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- Chu, Hencelyn, et al.
(författare)
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Candidate vaginal microbicides with activity against Chlamydia trachomatis and Neisseria gonorrhoeae
- 2010
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 36:2, s. 145-150
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Tidskriftsartikel (refereegranskat)abstract
- Vaginal microbicides with activity towards organisms that cause sexually transmitted infections have been proposed as a strategy to reduce transmission. Small-molecule inhibitors of Chlamydia trachomatis serovar D belonging to the class of salicylidene acylhydrazides (INPs) have been shown to work through a mechanism that involves iron restriction. Expanding on this work, ten INPs were tested against a lymphogranuloma venereum strain of C. trachomatis (serovar L2), Neisseria gonorrhoeae, and hydrogen peroxide-producing Lactobacillus crispatus and Lactobacillus jensenii. Seven INPs had minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations of <50 microM towards C. trachomatis L2. Three INPs had a MIC <12.5 microM against N. gonorrhoeae. Inhibition was reversed by iron, holo-transferrin and holo-lactoferrin but not by the iron-poor forms of these compounds. The compounds exhibited no bactericidal activity toward Lactobacillus. The INPs were not cytotoxic to HeLa 229 cells. When INP 0341 was tested in a mouse model of a Chlamydia vaginal infection there was a significant reduction in the number of mice shedding C. trachomatis up to 4 days after infection (P<0.01). In summary, select INPs are promising vaginal microbicide candidates as they inhibit the growth of two common sexually transmitted organisms in vitro, are active in a mouse model against C. trachomatis, are not cytotoxic and do not inhibit organisms that compose the normal vaginal flora.
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- Dhanani, Jayesh, et al.
(författare)
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Antimicrobial chemotherapy and lung microdialysis: a review
- 2010
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 36:6, s. 491-500
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Forskningsöversikt (refereegranskat)abstract
- Pneumonia is a form of lung infection that may be caused by various micro-organisms. The predominant site of infection in pneumonia is debatable. Advances in the fields of diagnostic and therapeutic medicine have had a less than optimal effect on the outcome of pneumonia and one of the many causes is likely to be inadequate antimicrobial concentrations at the site of infection in lung tissue. Traditional antimicrobial therapy guidelines are based on indirect modelling from blood antimicrobial levels. However, studies both in humans and animals have shown the fallacy of this concept in various tissues. Many different methods have been employed to study lung tissue antimicrobial levels with limited success, and each has limitations that diminish their utility. An emerging technique being used to study the pharmacokinetics of antimicrobial agents in lung tissue is microdialysis. Development of microdialysis catheters, along with improvement in analytical techniques, has improved the accuracy of the data. Unfortunately, very few studies have reported the use of microdialysis in lung tissue, and even fewer antimicrobial classes have been studied. These studies generally suggest that this technique is a safe and effective way of assessing the pharmacokinetics of antimicrobial agents in lung tissue. Further descriptive studies need to be conducted to study the pharmacokinetics and pharmacodynamics of different antimicrobial classes in lung tissue. Data emanating from these studies could inform decisions for appropriate dosing schedules of antimicrobial agents in pneumonia. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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- Di Paolo, Antonello, et al.
(författare)
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Population pharmacokinetics of daptomycin in patients affected by severe Gram-positive infections
- 2013
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 42:3, s. 250-255
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Tidskriftsartikel (refereegranskat)abstract
- A population pharmacokinetic analysis of daptomycin was performed based on therapeutic drug monitoring (TDM) data from 58 patients receiving doses of 4–12 mg/kg for the treatment of severe Gram-positive infections. At a daily dose of 8 mg/kg, daptomycin plasma concentrations (mean ± S.D.) were 76.9 ± 9.8 mg/L at the end of infusion and 52.7 ± 15.4 mg/L and 11.4 ± 5.4 mg/L at 0.5 h and 23 h after drug administration, respectively. The final model was a one-compartmental model with first-order elimination, with estimated clearance (CL) of 0.80 ± 0.14 L/h and a volume of distribution (Vd) of 0.19 ± 0.05 L/kg. Creatinine clearance (CLCr) was identified as having a significant influence on daptomycin CL, and a decrease in CLCr of 30 mL/min from the median value (80 mL/min) was associated with a reduction of daptomycin CL from 0.80 L/h to 0.73 L/h. These results confirm that the presence of severe infection may be associated with an altered disposition of daptomycin, with an increased Vd. MICs were available in 41 patients and results showed that 38 and 31 subjects achieved AUC/MIC values associated with bacteriostatic (>400) and bactericidal effects (>800), respectively. Of note, 31 of these 41 subjects experienced a clinical improvement or were cured. Although daptomycin pharmacokinetics may be influenced by infections, effective AUC/MIC values were achieved in the majority of patients. The present model may be applied in clinical settings for a TDM routine on the basis of a sparse blood sampling protocol.
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- Forthal, Donald N, et al.
