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Biomedical subjects

P Grecka

Publications and source records attributed to P Grecka.

8 recordsLinked to original sources

In-vitro activity and killing effect of quinupristin/dalfopristin (RP59500) on nosocomial Staphylococcus aureus and interactions with rifampicin and ciprofloxacin against methicillin-resistant isolates.

Quinupristin/dalfopristin (RP59500) is a novel streptogramin and a semisynthetic derivative of pristinamycins IA and IIB. The following properties of RP59500 were investigated: (i) its in-vitro activity against 164 hospital isolates of Staphylococcus aureus, 101 of which were methicillin-resistant (MRSA); (ii) its killing effect against 24 MRSA and seven methicillin-susceptible (MSSA) isolates; (iii) its interactions with rifampicin and ciprofloxacin against 18 MRSA isolates, six susceptible to both rifampicin and ciprofloxacin and 12 resistant to both, at 1 x MIC, 2 x MIC and 4 x MIC. Rifampicin and ciprofloxacin were applied at a concentration equal to their mean serum levels in order to establish the clinical relevance of the results. The MIC50, MIC90, MBC50 and MBC90 of quinupristin/dalfopristin were, respectively, < or = 0.015, 2, 0.12 and 2 mg/L for MRSA isolates and < or = 0.015, 0.06, < or = 0.015 and 0.25 mg/L for MSSA isolates. All isolates were inhibited by quinupristin/dalfopristin. Its killing effect varied with concentration and time, being optimal at 4 x MIC and after 24 h growth. Strains surviving 24 h exposure to this agent had much higher MICs than the parent strain, but only a limited number of them became resistant. Quinupristin/dalfopristin at 2 x MIC and 4 x MIC showed in-vitro synergy with rifampicin against highly resistant isolates mainly at 6 h and 24 h of growth involving 50-83% of MRSA isolates, and showed synergy with ciprofloxacin at 24 h involving 42-75% of isolates. The MIC increase in colonies surviving at 24 h was restricted by the presence of rifampicin or ciprofloxacin. In contrast, the above combinations acted synergically over the total number of MRSA strains susceptible to both rifampicin and ciprofloxacin. The above findings show that quinupristin/dalfopristin is a very potent antistaphylococcal agent, and that its activity against MRSA isolates is enhanced when it is combined with rifampicin or ciprofloxacin.

Anti-Bacterial Agents

Comparative in vitro interactions of ceftazidime, meropenem, and imipenem with amikacin on multiresistant Pseudomonas aeruginosa.

To evaluate the possibility of an enhanced killing effect by ceftazidime, meropenem, or imipenem with amikacin 26 multiresistant Pseudomonas aeruginosa isolates, to nine anti-pseudomonal antimicrobials of diverse chemical classes were studied. A modified time-kill curve procedure was used with a 16 micrograms/ml concentration of each antimicrobial, i.e. within the range of their serum level; a total of 248 killing-curves were performed. Any > or = 2 log10 decrease of viable cell counts by a combination compared to the most active single agent was considered an adequate enhanced killing effect. The latter was found to be mainly expressed at 24 h of growth and involved 30-50% of the tested isolates. The above findings were independent of the MIC level to any individual beta-lactam or to amikacin. It is concluded that there is no difference between the activity of the ceftazidime and amikacin combination and those of meropenem or imipenem with amikacin on multiresistant P. aeruginosa.

Amikacin

In-vitro interactions of DX-8739, a new carbapenem, meropenem and imipenem with amikacin against multiresistant Pseudomonas aeruginosa.

In order to investigate the antimicrobial interactions against multiresistant Pseudomonas aeruginosa, thirty-seven strains resistant to antimicrobial agents of five different chemical classes were exposed in vitro to the combination of three carbapenems. DX-8739, a novel DHP-I stable analogue, meropenem and imipenem with amikacin. The tested combinations expressed an enhanced killing activity against 38-46% of strains and an additive effect against 5-13%. These effects were the same whether the applied carbapenem was DX-8739, meropenem or imipenem; they were also independent of the MIC of any antimicrobial.

Amikacin

In-vitro inhibitory activity of gamma-linolenic acid on Escherichia coli strains and its influence on their susceptibilities to various antimicrobial agents.

