Model Infections: Staphylococcus aureus and Pseudomonas aeruginosa PDF

MODEL INFECTIONS Nigar Kirmani , M.D. [email protected] No Disclosures This Session’s Microbes for the Scaffolding Table Aspergillus fumigatus Cryptococcus neoformans Cytomegalovirus (CMV) Influenza virus Measles virus Pseudomonas aeruginosa Staphylococcus aureus...

MODEL INFECTIONS Nigar Kirmani , M.D. [email protected] No Disclosures This Session’s Microbes for the Scaffolding Table Aspergillus fumigatus Cryptococcus neoformans Cytomegalovirus (CMV) Influenza virus Measles virus Pseudomonas aeruginosa Staphylococcus aureus GatewayC U R R I C U L U M  OBJECTIVES Describe the virulence factors, host response, diseases and characteristics of Staphylococcus aureus Describe the virulence factors, host response, diseases and characteristics of Pseudomonas aeruginosa Describe the virulence factors, host response, diseases and characteristics of Cryptococcus neoformans and Aspergillus fumigatus Describe the characteristics, transmission and pathogenesis of Influenza virus Describe the characteristics, transmission and pathogenesis of Cytomegalovirus Describe the transmission and characteristics of Measles virus GatewayC U R R I C U L U M MODEL INFECTIONS Microbes cause disease in many ways EPICRDT Acute bacterial infection E – Ecology, Epidemiology Staphylococcus aureus P –Pathogenesis, Pseudomonas aeruginosa virulence Chronic bacterial infection I – Immune Mycobacterium tuberculosis response Fungal infections C - Clinical Cryptococcus neoformans presentation Aspergillus fumigatus R – Risk factors Viral infections D – Diagnosis, DD Influenza T - Treatment Cytomegalovirus Measles GatewayC U R R I C U L U M GatewayC U R R I C U L U M GatewayC U R R I C U L U M GatewayC U R R I C U L U M Staphylococcus aureus - ETIOLOGY (the pathogen) Gram-positive cocci in clusters, catalase positive and coagulase positive Found in anterior nares in 30% of people Most common bacterial pathogen isolated 1 million infections, 20K deaths/year in US Transmission is via skin Leading cause of skin, soft tissue infection Can spread via blood stream to many organs (heart valves, bones, joints, lungs) Increasing infection related to IV drug use https://bio.libretexts.org/ GatewayC U R R I C U L U M Staphylococcus aureus - Virulence Surface adhesins –bind to fibrinogen, fibronectin Invasins – help spread (leukocidin, hyaluronidase, hemolysins) Inhibit phagocytosis (Protein A) Biofilm formation Todars Textbook of Bacteriology Toxins TSST (toxic shock toxin, a superantigen) EFT (exfoliative toxin, scalded skin syndrome) SE (Staphylococcal enterotoxin - food Staphylococcal scalded skin poisoning; superantigen) syndrome GatewayC U R R I C U L U M GatewayC U R R I C U L U M Staphylococcus aureus – IMMUNE RESPONSE An acute suppurative response, with recruitment of polymorphonuclear neutrophils (PMNs) and pus formation Abscess formation and tissue destruction are common Recurrent staphylococcal infections are seen in patients with neutrophil defects; but also in immunocompetent hosts with overcrowding, prisons, day care (Community-acquired or CA-MRSA) Staphylococcal abscess https://www.cdc.gov/ GatewayC U R R I C U L U M Staphylococcus aureus – Clinical Diseases Localized infection Skin and soft tissue infections Surgical site infections Invasive infection Blood stream (bacteremia -never ignore!) Heart valve (endocarditis) Bone (osteomyelitis), joint (septic arthritis) Toxin mediated Toxic shock syndrome (TSS) Scalded skin syndrome (SSS) Robbins Pathologic Basis of Disease 10th edition Food poisoning GatewayC U R R I C U L U M GatewayC U R R I C U L U M Staphylococcus aureus – Antibiotic resistance Penicillin introduced in 1941, resistance by β- lactamase production developed by 1942 Methicillin resistance in 1960 by altering the binding site (PBP2 to PBP2 A); the era of MRSA is born MRSA became the dominant organism in hospital- Timeline of resistance S aureus acquired infection (HA-MRSA); 50-80% ICU isolates https://www.semanticscholar.org/ In 1990s, another MRSA emerged in the community with a different mobile genetic element (CA-MRSA); CA-MRSA is sensitive to more antibiotics, seen in overcrowding, prisons, athletes, day care Increasing resistance to many antibiotics - macrolides, clindamycin, aminoglycosides; even Antibiotic resistance mechanisms S vancomycin (VRSA), although this is rare aureus https://eprints.keele.ac.uk GatewayC U R R I C U L U M GatewayC U R R I C U L U M  Staphylococcus aureus – Antibiotics (reference