary TB (91.7%). Only a small proportion of TB patients had diabetes mellitus (8.5%), renal failure (23%), acquired immunodeficiency syndrome (3%), immunosuppression (1.9%), and cancer (1.5%). Equally 5.7% of patients had a previous history of TB and received the Bacillus Calmette-Guerin vaccine.


This is the second ever study from the western province of Saudi Arabia to analyze the prevalence and associated risk factors of MDR-TB among patients from Makkah city. Our data demonstrated that the prevalence rates of monodrug-resistant TB and MDR-TB were low (2.1-3.4% and 1.5% respectively). Diabetes and lung disease (other than TB) were not substantial factors correlated with higher occurrence of MDR-TB. Additional epidemiological studies are warranted to validate our results.