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Matthew E. Falagas - One of the best experts on this subject based on the ideXlab platform.

  • the safety of polymyxin antibiotics
    Expert Opinion on Drug Safety, 2015
    Co-Authors: Theodoros Kelesidis, Matthew E. Falagas
    Abstract:

    Introduction: The emergence of Multidrug-Resistant Gram-Negative Bacteria has led to the increasing use of polymyxins. Nephrotoxicity and, to a lesser degree, neurotoxicity occur often during systemic polymyxin therapy. Scientific evidence regarding safety associated with polymyxins remains limited.Areas covered: Case reports/case series, observational studies and clinical trials assessing safety and toxicity of polymyxins were critically reviewed.Expert opinion: Polymyxins are drugs with a narrow therapeutic range. Nephrotoxicity is associated with both host factors and polymyxin exposure, and recent studies suggest that the relative risk of nephrotoxicity is similar for colistin and polymyxin B. Studies that have examined the safety of polymyxins have several limitations. Considering the available evidence, toxicities that may develop while on polymyxin therapy most often are mild to moderate in magnitude and reversible in nature. Strategies to minimize toxicity associated with polymyxins have evolved a...

  • risk factors associated with the isolation of colistin resistant gram negative Bacteria a matched case control study
    Critical Care Medicine, 2008
    Co-Authors: Dimitrios K Matthaiou, Drosos E Karageorgopoulos, Petros I. Rafailidis, G Samonis, Argyris Michalopoulos, Vassiliki Papaioannou, Georgia Ntani, Matthew E. Falagas
    Abstract:

    Objective:The emergence of Multidrug-Resistant Gram-Negative Bacteria has led to the re-use of colistin, but resistance to this agent has already been reported. We aimed to investigate the potential risk factors for the isolation of colistin-resistant Klebsiella pneumoniae, Acinetobacter baumannii,

  • aerosolized colistin as adjunctive treatment of ventilator associated pneumonia due to multidrug resistant gram negative Bacteria a prospective study
    Respiratory Medicine, 2008
    Co-Authors: Argyris Michalopoulos, Zefi Mastora, Dimitrios Fotakis, Simona Virtzili, Christodoulos Vletsas, Sylvia Raftopoulou, Matthew E. Falagas
    Abstract:

    Summary Background Ventilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to Multidrug-Resistant (MDR) Gram-Negative pathogens. Methods To assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-Negative pathogens, we prospectively examined all patients, who received inhaled colistin. Results Sixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (±SD) daily dosage of aerosolized colistin was 2.2 (±0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%. Conclusions Aerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-Negative Bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety.

  • antimicrobial susceptibility of multidrug resistant gram negative Bacteria to fosfomycin
    European Journal of Clinical Microbiology & Infectious Diseases, 2008
    Co-Authors: M. D. Kanellopoulou, N. D. Skarmoutsou, George Dimopoulos, Drosos E Karageorgopoulos, Petros I. Rafailidis, Matthew E. Falagas, E. A. Papafrangas
    Abstract:

    We evaluated the antimicrobial activity of fosfomycin against a randomly selected sample of 30 Klebsiella pneumoniae, 30 Pseudomonas aeruginosa, and 30 Acinetobacter baumannii Multidrug-Resistant, clinical isolates from patients in a general tertiary care hospital in Athens, Greece. Standard laboratory methods were used for susceptibility testing to commonly used antibiotics and the detection of extended-spectrum-β-lactamase (ESBL) and metallo-β-lactamase (MBL) production. The minimum inhibitory concentration (MIC) of fosfomycin for each isolate was determined by the agar dilution method. All K. pneumoniae isolates were both ESBL and MBL producers; all P. aeruginosa isolates were ESBL producers. The K. pneumoniae strains had fosfomycin MICs distributed across a range of 8-64 μg/ml; MIC50 was 16 μg/ml and MIC90 32 μg/ml. The fosfomycin MICs of the P. aeruginosa strains had a distribution across a range of 4 to over 512 μg/ml; MIC50 was 32 μg/ml and MIC90 128 μg/ml. The fosfomycin MICs of the A. baumannii strains had a distribution across a range of 64 to over 512 μg/ml; MIC50 was 256 μg/ml and MIC90 more than 512 μg/ml. Although standardized fosfomycin MIC interpretative breakpoints for the species studied are lacking, the findings of our study support the idea that fosfomycin may be further investigated as one among a decreasing list of therapeutic options for the treatment of infections due to Multidrug-Resistant strains of, primarily, K. pneumoniae and, secondly, P. aeruginosa.

