Infectious Disease Pt 1 Flashcards
Classification of Bacteria
- Gram positive vs. gram negative via Gram ____
- Microbiological identification system based on _____ structure
- Differ in structural components, sh____
- Aerobic vs. anaerobic
- Differing ____ requirements for survival
-
Gram _____ has a thicker peptidoglycan layer
- also looks more _____ color under microscope
- Stain
- cellular
- shapes
- Aerobic vs. anaerobic
- oxygen
-
Positive = thicker
- purple
+Gram Stain
- Gram negative shape =
- _______ aeruginosa
- Gram positive shape =
- _______ aureus
General rule
- GPC in clusters =
- GPC in chains =
- rods
- Pseudomonas
- cocci in clusters
- Staphylococcus
- staphylococcus species
- streptococcus species
- Gram negative = pink and rod like shape*
- Gram positive = purple and in clusters (cocci- grape like appearance)*
Gram Positive Organisms of Importance
(8)
-
Staphylococcus aureus
- Methicillin-susceptible (MSSA)
- Methicillin resistant (MRSA)
- Coagulase-negative S**taphylococcus (CoNs)
- Streptococcus pneumoniae
- Streptococcus viridans
- Streptococcus pyogenes (Group A Strep)
- Streptococcus agalactiae (Group B Strep)
- Enterococcus faecalis and Enterococcus faecium
- Clostridium difficule (anaerobic)
- CoNs - often on skin - potentially a contaminant to blood cultures*
- Staph aureus never really a contaminant/found on skin so def treat it*
- Streps are not contaminants*
Gram-Negative Organisms of Importance
(8)
- Escherichia coli (E.coli)
- Klebsiella pneumoniae
- Enterobacter cloacae
- Pseudomonas aeruginosa
- Acinetobacter baumannii
- Haemophilus influenzae
- Mycoplasma pneumoniae
- Bacteroides fragilis (anaerobic)
Pseudomonas like MRSA is an umbrella term - if a drug covers these, probably will cover others under it
Minimum Inhibitory Concentration (MIC)
What is it?
Lowest drug oncentration required to inhibit the growth of an organism at 24 hours (Value determines if sensitive, intermediate, or resistant)
On the Susceptibility Panel, what does it mean when there are all S’s on the right side?
The bacteria is PANSENSTIVE - can be treated with all the abx listed
Poll 1
- Blood cx has come back with preliminary results:
- Gram-positive cocci (GPC) in clusters on gram-stain
- Which of the following organisms fits the description?
- Bacteroides fragilis
- Staphylococcus aureus
- Streptococcus pneumoniae
- Pseudomonas aeruginosa
Staphylococcus aureus
Poll 2
Which of the following is considered a gram-positive anaerobic organism?
- Streptococcus pneumoniae
- Bacteroides fragilis
- Clostridium difficile
- Streptococcus pyogenes
Clostridium Difficile
S/S of Infection
- Fever > 38.3 or 100.9F
- Elevated WBC (leukocytosis)
- AMS
- Altered hemodynamics (hypotension, tachycardia)
- Fatigue
- N/V
- Site specific sx (pain, difficulty, breathing, redness, others)
Fever Causes
- Roughly 75% of fever in hospitalized pts is _____
- Remaining causes (4)
- pyrogenic
- malignancy, tissue ischemia, drug-induced, neurogenic
Keep in mind, not all fevers are infectious such as in cancer or seizure pts
Fevers the Good vs. Bad
Pros (4)
Fever > ___/___ C harm outweighs benefit
Cons (3)
- Fevers are designed to be good - mostly the beginning of the fever but if a fever is unaddressed, extended esp > 39/40 can cause lots of bad things*
- Ie) pediatric febrile seizures (not uncommon in peds)*
- Ex of taking advantage of some of the pros: doc says hold the tylenol until fever is >39*
Identifying the Source
- CNS
- Respiratory
- CV
- GI
- Urinary
- Integumentary
- Skeletal
Work by organ system from head to toe
- Meningitis
- PNA
- Endocarditis, Blood infections
- Colitis, food borne illness
- UTI
- Skin infections
- Osteomyelitis
Normal Human Flora
- Oral (2)
- Pulmonary (3)
- GI (6)
- GU (3)
- Integumentary (2)
- Streptococcus spp, Gram-positive anaerobes
- Streptococcus spp, Haemophilus inf, Mycoplasma spp
- E. coli, Klebsiella pneumoniae, streptococcus spp, Candida spp, Gram - anaerobes, other gram negatives
- Streptococcus spp, E.coli, Candida spp
- Streptococcus spp, Staphylococcus spp.
