The Antibiotic Susceptibility of Brucella spp. Isolated from Human Samples: A Systematic Review and Meta-Analysis

Darvishi, Mohammad; Nazer, Mohamad Reza; Hashemi Rafsanjani, Seyed Mahmoudreza; Nouri, Majid; Soleiman-Meigooni, Saeed

doi:10.30699/ijmm.17.6.620

year 17, Issue 6 (November - December 2023) Iran J Med Microbiol 2023, 17(6): 620-628 | Back to browse issues page

‎ 10.30699/ijmm.17.6.620

Mendeley

Zotero

RefWorks

Darvishi M, Nazer M R, Hashemi Rafsanjani S M, Nouri M, Soleiman-Meigooni S. The Antibiotic Susceptibility of Brucella spp. Isolated from Human Samples: A Systematic Review and Meta-Analysis. Iran J Med Microbiol 2023; 17 (6) :620-628
URL: http://ijmm.ir/article-1-2237-en.html

The Antibiotic Susceptibility of Brucella spp. Isolated from Human Samples: A Systematic Review and Meta-Analysis

Mohammad Darvishi¹

, Mohamad Reza Nazer²

, Seyed Mahmoudreza Hashemi Rafsanjani³

, Majid Nouri¹

, Saeed Soleiman-Meigooni

⁴

1- Infectious Diseases and Tropical Medicine Research Center (IDTMRC), Aja university of Medical Sciences, Tehran, Iran
2- Department of Infectious Diseases and Tropical Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
3- Department of General Medicine, Faculty of Medicine, Aja university of Medical Sciences, Tehran, Iran
4- Infectious Diseases and Tropical Medicine Research Center (IDTMRC), Aja university of Medical Sciences, Tehran, Iran , Dr.saeed.meigooni@gmail.com

Keywords: Brucella, Brucellosis, Antibiotic Susceptibility, Resistance, MIC

Full-Text [PDF 2409 kb] (124 Downloads) | Abstract (HTML) (504 Views)

Full-Text: (22 Views)

Introduction

Brucellosis, a zoonotic disease impacting both animals and humans, poses significant economic and public health challenges globally. Brucella melitensis and Brucella abortus are the primary culprits behind epidemic brucellosis (1, 2). Additionally, human brucellosis can stem from various Brucella species, including B. canis and B. suis, often transmitted through infected animal organs or the consumption of unpasteurized dairy products. This disease notably contributes to economic losses due to reduced milk production and livestock abortion. Despite therapeutic efforts, brucellosis treatment has not yielded absolute success, with instances of disease relapses documented. Moreover, widespread and inappropriate antibiotic use has raised concerns about antibiotic resistance in Brucella isolates (3-6).
It is now firmly established that Brucella is an intracellular bacterium capable of evading macrophage defenses. Furthermore, it induces significant mitochondrial fragmentation within 48 hours of entering various cell types. Consequently, effective antibiotics for brucellosis treatment must possess the ability to penetrate macrophages and eliminate the bacteria. However, in many clinical laboratories, routine antibiotic susceptibility testing is not feasible due to the absence of biosafety level 3 facilities (7-9). Consequently, there is limited available data regarding the antibiotic susceptibility of Brucella species, making it imperative to investigate. Thus, this study aimed to assess the antibiotic susceptibility profile of Brucella spp. isolated from humans in a systematic review and meta-analysis.

