Synergistically Active and Safe Fixed Dose Combination of Meropenem and Sulbactam

Vijender Singh Beniwal, Parmjit Arora

Abstract


Meropenem is a third generation broad spectrum antibiotic. Emergence of meropenem resistance has been reported due to development of mutant plasmid mediated metallo-β-lactamases (IMP-6) and AmpC β–lactamases. Sulbactam, a stable β-lactamase inhibitor, increase antimicrobial activity of meropenem by inhibiting the enzyme β-lactamase. Fixed dose combination of Meropenem-sulbactam in the proportion of 1:1, 1:2, 1:3, 2:1 and 3:1 were evaluated for the antimicrobial activity. Combination of meropenem and sulbactam in the ratio of 2:1 exhibited the synergistic activity. This combination was checked for the subchronic toxicity on wistar rats and no change in biochemical and physiological parameters was observed.


Keywords


Meropenem resistance, β-lactamase inhibitors, meropenem toxicity

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References


Bharadwaj R, Dewan V and Pal A. An in vitro study to evaluate the synergistic activity of Norfloxacin and metronidazole. Indian J Pharmacol 2003; 35: 220-226.

Cécile A, Poirel L, Ronald JA and Nordmann P. Carbapenemase-producing Enterobacteriaceae in U. S. Rivers. Emerging Infectious Diseases (www.cdc.gov/eid) 2005; 11:2.

Hernández JR, Velasco C, Romero L, Martiìnez ML and Pascual A. Comparative in vitro activity of ertapenem against extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumonia isolated in Spain. Int J Antimicrob Agents 2006; 28:457-459.

Hsu HL, Lu CY, Tseng HY, Lee PI, Lai HP, Lin WC, et al., Empirical monotherapy with meropenem in serious bacterial infections in children. Microbiol Immunol Infect 2001; 34: 275-280.

Huizinga WKJ, Warren BL, Baker LW, Valleur P, Pezet DM, Hoogkamp KJA, et al., Antibiotic monotherapy with meropenem in the surgical management of intraabdominal infections. J Antimicrob Chemother 1995; 36: 179-189.

Laure M, Guillou J, Kemp M, Cavallo JD, Chomara M, Dubreuil L et al., comparative in vitro activity of Meropenem, Imipenem and Piperacillin/tazobactam against 1071 clinical isolates using 2 different methods: a French multicentre study. BMC Infectious Dis 2010; 10:72-76.

Lee CM, Lim HK, Liu CP, Tseng HK. Treatment of pan-drug resistant Acinetobacter baumannii. Scand J Infect Dis 2005;37(3):195-9.

Lim VK and Cheong YM. In-vitro activity of cefoperazone-sulbactam combination against cefoperazone resistant clinical isolates in a Malaysian general hospital., Malays J Pathol 1995; 17: 73-6.

Masuda N and Ohya S. Cross-Resistance to Meropenem, Cephems, and Quinolones in Pseudomonas aeruginosa. Antimicrob Agents Chemother 1992; 36: 1847-1851.

Mouton YJ and Beuscart C. Meropenem Study Group. Empirical monotherapy with meropenem in serious bacterial infections. J Antimicob Chemother 1995; 36: 145-156.

Nordmann P and Poirel L. Emerging carbapenemases in Gram-negative aerobes. Clin Microbiol Infect 2002; 8:321–331.

Pfaller MA and Ronald NJ. MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) results from the Americas: resistance implications in the treatment of serious infections. J Antimicrobial ChemothL 2000; 46: 25-37.

Ryoo NH, Lee K, Limb JB, Lee YH, Baed K and Jeongb SH. Outbreak by meropenem-resistant Pseudomonas aeruginosa producing IMP-6 metallo-β-lactamase in a Korean hospital., Diagnostic Microbiology and Infectious Disease 2009; 63: 115–117.

Sinha M and Srinivasa H. Mechanisms of resistance to carbapenems in meropenem- resistant Acinetobacter isolates from clinical samples. Indian J Med Microbiol 2010; 25:121-125.

Wise R, Andrews JM, and Bedford KA. Clavulanic acid and CP-45,899: a comparison of their in vitro activity in combination with penicillins. J Antimicrob Chemother 1980; 6:197-206.

Yano H, Kuga A, Okamoto R, Kitasato H, Kobayashi T and Inoue M. Plasmid-encoded metallo-β-lactamase (IMP-6) conferring resistance to carbapenems, especially meropenem. Antimicrob Agents Chemother 2001; 45: 1343–1348.




DOI: https://doi.org/10.5195/iioablett.2012.6

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