Week 1 Flashcards
Minimum inhibitory concentration
concentration of drug bacteria stops growth
Minimum bactericidal concentration
concentration of bactericidal drug at which 99% of bacteria are killed
DQ CRIMES
important metabolism and/or hepatic elimination:
Clindamycin, Chloramphenicol Rifampin Isoniazid Metronidazole Erythromycins Sulfonamides, Streptogramins Doxycycline Fluoroquinolones
Features of Gram Positive organisms
1) Lipoteichoic acid
2) Thick peptidoglycan cell wall (accessible outer PG wall)
- PG can be up to 90% of cell wall
→ blue/purple
Features of Gram Negative organisms
1) Porins inserted in LPS outer membrane (endotoxin)
2) Thin peptidoglycan cell wall
3) Periplasmic space between cytoplasmic membrane and thin PG layer (B-lactamase location)
→ pink
Pattern Recognition Receptors (PRRs)
on epithelium, T, B, NK cells, phagocytes, dendritic cells
1) Transmembrane (surface) = TLR
2) Cytosolic = NOD, TLR
3) Extracellular = CD14, LBP
PRRs recognize PAMPs and DAMPs
Gram + Cocci (2)
1) Staph
2) Strep
Gram + Rods (bacilli) (7)
1) Bacillus
2) Clostridium
3) Gardnerella (gram variable)
4) Lactobacillus
5) Listeria
6) Myobacterium (acid fast)
7) Propionibacterium
Gram + branching filamentous (2)
1) Actinomyces
2) Nocardia (weakly acid fast)
No cell wall (2)
1) Mycoplasma
2) Ureaplasma (contains sterols, which do not gram stain)
Gram - cocci (2)
1) Moraxella catarrhalis
2) Neisseria
Gram - bacilli enterics (13)
1) Bacteroides
2) Camplyobacter
3) E. Coli
4) Enterobacter
5) Helicobacter
6) Klebsiella
7) Proteus
8) Pseudomonas
9) Salmonella
10) serratia
11) Shigella
12) Vibrio
13) Yersinia
Gram - bacilli respiratory
1) Bordatella
2) Haemophilus (pleomorphic)
3) Legionella (silver stain)
Gram - bacilli zoonotic
1) Bartonella
2) Brucella
3) Francisella
4) Pasteurella
Gram - pleomorphic (2)
1) Chlamydia (giemsa)
2) Rickettsiae (giemsa)
Gram - spirochettes (3)
1) Borrelia (giemsa)
2) Leptospira
3) Treponema
Penicillin G and V
Mechanism
Cell wall synthesis inhibitors
-Bind penicillin-binding proteins (transpeptidases) and block transpeptidase crosslinking of peptidoglycan in cell wall
Penicillin G and V
Toxicity (3)
1) Type I anaphylaxis reaction
2) Type III rash
3) convulsions at very high doses
Penicillin G and V
Resistance
Penicillinase (B-lactamase) cleaves B-lactam ring
Penicillin G and V
Administration / metabolism
Pen G = IV and IM
Pen V = oral
renal excretion
bactericidal
Penicillin G and V
Clinical use (3)
1) Gram + cocci and rods (staph, strep, entero, actinomyces)
2) Gram - rods (Neisseria, M. catarrhalis)
3) Spirochete (T. pallidum)
Amoxicillin, Ampicillin
Mechanism
Cell wall synthesis inhibitors
-Bind penicillin-binding proteins (transpeptidases) and block transpeptidase crosslinking of peptidoglycan in cell wall
MUST COMBINE with Clavulanic acid to protect against destruction by B-lactamase
Amoxicillin, Ampicillin
Clinical use (8)
Extended spectrum penicillin
“HHELPSS kill enterococci”
1) H. pylori
2) H. influenzae
3) E. coli
4) Listeria monocytogenes
5) proteus mirabilis
6) Salmonella
7) Shigella
8) Enterococci
Amoxicillin, Ampicillin
Toxicity (4)
1) Type I anaphylaxis reaction
2) Type III rash
3) convulsions at very high doses
4) Pseudomembranous colitis
Amoxicillin, Ampicillin
Mechanism of resistance
Penicillinase in bacteria (B-lactamse) cleaves B-lacta ring
Amoxicillin, Ampicillin
administration / metabolism
Oral
AmOxacillin is better oral
Renal excretion
Diclocacillin, Nafcillin, Oxacillin, Methicillin
Mechanism
PENICILLINASE-RESISTANT
–> bulky R group blocks B-lactamase from accessing B-lactam ring
Cell wall synthesis inhibitors
-Bind penicillin-binding proteins (transpeptidases) and block transpeptidase crosslinking of peptidoglycan in cell wall
Diclocacillin, Nafcillin, Oxacillin, Methicillin
Clinical use (1)
1) MSSA (not MRSA)
Diclocacillin, Nafcillin, Oxacillin, Methicillin
Toxicity (2)
1) Hypersensitivity reactions
2) Interstitial nephritis
Diclocacillin, Nafcillin, Oxacillin, Methicillin
Administration / excretion
Renal excretion
Oral (not methicillin or nafcillin)
Piperacillin, Ticarcillin
Mechanism
ANTI-PSEUDOMONAL
Cell wall synthesis inhibitors
-Bind penicillin-binding proteins (transpeptidases) and block transpeptidase crosslinking of peptidoglycan in cell wall
Piperacillin, Ticarcillin
administration / metabolism
IV ONLY
renal excretion
Piperacillin, Ticarcillin
Clinical use (2)
EXTENDED SPECTRUM
1) Pseudomonas
2) Bacteroides
Piperacillin, Ticarcillin
Toxicity
1) Hypersensitivity reactions (I and III)
Cephalosporins (generation 1-5)
mechanism of action
Toxicity?