Materials and Methods

This systematic review and meta-analysis study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline 2020 (1).
Search Strategy
Two authors performed a systematic search of literature in the following electronic databases: PubMed, Web of Science, and Scopus. No time limitation was defined and all English studies from the beginning until September 2023 were included. The relevant medical subject heading (MeSH) terms and related keywords were used in combination to build the search strategy; (“brucella” OR “brucellosis” OR “brucel*”) AND (“antibiotic” OR “susceptibility” OR “resistance” OR “sensitivity” OR “sensitive” OR “resistant”).
Eligibility Criteria
Our eligibility criteria were defined based on the PICO framework: (P) Population: patients with brucellosis. (I) antibiogram test. (C) susceptibility or resistance. (O) Not applicable. Those studies that did not include human samples, did not report outcomes, or performed any antibiogram tests were excluded. Studies that were not in English, were also excluded.
Data Extraction and Outcome Measures
A standardized Excel sheet was prepared for data extraction. Two independent authors performed the data extraction. Disagreement between these two authors was discussed and resolved by a third author. The data extraction sheet included the following study characteristics: first author’s name, year of publication, country, total number of samples, susceptible and resistant samples for trimethoprim, rifampicin, doxycycline, tetracycline, ciprofloxacin, gentamicin, and streptomycin.
Data Synthesis and Statistical Analysis
The pooled susceptibility/resistance ratios were calculated using the random effects model and Mantel-Haenszel method along with the 95% confidence intervals. For assessing the heterogeneity of the included studies, the I² (I square) test was used. The Mantel-Haenszel method and random effects model were used for pooling the effect sizes. For testing the overall significance of the random model, a z-test was performed Potential publication bias was graphically assessed by creating funnel plots for each of the aforementioned groups. R (R Foundation for Statistical Computing, Vienna, Austria) and RStudio (RStudio, Inc., Boston, MA) were used for the statistical analysis and creation of forest and funnel plots.

Results

Our initial search retrieved 931 articles from PubMed, Scopus, and Web of Science, from which 185 duplicates were removed. After screening the title and abstract of 746 records, 66 full texts were retrieved, among which 15 studies (Figure 1) were included based on our eligibility criteria (4, 5, 10-22). More detail regarding the study characteristics of the included studies is summarised in Table 1.
Based on the pooled susceptibility ratios, among the 630 samples of Brucella spp., 98% (95% CI: 85% - 100%) were susceptible to trimethoprim. Further information regarding the susceptibility of Brucella spp. against trimethoprim is available in Figure 2. The pooled resistance ratio of Brucella spp. against trimethoprim is available in Appendix 1.

Figure 1. PRISMA flowchart of the included studies

Figure 2. The pooled susceptibility ratio of Brucella spp. against trimethoprim

Based on the pooled susceptibility ratios, among the 1255 samples of Brucella spp., 82% (95% CI: 54% - 95%) were susceptible to rifampicin. Further information regarding the susceptibility of Brucella spp. against rifampicin is available in Figure 3. The pooled resistance ratio of Brucella spp. against rifampicin is available in Appendix 2.
Based on the pooled susceptibility ratios, among the 1344 samples of Brucella spp., 100% (95% CI: 78% - 100%) were susceptible to doxycycline. Further information regarding the susceptibility of Brucella spp. against doxycycline is available in Figure 4. The pooled resistance ratio of Brucella spp. against doxycycline is available in Appendix 3.

Figure 3. The pooled susceptibility ratio of Brucella spp. against rifampicin

Figure 4. The pooled susceptibility ratio of Brucella spp. against doxycycline

Based on the pooled susceptibility ratios, among the 942 samples of Brucella spp., 100% (95% CI: 85% - 100%) were susceptible to tetracycline. Further information regarding the susceptibility of Brucella spp. against tetracycline is available in Figure 5. The pooled resistance ratio of Brucella spp. against tetracycline is available in Appendix 4.
Based on the pooled susceptibility ratios, among the 893 samples of Brucella spp., 100% (95% CI: 82% - 100%) were susceptible to ciprofloxacin. Further information regarding the susceptibility of Brucella spp. against ciprofloxacin is available in Figure 6. The pooled resistance ratio of Brucella spp. against ciprofloxacin is available in Appendix 5.

Figure 5. The pooled susceptibility ratio of Brucella spp. against tetracycline

Figure 6. The pooled susceptibility ratio of Brucella spp. against ciprofloxacin

Based on the pooled susceptibility ratios, among the 906 samples of Brucella spp., 97% (95% CI: 96% - 98%) were susceptible to gentamicin. Further information regarding the susceptibility of Brucella spp. against gentamicin is available in Figure 7. The pooled resistance ratio of Brucella spp. against gentamicin is available in Appendix 6.

