Antibiotics Flashcards
6 general antimicrobial therapy principles
- Suspected or known organism
- Antibiotic spectrum
- Bacteria susceptibility to antibiotic
- Concentration of antibiotic at site of infection
- Activity of immune system
- Bacterial resistance mechanisms
Interfere with growth or replication but do not kill the organism
Bacteriostatic agents
Kill the organism
Bactericidal agents
Lowest concentration of a given antimicrobial at which an organism’s growth is inhibited
Minimum inhibitory concentration (MIC)
When does MIC increase?
With reduced susceptibility
What is MBC?
Minimum bactericidal concentration
What is cell wall acting typically?
Bactericidal
What is protein synthesis inhibitors typically?
Bacteriostatic
Is bacteriostatic inhibitory antibiotics concentration lower or higher than bactericidal concentrations?
Much lower
What do you use for immunosuppressed patients and serious infections?
Bactericidal agents
How can bactericidal be further divided?
Concentration (dependent killing)
Time (dependent killing)
What do you want for concentration of bactericidal?
Certain peak concentration or AUC
When does time of bactericidal continue?
Concentration > than MIC (duration of time concentration above MIC)
Which part of bactericidal is more important for surgical site injection prophylaxis?
Time of bactericidal
What is persistent suppression of bacterial growth after antibiotic concentration has fallen?
Post antibiotic effect (PAE)
What are 3 possible mechanisms for post antibiotic effect?
- Persistence of drug at binding site
- Need to synthesize new enzymes
- Slow recovery from damage
What is when the bacteriostatic and bactericidal effects of two antibiotic agents used together is greater than their effects when administered alone?
Synergism
Example of synergism
Ampicillin + gentamicin for enterococcal endocarditis
5 physical barriers for drug penetration into anatomical compartments
- Epithelial and endothelial cell layers
- Hydrophobic/hydrophilic properties of drug
- Molecule charge
- Molecule size
- Membrane transporters (P glycoprotein)
4 antibiotic compartment penetration
- CNS (blood-brain barrier)
- Eye (from plasma to retina or ocular cavity)
- Pneumonia (pathogens in epithelial lining fluid
- Placental barrier (fetal harm)
3 unusual compartments for antibiotic
- Endocardial vegetation (heart valves)
2. Biofilm formed by bacteria or fungi (prosthetic devices)
Colony of slow growing cells enclosed in an exopolymer matrix
Biofilm
Is biofilm negative or positive and why?
Negatively charged
Restricts antibiotic access
2 things that alter pharmacokinetics for antibiotics?
Renal impairment
Hepatic impairment
Conditions or populations that lead to increased dose requirements of antibiotics
Cystic fibrosis
Burn patients
Does renal impairment or hepatic impairment have more effect on dosage adjustments with antibiotics?
Renal impairment
Which drug concentration monitoring to avoid toxicity is used?
Vancomycin
Which drug concentration monitoring is established with efficacy?
Aminoglycosides
Vancomycin
What are the 4 different types of selection for antibiotics are there?
Empiric therapy
Definitive therapy
Preventive therapy
Prophylaxis
Patient is symptomatic
Empirical therapy
Which are the most likely organisms for empirical therapy?
UTI
CAP
SSTI-cellulitis
When are situation need immediate treatment with empirical therapy?
Neutropenia
Examination of infected secretion or body fluid to determine pathogen
Definitive therapy
What is most likely used to narrow antibiotic to target organism with definitive therapy?
Monotherapy
Combo therapy indicated for certain infections (TB, HIV, hepatitis)
What are the 3 types of infections?
Acquired
Normal flora
Deactivation or activation
How can you get acquired type of injection?
By the community or health care
How can you get normal flora type of injection?
Changes in population or normal body organisms, overgrowth of one becomes a pathogen
How can you get reactivating or activation type of infection?
Usually immunocompromised host
Fungal infections
TB
viral, CMV, HSV
4 different target microorganism
Bacteria - antibacterial
Viruses - antiviral
Fungi - antifungal
Parasites - antiparasitic
3 different classification of antibiotic
Class and spectrum of microorganisms it kills
Biochemical pathway it interferes with
Chemical structure of its pharmacophore
4 different classification of antibiotic mechanism of action:
- Cell wall (or cell membrane) acting
- Protein synthesis inhibitors
- Inhibit DNA synthesis
- Antimetabolites
Antibiotic mechanism of action for cell wall acting
Inhibitors of peptidoglycan
Antibiotic mechanism of action for protein synthesis inhibitors
Acts on 50S ribosomal unit
Acts on 30S ribosomal unit
What are beta lab tam antibiotics named for?
