In vitro antimicrobial activity of daptomycin alone and in adjunction with either amoxicillin, cefotaxime or rifampicin against the main pathogens responsible for bacterial meningitis in adults

Maldiney, Thomas; Bonnot, Dorian; Anzala, Nelson; Albac, Sandrine; Labrousse, Delphine; Varon, Emmanuelle; Amoureux, Lucie; Chapuis, Angélique; Bador, Julien; Neuwirth, Catherine; Croisier, Delphine; Chavanet, P.

doi:10.1016/j.jgar.2021.03.007

Cited by 7 publications

(11 citation statements)

References 22 publications

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“…Using bactericidal but non-bacteriolytic antibiotics such as daptomycin may bypass this problem (Principi and Esposito, 2020 ). The adjunction of daptomycin in the treatment of bacterial meningitis has recently proven its therapeutic potential in vitro (Maldiney et al, 2021 ) and it is the subject of an ongoing clinical trial to improve the prognosis and survival of pneumococcal meningitis (AddaMAP, NCT03480191). Finally, due to its relevance in neuroinflammation and brain disease, and its implication in neuron cell death, inflammasome modulation is considered a promising target in the context of bacterial meningitis (Walsh et al, 2014 ) and neurodegenerative diseases (Heneka et al, 2018 ).…”

Section: Translational Approaches To Prevent Infection-derived Neuronal Damagementioning

confidence: 99%

Neuronal Damage and Neuroinflammation, a Bridge Between Bacterial Meningitis and Neurodegenerative Diseases

Farmen

Tofiño-Vian

Iovino

2021

Front. Cell. Neurosci.

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Bacterial meningitis is an inflammation of the meninges which covers and protects the brain and the spinal cord. Such inflammation is mostly caused by blood-borne bacteria that cross the blood-brain barrier (BBB) and finally invade the brain parenchyma. Pathogens such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae are the main etiological causes of bacterial meningitis. After trafficking across the BBB, bacterial pathogens in the brain interact with neurons, the fundamental units of Central Nervous System, and other types of glial cells. Although the specific molecular mechanism behind the interaction between such pathogens with neurons is still under investigation, it is clear that bacterial interaction with neurons and neuroinflammatory responses within the brain leads to neuronal cell death. Furthermore, clinical studies have shown indications of meningitis-caused dementia; and a variety of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are characterized by the loss of neurons, which, unlike many other eukaryotic cells, once dead or damaged, they are seldom replaced. The aim of this review article is to provide an overview of the knowledge on how bacterial pathogens in the brain damage neurons through direct and indirect interactions, and how the neuronal damage caused by bacterial pathogen can, in the long-term, influence the onset of neurodegenerative disorders.

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Section: Translational Approaches To Prevent Infection-derived Neuronal Damagementioning

confidence: 99%

Neuronal Damage and Neuroinflammation, a Bridge Between Bacterial Meningitis and Neurodegenerative Diseases

Farmen

Tofiño-Vian

Iovino

2021

Front. Cell. Neurosci.

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“…1 In addition, the in vitro activity and safety profile of daptomycin, despite its low CSF penetration, could lead to its consideration as alternative medication for the treatment of bacterial meningitis. 4 Therefore, despite a paucity of available evidence, additional therapy with nonbacteriolytic antibiotics may provide further protection against mortality and adverse neurological sequelae in patients with bacterial meningitis.…”

Section: Review Of Progress and Challenges In Bacterial Meningitismentioning

confidence: 99%

“…Since that study was published, adjunctive dexamethasone has been recommended by meningitis guidelines for pneumococcal meningitis, and I am not aware of any published studies that examine whether this benefit persists in patients receiving steroids. 1 Furthermore, use of daptomycin at high doses (10 mg/kg) has resulted in minimal CSF penetration in patients with meningitis, 4 and case reports have reported clinical failure. 5 In addition, daptomycin has not been formally recommended by recent UK guidelines on meningitis.…”

Section: Simone Giuliano MD Francesco Sbrana Md Carlo Tascini Mdmentioning

confidence: 99%

“…It is important to consider the potential effect of additional rifampin therapy on toxin release, and we believe that pretreatment or concomitant therapy with rifampin should have been included in this Review . In addition, the in vitro activity and safety profile of daptomycin, despite its low CSF penetration, could lead to its consideration as alternative medication for the treatment of bacterial meningitis . Therefore, despite a paucity of available evidence, additional therapy with nonbacteriolytic antibiotics may provide further protection against mortality and adverse neurological sequelae in patients with bacterial meningitis.…”

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confidence: 99%

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Review of Progress and Challenges in Bacterial Meningitis

Giuliano

Sbrana

Tascini

2023

JAMA

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“…The well-known lipopeptide daptomycin is highly active against susceptible or resistant pneumococci,47–49 and it interacts synergistically with cephalosporins 38. It has a low resistance rate48 and above all, it has been shown to be highly bactericidal but without initiating lysis both in vitro49 and in vivo in murine and rabbit models of meningitis50 51 even against cephalosporin-resistant pneumococci 52 53…”

Section: Introductionmentioning

confidence: 99%

Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study

et al. 2023

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BackgroundThe leading cause of acute bacterial meningitis in adults isStreptococcus pneumoniae. This infection is associated with high rates of mortality and morbidity related, among other factors, to the excessive host response to the pneumococcal lysis. Experimental in vitro and in vivo data show that the combination of corticosteroids/third-generation cephalosporins and the non-lytic antibiotic, daptomycin, has synergistic effects with (1) a rapid cerebrospinal fluid sterilisation, (2) less brain damages and (3) less loss of cognitive performances. Despite these encouraging results, daptomycin has never been evaluated in adult patients with pneumococcal meningitis.Methods and analysisThe AddaMAP trial is a phase II, open-label, Simon’s two-stage, multicentre trial that has been designed to assess the efficacy and safety of adding daptomycin (10 mg/kg/d for 8 days) to the recommended treatment (corticosteroids+third generation cephalosporin) in adults with confirmed pneumococcal meningitis. The main endpoint is the disability-free survival (defined as modified Rankin Scale mRS≤2) at day 30. Secondary outcomes are overall mortality, disability at D30 and D90 (mRS, Glasgow Coma Scale and Glasgow Outcome Scales, mini-mental score), hearing loss (Hearing Handicap Inventory Test at D30 and D90, routine audiometric test and Hearing-it test at D30), and quality of life (12-item Short Form Survey and WHO QOL BREF). Seventy-two analysable patients are required.Ethics and disseminationThe study protocol was approved by the Institutional Review Board of the IDF 1 of the ethics committee on 16 January 2018, and authorisation was obtained from the Agence Nationale de Securité des Médicaments et des Produits de Santé on 22 September 2017. The results will be submitted for publication in a peer-reviewed journal.Trial registration numberNCT03480191.

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In vitro antimicrobial activity of daptomycin alone and in adjunction with either amoxicillin, cefotaxime or rifampicin against the main pathogens responsible for bacterial meningitis in adults

Cited by 7 publications

References 22 publications

Neuronal Damage and Neuroinflammation, a Bridge Between Bacterial Meningitis and Neurodegenerative Diseases

Neuronal Damage and Neuroinflammation, a Bridge Between Bacterial Meningitis and Neurodegenerative Diseases

Review of Progress and Challenges in Bacterial Meningitis

Addition of daptomycin for the treatment of pneumococcal meningitis: protocol for the AddaMAP study

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