Short Communication - (2021) Volume 12, Issue 6
Shilpakala Sainath Rao1*, Malathi Raghunathan1, Rathna Durga Manian2 and Raghunathan R2
1Department of Genetics, Dr. ALMPGIBMS, University of Madras, Tamilnadu, India
2Department of Organic Chemistry, University of Madras, Tamilnadu, India
Received Date: August 25, 2021; Accepted Date: September 08, 2021; Published Date: September 15, 2021
Citation: Rao SS, Raghunathan M, Manian RD, Raghunathan R (2021) In vitro Activities of RD-3 and Other Antimicrobial Agents against Ureaplasma urealyticum Isolates. Arch Clin Microbial Vol.12 No.6: 182.
About the Study
RD-3 is a quinoline derivative with the formula bis(4,9,9a,10- tetrahydro-9-phenyl-3bH-pyrrolizino-(1,2b)quinolin-7-) methane12 (Figure 1) and has shown broad spectrum of activity against different microorganisms [1,2]. Currently this drug is under consideration for development by a pharmaceutical company. Ureaplasma urealyticum is known to cause a variety of urogenital infections [3]. It is known to cause systemic infections in newborns. Tetracycline is the treatment of choice in adults and erythromycin is used in the case of children and neonates [4]. Resistance to fluoroquinolones due to mutations in parC and parE genes, and resistance to macrolides due to mutations in 23SrRNA have been increasing in these isolates worldwide [5]. In this study we examined the activity of RD-3 and other antimicrobial agents against clinical isolates of Ureaplasma urealyticum.
Figure 1: Chemical structure of RD-3.
Organisms included 32 isolates of Ureaplasma urealyticum strains collected since 2008. Organisms included 18 isolates resistant to tetracyclines, macrolides, fluoroquinolones, alone or in combination.
The comparator agents, tetracycline, azithromycin and moxifloxacin were from Sigma-Aldrich (St. Louis, MO,USA).
Antimicrobial powders were used according to the manufacturer’s protocol. Working dilutions of the drugs were prepared fresh on the day of the assay.
Antimicrobial Susceptibility testing was performed by the standard agar-dilution method as described in accordance with Clinical and Laboratory Standards Institute (CLSI) guideline [6]. Inoculum was prepared and MICs were determined and interpreted. Organisms were stored frozen at -80° until thawing for testing.
The MICs of U. urealyticum against different drugs are given in (Table 1). RD-3 was most active with an MIC90 of 0.032 mg/L (range 0.016-0.032 mg/L). Moxifloxacin showed better activity than azithromycin and tetracycline with an MIC90 of 2 mg/L. Tetracycline and azithromycin had an MIC90 several fold higher than RD-3 at 4 mg/L and 8 mg/L respectively.
| Organism or drug (n= 32) | MIC range | MIC50 (mg/L) | MIC90 (mg/L) |
|---|---|---|---|
| RD-3 | 0.016-0.032 | 0.016 | 0.032 |
| Tetracycline | 0.125-16 | 0.25 | 4 |
| Azithromycin | 0.25-32 | 4 | 8 |
| Moxifloxacin | 0.125-4 | 0.25 | 2 |
Table 1: Activities of RD-3 and other antibiotics against clinical isolates of U. urealyticum.
Among the 32 isolates, 8 isolates were resistant to tetracycline (MICs 16 to >32 mg/L, 5 isolates were resistant to macrolide, azithromycin (MICs>32 mg/L), and 2 isolates were resistant to fluoroquinolone, moxifloxacin (MICs 4 to 8 mg/L). 2 isolates of U. urealyticum were resistant to both azithromycin and tetracycline. One isolate was resistant to tetracycline and moxifloxacin. RD-3 was highly active against these resistant isolates with MICs ranging from 0.016 to 0.032 mg/L. This shows that resistance to moxifloxacin, azithromycin and tetracycline did not affect RD-3’s activity. Since there are no CLSI breakpoints for Ureaplasmas, susceptibility testing to different antibacterials was difficult to compare. Previous studies showed that RD-3 was highly active against M. pneumoniae and M. hominis (2). These studies suggest that RD-3 could be used as an alternative drug to treat upper respiratory tract infections and urogenital infections caused by human Mycoplasmas and Ureaplasma, requiring further clinical studies.
Conclusion
Rise in antimicrobial resistance to microorganisms had led researchers to look for new strategies and novel mechanisms to combat this microbial resistance. Some novel methods have been to use antimicrobial peptides, new drug classes etc. Ureaplasma sp causes a variety of urogenital infections in humans. Treatment of Ureaplasmas has been complicated by resistance to macrolides and fluoroquinolones. Tetracycline resistance occurs due to ribosomal protection mediated by the term transposon. Urogenital Mycoplasmas and Ureaplasmas have different antimicrobial resistance patterns. The reasons like this have prompted researchers to look for new antimicrobials that are not affected by cross-resistance to other drugs. Even in the absence of resistance genes Ureaplasmas have higher MICs than other organisms for fluoroquinolones and tetracycline. quinoline derivatives are drugs that have shown broad spectrum activity. These drugs have also shown potent antimicrobial activity against Mycoplasmas, Chlamydias etc. Earlier work demonstrated that RD-3 inhibited gyrase supercoiling with activity that was comparable to ciprofloxacin and down-regulated gyrase A expression in Escherichia coli. These in vitro data suggests that RD-3 may show considerable promise in treating genital and respiratory infections.
Acknowledgement
This study was funded partially by University of Madras.
41866