S. Aureus Infections PDF

Nosocomial infections are infections originating in a hospital. Nosocomial infections are also known as Hospital acquired infections (HAI) or Healthcare associated infections (HCAI) are infections that are are not present at the time of admission, but occur in a patient during admission to a hospita...

Nosocomial infections are infections originating in a hospital. Nosocomial infections are also known as Hospital acquired infections (HAI) or Healthcare associated infections (HCAI) are infections that are are not present at the time of admission, but occur in a patient during admission to a hospital or healthcare facility. Community acquired infections are infections that are contracted outside of a hospital, in the community According to NICE, 300,000 patients a year in England acquire infections after care within the NHS. HAIs place a huge cost burden of approximately £1 billion per year to the NHS. In developing countries, 1 in 10 patients hospitalized will acquire at least one HAI. HAIs are generally associated with medical devices or surgical wounds. These can range from infections associated with catheters to serious blood stream infections associated with ventilators or surgical site infections. HAI are caused by a number of bacterial, viral and bacterial pathogens, and in many cases caused by bacteria that are carried by patients. These include several highly antibiotic resistant bacteria such as Acinetobacter baumannii, ESBL producing Enterobacteriaciae, Staphylococcus aureus and Clostridium difficile. Staphylococcus aureus is a Gram positive coccus, which is seen in typical grape-like (staphylo) clusters. The species was named 'aureus' due to the golden (aurum) pigment it produces. S. aureus produces coagulase, one of the enzymes that can cause blood clotting, and hence can be differentiated from other pathogenic staphylococci which are coagulase-negative. S. aureus is able to survive with and without oxygen and is hence a facultative anaerobe. Interestingly, S. aureus is a member of the human microbiota, and is found in the nares and the skin of upto 30% of the population in 'carriers' of S. aureus. S. aureus can thus colonize the nose and skin of healthy individuals without causing an infection. Usually, this bacterium can invade and cause an infection when there is a breach of the barrier, i.e a cut in the skin or the skin barrier or damaged mucosa. S. aureus produces a range of surface proteins, enzymes (e.g. lipase, nucleases) and secreted toxins ( e. g. alpha toxin, leucocidins) that help it colonize and invade tissue. Some of the key processes during infection such as bacterial adhesion, tissue invasion, biofilm formation and intracellular survival are summarized here. Adhesion to the host epithelium or mucosal lining in the skin or nares. The bacterium has several adhesins, which are proteins that aid bacterial attachment to the host cell surface [e.g. fibrinogen binding proteins (Fnbp), clumping factor A]. These adhesins can bind to host cell receptors (e.g. Fnbp binds to integrin receptors on host epithelial cells). Invasion into tissue: When there is a breach in the epithelial layer (e.g. skin) S. aureus is able to penetrate to the lower layers of tissue. At this point, tissue resident macrophages and other phagocytes like the neutrophils are recruited to site of infection. Neutrophils phagocytose bacteria to kills them via multiple mechanisms, including production of reactive oxygen species (ROS), myeloperoxidases and formation of neutrophil extracellular traps. The local immune response leads to the formation of an abscess. However if the immune cells are not successful at containing the pathogen, then they can invade deeper tissues and eventually enter the blood stream. Biofilm formation. S. aureus is adept at forming biofilms. Biofilms are bacterial communities or aggregates that are bound together by an extracellular matrix. S. aureus can form biofilms on tissues (e.g wounds) and on medical devices like catheters. Antibiotics are not able to penetrate biofilms very efficiently, and hence biofilm infections are very hard to treat effectively, resulting in recurrence of infections. Intracellular survival within cells. S. aureus is a facultatively intracellular pathogen- so it can enter different types of host cells, including immune cells like macrophages. Bacteria can replicate, and then eventually lyse the cells to disseminate, or they can also persist