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 Table of Contents  
LETTER TO EDITOR
Year : 2014  |  Volume : 1  |  Issue : 3  |  Page : 210-211

In vitro microbial efficacy of sulbactomax: A novel fixed dose combination of ceftriaxone, sulbactum, and ethylenediamine-tetraacetic acid against metallo β-lactamases producing strains of non-fermenters


Department of Microbiology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal, India

Date of Web Publication17-Aug-2014

Correspondence Address:
Kalidas Rit
Department of Microbiology, Institute of Post Graduate Medical Education and Research, Kolkata, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2348-3334.138911

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How to cite this article:
Rit K, Naha A. In vitro microbial efficacy of sulbactomax: A novel fixed dose combination of ceftriaxone, sulbactum, and ethylenediamine-tetraacetic acid against metallo β-lactamases producing strains of non-fermenters. CHRISMED J Health Res 2014;1:210-1

How to cite this URL:
Rit K, Naha A. In vitro microbial efficacy of sulbactomax: A novel fixed dose combination of ceftriaxone, sulbactum, and ethylenediamine-tetraacetic acid against metallo β-lactamases producing strains of non-fermenters. CHRISMED J Health Res [serial online] 2014 [cited 2019 Oct 21];1:210-1. Available from: http://www.cjhr.org/text.asp?2014/1/3/210/138911

Sir,

Non-fermenters (NF) are a heterogeneous group of aerobic, non-spore-forming gram-negative bacteria of the division Proteobacteria unable to ferment carbohydrate (e.g. glucose). There has been a steady increase in metallo β-lactamases (MBLs) producing strains of NF among clinical isolates (from wound swab, pus, sputum, blood, urine, tracheal aspirate, and various body fluids). MBLs are enzymes belonging to Ambler ' s Class B that can hydrolyze a wide variety of beta-lactam antibiotics. [1] Verona integron mediated MBL (VIM) and IMP (active on imipenem) are the most frequently acquired Class B enzymes. New Delhi metallo β-lactamases 1 (NDM1) has been found in multiple cases of India. [2] A total of hundred isolates of NF were obtained from various types of specimens. In this study, 20 out of 100 (20%) strains were resistant to imipenem. Out of 20 strains, 12 were (60%) found positive for MBL production by disc approximation test. A polymerase chain reaction (PCR) assay was performed to detect MBL encoding genes using specific primers. In this study, majority of the MBL production was because of blaNDM1 encoding gene (about ten of the isolates), and in other two cases, blaVIM1 and blaIMP1 were found. For patients infected with MBL producing NF, last resort compounds such as tigecycline and colistin offer the only means of treatment and in case of colistin, often at the cost of serious side effects. Moreover tigecycline is currently not licensed for treatment of urinary tract infection. Also the higher cost precludes their use in routine condition. Thereby, this study is aimed at evaluating antimicrobial efficiency of sulbactomax (a novel fixed dose combination of ceftriaxone, sulbactum, and EDTA) in comparison with ceftriaxone, tigecycline, amoxicillin-clavulanic acid combination, piperacillin-tazobactum combination, colistin by antimicrobial susceptibility testing, time-kill curve analysis, and minimum inhibitory concentration (MIC) assay. Combination of ceftriaxone with sulbactum is a stable one and it enhances the spectrum of activity of ceftriaxone. Sulbactum demonstrates synergistic activity by reducing minimum inhibitory concentration for the combination. [3] Comparative in vivo study proved the efficacy and safety of the sulbactomax. [4] In house MBL producing NF were used for susceptibility study. Among the 12 MBL-positive isolates, 7 were Pseudomonas aeruginosa, 3 were Acinetobacter baumanii, and remaining 2 were A. lowfii. Ceftriaxone, sulbactomax, tigecycline, amoxicillin-clavulanic acid combination, piperacillin-tazobactum combination, and colistin used in this study were provided by Venus Remedis Limited, India. Susceptibility discs used in this study was procured from Hi media Lab Ltd. India. Susceptibility testing was done according to Kirby Bauer's disc diffusion following Clinical and Laboratory Standards Institute (CLSI) protocol. [5],[6] MIC was determined by agar dilution method according to CLSI guidelines. [7] The range of drug concentration of each antibiotic tested was 0.0625-250 mg/L. Results from our study proved that ceftriaxone has higher MIC value than sulbactomax, suggesting higher bactericidal activity in sulbactomax. In case of Pseudomonas aeruginosa, the range of MIC were found to be 4-16 mg/L against ceftriaxone, 1-2 mg/L against sulbactomax, which was distinctly much lower. In case of Acinetobacter spp. the range of MIC were found to be 16-64 mg/L against ceftriaxone, 2-4 mg/L against sulbactomax, which was also distinctly much lower. Findings from our study also demonstrated that sulbactomax has lower MIC value in comparison with other antimicrobials tested except in case of colistin and tigecycline having comparative MIC values. The susceptibility zone of NF was higher [Figure 1] in cefoperazone sulbactum disc when compared with ceftriaxone, amoxicillin-clavulanic acid, piperacillin-tazobactum discs, and comparable with that of colistin and tigecycline. Muller-Hinton broth supplemented with calcium (25 mg/L) and magnesium (12.5 mg/L) was used for susceptibility testing and killing curve experiment. Time-kill curve analysis revealed bactericidal effect with 2× the MIC of sulbactomax and other antimicrobial tested achieved the earliest killing at 2 hours. In all organisms under study, time-kill curve analysis demonstrated maximum bacterial killing at 6 hours against each of the antibiotic tested. Sulbactomax demonstrated better bactericidal activity than comparison to ceftriaxone, amoxicillin-clavulanic acid, piperacillin-tazobactum, colistin. Tigecycline showed slightly better activity in comparison to sulbactomax. Our study demonstrated that ceftriaxone, amoxicillin-clavulanic acid combination, piperacillin-tazobactum combination have higher MIC values than sulbactomax. The MIC values of colistin and tigecycline were comparable with that of sulbactomax. Thus, it can be concluded that sulbactomax is a relatively cheap, safe novel antimicrobial combination that can be effective against MBL producer NF.
Figure 1: Antimicrobial susceptibility test showed wide susceptibility zone of sulbactomax in comparison with imipenem

