In Vitro Evaluation of
            <i>N</i>
            -Formimidoyl Thienamycin (MK0787) Combined with Amikacin Against Gram-Negative Bacilli and
            <i>Staphylococcus aureus</i>

The combinations of imipenem plus ciprofloxacin and imipenem plus amikacin were investigated for their activity against Pseudomonas aeruginosa and other bacterial pathogens. For imipenem-susceptible P. aeruginosa, synergy of imipenem plus ciprofloxacin and imipenem plus amikacin was observed against 36 and 45% of the strains, respectively. The incidence of synergy against imipenem-resistant isolates of P. aeruginosa was 10% for both combinations. Antagonism was not observed with either combination.

contrasting

confidence: 54%

Synergism of the combinations of imipenem plus ciprofloxacin and imipenem plus amikacin against Pseudomonas aeruginosa and other bacterial pathogens

Bustamante¹,

Drusano²,

Wharton³

et al. 1987

“…However, in this series of studies, investigations of its interactions with other antimicrobial agents are relatively limited. Overall, synergism has been demonstrated in combinations of imipenem with aminoglycosides against enterococci (3, 8, 10, 24) and Listeria monocytogenes (8) and less frequently against staphylococci, enteric gram-negative bacteria, and nonfermentative bacteria (7,11,14,18,19). Conversely, imipenem has shown antagonistic interactions with other ,-lactam antimicrobial agents against Pseudomonas aeruginosa (1,4, 25) and Serratia marcescens (17) and with chloramphenicol against Klebsiella pneumoniae (6).…”

mentioning

confidence: 99%

In vitro activity of imipenem against enterococci and staphylococci and evidence for high rates of synergism with teicoplanin, fosfomycin, and rifampin

Debbia¹,

Varaldo²,

Schito³

1986

The in vitro activities of imipenem alone and in combination with teicoplanin, fosfomycin, and rifampin were tested against clinical isolates of enterococci and staphylococci. In both groups of organisms, the three combinations demonstrated high rates of synergism in both checkerboard ahd time-kill studies.Imipenem is the first clinically useful member of the carbapenems, a new class of antimicrobial agents that are unique among ,-lactams both for their chemical structure and because of their extraordinarily broad antibacterial spectrum. Since its development from thienamycin as the N-formimidoyl derivative, imipenem has been studied extensively in recent years, and the data available about its in vitro antibacterial activity have been reviewed repeatedly (5,12,13,16). However, in this series of studies, investigations of its interactions with other antimicrobial agents are relatively limited. Overall, synergism has been demonstrated in combinations of imipenem with aminoglycosides against enterococci (3, 8, 10, 24) and Listeria monocytogenes (8) and less frequently against staphylococci, enteric gram-negative bacteria, and nonfermentative bacteria (7,11,14,18,19). Conversely, imipenem has shown antagonistic interactions with other ,-lactam antimicrobial agents against Pseudomonas aeruginosa (1,4, 25) and Serratia marcescens (17) and with chloramphenicol against Klebsiella pneumoniae (6).In this study, enterococcal and staphylococcal strains freshly isolated from clinical material were tested for susceptibility to imipenem, teicoplanin, fosfomycin, and rifampin. Interactions between imipenem and each of the three other antimicrobial agents were then determined both by checkerboard titration and by time-kill curves.Enterococci were identified as Streptococcus faecalis (71 isolates) or Streptococcus faecium (10 isolates) on the basis of standard criteria. Staphylococci were identified on the basis of lytic activity patterns (23) and other conventional tests, and their susceptibility to methicillin was preliminarily determnined by agar diffusion on plates of Mueller-Hinton agar (Difco Laboratories, Detroit, Mich.) supplemented with 5% NaCl. Staphylococcal strains were subdivided into Staphylococcus aureus (38 isolates, of which 16 were methicillin resistant), Staphylococcus epidermidis (18 isolates, of which 7 were methicillin resistant), and Staphylococcus sp. (17 isolates, of which 6 were methicillin resistant, belonging to other coagulase-negative species).Antimicrobial agents were supplied as follows: imipenem, Merck Sharp & Dohme Italia, Rome, Italy; teicoplanin and rifampin, Gruppo Lepetit, Milan, Italy; and fosfomycin, Zambon, Milan, Italy.The MICs and MBCs of the four antimicrobial agents were determined for all isolates from broth dilutions in microtiter * Corresponding author. trays with Mueller-Hinton broth (Difco) as the test medium. Twofold dilutions of each drug, prepared so as to obtain final concentrations ranging from 0.004 to 64 ,ug/ml, were made with a hand-held multidilution device that delive...

