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1.
Imipenem (IPM) and beta-lactams have been reported to possess a synergistic relationship in their activities against methicillin (DMPPC)-resistant strains of Staphylococcus aureus (MRSA). The purpose of this study was to determine activities of IPM and ampicillin (ABPC) singly and in combination against MRSA. Activities of the 2 antibiotics against 19 strains of S. aureus resistant to DMPPC were investigated by means of the checkerboard method, the disk diffusion technique and the killing-curve method. MICs of DMPPC against these strains determined using the agar dilution method were greater than or equal to 100 micrograms/ml and MICs of IPM and ABPC ranged from 12.5 to 100 micrograms/ml and from 12.5 to 50 micrograms/ml, respectively, when used singly. The following results were obtained with the checkerboard method: Synergistic effects and additive effects were found against 13/19 and against 6/19 strains, respectively, and no antagonistic effect was found according to the FIC (fractionary inhibitory concentration) index. The disk diffusion technique indicated synergistic results. Killing-curves with the following drug concentration combinations were examined in Mueller-Hinton broth against 5 fosfomycin(FOM)-resistant and 5 FOM-susceptible stains: (1) IPM 12.5 micrograms/ml, (2) ABPC 25 micrograms/ml, (3) IPM 12.5 micrograms/ml + ABPC 25 micrograms/ml, (4) IPM 6.25 micrograms/ml + ABPC 25 micrograms/ml, (5) IPM 6.25 micrograms/ml + ABPC 12.5 micrograms/ml, (6) IPM 6.25 micrograms/ml + ABPC 12.5 micrograms/ml + FOM (fosfomycin) 25 micrograms/ml, (7) IPM 12.5 micrograms/ml + ABPC 25 micrograms/ml + FOM 50 micrograms/ml, (8) FOM 50 micrograms/ml. The following results were obtained with the killing-curve method; (1) Synergistic effects were found against 8/10 strains and no antagonistic effect was found with the combinations of IPM and ABPC. (2) Synergistic effects were found against 3/5 strains and no antagonistic effect was found with the combinations of IPM, ABPC and FOM against 5 FOM-susceptible strains. Conclusions: IPM in combination with ABPC produced synergistic effects against MRSA. This combination therapy should be evaluated in treating MRSA infections.  相似文献   

2.
《Pharmaceutical biology》2013,51(11):1285-1290
Methicillin-resistant Staphylococcus aureus (MRSA) is a substantial contributor to morbidity and mortality. In search of a natural products capable of inhibiting this multidrug resistant bacteria, we have investigated the antimicrobial activity of emodin (EM) isolated from Rheum palmatum L. (Polygonaceae) against 17 different strains of the bacterium. New antimicrobial activity was found using the paper disc diffusion method, agar dilution as well as checkerboard method. Against the 17 strains, the disc diffusion test was in the range of 18–30?mm, and the minimum inhibitory concentrations (MICs) of EM were in the range of 1.5–25 μg/mL. From those results we performed the checkerboard test to determine the synergism of EM in combination with ampicillin (AM) or oxacillin (OX) against all strains. The combined activity of EM and two antimicrobial agents (AM, OX) against all strains resulted in a fractional inhibitory concentrations index (FICI) ranging from 0.37–0.5 and from 0.37–0.75, respectively. The effect of EM with AM and OX was found to be synergistic or partially synergistic. We found that EM reduced the MICs of AM and OX. EM and in combination with AM or OX could lead to the development of new combination antibiotics against MRSA infection.  相似文献   

3.
Methicillin-resistant Staphylococcus aureus (MRSA) is a substantial contributor to morbidity and mortality. In search of a natural products capable of inhibiting this multidrug resistant bacteria, we have investigated the antimicrobial activity of emodin (EM) isolated from Rheum palmatum L. (Polygonaceae) against 17 different strains of the bacterium. New antimicrobial activity was found using the paper disc diffusion method, agar dilution as well as checkerboard method. Against the 17 strains, the disc diffusion test was in the range of 18-30?mm, and the minimum inhibitory concentrations (MICs) of EM were in the range of 1.5-25 μg/mL. From those results we performed the checkerboard test to determine the synergism of EM in combination with ampicillin (AM) or oxacillin (OX) against all strains. The combined activity of EM and two antimicrobial agents (AM, OX) against all strains resulted in a fractional inhibitory concentrations index (FICI) ranging from 0.37-0.5 and from 0.37-0.75, respectively. The effect of EM with AM and OX was found to be synergistic or partially synergistic. We found that EM reduced the MICs of AM and OX. EM and in combination with AM or OX could lead to the development of new combination antibiotics against MRSA infection.  相似文献   