- After identifying the source - think about whats normally there?-* Translocation of our normal bacteria when we have infections
- Ex) treating cellulitis on my leg - targeting strep and staph*
Pharmacokinetics (PK)
- The study of the actions the ____ has on the ____
- Concerned with concentration/drug availability
- Incorporates four major body processes
- ______ - drug into the body
- ______ - drug into various tissues
- _______-changing drug into other molecules
- ______ - removal of drug from body
- Imp: above processes ___ the same in all patients
- Genetics: age, comorbities, organ function
body has on the drug
4 processes
- Absorption
- Distribtuion
- Metaboism
- Excretion
NOT
depending on severity of infection/keep in mind PO drugs not fully absorbed compared to IV
Pharmacodynamics (PD)
- The study of actions the ____ has on the ____
- E_____ of drug activity
- Unique in ID- targets bacterial pathogens instead of human receptors/target sites
- drug on the body
- Efficacy
+Time vs. Concentration Dependent
-
Time dependent
- Greater bactericidal (killing) activity as:
- PKPD parameter: __ > ___
- Example: ___-____ abx
- Greater bactericidal (killing) activity as:
-
Concentration Dependent
- Greater bactericidial (killing) activity as:
- PKPD parameter: C__/____ or AUC/MIC
- Example: _______
- Greater bactericidial (killing) activity as:
- Time Dependent
-
Drug concentrations remain above the MIC
- T > MIC
- Beta-lactam
-
Drug concentrations remain above the MIC
- Concentration Dependent
-
Drug concentrations (Cmax) exceed the MIC
- Cmax/MIC
- Aminoglycoside
-
Drug concentrations (Cmax) exceed the MIC
PKPD Parameters
- Concentration dependent - ____ a day, get to that ____
- Time dependent - _____ concentration for as long as possible, dosing more ____*
- once, peak
- maintain, frequent
Mechanism of Action Overview
- Targeting diff parts of the cell
-
Two main classes
- Intracellular =
- Extracellular =
- inhibits protein synthesis
- inhibits cell wall synthesis
+Beta Lactams
(4)
Natural Penicillins
Anti-Staphylococcal Penicillins
Amino-Penicillin
Anti-Pseudomonal Penicillins
+Penicillin Evolution
All belong to the ___-____ family
MOA
Increasing spectrum of gram _____ organisms
Beta-Lactam
Bind to penicillin binding proteins (PBPs) within the cell wall -> inhibiting cell wall synthesis -> cell lysis -> destruction
negative
+Natural Penicillins
(2)
Discovered in 1928, forever changed medicine
Penicillin G
Penicillin V
Prior to discovery of penicillins, we really didn’t have much to treat infections…a slow agonizing death, really reserved for skin infections, doesn’t really cover gram -
+Natural Penicillins
Spectrum
Staph aureus (penicillin-susceptible); Streptococcus spp, others
Minimal to NO gram-negative activity
+Natural Penicillins
Indications
- Initially excellent for skin infections
- Resistance developed over time
- Drug of choice for: Syphilis
+Natural Penicillins
Routes
- Pencillin G
- Penicillin V
- IV, IM as Pen G benzathine
- PO - low absoprtion of oral tablet limits its use
Limitiation with Oral beta lactams - poorly absorbed so with serious infections not good enough
+Anti-Staphylococcal Penicillins
(3)
Oxacillin
Nafcillin
Dicloxacillin
+Anti-Staphylococcal Penicillins
Spectrum
Developed to treat Penicillin-RESISTANT Staph Aureus
- Originally methicillin-since discontinued (dt hepatotoxicity)
Methicillin-Susceptible Staph Aureus (MSSA)
+Anti-Staphylococcal Penicillins
Indications
Drug of Choice for?
