Lecture 9 CH08 Pathogenic Microorganisms PDF

Pathogenic Microorganisms Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives ▪ Describe the mechanism by which antibiotics inhibit the growth and metabolism of bacteria. ▪ Explain the adverse effects of antibiotics. ▪ Explain th...

Pathogenic Microorganisms Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com. Learning Objectives ▪ Describe the mechanism by which antibiotics inhibit the growth and metabolism of bacteria. ▪ Explain the adverse effects of antibiotics. ▪ Explain the mode of action in virus infections, and describe how the body’s response to viral infection leads to recovery. ▪ List the common infections caused by chlamydiae, mycoplasmas, and rickettsiae. ▪ Discuss the spectrum of infections caused by fungi. Explain the factors that predispose to systemic infections. Describe the methods used to treat fungal infections. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Explain how bacteria are classified. List and describe the major groups of pathogenic bacteria. Pathogenic Microorganisms Bacteria ▪Chlamydiae ▪Rickettsiae and ehrlichiae ▪Mycoplasma Viruses Fungi Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Classified into several large groups Classification of Bacteria Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Previously classified according to four major characteristics: ▪ Shape and arrangement: Coccus, bacillus, spiral ▪ Gram stain reaction: Gram-positive and gram-negative ▪ Biochemical and growth characteristics ▪ Aerobic and anaerobic ▪ Spore formation ▪ Biochemical profile ▪ Antigenic structure: Antigens in cell body, capsule, flagella (motility) ▪ Laborious and time consuming but low tech Modern Bacterial Classification Essential for bacterial function ▪Also based on array of proteins and peptides ▪Tests are automated using MALDI-TOF-MS (matrix assisted laser desorption/ionization time of flight mass spectrometry) ▪PCR amplification (Viruses) ▪Can identify bacteria specific peptide/protein profiles minutes to hours instead of days ▪Fast, specific Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪Modern taxonomy based on genomic sequence particulaly 16S ribosomal RNA Major Classes of Pathologic Bacteria not quite spherical or rod shaped Bacillus (rod shaped) ▪ Square ends: Bacillus anthracis (anthrax) ▪ Rounded ends: Mycobacterium tuberculosis (TB) ▪ Club shaped: Corynebacterium (Diptheria) ▪ Comma shaped: Vibrio (Cholera) Spiral organisms ▪ Tightly coiled: Treponema pallidum (Syphilis) ▪ Relaxed coil: Borrelia (Lyme) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Coccus (spherical) ▪ Clusters: Staphylococci ▪ Chains: Streptococci ▪ Pairs: Diplococci ▪ Kidney bean-shaped, in pairs: Neisseriae Gram Staining ▪Based on the chemical and physical properties of their cell walls Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪Bacteria are classified as either gram-positive or gram-negative based on ability to resist or retain certain dyes Gram Staining Red dye won’t be seen since purple is darker ▪ Gram-positive: Resists decolorization and retains purple stain ▪ Gram-negative: Can be decolorized and stains red ▪ Can also be gram variable in bacteria with thin peptidoglycan layers (Clostridium) stain light pink or dark purple ▪ Not all bacteria can be stained (Mycobacterium- no cell wall) Or bacteria with waxy coating Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Dried fixed suspension of bacteria prepared on a microscopic slide ▪ Step 1: Crystal violet (purple dye) – stains peptidoglycan ▪ Step 2: Gram iodine (acts a mordant) ▪ Step 3: Alcohol or acetone (rapid decolorization) ▪ Step 4: Safranin (red dye) Summary of Major Bacterial Pathogens and the Diseases They Cause Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com FIGURE 8-2 A comparison of cell walls of gram-positive and gram-negative bacterial cells. (A) The structure of peptidoglycan of the cell wall is shown as units of NAG and NAM joined laterally and vertically by amino acids. Summary of Major Bacterial Pathogens and the Diseases They Cause FIGURE 8-2 A comparison of cell walls of gram-positive and gram-negative bacterial cells. (B) The cell wall of a gram-positive bacteria is composed of multiple peptidoglycan layers combined with teichoic acid (a bacterial polysaccharide). Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com peptidoglycan layer on top of cell membrane • tend to be tougher Summary of Major Bacterial Pathogens and the Diseases They Cause Very thin pepidtoglycan layer, in between two other layers Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com FIGURE 8-2 A comparison of cell walls of gram-positive and gram-negative bacterial cells. (C) In the gram-negative cell wall, the peptidoglycan layer is much thinner and lacks teichoic acid. In addition, the cell wall has both an outer and inner cell membrane. Gram-negative bacteria are also unique in having lipid A (a lipopolysaccharide important in bacterial virulence) and unique proteins called porins in the outer membrane that contribute to the resistance of this class of bacteria to certain antimicrobial agents. Gram -ve The peptidoglycan layer is thick with multiple layers. – susceptible toaffect penicillin cell wall synthesis The peptidoglycan layer is thin having a single layer, protected lipopolysaccharide absent. lipopolysaccharide present Cell wall is very rigid less rigid Inner membrane Inner/Outer membrane Periplasmic space small Periplasmic regulated usually produce exotoxins. They produce both exotoxins and endotoxins.responsible for a lot of complications in a lot of diseases They show high tolerance towards dryness/physical stress less tolerance – rarely spore forming Important for controlling what will come into and out of the cell https://thebiologynotes.com/gram-positive-and-gram-negative-bacteria-with-commercial-uses/ G+ve Spore forming Clostridium/Bacillus https://onlinesciencenotes.com/differences-between-gram-positive-and-gram-negative-bacteria/ Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com gram +ve Important Pathogenic Bacteria Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Groups pathogens into appropriate groups Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Gram +ve/-ve, shape or chained - does not relate to pathogenicity – wide variety Staphylococci Normal inhabitants ▪ Skin (Staphylococcus epidermidis) ▪ Nasal cavity (Staphylococcus aureus) Commonly found on skin and in nose of patients and hospital staff Normally not pathogenic (skin provide barrier) Opportunistic organisms breaks in the skin, someone is immunocompromised, etc. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Gram-positive cocci arranged in grapelike clusters Staphylococci If they get into blood stream Cause disease by causing inflammation Can be distinguished by culture on blood agar plates Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Pathogenic strains cause disease by producing toxins ▪ Vomiting and diarrhea; toxic shock ▪ Tissue necrosis ▪ Hemolysis Staphylococci Infections yellow crusts on skin - Don’t heal as properly Sepsis: Wounds and IV drug use causes trouble wherever it goes • bacteria are just trying to live somewhere - find compartment and cause problems - don’t specifically target a place and hide like viruses do Endocarditis: Infection of lining of heart and valves ▪ Normal and prosthetic valves, IV drug use Pneumonia Some strains are highly resistant to antibiotics (methicillin-resistant Staphylococcus aureus, or MRSA) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Common skin infections: Impetigo; boils (furuncles, carbuncles); nail infection (paronychia); cellulitis; surgical wound infection; eye infection; postpartum breast infections (mastitis), Abscess Streptococci ▪ Normal inhabitants of skin, mouth, pharynx (Streptococcus viridans), gut, female genital tract (peptostreptococci) ▪ Opportunistic organisms When they gain access to blood stream, etc. Diseases: - production of pus ▪ Pyogenic: Pharyngitis, cellulitis, endocarditis, urinary tract infection ▪ Toxigenic: Scarlet fever, toxic shock syndrome ▪ Immunologic: Rheumatic fever, glomerulonephritis (induce hypersensitivity) inflammation and damage to the filtering part of the kidneys (glomerulus) autoimmune disorder that damages the kidneys Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Gram-positive cocci arranged in chains or pairs Streptococci Classification Pathogenic Most important significant medically are A,B and D Categorized further based on blood agar culture Beta hemolysis: Complete lysis of red cells ▪ Group A: many pathogenic strains (Streptococcus pyogenes): Causes pharyngitis, strep throat, tissue infections (necrotizing fasciitis, gangrene) ▪ Group B (Streptococcus agalactiae): Anal/Genital tract of women, neonatal transmission risk, meningitis, sepsis ▪ Group D (Enterococcus faecalis, Streptococcus