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Find video protocols related to scientific articles indexed in Pubmed.
Drug interactions between antiretrovirals and new or emerging direct-acting antivirals in HIV/hepatitis C virus coinfection.
Curr. Opin. Infect. Dis.
PUBLISHED: 07-25-2014
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We reviewed the pharmacokinetic interactions between direct-acting antivirals against hepatitis C virus (HCV) and antiretroviral agents.
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Deaths attributable to carbapenem-resistant Enterobacteriaceae infections.
Emerging Infect. Dis.
PUBLISHED: 06-25-2014
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We evaluated the number of deaths attributable to carbapenem-resistant Enterobacteriaceae by using studies from around the world published before April 9, 2012. Attributable death was defined as the difference in all-cause deaths between patients with carbapenem-resistant infections and those with carbapenem-susceptible infections. Online databases were searched, and data were qualitatively synthesized and pooled in a metaanalysis. Nine studies met inclusion criteria: 6 retrospective case-control studies, 2 retrospective cohort studies, and 1 prospective cohort study. Klebsiella pneumoniae was the causative pathogen in 8 studies; bacteremia was the only infection in 5 studies. We calculated that 26%-44% of deaths in 7 studies were attributable to carbapenem resistance, and in 2 studies, which included bacteremia and other infections, -3% and -4% of deaths were attributable to carbapenem resistance. Pooled outcomes showed that the number of deaths was significantly higher in patients with carbapenem-resistant infections and that the number of deaths attributable to carbapenem resistance is considerable.
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Severe Plasmodium vivax malaria complicated with acute respiratory distress syndrome: a case associated with focal autochthonous transmission in Greece.
Vector Borne Zoonotic Dis.
PUBLISHED: 04-18-2014
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In 2011, autochthonous Plasmodium vivax malaria emerged in a focal geographical area in Greece after importation by immigrants from the Indian subcontinent. We report the case of complicated P. vivax malaria in a previously healthy 42-year-old Greek female. The patient presented acute respiratory distress syndrome (ARDS), worsening jaundice, and thrombocytopenia after the administration of antimalarial treatment and despite a decreasing burden of parasitemia. She recovered fully after admission in the intensive care unit and support with mechanical ventilation. We discuss the risks potentially associated with the reappearance of P. vivax malaria in a previously malaria-free area.
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In vitro activity of fosfomycin in combination with linezolid against clinical isolates of methicillin-resistant Staphylococcus aureus.
J. Antibiot.
PUBLISHED: 01-14-2014
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The objective of this paper was to investigate the in vitro effects of fosfomycin combined with linezolid against methicillin-resistant Staphylococcus aureus (MRSA). A total of 102 MRSA isolates isolated from clinical specimens of human infections from three hospitals in China were studied. The microdilution checkerboard method was used to determine whether combinations act synergistically against these isolates. The susceptibility results for fosfomycin and linezolid were interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. Synergy and indifference were defined as a fractional inhibitory concentration index of ?0.5 and >0.5 but ?4, respectively. The combination of fosfomycin and linezolid demonstrated the following interactions: 98.04% (100/102) synergism; 1.96% (2/102) indifference; no antagonism was seen. Thus, the combination between fosfomycin and linezolid shows synergism for most of the MRSA isolates tested in this study. If these findings are confirmed in further in vitro or in vivo studies, the above combination could be tested clinically for difficulty to treat MRSA infections, particularly those warranting prolonged oral therapy.
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Frequency of the off-label use of monoclonal antibodies in clinical practice: a systematic review of the literature.
Curr Med Res Opin
PUBLISHED: 11-12-2013
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Abstract Background: The monoclonal antibodies represent novel therapeutic options for many clinical entities. This study aimed to study the frequency of the off-label use to total use of different monoclonal antibodies in clinical practice. Methods: This study systematically searched the PubMed and Scopus databases for relevant studies. Results: Fifteen studies were considered eligible for inclusion in this review. Eight of the included studies referred to the off-label use of anti-neoplastic monoclonal antibodies, three referred to immunosuppressive ones, and four to other types of monoclonal antibodies. The most studied anti-neoplastic monoclonal antibody was rituximab; which was prescribed off-label at a frequency varying between 16-75%, mostly for an unapproved diagnosis. Bevacizumab was prescribed off-label for age-related macular degeneration more often than ranibizumab, the approved monoclonal antibody for this condition. Of the immunosuppressive monoclonal antibodies, infliximab was used off-label in an average of 15.4% (range?=?2.8-25%) and adalimumab in 10.5% (range?=?0-15.4% in different years). Conclusion: The frequency of off-label use of different types of monoclonal antibodies varies, but appears to be considerably high for specific monoclonal antibodies or indications. In certain examples, this might reflect implementation into clinical practice of relevant scientific data, albeit not of the strength or quality that suffices for receipt of regulatory approval. In others, it might relate to the sub-optimal effectiveness and considerable toxicity of the conventional therapies. Still, the clinician should bear in mind the potential costs and toxicity that can be associated with off-label use of monoclonal antibodies.
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A prospective observational study of chronic prostatitis with emphasis on epidemiological and microbiological features.