4.
Meticillin-resistant Staphylococcus aureus (MRSA) is a very significant agent of recalcitrant healthcare-associated infections. A major risk of acquiring such infections is thought to be modulated by the use of particular antimicrobial therapies. The aim of this research was to evaluate prospectively the impact of using either ciprofloxacin or Tazocin (piperacillin+tazobactam) on the incidence of MRSA in an Intensive Care Unit (ICU). The 1-year (2 x 6 months) cross-over study was carried out in a medium-sized (426 beds) teaching hospital. During the first 6-month period, ciprofloxacin was used as the first-line broad-spectrum antibiotic therapy of choice. During the second 6-month period, Tazocin was used as first-line therapy. The incidence of hospital-acquired MRSA (i.e. colonised and/or infected) and rates of compliance of the ICU healthcare workers to optimal hand hygiene practices were recorded throughout the study. The study observed no statistically significant differences (P = 0.1) between MRSA incidence rates in the ICU during the ciprofloxacin (4.4/1000 bed-days) or Tazocin (11.4/1000 bed-days) arms of the study. Interestingly, observing healthcare workers' hand hygiene practices throughout the entire study showed that healthcare workers adhered to these practices 59.2% of the time during the ciprofloxacin arm and 66.0% during the Tazocin arm. The low incidence rates within the unit demonstrated the importance of infection control in limiting the spread of MRSA despite the extensive use of antibiotics in a high-risk setting.  相似文献   

5.
A case of infective endocarditis caused by methicillin-resistant Staphylococcus aureus (MRSA) was successfully treated with a combination therapy with cefmetazole (CMZ) and fosfomycin (FOM). A 55 year old man was admitted to the Keio Hospital because of fever of unknown origin. Physical examination revealed blood pressure of 132/62 mmHg, heart rate of 118/min and body temperature of 39.8 degrees C. Diastolic regurgitant murmur (Levine II/VI) was heard at the left sternal border on the third intercostal space. Chest X-ray showed mild cardiomegaly. Two dimensional echocardiography and color flow mapping demonstrated mildly dilated and hyperkinetic left ventricle, redundant aortic valve, giant vegetation from the aortic valve and severe aortic regurgitation. MRSA was isolated from the blood of this patient. Bacteriostatic synergism between CMZ and FOM against S. aureus isolated from the blood of this patient was detected both by the Kirby-Bauer method and by the checker-board method. The combination therapy with CMZ and FOM cleared the clinical symptoms and normalized the inflammatory reactions. No relapse was observed for at least 10 months. We concluded that the combination therapy with CMZ and FOM was invaluable for the treatment of infections endocarditis by MRSA.  相似文献   

6.
The in vitro combination effects of pazufloxacin (PZFX) with various antibiotics were investigated by the checkerboard dilution method using piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ), cefozoprane (CZOP), imipenem/cilastatin (IPM/CS), meropenem (MEPM), panipenem/betamipron (PAPM/BP), amikacin (AMK) and isepamicin (ISP) for clinical isolates of 27 Pseudomonas aeruginosa strains, vancomycin (VCM), teicoplanin (TEIC) and arbekacin (ABK) for clinical isolates of methicillin-resistant 26 Staphylococcus aureus (MRSA) strains, respectively. The following results were obtained. 1. For 27 P. aeruginosa strains, the synergistic effects were observed with the combination of PZFX and CAZ or MEPM (11.1%: 3 strains), and PZFX and CZOP or PAPM/BP (3.7%: 1 strain), respectively. The additive and synergistic effects of PZFX were observed with the combination in all beta-lactams tested in the strains more than 50%. No antagonistic effect was observed. The additive effects were also observed with the combination of PZFX and AMK or ISP in the strains more than 50% of the test strains and no antagonistic effect was observed. 2. For 26 MRSA strains, no antagonistic effect was observed with the combination of all antibiotics tested. The indifference was observed with the combination of PZFX and VCM or ABK in the strains more than 60%, and the additive effects were observed with the combination of TEIC in the strains more than 80%. In conclusion, no antagonistic effect was observed in PZFX with the combination of beta-lactams and anti-MRSA agents, suggesting that the combination therapy of PZFX with these antibiotics would be possible to use for the infections caused by P. aeruginosa and MRSA.  相似文献   

