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| 2. |
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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 8. |
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| 9. |
- 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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| 11. |
- Johansen, Truls E. Bjerklund, et al.
(författare)
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Critical review of current definitions of urinary tract infections and proposal of an EAU/ESIU classification system
- 2011
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 38:Suppl., s. 64-70
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Forskningsöversikt (refereegranskat)abstract
- Classification of urinary tract infections (UTI) is important for clinical decisions, research, quality measurement and teaching. Current definitions of UTI are above all based on the concept of the two main categories, complicated and uncomplicated UTI. The category "complicated UTI" especially is very heterogeneous and not always clear. We propose the EAU/ESIU classification system ORENUC based on the clinical presentation of the UTI, categorisation of risk factors and availability of appropriate antimicrobial therapy, which finally may result in the definition of UTI severity groups. (C) 2011 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.
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| 12. |
- Kondori, Nahid, 1967, et al.
(författare)
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Fungicidal activity of human lactoferrin-derived peptides based on the antimicrobial alpha beta region
- 2011
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 37:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- Owing to the increasing number of infections in hospitalised patients caused by resistant strains of fungi, there is a need to develop new therapeutic agents for these infections. Naturally occurring antimicrobial peptides may constitute models for developing such agents. A modified peptide sequence (CFQWKRAM-RKVR; HLopt2) based on amino acid residues 20-31 of the N-terminal end of human lactoferrin (hLF) as well as a double-sized human lactoferricin-like peptide (amino acid residues 16-40; HLBD1) were investigated for their antifungal activities in vitro and in vivo. By in vitro assay, HLopt2 was fungicidal at concentrations of 12.5-25 mu g/mL against Cryptococcus neoformans, Candida albicans, Candida krusei, Candida kefyr and Candida parapsilosis, but not against Candida glabrata. HLopt2 was demonstrated to have >= 16-fold greater killing activity than HLBD1. By inducing some helical formation caused by lactam bridges or by extending the assay time (from 2 h to 20 h), HLBD1 became almost comparable with HLopt2 in its fungicidal activity. Killing of C. albicans yeast cells by HLopt2 was rapid and was accompanied by cytoplasmic and mitochondrial membrane permeabilisation as well as formation of deep pits on the yeast cell surface. In a murine C. albicans skin infection model, atopic treatment with the peptides resulted in significantly reduced yields of Candida from the infected skin areas. The antifungal activities of HLopt2 in vitro and in vivo suggest possible potential as a therapeutic agent against most Candida spp. and C. neoformans. The greatly improved antifungal effect of the lactam-modified HLBD1 indicates the importance of amphipathic helix formation for lethal activity.
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| 13. |
- Kostamo, Pirkko, et al.
(författare)
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Recent trends in primary antimicrobial resistance of Helicobacter pylori in Finland
- 2011
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 37:1, s. 22-25
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Tidskriftsartikel (refereegranskat)abstract
- The antimicrobial susceptibility of Helicobacter pylori is an important predictor of the success of eradication therapy. To evaluate recent changes in primary antimicrobial resistance of H. pylori isolated from Finnish patients, the clinical records of H. pylori-positive patients referred for endoscopy to Herttoniemi Hospital (Helsinki, Finland) during 2000-2008 were investigated retrospectively. Stored H. pylori strains from 505 patients without previous eradication therapy were tested for clarithromycin, metronidazole, levofloxacin, tetracycline and amoxicillin susceptibility by Etest. Data on local consumption of antimicrobials were collected and correlations between consumption and resistance were calculated. During the 9-year study period, metronidazole resistance was high (range 29-59%, overall 41%). After an initial increase in clarithromycin resistance (0% in 2000 to 16% in 2003), resistance to clarithromycin decreased to 4% in 2008. No significant correlation was detected between consumption of macrolides and resistance of clarithromycin. Resistance to levofloxacin varied between 0% and 12%. Primary metronidazole resistance in H. pylori is at a high level, however levofloxacin and clarithromycin resistances are still at a reasonable level. Thus, primary clarithromycin resistance in H. pylori in Finland has not become such a problem as in many other countries. Primary resistance to the antimicrobials studied varied considerably from year to year.
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| 15. |
- Marcusson, Linda L., et al.
(författare)
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Mutant prevention concentrations of pradofloxacin for susceptible and mutant strains of Escherichia coli with reduced fluoroquinolone susceptibility
- 2014
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 44:4, s. 354-357
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Tidskriftsartikel (refereegranskat)abstract
- Pharmacodynamic and mutant prevention properties of the fluoroquinolone pradofloxacin (PRA) were measured against a set of 17 Escherichia coli strains carrying no, one or two known mutations conferring reduced fluoroquinolone susceptibility. The strains included susceptible wild-types, isogenic constructed mutants, isogenic selected mutants and clinical isolates. The effectiveness of PRA was determined with regard to preventing the selection of resistant mutants, using static and changing concentrations of drug. Ciprofloxacin was used as a reference drug. Minimum inhibitory concentrations (MICs) and mutant prevention concentrations (MPCs) of PRA for the susceptible wild-type strains were in the range 0.012-0.016 mg/L and 0.2-0.3 mg/L, respectively, giving a mean +/- standard deviation mutant prevention index (MPI=MPC/MIC) of 17.7 +/- 1.1. The mean MPI PRA of the 14 mutant strains was 19.2 +/- 12, and the mean MPI across all 17 strains was 18.9 +/- 10.8. In an in vitro kinetic model in which PRA was diluted with a half-life of 7h to mimic in vivo conditions, an initial concentration of PRA of 1.6-2.4 mg/L (8-10x MPC), giving a PRA AUC/MPC ratio of 73-92, and a T->MPC of 21-23 h was sufficient to prevent the selection of resistant mutants from the three susceptible wild-type strains. Dosing to reduce selection for antibiotic resistance in veterinary therapy has a role in reducing the reservoir of resistant mutants. We conclude that a level of dosing that prevents the selection of resistant mutants during therapy should be achievable in vivo.
