Endemic, epidemic and pandemic infections: the roles of natural and acquired herd immunity.

Purpose Of Review: This review summarizes the general concepts of innate and acquired immunity, including vaccine use and hesitancy, as they relate to reduction of the global burden of highly communicable infectious diseases.

Recent Findings: Vaccination to increase herd immunity remains the cornerstone of disease prevention worldwide yet global vaccination goals are not being met. Modern obstacles to vaccine acceptance include hesitancy, reduced altruistic intentions, impact of COVID-19, distrust of science and governmental agencies as well as recent geopolitical and environmental disasters.

Investigating the immunomodulatory activities of omadacycline.

Background: Apart from their antimicrobial activities, some antibiotics have immunomodulatory effects on host cells, particularly monocytes. Because hyperactivation of the pro-inflammatory cytokine response contributes to acute lung injury in patients with bacterial pneumonia and other lung diseases, antimicrobial agents with immunomodulatory activity can reduce cytokine-mediated tissue injury and improve outcomes.

Objectives: Omadacycline has been recently FDA-approved for community-acquired bacterial pneumonia and acute bacterial skin and skin-structure infections.

NAD+-Glycohydrolase Reduces Skeletal Muscle βNAD+ Levels Independently of Streptolysin O.

Necrotizing soft tissue infections caused by (group A streptococcus [GAS]) are characterized by rapid and extensive necrosis of fascia and muscle. Molecular epidemiological studies have demonstrated a positive correlation between GAS isolates that cause invasive infections and the production of NAD+-glycohydrolase (SPN), an NADase secreted by GAS, but the effect of SPN on muscle cells has not been described. Thus, using standard βNAD+ and ATP quantification assays, we investigated the effects of SPN on cultured human skeletal muscle cell (SkMC) βNAD+ and ATP with and without streptolysin O (SLO)-a secreted cholesterol-dependent cytolysin known to act synergistically with SPN.

Characterization of Paeniclostridium sordellii Metalloproteinase-1 in vitro and in an experimental model of infection.

Objective: Paeniclostridium sordellii is a pathogen that causes rapidly fatal infections characterized by severe edema, extreme leukemoid reaction and lack of an innate immune response. We recently identified a metalloproteinase of P. sordellii-1 (Mcs1) that cleaves human vascular cell adhesion molecule 1, an adhesion molecule important to hematopoietic precursor retention and leukocyte diapedesis.

Necrotizing Soft Tissue Infections.

Necrotizing soft tissue infections occur after traumatic injuries, minor skin lesions, nonpenetrating injuries, natural childbirth, and in postsurgical and immunocompromised patients. Infections can be severe, rapidly progressive, and life threatening. Survivors often endure multiple surgeries and prolonged hospitalization and rehabilitation.

Emerging erythromycin and clindamycin resistance in group A streptococci: Efficacy of linezolid and tedizolid in experimental necrotizing infection.

Objectives: Clindamycin (CLI) and erythromycin (ERY) resistance is increasing among group A streptococci (GAS) causing invasive disease and alternative treatments are urgently required. In this study, the efficacy of the newer oxazolidinone tedizolid (TZD) was compared with the first drug in this class, linezolid (LNZ), in experimental murine myonecrosis caused by ERY-susceptible/CLI-susceptible (ERY/CLI) or ERY- resistant/CLI-resistant (ERY/CLI) GAS.

Methods: Normal adult outbred Swiss Webster female mice (10 per group) were infected intramuscularly with ERY/CLI (ATCC 12384) or ERY/CLI (15-003) GAS.

Enrichment of Antigen-Specific Class-Switched B Cells from Individuals Naturally Immunized by Infection with Group A Streptococcus.

The low frequency of circulating antigen-specific memory B cells is a considerable obstacle in the discovery and development of human monoclonal antibodies for therapeutic application. Here, we evaluate two solid-phase isolation methods to enrich the number of antigen-specific B cells from individuals naturally immunized against streptolysin O (SLO), a key virulence factor and known immunogen of group A streptococcus (GAS). Class-switched B cells obtained from individuals with a history of GAS infection were separated from peripheral blood mononuclear cells (PBMCs) by immunomagnetic methods.

