Edited by: Octavio Luiz Franco, Universidade Católica de Brasília, Brazil
Reviewed by: Amit Kumar Mandal, Vidyasagar University, India; Sónia Gonçalves, Instituto de Bioquímica, Portugal
*Correspondence: Setareh Mamishi
This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Tuberculosis (TB) remains as one of the most common infectious disease in developing countries (Nasiri et al.,
“
We sought any articles of antimicrobial susceptibility testing of
Studies with at least one of the following aspects were excluded: (1) Studies that were not relevant. (2) Articles with only available abstracts (without full text). (3) Studies that did not use laboratory methods (using patients records). (4) Articles that use of second line of antimicrobial drug resistance. (5) Articles that were review. (6) Articles which contain no eligible data. (7) Case series reports. (8) Articles that sample size is too small (
At this stage, articles with the following features were excluded as well: (1) Any articles were published both in English and Persian. (In these cases, the article published with more detailed results was chosen). (2) Duplicate publications. For all studies, we extracted the following data from the original publications. Literature identification and data extraction was performed by two researchers independently. Quality assessment of methodological sections and results of included articles was performed by use of STROBE checklist (
A total of 15,979 articles were achieved by literature search using different combination of key terms from the databases (Figure
% | % | % | % | |||||||||
Ardebil | Velayati et al., |
2010–2011 | PCR(a) | 65 | 2 | 3 | 4 | 6 | … | … | … | … |
Fars | Velayati et al., |
2010–2011 | PCR(a) | 40 | 2 | 5 | 5 | 12.5 | … | … | … | … |
Gilan | Velayati et al., |
2010–2011 | PCR(a) | 39 | 1 | 2.5 | 2 | 5 | … | … | … | … |
Golestan | Javid et al., |
2008 | PCR(b) | 87 | 6 | 7 | 4 | 5 | … | … | … | … |
Agar proportion | 45 | 4 | 9 | 6 | 13 | … | … | … | … | |||
Livani et al., |
… | MGIT | 148 | 26 | 18 | 5 | 3 | … | … | … | … | |
Velayati et al., |
2010–2011 | PCR(a) | 47 | 3 | 6 | 2 | 4 | … | … | … | … | |
Qom | Velayati et al., |
2010–2011 | PCR(a) | 61 | 3 | 5 | 3 | 5 | … | … | … | … |
Hormozgan | Velayati et al., |
2010–2011 | PCR(a) | 38 | 3 | 8 | 3 | 8 | … | … | … | … |
Nasiri et al., |
2010–2012 | Agar proportion | 48 | 3 | 6 | 2 | 4 | 4 | 8 | 2 | 4 | |
Hamedan | Velayati et al., |
2010–2011 | PCR(a) | 21 | 1 | 5 | 2 | 10 | … | … | … | … |
Isfahan | Velayati et al., |
2010–2011 | PCR(a) | 42 | 5 | 12 | 3 | 7 | … | … | … | … |
Nasiri et al., |
2010–2012 | Agar proportion | 45 | 2 | 7 | 2 | 9 | 1 | 2 | 0 | 0 | |
Moniri, |
1998–2009 | Agar proportion | 94 | 17 | 18 | 41 | 44 | 14 | 15 | 3 | 3 | |
Khorasan | Namaei et al., |
2001–2002 | indirect proportion | 105 | 1 | 1 | … | … | 27 | 26 | … | … |
Velayati et al., |
2010–2011 | PCR(a) | 117 | 10 | 8.5 | 9 | 8 | … | … | … | … | |
Sani et al., |
2012–2013 | Agar proportion | 100 | 7 | 7 | 7 | 7 | 9 | 9 | 3 | 3 | |
Kermanshah | Izadi et al., |
2006–2008 | Agar proportion | 14 | 8 | 57 | 6 | 43 | … | … | … | … |
Velayati et al., |
2010–2011 | PCR(a) | 16 | 1 | 6 | 2 | 12.5 | … | … | … | … | |
Nasiri et al., |
2010–2012 | Agar proportion | 15 | 4 | 26.6 | 3 | 20 | 3 | 20 | 3 | 20 | |