Urologia
PUBLISHED: 10-18-2013
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OBJECTIVES: Despite the progress made in recent years in understanding and diagnosing chronic prostatitis (CP) many cases are still underdiagnosed and undertreated for unknown reasons. The purpose of this study is to investigate the epidemiological data of patients with symptoms of CP and to associate data from medical history and clinical examination with the results of laboratory tests.METHODS: The study population consisted of individuals with reported pelvic discomfort and genital pain with or without lower urinary tract symptoms and sexual dysfunction visiting our department from 03/2009 to 03/2011. Patients underwent Meares-Stamey test (a few cases underwent the two-glass test). Depending on history and specific symptoms, urethral smear and sperm cultures were additionally obtained from several patients. The processes and reading of the samples were performed by a specialist microbiologist, who has not notified the patient record.RESULTS: 114 out of 155 patients who finally enrolled into the study had a medical history, 69 had sexual behavior and 72 sexual habits that predispose to chronic prostatitis. The clinical examination was not diagnostic in 43.8% of cases. The urethral smear and sperm culture diagnosed coexistent urethral infection in 22 cases. 54 out of the 72 positive EPS/VB3/PPM cultures grew one, 11 two to three and 5 cultures grew more than three different organisms.CONCLUSIONS: Findings of this study debate some widely accepted considerations on the etiology and diagnosis of chronic prostatitis and highlight the uncertainties and controversies regarding chronic prostatitis etiology, pathophysiology, presentation and diagnosis.
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Extended or continuous versus short-term intravenous infusion of cephalosporins: a meta-analysis.
Expert Rev Anti Infect Ther
PUBLISHED: 06-12-2013
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The authors sought to study whether extended or continuous infusion of cephalosporins is associated with better clinical outcomes than short-term infusion. PubMed and Scopus databases were systematically searched. Studies reporting the clinical outcomes of patients receiving extended or continuous infusion (?3 or 24 h, respectively) versus short-term infusion (?1 h) of cephalosporins were considered eligible. Eleven studies (1250 clinically evaluable patients) were included. Clinical cure and mortality were not statistically different between the compared groups (risk ratio: 1.14; 95% CI: 0.94-1.37 and risk ratio: 0.96; 95% CI: 0.80-1.15, respectively). This meta-analysis did not show a difference in clinical cure or mortality regarding extended or continuous versus short-term intravenous infusion of cephalosporins. However, in most of the included studies, patients in the extended/continuous infusion group received a substantially lower total dosage of antibiotic than those in the short-term group for the total duration of treatment.
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Impact of antimicrobial multidrug resistance on inpatient care cost: an evaluation of the evidence.
Expert Rev Anti Infect Ther
PUBLISHED: 03-06-2013
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This article evaluates the in-hospital costs attributable to antimicrobial multidrug resistance, defined as the difference in averaged costs of the patients infected with a multidrug-resistant (MDR) versus a non-MDR organism. PubMed and Scopus databases were searched to identify relevant studies. Twenty four studies were included: four on carbapenem-resistant or MDR Gram negative nonfermenters, eight on extended-spectrum b-lactamase-producing Enterobacteriaceae and 12 on methicillin-resistant Staphylococcus aureus. In two studies on carbapenem-resistant nonfermenters, the attributable mean hospital charges were US$58,457 and 85,299, respectively. The attributable mean total costs were US$4484 in a study referring to MDR Acinetobacter baumannii, while that varied from US$1584 to 30,093 among studies on extended-spectrum b-lactamase-producing Enterobacteriaceae. With respect to methicillin-resistant S. aureus, the attributable mean total costs varied from US$1014 to 40,090. The in-hospital costs attributable to multidrug resistance are alarmingly high, justifying the application of strict infection control measures in medical institutions with increased rate of MDR infections.
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The impact of article length on the number of future citations: a bibliometric analysis of general medicine journals.
PLoS ONE
PUBLISHED: 02-06-2013
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The number of citations received is considered an index of study quality and impact. We aimed to examine the factors associated with the number of citations of published articles, focusing on the article length.
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Severe sepsis and septic shock due to Plasmodium vivax infection.
Am J Emerg Med
PUBLISHED: 02-04-2013
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Plasmodium vivax malaria is typically characterized by a mild and benign clinical course. Organ dysfunction is rarely seen, whereas acute lung injury has been found to occur after starting antimalarial treatment. We present an unusual case of severe sepsis and septic shock due to Plasmodium vivax monoinfection.
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Weight-adjusted versus fixed dose of linezolid for Chinese healthy volunteers of higher and lower body weight: a Phase I pharmacokinetic and pharmacodynamic study.
Expert Opin Investig Drugs
PUBLISHED: 01-30-2013
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The objective was to evaluate the pharmacokinetic and pharmacodynamic properties of a single intravenous fixed dose compared with a weight-adjusted dose of linezolid.
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Continuous versus Conventional Infusion of Amphotericin B Deoxycholate: A Meta-Analysis.
PLoS ONE
PUBLISHED: 01-01-2013
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Treatment with Amphotericin B (AmB) deoxycholate, which is still used widely, particularly in low-resource countries, has been challenged due to nephrotoxicity. We sought to study whether continuous infusion of AmB deoxycholate reduces nephrotoxicity retaining, however, the effectiveness of the drug.
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Incidence, clinical, microbiological features and outcome of bloodstream infections in patients undergoing hemodialysis.
Int J Med Sci
PUBLISHED: 01-01-2013
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Infection is a common cause of death among hemodialysis patients. The study investigated incidence, risk factors, clinical features and outcome of bloodstream infections (BSIs) in haemodialysis patients.
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MRSA in Africa: filling the global map of antimicrobial resistance.
