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157 Cards in this Set
- Front
- Back
Lowest concentration of drug required to inhibit growth of bacterium in vitro
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MIC- min inhibitory concentration
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the MIC that defines whether a bacterium is resistant or susceptible to a drug. Determined by usual drug serum levels
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break point
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All penicillin-family antibiotics have ____________
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beta-lactam ring (called beta-lactam antibiotics)
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What happens when transpeptidase enzyme is bound by beta-lactam ring?
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Competitively inhibited -> cell wall synthesis is arrested --> DEATH of bacteria
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Lowest antibiotic concentration (in μg/ml) that kills 99.99%
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Minimal bactericidal concentration (MBC)
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b-lactams, aminoglycosides, quinolones, vancomycin have what in common?
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they are bacteriacidal
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In gram negative bugs, what must penicillin pass through?
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Porins
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What is one way that only gram negative bacteria can defend against penicillin?
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Altering the porins
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How do both gram neg and pos bacteria defend against penicillin?
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They can have beta-lactamase enzymes that cleave the C-N bond in beta lactam ring.
They can have an efflux pump to actively pump out the penicillin |
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Gram _____ secrete beta-lactamase (penicillinase) and thus try to intercept antibiotic outside peptidoglycan wall
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Positive (like staph)
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Gram _____ try to destroy beta-lactam penicillins in the periplasmic space, locally
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neg
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How is MRSA resistant to all penicillin family drugs?
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It alters the sturcture of the transpeptidase so beta-lactam can't bind
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polymixin, daptomycin: mech of action
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membrane perturbation
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beta-lactams, vancomycin: mech of action
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interference with cell wall synthesis
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sulfonamides and trimethoprim: mech of action
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Interference with folic acid metabolism/aka antimetabolite
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Most important adverse effect of penicllins
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allergic reaction (IgE mediated). Bronchospasm, urticaria, anaphylactic shock
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Original penicillin used in 1940s.
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Penicillin G
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Penicillins offering better coverage of gram-neg bacteria
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Aminopenicillins
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Penicillins useful against beta-lactamase-producing S. aureus
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penicillinase-resistant penicillins
(methicillin, nafcillin, oxacillin) MET a NAsty OX |
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Group offering even wider coverage against gram-neg bacteria, including pseudomonas aeruginosa. Includes carboxypenicillins, ureidopenicillins, and monobactams
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Anti-Pseudomonal penicillins
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Widely used group of antibiotics with a beta-lactam ring, resistant to beta-lactamase, cover broad spectrum of gram postive and neg bacteria
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cephalosporins
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What is penicillin G used for?
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pneumonia caused by Strep pneumoniae, group A Strep (Strep pyogenes)
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oral form of penicillin
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Penicillin V
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What is penicillin V used for?
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Group A beta hemolytics strep-caused pharyngitis
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Ampicillin and Amoxicillin part of what class?
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Aminopenicillins. broader spectrum (gram negative) than penicillin G
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6 bacteria most resistant to current antibiotics
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Enterococcus faecium
Staphylococcus aureus Klebsiella pneumonia Acinetobacter baumanii Pseudomonas aeruginosa Enterobacter species (ESKAPE) |
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One of few drugs effective against gram-positive enterococci
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aminopenicillins
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Drug of choice for Listeria infections
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amoxicillin (more effective orally)
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What is the amp-gent combo?
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Ampicillin-gentamicin (aminoglycosides); often started until cultures reveal exact organism. broad spectrum
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Penicillinase - resistant penicillins (3)
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methicillin, nafcillin, oxacilin
I MET a NAsty Ox. |
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What are the oral beta-lactamase resistant penicillins?
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The CLOX were ticking.
CLOXacillin, diCLOXacillin |
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Once MRSA has been excluded, what are DOC for penicillinase resistant S aureus?
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Penicillinase-resistant penicillins.
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Resistance that is innate to every membrane of a species or genus;characteristic of a species or genus
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Intrinsic resistance
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Resistance acquired by microbes due to genetic mutation or acquisition of new genes (due to conjugation, transduction, or transformation)
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Acquired resistance
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Anti-Pseudomonal Penicillins
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Remember James Bond weapons:
CAR, TICK, PIPE carbenicillin, ticarcillin, piperacillin |
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beta Lactamase inhibitors: what are they, when are they used?
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Inhibits beta lactamase, given in combination with penicillins.