Serious MSSA infections (e.g blood stream)
+Anti-Staphylococcal Penicillins HF/Dosing
Half life is long or short?
Dosed how frequently?
Very short
Every 4 hours (requires frequent dosing) -> not commonly used
+Anti-Staphylococcal Penicillins
Clearance
Liver = no renal adjustments
Unique - most of the other beta-lactams renally adjusted
+Anti-Staphylococcal Penicillins
Routes
PO option for dicloxacillin
+Amino-Penicillin
(2)
Amoxicillin (Amoxil)
Ampicillin
+Amino-Penicillin
Developed to provide?
Spectrum
Gram negative in addition to gram positive coverage
Streptococcus spp, E.coli, Haemophilus influenzae, Enterococcus faecalis
Not reliable for Staph aureus (often resistant dt beta-lactamase production)
Expanded spectrum to include gram neg, however is a more advanced penicillin that doesn’t work on staph aureus, only these organisms above though -doesn’t really cover hospital infections (Pseudomonas)
+Amino Penicillin
Routes
- Amoxicillin
- Ampicillin
- PO, used as oral therapy (better bioavailability)
- PO and IV, mainly used in IV form (oral with poor bioavailability) compared to PO amoxicillin
+Amino-Penicillin Indications
Clinical Use (2)
Not used empirically for?
Otitis Media, Acute Pharyngitis
Not used for hospital infections -> Gram-negatives are usually resistant
Anti-Pseudomonal Penicillins
(1)
- Developed to include coverage of _______ (hospital associated, gram-negative organism)
- Spectrum:
- Route: only ___ used in hospital combined with _____ for hospital acquired infections (_____)
- Not used _____ (ie. with tazobactam) due to _______
- _____-________
Piperacillin
- Pseudomonas aeruginosa
- Same as Aminopenicillins (+ Pseudomonas)
- IV, tazobactam, Zosyn
- alone, resistance
- Beta-lactamases
Again if a drug can cover pseudomonas, it can probably cover other gram negatives
What is Beta-Lactamase?
- ______ that hydrolyzes the beta-lactam _____ -> antibiotic becomes _____
- 1,000’s of beta lactamases - classified based on s____/a____ it inactivates
- ______ beta lactamases vs. _____ beta-lactamases vs. others
- Enzyme, ring, inactive
- structure/antibiotic
- simple, expanded
Beta-lactamases are enzymes produced by bacteria that provide multi-resistance to β-lactam antibiotics such as penicillins, cephalosporins, cephamycins, and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase.
+Beta Lactamase Inhibitors
(3)
Amoxicillin-_Clavulanate_ (Augmentin)
Ampicillin- Sulbactam (Unasyn)
Piperacillin-_Tazobactam_ (Zosyn)
+Beta Lactamase Inhibitors
- Developed to: _____ the activity of simple _________
- P_____/e_____ the activity of its ______
- Routes: Unasyn/Zosyn -___ only, Augmentin - __ only
- Indication:
- Also includes ________ activity (with the exception of _____)
- Augmentin associated with high rates of ___ complaints
- inhibit the activity of simple beta-lactamases
- Preserve/expand, counterpart
- IV, PO
- Used empirically for hospital infections due to their expanded spectrum of activity
- anaerobic, X c.diff
- GI
Example of Beta-Lactamase Producing Organism
How can you tell if something is producing beta-lactamase?