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  Acknowledgments Top


Venus Remedis Limited, India.

 
  References Top

1.Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother 1995;39:1211-33.  Back to cited text no. 1
    
2.Kumarasamy KK, Toleman MA, Walsh TR, Bagaria J, Butt F, Balakrishnan R, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: A molecular, biological, and epidemiological study. Lancet Infect Dis 2010;10:597-602.  Back to cited text no. 2
    
3.Shrivastava SM, Singh R, Tariq A, Siddiqui MR, Yadav J, Negi PS, et al. A novel high performance liquid chromatographic method for simultaneous determination of ceftriaxone and sulbactum in sulbactomax. Int J Biomed Sci 2009;5:37-43.  Back to cited text no. 3
    
4.Dwivedi VK, Chowdhary M, Soni A, Yadav J, Tariq A, Siddiqui MR, et al. Diffusion of sulbactomax and ceftriaxone into cerebrospinal fluid of meningitis induced rat model. Int J Pharmacol 2009;5:307-12.  Back to cited text no. 4
    
5.Bauer AW, Kirby WM, Sherris JC, Turck M. Antibiotic susceptibility testing by a standardized single disc method. Am J Clin Pathol 1966;45:493-6.  Back to cited text no. 5
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6.Wikler MA, Cockerill FR, Craiz WA, Low DE, Sheehan D, Tenover FC, et al. Clinical Laboratory Standard Institute. Performance Standards for Antimicrobial Disc Susceptibility Tests. 9 th ed., Vol. 26. 2006. p. M2-A9.  Back to cited text no. 6
    
7.National Committee for Clinical Laboratory Standards. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. 4 th ed. Approved standard M7-A4. Wayne: National Committee for Clinical Laboratory Standards; 1997.  Back to cited text no. 7
    


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