B-lactam drug, inhibits cell wall synthesis but less susceptible to penicillinases
Bactericidal
Less severe allergy than penicillins (can give to patient with type III allergy, but not type I allergy to penicillins)
1st generation cephalosporins
2 names
cefazolin, cephalexin
cefazolin, cephalexin (1st gen)
uses (4)
PEcK
1) Proteus mirabilis
2) E. Coli
3) Klebsiella pneumoniae
4) **used before surgery to prevent S. aureus wound infections
2nd generation cephalosporins
3 names
cefoxitin, cefaclor, cefuroxime
cefoxitin, cefaclor, cefuroxime (2nd gen)
Use (7)
HEN PEcKS
1) Haemophilus influenzae
2) Enterobacter aerogenes
3) Neisseria
4) Proteus mirabilis
5) E. Coli
6) Klebsiella pneumoniae
7) Serratia
3rd generation cephalosporins
3 names
ceftriaxone, cefotaxime, ceftazidime
ceftriaxone, cefotaxime, ceftazidime (3rd gen)
uses
1) serious gram - infections resistant to other B-lactams
Ceftriaxone –> meningitis, gonorrhea, disseminated Lyme disease
Ceftazidime –> Pseudomonas
Ceftaroline
5th gen cephalosporin
action against MRSA
does not cover pseudomonas
Cephalosporins
mechanism of resistance
structural changes in penicillin binding proteins (transpeptidases) e.g. MRSA
Carbapenems
(imipenem, Ertapenem, meropenem, doripenem)
Mechanism
Broad spectrum B-lactamase-resistant cell wall synthesis inhibitor
Imipenem
Broad spectrum B-lactamase-resistant carbapenem
always coadministered with CILASTATIN (inhibits renal dehydropeptidase I) –> decreases inactivation of drug in renal tubules
Carbapenems
administration / metabolism
IV ONLY
renal excretion
Carbapenems
Toxicity (1)
GI distress
Carbapenems
Clinical use
1) Wide spectrum reserved for resistant organisms
Monobactams (Aztreonam)
Mechanism
Cell wall synthesis inhibitor
Less susceptible to B-lactamases
synergistic with aminoglycosides
**NO cross allergenicity with penicillins
Monobactams (Aztreonam)
Clinical use (1)
1) Gram negative rods only
* for penicillin-allergic patients or renal insufficiency who cannot tolerate aminoglycosides
Vancomycin
Mechanism
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors
bactericidal
not susceptible to B-lactamases
Vancomycin
administration / metabolism
Poor oral absorption
given IV or oral
renal excretion
Vancomycin
Toxicity (5)
1) Nephrotoxicity
2) Ototoxicity
3) Thrombophlebitis
4) Chills, fever, rash
5) Red Man Syndrome (prevent with pre tx with anti-histamine, slow infusion rate)
Vancomycin
Clinical use
1) Narrow spectrum, Gram + (**MRSA, staph epidermidis, enterococcus, C. diff/oral)
for serious multi-drug resistant organisms
Vancomycin
Mechanism of resistance
modification of amino acids D-ala D-ala –> D-ala D-lac
Fluoroquinolones
drug names
Ciprofloxacin Norfloxacin Levofloxacin Ofloxacin Moxifloxacin Gemifloxacin Enoxacin
Fluoroquinolones
Mechanism
Inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topoisomerase IV
Bactericidal
Fluoroquinolones
Administration / metabolism
Good PO or IV
Renal/HEPATIC* excretion
Fluoroquinolones
Toxicity (5)
1) CANNOT take with antacids or theophylline
2) GI upset
3) Contraindicated in PREGNANT WOMEN, nursing mothers, and CHILDREN (< 18 yrs) –> Cartilage damage
4) Tendonitis/tendon rupture in people > 60 yrs or pt taking prednisone
5) May prolong QT
“FluroquinolONES hurt attachments to your BONES”
Fluoroquinolones
Clinical use (1)
1) Gram - rods in urinary and GI tracts (including Pseudomonas and Neisseria)
Fluoroquinolones
Mechanism of resistance (3)
