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  1. Article ; Online: In vivo

    Lepak, Alexander J / VanScoy, Brian / Rubino, Chris / Ambrose, Paul G / Andes, David R

    Antimicrobial agents and chemotherapy

    2024  Volume 68, Issue 3, Page(s) e0163123

    Abstract: SF001 is a next-generation polyene antifungal drug in development, designed to have increased specificity to fungal ergosterol, which is absent in humans, and decreased binding to cholesterol. SF001 demonstrates long-acting, potent, broad-spectrum ... ...

    Abstract SF001 is a next-generation polyene antifungal drug in development, designed to have increased specificity to fungal ergosterol, which is absent in humans, and decreased binding to cholesterol. SF001 demonstrates long-acting, potent, broad-spectrum fungicidal activity. The goal of the current study was to determine the pharmacodynamic index and target of SF001 in an immunocompromised mouse model of invasive pulmonary aspergillosis against six
    MeSH term(s) Humans ; Animals ; Mice ; Invasive Pulmonary Aspergillosis/drug therapy ; Invasive Pulmonary Aspergillosis/microbiology ; Antifungal Agents/therapeutic use ; Antifungal Agents/pharmacokinetics ; Aspergillus fumigatus ; Lung/microbiology ; Microbial Sensitivity Tests
    Chemical Substances Antifungal Agents
    Language English
    Publishing date 2024-02-06
    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.01631-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Diagnostic and Therapeutic Utility of Positive Intravascular Catheter Tip Cultures.

    Ulrich, Patrizia / Lepak, Alexander J / Chen, Derrick J

    Microbiology spectrum

    2022  , Page(s) e0402222

    Abstract: This study evaluated the performance and clinical utility of performing intravascular catheter tip cultures (CTC). A retrospective chart review was conducted over a 2.5 year period on all patients who demonstrated growth of at least one organism on CTC. ... ...

    Abstract This study evaluated the performance and clinical utility of performing intravascular catheter tip cultures (CTC). A retrospective chart review was conducted over a 2.5 year period on all patients who demonstrated growth of at least one organism on CTC. There were a total of 391 CTC performed. 88 (23%) grew at least one organism, while 303 (77%) had no growth. Of the positive CTC, 81 (92%) had blood cultures (BC) collected within 14 days, whereas 7 (8%) did not. Of the positive CTC with BC, 67 (83%) were BC-positive, whereas 14 (17%) were negative. For cases with growth on both CTC and BC, the organisms identified were concordant for 46 (69%) cases and discordant for 21 (31%). Of the concordant cases, 43 (93%) were clinically considered to be bacterial bloodstream infections that were secondary to a catheter infection. For all of the positive CTC cases total, there was no change in the antibiotics or management, with the exceptions of 2 out of 88 (2%) cases. Catheters were removed and cultured for an average of 38.6 h (range: -98 to 288 h) after positive BC results were available. Most CTC are negative, and for the CTC that are positive, most are concordant with BC results. CTC results are generally only available several days after positive BC results are known. The CTC results did not alter the antibiotic therapy or management, with the exceptions of rare cases. As such, this study concludes that CTC do not contribute diagnostic or therapeutic value. Therefore, current guidelines by the Infectious Diseases Society of America on catheter-related bloodstream infection diagnosis should be revised to exclude CTC collection.
    Language English
    Publishing date 2022-11-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.04022-22
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  3. Article ; Online: Letter to the Editor.

    Baus, Courtney J / Schulz, Lucas T / Lepak, Alexander J / Safdar, Nasia

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2021  Volume 73, Issue 8, Page(s) 1548

    Language English
    Publishing date 2021-07-28
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciab661
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  4. Article ; Online: Neutropenic Fever-Associated Admissions Among Patients With Solid Tumors Receiving Chemotherapy During the COVID-19 Pandemic.