  • Antimicrobial susceptibility of Multidrug-Resistant Gram negative Bacteria to fosfomycin
    European Journal of Clinical Microbiology and Infectious Diseases, 2008
    Co-Authors: Matthew E. Falagas, M. D. Kanellopoulou, N. D. Skarmoutsou, George Dimopoulos, Drosos E Karageorgopoulos, Petros I. Rafailidis, E. A. Papafrangas
    Abstract:

    We evaluated the antimicrobial activity of fosfomycin against a randomly selected sample of 30 Klebsiella pneumoniae, 30 Pseudomonas aeruginosa, and 30 Acinetobacter baumannii Multidrug-Resistant, clinical isolates from patients in a general tertiary care hospital in Athens, Greece. Standard laboratory methods were used for susceptibility testing to commonly used antibiotics and the detection of extended-spectrum-beta-lactamase (ESBL) and metallo-beta-lactamase (MBL) production. The minimum inhibitory concentration (MIC) of fosfomycin for each isolate was determined by the agar dilution method. All K. pneumoniae isolates were both ESBL and MBL producers; all P. aeruginosa isolates were ESBL producers. The K. pneumoniae strains had fosfomycin MICs distributed across a range of 8-64 microg/ml; MIC(50) was 16 microg/ml and MIC(90) 32 microg/ml. The fosfomycin MICs of the P. aeruginosa strains had a distribution across a range of 4 to over 512 microg/ml; MIC(50) was 32 microg/ml and MIC(90) 128 microg/ml. The fosfomycin MICs of the A. baumannii strains had a distribution across a range of 64 to over 512 microg/ml; MIC(50) was 256 microg/ml and MIC(90) more than 512 microg/ml. Although standardized fosfomycin MIC interpretative breakpoints for the species studied are lacking, the findings of our study support the idea that fosfomycin may be further investigated as one among a decreasing list of therapeutic options for the treatment of infections due to Multidrug-Resistant strains of, primarily, K. pneumoniae and, secondly, P. aeruginosa

Neil Gregory Almstead - One of the best experts on this subject based on the ideXlab platform.

  • Discovery and Optimization of Indolyl-Containing 4-Hydroxy-2-Pyridone Type II DNA Topoisomerase Inhibitors Active against Multidrug Resistant Gram-Negative Bacteria
    Journal of Medicinal Chemistry, 2018
    Co-Authors: Aleksey I. Gerasyuto, Michael A. Arnold, Jiashi Wang, Guangming Chen, Xiaoyan Zhang, Sean M. Smith, Matthew G. Woll, John Baird, Nanjing Zhang, Neil Gregory Almstead
    Abstract:

    There exists an urgent medical need to identify new chemical entities (NCEs) targeting multidrug resistant (MDR) Bacterial infections, particularly those caused by Gram-Negative pathogens. 4-Hydroxy-2-pyridones represent a novel class of nonfluoroquinolone inhibitors of Bacterial type II topoisomerases active against MDR Gram-Negative Bacteria. Herein, we report on the discovery and structure–activity relationships of a series of fused indolyl-containing 4-hydroxy-2-pyridones with improved in vitro antiBacterial activity against fluoroquinolone resistant strains. Compounds 6o and 6v are representative of this class, targeting both Bacterial DNA gyrase and topoisomerase IV (Topo IV). In an abbreviated susceptibility screen, compounds 6o and 6v showed improved MIC90 values against Escherichia coli (0.5–1 μg/mL) and Acinetobacter baumannii (8–16 μg/mL) compared to the precursor compounds. In a murine septicemia model, both compounds showed complete protection in mice infected with a lethal dose of E. coli.