PLoS ONE
PUBLISHED: 01-01-2013
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We sought to assess the prevalence of methicillin-resistance among Staphylococcus aureus isolates in Africa. We included articles published in 2005 or later reporting for the prevalence of MRSA among S. aureus clinical isolates. Thirty-two studies were included. In Tunisia, the prevalence of MRSA increased from 16% to 41% between 2002-2007, while in Libya it was 31% in 2007. In South Africa, the prevalence decreased from 36% in 2006 to 24% during 2007-2011. In Botswana, the prevalence varied from 23-44% between 2000-2007. In Algeria and Egypt, the prevalence was 45% and 52% between 2003-2005, respectively. In Nigeria, the prevalence was greater in the northern than the southern part. In Ethiopia and the Ivory Coast, the prevalence was 55% and 39%, respectively. The prevalence of MRSA was lower than 50% in most of the African countries, although it appears to have risen since 2000 in many African countries, except for South Africa.
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Fosfomycin: evaluation of the published evidence on the emergence of antimicrobial resistance in Gram-negative pathogens.
J. Antimicrob. Chemother.
PUBLISHED: 11-16-2011
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Fosfomycin has attracted renewed interest for the treatment of lower urinary tract and even systemic infections caused by Gram-negative pathogens with resistance to traditionally used agents. The main concern regarding the clinical utility of fosfomycin refers to the potential for the emergence of resistance during therapy. In this review, we evaluate the available published evidence regarding the mechanisms and the frequency of in vitro mutational resistance to fosfomycin in Gram-negative pathogens. We also review data regarding the emergence of resistance in clinical studies of fosfomycin therapy in various infectious syndromes and data from studies that evaluate the evolution of fosfomycin resistance over time. There appears to be discordance between the high frequency of mutational resistance to fosfomycin in vitro and the lower extent of this phenomenon in clinical studies. This discordance could at least partly be attributed to a biological cost associated with common mutations that confer resistance to fosfomycin, including decreased growth rate and low adherence to epithelial cells for the resistant mutants. The development of resistance appears to be more frequent both in vitro and in clinical studies for Pseudomonas aeruginosa in comparison with Escherichia coli, whereas relevant data for other Enterobacteriaceae are relatively scarce. The urinary tract seems to provide a favourable environment for the use of fosfomycin with a low associated likelihood for the emergence of resistance, owing to high drug concentrations and acidic pH. Additional data are needed to further clarify the optimal use of fosfomycin for different infectious syndromes caused by contemporary multidrug-resistant pathogens.
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In vitro activity of minocycline combined with fosfomycin against clinical isolates of methicillin-resistant Staphylococcus aureus.
J. Antibiot.
PUBLISHED: 07-20-2011
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This study aimed to evaluate the in vitro activity of minocycline combined with fosfomycin against isolates of methicillin-resistant Staphylococcus aureus (MRSA). A total of 87 clinical isolates of MRSA collected from three Chinese hospitals were included in the study. The checkerboard method with determination of the fractional IC index (FICI) was used to determine whether antibiotic combinations act synergistically against these isolates. The susceptibility results for minocycline and fosfomycin were interpreted according to the most relevant criteria. The results demonstrated the following interactions: 76 isolates (87.4%) showed synergistic interactions (FICI?0.5) and 11 isolates (12.6%) showed indifferent interactions (0.5
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Therapeutic options for infections with Enterobacteriaceae producing carbapenem-hydrolyzing enzymes.
Future Microbiol
PUBLISHED: 06-29-2011
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Enterobacteriaceae that produce serine carbapenemases or metallo-?-lactamases, such as KPC, OXA-48, VIM or NDM, respectively, are spreading mostly as nosocomial pathogens worldwide. Such strains are typically resistant to most if not all available antimicrobials. Specific relevant clinical data are scarce to guide the determination of the most appropriate treatment options. Data on antimicrobial susceptibility, resistance development, synergy, pharmacokinetic and pharmacodynamic parameters of the candidate regimens, as well as the experience from the treatment of infections with nonfermenting Gram-negative pathogens, can aid in this regard. Colistin and tigecycline are most likely to be active in vitro against Enterobacteriaceae producing carbapenem-hydrolyzing ?-lactamases, but resistance development is of concern. Individual members of the aminoglycoside class can also be active in vitro, while carbapenems or aztreonam (specifically for metallo-?-lactamase producers) can have low minimum inhibitory concentrations. Current data do not reliably support the use of these agents as monotherapy for systemic infections. Several expanded-spectrum cephalosporins, such as ceftazidime, may be active against OXA-48 type producers. Fosfomycin might be useful as a last-resort option as part of combination regimens. Combination antimicrobial therapy with agents exhibiting synergy might also be of benefit, until novel effective agents could become clinically available.
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Predictors of impaired glucose regulation in patients with non-alcoholic fatty liver disease.
Exp Diabetes Res
PUBLISHED: 06-15-2011
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INTRODUCTION. Many patients with non-alcoholic fatty liver disease (NAFLD) have impaired glucose regulation or type 2 diabetes mellitus (DM). We investigated characteristics of NAFLD patients associated with hyperglycemia. METHODS. During a 2-hour oral glucose tolerance test (OGTT), serum glucose and insulin were measured in 152 NAFLD patients. RESULTS. 48.7% of NAFLD patients had hyperglycemia. Age (odds ratio (OR) = 1.08, 95% confidence interval (CI): 1.03-1.13), body mass index (BMI) (OR = 1.12, 95% CI: 1.01-1.25), and lower high-density lipoprotein cholesterol (HDL-C) (OR = 0.95, 95% CI: 0.92-0.98) proved to be independent predictors of hyperglycemia. After OGTT, 30?min insulin was lower in hyperglycemic patients (74.2 ± 49.7 versus 94.5 ± 53.9??IU/mL, P = 0.02), while 90?min insulin (170.1 ± 84.6 versus 122.9 ± 97.7??U/mL, P = 0.01) and 120?min insulin (164.0 ± 101.2 versus 85.3 ± 61.9??IU/mL, P < 0.01) were higher. CONCLUSIONS. NAFLD patients with higher BMI, lower HDL-C, or older age were more likely to have impaired glucose metabolism. An OGTT could be of value for early diagnosis of DM among this population.
