Module 16 Flashcards
Bacteria
Single celled organisms shaped as rods, spheres, spirals
Bacteria + the body
- most rendered harmless by immune system
- some are beneficial
- some are pathogenic + cause disease
Bacterial Pathogenicity - virulence factors
- Fimbriae and pilli
- flagella
- secretion of toxins and enzymes
- invasion
Fimbriae and Pilli - what
Hair-like structures that project from the surface of bacteria cells
Fimbriae and Pilli - function
allow bacteria to attach to certain sites in our body so they are not washed away
Fimbriae and Pilli - example of bacterium
E. Coli (use fimbriae that attach to urogenital tract –> bladder infection)
Flagella - what, function
- projection of bacteria
- allows bacteria to “swim” through aqueous environment –> get to sites where they may survive
Toxin symptoms (bacteria) (7)
- nausea, vomiting, diarrhea, cramps, pain, fever, paralysis
Toxin function (bacteria)
- (some cases) bacterial toxins produced outside of our body can mediate toxic reactions if the gain entry to our body
- ex poisoning
Enzymes (bacteria)
- can degrade tissue or breakdown antibodies (our defense against infection)
Invasion (what, Example x2)
some bacteria can invade our cells
- EX salmonella invade cells of intestine –>diarrhea
- EX2 tuburculosis causing bacteria enter body in the lungs and can “hide” inside cells making it impossible for immune system to act on the
Gram staining of Bacteria
- classify bacteria as gram positive or gram negative
- gram stain –> tells us about cell wall structure of bacteria (amount of peptidoglycan) which impacts antibiotic use
Characteristics of Gram positive stain (6)
- thick peptidoglycan wall (Cell wall)
- stains purple
- Techoic acids (rigid cell wall)
- no LPS
- no outer membrane
- Do not have porins
Characteristics of Gram negative bacteria (6)
- thin peptidoglycan layer (cell wall)
- no techoic acids
- LPS (lipopolysaccharides) are component of outer membrane
- outer membrane (protect bacteria from bile salt + detergents)
- stain pink during staining
- porins (allow sugar, ions, amino acids to enter)
Signs of Infection
- fever, malaise, local redness, swelling
- increased respiratory rate, tachycardia
- other specific symptoms (ex UTI = frequency of urination)
Selective toxicity (bacteria)
Therapy that destroys bacteria without harming the host
- target differences between cellular chemistry of bacteria and humans
Antibiotic therapy produces selective toxicity by (3)
- disrupting bacterial cell wall (human cells do not have cell wall)
- targeting enzymes unique to bacteria
- disrupting bacterial protein synthesis (bacterial and human ribosomes are different)
4 questions for selection of an antibiotic
1) has the infectious bacteria been identified
2) bacterial sensitivity to the antibiotic?
3) can antibiotic access site of infection?
4) is the patient able to battle the infection?
Identification of the Bacteria (2)
- ideally done before selection of treatment
- gram stain (rapid, provides info on structural features of bacteria)
- culturing = best basis for selection of the therapy
Identification of Bacteria - barriers (2)
- cant take culture from child ear infection
- lower respiratory infections may have several species of bacteria)
Bacterial Sensitivity to Antibiotic - 2 categories
- bacteriostatic
- bactericidal
Bacteriostatic
- stops growth and replication of bacteria (stops spread of infection)
- body’s immune system can then attack and remove bacteria
Bactericidal
drugs kill the bacteria
MIC
MIC = minimum inhibitory concentration
MBC
minimum bactericidal concentration
Penetration to the site of action - which infections require careful selection of antibiotics?
- meningitis
- urinary tract infections
- osteomyelitis
- abscesses
- otitis Media
Meningitis (what)
- infection of the meninges (membranes covering brain and spinal cord)
- bacterial meningitis (rare, more life threataning)
Meningitis - treatment
- antibiotic that penetrates the meninges
Urinary Tract Infections (UTIs) = what?