Recent experimental evidence implies that polyunsaturated fatty acids (PUFAs) possess anti-infective activity which is unrelated to any alteration of eicosanoid biosynthesis or cytokine production provoked by PUFAs and it seems necessary to establish their possible influence on Gram-negative bacteria. Forty-two Escherichia coli strains were cultured in vitro in the presence of gamma-linolenic acid (GLA) at concentrations of 50 mg/L and 300 mg/L and a total of 77 killing curves were performed with GLA concentrations of 100, 200 and 300 mg/L GLA. At 50 and 300 mg/L, GLA inhibited 9.5% and 33.3% of strains respectively; GLA killing curves demonstrated a > or = 1 log GLA inhibitory effect in 0%, 18.2% and 72.7% of strains after the 5 h sequential exposures at 100, 200 and 300 mg/L GLA but this was not observed after the 24 h GLA exposure. Following removal of the E. coli strains from the culture medium with GLA, > or = four-fold increases in MICs and/or MBCs of various antimicrobials, were observed in 42.9% and 60% of strains after exposure to 50 and 300 mg/L GLA respectively; most of these increases involved aminoglycosides. The reproducibility of GLA inhibitory effects and increase in MICs and/or MBCs for E. coli in the two different experimental procedures used, was 82% and 73% respectively. Further studies are necessary to clarify the mechanism of GLA action on E. coli and assess the clinical relevance of these findings.

Anti-Bacterial Agents

In vitro activity and killing effect of DX-8739, a new carbapenem, compared with those of meropenem and imipenem against multiresistant Pseudomonas aeruginosa.

DX-8739 is a new dehydropeptidase I-stable carbapenem. In order to evaluate its activity in comparison with those of meropenem and imipenem, 147 multiresistant Pseudomonas aeruginosa isolates acquired nosocomially were simultaneously exposed to the actions of the three carbapenems in vitro, whereas to compare their killing effects on 14 strains, 56 killing curve studies were performed. Overall DX-8739 was found to possess inhibitory activity as well as bactericidal activity statistically superior to those of meropenem and imipenem. At a concentration of 4 micrograms/ml, 106 strains (72.1%) were found to be imipenem resistant; 33 and 27.4% of these strains were inhibited by DX-8739 and meropenem, respectively, a statistically significant difference (P < 0.05). DX-8739 was also shown to possess intrinsic activity in vitro superior to those of meropenem and imipenem against the imipenem-susceptible population of strains. However, no statistically significant difference regarding the comparative killing activities of the three studied carbapenems was observed. Following exposure to carbapenem for 24 h, 33.3, 44.4, and 70% of the strains which survived became resistant to DX-8739, meropenem, and imipenem, respectively. The reported results demonstrate the significant activity of DX-8739 against multiresistant P. aeruginosa strains acquired nosocomially. The mechanism of action of DX-8739 on P. aeruginosa is unknown, and various hypotheses that might explain its in vitro superiority over meropenem and imipenem are proposed.

Anti-Bacterial Agents

Comparative in vitro killing activity of meropenem versus imipenem against multiresistant nosocomial Pseudomonas aeruginosa.

In order to compare the in vitro killing activity of meropenem and imipenem against multiresistant P.aeruginosa 14 strains were used. All nosocomial isolates were susceptible to meropenem and imipenem minimum inhibitory concentration (MIC < or = 4 micrograms/ml) and resistant to at least two other antimicrobial agents of diverse chemical class with antipseudomonal activity. Forty-two killing curves were performed by exposing a 5 x 10(5) CFU/ml log-phase inoculum to 1x minimum bactericidal concentration (MBC) of each carbapenem. Meropenem was found to possess a slower killing rate than imipenem over the first 5 hours of P.aeruginosa exposure, but to be equally effective as imipenem after 24 hours of incubation. Forty percent and 11.1% of P.aeruginosa strains developed resistance to imipenem and meropenem respectively after a 24-hour exposure to carbapenem. The authors speculate about the underlying mechanisms explaining the higher rate of resistance development to imipenem than to meropenem.

Cross Infection

Do Escherichia coli susceptibilities to various antibiotics decrease in the presence of polyunsaturated fatty acids? A preliminary report.

Polyunsaturated fatty acids (PUFAs) constitute an ingredient of the daily diet and therefore they might be in close contact with the polymicrobial gastrointestinal flora. In order to study the interaction of bacteria and PUFAs, eight Escherichia coli strains were cultured in the presence of docosahexaenoic acid (DHA) at a concentration of 100 micrograms/ml, and six of the latter eight at 75 micrograms/ml whereas nine other E. coli strains were cultured in the presence of 50 micrograms/ml gamma-linolenic acid (GLA). DHA provoked > or = 4-fold increases in the minimum inhibitory and bactericidal concentrations of various antibiotics in six strains at 100 micrograms/ml and in three strains at 75 micrograms/ml, which were not antibiotic-specific and involved mainly aminoglycosides. GLA provoked in four strains > or = 4-fold increases in MICs-MBCs of ampicillin. The clinical relevance of these observations require further study.

Anti-Bacterial Agents