Figure 7. The pooled susceptibility ratio of Brucella spp. against gentamicin

Discussion

In our systematic review and meta-analysis study, we evaluated the susceptibility of Brucella spp. to various antibiotics. The results demonstrated varying levels of susceptibility among these samples, indicating that certain antibiotics, such as trimethoprim, doxycycline, tetracycline, ciprofloxacin, and gentamicin, were effective against Brucella spp. infections. However, susceptibility to rifampicin was lower in comparison. These findings provide insights into potential treatment options for Brucella infections, supporting the importance of antibiotic selection in managing this disease.
Brucellosis primarily affects individuals who come into contact with farm animals, particularly cattle, sheep, and goats. Additionally, cases have been reported in those who consume raw milk, driven by traditional beliefs in its health benefits. Diagnosis typically relies on serological tests for antibodies or isolating the Brucella bacterium (10, 23, 24). However, the gold standard involves isolating the causative agent, which requires high-level biosafety laboratories due to the organism's high infectivity. Consequently, limited efforts are made to isolate and identify Brucella spp. from clinical samples, leading to potential misidentifications (11, 25-27).
Similarly, Lopez-Merino et al. found that cotrimoxazole and rifampin exhibited limited inhibitory activity against Brucella strains. In an endemic region for human brucellosis in Turkey, B. melitensis isolates demonstrated the highest resistance rate to cotrimoxazole (46.3%), while resistance to rifampin was observed in only 9.7%. In many developing countries, inappropriate antibiotic use is the primary driver of antibiotic resistance, resulting in the annual consumption of a multitude of antibiotics (28-31). Furthermore, Iran has reported significantly higher usage of systemic antibacterial agents like broad-spectrum penicillin, third-generation cephalosporins, and quinolones compared to other countries. It is known to exert an in vitro inhibitory effect against Brucella spp. due to its efficient intracellular diffusion. In our study, 98.5% (59/60) of the tested Brucella isolates with MIC≤1 μg/mL were classified as sensitive to rifampin based on the CLSI breakpoints for slow-growing bacteria. However, one Brucella strain exhibited resistance to rifampin with a MIC of 1.5 μg/mL. Notably, a high rate of rifampin resistance has been previously documented in Egyptian field strains (64%), as well as in Brazil (36.73%), Turkey (9.7%), and Malaysia (70%) (13, 32-35).
It's important to take into account that a significant portion of individuals with brucellosis cannot endure extended rifampin therapy due to its adverse gastrointestinal effects. Consequently, the concurrent use of streptomycin and doxycycline has been identified as the preferred treatment regimen, followed by the combination of rifampin and doxycycline, as there have been no reported treatment failures or relapses with these regimens. Nevertheless, several studies have cautioned against the indiscriminate use of rifampin due to the increased occurrence of intermediate sensitivity to these drugs (15, 36-39).
The World Health Organization has provided treatment recommendations for adults with acute brucellosis, endorsing a six-week regimen that combines doxycycline with either rifampicin or streptomycin. These guidelines remain applicable today. Nonetheless, there have been reports indicating that cases of brucellosis accompanied by osteoarticular and visceral complications are less prone to relapse when treated with a triple therapy approach involving streptomycin, rifampicin, and doxycycline (17, 40-44). Furthermore, an extensive review and meta-analysis of 30 randomized controlled trials have suggested that the preferred treatment should include combinations like doxycycline with gentamicin or triple regimens (e.g., doxycycline, rifampicin, and gentamicin). Despite combination therapy, there have been reports of relapse rates as high as 10%. Importantly, these relapses were primarily attributed to inadequate treatment due to issues such as incorrect dosing or poor patient compliance, rather than antimicrobial resistance. As a result, antimicrobial susceptibility testing is currently not considered indispensable in the management of brucellosis cases. Also, doxycycline has become the preferred tetracycline derivative for Brucella infection treatment due to its favorable pharmacokinetics (45-49).

Conclusion

In our systematic review and meta-analysis, we assessed the susceptibility of Brucella spp. to different antibiotics. Our findings revealed varying degrees of susceptibility among these samples. Notably, trimethoprim, doxycycline, tetracycline, ciprofloxacin, and gentamicin exhibited effectiveness against Brucella spp. infections. In contrast, rifampicin showed lower susceptibility. These results offer valuable insights into potential antibiotic choices for treating Brucella infections, emphasizing the significance of antibiotic selection in the management of this disease.

Acknowledgment

Not applicable.

Conflicts of Interest

The authors declare that they don’t have any conflict of interest.

Funding

None .