7.
Korean red ginseng saponins (ginsenosides) have been reported as having various biological properties, but the combinational effects with commercial antibiotics and the mode of action of ginsenosides remain mostly unknown. In this study, saponins were isolated from Korean red ginseng, and the antibacterial effects of ginsenosides were investigated. Ginsenosides showed antibacterial activities toward pathogenic Gram-positive and Gram-negative bacteria. To elucidate the antibacterial mode of action of ginsenosides, we measured the release of the fluorescent marker calcein from negatively charged PC/PG (1 : 1, w/w) liposomes, which mimic bacterial membranes. The results suggest that ginsenosides may exert antibacterial activity by disrupting the cell membrane. To estimate the general combination effects of ginsenosides and commercial antibiotics, such as kanamycin and cefotaxime, on antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains that were clinically isolated from an infected patient, the fraction inhibitory concentration (FIC) indexes were determined by a checkerboard study. The FIC indexes showed synergistic or additive effects between the ginsenosides and antibiotics tested.  相似文献   

8.
Natural antimicrobial peptides (AMPs) are promising candidates for developing a generation of new antimicrobials to meet the challenge of antibiotic-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA). To facilitate the search for new candidates, we have utilised the Antimicrobial Peptide Database (APD), which contains natural AMPs from bacteria, fungi, plants and animals. This study demonstrates the identification of novel templates against MRSA by screening 30 peptides selected from the APD. These peptides are short (<25 residues), cysteine-free, cationic and represent candidates from different biological sources such as bacteria, insects, arachnids, tunicates, amphibians, fish and mammals. Six peptides, including ascaphin-8, database-screened antimicrobial peptide 1 (DASamP1), DASamP2, lycotoxin I, maculatin 1.3 and piscidin 1, were found to exert potent antimicrobial activity against an MRSA USA300 isolate. Although five of the six peptides showed broad-spectrum antibacterial activity, DASamP1 displayed killing of MRSA in vitro but not of Escherichia coli, Bacillus subtilis or Pseudomonas aeruginosa. In addition, DASamP1 suppressed early biofilm formation in a mouse model of catheter-associated MRSA infection. DASamP1 is a novel, short and potent peptide that will be a useful starting template for further developing novel anti-MRSA peptides.  相似文献   

9.
Indifference or even antagonism has mainly been reported with combinations including linezolid. The presence of in vitro antagonism is not always correlated with in vivo failure. The purpose of this study was to evaluate the in vivo activity of linezolid combined with gentamicin using a methicillin-resistant Staphylococcus aureus (MRSA) endocarditis experimental model. A human-like pharmacokinetic simulation was used for linezolid and gentamicin to improve the extrapolation of the results to human therapy. Contrary to the antagonism previously described in vitro, linezolid combined with gentamicin exhibited bactericidal activity on the two strains with a decrease of at least 4 log(10)cfu/g of vegetation compared with controls. These data suggest that linezolid plus gentamicin could be an appropriate combination for the treatment of severe MRSA infections.  相似文献   

