Antibiotics Flashcards
Natural Prevention
- Anatomical/Physiological barriers
- Skin
- pH
- Barrier
- Lungs
- Ciliary clearance
- Stomach
- Lower stomach pH
- Skin
- Innate immunity
- Non-specific
- Adaptive immunity
- Takes several days to develop response
- Long-term memory of a specific pathogen
- Modulating immune system:
- GCSF
- Immuneglobulins
Infection definition
- Infection: An invasion of any host organism by disease-causing organisms
Micro-organisms classification
- Bateria
- Fungi/Mold
- Viruses
- Parasites
Antibiotic Classification
- Antibacterial
- Antifungal
- Antiviral
- Antiparasitic
Increased Risk of Infection
- Age
- Nutrition
- Pregnancy
- Decreased defense barriers (ex. Severe burns)
- Cancer, HIV, other infections
- Immunocompromised
- Immunization history
- Indwelling catheters
- Corticosteroids
Considerations of Treatment – General
- General considerations
- Cost
- Insurance formulary
- Administration considerations (IV vs. PO, q24 vs. q8)
- Patient population (antibiogram)
Considerations of Treatment – medication consideration
Medication considerations
- Combination therapy (synergy)
- Antibiotic susceptibility
- Empiric Therapy
- Targeted “narrower” treatment
- Diagnostic tests
- PK/PD parameters
Considerations of Treatment - patient
Patient considerations
- Age
- Immune function
- Allergies
- Response to antibiotics (improving or worsening)
- Adverse events (ADRs)
Antibacterial Testing
Diagnostic testing
- Gram Stain
- Gram (+) vs. Gram (-)
- Cultures
- Growth of causative infection taken from site of infection
- Susceptibility
- Serology
- Titers or antibodies measured
- CBC
- Elevation (or decrease) in WBC
- PCR testing
Obtaining Cultures
- Ideally should always be done BEFORE starting antibiotic therapy
- Depending on infection concern, multiple cultures should be drawn simultaneously
Antibiotic Pharmacokinetic and Pharmacodynamic Concepts
- Pharmacokinetics and Pharmacodynamics of Antibacterial Agents
- Best antibiotic choice may depend on the different PK and PD properties
- Example: Daptomycin
- Best antibiotic choice may depend on the different PK and PD properties
Medication considerations – antibiotics
- Pharmacodynamics
- Pharmacokinetics
- Tissue penetration
Routes of Admin
- Bioavailability
- Severity of infection
- Location of infection
- Organ function
- Drug levels required
Bactericidal
- Destroy microbes
- Example: Penicillin
Bacteriostatic
- Inhibit the growth of bacteria but do not kill them
- Need immunologic response to eliminate organisms
Pharmacodynamic Efficacy – Both
- Some antibiotics exhibit bactericidal and bacteriostatic properties depending on concentration in the blood
Spectrum of Activity
Narrow vs. Broad
- Narrow spectrum
- Active against limited groups of pathogens
- Generally, may only work against gram (-) or gram (+) organisms but not both
- Broad spectrum
- Active against wide range of pathogens
- Often used for empiric therapy
- Generally, has activity against both gram (-) and gram (+) organisms
Time-dependent kinetics
Relies on the amount of time the serum concentration remains above the MIC
Concentration-dependent kinetics
- Relies on the highest concentration in the serum reached, must greatly exceed the MIC
Post antibiotic effect (PAE)
- Delayed regrowth of bacteria following antibiotic exposure
Aerobic
Grow and live in the presence of oxygen
Anaerobic
Grow and live in the absence of oxygen
Gram Positive
- Thick peptidoglycan cell wall
- Cocci
- Bacilli
Gram Negative
- Thin peptidoglycan cell wall
- Addition of a thick outer lipid membrane
- Coccobacilli
- Cocci
- Bacilli
- Minimum Inhibitory Concentration (MIC)
- The lowest concentration of an antibacterial agents to prevent growth
- Predicts bacteriological response to therapy
Testig for susceptibility is defined by…
Clinical laboratory standard institute (CLSI)