    Baus, Courtney J / Kelley, Broc / Dow-Hillgartner, Elizabeth / Kyriakopoulos, Christos E / Schulz, Lucas T / Lepak, Alexander J / LoConte, Noelle K

    JAMA network open

    2023  Volume 6, Issue 3, Page(s) e234881

    MeSH term(s) Humans ; Pandemics ; COVID-19 ; Neoplasms/complications ; Neoplasms/drug therapy ; Hospitalization
    Language English
    Publishing date 2023-03-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2574-3805
    ISSN (online) 2574-3805
    DOI 10.1001/jamanetworkopen.2023.4881
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  5. Article ; Online: Pharmacodynamic Evaluation of MRX-8, a Novel Polymyxin, in the Neutropenic Mouse Thigh and Lung Infection Models against Gram-Negative Pathogens.

    Lepak, Alexander J / Wang, Wen / Andes, David R

    Antimicrobial agents and chemotherapy

    2020  Volume 64, Issue 11

    Abstract: MRX-8 is a novel polymyxin analogue in development for the treatment of infections caused by Gram-negative pathogens, including those resistant to other antibiotic classes. In the present study, we examined the pharmacodynamic activity of MRX-8 against a ...

    Abstract MRX-8 is a novel polymyxin analogue in development for the treatment of infections caused by Gram-negative pathogens, including those resistant to other antibiotic classes. In the present study, we examined the pharmacodynamic activity of MRX-8 against a variety of common Gram-negative pathogens in the neutropenic mouse thigh and lung models. Additionally, we examined polymyxin B (PMB) as a comparator. Plasma pharmacokinetics of MRX-8 and PMB were linear over a broad dosing range of 0.156 to 10 mg/kg of body weight and had similar AUC
    MeSH term(s) Animals ; Anti-Bacterial Agents/therapeutic use ; Escherichia coli ; Lung ; Mice ; Microbial Sensitivity Tests ; Polymyxins ; Thigh
    Chemical Substances Anti-Bacterial Agents ; Polymyxins
    Language English
    Publishing date 2020-10-20
    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.01517-20
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  6. Article ; Online: WCK 5222 (Cefepime/Zidebactam) Pharmacodynamic Target Analysis against Metallo-β-lactamase producing

    Lepak, Alexander J / Zhao, Miao / Andes, David R

    Antimicrobial agents and chemotherapy

    2019  Volume 63, Issue 12

    Abstract: WCK 5222 is a combination of cefepime and the novel β-lactam enhancer (BLE) zidebactam. Zidebactam has a dual mechanism of action involving high-affinity penicillin binding protein (PBP) 2 binding as well as inhibition of Ambler class A, and C, enzymes. ... ...

    Abstract WCK 5222 is a combination of cefepime and the novel β-lactam enhancer (BLE) zidebactam. Zidebactam has a dual mechanism of action involving high-affinity penicillin binding protein (PBP) 2 binding as well as inhibition of Ambler class A, and C, enzymes. In the current study, we evaluated the effect of zidebactam on the cefepime pharmacodynamic target time above MIC (T>MIC) exposure required for efficacy against a diverse group of carbapenem-resistant
    Language English
    Publishing date 2019-10-07
    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.01648-19
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  7. Article ; Online: Clinical Utility of Dual Anterior Nares and Oropharynx MRSA Screening PCR for Patients with Suspected Pneumonia - ERRATUM.

    Kessler, Michael A / Biswas, Sandip / Choera, Tsokyi / Chen, Derrick J / Lepak, Alexander J

    Infection control and hospital epidemiology

    2021  Volume 43, Issue 9, Page(s) 1313

    MeSH term(s) Carrier State/diagnosis ; Humans ; Methicillin-Resistant Staphylococcus aureus/genetics ; Nasal Cavity ; Oropharynx ; Pneumonia ; Polymerase Chain Reaction ; Staphylococcal Infections/diagnosis
    Language English
    Publishing date 2021-12-21
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 639378-0
    ISSN 1559-6834 ; 0195-9417 ; 0899-823X
    ISSN (online) 1559-6834
    ISSN 0195-9417 ; 0899-823X
    DOI 10.1017/ice.2021.508
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  8. Article ; Online: Determination of Pharmacodynamic Target Exposures for Rezafungin against Candida tropicalis and Candida dubliniensis in the Neutropenic Mouse Disseminated Candidiasis Model.