10.
The activity of six fluoroquinolones (FQs) was determined against 100 methicillin-resistant Staphylococcus aureus (MRSA) isolated in 2002 along with mutations in the grlA and gyrA genes and in the norA promoter of these isolates. Of the isolates tested, 97% had mutations in grlA and gyrA. A single mutation in grlA and gyrA resulted in a decrease of susceptibility to old generation FQs (norfloxacin, enoxacin, ciprofloxacin, fleroxacin, sparfloxacin and levofloxacin) but not to new generation FQs (gatifloxacin and moxifloxacin). Double mutations of both grlA and gyrA resulted in high-level resistance to all FQs tested. All norA mutants (15%) contained double mutations in grlA and gyrA and showed no decrease of MIC in the presence of reserpine, which is known to inhibit the drug-efflux pump. Our results showed that double mutations in grlA and gyrA were necessary for the expression of high-level resistance to new generation FQs. As different FQ-resistant mutants occur in the same PFGE type, FQ-resistant MRSA may well develop individually.  相似文献   

11.
OBJECTIVES: To quantify the direct medical costs associated with using vancomycin, as inpatient treatment, in methicillin-resistant Staphylococcus aureus infections, in four clinical indications: complicated skin and soft tissue infections (SSTI), bacteremia, infective endocarditis (IE), and hospital-acquired pneumonia (HAP). Research design and methods: A decision-analytic model was constructed to evaluate the cost of administering intravenous vancomycin. Cost inputs included hospitalization, drug procurement, materials, preparation and administration, renal function and drug monitoring, treating adverse events, and treatment failure. Probabilities and lengths of stay and treatment were obtained from the literature, an antimicrobial therapy database and clinical expert opinion. Univariate and multivariate sensitivity analyses were conducted to confirm the robustness of the baseline scenario. MAIN OUTCOME MEASURES: The cost of using vancomycin in the four indications, including and excluding hospital cost. RESULTS: Whereas the drug acquisition price of vancomycin 1g is US dollars 9.01 per dose, when all costs associated with using vancomycin were included, the cost per dose rose to US dollars 29-US dollars 43 per patient. Total costs per patient receiving multiple doses in a single course of treatment, excluding hospital room costs, were for SSTI, bacteremia, IE, and HAP,US dollars 779, US dollars 749, US dollars 2261, and US dollars 768, respectively. Total costs, including hospital length of stay, were for SSTI US dollars 23616, bacteremia US dollars 26446, IE US dollars 48925, and HAP US dollars 22493. In univariate analyses varying per diem hospital costs and length of stay had the greatest impact. Results of the multivariate analysis were comparable to the costs in the baseline scenario for all indications. CONCLUSIONS: This analysis highlights the importance of capturing all costs associated with using a drug and not simply focusing on drug acquisition cost. Future economic analyses should identify and account for the key cost burdens of a particular treatment to calculate its true cost.  相似文献   

12.
SUMMARY

Objectives: To quantify the direct medical costs associated with using vancomycin, as inpatient treatment, in methicillin-resistant Staphylococcus aureus infections, in four clinical indications: complicated skin and soft tissue infections (SSTI), bacteremia, infective endocarditis (IE), and hospital-acquired pneumonia (HAP).

Research design and methods: A decision-analytic model was constructed to evaluate the cost of administering intravenous vancomycin. Cost inputs included hospitalization, drug procurement, materials, preparation and administration, renal function and drug monitoring, treating adverse events, and treatment failure. Probabilities and lengths of stay and treatment were obtained from the literature, an antimicrobial therapy database and clinical expert opinion. Univariate and multivariate sensitivity analyses were conducted to confirm the robustness of the baseline scenario.

Main outcome measures: The cost of using vancomycin in the four indications, including and excluding hospital cost.

Results: Whereas the drug acquisition price of vancomycin 1?g is $9.01 per dose, when all costs associated with using vancomycin were included, the cost per dose rose to $29–$43 per patient. Total costs per patient receiving multiple doses in a single course of treatment, excluding hospital room costs, were for SSTI, bacteremia, IE, and HAP, $779, $749, $2261, and $768, respectively. Total costs, including hospital length of stay, were for SSTI $23?616, bacteremia $26?446, IE $48?925, and HAP $22?493. In univariate analyses varying per diem hospital costs and length of stay had the greatest impact. Results of the multivariate analysis were comparable to the costs in the baseline scenario for all indications.