Amoxicillin and clavulanic acid (augmentin). Ticaricillin and clavulanic acid (Timentin) Ampicillin and sulbactam Piperacillin and tazobactam |
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What are the beta-lactamase inhibitors (without combos)
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Clavulanic acid, sulbactam, tazobactam
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Advantages of cephalosporins over penicillins
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1) Addition of new basement makes more resistant to beta-lactamases
2) New R group side chain (new antenna cable) allows for double the manipulation in lab |
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Why is MRSA resistant to all cephalosporins?
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because it's changed the structure of its penicilin binding protein (transpeptidase)
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First generation cephalosporins have what sound in their name?
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CEF (like all cephalosporins) but usually spelled with a PH. EXCEPT: cefazolin (don't let it FAZE you)
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T/F any disruption to beta lactam ring ruins the antibiotic
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T
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Second generation cephalosporins have what in their names?
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fam, fa, fur, fox, tea
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Third generation cephalosporins have what in their name?
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Cef followed by a TRI (T)
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Only 4th gen cephalosporin
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Cefepime
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Advantages of 2nd gen cephalosporins
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Covers more gram negs. Good when cmomunity acquired pneumonia sputum is neg and don't know what organism is
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What is charge of most beta-lactams?
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negative
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Which beta-lactams are highly albumin bound (>80%)
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nafcillin and ceftriaxone
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How are most beta lactams eliminated?
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by kidney (secretion mainly)
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How long is serum half-life for most beta lactam antibiotics?
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short (30-120 minutes) necessitating frequent dosing intervals (4-8 hours) for serious infection.
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What is the exception to the short half-life rule of beta-lactams?
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Ceftriaxone-6-8 hour half life can be dosed daily
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What are 3 2nd-gen cephalosporins covering anaerobic bacteria and therefore useful for intra-abdominal infections, aspiration pneumonias, and colorectal surfery prophylaxis?
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Cefotetan, cefoxitan, cefmetazole
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Gram positive and gram neg coccal bacterial infections generally treated by what class?
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penicillins
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T/F Cephalosporins generally more active against enteric gram-neg rods with activity increasing with later generations
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T
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How is broader spectrum of later generation cephalosporins obtained?
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1) Resistance to beta lactamase
2) Increase penetrance thru gram-negative outer membrane |
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___________ has broadest spectrum of any beta lactam
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imipenem
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imipenem is administered with _______ to prevent enzymatic degradation
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cilastatin
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Identical spectrum to 3rd gen cephalosporins, but with fewer allergic reactions
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Aztreonam
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Major dose-related side fx of beta-lactams other than allergies
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seizures, bleeding due to platelet dysfunction (high doses)
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Drug of choice for syphilis
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penicillin
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Drug of choice for Group A and B strep
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penicillin
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Drug of choice for viridans strep endocarditis
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penicillin
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Drug of choice for tetanus
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penicillin
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Drug of choice for listeria monocytogenes meningitis
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Ampicillin/Amoxicillin (po)
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Drug of choice for all staph infections except those caused by MRSA
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methicillin, oxacillin, nafcillin
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One of drugs of choice for pseudomonas and acinetobacter; susceptible to all beta-lactamase
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piperacillin
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Drug of choice for broad spectrum hospital gram-neg coverage including pseudomonas aeruginosa
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amoxicillin + clavulanic acid; piperacillin + tazobactam
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Gram negatives producing class C β-lactamase
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Serratia, Providentia,indole-pos proetus, citrobacter, Enterobacter
SPICE |
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Drug of choice for Gram negatives producing class C β-lactamase
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imipenem (a carbapenem)
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Drug of choice for patients with immediate hypersensitivity (Type I) reactions to other β lactam antibiotics
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aztreonam
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T/F pathogenic anaerobic bacteria are immediately killed by O2
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False. They're usually bacteriostatic - O2 will prevent growth but won't immediately kill
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Characteristics (4) of anaerobic infection
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1) Predisposing conditions (eg, tissue damage or impaired circulation)
2) Endogenous organisms (usually normal flora) cause the infection 3) Multiple types of organisms in infection site 4) Abscess formation and tissue necrosis present 5) Foul odor due to fermentative end products |
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T/F Stomach and small intestine contain high numbers of bacteria
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F. There are increasing numbers of bacteria with distance from stomach
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Bacteroides fragilis
Prevotella melanogenicus Fusobacterium nucleatum All fall into what category? |
Anaerobic, gram-negative bacteria encountered clinically
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Clostridium perfringens
Clostridium difficile All fall into what category? |
Anaerobic, Gram-positive spore forming bacilli encountered frequently clinically
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Most common colonic bacteria
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In decreasing order: Bacteroides, Bifidobacterium, coliforms, strep, clostridium
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What are functions of normal intestinal microflora?