    Lepak, Alexander J / Zhao, Miao / Andes, David R

    Antimicrobial agents and chemotherapy

    2019  Volume 63, Issue 11

    Abstract: Rezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against ... ...

    Abstract Rezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against 4
    MeSH term(s) Animals ; Antifungal Agents/administration & dosage ; Antifungal Agents/pharmacokinetics ; Antifungal Agents/pharmacology ; Antifungal Agents/therapeutic use ; Candida/drug effects ; Candida tropicalis/drug effects ; Candidiasis, Invasive/drug therapy ; Disease Models, Animal ; Drug Administration Schedule ; Echinocandins/administration & dosage ; Echinocandins/pharmacokinetics ; Echinocandins/pharmacology ; Echinocandins/therapeutic use ; Mice ; Microbial Sensitivity Tests ; Neutropenia/microbiology
    Chemical Substances Antifungal Agents ; Echinocandins ; Rezafungin (G013B5478J)
    Language English
    Publishing date 2019-10-22
    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.01556-19
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  9. Article ; Online: Clinical Utility of Dual Anterior Nares and Oropharynx MRSA Screening PCR for Patients with Suspected Pneumonia.

    Kessler, Michael A / Biswas, Sandip / Choera, Tsokyi / Chen, Derrick J / Lepak, Alexander J

    Infection control and hospital epidemiology

    2021  Volume 43, Issue 9, Page(s) 1242–1244

    Abstract: We reviewed the electronic health records of 1,419 inpatients with anterior nares (AN) and oropharynx (OP) MRSA PCR tests. Concordance was 96.5%. In discordant cases, AN negative-OP positive results increased detection of probable MRSA pneumonia by only ... ...

    Abstract We reviewed the electronic health records of 1,419 inpatients with anterior nares (AN) and oropharynx (OP) MRSA PCR tests. Concordance was 96.5%. In discordant cases, AN negative-OP positive results increased detection of probable MRSA pneumonia by only 0.3%. A dual testing approach has limited utility in detecting MRSA pneumonia and increases resource utilization.
    MeSH term(s) Humans ; Methicillin-Resistant Staphylococcus aureus/genetics ; Nasal Cavity ; Oropharynx ; Pneumonia, Staphylococcal/diagnosis ; Polymerase Chain Reaction/methods ; Staphylococcal Infections/diagnosis
    Language English
    Publishing date 2021-11-22
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639378-0
    ISSN 1559-6834 ; 0195-9417 ; 0899-823X
    ISSN (online) 1559-6834
    ISSN 0195-9417 ; 0899-823X
    DOI 10.1017/ice.2021.463
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  10. Article ; Online: Pharmacodynamic Evaluation of Rezafungin (CD101) against Candida auris in the Neutropenic Mouse Invasive Candidiasis Model.

    Lepak, Alexander J / Zhao, Miao / Andes, David R

    Antimicrobial agents and chemotherapy

    2018  Volume 62, Issue 11

    Abstract: Rezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against ... ...

    Abstract Rezafungin (CD101) is a novel echinocandin under development for once-weekly intravenous (i.v.) dosing. We evaluated the pharmacodynamics (PD) of rezafungin against 4
    MeSH term(s) Animals ; Antifungal Agents/pharmacology ; Candida/drug effects ; Candidiasis/drug therapy ; Disease Models, Animal ; Echinocandins/pharmacology ; Mice ; Microbial Sensitivity Tests/methods
    Chemical Substances Antifungal Agents ; Echinocandins ; Rezafungin (G013B5478J)
    Language English
    Publishing date 2018-10-24
    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.01572-18
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