In vitro activity of aztreonam in combination with newer beta-lactams and amikacin against multiply resistant gram-negative bacilli

Abstract

The in vitro synergistic activity of aztreonam in combination with piperacillin, moxalactam, cefotaxime, cefoperazone, and amikacin was examined against multiply resistant isolates of the family Enterobacteriaceae accommodating a volume of 1 ml of Mueller-Hinton broth (Difco Laboratories) were utilized. Each test isolate was grown overnight on sheep blood agar; then an inoculum of 5 x 105 CFU/ml was prepared by suspending growth to a predetermined optical density. Viable cell counts were performed with each test to verify the actual inoculum density which'was later utilized for MBC determinations. The cuvettes were immediately placed in an MS-2 analysis module and incubated at 35.5°C for 16 h with constant agitation. Optical density-versus-time plots were programmatically derived by the MS-2 system for each bacterial strain and antibiotic. The MIC was defined as the lowest concentration of drug which yielded consistent growth inhibition during the test period as evidenced by review of the kinetic plots. MBCs were determined at the conclusion of the incubation period by removing two 0.1-ml samples from each cuvette well demonstrating growth inhibition and spreading the samples over the entire surface of duplicate Trypticase soy agar (BBL Microbiology Systems) plates. Resultant colonies were counted after 18 to 20 h of incubation at 35°C. The MBC was defined as the lowest concentration of antibiotic resulting in a 23-log decrease in the number of viable organisms (99.9% kill) based on the previously determined inoculum density for each test.To determine possible synergistic effects, the separate MICs for each drug tested separately were combined in MS-2 research cuvettes as follows:

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

“…The cumulative data, which are reviewed in great detail in subsequent sections of this article, suggest that beta-lactam combinations produce an enhanced killing effect versus Gram-negative pathogens, rivaling that of combination therapy with an aminoglycoside and beta-lactam (Bosso et al, 1991;Buesing and Jorgensen, 1984;Kurtz et al, 1981;Moody et al, 1984;Zinner et al, 1981). Yet, to date, there has been little investigation into the exact mechanism of enhanced killing/synergy with dual beta-lactam combinations.…”

“…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;…”

In vitro Synergy Studies Using Aztreonam and Fluoroquinolone Combinations against Six Species of Gram-Negative Bacilli

“…A number of studies have reported positive outcomes for aztreonam and amikacin combinations and have successfully demonstrated synergy or partial synergy against gram-negative pathogens [6][7][8][9]. There are also published reports describing synergy against gram-negative isolates when aztreonam was tested in combination with either ciprofloxacin or levofloxacin [10][11][12][13].…”

Aztreonam concentration in abdominal tissues and bile

“…AGENTS CHEMOTHER. Common duct 3.16 (2) bile Gallbladder bile 1.17 ± 0.32 (7) 3.26 ± 1.08 (6) The data document that therapeutic levels of aztreonam were present in several body tissues and fluids several hours after a single 2-g dose. The levels in most tissues and fluids were found to exceed the MICs for 90% of most susceptible aerobic and facultative gram-negative isolates at 6 h after drug administration.…”