Some bacteria are inherently resistant to certain classifications
- CLSI Breakpoints –
- Sensitive
- Intermediate
- Resistant
Beta-Lactams General
- Generally considered ‘broad spectrum’ antibiotics
- Gram (+)
- Gram (-)
- Anaerobes
- Pseudomonas
Beta-Lactam Classifications
- Penicillins
- Extended-Spectrum Penicillin (ESPCN)
- ß-Lactam/ß-Lactamase Inhibitors
- Cephalosporins
- Carbapenems
- Monobactam
Beta-Lactams Mechanism of Action
- Bactericidal
- Binds to cell wall and inactivates Penicillin Binding Proteins (PBPs)
- Interferes with the last step of bacterial wall synthesis
- Time dependent killing
Penicillins
General
- Natural penicillins
- Aminopenicillins
- Penicillinase-Resistant Synthetic Penicillins (PRSPs)
- Extended-Spectrum Penicillins (ESPCN)
- Beta-Lactam/Beta-Lactamase Inhibitors
Natural Penicillin
Clinical use
- Clinical use
- Pneumococcal and streptococcal infections
- Drug of Choice (DOC) for syphilis
- Prophylaxis of enapsulated organisms
Penicillin
IM
Oral
IM=Penicillin G
Oral = Penicillin VK
Aminopenicillin
Clinical Use
- Minimal activity against Gram (-)
- Clinical Use
- DOC for enterococcal infections
- Community-acquired respiratory infections
- Otitis media
Aminopenicillin
IV/IM
Oral
IM/IV = ampicillin (IV/IM), ampicillin (IV/IM)
Oral = ampicillin, amoxicillin
Penicillinase-Resistant Synthetic Penicillins (PRSPs)
Clinical Use
- No enterococcal coverage
- No coverage of Methicillin Resistant S. Aureus (MRSA)
- Clinical Use
- DOC for beta-lactamase (penicillinase) positive
PRSPs
IV/IM agent
Oral agent
IV/IM = oxacillin, nafcillin
Oral = dicloxacillin, dicloxacillin
Extended-Spectrum Penicillin
Clinical Use
- Pseudomonasaeruginosa
- Usually in combination with an aminoglycoside
- Monotherapy okay for UTI
- Enterococcalactivity
- Goodanaerobicactivity
Extended-Spectrum Penicillin
IV formulation
- Only available as IV formulation
- Piperacillin
- Ticarcillin
Extended spectrum penicillin is used in combination with
B-lactamase inhibitor
B-Lactamase Inhibitor
- The beta-lactamase inhibitor restores the activity of the beta- lactam component in the presence of beta-lactamase
- Increases spectrum of activity
Selected B-Lactamase Producing Organisms
Staph aureus (Not MRSA)
H. influenza
Most anaerobes
Many gram negative bacilli
B-Lactam – Mixed Infections
Respiratory infections
Abdominal infections
Skin/soft tissue infections
Bite wound infections
Resistant UTIs
B-Lactams
IV/IM Agents
IV/IM
- Piperacillin/Tazobactam (Zosyn)
- Ampicillin/Sulbactram (unasyn)
- Ticarcillin/Clavulanate (Timentin)
Oral
- Amoxicillin/clavulanate (Augmentin) – depending on infection
- SAME^
- N/A (change antibiotic class)
PCN ADE
- Rash (usually delayed)
- Seizures (rare)
- Abdominal discomfort
- Neutropenia
- Fever (drug-induced fever)
- Acute renal failure (AKI)
- Elevated LFTs (oxacillin and nafcillin)
PCN CLINICAL PEARLS
- Generally considered broad spectrum
- Increasing rates of resistance seen
- Specifically Enterobacteriaceae
- Common with failure to narrow therapy
- Common with prolonged duration of use
- Should not be used for MRSA infections
Cephalosporins Generations
- 1st generation
- 2nd generation
- Enteric
- Respiratory
- 3rd generation
- Non-pseudomonal
- Pseudomonal
- 4th generation
1st Generation Cephalosporin
Clinical uses
- Primarily for GPC infections
- EXCEPT: Enterococcus
- Garden-variety gram (-) bacillary infections (PECK)
- Proteus
- E. Coli
- Klebsiella
Cephalosporins 1st generation
IV/IM – Oral
IV/IM
- Cefazolin (IV)
Oral
- Cephalexin
- Cefadroxil
2nd Generation Cephalosporins
- Enteric Cephalosporins
- Only available as IV/IM formulations
- Cefoxitin
- Cefotetan
2nd generation ceph
Clinical uses
- Anaerobic coverage (Bacteroides fragilis)
- Enhanced GNR activity, but not GPC activity
- Surgical prophylaxis (colorectal, abdominal)
2nd generation ceph
Enteric cephalosporins
