Staphylococci - Gram Positive Cocci.pdf

MIC 541 Gram Positive Cocci The Staphylococci Richard Goering, Ph.D. [email protected] Staphylococci: round spherical, gram+ organisms that grow in clusters nonmotile, no spores, facultative, catalase + togrowin presenceofOz (more than 20 species) major problem organisms: Staphylococcus aureus St...

MIC 541 Gram Positive Cocci The Staphylococci Richard Goering, Ph.D. [email protected] Staphylococci: round spherical, gram+ organisms that grow in clusters nonmotile, no spores, facultative, catalase + togrowin presenceofOz (more than 20 species) major problem organisms: Staphylococcus aureus Staphylococcus epidermidis Gram stain of Staphylococcus aureus in pustular exudate roundin clusters hydrolyz aseenzyme Plasma carbon Halophilic blood Beta hemolysis DNA goDNase pigment mannitol coagulase clots gy S. aureus S. epidermidis + degrades + - + - - yellow white Id'd p salt) (7.5% beyond + + - sat + goldencolor Hysiology woodsaine Novobiocin resistance S. epidermidis S. saprophyticus specificantibiotic + cancontinue togrow arounddisc bleresistanttoABX disc NOTresistant in susceptibility susceptible cannotgrowarounddisc b c ABX isinhibiting S. aureus: the primary pathogen S. epidermidis: endocarditis heart infections S. saprophyticus: u.t.i / females 18-30 E Coli is major outs yauldronicacid encement 9E.ph 5fh Gotsnoodanfymgg'Ikea exfoliatin lipase IE i KillsWBClpyogenic pusforming causesscalded skin syndrome Virulence factors of Staphylococcus aureus Structural Virulence Factors (1) Capsule or slime layer protects against phagocytosis promotes adherence to synthetic materials Frgiaimplatsfhavdwar g.am Cell wall (peptidoglycan, teichoic acid) bind to exposed fibronectin in wounds promotes S aureus wound infections foreign, so stimulate immune response helpforminfections Structural Virulence Factors (2) Protein A on surface of S. aureus constantportion binds Fc portion of most types of IgG inhibits antibody-mediated opsonization protects against complement activation makes organisms look less foreign masks how harmful thebacteria is bybinding to the antibody itself Enzymatic Virulence Factors (1) causesbloodplasmatoclot movedifficulttophagocytize Coagulase – converts fibrinogen to fibrin allows organisms to clump together walls off in abscesses to protect from phagocytes hydrogepheroxide Catalase – breaks down H2O2 to O2 and H2O toxicfree radical breakdown protects against neutrophil killing AKA immuneresponse Hyaluronidase – damages connective tissue produced by >90% of S. aureus strains “spreading” factor – breaks down hyaluronic acid Enema Enzymatic Virulence Factors (2) barrier skin containslipidas antibacterial layer lipasebreaks down thisprotective Lipases – break down lipids for fuel produced by all S. aureus produced by 30% of coagulase (-) staphs important for surviving on human skin used when invading skin to cause boils Staphylococcus aureus humansare natural reservoir “carried” by ca. 1/3 of population (anterior nares, skin, hair) ffhffhfff.defdhfsauce parotitis stiff fmarily Sites of infection and diseases caused by Staphylococcus aureus 1 causeofboneinfections S. aureus Skin Infections (1) Boils, sties, abscesses infection of hair follicles rearto these surgical or trauma wound coagulase walls off lesion painful inflammation pus formation often heals quickly after pus is drained Staphylococcal Skin Infections (2) seencommonlyin infants Pustular impetigo superficial infection scabw liquidsurrounding pustules rupture, crust easily spread due to growth of No toxin S. aureus ± Streptococcus pyogenes Ines rather than toxin production “Early” Staphylococcal Skin Infection Staphylococcal Skin Infection / Cellulitis Deeper Staphylococcal Infections – – – Generally spread from local infection through bloodstream or lymphatics bacteremia, endocarditis, pneumonia, meningitis S. aureus is most common cause of osteomyelitis More common in hospitalized, immunoTimmuneresponse Fggletomountpro compromised patients High mortality rate, long i.v. antibiotic tx Staphylococcal Toxins (1) – – – – – – Cytotoxins – attack many host cell types damage cell membranes lyse cells or disturb their funtions leukocidins - kill white blood cells responsible for cellular destruction β toxinexcretedcauseskin to comeoff Exfoliative exotoxin – causes skin to slough splits intracellular bridges in epidermis cause of staphylococcal scalded skin syndrome Scalded Skin Syndrome redness around mouth spreads over body common in infants skin blisters, sloughs off – no organism, wbc’s in blisters due to exfoliative toxin action healing after antibody forms to toxin mortality low, no scarring artiliseeninmen superantigen Toxic Shock Syndrome (2) connect.io wlsuperabsorbanttampons bacteriainvaginasnolongerseentoday