The effects of iclaprim on exotoxin production in methicillin-resistant and vancomycin-intermediate Staphylococcus aureus.

Purpose: Extracellular protein toxins contribute to the pathogenesis of Staphylococcus aureus infections. The present study compared the effects of iclaprim and trimethoprim - two folic acid synthesis inhibitors - with nafcillin and vancomycin on production of Panton-Valentine leukocidin (PVL), alpha haemolysin (AH) and toxic-shock syndrome toxin I (TSST-1) in methicillin-resistant and vancomycin-intermediate S. aureus (MRSA and VISA, respectively).

Subinhibitory concentrations of tedizolid potently inhibit extracellular toxin production by methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

Purpose: Potent extracellular toxins including alpha-haemolysin, Panton-Valentine leukocidin (PVL) and toxic-shock syndrome toxin 1 (TSST-1) significantly contribute to Staphylococcus aureus pathogenesis, thus, toxin suppression is a primary focus in treatment of staphylococcal disease. S. aureus maintains complex strategies to regulate toxin expression and previous data have demonstrated that subinhibitory concentrations of beta-lactam antibiotics can adversely increase S.

Sub-lethal doses of surotomycin and vancomycin have similar effects on Clostridium difficile virulence factor production in vitro.

Purpose: Clostridium difficile is an anaerobic spore-forming bacterial pathogen that causes a spectrum of illness severity ranging from mild diarrhoea to severe life-threatening pseudomembranous colitis. C. difficile infection (CDI) is antibiotic-associated and primarily mediated by two exotoxins, Toxins A and B.

Comparative efficacy of antibiotics in treating experimental Clostridium septicum infection.

Clostridium septicum is a highly pathogenic microbe that causes gas gangrene in humans, and is the principal cause of spontaneous gas gangrene in patients with gastrointestinal maladies, including adenocarcinoma of the colon. Despite modern approaches to manage C. septicum infection, morbidity and mortality remain high (>60%).

Fidaxomicin reduces early toxin A and B production and sporulation in Clostridium difficilein vitro.

Purpose: Fidaxomicin, a macrocyclic antibiotic, has been approved for the treatment of Clostridium difficile infection (CDI). Previous work by our group has demonstrated that some antibiotics at sub-inhibitory concentrations stimulate early toxin production and sporulation by C. difficile.

Subinhibitory Dalbavancin Attenuates Exotoxin Production from Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus .

This study investigated the effects of subinhibitory doses of the lipoglycopeptide antibiotic dalbavancin on toxin production toxin production levels were compared to those seen with the natural glycopeptide antibiotic vancomycin and with representative beta-lactam and oxazolidinone antibiotics. While neither dalbavancin nor vancomycin adversely affected toxin production, of these glycopeptide antibiotics, only dalbavancin significantly attenuated toxin production at subinhibitory concentrations. These findings support the recent success of dalbavancin for treatment of staphylococcal infections.

Spontaneous C. septicum gas gangrene: A literature review.

As the infectious disease paradigm undergoes a subtle shift, unusual infections associated with malignancy and immunosuppression are being increasingly reported. Spontaneous or non-traumatic Clostridium septicum infection is one such unusual infection which has gained prominence. This article aims to understand the pathophysiology, clinical manifestations and current trends in diagnosing and treating this rare but deadly infection.

Effects of delayed NSAID administration after experimental eccentric contraction injury - A cellular and proteomics study.

Background: Acute muscle injuries are exceedingly common and non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed to reduce the associated inflammation, swelling and pain that peak 1-2 days post-injury. While prophylactic use or early administration of NSAIDs has been shown to delay muscle regeneration and contribute to loss of muscle strength after healing, little is known about the effects of delayed NSAID use. Further, NSAID use following non-penetrating injury has been associated with increased risk and severity of infection, including that due to group A streptococcus, though the mechanisms remain to be elucidated.

Advances in the medical management of skin and soft tissue infections.

Skin and soft tissue infections are some of the most common infectious disease diagnoses in both inpatient and outpatient settings. With bacterial resistance to antimicrobials growing, decision making on empiric antibiotics is becoming increasingly difficult. Additionally, the most recent guidance from a professional society on the treatment of skin and soft tissue infections was published in 2014 by the Infectious Diseases Society of America and is now two years old.