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1) Metabolize dietary fiber resulting in increased caloric intake (increased in obese people)
2) Gas metabolism (Produces H2S, Co2, H2, CH4) depending on diet 3) Biosynthesis of Vitamin K and B12 4) Protects against colonization of pathogens 5) Stimulates non specific immunity and induces antibacterial peptides |
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T/F Essentially every type of infection can be caused by anaerobic bacteria
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T
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Most common blood culture in patients with anaerobic bacteremia
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Bacteroides fragilis (gram neg, non spore forming obligately anaerobic rods)
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Most predominant species of Bacteroides isolated from clinical specimens
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bacteroides fragilis
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Major virulence factor of B fragilis
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Capsular polysaccharide, that inhibits phagocytosis and induces abscesses. The purified capsule alone can induce abscess formation in lab animals.
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Type of infections caused by B fragilis
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Disease:
Causes abscesses alone or in mixed infections Usually in the peritoneal cavity |
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Minor virulence factors
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Proteolytic enzymes
Same strains (10%) produce an “exotoxin” - metalloprotease, may disrupt colonic epithelial cells |
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Gas Gangrene
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generally occurs at the site of trauma or a recent surgical wound in patients with vascular disease. The onset of gas gangrene is sudden and dramatic.
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Gas gangrene: common causative agent
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Clostridium perfringens
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characteristics of clostridium
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gram positive, spore forming bacteria, naturally in intestinal tracts of man and animals
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What do most species of clostridium ferment?
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carbs or AMINO ACIDS via stickland rxn producing large amounts of gas.
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What is lecithinase and what does it do?
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An α toxin produced by C perfringens causing membrane damage by destruction of lecithin --> increased vascular permeability
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Has box car shaped rod on gram stain and rapid generation time
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C perfringens
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Major virulence factor of C perfringens
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alpha toxin: lecithinase
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Types of wound infections caused by C perfringens
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Wound contamination; Anaerobic cellulitis; Myonecrosis (aka gas gangrene)
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What happens in clostridial myonecrosis?
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Clostridia infects necrotic tissue. Associated with toxemia, local edema, gas, and 15-30% death rate in untreated cases.
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CAUSATIVE AGENT OF PSEUDOMEMBRANOUS COLITIS (PMC)
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C difficile
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Major virulence factors of C difficile
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Ability to overgrow in the colon if predominant colonic anaerobes decimated by antibiotics
Toxins A and B |
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Food poisoning by __________ is 2nd in incidence behind Staph Aureus
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C perfringens
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What is the course of illness for C perfringens food poisoning?
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After ingested, bacteria sporulates in small intestines producing enterotoxin causing diarrhea lasting 24-48hours. Usually no vomiting.
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Major risk factor for pseudomembranous colitis
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Recent antimicrobial use
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What antibiotics implicated in pseudomembranous colitis?
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Almost all except vancomycin and metronidazole, parentally administered aminoglycosides and erythromycin
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What do C difficile's A and B toxins do?
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Catalyze a monoglycosylation of GTP binding proteins (Rho, Rac, CDC 42) known to be involved in regulation structural proteins controlling cell shape
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What is used to treat C difficile?
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Vancomycin, metronidazole
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Gram-positive rod
Obligate anaerobe Sporeformer Normally found in less than 5% of people outside of hospitals Characteristics of what? |
C difficile
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Structure of C diff toxin
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Binding domain – binds mammalian cell receptor
TcdA – receptor is disaccharide TcdB – receptor unknown Translocation domain – translocation of enzymatic domain into host cell Enzymatic domain – catalyzes glucosylation of G protein |
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Difference between frank and opportunistic infections
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frank infections cause disease in normal, unvaccinated humans. Opportunistic pathogens show low invasiveness but once established can cause life-threatening disease
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Pseudomonas aeruginosa
is an example of what? |
opportunistic infection
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Pseudomonas aeruginosa: characteristics
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The premier opportunistic pathogen
Gram-negative rod Single Polar flagellum Aerobe, Nonfermenter (no acid from glucose). Grows from 20° to 42°C (i.e., body temp.) Ubiquitous - free-living in all environmental habitats (especially soil/water) Simple growth requirements Versatile nutrition |
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What is electron acceptor for Pseudomonas aeruginosa?
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Inorganic - eg., O2, NO3
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What color is characteristic of the species?
