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  1. Article ; Online: Optimization of Antimicrobial Stewardship Programs Using Therapeutic Drug Monitoring and Pharmacokinetics-Pharmacodynamics Protocols: A Cost-Benefit Review.

    Telles, João Paulo / Morales, Ronaldo / Yamada, Carolina Hikari / Marins, Tatiana A / D'Amaro Juodinis, Vanessa / Sztajnbok, Jaques / Silva, Moacyr / Bassetti, Bil Randerson / Albiero, James / Tuon, Felipe Francisco

    Therapeutic drug monitoring

    2023  Volume 45, Issue 2, Page(s) 200–208

    Abstract: Purpose: Antimicrobial stewardship programs are important for reducing antimicrobial resistance because they can readjust antibiotic prescriptions to local guidelines, switch intravenous to oral administration, and reduce hospitalization times. ... ...

    Abstract Purpose: Antimicrobial stewardship programs are important for reducing antimicrobial resistance because they can readjust antibiotic prescriptions to local guidelines, switch intravenous to oral administration, and reduce hospitalization times. Pharmacokinetics-pharmacodynamics (PK-PD) empirically based prescriptions and therapeutic drug monitoring (TDM) programs are essential for antimicrobial stewardship, but there is a need to fit protocols according to cost benefits. The cost benefits can be demonstrated by reducing toxicity and hospital stay, decreasing the amount of drug used per day, and preventing relapses in infection. Our aim was to review the data available on whether PK-PD empirically based prescriptions and TDM could improve the cost benefits of an antimicrobial stewardship program to decrease global hospital expenditures.
    Methods: A narrative review based on PubMed search with the relevant studies of vancomycin, aminoglycosides, beta-lactams, and voriconazole.
    Results: TDM protocols demonstrated important cost benefit for patients treated with vancomycin, aminoglycosides, and voriconazole mainly due to reduce toxicities and decreasing the hospital length of stay. In addition, PK-PD strategies that used infusion modifications to meropenem, piperacillin-tazobactam, ceftazidime, and cefepime, such as extended or continuous infusion, demonstrated important cost benefits, mainly due to reducing daily drug needs and lengths of hospital stays.
    Conclusions: TDM protocols and PK-PD empirically based prescriptions improve the cost-benefits and decrease the global hospital expenditures.
    MeSH term(s) Humans ; Aminoglycosides ; Anti-Bacterial Agents/therapeutic use ; Antimicrobial Stewardship ; Ceftazidime ; Cost-Benefit Analysis ; Drug Monitoring ; Vancomycin/therapeutic use ; Voriconazole
    Chemical Substances Aminoglycosides ; Anti-Bacterial Agents ; Ceftazidime (9M416Z9QNR) ; Vancomycin (6Q205EH1VU) ; Voriconazole (JFU09I87TR)
    Language English
    Publishing date 2023-01-02
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 424443-6
    ISSN 1536-3694 ; 0163-4356
    ISSN (online) 1536-3694
    ISSN 0163-4356
    DOI 10.1097/FTD.0000000000001067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pharmacodynamic Attainment of the Synergism of Meropenem and Fosfomycin Combination against Pseudomonas aeruginosa Producing Metallo-β-Lactamase.

    Albiero, James / Mazucheli, Josmar / Barros, Juliana Pimenta Dos Reis / Szczerepa, Marcia Maria Dos Anjos / Nishiyama, Sheila Alexandra Belini / Carrara-Marroni, Floristher Elaine / Sy, Serubbabel / Fidler, Matthew / Sy, Sherwin K B / Tognim, Maria Cristina Bronharo

    Antimicrobial agents and chemotherapy

    2019  Volume 63, Issue 6

    Abstract: Fosfomycin combined with other antimicrobials has shown good efficacy against multidrug-resistant (MDR) bacteria in ... ...

