Staphylococcus aureus: Treatment and Spread

• Nosocomial infections originate in hospitals and are also known as hospital-acquired infections (HAI) or healthcare-associated infections (HCAI).
• HAIs are not present at the time of admission but occur during a hospital or healthcare facility stay.
• Community-acquired infections are contracted outside of a hospital/healthcare facility.
• In England, 300,000 patients acquire infections post-care within the NHS per year.
• HAIs cost the NHS approximately £1 billion annually.
• In developing countries, 1 in 10 hospitalized patients get an HAI.
• HAI's are often associated with medical devices, surgical wounds, catheters, ventilators and surgical sites.
• HAIs can be caused by bacterial, viral, or bacterial pathogens, and are sometimes carried by patients.
• Antibiotic-resistant bacteria include Acinetobacter baumannii, ESBL-producing Enterobacteriaceae, Staphylococcus aureus, and Clostridium difficile.

Staphylococcus aureus

• Staphylococcus aureus is a Gram-positive coccus seen in grape-like clusters is named after golden pigment it produces
• S. aureus produces coagulase, an enzyme that causes blood clotting and differentiates it from other coagulase-negative staphylococci.
• S. aureus is a facultative anaerobe, able to survive with or without oxygen.
• S. aureus is found in the nares and skin of up to 30% of the population, colonizing healthy individuals without causing infection.
• When the skin barrier is breached, it can invade and cause infection.
• S. aureus produces surface proteins, enzymes (lipase, nucleases), and secreted toxins (alpha toxin) to colonize and invade tissue.
• Adhesins, such as fibrinogen-binding proteins, aid bacterial attachment to host cells.
• Adhesins can bind to host cell receptors, like Fnbp binding to integrin receptors.
• When the epithelial layer is breached S. aureus invades tissue, attracting macrophages and neutrophils.
• Neutrophils kill bacteria via ROS production, myeloperoxidases, and NET formation.
• This immune response can lead to abscesses; if unsuccessful, the bacteria invade deeper tissues and enter the bloodstream.
• S. aureus forms biofilms, bacterial communities bound by an extracellular matrix, on tissues and medical devices.
• Biofilm infections are hard to treat due to antibiotic penetration issues, leading to recurrence.
• S. aureus is a facultative intracellular pathogen, entering host cells like macrophages to replicate or persist.
• Similar to biofilms, these intracellular bacteria are difficult to target with drugs.
• S. aureus is a leading cause of healthcare and community-associated infections, impacting health systems globally.
• It causes infections ranging from minor skin abscesses to serious conditions like endocarditis.
• Infections include skin and soft tissue infections (SSTI), bone and joint infections (osteomyelitis), heart valve infections (endocarditis), pulmonary infections (pneumonia), medical device-related infections, and bacteremia.
• S. aureus has developed resistance to antibiotics, including penicillin, and methicillin.
• MRSA caused 12,878 bacteraemia cases in the UK (2018-2019), with ~26% mortality.
• MRSA can be community-associated (CA-MRSA) or hospital-acquired (HA-MRSA).
• Vancomycin-intermediate/resistant S. aureus (VISA/VRSA) strains are increasing.
• Drug resistance and high recurrence rates complicate S. aureus infection treatment.
• Resistance mechanisms include target modification, enzymatic inactivation, and active drug efflux.
• Beta-lactams (penicillin, methicillin) inhibit bacterial cell wall synthesis by targeting penicillin-binding proteins.
• MRSA carries the mecA gene, encoding PBP2a, which isn't sensitive to beta-lactams, preventing cell wall synthesis inhibition.
• Vancomycin inhibits cell wall synthesis by blocking specific peptides.
• VRSA strains have an altered peptide structure, preventing vancomycin binding.
• MSSA strains are treated with penicillin derivatives or cephalosporins; MRSA strains are treated with vancomycin.
• Drugs like Daptomycin (for SSTI caused by MSSA and MRSA) and Linezolid treat MRSA.
• High recurrence rates (10-50%) are a challenge with S. aureus infections.
• Relapse after initial treatment is common in prosthetic joint infections and SSTI.
• Infections that are recurrent are attributed to bacteria persisting in tissues within biofilms or in cells.
• S. aureus Transmission within hospitals can be endogenous or exogenous.
• Endogenous transmission (through carriers) where bacteria spread from one body part to another.
• Exogenous spread occurs through direct contact with skin, equipment, or surfaces
• S. aureus can be shed into the environment via skin scales or dust.
• Infection control measures to prevent MRSA spread include hand hygiene, hospital cleanliness, wound coverage, and using protective equipment.

This quiz explores challenges in treating S. aureus infections, including factors complicating long-term strategies and effective control measures. It addresses the spread, recurrence, and resistance mechanisms of S. aureus, especially MRSA, VISA, and VRSA strains. Critical research areas for combating resistant infections are also examined.