in this niche for longer times. Similar to biofilms, drugs cannot kill intracellular bacteria effectively. Staphylococcus aureus is a leading cause of healthcare and community- associated infections and have placed a huge financial burden on health systems world wide. It can infect different parts of the body causing a wide range of infections from minor skin abscesses to serious life threatening conditions like endocarditis. Some of the infections caused by this pathogen include  Skin and soft tissues infections (SSTI) bone and joint infections, e.g. osteomyelitis Infection of the heart valves- Infectious endocarditis Pulmonary infections e.g. pneumonia Medical device or implant related infections Bacteremia or bacteria in the blood S. aureus have gained resistance to a number of antibiotics in use. Historically, beta-lactamases produced by S. aureus strains inactivated the first beta-lactam antibiotic, penicillin. Beta-lactamase resistant methicillin and oxacillin were developed later but S. aureus has also developed widespread resistance to these versions of the antibiotic. According to the PHE, the methicillin resistant S. aureus (MRSA) were responsible for 12,878 cases of bacteraemia in the UK between 2018-2019, with ~26% (30-day) mortality rates. MRSA can be community associated (CA-MRSA) as well as hospital acquired (HA-MRSA) Vancomycin intermediate resistant S. aureus (VISA) or Vancomycin resistant S. aureus (VRSA) strains that are partly or completely resistant to resistant to vancomycin, a glycopeptide antibiotic that is used against MRSA, are also increasing. A rise in highly drug-resistant strains and high rates of recurrence, have made it challenging to effectively treat S. aureus infections. S. aureus elaborates many resistance mechanisms including modification of the drug target (e.g. vancomycin, beta lactams), enzymatic inactivation of the drug (e.g. beta lactamases), and active efflux of the drug (e.g. fluoroquinolones via NorA efflux pump). Beta-lactam antibiotics (penicillin, methicillin) inhibit bacterial cell wall synthesis. They target the penicillin binding proteins (PBPs) which are essential for synthesis of peptidoglycan, a key component of the Gram positive cell wall. MRSA have acquired a mobile genetic element SCCmec that contains the mecA gene. MecA encodes a variant form of PBP, PBP2a, which is not sensitive to beta-lactam antibiotics, and hence failing to inhibit cell wall synthesis in MRSA strains. Vancomycin is a glycopeptide antibiotic that inhibits cell wall synthesis, by blocking specific D-Ala-D-Ala (alanine) peptides and preventing polymerization of peptidoglycan. In VRSA strains the binding of vancomycin does not effect polymerization due to the presence of only one Ala residue, with one Ala replaced by a D-lactate residue (D-Ala-D-Lac), which results in failure to inhibit cell wall synthesis. Treating S. aureus infections effectively has become increasingly difficult due the increasing numbers of strains resistant to different antibiotics. Treatment of methicillin sensitive S. aureus (MSSA) strains is usually with penicillin derivatives like oxacillin, or cephalosporins. MRSA strains are usually treated with vancomycin. However, with the increasing number of VISA and VRSA strains, treatment options are limited. Treatment drugs are often chosen based on the type of infection. For e.g. Daptomycin is often preferred for SSTI caused by MSSA and MRSA. Linezolid is another drug that is used to treat MRSA. A major challenge is the high recurrence rates (10-50%) of S. aureus infections. Recurrence (relapse) of infection after successful initial treatment is very common in prosthetic joint infections and SSTI. Reccurrent infections are attributed to the bacteria persisting in tissues within biofilms or inside cells. There are two main ways in which S. aureus can be transmitted in a hospital setting. 1. endogenously, if the patient is already colonized by S. aureus (carriers), bacteria can be spread to another part of the body. 2. exogenous spread: from person to person, usually but direct contact with skin, equipment or other surfaces. S. aureus can also be shed into the environment through skin scales or dust. To prevent MRSA spread, several infection control measures are in place in hospitals. These include Practicing hand hygiene General cleanliness of hospital premises Covering wounds and lesions Using appropriate personal protective equipment when handling body fluids