Conclusions: This analysis highlights the importance of capturing all costs associated with using a drug and not simply focusing on drug acquisition cost. Future economic analyses should identify and account for the key cost burdens of a particular treatment to calculate its true cost.  相似文献   

13.
14.
BACKGROUND: Vancomycin is commonly used to treat staphylococcal infections, but there has not been a definitive analysis of the pharmacokinetics of this antibacterial in relation to minimum inhibitory concentration (MIC) that could be used to determine a target pharmacodynamic index for treatment optimisation. OBJECTIVE: To clarify relationships between vancomycin dosage, serum concentration, MIC and antimicrobial activity by using data gathered from a therapeutic monitoring environment that observes failures in some cases. METHODS: We investigated all patients with a Staphylococcus aureus lower respiratory tract infection at a 300-bed teaching hospital in the US during a 1-year period. Clinical and pharmacokinetic information was used to determine the following: (i) whether steady-state 24-hour area under the concentration-time curve (AUC24) divided by the MIC (AUC24/MIC) values for vancomycin could be precisely calculated with a software program; (ii) whether the percentage of time vancomycin serum concentrations were above the MIC (%Time>MIC) was an important determinant of vancomycin response; (iii) whether the time to bacterial eradication differed as the AUC24/MIC value increased; (iv) whether the time to bacterial eradication for vancomycin differed compared with other antibacterials at the same AUC24/MIC value; and (v) whether a relationship existed between time to bacterial eradication and time to significant clinical improvement of pneumonia symptoms. RESULTS: The median age of the 108 patients studied was 74 (range 32-93) years. Measured vancomycin AUC24/MIC values were precisely predicted with the A.U.I.C. calculator in a subset of our patients (r2 = 0.935). Clinical and bacteriological response to vancomycin therapy was superior in patients with higher (> or = 400) AUC24/MIC values (p = 0.0046), but no relationship was identified between vancomycin %Time>MIC and infection response. Bacterial eradication of S. aureus (both methicillin-susceptible and methicillin-resistant) occurred more rapidly (p = 0.0402) with vancomycin when a threshold AUC24/MIC value was reached. S. aureus killing rates were slower with vancomycin than with other antistaphylococcal antibacterials (p = 0.002). There was a significant relationship (p < 0.0001) between time to bacterial eradication and the time to substantial improvement in pneumonia score. CONCLUSIONS: Vancomycin AUC24/MIC values predict time-related clinical and bacteriological outcomes for patients with lower respiratory tract infections caused by methicillin-resistant S. aureus.  相似文献   

15.
Since methicillin-resistant Staphylococcus aureus (MRSA) is resistant to multiple antibiotics, only a limited number of antibacterial agents shows efficacy against this bacteria. Therefore, combination therapy is often attempted for MRSA infections. Most of the MRSA strains recently isolated, however, have been found to show very high resistance, and some of the antibiotics which had previously been effective have been failing to produce good responses in increasing numbers of patients. Thus, the drugs used for combination therapy in MRSA infections need to be reevaluated. We assessed the bacteriological efficacy of cefotiam (CTM) plus minocycline (MINO) therapy against MRSA in an in vitro system (CTM shows relatively strong antibacterial activities against MRSA with moderate resistance, and MINO shows strong antibacterial activities against highly resistant MRSA. 1. Against MINO-susceptible MRSA strains, CTM + MINO demonstrated potent antibacterial activities at MINO concentrations of MIC or sub-MIC levels, irrespective of the MIC of CTM against MRSA strains being tested. 2. Against MINO-resistant MRSA strains (strains for which MICs of MINO exceeded the upper limit of the clinically expected plasma MINO level), CTM + MINO showed no significant antibacterial activity. These results suggested that the effect of this combination was dependent on the antibacterial activity of MINO. Therefore, the usefulness of this combination in patients with MRSA infections can be predicted based on susceptibilities of involved strains to MINO. 3. The potent antibacterial effect of this combination against MINO-susceptible MRSA strains was considered to be the result of damage to the cellular membrane by MINO and the subsequent antibiotic effect of CTM.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