- when bacteria enteres any part of urinary system
- most often = infection of bladder (cathaterization)
UTI treatment
antibiotic that enters urinary system
Osteomyelitis (what)
- infection of the bone
Osteomyelitis - treatment
- very few antibiotics enter bone = limited treatment
- usually treat with antibiotics for 4-6 weeks
Abscesses (what)
- pus or other infected material collect under skin
Abscesses - treatment
- difficult to treat with antibiotics (poorly perfused with blood)
Otitis Media (what)
- infection of the middle ear (ear infection)
- much more common in children
Otis Media - treatment
- many antibiotics do not penetrate inner ear = not effective to treat otitis media
Ability of the patient to battle infection - selection of antibiotic
- immunological state
- bactericidal antibiotics KILL bacteria –> can be used in
immunocompromised patients
- bacteriostatic antibiotics require actions of immune function = less
used in immunocomprimised patients
- bactericidal antibiotics KILL bacteria –> can be used in
Complications of antibiotic therapy (6)
- resistance
- allergy
- serum sickness
- superinfection
- destruction of normal bacterial flora
- bone marrow toxicity
Antibiotic resistance
- a bacteria that did respond to an antibiotic and has lost sensitivity over time
Antibiotic resistance (3 major mechanisms)
- Reduction of the drug at the site of target
- increased drug inactivation
- alteration of the bacterial target
Antibiotic resistance - reduction of the drug at the site of the target
- bacteria decreases uptake of antibiotics
- bacteria increases expression of efflux pumps (extrude antibiotics)
- COMBo - drug that is less able to access its bacterial target
Antibiotic resistance - increased drug inaction (+ example)
- bacteria that evolved to produce increased enzymes that inactivate antibiotics
- EX enzyme beta lactamase will degrade antibiotics with beta lactam ring (penicillin, cephalosporins)
Alteration of bacterial target (Antibiotic resistance)
- bacteria may evolve mutations in the target htat make antibiotic ineffective
- EX a mutation in bacterial ribosomes renders some antibiotics ineffective
Preventing resistance (4)
1) prevent infection (vaccinate, get catheters out if possible)
2) diagnose and treat effectively (patients with cold / a virus want antibiotics despite that it will not be effective)
3) use antibiotics wisely (only when necessary)
4) prevent transmission (isolate pathogen and prevent its spread, wash hands)
Allergy - most common antibiotic
penicillin
Signs of allergy (antibiotics) (5)
- urticaria (hives)
- anxiety
- swelling of hands, feet, throat
- difficulty breathing
- hypotension
time of onset (fatal allergy to antibiotic)
20 minutes of dosing
What to do if patient is experiencing an allergic reaction?
- stop antibiotic
- monitor vitals
- diphenhydramine (antihistamine)
- epipen (epinephrine, vasoconstrictor)
Serum sickness (time of onset)
- similar to allergy but deveops 7-21 days after antibiotic exposure
What is serum sickness
- body’s immune system improperly identifies drug or drug protein complex as harmful
- body then produces immune reaction (inflammation)
Serum sickness symptoms (7)
- fever
- hives
- rash
- joint pain
- itching
- angioedema
- enlarged lymph nodes
Serum Sickness - treatment (4)
- antihistamine (for itching)
- analgesics (for pain)
- corticosteroids (for inflammation)
- stop antibiotic???
Superinfection
- type of resistance
- when a new type of infection develops during the course of antibiotic therapy
- broad spectrum antibiotics kill both pathogenic bacteria and normal flora
- -> allowing new bacteria to flourish
- superinfection caused by drug-resistant bacteria
Superinfection - treatment
hard to treat (drug resistant bacteria has grown)
Destruction of normal bacterial flora - 3 effects
1) impair intestinal bacterial synthesis of vitamin K. (danger = anticoagulant Warfarin requires vitamin K –> increased risk of bleeding)
2) impair Intestinal bacteria metabolize + first pass effect (danger = increased blood drug levels = toxicity
3) Enterohepatic recycling of drugs (danger = drug therapy, contraceptive failure with birth control pills)
Bone marrow toxicity (what, signs, symptoms)
- rare but serious complication
- SIGNS = aplastic anemia, thrombocytopenia, agranulocytosis, leukopenia
- symptoms = sore throat, bruising, fatigue
Autolysins
- bacterial enzymes that degrade peptigdoglycan cell wall
Transpeptidases
- enzymes that function to form cross bridges between peptidoglycan strands therefore making cell wall strong
Penicillin Binding Proteins (PBPs)
- transpeptidases
- autolysis
Penicillins - mechanism of action
- inhibid transpeptidases (disrupt synthesis of cell wall)
- activate autolysins (promote cell wall destruction)
- net result = cells take up excess water and die (lyse)
Penicillin - target bacteria
more effective against gram positive bacteria (since they do not have outer membrane)
Penecillin - class of antibiotic
- bactericidal
- only effective against bacteria that are actively growing and dividing
Penicillin resistance (3 types)
- inability to reach target
- inactivation
- mutation in PBPs (low affinity for penicillins IE MRSA)
- PREDOMINANT = beta lactamase inhibiting
- treat with beta lactamase inhibitors
Classes of penicillins
- narrow spectrum penicillins
- narrow spectrum penicillinase resistant penicillins
- broad spectrum penicillins
- extended spectrum penicilins
Narrow Spectrum Penicillins - target bacteria
- gram positive bacteria
Narrow Spectrum Penicillins - route of administration
- IV or IM (destroyed by gastric acid)
Narrow Spectrum Penicillins - target types infections
- pneumonia and meningitis
Narrow Spectrum Penicillins - adverse effects
allerguy
Narrow Spectrum Penicillinase Resistant Penicillins - what
- altered side chain that makes them not susceptible to inactivation by beta lactamase enzymes
Narrow Spectrum Penicillinase Resistant Penicillins - target bacteria
- effective in treating penicillinase producing staphylococci
Narrow Spectrum Penicillinase Resistant Penicillins - not effective (bacteria, and condition)
- bacteria - non-penicillinase producing bacteria
- not effective in treating absecess or penetrating into bone
Narrow Spectrum Penicillinase Resistant Penicillins - resistance?