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| 16. |
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| 17. |
- Naber, Kurt G., et al.
(författare)
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Antibiotic treatment of uncomplicated urinary tract infection in premenopausal women
- 2011
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 38, s. 21-35
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Tidskriftsartikel (refereegranskat)abstract
- Uncomplicated urinary tract infections (UTIs) in otherwise healthy premenopausal women are one of the most frequent infections in the community. Therefore any improvement in management will have a high impact not only on the quality of life of the individual patient but also on the health system. In placebo-controlled studies antimicrobial treatment was significantly more effective than placebo, but on the other hand showed more adverse events. The choice of antibiotic depends on the spectrum and susceptibility patterns of the uropathogens, its effectiveness for this indication, its tolerability, its collateral effects and cost. After a systematic literature search, recommendations for empiric treatment of acute uncomplicated cystitis and acute uncomplicated pyelonephritis and for follow-up strategies were developed. (C) 2011 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.
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| 18. |
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| 19. |
- Puiac, Speranta, et al.
(författare)
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Small-molecular virulence inhibitors show divergent and immunomodulatory effects in infection models of Salmonella enterica serovar Typhimurium
- 2011
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 0924-8579 .- 1872-7913. ; 38:5, s. 409-416
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Tidskriftsartikel (refereegranskat)abstract
- The virulence-associated Salmonella pathogenicity island 2 (SPI2) type III secretion system supports intracellular replication of Salmonella enterica serovar Typhimurium in macrophage-like RAW264.7 cells. In contrast, the salicylidene acylhydrazide INP0010 and the benzimidazole omeprazole prevent virulence factor-mediated replication of S. Typhimurium in these cells. Here we show that INP0010 enhances expression of inducible nitric oxide synthase (iNOS), nitric oxide (NO) production, the oxidative burst and tumour necrosis factor-alpha (TNF alpha) release in infected RAW264.7 cells. INP0010 also inhibited SPI2 activity in RAW264.7 cells. The ability of INP0010 to suppress bacterial intracellular replication correlated with NO production. The iNOS inhibitor N-monomethyl-L-arginine restored SPI2 activity and antagonised the bacteriostatic effect of INP0010. Omeprazole, which inhibited iNOS expression in RAW264.7 cells, likewise antagonised INP0010. In infected epithelioid MDCK cells that did not express NO upon infection, INP0010 enhanced bacterial intracellular replication. In Caenorhabditis elegans, INP0010 significantly attenuated the virulence of S. Typhimurium. In this infection model, the attenuating effect of INP0010 was further enhanced by omeprazole. These results demonstrate that chemically unrelated virulence inhibitors may act in an antagonistic or additive manner, that their effect depends on the infection model applied, and that the attenuating effects of INP0010 in part relate to its ability to promote the SPI2 antagonist NO.
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| 24. |
- Wagenlehner, Florian M. E., et al.
(författare)
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Antimicrobials in urogenital infections
- 2011
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Ingår i: International Journal of Antimicrobial Agents. - : Elsevier BV. - 1872-7913 .- 0924-8579. ; 38:Suppl., s. 3-10
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Tidskriftsartikel (refereegranskat)abstract
- Urinary tract infections (UTIs) and male genital infections are amongst the most prevalent infections. A prudent antibiotic policy therefore has a large impact on society. The clinical classification in uncomplicated cystitis, uncomplicated pyelonephritis, complicated UTI and genital infections is useful, also for the right choice of antibiotic treatment. In this regard pharmacokinetic and pharmacodynamic aspects have to be considered. Nowadays in uncomplicated cystitis antibiotics exclusively reserved for this indication are preferred, such as fosfomycin trometamol, nitrofurantoin and pivmecillinam, in order to reduce antibiotic pressure in this extremely frequent entity. In complicated UTI a broad bacterial spectrum has to be considered. Different antibiotic substances should be used for treatment, such as penicillins, with beta-lactamase inhibitors, cephalosporins or carbapenems, fluoroquinolones, aminoglycosides or cotrimoxazole, if tested susceptible. For genital infections the pharmacokinetic properties of the antibiotics should especially be considered, such as in prostatitis, where mainly fluoroquinolones and macrolides show sufficient pharmacokinetic parameters for treatment of bacterial infections. Furthermore in genital infections fastidious organisms, such as Chlamydia or Mycoplasma spp. have to be considered with respect to their antimicrobial susceptibility. (C) 2011 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved.
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