Effect of Clarithromycin in Patients with Sepsis and Ventilator‐Associated Pneumonia

Giamarellos‐Bourboulis, Evangelos J.; Péchère, Jean-Claude; Routsi, Christina; Plachouras, Diamantis; Kollias, Spyridon; Rosario, Maria; Zervakis, Dimitrios; Baziaka, Fotini; Koronaios, Apostolos; Antonopoulou, Anastasia; Markaki, Vasiliki; Koutoukas, Pantelis; Papadomichelakis, Evangelos; Τσαγανός, Θωμάς; Armaganidis, Apostolos; Koussoulas, Vassilios; Κοτανίδου, Αναστασία; Roussos, Charis; Giamarellou, Helen

doi:10.1086/529439

Cited by 148 publications

(104 citation statements)

References 29 publications

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“…This modulation was pronounced in patients with septic shock and MODS, although significant effects were found, albeit to a lesser extent, in patients without septic shock and MODS. Septic shock and MODS were the main drivers for death in this study (4). These patients were almost 35% of the total enrolled patients, and their number was adequate to draw safe statistical conclusions.…”

Section: Discussionmentioning

confidence: 87%

“…The resulting normally distributed variables were subsequently subjected to the two-way analysis of variance (ANOVA) procedure with the treatment (placebo/clarithromycin) and the presence of MODS and septic shock (no/yes) as the between-subjects factors. This was done because a significant benefit in mortality was found in that subgroup of patients (4). Apart from the main effects, the two-way interaction effect (treatment group by presence of septic shock and MODS) was considered.…”

Section: Methodsmentioning

confidence: 99%

“…Thirty-six of the patients allocated to placebo and 33 of the patients allocated to clarithromycin, i.e., 69 in total, presented with septic shock and MODS. The two treatment groups did not differ in their clinical characteristics, namely, gender, age, underlying diseases, disease severity, implicated pathogens, and appropriateness of administered antimicrobials, as presented in detail elsewhere (4).…”

Section: Study Populationmentioning

confidence: 99%

“…Twenty-five patients allocated to the placebo group and 22 patients allocated to the clarithromycin group were undergoing replacement therapy with low intravenous doses of hydrocortisone to compensate for stress (4). Since hydrocortisone is an anti-inflammatory agent, the possibility of an interaction with clarithromycin in any of the measured parameters was investigated.…”

Section: Study Populationmentioning

confidence: 99%

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Effect of Clarithromycin in Inflammatory Markers of Patients with Ventilator-Associated Pneumonia and Sepsis Caused by Gram-Negative Bacteria: Results from a Randomized Clinical Study

Spyridaki

Rosario

Antonopoulou

et al. 2012

Antimicrob Agents Chemother

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dOne recent, double-blind, randomized clinical trial with 200 patients showed that clarithromycin administered intravenously for 3 days in patients with ventilator-associated pneumonia (VAP) accelerated the resolution of pneumonia and decreased the risk of death from septic shock and multiple organ dysfunctions (MODS). The present study focused on the effect of clarithromycin on markers of inflammation in these patients. Blood was drawn immediately before the administration of the allocated treatment and on six consecutive days after the start of treatment. The concentrations of circulating markers were measured. Monocytes and neutrophils were isolated for immunophenotyping analysis and for cytokine stimulation. The ratio of serum interleukin-10 (IL-10) to serum tumor necrosis factor alpha (TNF-␣) was decreased in the clarithromycin group compared with the results in the placebo group. Apoptosis of monocytes was significantly increased on day 4 in the clarithromycin group compared with the rate of apoptosis in the placebo group. On the same day, the expression of CD86 was increased and the ratio of soluble CD40 ligand (sCD40L) to CD86 in serum was unchanged. The release of TNF-␣, IL-6, and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by circulating monocytes after stimulation was greater in the clarithromycin group than in the placebo group. The expression of TREM-1 on monocytes was also increased in the former group. These effects were pronounced in patients with septic shock and MODS. These results suggest that the administration of clarithromycin restored the balance between proinflammatory versus anti-inflammatory mediators in patients with sepsis; this was accompanied by more efficient antigen presentation and increased apoptosis. These effects render new perspectives for the immunotherapy of sepsis.