some are (ex MRSA)
Broad Spectrum Penicillins - target bacteria
- gram positive and gram negative bacteria (bc it can penetrate outer wall)
Broad Spectrum Penicillins - resitance
easily inactivated by beta lactamases
Extended Spectrum Penicillins - target bacteria (2)
- gram positive and gram negative bacteria +
- Pseudomonas aeruginosa (is resistant to all other penicillins)
Extended Spectrum Penicillins - resistance
degradation by beta lactamase enzymes
Cephalosporins - mechanism of action
- same mechanism of action as penicillin
- inhibit transpeptidases, activate autolysins
Cephalosporins - classification
bactericidal, 4 generations
1st generation
2nd generation
3rd generation
4th generation
Cephalosporins - difference between generations (3)
moving from 1 to 4, drugs will
- increase in activity against gram negative bacteria
- increase in resistance to destruction by beta lactamases
- increase in ability to penetrate cerebrospinal fluid
Cephalosporins - adverse effect
- allergy
- cross sensitivity with allergy to penicillin is rare
Vancomycin - when used
- potentially toxic drug
- only treats serious infection (ex caused by MRSA)
Vancomycin - target infections
MRSA infecting osteomyelitis, meningitis, pneumonia, septicemia
Vancomysin - mechanism of action
- inhibits cell wall synthesis by binding to precursors of cell wall synthesis to block the transglycosylation step in cross bridge synthesis
Vancomysin - adverse events
- ototoxicity
- Red person syndrome = flushing, rash, itching, hypotension
Tetracylines - mechanism of action
- bind to 30S ribosomal subuint of bacteria and prevent amino acid addition to peptide chain
tetracyclines - class
- Bacteriostatic
tetracyclines - target infections
- typhys fever, clamydia, cholera
tetracyclines - adverse effects
- GI upset
- photosensitivity (avoid UV and wear sun block)
- susceptibility to superinfection
Macrolide Antibiotics - mechanism of action
- block 50S ribosomal subunit of bacteria –> block addition of amino acids to peptide chain
Macrolide Antibiotics - classification
- bacteriostatic
Macrolide Antibiotics - adverse effects (2)
- GI upset’
- QT interval prolongation
Tetracyclines - target bacteria
Broad spectrum (gram + and -)
Macrolide Antibiotics - target bacteria
- broad spectrum (gram + and - )
Oxazolidinones - classification
bacteriostatic
Oxazolidinones - target bacteria
- narrow spectrum
- gram positive bacteria
Oxazolidinones - mechanism of action
- bind to specific region of 50S ribosomal subunit to inhibit protein synthesis
Oxazolidinones - target bacteria species
treat MRSA and vancomycin resistant enterococci (VRE)
Oxazolidinones - adverse events
- reversible myelosupression
Aminoglycosides - class
- bacteriocidal
Aminoglycosides - target bacteria
narrow spectrum (gram negative)
Aminoglycosides - mechanism of action
- protein synthesis inhibitors
- bind to 30S ribosomal subunit to prevent protein synthesis
Aminoglycosides - mechanism of action
- rapidly lethal to bacteria
- mechanism unknown
Aminoglycosides - adverse effects (2)
- irreversible ototoxicity
- reversible nephrotoxicity
Sulfonamides and trimethoprim - mechanism of action
- bacteria depend on synthesis of folic acid to incorporate into DNA
- Sulfoamides and trimethoprim act on different stages to block synthesis of folic acid
Sulfonamides and trimethoprim - class
- bactericidal
Sulfonamides and trimethoprim - target infection
- UTIS
Sulfonamides and trimethoprim - adverse effect
- hypersensitivity reactions (fever, photosensitivity)
- small risk of severe hypersensitivity reaction called Stephens-JOHNSON SYNDROME
Fluroquinoones - mechanism of action
- inhibit DNA replication
- inhibit 2 enzymes, DNA gyrase and topoisomerase IV
Fluroquinoones - class
- bacgtericidal
Fluroquinoones - target bacteria
broad spectrum (gram + and -
Fluroquinoones - target infection
- UTI, osteomyelitis, soft tissue infections
Fluroquinoones - adverse effects
GI symptoms (nausea, vomitting, diarrhea)
Isoniazid - target infection
tuburculosis
Isoniazid - mechanism of action
inhibiting synthesis of mycolic acid, component unique to cell wall of tuburculosis causing bacteria
Isoniazid - adverse effects (2)
peripheral neuropathy and hepatotoxicity
