In vitro activity of moxalactam and mecillinam, singly and in combination, against multi-drug-resistant Enterobacteriaceae and Pseudomonas species

Abstract

The in vitro interaction of moxalactam and mecillinam against multi-drug-resistant gram-negative enteric bacilli was studied by checkerboard microdilution susceptibility tests and by killing curve kinetics. Against Enterobacteriaceae, the combination was unpredictable; the frequencies of synergy, indifference, and antagonism were 11, 76, and 13%, respectively. Against Pseudomonas sp., the two drugs were consistently indifferent. Overall, the combination of moxalactam and mecillinam was no more active than moxalactam alone.

Dual beta-lactam therapy for serious Gram-negative infections: is it time to revisit?

“…Consistent with the P. aeruginosa in vitro studies, synergy was commonly observed with dual beta-lactam combination regimens that included aztreonam (Buesing and Jorgensen, 1984;Sader et al, 2003;Stutman et al, 1984) or a third-generation cephalosporin (Buesing and Jorgensen, 1984;Daschner and Hoffmann, 1982;Tsuchiya, 1981a, 1981b;Kurtz et al, 1981;Miles et al, 1981;Neu, 1982;Sader et al, 2003;Verbist and Verhaegen, 1984;Zinner et al, 1981). Combinations including mecillinam were also found to be highly successful against Enterobacteriaceae in earlier analyses, where synergistic interactions were observed against a high proportion of all pathogens (Anderson et al, 1981;Baltimore et al, 1976;Chattopadhyay and Hall, 1979;Cleeland and Squires, 1983;Fass, 1980Fass, , 1982aFass, , 1982bTsuchiya, 1981a, 1981b;Schaad et al, 1982;Scheld et al, 1979;Tybring and Melchior, 1975;van der Voet et al, 1983). In more recent studies, carbapenems were synergistic when used with another beta-lactam.…”

“…Moxalactam and first-generation cephalosporins, such as cefazolin and cephalothin, were also found to be antagonistic when combined with other beta-lactams (Buesing and Jorgensen, 1984;Fass, 1982aFass, , 1982bFu and Neu, 1978;Kuck et al, 1981;Neu and Fu, 1978;Verbist and Verhaegen, 1984). An exception to this was found when these agents were combined with mecillinam.…”

“…Most of these studies used broth or agar dilution or the checkerboard method to test for synergy (Anderson et al, 1981;Baltimore et al, 1976;Bosso et al, 1990;Bosso et al, 1991;Buesing and Jorgensen, 1984;Chattopadhyay and Hall, 1979;Chen et al, 2004;Cleeland and Squires, 1983;Daschner and Hoffmann, 1982;Drusano et al, 1985;Fass, 1980;Fass, 1982aFass, , 1982bFoweraker et al, 2009;Fu and Neu, 1978;Tsuchiya, 1981a, 1981b;Kuck et al, 1981;Kurtz et al, 1981;Markowitz and Sibilla, 1983;Miles et al, 1981;Moody et al, 1984;Neu, 1982;Neu and Fu, 1978;Peterson et al, 1984;Sader et al, 2003;Schaad et al, 1982;Scheld et al, 1979;Scribner et al, 1982;Song et al, 2003;Stutman et al, 1984;Tybring and Melchior, 1975;van der Voet et al, 1983;Verbist and Verhaegen, 1984;Wu et al, 1984;Zinner et al, 1981), but time-kill studies were also done (Foweraker et al, 2009;Fu and Neu, 1978;Tsuchiya, 1981a, 1981b;Lister et al, 1998;Markowitz and Sibilla, 1983;…”