Effect of Dexamethasone and Pentoxifylline in Combination with Amoxicillin in the Treatment of Penicillin-Insensitive Pneumococcal Pneumonia in Guinea Pigs

Parra, Araceli; Garcı́a-Olmos, M.; Nieto, Eva; Garcı́a-Calvo, Gloria; Ponte, Carmen; Granizo, Juan José; Soriano, Francisco

doi:10.1007/s15010-002-2098-x

Cited by 1 publication

(1 citation statement)

References 17 publications

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“…Although corticosteroids are used in influenza infection and community-acquired pneumonia, there is no consensus on their benefit, particularly in cases of secondary bacterial superinfection, and use of corticosteroids in animal models of dual infection has been scarcely attempted. 23e29, 40 In our study, we show that, although DEX treatment alone did not improve survival, DEX/AZI-treated mice had the quickest recovery, showing that the clinical outcome is most efficiently improved by treatment with both AZI and DEX. Furthermore, DEX/AZI mice had the most significantly decreased bacterial burden in the lungs, with no systemic dissemination, no excessive neutrophil influx into the lungs, and the lowest MPO activity and cytokine/chemokine expression of all of the groups.…”

Section: Discussionmentioning

confidence: 57%

Marked Improvement of Severe Lung Immunopathology by Influenza-Associated Pneumococcal Superinfection Requires the Control of Both Bacterial Replication and Host Immune Responses

Damjanovic

Lai

Jeyanathan

et al. 2013

The American Journal of Pathology

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Bacterial superinfection and associated lung immunopathology are major contributors to hospitalizations and mortality after influenza. However, the underlying mechanisms and effective intervention strategies remain poorly defined. By using a model of influenza and pneumococcal superinfection, we found that dual-infected animals experienced rapid weight loss and succumbed to infection. Bacterial outgrowth, dysregulated cytokines, including keratinocyte-derived chemokine and macrophage inflammatory protein 2, and severe lung neutrophilia and immunopathology were linked to the poor clinical outcome. In vivo neutralization of highly induced macrophage inflammatory protein 2 did not affect clinical outcome, bacterial loads, or lung immunopathology. On the other hand, in vivo neutrophil depletion did not alter the clinical outcome and bacterial burden, although it moderately improved lung immunopathology. Treatment with a bacteriostatic antibiotic, azithromycin, alone significantly improved clinical outcome and bacterial clearance, but failed to reduce lung immunopathology. In comparison, treatment with a global inflammation inhibitor, dexamethasone, alone failed to alter clinical outcome, bacterial infection, and immunopathology, despite its moderate reducing effects on neutrophilic and cytokine responses. In contrast, combined treatment with both azithromycin and dexamethasone best improved clinical outcome, bacterial clearance, lung cellular and cytokine responses, and immunopathology. Our study suggests that marked improvement of clinical outcome and lung immunopathology caused by bacterial superinfection requires the control of both bacterial infection and aberrant host immune responses. Our findings hold implications in clinical management for influenza-associated bacterial superinfections.

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Section: Discussionmentioning

confidence: 57%