only) MSSA Antistaphylococcal penicillin (oxacillin) First generation cephalosporin (cefazolin) Oral – 1st generation cephalosporin MRSA Vancomycin Daptomycin Ceftaroline (fifth generation cephalosporin) Linezolid Oral – Trimethoprim-sulfamethoxazole GatewayC U R R I C U L U M KEY POINTS – Staphylococcus aureus Gram positive cocci in clusters, coagulase positive Colonizes anterior nares frequently Virulence factors – adhesins, invasins, biofilms, toxins Causes necrosis, pus, abscesses; destructive infections Diseases – skin and soft tissue infections, invasive infections (heart, bone, joints), toxin mediated infection (TSS, SSS) Methicillin sensitive (MSSA, β lactamase ) or resistant (MRSA, by altered penicillin binding protein PBP2 to PBP2A) MSSA and MRSA are treated with different antibiotics Community MRSA is different from hospital acquired; seen in overcrowding, prisons, athletes; sensitive to more antibiotics GatewayC U R R I C U L U M GatewayC U R R I C U L U M Gram-Negative Bacilli BJH 2017 Organism Number Escherichia coli 7091 Enterobacter aerogenes 226 Enterobacter cloacae complex 509 Klebsiella pneumoniae 1522 Klebsiella oxytoca 293 Proteus mirabilis 969 Citrobacter freundii complex 204 Serratia marcescens 207 Pseudomonas aeruginosa 1430 GatewayC U R R I C U L U M PSEUDOMONAS AERUGINOSA PSEUDOMONAS AERUGINOSA – Etiology (the pathogen) Gram negative bacilli, aerobic; produces green pigment Common in the environment; found in water, soil, in hospital sinks, showers, respiratory therapy equipment, mops Gram negative bacilli Green pigment Pseudomonas Does not usually colonize the skin or gut Very common cause of hospital acquired infection (5th), many multidrug resistant In 2017, over 32,600 MDR healthcare infections and 2700 deaths By 2020, rate increased by 32% MDR Pseudomonas https://www.cdc.gov/ GatewayC U R R I C U L U M PSEUDOMONAS AERUGINOSA - Virulence Several virulence factors - pili, flagella, LPS, exotoxins, biofilms Pili allow adherence to cell surfaces Flagella help motility and adherence LPS – lipopolysaccharide (endotoxin) Virulence factors promotes cell activation, inflammatory https://www.researchgate.net response; can lead to septic shock Biofilms are made of viscous extracellular Mucoid colonies polysaccharide, protect bacteria from host defenses and antibiotics; mucoid strains in biofilms persist in cystic fibrosis Biofilm formation https://www.researchgate.net GatewayC U R R I C U L U M GatewayC U R R I C U L U M PSEUDOMONAS AERUGINOSA – IMMUNE RESPONSE Mechanical barriers – the skin is a significant barrier to entry of microbes; surgical incisions, burns can get infected with Pseudomonas Respiratory tract – mucus, cilia help get rid of pathogens; damage to mucociliary defense (cystic fibrosis, intubation) leads to ↑ infection; mucoid strains form biofilms Catheters – intravenous, urinary catheters provide direct access to blood, urinary tract Intact immune system – infections worse in immunocompromised, especially neutropenia (decreased polymorphonuclear neutrophils) GatewayC U R R I C U L U M GatewayC U R R I C U L U M PSEUDOMONAS AERUGINOSA- Clinical Diseases Hot tub folliculitis – pustules on skin Burn superinfection https://www.woundsource.com/ Catheter-associated urinary tract infection; IV catheter bacteremia Hot tub folliculitis VAP http://www.yogavanahill.com/ https://www.researchgate.net Bacteremia, sepsis; common in patients with low white blood cells (neutropenia) especially after chemotherapy Hospital, ventilator acquired pneumonia (HAP, VAP) VAP https://www.hindawi.com/ Cystic fibrosis – chronic lung infection and inflammation Pseudomonas diseases https://www.mdpi.com/ GatewayC U R R I C U L U M GatewayC U R R I C U L U M PSEUDOMONAS AERUGINOSA- ANTIBIOTIC RESISTANCE Resistance occurs to all classes of antibiotics with increased use Multidrug resistant (MDR) and extreme (XDR) is increasing ESBL (extended spectrum beta lactamases, cefepime) Carbapenamase producing Pseudomonas resistance Pseudomonas (meropenem) https://www.sciencedirect.com Pseudomonas resistance https://www.researchgate.net Efflux pumps (ciprofloxacin) Porin loss of outer membrane (beta lactams) Aminoglycoside inactivating enzymes (gentamicin) ↑ Pseudomonas resistance: L - low level, M -multi drug, X - extreme https://www.scielo.br GatewayC U R R I C U L U M  PSEUDOMONAS AERUGINOSA- TREATMENT (reference only) There are limited antibiotic choices for Pseudomonas aeruginosa infections Antipseudomonal penicillins (piperacillin/tazobactam) Third and