Resistant to Ampicillin vs. Sensitive to Ampicillin-Sulbactam
+Penicillin Class AE
(3)
-
Hypersensitivity reactions
- 10% of US population reports being allergic- Rash most common
- Almost all agents are Renally eliminated (require adjustments)
- Notable Exception: Oxacillin and Nafcillin (hepatically eliminated, must monitor LFTs and avoid in elevated LFTs at baseline)
-
GI intolerances (ie diarrhea)
- more commonly with oral agents
Cephalosporins
- Inhibits ____-____ synthesis (same as _____ class - ___-____family)
- MANY DRUGS IN THIS CLASS (will almost always begin with ___/___)
- Grouped into _______ based on spectrum of activity/characteristics
- cell-wall, penicillin, beta-lactam
- ceph/cef
- generations
+ First Generation Cephalosporins
(2)
Routes
Cephalexin (Keflex) PO
Cefazoline (Acnef) IV
+First Generation Cephalosporins Indications
- _______ to Anti-staphylococccal ______ (e.g. oxacillin/nafcillin/dicloxacillin)
- Very commonly used for ____ infections and _____ prior to _____
- Alternative, penicillins
- skin, prophylaxis to surgeries
+First Generation Cephalosporins
Spectrum
Streptococcus, Staph aureus (MSSA)
NOT MRSA
Minimal gram-negative activity (resistance)
+First Generation Cephalosporins
Half Life
Dosing
Short half-life
3-4x/day
+Third Generation Cephalosporins
(4)
Routes
Ceftazidime (Fortaz) IV
Ceftriaxone (Rocephin) IV
Cefpodoxime (Vantin) PO
Cefdinir (Omnicef) PO
Very important class: Extended spectrum beta lactams
+Third Generation Cephalosporins Spectrum
- Developed to further _____ gram-____ spectrum
- These beta-lactams have an ______ spectrum
- Spectrum (5)
- EXCEPTIONS: ______ ONLY one in the group that does ___ cover gram-positive organisms and only one that covers _______ aeruginosa
- ______ stability against beta-lactamases
- expand, gram-negative
- Extended
- Streptococcus spp, MSSA, E.coli, K. penumoniae, Proteus spp
- Ceftazidime, NOT +, yes Pseudomonas
- Increased
Ceftaz = TAZMANIAN DEVIL -> covers pseudomonas and doesn’t cover the gramp positive strep and MSSA
+Third Generation Cephalosporins
Inactivated by?
Extended-spectrum beta lactamases (ESBLs)
ESBLs will inactivate these drugs (very prominent in the Northeast)
+Third Generation Cephalosporins PK
Half Life
Dosing Frequency
Elimination
Longer half life
Once daily for most infections
Hepatically eliminated = no renal adjustments (unique for cephalosporin class)
Ceftriaxone and Oxacillin class not renally dose adjusted
+Third Generation Cephalosporins
Indications
Commonly used in hospital and outpatient (community-acquired PNA, UTI, skin, bacteremia, osteomyelitis, CNS infections)
Example of an ESBL Producing Organism
Fourth Generation Cephalosporins
(1) Route
- Further expanded gram-_____ coverage
- Spectrum:
- Reserved for serious ____-associated infections
- Concern for _____ (including seizure) if not dosed properly
- Risk highest in e____, ____ impairment
Cefepime (Maxipime) IV
- expanded gram-negative coverage
- Same as 3rd gen + additional gram negs including Pseudomonas Aeruginosa
- serious hospital
- encephalopathy
- elderly, renal
Fifth Generation Cephalosporines
(1) Route
- _____ the rule
- Spectrum:
- “Think Cetriaxone with ____ coverage”
- Approved for (2)
- Used off label for b____, endo____ and osteo____ (as salvage therapy)
Ceftaroline (Teflaro) IV
- Breaks
- Expands gram positive, doesn’t cover pseudomonas but does cover MRSA by binding to PBP-2a
- MRSA
- CAP, ABSSSI
- bacteremia, endocarditis, osteomyelitis
+Cephalosporins AE
- Overall:
- _____ less commonly seen as compared to penicillin
- <__% cross reactivity seen in those allergic to penicllins
- Clinically okay to challenge if pt experienced just a ____
- Requires allergy testing or avoid use if: H___, S____, A____
- <__% cross reactivity seen in those allergic to penicllins
- ______ if not dosed properly (more common with what drug?)