Chromosome encoded mutations in DNA gyrase, plasmid-mediated resistance, efflux pumps
Aminoglycosides
drug names
Gentamycin
Neomycin
Tobramycin
Streptomycin
Aminoglycosides
administraiton / metabolism
Renal excretion
IV or IM
Aminoglycosides
toxicity (4)
accumulates in kidneys and ear –>
1) nephrotoxicity
2) Ototoxicity (especially with loop diuretics)
3) Neuromuscular blockade
4) Teratogen
Aminoglycosides
Mechanism
Bactericidal
IRREVERSIBLE inhibition of initiation complex through binding of 30S subunit
can cause misreading of mRNA and block translocation
Require O2 for uptake –> ineffective against anaerobes
Aminoglycosides
Clinical use
1) Severe gram - rod infections
- synergistic with B-lactam abx
2) Neomycin for BOWEL SURGERY
Aminoglycosides
Mechanism of resistance (1)
Bacterial transferase enzymes inactivate drug by acetylation, phosphorylation, or adenylation
Tetracyclines
drug names
Tetracycline, doxycycline, minocycline
Tetracyclines
Mechanism
BacterioSTATIC
Bind 30S and prevent attachment of aminoacyl-tRNA
Tetracyclines
administration / metabolism
good PO
Doxy eliminated fecally –> can use in pts with renal failure
others renally excreted
Tetracyclines
Toxicity (5)
1) do not take with MILK or ANTACIDS, or IRON-containing preparations (divalent cations bind drug in gut and inhibit absorption)
2) GI distress
3) Discoloration of teeth and inhibition of bone growth in children < 8yrs
4) Photosensitivity
5) Fungal superinfections
Tetracyclines
Clinical use (4)
1) Borrelia Burgdorferi
2) M. Pneumoniae
3) Rickettsia
4) Chlamydia
Tetracyclines
Mechanism of resistance (1)
Decrease uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps
Chloramphenicol
mechanism
blocks peptidyl transferase at 50S ribosomal subunit
BacterioSTATIC
Chloramphenicol
Clinical use
1) Meningitis (H. influenzae, N. Meningitis, Strep. Pneumoniae)
2) Rocky Mountain Spotted Fever (Rickettsia, rickettsii)
**Limited use due to severe toxicity (but cheap so used in developing countries)
Chloramphenicol
Toxicity (3)
1) Anemia (dose dependent)
2) Aplastic anemia (dose independent)
3) Gray baby syndrome (in premature infants - lack liver UDP-glucuronyl transferase)
High toxicity
Chloramphenicol
Metabolism / administration
Glucuronidation (hepatic)
PO or IV
Chloramphenicol
Mechanism of resistance (1)
plasmid encoded acetyltransferase inactivates the drug
Clindamycin (Licosamide)
Mechanism
Blocks peptide transfer (translocation) at 50S ribosomal subunit
BacterioSTATIC
Clindamycin
Clinical use (3)
1) Anaerobic infections (bacteroides, C. perfringens) in aspiration pneumonia, lung abscesses, and oral infections
2) Invasive group A strep infections
3) **treats anaerobic infections ABOVE the diaphragm
Clindamycin
Toxicity (2)
1) Pseudomembranous colitis
2) fever, diarrhea
Clindamycin
administration / metabolism
PO or IV
penetrates BONE
Hepatic metabolism
Oxazolidinones (Linezolid)
Mechanism
inhibit protein synthesis by binding 50S subunit and preventing formation of the initiation complex
Oxazolidinones (Linezolid)
Metabolism / administration
Good PO and IV
Hepatic metabolism
Oxazolidinones (Linezolid)
Clinical use (1)
1) Gram + including MRSA and VRE (severe infections)
Oxazolidinones (Linezolid)
Toxicity (5)
1) headaches
2) GI - diarrhea, nausea
3) Inhibits MAO –> serotonin syndrome
4) Bone marrow suppression (especially thrombocytopenia)
5) Peripheral neuropathy
Oxazolidinones (Linezolid)
Mechanism of resistance (1)
point mutation of ribosomal RNA
Macrolides