Mohajeri et al., |
2011–2012 | Agar proportion | 112 | 18 | 16 | 16 | 14 | 25 | 22 | 15 | 13 | |
Kermanshah | Mohajeri et al., |
2011–2013 | Agar proportion | 125 | … | … | 35 | 28 | … | … | … | … |
Khozestan | Khosravi et al., |
2001 | PCR(c) | 80 | 5 | 6 | 6 | 7.5 | … | … | … | … |
Velayati et al., |
2010–2011 | PCR(a) | 119 | 7 | 6 | 3 | 2.5 | … | … | … | … | |
Kerman | Velayati et al., |
2010–2011 | PCR(a) | 24 | 1 | 4 | 3 | 12.5 | … | … | … | … |
Kordestan | Velayati et al., |
2010–2011 | PCR(a) | 16 | 2 | 12.5 | 0 | 0 | … | … | … | … |
Lorestan | Velayati et al., |
2010–2011 | PCR(a) | 24 | 0 | 0 | 5 | 21 | … | … | … | … |
Mazandaran | Pourhajibagher et al., |
2010–2011 | PCR(d) | 59 | 4(use of katG gene) 3(use of inhA gene) | 7 5 | 1 | 2 | … | … | … | … |
Velayati et al., |
2010–2011 | PCR(a) | 26 | 1 | 4 | 1 | 4 | … | … | … | … | |
Babamahmoodi et al., |
… | LPA(e) | 54 | 2 | 4 | 3 | 5.5 | 4 | 7 | … | … | |
Markazi | Taherahmadi et al., |
… | Agar proportion PCR-RFLP (f) | 60 | … | … | … | … | … | … | 43 19 | 72 32 |
Farazi et al., |
2011–2012 | Agar proportion | 115 | 3 | 3 | 2 | 2 | 3 | 3 | 8 | 7 | |
Velayati et al., |
2010–2011 | PCR(a) | 15 | 3 | 20 | 3 | 20 | … | … | … | … | |
Qazvin | Velayati et al., |
2010–2011 | PCR(a) | 10 | 1 | 10 | 0 | 0 | … | … | … | … |
Semnan | Velayati et al., |
2010–2011 | PCR(a) | 21 | 0 | 0 | 0 | 0 | … | … | … | … |
Zakerbostanabad et al., |
2005–2006 | Agar proportion | 91 | 28 | 31 | 4 | 4 | 23 | 25 | 8 | 9 | |
Sistan va Balochestan | Bahrmand et al., |
2005–2006 | Agar proportion | 286 | … | … | 78 | 27 | … | … | … | … |
Velayati et al., |
2010–2011 | PCR(a) | 165 | 8 | 5 | 10 | 6 | … | … | … | … | |
Nasiri et al., |
2010–2012 | Agar proportion | 59 | 5 | 8 | 3 | 5 | 8 | 13.5 | 3 | 5 | |
Tehran | Ostadzadeh et al., |
… | Agar proportion | 50 | … | … | 25 | 50 | … | … | … | … |
Farnia et al., |
… | Agar proportion MGMT Both of them | 60 | 0 0 30 | 0 0 50 | 0 0 30 | 0 0 50 | 4 3 29 | 7 5 48 | 3 5 28 | 5 8 47 | |
Sheikholslami et al., |
… | Agar proportion PCR-SSCP(g) | 74 | 17 10 | 23 13.5 | 7 4 | 9 5 | … | … | … | … | |
Seyed-Davood Mansoori et al., |
1996–2000 | Agar proportion | 273 | 76 | 28 | 50 | 18.5 | 50 | 18.5 | 28 | 10 | |
Bahrmand et al., |
1998–1999 | Agar proportion | 563 | 35 | 6 | 25 | 4 | 55 | 10 | 17 | 3 | |
Mohammadi et al., |
1999–2000 | MGIT Direct MGIT in Direct Agar proportion | 15 | 10 10 7 | 67 67 47 | 11 11 8 | 73 73 53 | 5 6 7 | 33 40 47 | 5 5 5 | 33 33 33 | |
Dinmohammadi et al., |
1999–2008 | Agar proportion | 90 | 52 | 58 | … | … | … | … | … | … | |
Shamaei et al., |
2000–2003 | Agar proportion | 548 | 152 | 28 | 119 | 22 | 184 | 34 | 75 | 14 | |
Merza et al., |
2000–2005 | Agar proportion | 1742 | 414 | 24 | 307 | 18 | 478 | 27 | 207 | 12 | |
Mirsaeidi et al., |
2003–2004 | Agar proportion | 264 | 93 | 35 | 52 | 20 | 96 | 36 | 35 | 13 | |
Marjani et al., |
2003–2008 | Agar proportion | 554 | 81 | 15 | 27 | 5 | 116 | 21 | 22 | 4 | |
Varahram et al., |
2003–2011 | Agar proportion and Allele specific PCR | 4825 | 296 | 6 | … | … | … | … | … | … | |
Farnia et al., |
2006–2007 | Agar proportion | 258 | 9 | 3 | 3 | 1 | 7 | 3 | 1 | 0.4 | |
Mohammadi, |
2006–2008 | Agar proportion MAS-PCR(h) | 90 | … | … | 37 29 | 41 32 | … | … | … | … | |