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Age distribution of cases of 2009 (H1N1) pandemic influenza in comparison with seasonal influenza.
PLoS ONE
PUBLISHED: 06-08-2011
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Several aspects of the epidemiology of 2009 (H1N1) pandemic influenza have not been accurately determined. We sought to study whether the age distribution of cases differs in comparison with seasonal influenza.
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Trimethoprim/sulfametrole: evaluation of the available clinical and pharmacokinetic/pharmacodynamic evidence.
Int. J. Antimicrob. Agents
PUBLISHED: 04-19-2011
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Emergence of resistance to widely used trimethoprim/sulfamethoxazole (TMP/SMX) as well as common adverse events in human immunodeficiency virus (HIV)-infected patients casts interest on combinations of TMP with other sulfonamides. Sulfametrole (SMT) combined with TMP could provide a choice for difficult-to-treat infections, particularly when administered intravenously. The objective of this review was to evaluate the available clinical and pharmacokinetic/pharmacodynamic (PK/PD) evidence regarding TMP/SMT, particularly in comparison with TMP/SMX. We reviewed the available evidence retrieved from searches in PubMed/Scopus/Google Scholar and by bibliography hand-searching. In total, 46 eligible studies (most published before 1997) were identified, 7 regarding intravenous (i.v.) TMP/SMT, 24 regarding oral TMP/SMT and 15 providing comparative data for TMP/SMT versus TMP/SMX. The antimicrobial activity of TMP/SMT was similar to TMP/SMX for Gram-positive isolates. A greater percentage of Escherichia coli and Proteus spp. isolates were susceptible to TMP/SMT compared with TMP/SMX. PK/PD data suggest a dosage adjustment of i.v. TMP/SMT in patients with seriously impaired renal function. Four randomised controlled trials and 16 non-comparative studies reported good effectiveness/safety outcomes for oral TMP/SMT in genital ulcers (mainly chancroid), respiratory tract infections and urinary tract infections (UTIs). Moreover, i.v. TMP/SMT was effective against Pneumocystis jiroveci infection in HIV-infected patients, severe pneumonia and UTIs. In one study, hypersensitivity reactions occurred in 18/52 (34.6%) of HIV-infected patients; 2/52 (3.8%) developed psychosis. Gastrointestinal adverse events were mild and rare. Excipients in i.v. TMP/SMT formulations might be less toxic compared with i.v. TMP/SMX formulations, particularly for children. In conclusion, despite the scarcity of contemporary evidence, available data suggest that TMP/SMT could be an alternative treatment option to TMP/SMX, even in serious infections, when administered intravenously.
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Serum procalcitonin as a diagnostic marker for neonatal sepsis: a systematic review and meta-analysis.
Intensive Care Med
PUBLISHED: 03-05-2011
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To assess the value of serum procalcitonin (PCT) for the differentiation between patients with and without neonatal sepsis.
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?-D-glucan assay for the diagnosis of invasive fungal infections: a meta-analysis.
Clin. Infect. Dis.
PUBLISHED: 03-04-2011
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We aimed to assess the accuracy of measuring serum or plasma (1?3)-?-D-glucan (BDG) for the diagnosis of invasive fungal infections (IFIs) by means of a meta-analysis of relevant studies. We searched in bibliographic databases for relevant cohort or case-control studies. We primarily compared BDG between patients with proven or probable IFIs (excluding Pneumocystis jirovecii infections), according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group or similar criteria, and patients without IFIs (excluding healthy individuals as controls). A total of 2979 patients (594 with proven or probable IFIs), included in 16 studies, were analyzed. The pooled sensitivity of BDG was 76.8% (95% confidence interval [CI], 67.1%-84.3%), and the specificity was 85.3% (95% CI, 79.6%-89.7%). The area under the summary receiver operating characteristic curve was 0.89. Marked statistical heterogeneity was noted. BDG has good diagnostic accuracy for distinguishing proven or probable IFIs from no IFIs. It can be useful in clinical practice, if implemented in the proper setting and interpreted after consideration of its limitations.
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Temporal trends in the impact factor of European versus USA biomedical journals.
PLoS ONE
PUBLISHED: 02-09-2011
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The impact factors of biomedical journals tend to rise over time. We sought to assess the trend in the impact factor, during the past decade, of journals published on behalf of United States (US) and European scientific societies, in four select biomedical subject categories (Biology, Cell Biology, Critical Care Medicine, and Infectious Diseases).
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Association between thyroid function tests at baseline and the outcome of patients with sepsis or septic shock: a systematic review.
Eur. J. Endocrinol.
PUBLISHED: 11-15-2010
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The severity of critical illness is associated with various patterns of thyroid hormone abnormalities. We sought to evaluate whether the outcome of patients with, specifically, sepsis or septic shock is associated with the thyroid function tests evaluated at diagnosis or admission in the intensive care unit (ICU).
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Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review.
