Studies on antibiotic synergism against enterococci

Plasmid-mediated resistance to antibiotic synergism in enterococci.

“…Donor and recipient cultures were grown to log phase and mixed for mating in the presence of DNase I (10 ,Lg/ml) and MgSO4 (5 mM) (12). These mating mixtures and controls were incubated for only 4 [1.2 ,umol of DNA nucleotide/ml) and water (120 1ul), followed by 10% TCA (0.5 ml) and held at 0°C for 10 min (Carrier DNA was diluted to 1.2 mM with the molar extinction coefficient, 6.9 mM at 260 j,m). After the addition of 3.0 ml of chilled 1.0 N HCI, the mixture was pipetted onto prewetted (1.0 N HCI) glass fiber filter paper disks (Whatman GF/C, Whatman, Inc., Clifton, N. J., W and R Balston, Ltd., England), flushed twice with 3.0 ml of chilled HCI and washed with 80 ml of HCI, before the addition of absolute ethanol (5.0 ml).…”

“…However, since the reports of Hunter in 1947 (2), and Jawetz et al in 1950 (3), it has been known that combinations of penicillin and an aminoglycoside synergize to produce enhanced killing of' enterococci both in vitro (4) and in vivo (5), and are significantly more effective than penicillin alone. Previous studies from this laboratory have suggested that synergism results from enhanced uptake of aminoglycosides into enterococci in the presence of' penicillin or other agents which inhibit bacterial cell wall synthesis (6).…”

Antibiotic-induced lysis of enterococci.

“…The idea that inhibition of cell wall synthesis and killing induced by penicillin may have different mechanisms is supported by the occurrence of enterococci and other bacteria that are much more resistant to the lethal effect of penicillin than they are to its growth inhibitory effect. The resistance of enterococci to penicillin killing in vitro has been demonstrated by time-kill studies (3)(4)(5) and by the high ratio of the minimal bactericidal concentration (MBC)1 to the minimal inhibitory concentration (MIC) of penicillin for these strains (4,(6)(7)(8)(9)(10)(11). The clinical relevance of these in vitro results is supported by the observation that enterococcal endocarditis is resistant to treatment with penicillin alone (12,13), in contrast to endocarditis caused by most other streptococci (14).…”

KEMOTERAPöTİK İLAÇLAR ARASINDA ETKİLEŞME TİPLERİ VE KOMBİNASYON SEÇENEKLERİ

“…Penisilinler, sikloserin, basitrasin ve vankomisin'in enterokok,. larda C 1 ı ilc işaretlenmiş strcptomisin'in hücreye alınma oranlJ1l art ırdıkları saptanmıştır (32). Belirtilen sinerjizmanın sadeı:~bölünme: döne~inde olan' bakteri populasyonlarındagerçekleştiği göz önünde bulundurulursa:,penisilinler ve benzeri şekilde etkiyen antibiyotiklerin duyarlı bakterilerde hücre duvarı sentezini bozmak suretiyle aminoglikozid yapılı antibiyotiklerin hücreye geçişini artırdıkları ve dolayı-siyle bakterisid etkinin gerçekleşmesini sağladıkları kolayca anlaşılır (6,34,42).…”

“…Ancak diğer iki antibiyotikten biri linkomisin ile birlikte verilirse, protein sentezi için bağlanmaları gereken ribozomal kesimler önceden linkomisin moleküllerince tutulduğundan, ikinci ilaç bakteriyostatik etkisini gösteremez (29,38 4, 15, 25). En terokoklara bağlı enfeksiyonlarda ampilisin ve streptomisin kombinasyonunun da sinerjistik etkileşme yaptığı beilrlenmiştir (15,32,34). Bu iki antibiyotik, d~ğer bazı enfeksiyonlarda da antibakteriyel spektrumu genişletmek amacıyla da bir araya getirilirler.…”