Tasbiti et al., |
2006–2009 | Agar proportion | 1027 | 116 | 11 | 110 | 11 | 232 | 23 | 104 | 10 | |
Taghavi et al., |
2008–2009 | Agar proportion MAS-PCR(i) | 96 | 56 43 | 58 45 | … | … | … | … | |||
Ali et al., |
2009–2011 | Agar proportion PCR-SSCP | 103 | 12 5 | 12 5 | 9 4 | 9 4 | … | … | … | … | |
Velayati et al., |
2010–2011 | PCR(a) | 324 | 20 | 6 | 26 | 8 | |||||
Derakhshani Nezhad et al., |
2010–2011 | Agar proportion Allele-specific PCR | 106 | … | … | … | … | … | … | 36 13 | 34 28 | |
Tahmasebi et al., |
2010–2011 | Agar proportion | 97 | 68 | 70 | 63 | 65 | 28 | 29 | 47 | 48 | |
Bahrami et al., |
2010–2012 | Agar proportion | 176 | … | … | … | … | … | … | 48 | 27 | |
Nasiri et al., |
2010–2012 | Agar proportion | 85 | 6 | 7 | 7 | 8 | 14 | 16 | 6 | 7 | |
Sheikh Ghomi et al., |
2012–2013 | Agar proportion and Multiplex PCR | 83 | 35 | 42 | 47 | 56 | … | … | … | … | |
Tabriz | Zamanlou et al., |
2005–2007 | Agar proportion | 50 | 25 | 50 | … | … | … | … | … | … |
Rafi et al., |
… | Agar proportion | 90 | 6 | 7 | 3 | 3 | 17 | 19 | … | … | |
Moadab and Rafi, |
1999–2003 | Agar proportion | 90 | 7 | 8 | 2 | 2 | 17 | 19 | … | … | |
Asgharzadeh et al., |
… | Agar proportion MAS-PCR(j) | 120 | 13 | 11 | 12 | 10 | 27 | 22.5 | 4 10 | 3 8 | |
Roshdi and Moadab, |
… | Agar proportion | 103 | 2 | 2 | 0 | 0 | 8 | 8 | 0 | 0 | |
Varshochi et al., |
2003–2004 | Agar proportion | 90 | 20 | 22 | 9 | 10 | 28 | 31 | 5 | 5.5 | |
Hassan Heidarnejad and Nagili, |
… | Agar proportion | 155 | 12 | 8 | 1 | 1 | 20 | 13 | 0 | 0 | |
Asgharzadeh et al., |
… | Agar proportion | 120 | 13 | 11 | 12 | 10 | 27 | 22.5 | 4 | 3 | |
Yazd | Velayati et al., |
2010–2011 | PCR(a) | 12 | 0 | 0 | 1 | 8 | … | … | … | … |
Tehran-Arak | Taheri et al., |
… | Agar proportion | 40 | … | … | 20 | 50 | … | … | … | … |
Tehran–Alborz-Sistan va Blochestan-Hormozgan-Kermanshah | Haeili et al., |
2010–2012 | Agar proportion | 291 | 4 | 1 | 2 | 1 | 21 | 7 | 2 | 1 |
Tehran-Zabol-Kermanshah-Mashad-Tabriz | Bostanabad et al., |
2007–2008 | Agar proportion | 163 | 42 | 26 | 38 | 23 | 38 | 23 | 12 | 7 |
Unknown | Moaddab et al., |
… | Agar proportion and MIC | 50 | 25 | 50 | … | … | … | … | … | … |
Velayati et al., |
Ardebil | PCR | 4 | 6 | ||||||||||||||||||||
Velayati et al., |
Fars | PCR | 5 | 12.5 | ||||||||||||||||||||
Velayati et al., |
Gilan | PCR | 3 | 8 | ||||||||||||||||||||
Velayati et al., |
Golestan | PCR | 2 | 4 | ||||||||||||||||||||
Javid et al., |
Golestan | ProportionPCR | 4 2 | 9 2 | ||||||||||||||||||||
Livani et al., |
Golestan | MGIT | 5 | 3 | ||||||||||||||||||||
Velayati et al., |
Ghom | PCR | 4 | 6.5 | ||||||||||||||||||||
Velayati et al., |
Hormozgan | PCR | 3 | 8 | ||||||||||||||||||||
Nasiri et al., |
Hormozgan | Proportion | 2 | 4 | ||||||||||||||||||||
Velayati et al., |
Hamedan | PCR | 0 | 0 | ||||||||||||||||||||
Velayati et al., |
Isfahan | PCR | 2 | 5 | ||||||||||||||||||||
Moniri, |
Isfahan | Proportion | 16 | 17 | 9 | 10 | 2 | 2 | 12 | 13 | 8 | 8.5 | 1 | 1 | ||||||||||
Nasiri et al., |
Isfahan | Proportion | 2 | 4 | ||||||||||||||||||||
Velayati et al., |
Khorasan | PCR | 2 | 2 | ||||||||||||||||||||
Namaei et al., |
Khorasan | Proportion | 1 | 1 | 1 | 1 | ||||||||||||||||||
Sani et al., |
Khorasan | Proportion | 4 | 4 | 3 | 3 | 4 | 4 | 2 | 2 | ||||||||||||||