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Green (can be blue in pyocyanin)
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Common infections by P. aeruginosa
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1) Pulmonary infections (from respirator)
2) Bacteremia/fatal sepsis 3) Otitis externa (swimmer's ear) 4) UTI 5) Meningitis 6) Septic arthritis, endocarditis 7) Folliculitis/Dermatitis/Vasculitis 8) Eye infections |
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Cause and characteristics of P. aeruginosa pulmonary infections
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Very severe. Happens to people on ventilators (because of the humidifiers). Common in cystic fibrosis - 90% have chronic pulmonary disease from P aeruginosa
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seen in leukemia patients on immunosuppressive drugs, burn patients, diabetes patients, patients with neutropenia
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Bacteria/fatal sepsis caused by P. aeruginosa
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After bacteremia, invasion/destruction of blood vessel walls --> cutaneous papules --> black necrotic ulcers
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Ecthyma gangrenosum
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Ulcerative keratitis following corneal trauma caused by infection with what?
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P aeruginosa
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Presumptive Lab Dx of P aeruginosa
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Gram stain shows Gm-neg. rods
Lactose non-fermenting(white colonies on Lac-MacConkey). Oxidase Positive Blue-green pigment Fruity-aroma (grapes). |
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P aerignosa: oxidase pos or neg
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pos
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P aerignosa:gram neg or pos
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neg
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P aerignosa:MacConkey results
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Lactose non-fertilizing (white colonies)
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What is treatment for P aerignosa?
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Difficult because high innate resistance. Must be tailored to sensitivity of each isolate (can change during tx!)
Use combo therapy: Gentamycin+ppiperacillin Cipro for UT infections Aminoglycoside (gentamycin or tobramycin) + new b-lactam (azlocillin, ceftazidime, or imipenem) or a new Quinolone (Ciprofloxacin) |
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Treatment of Cystic Fibrosis
|
Antibiotics to minimize lung damage and treat lung infections. Nebulizer is sometimes used to deliver aerosolized antibiotics to the lungs to help open up the airways and prevent or treat respiratory infections.
Postural drainage using “chest physical therapy [CPT]” requires vigorous percussion (by using cupped hands) on the back and chest to dislodge the thick mucus from the lungs. |
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Why are CF patients especially susceptible to P aeruginosa?
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The CFTR Cl- ion pump is normally a cell receptor for P aeruginosa to internalize the organisms for destruction, so they can't get internalized
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T/F • Desquamation of bacteria-laden epithelial cells is a host defense mechanism to reduce the bacterial load.
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T
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What is mucoid conversion by Pseudomonas aeruginosa?
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Change whereby alginate (capsule, slime layer, glycocalyx) is produced, conferring resistance to opsonic phagocytosis
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What causes mucoid conversion by Pseudomonas aeruginosa?
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pathoadaptive mutation” in a gene (mucA) encoding an anti-sigma factor in vivo causes mucoid conversion.
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What are the virulence factors of Pseudomonas aeruginosa?
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Many - numerous toxic exoproducts secreted into the environment or directly into cells by type III secretion apparatus.
Exotoxin A blocks protein synthesis; Exoenzyme S, Proteases, PLC, etc |
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Characteristics of Exotoxin A (ETA)
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Secreted to environment, Extremely toxic
ADPR Transferase - modifies elongation factor-2 Blocks protein synthesis |
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Why is P. aeruginosa highly tolerant to most antibiotics ?
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P. aeruginosa is highly tolerant to most antibiotics due in part to efflux pumps
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What is quorum sensing?
|
system of stimulus and response correlated to population density. Many species of bacteria use quorum sensing to coordinate gene expression according to the density of their local population.
Bacteria that use quorum sensing constantly produce and secrete certain signaling molecules (called autoinducers or pheromones). These bacteria also have a receptor that can specifically detect the signaling molecule (inducer). When the inducer binds the receptor, it activates transcription of certain genes, including those for inducer synthesis. There is a low likelihood of a bacterium detecting its own secreted inducer. Thus, in order for gene transcription to be activated, the cell must encounter signaling molecules secreted by other cells in its environment. When only a few other bacteria of the same kind are in the vicinity, diffusion reduces the concentration of the inducer in the surrounding medium to almost zero, so the bacteria produce little inducer. However, as the population grows, the concentration of the |
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What are quorum sensing methods used by Pseudomonas aeruginosa?
|
When cell density is high, virulence genes are turned on.
N-(3-oxododecanoyl) homoserine lactone (3O-C12-HSL) re-enters cell when cell density high, activates LasR and turns on numerous virulence genes. |
|
causes Melioidosis - acute/chronic pneumonia, usually in tropical areas (SE Asia)
|
Burkholderia pseudomallei (gram neg)
|
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Pulmonary infection in CF patients
(other than P aeruginosa) |
Burkholderia cepacia
|
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Causes the following: Pneumonia - inhalation therapy infection
Urinary Infection - infected catheters Bacteremia - iv puncture Often antibiotic resistant, making treatment difficult |
Acinetobacter
|
|
TX for acinetobacter infections
|
Difficult due to high resistance.
