Clinical Profile of Prosthetic Valve Endocarditis due to Candida parapsilosis: An 11-year Retrospective Observational Study from a Quaternary Cardiac Referral Institute in India.

Background: Recent changes in the diagnostic criteria and the introduction of newer technologies like prosthetic valve replacement require the need to identify the changing epidemiology of prosthetic valve endocarditis (PVE). Materials and methods: This is a retrospective, cross-sectional, observational study. Patients diagnosed with Candida parapsilosis definite and possible PVE as per modified Duke's criteria for a period of 11 years from January 2010 to December 2020 were included for the analysis. Results: Twelve of the 47 PVE cases (25.5%) were caused by C. parapsilosis. The median age of the patients was 52 years. Males were predominantly affected (58%). Based on the modified Duke's criteria, eight (67%) were definite infective endocarditis (IE) cases. The single valve was affected in 11 cases (92%) with the mitral valve being the commonest (n = 8, 67%). The type of valve commonly involved was mechanical [n = 10, 83%]. The mean size of the vegetation was 13.15 mm. Most cases (n = 7, 58%) were late-onset PVE. The mean C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin (PCT) levels for C. parapsilosis PVE were 70.2 mg/L, 51.08 mm/hour, and 0.3 ng/mL, respectively. The rates of complications and in-hospital mortality were 75% each. The most common observed complication was embolic events (n = 8, 67%). Statistical significance (p ≤ 0.05) was observed for mean vegetation size, overall complications, embolic events, and mortality for C. parapsilosis PVE when compared with bacterial PVE. Conclusion: C. parapsilosis was the commonest etiological agent causing PVE. Predominant mitral valve involvement, higher rates of late-onset presentation, complications, and mortality were key differential characteristics observed. Highlights: The manuscript throws light on the changing epidemiology, clinical, and microbiological profile of PVE due to Candida sp., which are scarcely studied and reported in low- and middle-income countries like India. How to cite this article: Ponnambath DK, Gopalakrishnan A, Pillai VV, Kaviyil JE, Raja K. Clinical Profile of Prosthetic Valve Endocarditis due to Candida parapsilosis: An 11-year Retrospective Observational Study from a Quaternary Cardiac Referral Institute in India. Indian J Crit Care Med 2021;25(8):860-865.

Proteogenomics of Candida tropicalis--An Opportunistic Pathogen with Importance for Global Health.

The frequency of Candida infections is currently rising, and thus adversely impacting global health. The situation is exacerbated by azole resistance developed by fungal pathogens. Candida tropicalis is an opportunistic pathogen that causes candidiasis, for example, in immune-compromised individuals, cancer patients, and those who undergo organ transplantation. It is a member of the non-albicans group of Candida that are known to be azole-resistant, and is frequently seen in individuals being treated for cancers, HIV-infection, and those who underwent bone marrow transplantation. Although the genome of C. tropicalis was sequenced in 2009, the genome annotation has not been supported by experimental validation. In the present study, we have carried out proteomics profiling of C. tropicalis using high-resolution Fourier transform mass spectrometry. We identified 2743 proteins, thus mapping nearly 44% of the computationally predicted protein-coding genes with peptide level evidence. In addition to identifying 2591 proteins in the cell lysate of this yeast, we also analyzed the proteome of the conditioned media of C. tropicalis culture and identified several unique secreted proteins among a total of 780 proteins. By subjecting the mass spectrometry data derived from cell lysate and conditioned media to proteogenomic analysis, we identified 86 novel genes, 12 novel exons, and corrected 49 computationally-predicted gene models. To our knowledge, this is the first high-throughput proteomics study of C. tropicalis validating predicted protein coding genes and refining the current genome annotation. The findings may prove useful in future global health efforts to fight against Candida infections.

Correction: Membrane-active macromolecules resensitize NDM-1 gram-negative clinical isolates to tetracycline antibiotics.

Gram-negative 'superbugs' such as New Delhi metallo-beta-lactamase-1 (blaNDM-1) producing pathogens have become world's major public health threats. Development of molecular strategies that can rehabilitate the 'old antibiotics' and halt the antibiotic resistance is a promising approach to target them. We report membrane-active macromolecules (MAMs)that restore the antibacterial efficacy (enhancement by >80-1250 fold) of tetracycline antibiotics towards blaNDM-1 Klebsiella pneumonia and blaNDM-1 Escherichia coli clinical isolates.Organismic studies showed that bacteria had an increased and faster uptake of tetracyclinein the presence of MAMs which is attributed to the mechanism of re-sensitization. Moreover,bacteria did not develop resistance to MAMs and MAMs stalled the development of bacterial resistance to tetracycline. MAMs displayed membrane-active properties such as dissipation of membrane potential and membrane-permeabilization that enabled higher uptake of tetracycline in bacteria. In-vivo toxicity studies displayed good safety profiles and preliminary in-vivo antibacterial efficacy studies showed that mice treated with MAMs in combination with antibiotics had significantly decreased bacterial burden compared to the untreated mice. This report of re-instating the efficacy of the antibiotics towards blaNDM-1 pathogens using membrane-active molecules advocates their potential for synergistic co-delivery of antibiotics to combat Gram-negative superbugs.

Membrane-active macromolecules resensitize NDM-1 gram-negative clinical isolates to tetracycline antibiotics.

Gram-negative 'superbugs' such as New Delhi metallo-beta-lactamase-1 (blaNDM-1) producing pathogens have become world's major public health threats. Development of molecular strategies that can rehabilitate the 'old antibiotics' and halt the antibiotic resistance is a promising approach to target them. We report membrane-active macromolecules (MAMs) that restore the antibacterial efficacy (enhancement by >80-1250 fold) of tetracycline antibiotics towards blaNDM-1 Klebsiella pneumonia and blaNDM-1 Escherichia coli clinical isolates. Organismic studies showed that bacteria had an increased and faster uptake of tetracycline in the presence of MAMs which is attributed to the mechanism of re-sensitization. Moreover, bacteria did not develop resistance to MAMs and MAMs stalled the development of bacterial resistance to tetracycline. MAMs displayed membrane-active properties such as dissipation of membrane potential and membrane-permeabilization that enabled higher uptake of tetracycline in bacteria. In-vivo toxicity studies displayed good safety profiles and preliminary in-vivo antibacterial efficacy studies showed that mice treated with MAMs in combination with antibiotics had significantly decreased bacterial burden compared to the untreated mice. This report of re-instating the efficacy of the antibiotics towards blaNDM-1 pathogens using membrane-active molecules advocates their potential for synergistic co-delivery of antibiotics to combat Gram-negative superbugs.