Lancet Infect Dis
PUBLISHED: 02-05-2010
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Rising rates of resistance to antimicrobial drugs among Enterobacteriaceae limit the choice of reliably active forms of these drugs. We evaluated the evidence on fosfomycin as a treatment option for infections caused by members of the family Enterobacteriaceae with advanced resistance to antimicrobial drugs, including producers of extended-spectrum beta-lactamase (ESBL). We systematically reviewed studies evaluating the antimicrobial activity, or the clinical effectiveness of fosfomycin. 17 antimicrobial-susceptibility studies were found and included in our Review, accounting for 5057 clinical isolates of Enterobacteriaceae with advanced resistance to antimicrobial drugs (4448 were producers of ESBL); 11 of the 17 studies reported that at least 90% of the isolates were susceptible to fosfomycin. Using a provisional minimum inhibitory concentration susceptibility breakpoint of 64 mg/L or less, 1604 (96.8%) of 1657 Escherichia coli isolates producing ESBL were susceptible to fosfomycin. Similarly, 608 (81.3%) of 748 Klebsiella pneumoniae isolates producing ESBL were susceptible to fosfomycin. In two clinical studies, oral treatment with fosfomycin-trometamol was clinically effective against complicated or uncomplicated lower urinary tract infections caused by ESBL-producing E coli in, cumulatively, 75 (93.8%) of the 80 patients evaluated. Initial clinical data support the use of fosfomycin for the treatment of urinary tract infections caused by these pathogens, although further research is needed.
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Inadequate statistical power of published comparative cohort studies on ventilator-associated pneumonia to detect mortality differences.
Clin. Infect. Dis.
PUBLISHED: 01-21-2010
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Comparative cohort studies are often conducted to identify novel therapeutic strategies or prognostic factors for ventilator-associated pneumonia (VAP). We aimed to evaluate the power of such studies to provide clinically and statistically significant conclusions with regard to mortality differences.
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Antimicrobial susceptibility of Gram-positive non-urinary isolates to fosfomycin.
Int. J. Antimicrob. Agents
PUBLISHED: 01-05-2010
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We aimed to evaluate the antimicrobial activity of fosfomycin against Gram-positive non-urinary isolates collected at the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece, in 2008. Susceptibility testing was performed by the disk diffusion method for a total of 1846 isolates; 1275 isolates (69.1%) were susceptible to fosfomycin. Specifically, 416/419 Staphylococcus aureus (99.3%) [including 129/130 meticillin-resistant S. aureus (MRSA) isolates] and 745/961 coagulase-negative staphylococci (77.5%) were susceptible to fosfomycin. Among 42 Streptococcus pneumoniae, 64 Streptococcus pyogenes and 93 other streptococcal isolates, 61.9%, 40.6% and 48.4%, respectively, were susceptible to fosfomycin. Fosfomycin was inactive against the 166 enterococcal isolates tested. This old antibiotic may deserve consideration for further studies and use in clinical practice, especially for S. aureus (including MRSA) infections.
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New antibiotics: optimal use in current clinical practice.
Int. J. Antimicrob. Agents
PUBLISHED: 11-26-2009
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The optimal choice of antibacterial therapy among the few available options for infections caused by pathogens with advanced antimicrobial drug resistance is fundamental to maximize clinical effectiveness and minimize the likelihood for further resistance development. We herein review the available data on the effectiveness of antibiotics introduced in clinical practice during the past 10 years for specific clinical indications. Quinupristin-dalfopristin, linezolid, daptomycin and tigecycline have increased the available therapeutic options against specific types of meticillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium infections. The newer fluoroquinolones, moxifloxacin and gemifloxacin, along with the ketolide telithromycin and the oral third-generation cephalosporin cefditoren are particularly valuable for the treatment of specific types of multidrug-resistant Streptococcus pneumoniae infections. Tigecycline appears as a promising therapeutic option for infections caused by Enterobacteriaceae producing extended spectrum beta-lactamases (ESBLs), or multidrug-resistant Acinetobacter baumannii. Ertapenem and doripenem may be particularly useful against infections caused by ESBL-producing Enterobacteriaceae and multidrug-resistant Pseudomonas aeruginosa, respectively.
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Prevalence of hepatitis B, hepatitis C, and HIV infections among patients in a psychiatric hospital in Greece.
Psychiatr Serv
PUBLISHED: 09-03-2009
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Psychiatric patients are considered to be at increased risk of infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV.
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Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections.
Int. J. Antimicrob. Agents
PUBLISHED: 08-24-2009
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The advancing antimicrobial drug resistance in common bacterial pathogens, along with the relative shortage of new antibacterial agents, call for the re-evaluation of available therapeutic options. Fosfomycin is an established treatment option for uncomplicated urinary tract infections. Here we review and evaluate the main pharmacokinetic and pharmacodynamic parameters of intravenously administered fosfomycin with regard to its use for systemic infections. Fosfomycin is a relatively small, hydrophilic agent with almost negligible serum protein binding. It is excreted unchanged in urine, achieving high concentrations for a prolonged period. Fosfomycin has good distribution into tissues, achieving clinically relevant concentrations in sites such as serum, soft tissue, lungs, bone, cerebrospinal fluid and heart valves. Fosfomycin has shown antimicrobial activity against biofilms, particularly in combination with fluoroquinolones. It also exerts immunomodulatory effects, mainly on lymphocyte and neutrophil function. Potentially useful properties of fosfomycin regarding its use in combination regimens include reduction in the expression of certain penicillin-binding proteins and attenuation of nephrotoxicity caused by several antimicrobial agents. In conclusion, the pharmacokinetic and pharmacodynamic properties of fosfomycin do not preclude its use for various types of systemic infections and suggest further research on relevant clinical applications of this agent.
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Comparison of adverse events between oral and intravenous formulations of antimicrobial agents: a systematic review of the evidence from randomized trials.