  • Discovery and Optimization of Indolyl-Containing 4‑Hydroxy-2-Pyridone Type II DNA Topoisomerase Inhibitors Active against Multidrug Resistant Gram-Negative Bacteria
    2018
    Co-Authors: Aleksey I. Gerasyuto, Michael A. Arnold, Jiashi Wang, Guangming Chen, Xiaoyan Zhang, Matthew G. Woll, John Baird, Nanjing Zhang, Sean Smith, Neil Gregory Almstead
    Abstract:

    There exists an urgent medical need to identify new chemical entities (NCEs) targeting multidrug resistant (MDR) Bacterial infections, particularly those caused by Gram-Negative pathogens. 4-Hydroxy-2-pyridones represent a novel class of nonfluoroquinolone inhibitors of Bacterial type II topoisomerases active against MDR Gram-Negative Bacteria. Herein, we report on the discovery and structure–activity relationships of a series of fused indolyl-containing 4-hydroxy-2-pyridones with improved in vitro antiBacterial activity against fluoroquinolone resistant strains. Compounds 6o and 6v are representative of this class, targeting both Bacterial DNA gyrase and topoisomerase IV (Topo IV). In an abbreviated susceptibility screen, compounds 6o and 6v showed improved MIC90 values against Escherichia coli (0.5–1 μg/mL) and Acinetobacter baumannii (8–16 μg/mL) compared to the precursor compounds. In a murine septicemia model, both compounds showed complete protection in mice infected with a lethal dose of E. coli

Aleksey I. Gerasyuto - One of the best experts on this subject based on the ideXlab platform.

  • Discovery and Optimization of Indolyl-Containing 4-Hydroxy-2-Pyridone Type II DNA Topoisomerase Inhibitors Active against Multidrug Resistant Gram-Negative Bacteria
    Journal of Medicinal Chemistry, 2018
    Co-Authors: Aleksey I. Gerasyuto, Michael A. Arnold, Jiashi Wang, Guangming Chen, Xiaoyan Zhang, Sean M. Smith, Matthew G. Woll, John Baird, Nanjing Zhang, Neil Gregory Almstead
    Abstract:

    There exists an urgent medical need to identify new chemical entities (NCEs) targeting multidrug resistant (MDR) Bacterial infections, particularly those caused by Gram-Negative pathogens. 4-Hydroxy-2-pyridones represent a novel class of nonfluoroquinolone inhibitors of Bacterial type II topoisomerases active against MDR Gram-Negative Bacteria. Herein, we report on the discovery and structure–activity relationships of a series of fused indolyl-containing 4-hydroxy-2-pyridones with improved in vitro antiBacterial activity against fluoroquinolone resistant strains. Compounds 6o and 6v are representative of this class, targeting both Bacterial DNA gyrase and topoisomerase IV (Topo IV). In an abbreviated susceptibility screen, compounds 6o and 6v showed improved MIC90 values against Escherichia coli (0.5–1 μg/mL) and Acinetobacter baumannii (8–16 μg/mL) compared to the precursor compounds. In a murine septicemia model, both compounds showed complete protection in mice infected with a lethal dose of E. coli.

  • Discovery and Optimization of Indolyl-Containing 4‑Hydroxy-2-Pyridone Type II DNA Topoisomerase Inhibitors Active against Multidrug Resistant Gram-Negative Bacteria
    2018
    Co-Authors: Aleksey I. Gerasyuto, Michael A. Arnold, Jiashi Wang, Guangming Chen, Xiaoyan Zhang, Matthew G. Woll, John Baird, Nanjing Zhang, Sean Smith, Neil Gregory Almstead
    Abstract:

    There exists an urgent medical need to identify new chemical entities (NCEs) targeting multidrug resistant (MDR) Bacterial infections, particularly those caused by Gram-Negative pathogens. 4-Hydroxy-2-pyridones represent a novel class of nonfluoroquinolone inhibitors of Bacterial type II topoisomerases active against MDR Gram-Negative Bacteria. Herein, we report on the discovery and structure–activity relationships of a series of fused indolyl-containing 4-hydroxy-2-pyridones with improved in vitro antiBacterial activity against fluoroquinolone resistant strains. Compounds 6o and 6v are representative of this class, targeting both Bacterial DNA gyrase and topoisomerase IV (Topo IV). In an abbreviated susceptibility screen, compounds 6o and 6v showed improved MIC90 values against Escherichia coli (0.5–1 μg/mL) and Acinetobacter baumannii (8–16 μg/mL) compared to the precursor compounds. In a murine septicemia model, both compounds showed complete protection in mice infected with a lethal dose of E. coli

Argyris Michalopoulos - One of the best experts on this subject based on the ideXlab platform.