bovis): Urinary, biliary, cardiovascular infections – difficult to treat and Ab resistant not specific Not all Ab penetrate tissues equally Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Based on type of hemolysis and differences in carbohydrate antigens in the cell walls or C carbohydrate (Lancefield classification groups A to V) Streptococci Classification ▪ Alpha hemolysis: Incomplete lysis of red cells (Streptococcus pneumoniae, Strep mutans (tooth decay) ▪ Gamma hemolysis: Nonhemolytic, no lysis major cause of pneumonia in immunosurpressed people Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Nonbeta hemolysis Pathogenic Bacteria Gram-negative cocci ▪ Most are nonpathogenic members of the genus Neisseria 2 Pathogenic members: ▪ Meningococcus: Causes meningitis (Inflammation of membranes surrounding brain and spinal cord) ▪ Gonococcus: Causes gonorrhea (STI) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Pneumococci (Streptococcus Pneumoniae) ▪ Gram +ve, grow in pairs and short chains ▪ Common cause of bacterial pneumonia, ear infections ▪ One of the most common infections in humans Pathogenic Bacteria Gram-positive bacilli – Make of several important groups More pathogenic bacteria in this group ▪ Aerobic non-spore-forming gram-positive organisms Most are non-pathogenic ▪ Corynebacteria: Nonpathogenic inhabitants of the skin and squamous body surfaces with the exception of C.diptheriae (Ulcerative inflammation of throat and injure to heart and nerve tissues) ▪ Listeria monocytogenes: Food contaminant found widely in nature (soil, plants, intestinal tract Can cause systemic illness leading to meningitis, brain abscess and serious complications to fetus by transmission through placenta contained —> vaccinations done • some countries not so much Mothers stay away from raw, non-pasteurized food (honey, etc) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Characterized based on oxygen requirements and spore forming ▪ Corynebacteria ▪ Listeria ▪ Bacilli ▪ Clostridia Pathogenic Bacteria indestructible - decades Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Aerobic spore-forming gram-positive organisms (Bacillus) ▪ Only one pathogenic member - Bacillus anthracis: Anthrax ▪ Inhalation of spores (can survive “forever” as spores) germinate and spread rapidly in alveoli ▪ Lung macrophages ingest spores and carry to lymph nodes for germination ▪ Produce toxins – tissue destruction leading to severe pulmonary and systemic infection ▪ Fever, chest pain, SOB, 20% fatality w/o tx in days ▪ Bioweapon capability (storage – containment) ▪ Requires long course AB tx – spores not susceptible Pathogenic Bacteria Can destroy immune cells progresses slowly • also known as lockjaw a Paralysis/loss of sensation due to lesion in a n e r ve If you destroy most of gut flora, it starts to take over and produce toxins that cause diheraa (long standing and difficult to get rid of all these bacterias are difficult to deal with since they are spore forming - go into spore and hide Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Anaerobic spore-forming gram-positive organisms (Clostridia) – tend to produce potent toxins and are common in soil, environment ▪ Gas gangrene (Clostridium perfringens) – contaminate wounds, proliferate in dead/necrotic muscle tissue (ferment necrotic tissue), releasing tissue destroying toxins with systemic effects (sepsis). Toxins also cause neutrophil lysis ▪ Tetanus (C. Tetani) Produces neurotoxin that causes sustained muscular contractions (bone fractures) Symptoms days to weeks after exposure Fatal due to effect on respiratory muscles ▪ Botulism (C. botulinum) – food poisoning from toxin ingestion of improperly cooked/ stored food, infants particularly susceptible Produces neuroparalytic toxins – pathology not caused by infection ▪ Intestinal infection (C. Diff) Antibiotic – associated colitis (Broad spectrum Ab use) Gram negative Bacteria that cause diseases of interest ▪ Yersinia pestis (Plague) PNS degradation - lack of sensation leads to injury/limb loss ▪ Salmonella, Shigella, Campylobacter (Food poisoning – GI infection) ▪ Legionella (Legionnaire's disease) – severe pneumonia Inhaled from contaminated water (infects alveolar macrophages) ▪ Vibrio Cholerae (Cholera) – severe, acute watery diarrhea ▪ Helicobacter pylori (stomach inflammation - Ulcers) ▪ E.coli – common to GI tract resident but some strains that are ingested raw/uncooked animal products (typically on can develop toxic effects including: inflammation, anemia, bloody diarrhea and abdominal pain. Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Hemophilus Influenzae (variety of infections lung, CNS, Skin, blood) Pathogenic Bacteria Spiral organisms ▪ Syphilis (Tremponema pallidium) Immune cells leaving and coming to the site Acid-fast bacteria (waxy coat, difficult to stain) - cause granulatomas inflammation (Macrophage infection) dont have cell wall - not as strong but hard to treat since most Ab are for gram positive/negative ▪ Tuberculosis (Mycobacterium tuberculosis) – Primarily infects lungs (airborne – highly contagious) Most show no symptoms (latent) 10% progress (increased in immunodef) Chronic cough (blood in sputum) fever, wight loss “consumption” ▪ Leprosy (Mycobaterium leprae) Infection leads to skin lesions, peripheral nerve damage (lack of sensation, muscle weakness, vision loss Low infectivity and pathogenicity (95% do not progress to disease – often slow (up to 20y) to develop Binds to Schwann cells - chronic inflammation causes most/all damage Affect sensation in periphery Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Lyme disease (Borrelia burgdorferi) Transmitted though infected tick bite to spread throughout the body Stage 1: circular “bulls eye” rash accompanied with flu like symptoms Stage 2: cardio (heart palpitations), neuro (meningitis, facial paralysis) and joint pain Stage 3: chronic arthritis and neuro deficits (memory, fatigue, insomnia) Chlamydiae doesnt seem to belong - behave like viruses ▪ Gram-negative, nonmotile bacteria ▪ Obligate intracellular parasites ▪ Form inclusion bodies in infected cells after they are phagocytosed ▪ Have rigid cell wall and reproduce by a distinct intracellular cycle ▪ Susceptible to tetracycline and erythromycin ▪ No vaccine available Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Are deficient in enzyme production and can only live as parasite of infected cell Chlamydia infection Life cycle resembles that of a virus builds many copies of itself Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Cell burst causing spread Chlamydiae ▪ Psittacosis (pneumonia): Inhalation of dried bird feces ▪ Trachoma (Chlamydia trachomatis A,B, C): Chronic conjunctivitis, blindness ▪ Nongonococcal urethritis (men): Spread to other areas ▪ Cervicitis (women): Lead to salpingitis, pelvic inflammatory disease, infertility, ectopic pregnancy ▪ Neonatal inclusion conjunctivitis: Newborn from infected mother Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Chlamydial Diseases typically in the genetical tract but depends on where contact was made Rickettsiae and Ehrlichiae Obligate intracellular parasites (typically endothelial cells)– both transmitted by insect bites ▪ Both respond to some antibiotics ▪ Respond to some antibiotics Rickettsia Disease: Infects, proliferates endothelial cells in small blood vessels of skin - causing damage, leakage of blood into surrounding tissues (rash and edema) - build-up of fluid :n body's t i ss u e s ▪ Rocky Mountain Spotted Fever (ticks) ▪ East Coast spring and early summer; flu-like ▪ Rash after 2 to 6 days, hands and feet then trunk, affects CNS ▪ Rickettsialpox (mites from mice) flu like symptoms, full-body rash Typhus: flu-like, rash (epidemic: lice; endemic: fleas, mites) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Lack genes for glycolysis or biosynthesis of amino acids/nucleosides Rickettsiae and Ehrlichiae Ehrlichiosis: Susceptible to tetracycline or chloramphenicol ▪ Infect and multiply in neutrophils or monocytes Stay in endosomal component tot live inside such cells indefinitely ▪ Cause febrile flu like (muscle aches, chills) illness with skin rash ▪ Transmission enhanced by poor hygiene, overcrowding, wars, poverty Might have been engulfed Member of family is remarkably similar to possible mitochondria descendant Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Transmitted via bite of an arthropod vector (ticks, mites, lice, fleas) Mycoplasma ↓ discomfort -> muscle pain Smallest, no cell wall, free-living bacteria ▪ About the size of a virus (0.3 micrometer) ▪ Has a cell membrane (cholesterol), but no cell wall ▪ Medical implications: Stains poorly ▪ Penicillin and cephalosporin are not effective – but do respond to some antibiotics (tetracycline, erythromycin) ▪ Can reproduce outside living cells, can grow on artificial media Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Primary