Imipenem, meropenem |
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Morphology and Characteristics of Legionella pneumophila
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Gram-negative rod, motile
Difficult to stain Require a very rich medium to grow Grow slowly (5 days to form colonies) |
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Where is legionella pneumophila typcially found?
|
Common parasite of protozoa and amoeba in fresh water and soil
|
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Legionella pneumophila is gram (neg, pos)
|
neg
|
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Typical sources of Legionella pneumophila infection
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Inhalation of mist from warm stagnant water (whirlpools, showers, cooling towers, Hotel AC)
NO person to person spread |
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Symptoms of Legionellosis
|
Non-Specific Symptoms
Fever, chills, and a cough (dry or may produce sputum) Other symptoms: muscle aches, headache, tiredness, loss of appetite, abdominal pain, diarrhea, and confusion. Chest X-ray often shows pneumonia. The symptoms do not readily distinguish Legionnaires' disease from other types of pneumonia. |
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What is the range of Legionellosis?
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From Severe toxic pneumonia (Legionnaire's disease) to Pontiac Fever (100% recovery)
|
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Most severe form of legionellosis
|
Legionnaire's disease. Severe toxic pneumonia. 15% die.
A severe, toxic, progressive pneumonia 2-10 day incubation after exposure Fever, cough, chest pain, chills, shock 15% Mortality due to respiratory failure |
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Pontiac Fever: characteristics
|
A Non-pneumonic Febrile Illness
1-2 days incubation after exposure, acute onset Flu-like: Fever, dry cough, spontaneous recovery |
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Risk factors for Legionnaire's disease
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Age (middle age and older), smoking or chronic lung disease, immune system suppression
|
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What causes the lung damage seen in Legionnaire's disease?
|
Inflammatory response due to ingestion by alveolar macrophages.
Cellular immune response dominant Influx of monocytes and neutrophils leads to development of abscesses (seen as infiltrates on chest x-rays |
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How is Legionnaire's disease diagnosed?
|
Must order special tests when suspected.
Methods to detect bacteria in sputum: Gram stain shows no bacteria Direct fluorescent antibody stain PCR with specific DNA probe Detection of Legionella antigens in urine: Enzyme immunoassay Antibody levels in 2 blood samples taken 3-6 weeks apart (usually in a retrospective diagnosis). Culture organisms (specimen from lower respiratory tract) Takes 3-5 days, but most definitive for diagnosis |
|
What is Legionnaire's disease treatment?
|
Antibiotics effective
Use a -mycin or fluoroquinolone + rifampin. |
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T/F Legionnaire's is sensitive to penicillin derivatives
|
F. Usually resistant.
|
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Category of Klebsiella pneumoniae
|
Lac+ Enterobacteriacea, Normal flora
respiratory / intestinal tracts of 5% healthy individuals Related to e. Coli |
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What is the most common cause of nosocomial pneumonia?
|
Klebsiella pneumoniae
|
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Most common cause of bacteremia
|
E coli
|
|
Second most common cause of bacteremia
|
Klebsiella pneumoniae
|
|
What kind of infections does klebsiella pneumoniae cause?
|
Pneumonia - severe and destructive • most common cause of nosocomial pneumonia
Bacteremia - 2nd most common cause (1st is E. coli) Urinary tract infections - especially hospital acquired Burn wound infections |
|
Causes of virulence of Klebsiella pneumoniae
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Capsule - ~80 serotypes
High resistance to antimicrobial agents |
|
Tx of Klebsiella pneumoniae
|
Cefotaxime, ceftriaxome, ceftazidime, cefepime
|
|
What does Klebsiella pneumoniae look like when cultured on Endo agar?
|
Slimy, mucoid, raised, forms long stringy threads when drawn with a loop
|
|
Characteristics and risks of Serratia sp.
|
Normal flora
Produces a bright red pigment Opportunistic pathogen Causes serious hospital acquired infections, particularly in the newborn and debilitated. |
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Treatment of serratia
|
imipenem, meropenem
|
|
Which bacteria produces urease, raising urine pH which can facilitate formation of renal stones?
|
Proteus vulgaris
|
|
Classification of proteus vulgaris
|
rod-shaped, Gram negative bacterium.
Enterobacteriaceae Extremely motile - tend to "swarm" on an agar plate instead of forming distinct colonies |
|
Proteus vulgaris is implicated in what infection?
|
Urinary tract infections
|
|
Tx of proteus vulgaris
|
Cefotaxime, ceftriaxome, ceftazidime, cefepime
ampicillin; TMX-SMP |