Pharmacoepidemiol Drug Saf
PUBLISHED: 08-05-2009
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Some clinicians may favor a strategy of early switch to oral antimicrobial therapy for patients responding to initial intravenous therapy. An important relevant consideration refers to the comparative safety and tolerability between oral and intravenous antimicrobial therapy. LITERATURE SEARCH/STUDY SELECTION: We sought to evaluate the above-mentioned issue by performing a systematic review of randomized studies comparing the occurrence of adverse events between oral and intravenous antimicrobial therapy with the same agents.
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Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients.
Int. J. Antimicrob. Agents
PUBLISHED: 07-28-2009
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It is unclear whether the effectiveness of polymyxins depends on the site of infection, the responsible pathogen, dosage, and monotherapy vs. combination therapy. We investigated colistin therapy in a large, retrospective, single-centre, cohort study. Primary analysis outcomes were infection outcome, survival and nephrotoxicity. Over a 7-year period (October 2000 to October 2007), 258 patients received intravenous (i.v.) colistin for at least 72h for microbiologically documented multidrug-resistant Gram-negative bacterial infections, comprising 170 (65.9%) Acinetobacter baumannii, 68 (26.4%) Pseudomonas aeruginosa, 18 (7.0%) Klebsiella pneumoniae, 1 (0.4%) Stenotrophomonas maltophilia and 1 (0.4%) Enterobacter cloacae. Cure of infection occurred in 79.1% of patients, nephrotoxicity in 10% and hospital survival in 65.1%. In the multivariate analysis, independent predictors of survival were colistin average daily dose [adjusted odds ratio (aOR)=1.22, 95% confidence interval (CI) 1.05-1.42] and cure of infection (aOR=9, 95% CI 3.6-23.1), whilst the proportion of creatinine change (aOR=0.21, 95% CI 0.1-0.45), Acute Physiology and Chronic Health Evaluation (APACHE) II score (aOR=0.89, 95% CI 0.84-0.95) and haematological disease (aOR=0.23, 95% CI 0.08-0.66) were associated with mortality. Effectiveness of colistin was not dependent on the type of pathogen. No independent predictors for nephrotoxicity were observed. The findings of the largest cohort study to date on i.v. colistin show that colistin is a valuable antibiotic with acceptable nephrotoxicity and considerable effectiveness that depends on the daily dosage and infection site.
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Outcome of antimicrobial therapy in documented biofilm-associated infections: a review of the available clinical evidence.
Drugs
PUBLISHED: 07-09-2009
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Numerous laboratory findings indicate that microbial biofilms may be encountered in several types of human infections, affecting the activity of antimicrobial agents. We evaluated the clinical evidence regarding the effectiveness of antimicrobial therapy for infections documented to be biofilm-associated, by performing a review of 15 relevant studies, excluding dental and eye infections. In a clinical trial, a significant difference was noted in the effectiveness of antibacterial agents used for catheter-related urinary tract infections in which substantial bacterial adherence on uroepithelial cells was observed. In case series and case reports, 28 patients with biofilm-associated infections documented by electron microscopy scanning were identified. Infection sites included ear, urinary tract, CNS, bloodstream and foreign body implantation site. Pseudomonas and Staphylococcus spp. were the predominant microorganisms among the bacterial or fungal causative pathogens. In 24 cases, infections related to the presence of foreign bodies. Treatment failure or recurrence was noted in all eight patients in whom targeted antimicrobial therapy was instituted before foreign body removal. Foreign body removal coupled with antimicrobial therapy was effective in all ten relevant cases. In four cases of native tissue urinary tract infections, the outcome of the initial antimicrobial therapy was poor. The limited available relevant clinical evidence indicates that conventional antimicrobial therapy alone is not adequately effective against documented biofilm-associated infections. Although some regimens might be more appropriate in this setting, further research on novel therapeutic strategies is needed to improve the outcome of patients with biofilm-associated infections.
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Fosfomycin for the treatment of infections caused by Gram-positive cocci with advanced antimicrobial drug resistance: a review of microbiological, animal and clinical studies.
Expert Opin Investig Drugs
PUBLISHED: 06-25-2009
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The advancing antimicrobial drug resistance in Gram-positive cocci complicates the selection of appropriate therapy. The re-evaluation of older antibiotics may prove useful in expanding relevant therapeutic options.
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Antibiotics versus placebo or watchful waiting for acute otitis media: a meta-analysis of randomized controlled trials.
J. Antimicrob. Chemother.
PUBLISHED: 05-19-2009
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Recommendations on withholding antibiotics in children with acute otitis media (AOM) have been inadequately implemented in clinical practice.
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Serum procalcitonin for prediction of renal parenchymal involvement in children with urinary tract infections: a meta-analysis of prospective clinical studies.
J. Pediatr.
PUBLISHED: 03-09-2009
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To determine by meta-analysis whether serum procalcitonin (PCT) is a useful marker of acute renal parenchymal involvement (RPI) in children with culture-proven urinary tract infection (UTI), as diagnosed by acute-phase DMSA (Tc-99m dimercaptosuccinic acid) renal scintigraphy.
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Fosfomycin for the treatment of infections caused by multidrug-resistant non-fermenting Gram-negative bacilli: a systematic review of microbiological, animal and clinical studies.
