Major Adverse Cardiovascular Events During Invasive Pneumococcal Disease Are Serotype Dependent.

BACKGROUND: Up to 30% of patients admitted to hospitals with invasive pneumococcal disease (IPD) experience major adverse cardiovascular event (MACE) including new/worsening heart failure, new/worsening arrhythmia, and/or myocardial infarction. Streptococcus pneumoniae (Spn) is the most frequently isolated bacterial pathogen among community-acquired pneumonia (CAP) patients and the only etiological agent linked independently to MACE. Nevertheless, no clinical data exist identifying which serotypes of Spn are principally responsible for MACE. METHODS: This was an observational multicenter retrospective study conducted through the Public Health Secretary of Bogotá, Colombia. We included patients with a confirmed clinical diagnosis of IPD with record of pneumococcal serotyping and clinical information between 2012 and 2019. Spn were serotyped using the quellung method by the National Center of Microbiology. MACE were determined by a retrospective chart review. RESULTS: The prevalence of MACE was 23% (71/310) in IPD patients and 28% (53/181) in patients admitted for CAP. The most prevalent S. pneumoniae serotype identified in our study was the 19A, responsible for the 13% (42/310) of IPD in our cohort, of which 21% (9/42) presented MACE. Serotypes independently associated with MACE in IPD patients were serotype 3 (odds ratio [OR] 1, 48; 95% confidence interval [CI] [1.21-2.27]; P = .013) and serotype 9n (OR 1.29; 95% CI [1.08-2.24]; P = .020). Bacteremia occurred in 87% of patients with MACE. Moreover, serum concentrations of C-reactive protein were elevated in patients with MACE versus in non-MACE patients (mean [standard deviation], 138 [145] vs 73 [106], P = .01). CONCLUSIONS: MACE are common during IPD with serotype 3 and 9n independently of frequency.

Design, Synthesis and Evaluation of Branched RRWQWR-Based Peptides as Antibacterial Agents Against Clinically Relevant Gram-Positive and Gram-Negative Pathogens.

Multidrug resistance of pathogenic bacteria has become a public health crisis that requires the urgent design of new antibacterial drugs such as antimicrobial peptides (AMPs). Seeking to obtain new, lactoferricin B (LfcinB)-based synthetic peptides as viable early-stage candidates for future development as AMPs against clinically relevant bacteria, we designed, synthesized and screened three new cationic peptides derived from bovine LfcinB. These peptides contain at least one RRWQWR motif and differ by the copy number (monomeric, dimeric or tetrameric) and structure (linear or branched) of this motif. They comprise a linear palindromic peptide (RWQWRWQWR), a dimeric peptide (RRWQWR)2KAhx and a tetrameric peptide (RRWQWR)4K2Ahx2C2. They were screened for antibacterial activity against Enterococcus faecalis (ATCC 29212 and ATCC 51575 strains), Pseudomonas aeruginosa (ATCC 10145 and ATCC 27853 strains) and clinical isolates of two Gram-positive bacteria (Enterococcus faecium and Staphylococcus aureus) and two Gram-negative bacteria (Klebsiella pneumoniae and Pseudomonas aeruginosa). All three peptides exhibited greater activity than did the reference peptide, LfcinB (17-31), which contains a single linear RRWQWR motif. Against the ATCC reference strains, the three new peptides exhibited minimum inhibitory concentration (MIC50) values of 3.1-198.0 µM and minimum bactericidal concentration (MBC) values of 25-200 µM, and against the clinical isolates, MIC50 values of 1.6-75.0 µM and MBC values of 12.5-100 µM. However, the tetrameric peptide was also found to be strongly hemolytic (49.1% at 100 µM). Scanning Electron Microscopy (SEM) demonstrated that in the dimeric and tetrameric peptides, the RRWQWR motif is exposed to the pathogen surface. Our results may inform the design of new, RRWQWR-based AMPs.