In vitro synergistic activity between meropenem and other beta-lactams against methicillin-resistantStaphylococcus aureus

Abstract

The in vitro activity of meropenem, a carbapenem antibiotic, combined with eight other beta-lactams against methicillin-resistant Staphylococcus aureus (MRSA) was tested. The MICs of these antibiotics alone ranged from 12.5 to 1,600 micrograms/ml for the 25 clinical isolates of MRSA studied. All combinations with meropenem exhibited marked synergy as determined by the checkerboard method. The MICs in combinations of meropenem with other beta-lactams were reduced to 1/4-1/64 those of the antibiotics alone. No antagonism was observed for any of the combinations of meropenem with other beta-lactams. Synergism between meropenem and cefpiramide was the highest among the combinations tested, the geometric mean of the fractional inhibitory concentration index for this combination being 0.237. This combination also demonstrated strong bactericidal activity, the MBCs decreasing to 1/16-1/64 of those for the agents alone. In terms of the fractional inhibitory concentration index, this was the most effective combination against MRSA highly resistant to meropenem alone with synergism for 85% (81/95) of the strains. In addition, synergism of imipenem with cephalosporins against MRSA was demonstrated. The affinity of meropenem and cefpiramide for MRSA penicillin-binding protein (PBP) 2' was very low, and the combination of both antibiotics showed an additive increase in affinity for this protein, but not a synergistic increase. Thus, the mechanism of synergism did not seem to be related to affinity for PBP2'. It is possible that there is another factor besides PBP2' which increases the resistance that the combinations inhibit the unknown factor.

Nasal Carriage and Antibiotic Resistance Pattern of Methicillin-Resistant Staphylococcus aureus Isolates from Clinical Staff of a Referral Hospital, Zabol, Iran

“…[19][20][21] Moderate resistance to new carbapenem antibiotics like meropenem and ertapenem was observed among MRSA isolates in our study, which is supported by some studies reporting ineffective activity of these antibiotics alone against MRSA strains. 22,23 Therefore, administration of carbapenems in combination with other antibiotics is recommended to produce synergistic effects.…”

Antibacterial and Antifungal Activities of New Acylated Derivatives of Epigallocatechin Gallate

“…PBP2′ alone might not completely fulfill the functions of these other intrinsic S. aureus PBPs (Zapun et al, 2008). Actually, synergism between carbapenems and other β-lactams having different PBP affinities against MRSA has also been reported (Sumita and Mitsuhashi, 1991). Cell wall synthesis partially affected by β-lactam would provide an easy access for EGCG to the membrane of MRSA.…”

Potent In Vitro Activity of Tomopenem (CS-023) against Methicillin-Resistant Staphylococcus aureus and Pseudomonas aeruginosa

“…MRSA is characterized by the expression of a special penicillin-binding protein (PBP), PBP 2a. This PBP is not efficiently inhibited by commercially available carbapenems such as IPM and MEM (13,30). The recently reported carbapenems SM-216601 (36) and ME1036 (13), which exhibit activity against MRSA, have weak activities against P. aeruginosa, which has intrinsic and acquired antibiotic resistance.…”