Comparative in vitro activities of azlocillin-cefotaxime and azlocillin-tobramycin combinations against blood and multi-drug resistant bacterial isolates

Abstract

The in vitro activities of azlocillin and cefotaxime in combination and of azlocillin and tobramycin in combination against 100 blood isolates and 50 multidrug-resistant isolates were compared. With both combinations, antibacterial spectrums were complementary. Although synergy against individual strains was infrequently observed (except for azlocillin-cefotaxime against Streptococcus faecalis and azlocillin-tobramycin against Pseudomonas aeruginosa), 97% of blood isolates and 76% of multidrug-resistant isolates were susceptible to azlocillin-cefotaxime, and 94% of blood isolates and 36% of multidrug-resistant isolates were susceptible to azlocillin-tobramycin.Penicillin-aminoglycoside and cephalosporinaminoglycoside antibiotic combinations have broad antibacterial spectrums, are frequently synergistic in vitro, and are commonly used to treat a variety of serious bacterial infections (9). To avoid aminoglycoside toxicity, penicillincephalosporin combinations have also been used, but results using early derivatives have not been optimal (2). In recent years, new penicillins and cephalosporins which have greater potencies and spectrums of activity than their prototypes have been developed (4, 7). Therefore, a reexamination of the potential for using penicillin-cephalosporin combinations as alternatives to 3-lactam-aminoglycoside combinations for treating certain types of infections seems appropriate.In this study, we compared the in vitro activity of azlocillin (a new antipseudomonal penicillin) and cefotaxime (a third generation of cephalosporin) in combination with the activity of azlocillin and tobramycin (an aminoglycoside) (Difco Laboratories, Detroit, Mich.) and an inoculum size of approximately 2 x 105 colony-forming units per ml were used (6). Antibiotics were considered synergistic when there was a fourfold or greater reduction in MICs of both drugs in a combination compared with MICs of individual drugs, antagonistic when there was a fourfold or greater increase in MICs of both drugs or when the addition of an inactive antibiotic to an active antibiotic increased the MIC of the latter by fourfold or more, and indifferent when the results were intermediate. Results were considered indeterminate if the endpoints were not in the range of concentrations tested (0.25 to 256 ,ug/ml for azlocillin and 0.25 to 16 ,ug/ml for cefotaxime and tobramycin).

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;…”

Cystic fibrosis, pathophysiological and clinical aspects

“…Antibiotic therapy may lead to selection of pre-existing mutant resistent organisms. Combinations of antibiotics, or periodical changes in regimens may reduce the occurrence of such resistance [9,21,50,92].…”

Evaluation of azlocillin in-vitro and in discriminative animal models of infection

“…1982;Coppens & Klastersky, 1979;Eliopoulos & Moellering, 1982;Fass, 1982;Greenwood & Eley, 1982;Hoogkamp-Korstanje, Pot & Westerdaal, 1981;Slack, 1981;Tselentis et al. 1981;White, Comber & Sutherland, 1980;White et al.…”