    Abstract Fosfomycin combined with other antimicrobials has shown good efficacy against multidrug-resistant (MDR) bacteria in both
    MeSH term(s) Adult ; Anti-Bacterial Agents/pharmacology ; Drug Resistance, Multiple, Bacterial ; Female ; Fosfomycin/pharmacology ; Humans ; Male ; Meropenem/pharmacology ; Microbial Sensitivity Tests ; Pseudomonas Infections/drug therapy ; Pseudomonas Infections/microbiology ; Pseudomonas aeruginosa/drug effects ; Pseudomonas aeruginosa/enzymology ; beta-Lactamases/genetics
    Chemical Substances Anti-Bacterial Agents ; Fosfomycin (2N81MY12TE) ; beta-Lactamases (EC 3.5.2.6) ; Meropenem (FV9J3JU8B1)
    Language English
    Publishing date 2019-05-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.00126-19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Pharmacodynamic Effects of Sulbactam/Meropenem/Polymyxin-B Combination Against Extremely Drug Resistant

    Menegucci, Thatiany Cevallos / Fedrigo, Nayara Helisandra / Lodi, Fernanda Gomes / Albiero, James / Nishiyama, Sheila Alexandra Belini / Mazucheli, Josmar / Carrara-Marroni, Floristher Elaine / Voelkner, Nivea Maria Falcão / Gong, Hui / Sy, Sherwin K B / Tognim, Maria Cristina Bronharo

    Microbial drug resistance (Larchmont, N.Y.)

    2019  Volume 25, Issue 9, Page(s) 1266–1274

    Abstract: Aim: ...

    Abstract Aim:
    MeSH term(s) Acinetobacter Infections/drug therapy ; Acinetobacter Infections/microbiology ; Acinetobacter baumannii/drug effects ; Acinetobacter baumannii/isolation & purification ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/pharmacokinetics ; Anti-Bacterial Agents/pharmacology ; Area Under Curve ; Dose-Response Relationship, Drug ; Drug Combinations ; Drug Resistance, Multiple, Bacterial ; Drug Synergism ; Humans ; Meropenem/administration & dosage ; Meropenem/pharmacokinetics ; Meropenem/pharmacology ; Microbial Sensitivity Tests ; Polymyxin B/administration & dosage ; Polymyxin B/pharmacokinetics ; Polymyxin B/pharmacology ; Sulbactam/administration & dosage ; Sulbactam/pharmacokinetics ; Sulbactam/pharmacology
    Chemical Substances Anti-Bacterial Agents ; Drug Combinations ; Meropenem (FV9J3JU8B1) ; Polymyxin B (J2VZ07J96K) ; Sulbactam (S4TF6I2330)
    Language English
    Publishing date 2019-06-19
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 1290490-9
    ISSN 1931-8448 ; 1076-6294
    ISSN (online) 1931-8448
    ISSN 1076-6294
    DOI 10.1089/mdr.2018.0283
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Pharmacodynamic Evaluation of Fosfomycin against Escherichia coli and Klebsiella spp. from Urinary Tract Infections and the Influence of pH on Fosfomycin Activities.

    Fedrigo, Nayara Helisandra / Mazucheli, Josmar / Albiero, James / Shinohara, Danielle Rosani / Lodi, Fernanda Gomes / Machado, Ana Cristina Dos Santos / Sy, Sherwin K B / Tognim, Maria Cristina Bronharo

    Antimicrobial agents and chemotherapy

    2017  Volume 61, Issue 8

    Abstract: Fosfomycin is widely used for the treatment of uncomplicated urinary tract infection (UTI), and it has recently been recommended that fosfomycin be used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacilli. Whether urine ... ...

    Abstract Fosfomycin is widely used for the treatment of uncomplicated urinary tract infection (UTI), and it has recently been recommended that fosfomycin be used to treat infections caused by multidrug-resistant (MDR) Gram-negative bacilli. Whether urine acidification can improve bacterial susceptibility to fosfomycin oral dosing regimens has not been analyzed. The MIC of fosfomycin for 245 Gram-negative bacterial isolates, consisting of 158
    Language English
    Publishing date 2017-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.02498-16
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Pharmacodynamic Evaluation of the Potential Clinical Utility of Fosfomycin and Meropenem in Combination Therapy against KPC-2-Producing Klebsiella pneumoniae.

    Albiero, James / Sy, Sherwin K B / Mazucheli, Josmar / Caparroz-Assef, Silvana Martins / Costa, Bruno Buranello / Alves, Janio Leal Borges / Gales, Ana Cristina / Tognim, Maria Cristina Bronharo

    Antimicrobial agents and chemotherapy

    2016  Volume 60, Issue 7, Page(s) 4128–4139

    Abstract: KPC-producing Klebsiella pneumoniae causes serious infections associated with high death rates worldwide. Combination therapy consisting of fosfomycin and a carbapenem is better than monotherapy to combat multidrug-resistant microorganisms, but no ... ...