fourth generation cephalosporins (cefepime) Carbapenems (meropenem) Flouroquinolones (ciprofloxacin) Aminoglycosides (gentamicin) GatewayC U R R I C U L U M GatewayC U R R I C U L U M KEY POINTS: Pseudomonas aeruginosa Gram negative bacillus Virulent pathogen that can cause invasive infections Many virulence factors – pili, flagella, LPS, biofilms Diseases –skin infections (burns, hot tub folliculitis); lung infection in cystic fibrosis, bacteremia in neutropenic patients A leading cause of hospital acquired infection – ventilator associated pneumonia, catheter associated UTI, bacteremia Limited antibiotic susceptibility; increased resistance to many classes of antibiotics by several mechanisms - beta lactamases (ESBL), carbapenamases, efflux pumps GatewayC U R R I C U L U M COMMON FUNGAL PATHOGENS Opportunistic yeasts (unicellular Endemic dimorphic fungi organisms) (yeast at 37 C, mold at 25 C) Histoplasma capsulatum Candida species Blastomyces dermatitidis Cryptococcus neoformans Coccidioides immitis Molds (multicellular, form hyphae) Aspergillus species Zygomycetes GatewayC U R R I C U L U M CRYPTOCOCCUS NEOFORMANS CRYPTOCOCCUS NEOFORMANS – Etiology (the pathogen) Yeast with a large polysaccharide capsule Reproduces by budding Associated with pigeon guano, rotting India ink preparation CSF vegetation, soil https://phil.cdc.gov/ Infection occurs by inhalation Dissemination via blood to several sites can occur 220,000 cases of cryptococcal meningitis, 180K deaths yearly Pulmonary cryptococcosis https://radiopaedia.org/ GatewayC U R R I C U L U M CRYPTOCOCCUS NEOFORMANS - Virulence Has a large polysaccharide capsule that inhibits phagocytosis Strains without capsule rarely cause disease Melanin production – acts as antioxidant Polysaccharide capsule, budding https://ppdictionary.com Can survive in intracellularly in phagosomes in alveolar macrophages Tropism for the central nervous system, causes infection of meninges and brain Fontana mason stain Cryptococcus – stains melanin GatewayC U R R I C U L U M GatewayC U R R I C U L U M CRYPTOCOCCUS NEOFORMANS Automated blood cultures can recognize Cryptococcus In tissues, several stains are used to identify yeast forms – H&E, GMS, Mucicarmine Granulomas may be seen in immunocompetent patients, rare in immunocompromised Hematoxylin eosin(H&E) GMS -Methenamine silver Mucicarmine GatewayC U R R I C U L U M GatewayC U R R I C U L U M GatewayC U R R I C U L U M CRYPTOCOCCUS NEOFORMANS- Immune response Opportunistic fungus Most cases are seen with T cell depletion in immunocompromised hosts, including HIV, transplants, biologics, chemotherapy Granulomas seen in immunocompetent Minimal inflammatory response in Masses of mucicarmine staining (red) Cryptococci in brain Robbins Pathologic Basis of Disease 10 th edition immunocompromised, leading to masses of gelatinous organisms Most common cause of meningitis in AIDS when CD4 T cell counts are < 100 cells Incidence has decreased with ART (antiretroviral therapy) Cryptococcus in brain: https://www.stepwards.c om GatewayC U R R I C U L U M CRYPTOCOCCUS NEOFORMANS – Clinical Disease Meningitis – the most common manifestation; symptoms may be chronic and subtle (confusion, headache); leads to increased intracranial pressure Cryptococcoma - abscesses (brain, lung) Lung infection – pneumonia, nodules Crypococcomas brain: https://radiopaedia.org/ Disseminated infection; skin lesions indicate disseminated disease Cryptococcal pulmonary nodules: https://radiopaedia.org/ Cryptococcal skin lesions GatewayC U R R I C U L U M GatewayC U R R I C U L U M CRYPTOCOCCUS NEOFORMANS – TREATMENT (reference only) Initially, 2 drugs are used - Amphotericin plus flucytosine This is followed by high dose azole- fluconazole (maintenance) Treat elevated CSF pressure aggressively (repeated LPs) As immune system recovers, it responds to opportunistic infection with an overwhelming inflammatory response; patients may get worse (immune reconstitution, IRIS) Wait before starting antiretroviral treatment for patients with HIV (to avoid IRIS) GatewayC U R R I C U L U M GatewayC U R R I C U L U M KEY POINTS CRYPTOCOCCUS Encapsulated yeast, reproduces by budding Large polysaccharide capsule prevents phagocytosis; melanin is antioxidant Mucicarmine stain (in addition to H&E, silver stains) in tissue diagnosis Acquired by inhalation; tropism for CNS Disease in immunocompromised- advanced HIV, transplant Meningitis, pulmonary, skin lesions, disseminated infection Most common cause of meningitis in AIDS if CD4