  • risk factors associated with the isolation of colistin resistant gram negative Bacteria a matched case control study
    Critical Care Medicine, 2008
    Co-Authors: Dimitrios K Matthaiou, Drosos E Karageorgopoulos, Petros I. Rafailidis, G Samonis, Argyris Michalopoulos, Vassiliki Papaioannou, Georgia Ntani, Matthew E. Falagas
    Abstract:

    Objective:The emergence of Multidrug-Resistant Gram-Negative Bacteria has led to the re-use of colistin, but resistance to this agent has already been reported. We aimed to investigate the potential risk factors for the isolation of colistin-resistant Klebsiella pneumoniae, Acinetobacter baumannii,

  • aerosolized colistin as adjunctive treatment of ventilator associated pneumonia due to multidrug resistant gram negative Bacteria a prospective study
    Respiratory Medicine, 2008
    Co-Authors: Argyris Michalopoulos, Zefi Mastora, Dimitrios Fotakis, Simona Virtzili, Christodoulos Vletsas, Sylvia Raftopoulou, Matthew E. Falagas
    Abstract:

    Summary Background Ventilator-associated pneumonia (VAP) remains the leading cause of death in patients with intensive care unit (ICU) acquired infections associated with an attributable mortality around 30%. Increasing antimicrobial resistance in patients with VAP challenges intensivists to search for alternative therapeutic options. There is scarcity of data in the literature concerning the administration of aerosolized colistin in critically ill patients with VAP due to Multidrug-Resistant (MDR) Gram-Negative pathogens. Methods To assess the safety and effectiveness of aerosolized colistin as an adjunctive to the intravenous antimicrobial therapy for the treatment of VAP due to MDR Gram-Negative pathogens, we prospectively examined all patients, who received inhaled colistin. Results Sixty critically ill patients with a mean APACHE II score 16.7, received aerosolized colistin for the treatment of VAP due to MDR pathogens [Acinetobacter baumannii (37/60 cases), Pseudomonas aeruginosa (12/60 cases) and Klebsiella pneumoniae strains (11/60 cases)]. Half of the isolated pathogens were susceptible only to colistin. Mean (±SD) daily dosage of aerosolized colistin was 2.2 (±0.7) million international units (IU). All patients received 2946 inhalations of colistin and the mean duration of administration was 16.4 days. Fifty-seven patients received concomitant intravenous treatment with colistin or other antimicrobial agents. Bacteriological and clinical response of VAP was observed in 50/60 (83.3%) patients. No adverse effects related to inhaled colistin were recorded. All cause hospital mortality was 25% while mortality attributable to VAP was 16.7%. Conclusions Aerosolized colistin may be considered as adjunctive to intravenous treatment in patients with VAP due to MDR Gram-Negative Bacteria susceptible to colistin in critically ill patients. Although colistin is safe and effective, the best route of administration remains unclear. In addition, controlled comparative studies are needed to establish its effectiveness and safety.

  • the use of intravenous and aerosolized polymyxins for the treatment of infections in critically ill patients a review of the recent literature
    Clinical Medicine & Research, 2006
    Co-Authors: Matthew E. Falagas, Sofia K Kasiakou, Sotirios Tsiodras, Argyris Michalopoulos
    Abstract:

    Intravenous and aerosolized polymyxins are being used increasingly, especially in the critical care setting, for treating patients with infections due to Multidrug-Resistant Gram-Negative Bacteria, mainly Acinetobacter baumannii and Pseudomonas aeruginosa. Recent literature suggests that intravenous colistin and polymyxin B have acceptable effectiveness for the treatment of patients with bacteremia, as well as infections of various systems and organs, including pneumonia, bacteremia, skin and soft tissue, and urinary tract infections. Although data from recent studies have suggested that the toxicity of intravenous polymyxins is probably less than reported in the older literature, caution should be taken to monitor the renal function of patients who receive these antibiotics.