atypical pneumonia: Mycoplasma pneumoniae ▪ Most common in winter, young adults, outbreaks in groups ▪ Cough, sore throat, fever, headache, malaise, myalgia ▪ Resolves spontaneously in 10 to 14 days ▪ Responds to antibiotics: Tetracycline and erythromycin Viruses very specific - target specific cell and hijakc machinery Nucleoid: Genetic material, DNA or RNA, not both Capsid: Protective protein membrane surrounding genetic material Coat/Envelope – combination of host membrane and viral proteins (retrovirus) Also non-enveloped viruses (Adenovirus) Very specific in their target cells big problem as they are not even alive - hard to control https://en.wikipedia.org/wiki/Hepatitis_C_virus Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Classification ▪ Nucleic acid structure: Either DNA or RNA (ss,ds, +/-ve), enclosed in a capsid, with an Not always outer envelope made of lipoprotein (often from host cell) ▪ Size and complexity of genome varies (8-400 genes) HIV, HSV ▪ Smaller than cells (20 to 300 nm diameter) ▪ Cannot be seen under a light microscope Viruses Binds specifically to receptor and enters through endocytosis Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Obligate intracellular parasites ▪ Must reproduce or replicate within cells ▪ Lack metabolic enzymes; rely on host’s metabolic processes for survival ▪ Do not have nucleus, ribosomes, mitochondria, and lysosomes; cannot synthesize proteins or generate energy ▪ Do not multiply by binary fission or mitosis fuses with cell membrane and deposit materials that has instructions for more viral production Viruses eva r i c e l l a zoster Until they reemegere and cause damage in epithelial cells specific of liver cells c Production of viral DNA causes this Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Modes of action ▪ Invasion of susceptible cell ▪ Asymptomatic latent viral infection (HSV, VZV:Herpes Zoster/Shingles) – dormant in neural cells ▪ Acute cell necrosis and degeneration (Ebola) ▪ Cell hyperplasia and proliferation (HPV) ▪ Slowly progressive cell injury (HCV) Yep ▪ Neoplasia (HPV) ▪ Destruction of immune system (HIV) ▪ Formation of inclusion bodies (protein aggregates) from prolific viral replication resulting in cellular toxicity (smallpox, rabies) Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Viruses Bodily defenses against viral infections ▪ (Innate/Adaptive) formation of interferons: Broad-spectrum antiviral agent Inhibits viral replication (non-specific), activates immune cells ▪ Cell-mediated immunity (CD4/CD8 T cells -specific) ▪ Humoral defenses (B-cell – Ab production) ▪ Cell mediated (against infected cells) often superior to Humoral Both immune and non-immune cells can secrete this CD8 T-cells recognizing infected cells - only efficient method we have Treatment with antiviral agents ▪ Block viral replication (HIV/HCV) ▪ Prevent virus from invading cell (HIV) ▪ Limited application: Toxicity and limited effectiveness (not “alive”) ▪ Symptomatic, supportive 95% cure rate Effective viral treatments for these Makes it hard to kill not much drugs because of this • hard to control and produce rapidly • hard to control their replication as this is all they are doing Best Defense for most viral infections: Vaccination Preventive/Therapeutic Community vs Personal Immunity huge variation in immune systems • group immunity should be able to survive it Something you give to someone after they have been infected Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com not good against viruses - very few Fungi Plantlike organisms without chlorophyll ▪ Most are obligate aerobes need air - don’t have much access to it in the body ▪ Cell wall: Chitin versus peptidoglycan ▪ Cell membrane: Ergosterol and zymosterol versus cholesterol ▪ Growth factors: High humidity (moist), heat, dark areas with oxygen supply ▪ Other fungi: Bread, cheese, wine, beer production ▪ Frequently associated with decaying matter ▪ Molds: Spoilage of foods (fruits, grains, vegetables, jams) Common in soils Doesn’t cause much disease unless you are immunocompromised Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Two main types: Yeasts (small ovoid/spherical) and molds (branching/filamentous) Fungi Most are present ubiquitously in our natural habitat/ environment Immune system deals with them easily in normal person • Chronic disease chemo can suppress immune system • Immunocompromised (opportunistic) HIV, Cancer tx • Loss of regular