from tampons dueto Dmfr Toxin causes sudden onset of: – fever, hypotension (shock) – gastrointestinal symptoms – altered mental status – skin rash, peeling of hands and feet – multi-organ system failure, death in 2-5% Treatment with fluids and antibiotics Staphylococcal Toxins (3) causedbycreams promotestaphgrowth Akafoodpoisoning often Staphylococcal enterotoxins – exotoxins that affect the gut – eight types (A-E, G-I) – act like superantigens – bind, activate mast cells in gut – overproduction of cytokines – intense gastric peristalsis – causes staphylococcal food poisoning Staphylococcal Toxins (4) Leukocidin action: pyogenic (pus-producing) stimulate acute inflammatory reaction neutrophils accumulate S. aureus has virulence factors to protect itself from neutrophil-mediated killing Staphylococcal Food Poisoning (1) Can cause disease in absence of organism – toxin produced by S. aureus in food – storage at r.t. or higher – doesn’t produce bad taste in food – refrigerate foodcan not besalvaged not killed likeheating in C botulism resistant to boiling, gut enzymes Enterotoxins – work on CNS (vomiting center) – nausea, vomiting, diarrhea in 2-8 hr – rapid recovery within 24 hr Staphylococcal Food Poisoning (2) Treat dehydration, cramping and diarrhea Antibiotic treatment not necessary Norealantibodyresponseforfoodpoisoning Antibodies protective, but not against the other 7 serological types of toxin Predisposing factors: injury to the skin diabetic patients children with cystic fibrosis 8 d1j0ughup G immunodeficiency diseases anything which lowers resistance omonasmostcommonstapn.am Takeaway modifiedpenicillinbindingprotein PBP gene can causeresistancebyalteringcell wall Evolution of Antimicrobial Resistance Penicillin S. aureus Methicilli that breaksringtomakeABX noteffective producebeta lactamase n Penicillin-resistant [1950s] resistant Methicillin-resistant multidrug 9 S. aureus (MRSA) S. aureus [1980s] acquirenew genechange Vancomycin moai that [1990s] VancomycinResistant S. aureus Vancomycin Vancomycin-resistant (glycopeptide) intermediate enterococcus (VRE) resistant S. aureus t found on aplasmid lextrachromosomal Tracking the Movement of MRSA Hospital Associated Community Associated Historically, MRSA infections have been associated with a healthcare setting Nosocomial (hospital-acquired) infection is strictly and specifically an infection "not present or incubating prior to admittance to the hospital, but generally occurring more than 48 hours after admission Risk factors: prolonged hospitalization, intensive care unit, prolonged antimicrobial chemotherapy, surgery, close proximity to infected/colonized patient Usually considered an infection of chronically ill hospitalized patients MRSA in the “Community” (CA-MRSA) 1980-81 Detroit, Michigan IV Drug Users Early 1990’s Australia, New Zealand 1990’s Late 1990’s 1999-2000 Children’ w/o Identifiable Risks Native American Populations (AK, MN, WA) Urban Homeless populations Prison/jail populations 1980 2005 1990 Athletic teams MRSA in the “Community” (CA-MRSA) MRSA infections that are acquired by persons who have not been recently (within the past year) hospitalized or had a medical procedure (such as dialysis, surgery, catheters) are known as CAMRSA infections. Staph or MRSA infections in the community are usually manifested as skin infections, such as pimples and boils, and occur in otherwise healthy people. MRSA in the “Community” (CA-MRSA) Persons with MRSA infections meeting all of the following criteria likely have CA-MRSA infections: Diagnosis of MRSA made in the outpatient setting or by a culture positive for MRSA within 48 hours after admission to the hospital No medical history of MRSA infection or colonization No medical history in the past year of: Hospitalization Admission to a nursing home, skilled nursing facility, or hospice Dialysis Surgery No permanent indwelling catheters or medical devices that pass through the skin into the body. CA-MRSA Risk Factors Previous antibiotic use Intravenous drug use Incarceration Contact sports MSM (Men who have sex with men) Antibiotic Resistance (1) – – zyme β-lactamases – hydrolyse β-lactam ring makes penicillin-derived antibiotics inactive plasmid mediated, easily transferred Alter penicillin-binding proteins (PBP’s) – – chromosomally mediated most coagulase (-) and 30-50% of S. aureus – – Methicillin resistant S. aureus (MRSA) penicillin mediated by production of PBP2aFindingprotein many are resistant to multiple antibiotics Antibiotic Resistance (2) Rx for multi-drug resistant MRSA – vancomycin is only effective agent for some – occurrence of vancomycin resistance (VISA and VRSA) Alternative drugs for MRSA – oxazolidinones (linezolid) – streptogrammins (quinupristin-dalfopristin) – daptomycin