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Section: Discussionmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

Section: Study Populationmentioning

confidence: 99%

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Effect of Clarithromycin in Inflammatory Markers of Patients with Ventilator-Associated Pneumonia and Sepsis Caused by Gram-Negative Bacteria: Results from a Randomized Clinical Study

Spyridaki

Rosario

Antonopoulou

et al. 2012

Antimicrob Agents Chemother

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“…Un essai contrôlé au cours des PAVM à bacilles à Gram négatif n'a cependant pas montré d'effet favorable [43]. Des données expérimentales suggèrent l'efficacité d'anticorps monoclonaux anti-PcrV, facteur-clé de la virulence chez P. aeruginosa (appareil de sécrétion de type III) [44].…”

Section: Perspectives Immunologiquesunclassified

Multirésistance chezPseudomonas aeruginosa

Barbier

Wolff

2010

Med Sci (Paris)

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Pseudomonas aeruginosa occupe une position centrale dans la problématique actuelle des infections nosocomiales (IN). Ce bacille à Gram négatif ubiquitaire est responsable de 10 % à 15 % de l'ensemble des infections nosocomiales, une fréquence supérieure étant rapportée chez certaines catégories de patients à haut risque : pathologies broncho-pulmonaires chroniques (notamment la mucoviscidose), immunodépression (neutropénie, syndrome d'immunodéficience acquise), grands > Pseudomonas aeruginosa est un pathogène nosocomial majeur, en particulier chez les patients atteints de mucoviscidose et dans les services de réanimation. L'augmentation actuelle de l'incidence des souches multirésistantes de P. aeruginosa (PAMR) et les phénomènes épidémi-ques locaux qui en résultent sont donc particuliè-rement inquiétants. Ces souches sont définies par la résistance à au moins trois des quatre principales classes d'antibiotiques anti-Pseudomonas (pénicillines/céphalosporines/monobactames, carbapénèmes, aminosides et fluoroquinolones). Elles cumulent constamment plusieurs méca-nismes de résistance aux antibiotiques (efflux, imperméabilité, modification du site d'action ou inactivation enzymatique), conséquences d'évé-nements génétiques multiples (mutations et/ou transfert horizontal de gènes de résistance). La pression de sélection induite par une ou plusieurs antibiothérapies préalables est le principal facteur de risque d'infection à PAMR. La colistine (polymyxine E) reste active sur la quasi-totalité de ces souches et constitue fréquemment la dernière option thérapeutique disponible, au prix d'un risque non négligeable de néphrotoxicité. L'émergence d'isolats résistants à la colistine, actuellement exceptionnelle, fait cependant craindre une évolution vers la panrésistance dans un avenir proche. < [1,3]. Si la sévérité des infections nosocomiales à P. aeruginosa est conditionnée par la virulence propre à l'espèce et par les comorbidités des patients concernés, elle dépend également de la capacité du pathogène à accumuler les mécanismes de résistance aux antibiotiques et des difficultés thérapeutiques qui en résultent. Ces résistances acquises s'ajoutent aux nombreuses résistances naturelles de l'espèce et peuvent concerner l'ensemble des classes actives sur les souches sauvages (Tableau I). La prévalence globale des souches multirésistantes de P. aeruginosa (PAMR) reste actuellement peu élevée, notamment en France, avec d'importantes variations épidémiologiques locales. Elle a cependant augmenté de façon significative au cours des deux dernières décen-nies, en particulier dans les services de réanimation [4][5][6][7]. La colistine constitue fréquemment la dernière option thérapeutique disponible pour les isolats résistants à toutes les autres molécules. L'objectif de cette revue est de synthétiser les données disponibles sur les méca-nismes moléculaires, l'épidémiologie, et les conséquences cliniques et thérapeutiques de la multirésistance chez P. aeruginosa. Multirésistance chez P. aeruginosa : définition et mécanismesEn l'a...

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Antibiotics for ventilator-associated pneumonia

Arthur¹,

Kizor

Selim

et al. 2016

Cochrane Database of Systematic Reviews

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We did not find a difference between monotherapy and combination therapy for the treatment of people with VAP. Since studies did not identify patients with increased risk for multidrug-resistant bacteria, these data may not be generalisable to all patient groups. However, this is the largest meta-analysis comparing monotherapy to multiple antibiotic therapies for VAP and contributes further evidence to the safety of using effective monotherapy for the empiric treatment of VAP.Due to lack of studies, we could not evaluate the best antibiotic choice for VAP, but carbapenems as a class may result in better clinical cure than other tested antibiotics.

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Effect of Clarithromycin in Patients with Sepsis and Ventilator‐Associated Pneumonia

Cited by 148 publications

References 29 publications

Effect of Clarithromycin in Inflammatory Markers of Patients with Ventilator-Associated Pneumonia and Sepsis Caused by Gram-Negative Bacteria: Results from a Randomized Clinical Study

Effect of Clarithromycin in Inflammatory Markers of Patients with Ventilator-Associated Pneumonia and Sepsis Caused by Gram-Negative Bacteria: Results from a Randomized Clinical Study

Multirésistance chezPseudomonas aeruginosa

Antibiotics for ventilator-associated pneumonia

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