drug names
Erythromycin
Azithromycin
Clarithromycin
Macrolides
Mechanism
Inhibit protein synthesis by blocking translocation
bind 23S rRNA of 50S ribosomal subunit
BacterioSTATIC
Macrolides
administration / metabolism
Good PO and IV
Concentrations in lungs
HEPATIC metabolism to ACTIVE metabolite + BILIARY elimination
Macrolides
Clinical use (4)
1) Atypical pneumonias (Mycoplasma, Chlamydia, Legionella)
2) STIs (Chlamydia)
3) Gram + cocci (strep infections in penicillin allergic patients)
4) Bordatella Pertussis
Macrolides
Toxicity (7)
“MACRO”
1) gastrointestinal Motility issues
2) Arrhythmia caused by prolonged QT interval
3) acute Cholestatic hepatitis
4) Rash
5) eOsinophilia
6) Inhibits CYP450 (erythromycin, clarithromycin)
7) Increase serum concentration of theophyllines, oral anticogulants
Macrolides
mechanism of resistance
Methylation of 23S rRNA binding site prevents binding of drug
Trimethoprim
Mechanism
Inhibits bacterial dihydrofolate reductase
BacterioSTATIC
Sulfonamides
Mechanism
Inhibits folate synthesis
Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase
BacterioSTATIC
**BACTERICIDAL when combined with trimethoprim`
TMP/SMX
Clinical use (6)
1) UTIs
2) Shigella
3) Salmonella
4) Penumocystis jirovecii pneumonia treatment and prophylaxis
5) Toxoplasmosis prophylaxis
6) Chalmydia
TMP/SMX
toxicity (5)
1) Kernicterus in neonates
2) Hypersensitivity reactions
3) Photsensitivity
4) Can displace other drugs from albumin
5) TMP (“TREAT MARROW POORLY”) can cause megaloblastic anemia, leukopenia, granulocytopenia (alleviate with folinic acid supplementation)
Sulfonamides
Mechanism of resistance (3)
1) Altered enzyme (bacterial dihydropteroate synthase)
2) decrease uptake
3) Increased PABA synthesis
Daptomycin
Mechansim
Lipopeptide that disrupts cell membrane of gram + cocci
Daptomycin
Clinical use
1) S. aureus skin infections (Especially MRSA)
2) Bacteremia
3) Endocarditis
4) VRE
**Not used for pneumonia - avidly binds/inactivated by surfactant
Daptomycin
Toxicity (1)
1) Myopathy, rhabdomyolysis
Metronidazole
Mechanism
Forms toxic free radical metabolites in bacterial cell that damages DNA
Bactericidal, antiprotazoal
Metronidazole
Clinical use (7)
GET GAP on the Metro
1) Giardia
2) Entamoeba
3) Trichomonas
4) Gardnerella vaginalis
5) Anaerobes (bacteroides, C. diff)
6) Used with PPI and clarithromycin for triple therapy against H. Pylori
**Treats anaerobic infection BELOW the diaphragm
Metronidazole
Toxicity
1) Disulfuram-like reaction (severe flushing, tachycardia, hypotension) with alcohol
2) Metallic taste
3) Headache
Nitromidazoles (Nitrofurantoin)
Mechanism
DNA damaging agent
BacterioSTATIC
Nitromidazoles (Nitrofurantoin)
toxicity (2)
1) GI upset
2) Hypersensitivity
Nitromidazoles (Nitrofurantoin)
Clinical use (1)
1) UTI - e.coli
Strep pyogenes is also known as group ______ strep
1) Gram stain and shape?
2) Hemolysis?
3) Catalase?
4) Aerobe or anaerobe?
5) Bacitracin sensitive/resistant?
6) Pyrrolidonyl arylamidase test + or -
7) Penicillin susceptible or no?
Group A strep
1) Gram + cocci, form chains
2) Beta hemolytic
3) Catalase -
4) Facultative anaerobic
5) Bacitracin sensitive
6) Pyrrolidonyl arylamidase test positive (differentiate S. pyogenes and enterococci)
7) Penicillin susceptible
Disease caused by Strep. Pyogenes
1) Streptococcal pharyngitis
2) Scarlet fever
3) Toxic Shock-Like Syndrome
4) Skin/wound infections (non-bullous impetigo, erysipelas, cellulitis, nec. fasc.)