Type of Study: Meta-analysis Article | Subject: Antibiotic Resistance
Received: 2023/10/7 | Accepted: 2024/01/9 | ePublished: 2024/01/29

References

1. Yang XW, Wang YZ, Li JQ, Chen JJ, Liu JY, Tian GZ, et al. Genetic characteristics of an amikacin-resistant Brucella abortus strain first isolated from Marmota himalayana. Microb Pathog. 2022;164:105402. [DOI:10.1016/j.micpath.2022.105402] [PMID]

2. Tscherne A, Mantel E, Boskani T, Budniak S, Fasanella A, Feruglio SL, et al. Adaptation of Brucella melitensis Antimicrobial Susceptibility Testing to the ISO 20776 Standard and Validation of the Method. Microorganisms. 2022;10(7):1470. [DOI:10.3390/microorganisms10071470] [PMID] [PMCID]

3. Sheng X, Lu W, Li A, Lu J, Song C, Xu J, et al. ANT(9)-Ic, a Novel Chromosomally Encoded Aminoglycoside Nucleotidyltransferase from Brucella intermedia. Microbiol Spectr. 2023;11(3):e00620-23. [DOI:10.1128/spectrum.00620-23] [PMID] [PMCID]

4. Ma HR, Xu HJ, Wang X, Bu ZY, Yao T, Zheng ZR, et al. Molecular characterization and antimicrobial susceptibility of human Brucella in Northeast China. Front Microbiol. 2023;14:1137932. [DOI:10.3389/fmicb.2023.1137932] [PMID] [PMCID]

5. Dadar M, Alamian S, Brangsch H, Elbadawy M, Elkharsawi AR, Neubauer H, Wareth G. Determination of Virulence-Associated Genes and Antimicrobial Resistance Profiles in Brucella Isolates Recovered from Humans and Animals in Iran Using NGS Technology. Pathogens. 2023;12(1):82. [DOI:10.3390/pathogens12010082] [PMID] [PMCID]

6. Celik E, Kayman T, Buyuk F, Saglam AG, Abay S, Akar M, et al. The canonical Brucella species-host dependency is changing, however, the antibiotic susceptibility profiles remain unchanged. Microbial Pathogenesis. 2023;182:106261. [DOI:10.1016/j.micpath.2023.106261] [PMID]

7. Manafe RP, Bhembe-Magadaza NL, Green E. Antibiogram Screening and Detection of Virulence-Associated Genes in Brucella Species Acquired from Cattle in South Africa's Eastern Cape Province. Int J Environ Res Public Health. 2022;19(5):2813. [DOI:10.3390/ijerph19052813] [PMID] [PMCID]

8. Elbehiry A, Aldubaib M, Al Rugaie O, Marzouk E, Abaalkhail M, Moussa I, et al. Proteomics-based screening and antibiotic resistance assessment of clinical and sub-clinical Brucella species: An evolution of brucellosis infection control. PLoS One. 2022;17(1):e0262551. [DOI:10.1371/journal.pone.0262551] [PMID] [PMCID]

9. Arapović J, Kompes G, Dedić K, Teskeredžić S, Ostojić M, Travar M, et al. Antimicrobial resistance profiles of human Brucella melitensis isolates in three different microdilution broths: the first multicentre study in Bosnia and Herzegovina. J Glob Antimicrob Resist. 2022;29:99-104. [DOI:10.1016/j.jgar.2022.02.005] [PMID]

10. Wareth G, El-Diasty M, Abdel-Hamid NH, Holzer K, Hamdy MER, Moustafa S, et al. Molecular characterization and antimicrobial susceptibility testing of clinical and non-clinical Brucella melitensis and Brucella abortus isolates from Egypt. One Health. 2021;13:100255. [DOI:10.1016/j.onehlt.2021.100255] [PMID] [PMCID]

11. Gültekin E, Uyanık MH, Albayrak A, Kılıç S. Investigation of antibiotic susceptibilities of Brucella Strains isolated from various clinical samples in eastern Turkey. Eur J Med Res. 2021;26(1):57. [DOI:10.1186/s40001-021-00527-5] [PMID] [PMCID]

12. Yuan HT, Wang CL, Liu LN, Wang D, Li D, Li ZJ, Liu ZG. Epidemiologically characteristics of human brucellosis and antimicrobial susceptibility pattern of Brucella melitensis in Hinggan League of the Inner Mongolia Autonomous Region, China. Infect Dis Poverty. 2020;9(1):79. [DOI:10.1186/s40249-020-00697-0] [PMID] [PMCID]