  • combination therapy with intravenous colistin for management of infections due to multidrug resistant gram negative Bacteria in patients without cystic fibrosis
    Antimicrobial Agents and Chemotherapy, 2005
    Co-Authors: Sofia K Kasiakou, Matthew E. Falagas, G Samonis, Argyris Michalopoulos, Elpidoforos S Soteriades, George J Sermaides
    Abstract:

    Colistin, an antibiotic almost abandoned for intravenous administration for many years due to its reported toxicity, has been recently reintroduced in clinical practice due to the emergence of Multidrug-Resistant Gram-Negative Bacteria and the lack of development of new antibiotics to combat them. To assess the safety and effectiveness of intravenous colistin, in combination with other antimicrobial agents, in the treatment of serious infections in patients without cystic fibrosis, a retrospective cohort study in a 450-bed tertiary-care hospital in Athens, Greece, was performed. Patients who were hospitalized from 1 October 2000 to 31 January 2004 and received intravenous colistin for more than 72 h were further analyzed. The primary outcome measure was the in-hospital mortality; secondary end points were the clinical outcome of the infections and the occurrence of colistin toxicity. Fifty patients received intravenous colistin with a median (mean) daily dose of 3 (4.5) million IU for 16.5 (21.3) days for the management of 54 episodes of infections due to Multidrug-Resistant Gram-Negative Bacteria. The predominant infections were pneumonia (33.3%), bacteremia (27.8%), urinary tract infection (11.1%), and intra-abdominal infection (11.1%). The responsible pathogens were Acinetobacter baumannii (51.9%), Pseudomonas aeruginosa (42.6%), and Klebsiella pneumoniae (3.7%) strains (no pathogen was isolated from one case). In-hospital mortality was 24% (12/50 patients). Clinical response (cure or improvement) of the infection was observed in 66.7% of episodes (36/54). In the studied group, serum creatinine levels were decreased, at the end of colistin treatment, by an average of 0.2 ± 1.3 mg/dl compared to baseline levels. Deterioration of renal function during colistin therapy was observed in 4/50 patients (8%). Coadministration of other antimicrobial agents with spectrum against Gram-Negative microorganisms and the absence of a control group constitute the major limitations of this study. The use of intravenous colistin for the treatment of infections due to Multidrug-Resistant Gram-Negative Bacteria appears to be safe and effective.

  • outcome of infections due to pandrug resistant pdr gram negative Bacteria
    BMC Infectious Diseases, 2005
    Co-Authors: Matthew E. Falagas, Sofia K Kasiakou, Ioannis A Bliziotis, G Samonis, Panayiota Athanassopoulou, Argyris Michalopoulos
    Abstract:

    Background The increasing problem of infections due to Multidrug-Resistant Gram-Negative Bacteria has led to re-use of polymyxins in several countries. However, there are already clinical isolates of Gram-Negative Bacteria that are resistant to all available antibiotics, including polymyxins.

Evelina Tacconelli - One of the best experts on this subject based on the ideXlab platform.

  • escmid eucic clinical guidelines on decolonization of multidrug resistant gram negative Bacteria carriers
    Clinical Microbiology and Infection, 2019
    Co-Authors: Evelina Tacconelli, Fulvia Mazzaferri, A M G A De Smet, Damiano Bragantini, Philippe Eggimann, Benedikt Huttner, E J Kuijper, J C Lucet, Nico T Mutters
    Abstract:

    Abstract Scope The aim of these guidelines is to provide recommendations for decolonizing regimens targeting Multidrug-Resistant Gram-Negative Bacteria (MDR-GNB) carriers in all settings. Methods These evidence-based guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant EnteroBacteriaceae (3GCephRE), carbapenem-resistant EnteroBacteriaceae (CRE), aminoglycoside-resistant EnteroBacteriaceae (AGRE), fluoroquinolone-resistant EnteroBacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-Negative organisms (CoRGNB), and pan-drug-resistant Gram-Negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations. Recommendations The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.

