Bacteriophages Improve Outcomes in Experimental Staphylococcus aureus Ventilator-associated Pneumonia.

Rationale: Infections caused by multidrug-resistant bacteria are a major clinical challenge. Phage therapy is a promising alternative antibacterial strategy.Objectives: To evaluate the efficacy of intravenous phage therapy for the treatment of ventilator-associated pneumonia due to methicillin-resistant Staphylococcus aureus in rats.Methods: In a randomized, blinded, controlled experimental study, we compared intravenous teicoplanin (3 mg/kg, n = 12), a cocktail of four phages (2-3 × 10 <sup>9</sup> plaque-forming units/ml of 2003, 2002, 3A, and K; n = 12), and a combination of both (n = 11) given 2, 12, and 24 hours after induction of pneumonia, and then once daily for 4 days. The primary outcome was survival at Day 4. Secondary outcomes were bacterial and phage densities in lungs and spleen, histopathological scoring of infection within the lungs, and inflammatory biomarkers in blood.Measurements and Main Results: Treatment with either phages or teicoplanin increased survival from 0% to 58% and 50%, respectively (P < 0.005). The combination of phages and antibiotics did not further improve outcomes (45% survival). Animal survival correlated with reduced bacterial burdens in the lung (1.2 × 10 <sup>6</sup> cfu/g of tissue for survivors vs. 1.2 × 10 <sup>9</sup> cfu/g for nonsurviving animals; P < 0.0001), as well as improved histopathological outcomes. Phage multiplication within the lung occurred during treatment. IL-1β increased in all treatment groups over the course of therapy.Conclusions: Phage therapy was as effective as teicoplanin in improving survival and decreasing bacterial load within the lungs of rats infected with methicillin-resistant S. aureus. Combining antibiotics with phage therapy did not further improve outcomes

Benefits of Aerosolized Phages for the Treatment of Pneumonia Due to Methicillin-Resistant Staphylococcus aureus: An Experimental Study in Rats.

The optimal method for delivering phages in the context of ventilator-associated pneumonia (VAP) is unknown. In the current study, we assessed the utility of aerosolized phages (aerophages) for experimental methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. Rats were ventilated for 4 hours before induction of pneumonia. Animals received one of the following: (1) aerophages; (2) intravenous (IV) phages; (3) a combination of IV and aerophages; (4) IV linezolid; or (5) a combination of IV linezolid and aerophages. Phages were administered at 2, 12, 24, 48, and 72 hours, and linezolid was administered at 2, 12, 24, 36, 48, 60, and 72 hours. The primary outcome was survival at 96 hours. Secondary outcomes were bacterial and phage counts in tissues and histopathological scoring of the lungs. Aerophages and IV phages each rescued 50% of animals from severe MRSA pneumonia (P < .01 compared with placebo controls). The combination of aerophages and IV phages rescued 91% of animals, which was higher than either monotherapy (P < .05). Standard-of-care antibiotic linezolid rescued 38% of animals. However, linezolid and aerophages did not synergize in this setting (55% survival). Aerosolized phage therapy showed potential for the treatment of MRSA pneumonia in an experimental animal model and warrants further investigation for application in humans

Chapter 15: Dilated Cardiomyopathy at the Crossroad: Multidisciplinary Approach

Patients with dilated cardiomyopathy (DCM) can present for the first time with typical cardiac symptoms, as heart failure, arrhythmias, and syncope, with cardiomyopathy as the main presenting feature. However, DCM may be a common feature of systemic diseases or presenting in the contest of different clinical settings. Symptoms of multisystem disease may be described by patients themselves or be determined on routine examination. A cardiomyopathy-specific mindset, which combines conventional cardiologic assessment with non-cardiac clinical acumen and a systematic approach, is important, because it can be used to identify specific disorders, guide rational selection of diagnostic tests, and increase the chance that disorders with tailored management strategies can be identified. Moreover, in different clinical settings, phenotypic expression in other organs may precede cardiac manifestations, and the cardiologist\u2019s role is to search for cardiac involvement in a patient who already has a non-cardiac diagnosis. In the present chapter, we consider DCM and ventricular dysfunction in the contest of peculiar clinical settings ranging from inflammatory or autoimmune disorders to specific forms of systemic disease, infectious disease, as well as toxin-induced DCM