Evidence map›Paper›PMID 37726063›Full record

ArticleInternational journal of antimicrobial agents2023

Meropenem-vaborbactam restoration of first-line drug efficacy and comparison of meropenem-vaborbactam-moxifloxacin versus BPaL MDR-TB regimen.

Sanjay Singh, Tawanda Gumbo, Jan-Willem Alffenaar, Gunavanthi D Boorgula, Prem Shankar, Tania A Thomas, Keertan Dheda, Lesibana Malinga, Prithvi Raj, Santosh Aryal and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of antimicrobial agents, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 34% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Toward better cures forClinical microbiology reviews · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 7 institutions in 3 countries.

Sanjay SinghDepartment of Medicine, School of Medicine, University of Texas at Tyler, Tyler, TX, USA.
Tawanda GumboQuantitative Preclinical & Clinical Sciences Department, Praedicare Inc., Dallas, TX, USA; Hollow Fiber System & Experimental Therapeutics Laboratories, Praedicare Inc, Dallas, TX, USA.
Jan-Willem AlffenaarSydney Institute for Infectious Diseases, The University of Sydney, Sydney, New South Wales, Australia; School of Pharmacy, The University of Sydney Faculty of Medicine and Health, Sydney, New South Wales, Australia; Westmead Hospital, Sydney, New South Wales, Australia.
Gunavanthi D BoorgulaDepartment of Medicine, School of Medicine, University of Texas at Tyler, Tyler, TX, USA.
Prem ShankarDepartment of Medicine, School of Medicine, University of Texas at Tyler, Tyler, TX, USA.
Tania A ThomasDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA.
Keertan DhedaThe Center for Lung Infection and Immunity Unit, Division of Pulmonology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Lesibana MalingaDepartment of Medical Microbiology, University of Pretoria, Pretoria, South Africa.
Prithvi RajDepartment of Immunology, UT Southwestern Medical Center, Dallas, TX, USA.
Santosh AryalDepartment of Pharmaceutical Sciences and Health Outcomes, The Ben and Maytee Fisch College of Pharmacy, University of Texas at Tyler, Tyler, TX, USA.
Shashikant SrivastavaDepartment of Medicine, School of Medicine, University of Texas at Tyler, Tyler, TX, USA; Department of Cellular and Molecular Biology, UT Health Science Centre at Tyler, Tyler, TX, US. Electronic address: Shashi.kant@uthct.edu.
The University of Texas at Tyler · USBenedictine University · USSouthwestern Medical Center · USThe University of Sydney · AUUniversity of Cape Town · ZAUniversity of Pretoria · ZAUniversity of Virginia · US

Funding

PK/PD Optimized Cephalosporins Based Treatment Regimens for Children With MDR-TBR01HD099756 · NICHD · UNIVERSITY OF TEXAS HLTH CTR AT TYLER · PI KANT, SHASHI · 2019 to 2023
$1.6M
NICHD NIH HHS R01 HD099756
6 · The paper itself

Abstract

backgroundMeropenem in combination with β-lactamase inhibitors (BLIs) and other drugs was tested to identify alternative treatment regimens for multidrug-resistant tuberculosis (MDR-TB).

methodsThe following were performed: (1) MIC experiments; (2) static time-kill studies (STKs) with different BLIs; and (3) a hollow fibre model system of TB (HFS-TB) studies with meropenem-vaborbactam combined with human equivalent daily doses of 20 mg/kg or 35 mg/kg rifampin, or moxifloxacin 400 mg, or linezolid 600 mg vs. bedaquiline-pretonamid-linezolid (BPaL) for MDR-TB. The studies were performed using Mycobacterium tuberculosis (M. tuberculosis) H37Rv and an MDR-TB clinical strain (named M. tuberculosis 16D) that underwent whole genome sequencing. Exponential decline models were used to calculate the kill rate constant (K) of different HFS-TB regimens.

resultsWhole genome sequencing revealed mutations associated with resistance to rifampin, isoniazid, and cephalosporins. The meropenem-vaborbactam MIC of M. tuberculosis was H37Rv 2 mg/L and > 128 mg/L for M. tuberculosis 16D. Relebactam and vaborbactam improved both the potency and efficacy of meropenem in STKs. Meropenem-vaborbactam alone failed to kill M. tuberculosis 16D but killed below day 0 burden when combined with isoniazid and rifampin, with the moxifloxacin combination being the most effective and outranking bedaquiline and pretomanid. In the HFS-TB, meropenem-vaborbactam-moxifloxacin and BPaL had the highest K (log

conclusionAdding meropenem-vaborbactam could potentially restore the efficacy of isoniazid and rifampin against MDR-TB. The meropenem-vaborbactam-moxifloxacin backbone regimen has implications for creating a new effective MDR-TB regimen.

Indexed as

Mycobacterium tuberculosisTuberculosis, Multidrug-ResistantAntitubercular Agentsbeta-Lactamase InhibitorsBoronic AcidsDiarylquinolinesHumansIsoniazidLinezolidMeropenemMoxifloxacinRifampinAntitubercular Agentsbedaquilinebeta-Lactamase InhibitorsBoronic AcidsDiarylquinolinesIsoniazidLinezolidMeropenemMoxifloxacinRifampinvaborbactamBeta-lactamsBPaLHollow fiber model systemMultidrug-resistant tuberculosisPharmacokinetics/pharmacodynamics

Identifiers

PMID37726063
PMCPMC10850916
OpenAlexW4386811551

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.