bacterial flora (competition) Antibiotics • Lack of Hygiene – superficial skin infections (dematophytes) Treatment: Antifungal drugs or topical treatment in mild cases Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com May cause infection in the presence of certain conditions: Fungi Ex. Athletes foot ▪ Mucous membranes (Candida albicans): Common in immunocompromised patients with Infection on tongue, mouth, esophagus (thrush) ▪ Aspergillus fumigatus –spores from decaying plant matter Can result in severe pulmonary and systemic disease in immunocompromised Ccontributes and exacerbates allergic Asthma development can stimulate an attack ▪ Histoplasmosis, coccidioidomycosis, blastomycosis, cryptococcosis inhaled spores in dust – usually acute, self limited respiratory infection In severe cases if they can invade blood vessels – can cause widespread systemic disease No need for treatment would need anti-fungals in these rare cases Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Fungal Infections – most are pathogens of low virulence which only become life threatening in susceptible (from coinfection or chronic disease), immunocompromised patients ▪ Superficial fungal infections –skin Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Not as simple as presenting the virus to cells sometimes Antibiotics: Mechanisms of Action Penicillin family: Penicillin, methicillin, nafcillin, oxacillin, amoxicillin, ampicillin, piperacillin, ticarcillin make bacteria susceptible and weaker so that immune system can destroy them Cephalosporins: Cephalexin, cefoxitin, ceftazidime, ceftriaxone; vancomycin, bacitracin ▪ Inhibits synthesis microbial proteins, ribosomal subunits (targets DNA synthesis, replication) Chloramphenicol; tetracycline; macrolide; erythromycin, azithromycin, clarithromycin; clindamycin, gentamicin, netilmicin, streptomycin Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Inhibits synthesis of bacterial cell wall (leads to swelling-rupture) and cell membrane(injury-death) Antibiotics: Mechanisms of Action Inhibits bacterial DNA synthesis ▪ Ciprofloxacin, norfloxacin, ofloxacin, Need to consider route and delivery Ex: vancomycin (blocks cell wall synthesis ▪ only effective against gram +ve ▪ Not absorbed through inestine (good for C. diff) ▪ Must be IV for systemic use If taken orally, won’t leave GI tract and go anywhere else in the body have to consider resistance: • Some can have more resistance than others Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Inhibits bacterial metabolic functions (loss of metabolic functions) ▪ Inhibits folic acid synthesis: Sulfonamides, trimethoprim Antibiotic Sensitivity Tests bacteria are becoming more tolerant to these antibiotics Filtered out here Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Tube dilution: Measures the highest dilution that inhibits growth in test tube ▪ Disk method: Inhibition of growth around disk indicates sensitivity to antibiotic ▪ MALDI-TOF-MS identification of strains with known antibiotic-resistance characteristics ▪ Also need to consider patient allergy/ resistance, organ function and ability of Ab to access infection site ▪ Tetracycline levels – Kidney function ▪ need to consider route of administration/delivery Antibiotics: Adverse Effects ▪ Toxicity –kidney injury, other tissues ▪ Alteration of normal bacterial flora – C. Diff emerges in cases where broad ranged antibiotics are being used inappropriately ▪ Development of resistant strains ▪ Spontaneous mutation ▪ Plasmid-acquired resistance ▪ Mechanisms for circumventing effects of antibiotics ▪ Develop antibiotic enzymes (penicillinase) ▪ Change cell wall structure (repel Ab) ▪ Change internal metabolic machinery (Ab loses function/binding) Can spread as bacteria contact each other - bacteria can exchange DNA highly mutagenic - can adapt incredibly Need to make sure dose and schedule is maintained so that resistance is avoided Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com ▪ Hypersensitivity – Penicillin allergy/ anaphylaxis Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Lack of antibiotics that we have for these Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com Once you develop an antibiotic, bacteria will find a way to be resistant against it as they mutate rapidly Copyright © 2021 by Jones & Bartlett Learning, LLC an Ascend Learning Company. www.jblearning.com not developing as many antibiotics • fewer and fewer as time passes