5) Acute rheumatic fever
6) Acute glomerulonephritis
7) Poststreptococcal Reactive Arthritis
Streptococcal pharyngitis
self-limiting, life long type-specific immunity
Resolution mediated by anti-M protein antibody which allows phagocytosis and rapid killing of bacteria by PMNs/monocytes
**Can have acute RF strains OR acute GN strains
When should you culture a throat?
when shouldn’t you?
⅔ of sore throats are caused by VIRUSES (cough, runny nose) → don’t culture
Tender lymph nodes, close contact with strep → culture
Scarlet fever
systemic manifestation of pyrogenic exotoxins A, B, and C
Fever, pharyngitis, strawberry tongue, confluent erythematous “sandpaper like” rash (fine/blanching)
Rash begins on chest and neck, spreads out
-Spares nasolabial triangle and chin
Toxic Shock-Like Syndrome
systemic release of exotoxin A due to skin infection causes polyclonal activation of T cells
Fever, shock, multi-organ failure
How is staph TSS different from strep TSLS?
Different from staph because strep has 2 features NOT present in staph
1) Painful pre-existing skin infections
2) Positive blood cultures
Strep. Pyogenes skin/wound infections
include what 3 types?
rapid spread due to what?
Can cause what secondary complication?
- rapid spread due to spreading factors (streptokinase, hyaluronidase, etc.)
- Can cause acute GN (NOT RF)
1) Non-Bullous Impetigo
2) Erysipelas
3) Cellulitis
4) Necrotizing Fasciitis
Non-Bullous Impetigo
Strep. Pyogenes infection
pustular lesions, honeycomb-like crusts usually around mouth
→ PSGN
Erysipelas
Strep. Pyogenes infection
superficial infection of skin, well-defined borders
Red, tender, warm
Cellulitis due to Strep. Pyogenes infection
rapidly spreading skin infection in deeper subcutaneous tissues, ill-defined borders
Red, tender, warm
Necrotizing Fasciitis is due to what toxin?
Strep pyogenes
Exotoxin B production
Acute rheumatic fever
non-suppurative (non-pus producing) complications of strep infection
Type II hypersensitivity reaction: cross reaction between S. pyogenes antigens (M protein) and self antigens
Systemic disease 3-6 weeks after S. pyogenes infection (THROAT only, NOT skin infection)
JONES criteria
JONES criteria
Joints = migratory polyarthritis
O = endocarditis, myocarditis, pericarditis
Nodules = subcutaneous, extensor surfaces
Erythema marginatum rash
Sydenham chorea = neurologic disorder, abrupt, nonrhythmic involuntary movements, muscle weakness
Acute glomerulonephritis
non-suppurative (non-pus producing) complications of strep infection
Follows strep skin or throat infection by 2-4 weeks
Type III hypersensitivity reaction: circulating immune complex deposition causes glomerular damage
Elevated ASO or anti-DNase B titers
Poststreptococcal Reactive Arthritis
NSAID unresponsive
Evidence of recent strep infection
Arthritis in small and big AXIAL joints
Main structural and pathogenic features of Strep. Pyogenes (7)
1) Hyaluronic acid capsule
2) Attachment factors
3) M protein
4) Streptolysin O
5) Streptolysin S
6) Pyrogenic exotoxins A-C
7) Spreading factors
Hyaluronic acid capsule of strep. pyogenes
Antiphagocytic, non-immunogenic
Attachment factors of strep. pyogenes
pili, fibronectin-binding protein
Pili → mediate adhesion to epithelial cells (site specificity varies)
M protein (strep pyogenes)
surface fimbriae
> 80 serotypes, each strain expresses only a single type
Major virulence determinant:
ANTI-PHAGOCYTIC - prevent interaction of bacterial cell with complement components
Adherent to epithelial cells
If strain lacks M protein → avirulent
Immunity to strep based on development of antibodies, serotype specific
Streptolysin O
destroys RBCs
Inserts pores into RBCs causing lysis
Does not lyse neutrophils
Can measure ASO antibodies as indicator of infection
Streptolysin S
non antigenic, destroys RBCs and WBCs
Pyrogenic exotoxins A-C (strep pyogenes)
bacteriophage encoded toxin, subject to LYSOGENIC CONVERSION
-act as superantigens
Exotoxin A: causes toxic-shock like syndrome
Exotoxin B: protease precursor activated by cysteine protease → necrotizing fasciitis
Exotoxin A, B, and C → scarlet fever
4 main spreading factors present in strep pyogenes
1) Streptokinase
2) Hyaluronidase
3) DNase
4) Proteinase
Streptokinase
activates plasminogen to plasmin → fibrinolysis
spreading factor of strep. pyogenes
Hyaluronidase
degrades ground substance of connective tissue, facilitates spread through tissue
spreading factor of strep. pyogenes
DNase
nuclease which digests DNA, found in large concentrations in pus
Can get ab titers to DNase B
spreading factor of strep. pyogenes
Pathogenesis of strep pyogenes infection
- normal flora where?