13. Alamian S, Dadar M, Etemadi A, Afshar D, Alamian MM. Antimicrobial susceptibility of Brucella spp. isolated from Iranian patients during 2016 to 2018. Iran J Microbiol. 2019;11(5):363-7. [DOI:10.18502/ijm.v11i5.1953] [PMID] [PMCID]

14. Mani SSR, Gunasekaran K, Iyyadurai R, Prakash JAJ, Veeraraghavan B, Mishra AK, et al. Clinical spectrum, susceptibility profile, treatment and outcome of culture-confirmed brucellosis from South India. Indian J Med Microbiol. 2018;36(2):289-92. [DOI:10.4103/ijmm.IJMM_18_236] [PMID]

15. Liu ZG, Di DD, Wang M, Liu RH, Zhao HY, Piao DR, et al. In vitro antimicrobial susceptibility testing of human Brucella melitensis isolates from Ulanqab of Inner Mongolia, China. BMC Infect Dis. 2018;18(1):43. [DOI:10.1186/s12879-018-2947-6] [PMID] [PMCID]

16. Farazi A, Hoseini SD, Ghaznavirad E, Sadekhoo S. Antibiotic Susceptibility of Brucella Melitensis in Markazi Province of Iran. Int J Infect Dis. 2018;73:124. [DOI:10.1016/j.ijid.2018.04.3697]

17. Torkaman Asadi F, Hashemi SH, Yousef Alikhani M, Moghimbeigi A, Naseri Z. Clinical and diagnostic aspects of brucellosis and antimicrobial susceptibility of brucella isolates in Hamedan, Iran. Jpn J Infect Dis. 2017;70(3):235-8. [DOI:10.7883/yoken.JJID.2016.133] [PMID]

18. Shevtsov A, Syzdykov M, Kuznetsov A, Shustov A, Shevtsova E, Berdimuratova K, et al. Antimicrobial susceptibility of Brucella melitensis in Kazakhstan. Antimicrob Resist Infect Control. 2017;6:130. [DOI:10.1186/s13756-017-0293-x] [PMID] [PMCID]

19. Reza Irajian G, Masjedian Jazi F, Mirnejad R, Piranfar V, Zahraei Salehi T, Amir Mozafari N, et al. Species-specific PCR for the diagnosis and determination of antibiotic susceptibilities of brucella strains Isolated from Tehran, Iran. Iran J Pathol. 2016;11(3):238-47.

20. Razzaghi R, Rastegar R, Momen-Heravi M, Erami M, Nazeri M. Antimicrobial susceptibility testing of Brucella melitensis isolated from patients with acute brucellosis in a centre of Iran. Indian J Med Microbiol. 2016;34(3):342-5. [DOI:10.4103/0255-0857.188336] [PMID]

21. Hashemi SH, Alikhani MY, Asadi FT, Naseri Z. Antibiotic susceptibility pattern of Brucella melitensis clinical isolates in Hamedan, West of Iran. Int J Infect Dis. 2016;45:91-2. [DOI:10.1016/j.ijid.2016.02.244]

22. Abdel-Maksoud M, House B, Wasfy M, Abdel-Rahman B, Pimentel G, Roushdy G, Dueger E. In vitro antibiotic susceptibility testing of Brucella isolates from Egypt between 1999 and 2007 and evidence of probable rifampin resistance. Ann Clin Microbiol Antimicrob. 2012;11:24. [DOI:10.1186/1476-0711-11-24] [PMID] [PMCID]

23. Al-Afifi AH, Alewy Almashhadany D, Al-Azazi ASH, Khalaf AM, Naji Ahmed Odhah M, Al-Gabri NA. Prevalence of Brucella spp. in milk from aborted and non-aborted animals in Dhamar governorate, Yemen. Ital J Food Saf. 2022;11(4):10370. [DOI:10.4081/ijfs.2022.10370] [PMID] [PMCID]

24. Lama M, Chanakya PP, Khamari B, Peketi ASK, Kumar P, Muddu GK, et al. Genomic analysis of a multidrug-resistant Brucella anthropi strain isolated from a 4-day-old neonatal sepsis patient. J Glob Antimicrob Resist. 2021;26:227-9. [DOI:10.1016/j.jgar.2021.06.013] [PMID]