(författare)
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In vitro anti-HIV-1 activity of salicylidene acylhydrazide compounds
- 2012
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 40:4, s. 354-360
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Tidskriftsartikel (refereegranskat)abstract
- Salicylidene acylhydrazide compounds have been shown to inhibit bacterial pathogens, including Chlamydia and Neisseria gonorrhoeae. If such compounds could also target HIV-1, their potential use as topical microbicides to prevent sexually transmitted infections would be considerable. In this study, the in vitro anti-HIV-1 activity, cytotoxicity and mechanism of action of several salicylidene acylhydrazides were determined. Inhibitory activity was assessed using TZM-bl cells and primary peripheral blood mononuclear cells (PBMCs) as targets for HIV-1 infection. Antiviral activity was measured against cell-free and cell-associated virus and in vaginal fluid and semen simulants. Since the antibacterial activity of salicylidene acylhydrazides is reversible by Fe(2+), the ability of Fe(2+) and other cations to reverse the anti-HIV-1 activity of the compounds was determined. Real-time PCR was also employed to determine the stage affected in the HIV-1 replication cycle. Four compounds with 50% inhibitory concentrations against HIV-1 of 1-7μM were identified. In vitro toxicity varied but was generally limited. Activity was similar against three R5 clade B primary isolates and whether the target for virus replication was TZM-bl cells or PBMCs. Compounds inhibited cell-free and cell-associated virus and were active in vaginal fluid and semen simulants. Fe(2+), but not other cations, reversed the anti-HIV-1 effect. Finally, the inhibitory effect of the compounds occurred at a post-integration step. In conclusion, salicylidene acylhydrazides were identified with in vitro anti-HIV-1 activity in the micromolar range. The activity of these compounds against other sexually transmitted pathogens makes them potential candidates to formulate for use as a broad-spectrum topical genital microbicide.
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| 7. |
- Grabe, Magnus
(författare)
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Antibiotic prophylaxis in urological surgery, a European viewpoint.
- 2011
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 38, s. 58-63
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infections (SSI) including urinary tract infections (UTI) cause a significant morbidity in urological surgery. Antibiotic prophylaxis is one of several factors impacting on infection rates. Antibiotic prophylaxis is relevant only for clean and clean-contaminated operations and in the absence of bacterial growth in the urine. Strict classification of urological procedures is lacking, but a proposal is presented elsewhere. Only TURP and transrectal core prostate biopsy are well documented. The present review confirms that there is a lack of hard data, insufficient consistency in classification and definitions, and that new well-powered RCT and large multicentre quality cohort studies including risk factor analysis are necessary to improve recommendations for antibiotic prophylaxis in urologic surgery.
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- Hanberger, Håkan, et al.
(författare)
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Increased mortality associated with meticillin-resistant Staphylococcus aureus (MRSA) infection in the Intensive Care Unit: results from the EPIC II study
- 2011
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier. - 0924-8579 .- 1872-7913. ; 38:4, s. 331-335
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Tidskriftsartikel (refereegranskat)abstract
- Controversy continues regarding whether the presence of meticillin resistance increases mortality risk in Staphylococcus aureus infections. In this study, we assessed the role of meticillin resistance in survival of patients with S. aureus infection included in the EPIC II point-prevalence study of infection in critically ill patients performed on 8 May 2007. Demographic, physiological, bacteriological and therapeutic data were collected for 13 796 adult patients in 1265 participating Intensive Care Units (ICUs) from 75 countries on the study day. ICU and hospital outcomes were recorded. Characteristics of patients with meticillin-sensitive S. aureus (MSSA) and meticillin-resistant S. aureus (MRSA) infections were compared. Co-morbidities, age, Simplified Acute Physiology Score (SAPS) II, site of infection, geographical region and MRSA/MSSA were entered into a multivariate model, and adjusted odds ratios (ORs) [95% confidence interval (CI)] for ICU and hospital mortality rates were calculated. On the study day, 7087 (51%) of the 13 796 patients were classified as infected. There were 494 patients with MRSA infections and 505 patients with MSSA infections. There were no significant differences between the two groups in use of mechanical ventilation or haemofiltration/haemodialysis. Cancer and chronic renal failure were more prevalent in MRSA than in MSSA patients. ICU mortality rates were 29.1% and 20.5%, respectively (P andlt; 0.01) and corresponding hospital mortality rates were 36.4% and 27.0% (P andlt; 0.01). Multivariate analysis of hospital mortality for MRSA infection showed an adjusted OR of 1.46 (95% CI 1.03-2.06) (P = 0.03). In ICU patients, MRSA infection is therefore independently associated with an almost 50% higher likelihood of hospital death compared with MSSA infection.
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| 10. |
- Holmberg, Anna, et al.
(författare)
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Antibiotic regimens with rifampicin for treatment of Enterococcus faecium in biofilms.
- 2014
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 44:1, s. 78-80
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Tidskriftsartikel (refereegranskat)abstract
- Enterococcus faecium is an important pathogen that is resistant to many antibiotics and is able to form biofilms on implanted medical devices. In this study, the efficacy of rifampicin-containing antibiotic regimens against biofilms of E. faecium in vitro was investigated by determination of the minimum biofilm eradication concentration and by time-kill experiments of bacteria in biofilms formed on beads of bone cement. Rifampicin combined with tigecycline, daptomycin or linezolid was more efficient in reducing bacterial numbers and halting the development of rifampicin resistance than the combination of rifampicin and vancomycin.
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