- transmitted how?
Carried in normal flora of throat and skin
Transmitted via respiratory droplets, food, or direct inoculation to skin
Strep agalactiae
1) Group _____ strep
2) Gram stain? shape?
3) Bacitracin sensitive/resistant?
4) Hemolysis?
5) Two special tests that will be positive?
6) 6.5% NaCl Tolerance?
1) group B strep
2) Gram positive cocci
3) Bacitracin resistant
4) None/Beta hemolytic (weaker)
5) CAMP test +, Hippurate +
6) Variable 6.5% NaCl Tolerance
Strep agalactiae is normal flora where?
vagina
Treatment of Strep agalctiae?
penicillin G
Pregnant women with + culture → intrapartum penicillin prophylaxis (prevent neonatal disease)
Main virulence and structural features of strep agalactiae (4)
1) Lipoteichoic acid (LTA) - part of cell envelope, mediate adherence
2) Polysaccharide capsule (antiphagocytic) - mediates ab immunity
3) Neuraminidase (extracellular product)
4) CAMP factor (extracellular product)
Neuraminidase
Extracellular produce of strep agalactiae
enzyme cleaves sialic acid from polysaccharide and glycoprotein substrates
CAMP factor
enhances hemolysis of staph aureus
Used for identification
Extracellular produce of strep agalactiae
Vaccines for strep agalctiae
composed of purified HMW polysaccharides, can be given to high risk women to prevent GBS disease
Disease caused by strep agalactiae (3)
Most common cause of:
1) neonatal meningitis (<6 mo)
2) sepsis
3) pneumonia
(very high mortality)
Group D strep includes what two groups of bugs?
Enterococci and non-enterococci
Enterococci
1) gram stain?
2) hemolysis?
3) growth in bile?
4) growth in NaCl
5) Hydrolyzes ________
6) normal flora where?
1) Gram +
2) Alpha hemolytic
3) Grow well in 40% bile
4) Grow well in 6.5% NaCl
5) Hydrolyze esculin
6) Normal bowel flora
Diseases caused by enterococci (4)
1) UTI
2) Biliary infections
3) Bacteremia
4) Subacute bacterial endocarditis
Treatment of enterococcus is complicated by what?
High prevalence of ampicillin and vancomycin resistance
VRE = Vancomycin Resistant Enterococci: alter cell wall dipeptide d-ala, d-ala → d-ala, d-lac
2 important enterococci bugs
E. Faecalis, E. Faecium
Non-enterococci include…
Strep. Bovis (aka strep gallolyticus)
Non enterococci
1) gram stain? shape?
2) growth in bile?
3) growth in NaCl
4) uses _______
5) catalase
6) hemolysis
1) Gram + cocci
2) Grow in presence of 40% bile
3) Cannot grow in 6.5% NaCl
4) Uses Esculin
5) catalase -
6) non hemolytic (variable)
Are non-enterococci (S. Bovis) part of normal human flora?
NOT part of normal flora, enters humans via lower GI or oropharynx
Treatment of Strep bovis (3)
penicillin G, vancomycin, cephalosporins
Pathogenesis of strep bovis infection
Escapes immune detection using encapsulation while in lamina propria → penetrates bloodstream → bacteremia
Attaches to collagen-rich structures in blood (e.g. valves) via pilus-like structures
Diseases caused by strep bovis (3)
1) Infective endocarditis - CORRELATED WITH COLORECTAL NEOPLASM
2) Biliary system infection
3) Urinary tract infection
Viridans streptococci
1) normal flora?
2) gram stain?
3) hemolysis?
4) capsule?
5) optochin sensitive/resistant?
6) Bile sensitive or resistant?
1) commensal (non-pathogenic)
2) gram + bacteria
3) Alpha hemolytic
4) No capsule
5) Optochin resistant
6) Not bile soluble (bile resistant)
Common viridans streptococci bugs
Strep salivarius, Strep pyogenes sanguis, S. mitis, and S. mutans
S. Mutans causes ________
dental caries
S. Sanguinis causes ____________
subacute endocarditis
Viridans streptococci produce ________ which allows them to adhere to _______ and _________
dextrans
tooth surface and previously damaged heart valves
Strep pneumoniae
1) gram stain?
2) shape?
3) aerobe/anaerobe?
4) optochin sensitive/resistant?
5) hemolysis?
6) catalase?