Velayati et al., |
Kermanshah | PCR | 1 | 6 | ||||||||||||||||||||
Izadi et al., |
Kermanshah | Proportion | 5 | 36 | ||||||||||||||||||||
Nasiri et al., |
Kermanshah | Proportion | 3 | 20 | ||||||||||||||||||||
Mohajeri et al., |
Kermanshah | Proportion | 16 | 14 | ||||||||||||||||||||
Velayati et al., |
Khozestan | PCR | 6 | 5 | ||||||||||||||||||||
Khosravi et al., |
Khozestan | Proportion | 7 | 9 | ||||||||||||||||||||
Velayati et al., |
Kerman | PCR | 3 | 12.5 | ||||||||||||||||||||
Velayati et al., |
Kordestan | PCR | 0 | 0 | ||||||||||||||||||||
Velayati et al., |
Lorestan | PCR | 0 | 0 | ||||||||||||||||||||
Velayati et al., |
Mazandaran | PCR | 1 | 4 | ||||||||||||||||||||
Babamahmoodi et al., |
Mazandaran | LPA | 0 | 0 | ||||||||||||||||||||
Velayati et al., |
Markazi | PCR | 2 | 13 | ||||||||||||||||||||
Farazi et al., |
Markazi | Proportion | 9 | 8 | 2 | 2 | ||||||||||||||||||
Velayati et al., |
Qazvin | PCR | 2 | 20 | ||||||||||||||||||||
Velayati et al., |
Semnan | PCR | 0 | 0 | ||||||||||||||||||||
Velayati et al., |
Sistan va Blochestan | PCR | 1 | 1 | ||||||||||||||||||||
Nasiri et al., |
Sistan va Blochestan | Proportion | 3 | 5 | ||||||||||||||||||||
Bahrmand et al., |
Sistan va Blochestan | Proportion | 37 | 13 | ||||||||||||||||||||
Velayati et al., |
Tehran | PCR | 32 | 10 | ||||||||||||||||||||
Tahmasebi et al., |
Tehran | Proportion | 63 | 65 | ||||||||||||||||||||
Mohammadzadeh et al., |
Tehran | Proportion | 11 | 48 | ||||||||||||||||||||
Ostadzadeh et al., |
Tehran | Proportion | 13 | 26 | ||||||||||||||||||||
Taghavi et al., |
Tehran | Proportion MAS-PCR | 36 26 | 38 27 | ||||||||||||||||||||
Masjedi et al., |
Tehran | Proportion | 150 | 12 | ||||||||||||||||||||
Bahrami et al., |
Tehran | Proportion | 10 | 6 | 12 | 7 | 19 | 11 | 8 | 4.5 | ||||||||||||||
Shamaei et al., |
Tehran | Proportion | 106 | 19 | ||||||||||||||||||||
Mirsaeidi et al., |
Tehran | Proportion | 43 | 16 | 0 | 0 | 23 | 9 | 0 | 0 | 2 | 1 | 4 | 1.5 | 0 | 0 | 2 | 1 | 0 | 0 | 9 | 3 | 26 | 10 |
Seyed-Davood Mansoori et al., |
Tehran | Proportion | 42 | 15.5 | 26 | 9.5 | 40 | 14.5 | 21 | 7.5 | 22 | 8 | 23 | 8.5 | 17 | 6 | 21 | 7.5 | 21 | 7.5 | 22 | 8 | 17 | 6 |
Bahrmand et al., |
Tehran | Proportion | 3 | 0.5 | 4 | 1 | 1 | 0.1 | 1 | 0.1 | 7 | 1 | ||||||||||||
Farnia et al., |
Tehran | MGMT | 8 | 19 | ||||||||||||||||||||
Nasiri et al., |
Tehran | Proportion | 6 | 7 | ||||||||||||||||||||
Sheikholslami et al., |
Tehran | Proportion PCR-SSCP | 16 4 | 22 5 | ||||||||||||||||||||
Merza et al., |
Tehran | Proportion | 263 | 15 | ||||||||||||||||||||
Marjani et al., |
Tehran | Proportion | 12 | 2 | ||||||||||||||||||||
Sheikh Ghomi et al., |
Tehran | Proportion and PCR | 30 | 36 | ||||||||||||||||||||
Imani Fooladi et al., Ali et al., |
Tehran | Proportion PCR-SSCP | 9 3 | 9 3 | ||||||||||||||||||||
Rafi et al., |
Tabriz | Proportion | 2 | 2 | 1 | 1 | 3 | 3 | 2 | 2 | ||||||||||||||
Moadab and Rafi, |
Tabriz | Proportion | 1 | 1 | 6 | 7 | 1 | 1 | 1 | 1 | 3 | 3 | 2 | 2 | ||||||||||
Asgharzadeh et al., |
Tabriz | Proportion | 1 | 1 | 5 | 4 | 1 | 1 | 2 | 2 | 2 | 2 | ||||||||||||
Roshdi and Moadab, |
Tabriz | Proportion | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 2 | ||||||||||||||
Varshochi et al., |