    Abstract KPC-producing Klebsiella pneumoniae causes serious infections associated with high death rates worldwide. Combination therapy consisting of fosfomycin and a carbapenem is better than monotherapy to combat multidrug-resistant microorganisms, but no dosages for the combination have been defined. The MICs of meropenem and fosfomycin were evaluated against 18 clinical isolates of KPC-2-producing K. pneumoniae The activities of combination antimicrobials were also determined by the checkerboard method. The MIC50 and MIC90 of each agent alone and in combination were challenged against short (1.5-h) or prolonged (3-h) infusion regimens of meropenem (1 g every 8 h [q8h], 1.5 g q6h, 2 g q8h) and fosfomycin (4 g q8h, 6 g q6h, 8 g q8h) by Monte Carlo simulation to evaluate the time above the MIC of the free drug concentration as a percentage of the dosing interval (fT>MIC). The monotherapy MIC50s and MIC90s were 32 and 256 mg/liter for meropenem and 64 and 512 mg/liter for fosfomycin, respectively. Antimicrobial combination increased bacterial susceptibility to 1/4 the MIC50s and to 1/8 to 1/16 the MIC90s of monotherapy. The antimicrobial combination demonstrated a synergistic effect for at least two-thirds of the isolates. In combination therapy, fosfomycin regimens of 6 g q6h and 8 g q8h as a 3-h infusion against the MIC50 and MIC90 had better chances of achieving ≥90% probability of target attainment (PTA) of 70% fT>MIC. Meropenem regimens of 1.5 g q6h and 2 g q8h in prolonged infusion can achieve close to 90% PTA of 40% fT>MIC for MIC50 but not MIC90 The significant reduction in the MIC values and the achievement of appropriate PTA demonstrated that regimens containing fosfomycin with meropenem can be effective against KPC-2-producing K. pneumoniae.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Fosfomycin/pharmacology ; Klebsiella pneumoniae/drug effects ; Klebsiella pneumoniae/enzymology ; Microbial Sensitivity Tests ; Monte Carlo Method ; Thienamycins/pharmacology ; beta-Lactamases/genetics ; beta-Lactamases/metabolism
    Chemical Substances Anti-Bacterial Agents ; Thienamycins ; Fosfomycin (2N81MY12TE) ; beta-Lactamases (EC 3.5.2.6) ; meropenem (FV9J3JU8B1)
    Language English
    Publishing date 2016-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/AAC.03099-15
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Outbreak of Klebsiella pneumoniae carbapenemase-producing K pneumoniae: A systematic review.

    Campos, Anaelís C / Albiero, James / Ecker, Alessandra B / Kuroda, Cristina M / Meirelles, Lívia E F / Polato, Angelita / Tognim, Maria C B / Wingeter, Márcia A / Teixeira, Jorge J V

    American journal of infection control

    2016  Volume 44, Issue 11, Page(s) 1374–1380

    Abstract: Background: First detected in the United States in 1996, Klebsiella pneumoniae carbapenemase (KPC) has spread internationally among gram-negative bacteria, especially K pneumoniae. These microorganisms can cause serious infections in hospitalized ... ...

    Abstract Background: First detected in the United States in 1996, Klebsiella pneumoniae carbapenemase (KPC) has spread internationally among gram-negative bacteria, especially K pneumoniae. These microorganisms can cause serious infections in hospitalized patients, and there are few therapeutic options, culminating in increased mortality. The objective of this study was to describe the occurrence of outbreaks that were caused by KPC-producing K pneumoniae, emphasizing the interventions that were implemented to contain the outbreaks.
    Methods: PubMed, Web of Knowledge, and Literatura Latino Americana em Ciências da Saúde databases were searched for articles that were published between 2001 and 2012 according to the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
    Results: Of the 586 studies identified, 13 were selected for the final sample. Most studies showed that the containment of KPC outbreaks is possible in hospital settings through several actions, particularly use of surveillance cultures and the establishment of contact precautions.
    Conclusions: The results show that limiting the cross-transmission of these and other KPC-producing bacteria is possible in a hospital setting. However, such isolates need to be detected early with the aid of culture surveillance and contained early using appropriate actions immediately to prevent an outbreak.
    MeSH term(s) Bacterial Proteins/secretion ; Cross Infection/epidemiology ; Cross Infection/microbiology ; Cross Infection/prevention & control ; Disease Outbreaks ; Disease Transmission, Infectious/prevention & control ; Global Health ; Humans ; Infection Control/methods ; Klebsiella Infections/epidemiology ; Klebsiella Infections/microbiology ; Klebsiella Infections/prevention & control ; Klebsiella pneumoniae/enzymology ; Klebsiella pneumoniae/isolation & purification ; beta-Lactamases/secretion
    Chemical Substances Bacterial Proteins ; beta-Lactamases (EC 3.5.2.6) ; carbapenemase (EC 3.5.2.6)
    Language English
    Publishing date 2016-05-05
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 392362-9
    ISSN 1527-3296 ; 0196-6553
    ISSN (online) 1527-3296
    ISSN 0196-6553
    DOI 10.1016/j.ajic.2016.03.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Strategies for the treatment of polymyxin B-resistant Acinetobacter baumannii infections.