16.
We performed an in vitro assessment of the antibacterial activity of therapy with cefuzonam (CZON) plus minocycline (MINO) against methicillin-resistant Staphylococcus aures (MRSA) infections. 1. Studies using MINO-susceptible and MINO-resistant MRSA strains suggested that the antibacterial activity of CZON + MINO was dependent on the antibiotic action of MINO, similarly to the case with cefotiam (CTM) + MINO. 2. The antibacterial activity (including the FIC index) of this combination was slightly inferior to that of CTM + MINO. However, the time course of antibacterial efficacy of CZON + MINO in MRSA pretreated with MINO was comparable to that of CTM + MINO. 3. CZON + MINO appeared to be a very useful combination in patients with mixed infections due to MRSA and Gram-negative bacteria.  相似文献   

17.
Evidence is accumulating that active surveillance, when combined with appropriate infection control, is a successful measure for controlling hospital-acquired meticillin-resistant Staphylococcus aureus (MRSA). In this study, the impacts of a long-term control strategy of this type, including the use of chlorhexidine baths, on the clinical and molecular epidemiology of MRSA in the Intensive Care Unit of Aberdeen Royal Infirmary were investigated. Characterisation of 85 sequential index MRSA isolates was performed using phenotypic methods (biotyping), antibiotic susceptibility testing and three genotypic methods (pulsed-field gel electrophoresis, spa typing and multilocus sequence typing) over a 4-year period. There was no evidence of loss in effectiveness of the control strategy over the study period. Compliance with screening remained high (>85%) throughout and there was no significant increase in the prevalence of MRSA detected in surveillance (P=0.43 for trend) or clinical cultures (P=0.79). There were no significant trends in rates of other index surveillance organisms (P>0.5). Results of the three typing methods were in general agreement with three prevalent MRSA clones [clonal complex 22 (CC22), CC30 and CC45]. CC22 emerged as the dominant clonal complex alongside a significant decline in CC30 (P=0.002). CC45 was significantly more likely to be positive in glycopeptide resistance screens (P<0.001). There was no increase in antibiotic or chlorhexidine resistance. Long-term chlorhexidine bathing was not associated with any detectable loss of efficacy or increase in resistance in MRSA or with any increase in infection with other organisms. Changing clonal epidemiology occurred with no overall change in the prevalence of MRSA.  相似文献   

18.
The emergence of phenotypic resistance to ciprofloxacin and levofloxacin in methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MRSA) strains was studied. Twenty MRSA and 77 methicillin-sensitive S.aureus (MSSA) strains susceptible to both quinolones were investigated for resistance after single step or serial passages. No growth of 20 MRSA strains was observed at 4xMIC of levofloxacin after 48 h incubation, but 4 of 77 (5%) MSSA strains grew at the same concentration. At 4xMIC concentration of ciprofloxacin, 10 MSSA (13%) and five MRSA (25%) strains were grown. In the serial passages of MRSA strains, resistance to ciprofloxacin was 75 and 5% for levofloxacin by the third passage. In the seventh passage this resistance was 100 and 15%, respectively. In MSSA strains, resistance to ciprofloxacin was 75 and 19% to levofloxacin at the third passage and at the seventh passage, 100 and 61%, respectively. Emergence of ciprofloxacin resistance was more common and developed more rapidly than resistance to levofloxacin in both MRSA and MSSA strains.  相似文献   

19.
目的探讨医院感染控制教育对ICU医护人员洗手依从性的作用。方法临床观察ICU医护人员在进行感染控制教育前后1周,医护人员洗手的依从性,同时记录选择流水洗手和应用健之素手消毒液的比例,分别观察教育后第1、5、9、13周的依从性情况。采用提醒方式后,观察洗手依从性。结果在进行感染控制教育后,洗手依从性增高。选用免洗消毒液洗手的比率升高。教育后第1、5、9、13周,依从性呈下降趋势。采用早会提醒后,依从性重新提高。结论ICU感染控制教育和免洗消毒液可以提高医护人员洗手依从性,反复加强感染控制教育,有助于洗手依从性的保持。  相似文献   

20.
目的研究入住CCU病房患者的药学监护点。方法专职临床药师随医师查房1年,做查房记录,对危重及特殊患者建住院药历和对患者做住院用药交代。结果总结出CCU患者药学监护点。结论执行药学监护点保障患者用药安全、有效。  相似文献   

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