Tabriz | Proportion | 1 | 1 | ||||||||||||||||||||
Hassan Heidarnejad and Nagili, |
Tabriz | Proportion | 5 | 3 | ||||||||||||||||||||
Asgharzadeh et al., |
Tabriz | Proportion | 6 | 5 | ||||||||||||||||||||
Velayati et al., |
Yazd | PCR | 0 | 0 | ||||||||||||||||||||
Haeili et al., |
Tehran-Alborz Sistan va Blochestan Hormozgan Kermanshah | Proportion | 15 | 5 |
North | Golestan, Gilan, Mazandaran |
South | Fars, Hormozgan |
West | Kordestan, Kermanshah, Lorestan, Hamedan |
Center | Isfahan, Qom, Markazi, Yazd |
Northeast | Khorasan, Semnan |
Northwest | Ardebil, Ghazvin |
Southeast | Sistan-Blochestan, Kerman |
Southwest | Khozestan |
This review addressed the prevalence of first-line anti-tubercular drug resistance of
In Al-Akhali et al. (
Some limitations of this systematic review should be considered for results interpretation. First, few studies have been conducted in our country about resistance of TB to first and second line-drugs. Second, the probable influence of age, sex, ethnicity, economic level, and life styles could not be analyzed due to the limited information obtained from the original articles. Third, most included studies were hospital-based rather than population based which makes the results more prone to potential selection bias. Because of the small number of studies particularly in other cities except Tehran, we cannot judge about the prevalence of resistance against first-line anti-tuberculosis drugs properly. However, in recent years, emergence and spread of MDR-TB threaten the TB control strategy. In many law-and middle-income countries, due to inadequate laboratory capacity, most of the patients with MDR-TB are not diagnosed. Treatment of these cases mostly failed and significant expenditure of health care resources is needed.
In conclusion, this systematic review summarized the prevalence and distribution of first-line anti-tubercular drug resistance of
An important element in gaining control of this epidemic is developing an understanding of the molecular basis of resistance to the most important anti-tuberculosis drugs. Since the mechanism of action of rifampin is to inhibit mycobacterial transcription by targeting DNA-dependent RNA polymerase (Somoskovi et al.,
On the other hand, INH is activated by the mycobacterial enzyme KatG, a multifunctional catalase-peroxidase that has other activities including peroxynitritase and NADH oxidase. Therefore, inhibition of both cell wall lipid, and nucleic acid synthesis by INH-NAD and INH-NAPD adducts together with respiratory inhibition by INH-derived NO can provides a potent antituberculosis cocktail. Some strategies such as developing agents that produce the isonicotinoyl radical, screening for molecules which increase mycobacterial levels of NAD+ or NADP+ for in co-administration use with INH, to designing of more drug-like molecules using the structure of INH-NAD adducts to inhibit specifically mycobacterial enzymes; and developing of mycobacterial enzyme inhibitors which can inactivate INH might be useful to control INH-TB resistance propagation (Timmins and Deretic,
All authors listed, have made substantial, direct and intellectual contribution to the work, and approved it for publication.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.