Int. J. Antimicrob. Agents
PUBLISHED: 03-09-2009
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The treatment of multidrug-resistant (MDR), extensively drug-resistant or pandrug-resistant non-fermenting Gram-negative bacterial infections constitutes a challenge in an era of few new antibiotic choices. This mandates the re-evaluation of already existing antibiotics such as fosfomycin. We systematically reviewed the literature to assess the clinical and microbiological effectiveness of fosfomycin in the treatment of these infections by searching PubMed, Scopus and the Cochrane Library databases. In 23 microbiological studies identified, 1859 MDR non-fermenting Gram-negative bacterial isolates were examined. The susceptibility rate to fosfomycin of MDR Pseudomonas aeruginosa isolates was >or=90% and 50-90% in 7/19 and 4/19 relevant studies, respectively. Cumulatively, 511/1693 (30.2%) MDR P. aeruginosa isolates were susceptible to fosfomycin. Serotype O12 isolates exhibited greater susceptibility. Only 3/85 (3.5%) MDR Acinetobacter baumannii and 0/31 MDR Burkholderia spp. isolates were susceptible to fosfomycin. Variable criteria of susceptibility were used in the included studies. Fosfomycin was synergistic in combination with a beta-lactam, aminoglycoside or ciprofloxacin in 46/86 (53.5%) MDR P. aeruginosa isolates. One animal study found a good therapeutic effect of the combination fosfomycin/gentamicin against MDR P. aeruginosa endocarditis. In six clinical studies, 33 patients with MDR P. aeruginosa infections (mainly pulmonary exacerbations of cystic fibrosis) received fosfomycin (25/33 in combination with other antibiotics); 91% of the patients clinically improved. In conclusion, fosfomycin could have a role as a therapeutic option against MDR P. aeruginosa infections. Further research is needed to clarify the potential utility of this agent.
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Probiotics for the prevention of respiratory tract infections: a systematic review.
Int. J. Antimicrob. Agents
PUBLISHED: 01-28-2009
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We evaluated the clinical evidence regarding probiotic use for the prevention of respiratory tract infections (RTIs). Randomised controlled trials (RCTs) studying the effects of probiotics for the prevention of upper or lower RTIs were systematically identified. Fourteen RCTs (twelve involving healthy subjects and two involving patients with RTIs) were included. Various Lactobacillus strains were used in seven RCTs, combinations of Lactobacillus and Bifidobacterium strains were used in five RCTs, and a Bifidobacterium strain and a non-pathogenic Enterococcus faecalis strain were used in one RCT, respectively. In ten RCTs no difference was found regarding the incidence of RTIs in the probiotic arm compared with the control arm, whereas the remaining four RCTs favoured the use of probiotics. Reduction in the severity of symptoms related to RTIs was noted in five of six RCTs that provided relevant data. In three of nine RCTs that provided relevant data, the clinical course of RTIs was shorter in the probiotic arm, whereas no difference was found in the remaining six RCTs. In conclusion, probiotics may have a beneficial effect on the severity and duration of symptoms of RTIs but do not appear to reduce the incidence of RTIs.
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Trends of tuberculin skin test positivity rate among schoolchildren in Attica, Greece.
Scand. J. Infect. Dis.
PUBLISHED: 01-27-2009
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We sought to estimate the prevalence and temporal trends of tuberculin skin test (TST) positivity rate among schoolchildren, in a suburban area of Attica, Greece. We retrospectively analysed the prevalence of the TST positivity (forearm volar surface induration >10 mm) of schoolchildren, in the catchment area of the public primary healthcare centre of Vari, over a 16-y period (1990-2005). TSTs were performed in the context of a national, government-directed TB screening programme. We retrieved 11,105 records of TSTs performed on children aged 6 and 14 y. These tests referred to 7920 and 2969 BCG unvaccinated and vaccinated children, respectively, as well as 120 children who had close contact with a TB confirmed case, and 6 children with known active or latent TB. The prevalence of TST positivity among BCG unvaccinated children was 2.0% over the whole study period; this figure declined in the second compared to the first half of the study period (2.4% vs 1.4%, p<0.001). The gradual decline in TST positivity among BCG unvaccinated schoolchildren, despite the substantial rise in the number of immigrants in Greece, over our study period, may, at least in part, be attributed to relevant national screening and prevention measures.
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Effectiveness and safety of short vs. long duration of antibiotic therapy for acute bacterial sinusitis: a meta-analysis of randomized trials.
Br J Clin Pharmacol
PUBLISHED: 01-22-2009
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Treatment guidelines generally support that a 10-14-day antibiotic regimen should be administered to uncomplicated acute bacterial sinusitis patients. However, the level of evidence for such a recommendation is rather weak. Treatment of such duration may have disadvantages compared with a shorter duration but equally effective regimen, including the promotion of bacterial drug resistance, poorest patient compliance, higher toxicity, and a greater overall economic burden.
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Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of tigecycline.
Curr. Drug Metab.
PUBLISHED: 01-20-2009
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Tigecycline is a novel antibacterial agent with a wide spectrum of antimicrobial activity that includes pathogens with clinically significant resistance patterns. The clinical effectiveness of tigecycline has been evaluated in several non-inferiority, phase III, randomized, double-blind, controlled clinical trials regarding, mainly, complicated skin and skin structure infections and complicated intra-abdominal infections. Clinical data regarding the effectiveness of tigecycline against infections caused by multidrug-resistant pathogens that commonly affect severely ill patients as well as community acquired pneumonia are favorable, yet limited. The consideration of the pharmacokinetic and pharmacodynamic properties of tigecycline may aid in further understanding the therapeutic role of this agent. Respectively, the utility of tigecycline in the treatment of severe infections involving the bloodstream has not been substantiated, particularly regarding pathogens with borderline susceptibility. Moreover, the fact that a relatively small proportion of the administered tigecycline dose is excreted unchanged in the urine may compromise the effectiveness of this agent in serious urinary tract infections. Increasing the dose of tigecycline to maximize effectiveness against severe infections appears as an appealing therapeutic option, considering the linear pharmacokinetics exhibited by this agent. However, gastrointestinal toxicity (nausea and vomiting) is usually dose-limiting. Further research is recommended on therapeutic strategies to optimize the effectiveness and safety of tigecycline therapy in severely ill patients.