25. Castillo-Zeledón A, Ruiz-Villalobos N, Altamirano-Silva P, Chacón-Díaz C, Barquero-Calvo E, Chaves-Olarte E, Guzmán-Verri C. A Sinorhizobium meliloti and Agrobacterium tumefaciens ExoR ortholog is not crucial for Brucella abortus virulence. PLoS ONE. 2021;16(8):e0254568. [DOI:10.1371/journal.pone.0254568] [PMID] [PMCID]

26. Yang XW, Piao DR, Mao LL, Pang B, Zhao HY, Tian GZ, et al. Whole-genome sequencing of roughBrucella melitensisin China provides insights into its genetic features. Emerg Microbes Infect. 2020;9(1):2147-56. [DOI:10.1080/22221751.2020.1824549] [PMID] [PMCID]

27. Sofi-Mahmudi A, Masinaei M, Shamsoddin E, Tovani-Palone MR, Heydari M-H, Shoaee S, et al. Global, regional, and national burden and quality of care index (QCI) of lip and oral cavity cancer: a systematic analysis of the Global Burden of Disease Study 1990-2017. BMC Oral Health. 2021;21(1):1-11. [DOI:10.1186/s12903-021-01918-0] [PMID] [PMCID]

28. Khan S, Akhtar MU, Khan S, Javed F, Khan AA. Nanoniosome-encapsulated levoflaxicin as an antibacterial agent against Brucella. J Basic Microbiol. 2020;60(3):281-90. [DOI:10.1002/jobm.201900454] [PMID]

29. del Villar-Perez VM, Barreras-Serrano A, Tamayo-Sosa AR, Tinoco-Gracia L, Melgarejo T. Evaluation of the antimicrobial activity of the K9CATH peptides of 21 and 38 amino acids against Brucella abortus and Brucella melitensis. Thai J Vet Med. 2020;50(4):593-7. [DOI:10.56808/2985-1130.3067]

30. Aslam M, Shehroz M, Shah M, Khan MA, Afridi SG, Khan A. Potential druggable proteins and chimeric vaccine construct prioritization against Brucella melitensis from species core genome data. Genomics. 2020;112(2):1734-45. [DOI:10.1016/j.ygeno.2019.10.009] [PMID]

31. Shoaee S, Masinaei M, Moghaddam SS, Sofi-Mahmudi A, Hessari H, Shamsoddin E, et al. National and Subnational Trend of Dental Caries of Permanent Teeth in Iran, 1990-2017. Int Dent J. 2023;74(1):129-37. [DOI:10.1016/j.identj.2023.07.012] [PMID] [PMCID]

32. Liu ZG, Cao XA, Wang M, Piao DR, Zhao HY, Cui BY, et al. Whole-Genome Sequencing of a Brucella melitensis Strain (BMWS93) Isolated from a Bank Clerk and Exhibiting Complete Resistance to Rifampin. Microbiol Resour Announc. 2019;8(33):e01645. [DOI:10.1128/MRA.01645-18] [PMID] [PMCID]

33. Khan AU, Shell WS, Melzer F, Sayour AE, Ramadan ES, Elschner MC, et al. Identification, Genotyping and Antimicrobial Susceptibility Testing of Brucella spp. Isolated from Livestock in Egypt. Microorganisms. 2019;7(12):603. [DOI:10.3390/microorganisms7120603] [PMID] [PMCID]

34. Cama BAV, Ceccarelli M, Rullo EV, Ferraiolo F, Paolucci IA, Maranto D, et al. Outbreak of Brucella melitensis infection in Eastern Sicily: Risk factors, clinical characteristics and complication rate. New Microbiol. 2019;42(1):43-8.