    Menegucci, Thatiany Cevallos / Albiero, James / Migliorini, Letícia Busato / Alves, Janio Leal Borges / Viana, Giselle Fukita / Mazucheli, Josmar / Carrara-Marroni, Floristher Elaine / Cardoso, Celso Luiz / Tognim, Maria Cristina Bronharo

    International journal of antimicrobial agents

    2016  Volume 47, Issue 5, Page(s) 380–385

    Abstract: In this study, the activity of meropenem (MEM), fosfomycin (FOF) and polymyxin B (PMB), alone and in combination, was analysed. In addition, optimisation of the pharmacodynamic index of MEM and FOF against six isolates of OXA-23-producing Acinetobacter ... ...

    Abstract In this study, the activity of meropenem (MEM), fosfomycin (FOF) and polymyxin B (PMB), alone and in combination, was analysed. In addition, optimisation of the pharmacodynamic index of MEM and FOF against six isolates of OXA-23-producing Acinetobacter baumannii (including three resistant to PMB) that were not clonally related was assessed. Antimicrobial combinations were evaluated by chequerboard analysis and were considered synergistic when the fractional inhibitory concentration index (FICI) was ≤0.5. Pharmacodynamic analyses of the MEM and FOF dosing schemes were performed by Monte Carlo simulation. The target pharmacodynamic index (%ƒT>MIC) for MEM and FOF was ≥40% and ≥70%, respectively, and a probability of target attainment (PTA) ≥0.9 was considered adequate. Among the PMB-resistant isolates, combinations of PMB+MEM and PMB+FOF+MEM showed the highest synergistic activity (FICI ≤0.125); isolates that were previously PMB-resistant were included in the susceptible category using CLSI interpretive criteria. Pharmacodynamic evaluation found that for a FOF minimum inhibitory concentration (MIC) of ≤16μg/mL, treatment both by bolus dosing and prolonged infusion achieved adequate PTA, whilst for MIC=32μg/mL only infusion achieved adequate PTA. For a MEM MIC of 4μg/mL, only the bolus treatment scheme with 1.5g q6h and the infusion schemes with 1.0g q8h, 1.5g q6h and 2.0g q8h achieved PTA ≥0.9. Results of antimicrobial and pharmacodynamic analyses can assist in treating infections caused by multidrug-resistant A. baumannii. However, in vivo clinical studies are essential to evaluate the true role of these compounds, including intravenous antimicrobial FOF therapy.
    MeSH term(s) Acinetobacter Infections/drug therapy ; Acinetobacter Infections/microbiology ; Acinetobacter baumannii/drug effects ; Acinetobacter baumannii/isolation & purification ; Anti-Bacterial Agents/pharmacokinetics ; Anti-Bacterial Agents/pharmacology ; Drug Resistance, Bacterial ; Drug Synergism ; Fosfomycin/pharmacokinetics ; Fosfomycin/pharmacology ; Humans ; Microbial Sensitivity Tests ; Monte Carlo Method ; Polymyxin B/pharmacokinetics ; Polymyxin B/pharmacology ; Thienamycins/pharmacokinetics ; Thienamycins/pharmacology
    Chemical Substances Anti-Bacterial Agents ; Thienamycins ; Polymyxin B (1404-26-8) ; Fosfomycin (2N81MY12TE) ; meropenem (FV9J3JU8B1)
    Language English
    Publishing date 2016-05
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1093977-5
    ISSN 1872-7913 ; 0924-8579
    ISSN (online) 1872-7913
    ISSN 0924-8579
    DOI 10.1016/j.ijantimicag.2016.02.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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