7) positive _______ reaction
1) Gram +
2) Lancet shaped diplococci growing in chains
3) Facultative anaerobic
4) Optochin sensitive
5) Alpha hemolytic
6) Catalase -
7) Positive quellung reaction
Main virulence factors of strep pneumoniae (2)
1) IgA protease: cleaves secretory IgA allowing colonization of nares
2) Polysaccharide capsule (antiphagocytic): increase susceptibility to asplenic patients → prophylactic vaccination
Diseases caused by strep pneumoniae (5)
C-MOPS
1) Conjunctivitis: redness, discharge in one eye
2) Meningitis: fever, chills, headache, neck stiffness
- Elevated CSF protein, elevated PMNs, low CSF glucose
3) Otitis media: ear pain
4) Pneumonia
5) Sinusitis
Symptoms of strep pneumoniae pneumonia
fever, chills, cough, chest pain
Rusty-brown sputum
Treatment of strep pneumoniae
Respiratory fluoroquinolone (levofloxacin, moxifloxacin)
Beta-lactam + macrolide/doxycycline
Vaccines available for strep pneumoniae? (2)
1) Prevnar =conjugate vaccine (polysaccharide capsule + protein conjugate)
- Given to children < 5yrs, adults > 65 yrs
2) Pneumovax = polysaccharide vaccine
- Give to adults > 65, immunocompromised, or asplenic patients
Staph aureus:
1) gram stain?
2) shape?
3) aerobe/anaerobe?
4) grows on _______ but NOT ___________
5) catalase?
6) hemolysis?
7) _______ pigment
8) coagulase?
9) ferments ________
1) Gram +
2) Cocci in Clusters
3) Aerobic
4) Grows on blood agar, NOT MacConkey
5) Catalase +
6) B-hemolytic
7) Golden pigment
8) Coagulase +
9) Ferments mannitol (yellow on mannitol salt agar)
Which two types of patients are especially susceptible to staph aureus infections?
1) Chronic Granulomatous Disease
2) Job Syndrome
Chronic Granulomatous Disease
neutrophil defect in killing due to impaired H2O2 formation (NADPH oxidase deficiency)
Chronic Granulomatous Disease are susceptible to which bugs?
**Also susceptible to: Need PLACESS
Nocardia, Pseudomonas, Listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia
Job Syndrome
hyper IgE syndrome
Deficiency of Th17 cells due to STAT3 mutation → impaired recruitment and chemotaxis of neutrophils to sites of infection
Predisposed to staph abscesses
Staph aureus is normal flora where?
anterior nares
Disease caused by staph aureus (9)
1) Food poisoning
2) Pneumonia
3) Osteomyelitis
4) Acute endocarditis
5) Septic arthritis
6) Skin infections (impetigo, cellulitis, abscesses, furuncles, carbuncles, wound infections)
7) Otitis and sinusitis
8) Scalded skin syndrome
9) Toxic shock syndrome
Staph aureus Food poisoning
Associated virulence factors?
preformed toxin ingestion → vomiting/diarrhea
Associated virulence factors: enterotoxins
Staph aureus Pneumonia
hospitalized acquired pneumonia s/p viral infection, or ventilator-associated pneumonia
Symptoms: abrupt onset fever, chills, LOBAR consolidation, rapid destruction of lung parenchyma → CAVITATIONS, EMPYEMA (pus in pleural space)
Staph aureus Osteomyelitis
bone infection (usually boys < 12 yrs), due to hematogenous spread
Staph aureus Acute Endocarditis
violent destruction of heart valves, sudden onset, high fever → endocarditis with thrombophlebitis
IV drug user → tricuspid → pneumonia from bacterial embolization from infected valve
Mitral/aortic valve → embolism of vegetations to brain
Staph aureus Septic arthritis
invasion of synovial membrane by staph → closed infection of joint cavity
Symptoms: acutely painful, red, swollen joint, decreased ROM → can permanently lose function
Synovial fluid = > 100,000 PMNs, yellow/turbid
Staph aureus skin infections? 3 kinds
1) Impetigo: contagious, crusty/honey colored, wet flakey typically on face or around mouth
2) Cellulitis: deeper infection (fat), hot, red, shiny skin
3) Local abscess, furuncles, carbuncles, wound infections
**Staph likes to localize in one spot
Scalded skin syndrome
associated virulence factors?
painful, erythroderma, + Nikolsky sign, Bullous Impetigo
Infant → scalded skin syndrome
Older child → staph scarlet fever (no strawberry tongue)
Associated virulence factors: exfoliatins
3 staph exotoxins
1) TSST-1 = super antigen
2) Enterotoxin
3) Exfoliant
**can treat infection with abx, but exotoxin mediated effects persist
TSST-1
mechanism of action?
