Evidence map›Paper›PMID 34435316›Full record

ReviewPaediatric drugs2021

Potential Antibiotics for the Treatment of Neonatal Sepsis Caused by Multidrug-Resistant Bacteria.

Christopher A Darlow, Renata M A da Costa, Sally Ellis, François Franceschi, Mike Sharland, Laura Piddock, Shampa Das, William Hope

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Paediatric drugs, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
6.5field-weighted citation impact, top 3% 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

20 citing papers in PubMed, 46 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

Christopher A DarlowAntimicrobial Pharmacodynamics and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool Health Partners, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK. cdarlow@liverpool.ac.uk.ORCID http://orcid.org/0000-0002-5400-3413
Renata M A da CostaGlobal Antibiotic Research and Development Partnership, Geneva, Switzerland.
Sally EllisGlobal Antibiotic Research and Development Partnership, Geneva, Switzerland.
François FranceschiGlobal Antibiotic Research and Development Partnership, Geneva, Switzerland.
Mike SharlandPaediatric Infectious Diseases Research Group, St George's University of London, London, UK.
Laura PiddockGlobal Antibiotic Research and Development Partnership, Geneva, Switzerland.
Shampa DasAntimicrobial Pharmacodynamics and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool Health Partners, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.
William HopeAntimicrobial Pharmacodynamics and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool Health Partners, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, UK.
Global Antibiotic Research & Development Partnership · CHUniversity of Liverpool · GBSt George's, University of London · GB

Funding

Medical Research Council MR/N025989/1
6 · The paper itself

Abstract

Neonatal sepsis causes up to an estimated 680,000 deaths annually worldwide, predominantly in low- and middle-income countries (LMICs). A significant and growing proportion of bacteria causing neonatal sepsis are resistant to multiple antibiotics, including the World Health Organization-recommended empiric neonatal sepsis regimen of ampicillin/gentamicin. The Global Antibiotic Research and Development Partnership is aiming to develop alternative empiric antibiotic regimens that fulfil several criteria: (1) affordable in LMIC settings; (2) activity against neonatal bacterial pathogens, including extended-spectrum β-lactamase producers, gentamicin-resistant Gram-negative bacteria, and methicillin-resistant Staphylococcus aureus (MRSA); (3) a licence for neonatal use or extensive experience of use in neonates; and (4) minimal toxicities. In this review, we identify five antibiotics that fulfil these criteria: amikacin, tobramycin, fosfomycin, flomoxef, and cefepime. We describe the available characteristics of each in terms of mechanism of action, resistance mechanisms, clinical pharmacokinetics, pharmacodynamics, and toxicity profile. We also identify some knowledge gaps: (1) the neonatal pharmacokinetics of cefepime is reliant on relatively small and limited datasets, and the pharmacokinetics of flomoxef are also reliant on data from a limited demographic range and (2) for all reviewed agents, the pharmacodynamic index and target has not been definitively established for both bactericidal effect and emergence of resistance, with many assumed to have an identical index/target to similar class molecules. These five agents have the potential to be used in novel combination empiric regimens for neonatal sepsis. However, the data gaps need addressing by pharmacokinetic trials and pharmacodynamic characterisation.

Indexed as

Methicillin-Resistant Staphylococcus aureusNeonatal SepsisSepsisAnti-Bacterial AgentsBacteriaDrug Resistance, Multiple, BacterialHumansInfant, NewbornMicrobial Sensitivity TestsAnti-Bacterial Agents

Identifiers

PMID34435316
PMCPMC8418595
OpenAlexW3193478222

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.