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Impact of vancomycin minimum inhibitory concentration on clinical outcomes of patients with vancomycin-susceptible Staphylococcus aureus infections: a meta-analysis and meta-regression.
Int. J. Antimicrob. Agents
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Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ?2 mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure) of patients with S. aureus infections by high-VMIC (conventionally defined as VMIC >1 mg/L but ?2 mg/L) and low-VMIC (VMIC?1 mg/L) isolates were compared by performing a systematic review and meta-analysis. The effect of potential confounders was assessed by univariate meta-regression analyses. In total, 33 studies (6210 patients) were included. Most studies were retrospective (28/33), used the Etest (22/33) and referred to meticillin-resistant S. aureus (MRSA) infections (26/33) and bacteraemia (23/33). Irrespective of VMIC testing method, meticillin resistance and site of infection, the high-VMIC group had higher mortality [relative risk (RR)=1.21 (95% confidence interval 1.03-1.43); 4612 patients] and more treatment failures [RR=1.67 (1.26-2.21); 2049 patients] than the low-VMIC group. The results were not affected by the potential confounders and were reproduced in the subset of patients with MRSA infections [mortality, RR=1.19 (1.02-1.40), 2956 patients; treatment failure, RR=1.69 (1.26-2.25), 1793 patients]. In conclusion, infection by vancomycin-susceptible S. aureus with VMIC>1mg/L appears to be associated with higher mortality than VMIC?1mg/L. Further research is warranted to verify these results and to assess the impact of VMIC on meticillin-susceptible S. aureus infections. Evaluation of alternative antimicrobial agents also appears justified.
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Outbreak of OXA-48 carbapenemase-producing Klebsiella pneumoniae in Greece involving an ST11 clone.
J. Antimicrob. Chemother.
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First detected in Enterobacteriaceae isolates in Turkey, the OXA-48 carbapenemase has gradually disseminated in the wider Mediterranean area and Europe. Despite reports from other European regions, until now no such isolates have been detected in Greece. We describe the characteristics of the first outbreak caused by OXA-48-producing Klebsiella pneumoniae in Greece.
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Surveillance of community outbreaks of respiratory tract infections based on house-call visits in the metropolitan area of Athens, Greece.
PLoS ONE
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The traditional Serfling-type approach for influenza-like illness surveillance requires long historical time-series. We retrospectively evaluated the use of recent, short, historical time-series for recognizing the onset of community outbreaks of respiratory tract infections (RTIs).
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In vitro antimicrobial susceptibility to isepamicin of 6,296 Enterobacteriaceae clinical isolates collected at a tertiary care university hospital in Greece.
Antimicrob. Agents Chemother.
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The reevaluation of "forgotten" antibiotics can identify new therapeutic options against extensively drug-resistant Gram-negative pathogens. We sought to investigate isepamicin in this regard. We retrospectively evaluated the antimicrobial susceptibility to isepamicin of Enterobacteriaceae sp. isolates from unique patients, collected at the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece, from 2004 to 2009. Susceptibility testing was done with the automated Vitek 2 system. The breakpoints for susceptibility to isepamicin, tigecycline, and other antibiotics were those proposed by the Comité de lAntibiogramme de la Société Française de Microbiologie (CA-SFM), the FDA, and the CLSI, respectively. A total of 6,296 isolates were studied, including primarily 3,401 (54.0%) Escherichia coli, 1,040 (16.5%) Klebsiella pneumoniae, 590 (9.4%) Proteus mirabilis, and 460 (7.3%) Enterobacter sp. isolates. Excluding the species with intrinsic resistance to each antibiotic, antimicrobial susceptibility was highest for colistin (5,275/5,441 isolates [96.9%]) and isepamicin (6,103/6,296 [96.9%]), followed by meropenem (5,890/6,296 [93.6%]), imipenem (5,874/6,296 [93.3%]), and amikacin (5,492/6,296 [87.2%]). The antimicrobial susceptibility of the 1,040 K. pneumoniae isolates was highest for isepamicin (95.3%), followed by colistin (89.3%) and meropenem (63.0%). Regarding resistant K. pneumoniae isolates, susceptibility to isepamicin was observed for 91.1% of the 392, 87.7% of the 375, and 85.6% of the 111 isolates that were nonsusceptible to the carbapenems, all other aminoglycosides, and colistin, respectively. Isepamicin exhibited high in vitro activity against almost all of the Enterobacteriaceae species. It could particularly serve as a last-resort therapeutic option for carbapenem-resistant K. pneumoniae in our region, where it is endemic, as it does not show considerable cross-resistance with other aminoglycosides.
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Susceptibility of Gram-negative bacteria to isepamicin: a systematic review.
Expert Rev Anti Infect Ther
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We sought to review the potential role of isepamicin against infections with contemporary Gram-negative bacteria. We searched PubMed and Scopus databases to identify relevant microbiological and clinical studies published between 2000 and 2010, and we retrieved 11 and three studies, respectively. A total of 4901 isolates were examined in the in vitro studies. Isepamicin had higher in vitro activity compared with amikacin in four studies, was as active as amikacin in six studies and in the remaining study both were inactive. Regarding specifically the studies that included multidrug-resistant bacteria, isepamicin appeared superior to amikacin in two studies, as active as amikacin in one study and both did not exhibit activity in one study. In the clinical studies, isepamicin was as active as amikacin for the treatment of 55 children with urinary tract infections. In conclusion, isepamicin might be active in vitro against Gram-negative bacteria with resistance to amikacin and other aminoglycosides.
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