  • controversies in guidelines for the control of multidrug resistant gram negative Bacteria in eu countries
    Clinical Microbiology and Infection, 2015
    Co-Authors: Jonathan A Otter, Evelina Tacconelli, Nico T Mutters, Achilleas Gikas, A Holmes
    Abstract:

    The various guidelines that are available for Multidrug-Resistant Gram-Negative Bacteria are useful, and contain broad areas of agreement. However, there are also important areas of controversy between the guidelines in terms of the details of applying contact precautions, single-room isolation and active surveillance cultures, differences in the approach to environmental cleaning and disinfection, and whether or not to perform staff and patient cohorting, healthcare worker screening or patient decolonization. The evidence-base is extremely limited and further research is urgently required to inform an evidence-based approach to Multidrug-Resistant Gram-Negative Bacteria prevention and control.

  • escmid guidelines for the management of the infection control measures to reduce transmission of multidrug resistant gram negative Bacteria in hospitalized patients
    Clinical Microbiology and Infection, 2014
    Co-Authors: Evelina Tacconelli, Maria Adriana Cataldo, Stephanie J Dancer, G De Angelis, Marco Falcone, Uwe Frank, Gunnar Kahlmeter, Angelo Pan, Nicola Petrosillo, Jesus Rodriguezbano
    Abstract:

    Healthcare-associated infections due to Multidrug-Resistant Gram-Negative Bacteria (MDR-GNB) are a leading cause of morbidity and mortality worldwide. These evidence-based guidelines have been produced after a systematic review of published studies on infection prevention and control interventions aimed at reducing the transmission of MDR-GNB. The recommendations are stratified by type of infection prevention and control intervention and species of MDR-GNB and are presented in the form of ‘basic’ practices, recommended for all acute care facilities, and ‘additional special approaches’ to be considered when there is still clinical and/or epidemiological and/or molecular evidence of ongoing transmission, despite the application of the basic measures. The level of evidence for and strength of each recommendation, were defined according to the GRADE approach.

  • influx of multidrug resistant gram negative Bacteria in the hospital setting and the role of elderly patients with Bacterial bloodstream infection
    Infection Control and Hospital Epidemiology, 2009
    Co-Authors: Aurora Popvicas, Evelina Tacconelli, Stefan Gravenstein, Erika M C Dagata
    Abstract:

    Background.Multidrug-Resistant (MDR) Gram-Negative Bacteria are reported increasingly frequently among isolates recovered from elderly patients. The clinical epidemiology of bloodstream infection (BSI) due to MDR Gram-Negative Bacteria among elderly patients is unknown.Objective.To characterize the clinical epidemiology of BSI due to MDR Gram-Negative Bacteria among elderly patients at hospital admission in an effort to provide a greater understanding of these serious infections and ultimately to improve patient outcomes.Design.Case-control study.Setting.Tertiary care hospital in Boston, Massachusetts.Patients.Patients 65 years of age and older.Methods.From 1999 to 2007, computerized medical records were reviewed for BSI due to MDR Gram-Negative Bacteria within 48 hours of hospital admission. Risk factors for BSI due to these Bacteria were identified.Results.MDR Gram-Negative Bacteria were recovered from 61 (8%) of 724 elderly patients with BSI caused by Gram-Negative Bacteria. Over the -year study period, the percentage of MDR Gram-Negative Bacteria among bloodstream isolates increased from 2 (1%) of 199 to 34 (16%) of 216. Empiric therapy was ineffective for 38 (63%) of 60 patients with BSI caused by MDR Gram-Negative Bacteria. The variables independently associated with BSI due to these Bacteria were as follows: residency in a long-term care facility (odds ratio [OR], 4.9 [95% confidence interval {CI} 1.6–14.9]; P = .006), presence of an invasive device (OR, 6.0 [95% CI, 1.5–23.5]; P = .01), severe sepsis (OR, 7.9 [95% CI, 1.7–37.1]; P = .009), and delayed initiation of effective therapy (OR, 12.8 [95% CI, 3.9–41.1]; P<.001).Conclusion.The 16-fold increase in BSI due to MDR Gram-Negative Bacteria at hospital admission among elderly patients, especially among those who resided in long-term care facilities prior to admission, contributes further to the expanding body of evidence that these patients are the main reservoirs of MDR Gram-Negative Bacteria. Given their contribution to the influx of antimicrobial-resistant Bacteria in the hospital setting, infection control interventions that target this high-risk group need to be considered.