1) cross link ______________________ with ______________________
1) → antigen ___________ _______ cell activation
2) → increased _____ and _______ →
4) activate __________ →
5) increased ______, ________, and ________ pro-inflammatory cytokines
6) → SHOCK
staph aureus exotoxin
Acts as superantigen:
1) cross link a-chain of MHCII on APCs (macs, DCs) with variable region of B-chain of T-cell Receptors on CD4+ TH cells
1) → antigen independent TH cell activation
2) → increased IL-2, IFN-y →
4) activate macrophages →
5) increased IL-1, IL-6, TNF-a pro-inflammatory cytokines
6) → SHOCK
Signs and symptoms of toxic shock syndrome
fever, hypotension, nausea, vomiting
RASH: erythema starts on TRUNK, spreads to extremities, erythema on PALMS/SOLES, conjunctival hyperemia, strawberry tongue
-Rash desquamation (peeling) 1-2 weeks later
Elevated ALT, AST, bilirubin
Staph aureus Enterotoxin
superantigen
- Heat resistant, acid stabile
- Rapid onset food poisoning (within 1-6 hrs)
- -> Nausea, vomiting, watery diarrhea
Mediated by CYTOKINE release (mast cells)
Classic foods: meat, poultry, mayo, milk/egg/dairy products, custards
Staph aureus Exfoliant
Proteolytic exotoxin → cleaves desmoglein 1 → blister below stratum corneum = Bullous impetigo and staph scalded skin syndrome
Staph aureus proteins that disable our immune defenses: (8)
1) Protein A
2) Catalase
3) Coagulase
4) Hemolysins
5) Leukocidins (PVL)
6) Beta-lactamase (penicillinase)
7) Novel penicillin binding protein (transpeptidase)
8) Clumping factor
Staph aureus: Protein A
part of cell wall, binds Fc on IgG → protect from complement fixation (opsonization) and ab-mediated phagocytosis
Staph aureus: Catalase
catalyzes H2O2 → inhibits PMN killing
Staph aureus: Hemolysins
destroy RBCs, neutrophils, macrophages, and platelets
Staph aureus: Leukocidins (PVL)
destroys PMNs → protects from phagocytosis
Staph aureus: Beta-lactamase (penicillinase)
secreted B-lactamase that destroys B-lactam portion of penicillin molecule → inactivates antibiotic
Staph aureus: Novel penicillin binding protein (transpeptidase)
protein necessary for cell wall peptidoglycan formation altered conferring resistance to penicillinase-resistant penicillins and cephalosporins
Staph aureus: Clumping factor
binds fibrin → large clumps, blocks phagocytosis
Staph aureus: Coagulase
leads to fibrin formation around bacteria → protect it from phagocytosis
Staph aureus proteins to tunnel through tissue (4)
1) Hyaluronidase
2) Staphylokinase
3) Lipase
4) Protease
Staphylokinase
protein lyses formed fibrin clots
MRSA
staph with resistance conferred by altered penicillin binding proteins (MecA)
What can you treat MRSA with? (5)
1) Vancomycin
2) Linezolid
3) Ceftaroline (5th gen cephalosporin)
4) Daptomycin
5) Tigecycline
Vancomycin resistant staph
VISA and VRSA
Gets vanA gene from enterococcus
Must treat with alternative abx
Erythromycin-induced clindamycin resistance (D-test)
Seen with some staph aureus
Exposure to erythromycin causes resistance to clindamycin
S. epidermidis
1) Gram stain?
2) coagulase?
3) Novobiocin sensitive/resistant?
4) Urease +/-?
5) Hemolysis?
6) Normal flora where?
1) Gram +
2) Coagulase - (aka coag negative staph)
3) Novobiocin sensitive
4) Urease +
5) Non-hemolytic
6) Skin - Often a contaminant of blood cultures
S. Epidermidis produces _______ which allows it to do what?
biofilm that allows adherence and colonization of prosthetic materials
S. epidermidis causes what diseases? (2)
Common cause of catheter-associated UTI
Infects prosthetic devices: prosthetic heart valves, peritoneal dialysis catheters, prosthetic joints
S. saphrophyticus
1) gram stain?
2) coagulase
3) Novobiocin sensitive/resistant?
4) Urease +/-
5) Catalase +/-
6) Normal flora where?
7) causes what disease?
8) aerobe or anaerobe?
1) gram +
2) Coagulase -
3) Novobiocin resistant
4) Urease +
5) Catalase +
6) Normal flora of rectum and vagina
7) UTI in sexually active females
8) Facultative anaerobe
