Effectiveness of combination therapy versus monotherapy with a third-generation cephalosporin in bacteraemic pneumococcal pneumonia: A propensity score analysis

Calle, C. de la; Vega, Hugo Guillermo Ternavasio-de la; Morata, Laura; Marco, Francesc; Cardozo, Celia; García-Vidal, Carolina; Rı́o, Ana del; Cillóniz, Catia; Martínez, José Antonio; Soriano, Álex

doi:10.1016/j.jinf.2018.01.003

Cited by 15 publications

(11 citation statements)

References 42 publications

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“…Although multiple studies show evidence that inflammation in the gut as well as several diseases are associated with an altered gut-brain communication, evidence for a successful therapy in response to these complaints is rare (180). Two widely discussed therapies are probiotic interventions (95,185,186,223,224) and fecal microbiota transplantation (FMT) (225)(226)(227)(228).…”

Section: Possible Microbiome Therapies In Me/cfs Patientsmentioning

confidence: 99%

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

et al. 2022

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Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.

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Section: Possible Microbiome Therapies In Me/cfs Patientsmentioning

confidence: 99%

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

et al. 2022

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“…This is supported by a meta-analysis of studies on the clinical outcome of CAP and bacteraemia showing reduced mortality with macrolide-containing regimens [6] , but the mechanism underpinning this decreased mortality is not known. In hospitalised adults with proven pneumococcal pneumonia, treatment with a combination of a beta-lactam and macrolide antibiotic has also been found to be associated with lower mortality compared to beta-lactams alone [ 33 , 34 ]. Possible explanations for the added beneficial effect of macrolides include; 1) a broader spectrum of antibiotic activity encompassing penicillin-resistant organisms, although clinically relevant resistance to beta-lactams is infrequent [35] ; 2) concurrent anti-inflammatory or immunomodulatory effects reducing proinflammatory cytokine responses [32] ; and 3) interference with pneumococcal virulence factors such as pneumolysin [36] .…”

Section: Discussionmentioning

confidence: 99%

Splenic macrophages as the source of bacteraemia during pneumococcal pneumonia

et al. 2021

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Background Severe community-acquired pneumococcal pneumonia is commonly associated with bacteraemia. Although it is assumed that the bacteraemia solely derives from pneumococci entering the blood from the lungs it is unknown if other organs are important in the pathogenesis of bacteraemia. Using three models, we tested the relevance of the spleen in pneumonia-associated bacteraemia. Methods We used human spleens perfused ex vivo to explore permissiveness to bacterial replication, a non-human primate model to check for splenic involvement during pneumonia and a mouse pneumonia-bacteraemia model to demonstrate that splenic involvement correlates with invasive disease. Findings Here we present evidence that the spleen is the reservoir of bacteraemia during pneumonia. We found that in the human spleen infected with pneumococci, clusters with increasing number of bacteria were detectable within macrophages. These clusters also were detected in non-human primates. When intranasally infected mice were treated with a non-therapeutic dose of azithromycin, which had no effect on pneumonia but concentrated inside splenic macrophages, bacteria were absent from the spleen and blood and importantly mice had no signs of disease. Interpretation We conclude that the bacterial load in the spleen, and not lung, correlates with the occurrence of bacteraemia. This supports the hypothesis that the spleen, and not the lungs, is the major source of bacteria during systemic infection associated with pneumococcal pneumonia; a finding that provides a mechanistic basis for using combination therapies including macrolides in the treatment of severe community-acquired pneumococcal pneumonia. Funding Oxford University, Wolfson Foundation, MRC, NIH, NIHR, and MRC and BBSRC studentships supported the work.

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“…Non-interventional trials suggest that beta-lactam/macrolide combination therapy is associated with lower mortality, especially in patients with pneumococcal bacteremia [53].…”

Section: The Evidencementioning

confidence: 99%

Challenges in severe community-acquired pneumonia: a point-of-view review

et al. 2019

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Purpose: Severe community-acquired pneumonia (SCAP) is still associated with substantial morbidity and mortality. In this point-of-view review paper, a group of experts discuss the main controversies in SCAP: the role of severity scores to guide patient settings of care and empiric antibiotic therapy; the emergence of pathogens outside the core microorganisms of CAP; viral SCAP; the best empirical treatment; septic shock as the most lethal complication; and the need for new antibiotics. Methods: For all topics, the authors describe current controversies and evidence and provide recommendations and suggestions for future research. Evidence was based on meta-analyses, most recent RCTs and recent interventional or observational studies. Recommendations were reached by consensus of all the authors. Results and conclusions: The IDSA/ATS criteria remain the most pragmatic tool to predict ICU admission. The authors recommend a combination of a beta-lactam/beta-lactamase inhibitor or a third G cephalosporin plus a macrolide in most SCAP patients, and to empirically cover PES (P. aeruginosa, extended spectrum beta-lactamase producing Enterobacteriaceae, methicillin-resistant S. aureus) pathogens when at least two specific risk factors are present. In patients with influenza CAP, the authors recommend the use of oseltamivir and avoidance of the use of steroids. Corticosteroids can be used in case of refractory shock and high systemic inflammatory response.

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Effectiveness of combination therapy versus monotherapy with a third-generation cephalosporin in bacteraemic pneumococcal pneumonia: A propensity score analysis

Cited by 15 publications

References 42 publications

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

The Gut Microbiome in Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Splenic macrophages as the source of bacteraemia during pneumococcal pneumonia

Challenges in severe community-acquired pneumonia: a point-of-view review

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