- well tolerated
- Hypersensitivity
- <5%
- Rash
- Hives, Swelling, Anaphylaxis
- <5%
- Seizure (Cefepime)
Poll 3
How do beta-lactams exhibit their mechanism of action?
- Inhibiting cell wall synthesis
- Mixed martial arts
- Inhibiting protein synthesis
- Hydrolyzing the beta lactam ring
Inhibiting cell wall synthesis
Poll 4
This third generation cephalosporin is the only third generation to have activity against Pseudomonas aeruginosa making it a useful option when treating ventilator associated PNA
- Cetriaxone
- Ceftazidime
- Cefepime
- Ceftaroline
Ceftazidime
Poll 5
Which of the following requires hepatic elimination?
- Cefepime
- Penicillin
- Cefazolin
- Oxacillin
Oxacillin
Hepatic adjustment is really just avoiding it
Poll 6
People speak highly of me. For example, I am considered an agent who protects my couterpart, similar to a body guard. I am also known to enhance my counterpart’s spectrum of activity. What class of drug am I considered?
- Cephalosporin
- Penicillin
- Beta-Lactamase Inhibitor
- Beta Lactam
What is an example of a drug in that class? (Beta-Lactamase Inhibitor)
- Cefepime
- Sulbactam
- Oxacillin
- Piperacillin
Beta Lactamase Inhibitor
Sulbactam
Poll 6
Which of the following in the class can treat Pseudomonas aeruginosa?
- Amoxicillin-clavulanate
- Ampicillin-sulbactam
- Piperacillin-tazobactam
- None of the above
Piperacillin-tazobactam
Poll 6
Which of the following in the class can treat MRSA?
- Amoxicillin-clavulanate
- Ampicillin-sulbactam
- Piperacillin-tazobactam
- None of the above
None of the above
Poll 6
Which of the following in the class can treat anaerobic organisms (with the exception of C.diff)
- Amoxicillin-clavulanate
- Ampicillin-sulbactam
- Piperacillin-tazobactam
- All of the above
All of the above
+CarbaPENEMs
(4)
Routes
Ertapenem (Invanz) IV, IM
Meropenem (Merrem) IV
Imipenem/cilastatin (Primaxin) IV
Doripenem (Doribax) IV
+CarbaPENEMs Spectrum
- _______ beta-lactam class (also inhibits cell wall synthesis)
- Spectrum:
- ______**** does not cover Pseudomonas
Broadest
Streptococcus, MSSA, all GNR (including Pseudomonas aeruginosa) and anaerobic gram-negatives
Ertapenem
- On exam: ERRRRTT does not cover pseudomonas*
- The only 2 so far that cover gram negative anaerobes - penems and beta lactam combos*
+CarbaPENEMS Indications
Drug of choice for ______
Used as ___-line options in gram-negative _____ infections
Stable against many?
ESBL’s
last line - gram neg resistant
ESBLs
- Can use penems for ESBL’s (drug of choice or serious ESBL producing organisms)*
- ONly gram negative organisms produce ESBL*
Poll 7
AB is a 43 M admitted to the hospital with an intra-abdominal infection. He is allergic to penicillin (rash). AB has had several hospital admissions this year including 2 operations. You would like to empirically treat broadly for gram-negatives including Pseudomonas aeruginosa. In addition you would like to cover anaerobic organisms. Which of the following would be a viable option for AB?
- Ceftazidime
- Ertapenem
- Piperacillin-tazobactam
- Meropenem
Meropenem
- Cef does not cover the anaerobes*
- Ert does not cover pseudomonas*
- Penicillin rash - not going to give piperacillin*