4 member lactam ring
Beta lactam antibiotic
Penicillins
Is beta lactam bactericidal or bacteriostatic?
Bactericidal
MOA of beta lactams?
Inhibit bacteria growth by interfering with cell wall synthesis
-peptidoglycan (cell wall component)
5 different resistance to penicillins
Changes in PBPs Cell entry (size of drug vs porins) Beta lactamase enzymes Efflux pumps on gram negative Biofilms (adhere to devices, valves)
Anti-staph penicillin
Nafcillin
Beta lactamase producing staphylococci (streptococci)
4 adverse effects of penicillins
Hypersensitivity rxns .4%-7%
Rash, fever, anaphylaxis, vasculitis, SJS
Act as haptens
Seizure (rare with renal insufficiency)
MOA of cephalosporins
Similar to PCNs
How does cephalosporins spectrum compare?
Broader
1st generation of cephalosporins
Cefazolin
Gram positive, some negative
2nd generation of cephalosporins
Increasing gram negative
Cefotetan
3rd generation of cephalosporins
Decreasing gram positive, increasing gram negative
Ceftriaxone
Resistance of cephalosporins
Gram negative enters bacteria ear - produce beta lactamase (inactivate 1st and 2nd generation agents)
4 adverse effects of cephalosporins
Hypersensitivity < PCNs
Cross reactivity with penicillin allergy < 10%
Bleeding risk with cefotetan
Disulfiram rxn
2 beta lactamase inhibitors
Sulbactam
Tazobactam
Inactivate the beta lactamase to make antibiotic active
Suicide inhibitors
Is beta lactamase inhibitors:
Gram positive or negative
Aerobic or anaerobic
Gram negative
Anaerobic
What is vancomycin?
Glycopeptide
- inhibits synthesis of cell wall precursors
- high affinity for D-alanyl D-alanine terminus of cell wall precursor that attaches to the peptidoglycan
- inhibits transpeptidation
Is vancomycin gram positive or negative?
ONLY gram positive
Example of vancomycin that focuses on gram positive organism
Staph aureus (MRSA)
When will vancomycin resistance becomes a problem?
Enterobacter and staph aureus
Is vancomycin a beta lactam?
NO
Can you use vancomycin if have a penicillin allergy?
Yes because it may be an alternative
How is therapeutic drug monitoring done with vancomycin?
Peak and through concentrations
Adverse effects of vancomycin
- Ototoxicity
- Nephrotoxicity
- Red-man syndrome
What is red-man syndrome?
When you infuse vancomycin too quickly
What is aminoglycosides and name the 2 drugs
Protein synthesis inhibitors
Gentamicin
Tobramycin
Is aminoglycosides bactericidal or bacteriostatic?
Bactericidal
Is aminoglycosides anaerobic or aerobic?
Aerobic
Is aminoglycosides reversible?
No
Which ribosomal unit does aminoglycosides act on?
30S ribosomal subunit
3 possible mechanisms for aminoglycosides:
- Block of formation
- Miscoding of AA
- Block of translocation on mRNA
Aminoglycosides PK target peak concentrations
- post antibiotic effect
- once daily dose
What does macrolides do?
Inhibit protein synthesis at 50S
If allergic to macrolides, what other antibiotic can you give?
Penicillin
Is tetracyclines bacteriostatic or bactericidal
Bacteriostatic
What does tetracyclines inhibit with protein synthesis?
30S ribosome subunit
Clindamycin MOA
Inhibit protein synthesis like macrolides at 50S
Is clindamycin anaerobic or aerobic?
Anaerobic
Oxazolidinones (linezolid) MOA
Prevents formation of ribosome complex that initiates protein synthesis at 50S subunit (23S ribosomal RNA)
Is oxazolidinones anaerobic or aerobic
Anaerobic
How does quinolones block bacterial DNA synthesis?
Inhibit bacterial topoisomerase II (DNA gyrase) and IV
What do quinolone drugs end in?
“Floxacin”
Which antibiotics inhibit DNA synthesis?
Quinolones
Who should you avoid giving quinolone to?
Pregnancy and pediatrics
What are 2 antimetabolites?
Trimethoprim (inhibit dihydrofolic acid reductase)
Sulfamethoxazole (inhibit folate synthesis)
What is surgical prophylaxis?
