Chapters authored
Culture Negative Endocarditis: Advances in Diagnosis and Treatment
Culture-negative endocarditis (CNE) is a challenging clinical entity, both diagnostically and therapeutically. In this chapter, the changed epidemiology and microbiology of CNE are reviewed with cases highlighting typical pathogens in patients pre-treated with antibiotics, less common fastidious pathogens such as bacteria of the HACEK group, nutritionally deficient bacteria, Legionella spp. and Mycobacteria, “quintessential” CNE pathogens such as Bartonella spp., Coxiella burnetti and Tropheryma whipplei, as well as fungal CNE. Contemporary diagnostic methods are reviewed including polymerase chain reaction-based pathogen 16s RNA amplification coupled with electrospray ionization mass spectrometry (PCR/ESI-MS). Finally, treatment options per the recently updated 2015 American Heart Association and European Society for Cardiology guideline are presented.
Part of the book: Contemporary Challenges in Endocarditis
Left Ventricular Assist Device Infections
Left ventricular assist device (LVAD) infections are important causes of morbidity and mortality in patients who receive these mechanical circulatory supports as a bridge to transplantation (BTT) or as destination therapy (DT) (for individuals who are not candidates for cardiac transplant). Infections are more common among persons who received pulsatile flow LVADs as opposed to newer continuous flow (CF) devices. Other risk factors for infection include obesity, renal failure, depression and immunosuppression. An LVAD infection increases the risk of infections in persons who undergo cardiac transplantation. Infections include percutaneous site, driveline, pump pocket and pump/cannula infections; sepsis, bacteremia, mediastinitis and endocarditis. Diagnosis is achieved by monitoring LVAD flow parameters and observing typical clinical and laboratory manifestations of infection. Imaging such as PET-CT or SPECT-CT imaging can be helpful to establish a diagnosis of pump pocket infection. Echocardiography may aid in detecting native valve endocarditis and thrombus associated with the LVAD. The most common pathogens include Staphylococcus, Corynebacterium, Enterococcus, Pseudomonas and Candida spp. Treatment requires targeted antimicrobials plus surgical debridement of infected tissue and device components. In cases of pump/cannula/LVAD endocarditis, especially if fungal pathogens or Mycobacterium chimaera are involved, LVAD removal/reimplantation vs. transplant is necessary, combined with extended antimicrobial therapy.
Part of the book: Advanced Concepts in Endocarditis
Bulgecins as β-Lactam Enhancers Against Multidrug Resistant (MDR) Pseudomonas aeruginosa
Antibiotic resistance in non-lactose fermenting pathogens such as Pseudomonas aeruginosa (P. aeruginosa) is increasing, making these clinical pathogens more difficult to treat. Multiple resistance mechanisms exist within P. aeruginosa that affect all classes of antibiotics used in the clinic. New strategies and treatment targets within these MDR pathogens must be exploited. One heretofore untapped target is the family of cell wall enzymes known as lytic transglycosylases (Lts). Lts work in concert with penicillin binding proteins (PBPs) and other cell wall proteins such as amidases and peptidoglycan hydrolases to affect normal cell division, and during stress and programmed cell death. Lts are inhibited by natural products called bulgecins, produced by non-pathogenic Paraburkholderia and Burkholderia spp. New research describing the ability of Lt inhibition to restore susceptibility to β-lactams in MDR P. aeruginosa, as well as the structural biologic basis for the activity of bulgecins will be reviewed. Other targets and applications of bulgecins will also be discussed.
Part of the book: Pseudomonas Aeruginosa