35. Moscowchi A, Moradian-Lotfi S, Koohi H, Sarrafan Sadeghi T. Levels of smoking and outcome measures of root coverage procedures: a systematic review and meta-analysis. Oral Maxillofac Surg. 2023. [DOI:10.1007/s10006-023-01172-4] [PMID]

36. Trott DJ, Abraham S, Adler B. Antimicrobial Resistance in Leptospira, Brucella, and Other Rarely Investigated Veterinary and Zoonotic Pathogens. Microbiol Spectr. 2018;6(4):A11. [DOI:10.1128/microbiolspec.ARBA-0029-2017] [PMID]

37. Singh DK, Kumar B, Shrinet G, Singh RP, Das A, Mantur BG, et al. Draft genome sequence of field isolate Brucella melitensis strain 2007BM/1 from India. J Glob Antimicrob Resist. 2018;13:152-3. [DOI:10.1016/j.jgar.2018.04.008] [PMID]

38. Monti SM, Meccariello A, Ceruso M, Szafrański K, Sławiński J, Supuran CT. Inhibition studies of Brucella suis β-carbonic anhydrases with a series of 4-substituted pyridine-3-sulphonamides. J Enzyme Inhib Med Chem. 2018;33(1):255-9. [DOI:10.1080/14756366.2017.1413097] [PMID] [PMCID]

39. Shoaee S, Saeedi Moghaddam S, Masinaei M, Sofi-Mahmudi A, Hessari H, Heydari M-H, et al. Trends in dental caries of deciduous teeth in Iran: a systematic analysis of the national and sub-national data from 1990 to 2017. BMC Oral Health. 2022;22(1):634. [DOI:10.1186/s12903-022-02634-z] [PMID] [PMCID]

40. Basyony AF, Aboulwafa MM, Hafez MM, Abou-Gazia KAS. Antimicrobial susceptibility profile, Adherence and invasion to mammalian cells of Brucella melitensis isolates. Pak J Pharm Sci. 2018;31(6):2379-90.

41. Zuo SW, Ni ZL, Yao YB, Yang RS, Wang SK, Zhou YH. [Study on antimicrobial susceptibility of Brucella in a city]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2017;35(12):939-41.

42. Qian J, Bu Z, Lang X, Yan G, Yang Y, Wang X, Wang X. A safe and molecular-tagged Brucella canis ghosts confer protection against virulent challenge in mice. Vet Microbiol. 2017;204:121-8. [DOI:10.1016/j.vetmic.2017.04.027] [PMID]

43. Monti SM, Meccariello A, Ceruso M, Szafranski K, Slawinski J, Supuran CT. Inhibition studies of Brucella suis beta-carbonic anhydrases with a series of 4-substituted pyridine-3-sulphonamides. J Enzyme Inhib Med Chem. 2017;33(1):255. [DOI:10.1080/14756366.2017.1413097] [PMID] [PMCID]

44. Mortazavi H, Sadeghian A, Hazrati P, Heydari M-H, Madihi S. Oral hemorrhagic blister and its possible related factors: Analyses of reported cases in the literature. J Oral Maxillofac Surg Med Pathol. 2023;35(4):358-67. [DOI:10.1016/j.ajoms.2022.12.009]

45. Khazaei Z, Najafi A, Piranfar V, Mirnejad R. Microarray-based long oligonucleotides probe designed for Brucella Spp. detection and identification of antibiotic susceptibility pattern. Electron Physician. 2016;8(4):2297-303. [DOI:10.19082/2296] [PMID] [PMCID]

46. Wu T, Wang S, Wang Z, Peng X, Lu Y, Wu Q. A multicopper oxidase contributes to the copper tolerance of Brucella melitensis 16M. FEMS Microbiol Lett. 2015;362(12):fnv078. [DOI:10.1093/femsle/fnv078]

47. Maansi M, Upadhyay AK. Antibiotic susceptibility of smooth Brucella Abortus S99 and rough Brucella Melitensis B115 strains. Indian Vet J. 2015;92(7):80-1.

48. Deshmukh A, Hagen F, Sharabasi OA, Abraham M, Wilson G, Doiphode S, et al. In vitro antimicrobial susceptibility testing of human Brucella melitensis isolates from Qatar between 2014 - 2015. BMC Microbiol. 2015;15:121. [DOI:10.1186/s12866-015-0458-9] [PMID] [PMCID]

49. Shoaee S, Rezaie F, Payab M, Bakhtiari F, Heydari M-H. Experiences from the management of COVID-19 pandemic in a nursing home in Iran (March-April, 2020). J Diabetes Metab Disord. 2022;21(1):1195-9. [DOI:10.1007/s40200-022-01005-3] [PMID] [PMCID]