Decrease risk for surgical site infection (SSI)
Surgical classification of clean
1-4%
Surgical classification of clean contaminated
5-15%
Surgical classification of contaminated
16-25%
Surgical classification of dirty
30-45%
no entry into respiratory, GI, GU tracts or oropharyngeal cavity. Generally elective with no break in technique and no inflammation encountered
Clean
entry into the respiratory, GI, GU, biliary, oropharyngeal cavity without unusual contamination. Also includes clean procedures with minor break in technique
Clean contaminated
fresh traumatic wounds, gross spillage from GI (no mechanical bowel prep), major break in technique, incisions encountering acute, nonpurulent inflammation
Contaminated
procedures involving old traumatic wounds, perforated viscera, clinically evident infection
Dirty
When do you want to being first does for surgical prophylaxis?
Infusion 60min prior to incision
When do you want to start quinolone or vancomycin for surgical prophylaxis
120min prior to incision
When do you redose throughout operative period?
Longer than 4hrs or >2 half lives of antibiotic or major blood loss
Duration of prophylaxis
Unnecessary beyond surgery
Not greater than 24 (48) hrs
What does prolong duration of prophylaxis do?
Lead to resistance
If have beta lactam allergy, what is an alternative for surgical prophylaxis
Vancomycin
Clindamycin
What is surgical care improvement project (SCIP)
Quality measure to Medicare for public display
4 key concepts for SSI prophylaxis
- Antibiotic choice
- Dose and therapeutic coverage
- Timing of pre-op dose
- Duration of post-op antibiotics
What should be used when need 30min prior of pre-op dose
Cefazolin
What should be used when need longer infusion time for pre-op dose?
Vancomycin or quinolone
5 antibiotics that may affect NMJ
Aminoglycosides Quinolones Polymyxins Tetracyclines Clindamycin
What are antibiotics additive with
Non depolarizing NM blocker
Volatile anesthetics
Local anesthetics
Underlying disease that should be used in caution with antibiotics
Myasthenia gravis
3 different varying mechanisms with antibiotics and NM blockers
- Inhibit pre synaptic ACh release
- Post-synaptic receptor block
- Local anesthetic like (inhibit axon AP propagation)
How can antibiotics and NM blockade be reversed?
Calcium
Neostigmine
Which drug does not reverse NM blockade with antibiotics
Polymyxin
Some general adverse effects of antibiotics?
Reasons to be conservative with antibiotic use
Allergic and allergic-like rxns
Effect on normal flora
Resistance
What if pt has penicillin allergy?
Avoid agents with similar side chain
-penicillins, cefaclor, cefadroxil, cefatrizine, cefprozil, cephalexin, cephradine
Which drug does impact oral contraceptive
Rifampin does induce estrogen metabolism that leads to increase clearance
What to avoid if patient is pregnant?
- TMP/SMX in 3rd trimester
- doxycycline during all trimester
- quinolones during all trimester
Is metronidazole anaerobic or aerobic?
Anaerobic
What does mupirocin do?
Inhibits tRNA synthetase
3 concerns with ALL antibiotics
- Hypersensitivity rxn
- Effect on normal flora
- Resistance
Penicillin:
- or +
Anaerobic or aerobic
-/+
Anaerobic
Piperacillin/tazobactam/sulbactam:
- or +
Anaerobic or aerobic
-
Anaerobic
What is piperacillin?
Antipseudomonal penicillin
What is the combo of tazobactam?
Piperacillin and tazobactam
What is the combo of sulbactam?
Ampicillin and sulbactam
What is Doripenem?
Resistant to beta lactamase
Doripenem:
- or +
Anaerobic or aerobic
-/+
Anaerobic
Cefazolin:
- or +
Anaerobic or aerobic
-/+
Anaerobic
Cefotetan:
- or +
Anaerobic or aerobic
Increasing -
Anaerobic
Ceftiaxone:
- or +
Anaerobic or aerobic
Decreasing + and increasing -
Anaerobic
Gentamicin:
- or +
Anaerobic or aerobic
-
Aerobic
Tobramycin:
- or +
Anaerobic or aerobic
-
Aerobic
Erythromycin:
- or +
+
Tetracycline and Doxycline:
- or +
+
Clindamycin:
Anaerobic or aerobic
Anaerobic
Linezolid:
- or +
Anaerobic or aerobic
+
Anaerobic
MOA of metronidazole?
Nitro radical anion targets DNA
Metronidazole:
Anaerobic or aerobic
Anaerobic
Mupirocin:
- or +
+