“…Synergism at clinically attainable concentrations was defined, for the purpose of this study, as the inhibition of growth at concentrations of antibiotics in combination that were no more than one-fourth the initial MIC of each drug and .16 ,ug/ml for amikacin, .8 p.g/ml for netilmicin, . 4 Fig/ml for gentamicin and tobramycin, s8 pLg/ml for cefotaxime, ceftizoxime, imipenem, and Sch 29482, s16 ,ug/ml for cefsulodin and ceftazidime, s64 ,ug/ml for cefpiramide and ceftriaxone, and s32 ,ug/ml for all other ,B-lactams. These concentration breakpoints were based on a review of the pharmacokinetic data in published articles and from pharmaceutical companies and represent levels generally attainable at the midpoint of dosing intervals at intervals and doses that one might use to treat serious infections.…”

mentioning

confidence: 99%

“…All isolates were identified by standard microbiological methods. We evaluated 4 amino-glycoside-p3-lactam pairs were evaluated for synergism (1,680 assays were done). Synergism at clinically attainable concentrations was defined, for the purpose of this study, as the inhibition of growth at concentrations of antibiotics in combination that were no more than one-fourth the initial MIC of each drug and .16 ,ug/ml for amikacin, .8 p.g/ml for netilmicin, .…”

mentioning

confidence: 99%

Synergism at clinically attainable concentrations of aminoglycoside and beta-lactam antibiotics

Hooton¹,

Blair²,

Turck³

et al. 1984

We evaluated the in vitro synergistic activity at clinically attainable concentrations of combinations of aminoglycoside and ,-lactam antibiotics against 30 gentamicin-resistant clinical isolates of gram-negative bacilli. All 56 pairs of 4 aminoglycosides and 14 1-lactams were evaluated. Combinations with amikacin demonstrated inhibitory synergistic activity in 29% of the assays, as compared with 22% for netilmicin (P = 0.018), 17% for gentamicin (P < 0.001), and 13% for tobramycin (P < 0.001 Antimicrobial synergism is said to occur when two or more antibiotics in combination exert an inhibitory effect on microorganisms that is greater than the additive effects of the individual antibiotics. Several animal (2,3,16,18,24) and human (1, 17) studies have demonstrated that certain antibiotic combinations are more effective than single antibiotics in eradicating serious infections and preserving life. Moreover, those combinations resulting in a successful therapeutic outcome are more likely to demonstrate in vitro synergism against infecting strains than less successful combinations (1,9,10,14,19,25). Thus, it seems rational to use such in vitro data in selecting optimal combinations of antibiotics for the empirical therapy of serious bacterial infections. Most previous investigations of in vitro synergism have involved small numbers of different antibiotic combinations and bacterial species. In this study, we compared the in vitro synergistic activity of a large number of combinations of aminoglycoside and ,-lactam antibiotics against a group of 30 gram-negative bacilli. Because synergism obtained at concentrations higher than those achieved with usual dosage regimens probably has little practical value, we expressed our results in terms of synergism obtained at clinically attainable concentrations of antibiotics.(These studies were presented in part at the 13th International Congress of Chemotherapy, Vienna, Austria, 1983.) MATERIALS AND METHODS We selected for study 30 isolates of gentamicin-resistant (MIC, >8 pug/ml) gram-negative bacilli of several species from clinical specimens submitted to microbiology laboratories at the Seattle Veterans Administration Hospital and Harborview Medical Center in Seattle, Wash. Among the 30 isolates were (number of isolates in parentheses) species of Achromobacter (1), Acinetobacter (1), Citrobacter (2), Enterobacter (2), Escherichia (3), Klebsiella (5), Providencia (1), Pseudomonas (9), and Serratia (6). All isolates were identified by standard microbiological methods. We evaluated 4 aminoglycoside and 14 P-lactam antibiotics, including * Corresponding author. 8 cephalosporins and 6 non-cephalosporins. The antibiotics evaluated were amikacin, gentamicin, netilmicin, tob--ramycin, cefoperazone, ceforanide, cefotaxime, cefpiramide (SM-1652), cefsulodin, ceftazidime, ceftizoxime, ceftriaxone, imipenem, moxalactam, Sch 29482, apalcillin, mezlocillin, and piperacillin. Standard powders for these antibiotics were supplied by their manufacturers (see Acknowledgments).Antimicrobial su...