[Antibacterial activities and electron microscopic studies of imipenem in combination with fosfomycin against methicillin and fosfomycin resistant strains of Staphylococcus aureus].
Imipenem (IPM) and fosfomycin (FOM) have been reported to possess a synergistic relationship in their activities against both methicillin (DMPPC)-susceptible and -resistant strains of Staphylococcus aureus. However it was not concluded whether these antibacterial activities were bacteriostatic or bactericidal. The purpose of this report is to elucidate this point clearly. Activities of the 2 antibiotics against 15 strains S. aureus resistant to both DMPPC and FOM were investigated by means of the killing-curve method and electron microscopic studies. MICs of DMPPC and FOM against these strains determined using the agar dilution method were greater than or equal to 50 micrograms/ml and MICs of IPM by the broth dilution method ranged from 12.5 to 50 micrograms/ml. The killing-curves with the following drug concentration combinations were examined in Mueller-Hinton broth: 1. FOM 25 micrograms/ml, 2. FOM 25 micrograms/ml + IMP 1/2 MIC, 3. IPM 1MIC, 4. FOM 25 micrograms/ml + IPM 1 MIC and 5. FOM 25 micrograms/ml + IPM 2MIC. Morphological changes produced in 1 strain by 2 of the combinations, 2. FOM 25 micrograms/ml + IPM 1/2 MIC and 4. FOM 25 micrograms/ml + IPM 1MIC, were observed using scanning and transmission electron microscopy. The following results were obtained; (1) The synergistic effects were found in 6/15 strains (40%) and no antagonistic effect was found. (2) Electron microscopic observation showed that IPM in combination with FOM caused lysis of the cells.


CONCLUSIONS
IPM in combination with FOM produced bactericidal and bacteriolytic effects on DMPPC-resistant S. aureus (MRSA). This combination therapy should be evaluated for FOM resistant MRSA infections.
Saionji
K
K
Department of Clinical Laboratory, Kosei General Hospital.
Shitara
S
S
Kobayashi
I
I
D001433:Bacteriolysis; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D005578:Fosfomycin / Q000494:pharmacology*; D015378:Imipenem / Q000494:pharmacology*; D008712:Methicillin / Q000494:pharmacology; D008826:Microbial Sensitivity Tests / Q000379:methods; D010403:Penicillin Resistance; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000648:ultrastructure
D005578:Fosfomycin; D015378:Imipenem; D008712:Methicillin