Available agents – cefoxitin (IV/IM)
Clinical use
- Surgical prophylaxis (colorectal, abdominal)
Spectrum of activity
- Anaerobic coverage (Bacteroides fragilis)
- Enhanced GNR activity (lacks GPC activity)
2nd generations cephalosporins
Respiratory
Available agent, clinical use, Spectrum of activity
Available agents – Cefuroxime (IV/IM/PO)
Clinical Use
- Lower respiratory tract infections
Spectrum of Activity
- Streptococcus pneumonia
- H. Influenza
3rd Generation Cephalosporins
Spectrum of Activity
- Enhanced Gram (-) activity
- Activity against PCN-resistant pneumococcus
- Ceftazidime effective against Pseudomonas
3rd Generation Cephalosporins
Clinical use
- Community Acquired Pneumonia (CAP)
- Meningitis
- Gonorrhea
3rd Generation Cephalosporins
Benefit
- Once daily dosing (ceftriaxone and forms)
3rd Generation Cephalosporin
IV/IM
Oral
IV/IM agents
- Cefotaxime
- Ceftriaxone (Rocephin)
- Ceftazidime
- Cefotaxime
Oral
- Cefpodoxime (Vantin)
- Cefixime (Suprax)
- Cefdinir (Omnicef)
4th Generation Cephalosporins
Clinical Use
- Best cephalosporin for GNR
- Any serious infection
4th Generation Cephalosporin
Spectrum of Activity
- Exhibits excellent gram (+) and gram (-) activity
- Covers Staphylococcus, Streptococcus, P. aeruginosa
- IV/IM Agent
4th Generation Cephalosporin
Oral Agent Equivalent
- Can sometimes be used even if isolate is resistant Cefepime (IV/IM)
- None to 3rd generation cephalosporins
4th generation
IV/IM
Oral
IV/IM – cefepime
Oral – none
Cephalosporin ADE
- Rash (usually delayed)
- Seizures (rare)
- Abdominal discomfort
- Neutropenia
- Fever (drug induced fever)
- Biliary sludging (ceftriaxone)
Cephalosporin Clinical Pearls
- Use in caution in patients with PCN allergies
- ~10% cross sensitivity
- Coverage changes with change in generation
- GPC
- GNR
- Pseudomonas
Carbapenems
General
- Broadest spectrum of all antibiotics
- Potential cross sensitivity for PCN allergies
- ~15%
Carbapenems
Spectrum of Activity
- Pseudomonas infections
Carbapenems
Clinical Use
- Serious infections with multiple resistant bacteria
- Febrile neutropenia
- Monotherapy for polymicrobial infections
Organisms intrinsically resistant to carbapenems (7)
- MRSA
- E. faecium
- Stenotrophomonas
- Burkholderia
- Chlamydia
- Mycoplasma
- Corynebacterium
Carbapenems
IV/IM
Imipenem
Meropenem
Doripenem
Ertapenem (IV/IM)
Monobactam (Aztreonam)
Spectrum of Activity
- NO activity against GPC or anaerobes
- ONLY active against GNR
- No apparent cross-reactivity in ß-lactam allergic patients
Aminoglycosides
Mechanism of Action
- Bactericidal
- Concentration dependent killing
- Inhibits protein synthesis at 30s ribosome
Aminoglycosides
Spectrum of Activity
- Gram Negative Rod infections
- Used in combination for gram (+) organisms (i.e. endocarditis)
- GI bacterial overgrowth
Aminoglycosides
Clinical Use
- Gram (-) infections
- Poor penetration in to abscesses
Aminoglycosides
Specific Agents
- Amikacin
- Greatest risk of toxicity
- Tends to defer resistance compared to gentamicin and tobramycin
- Gentamicin
- Tobramycin
- Pseudomonal coverage than gentamicin
- (Streptomycin)
Aminoglycosides
Dosing
- Requires narrow therapeutic monitoring
- Interval dosing can be traditional or extended
Aminoglycosides
Toxicity (associated with long-term use and acute toxicity)
- Nephrotoxicity (renal tubular damage)
- Ototoxicity (Irreversible hearing loss)
Sulfonamides (Sulfamethoxazole)
AKA…
Folic acid metabolism inhibitors
Sulfonamides (Sulfamethoxazole)
Mechanism of Action
Bacteriocidal vs. static?
- Bacteriostatic
- Inhibits cell growth via interfering with folic acid synthesis
- Generally abbreviated as ‘sulfa’ medications
Sulfonamides (Sulfamethoxazole)
Spectrum of Activity
Drug of choice for (3)
- Gram (-) & gram (+)
- MSSA & MRSA
- Drug of choice for: Stenotrophomonas, Nocardia, & Pneumocystis jiroveci pneumonia (PCP)
Sulfonamides (Sulfamethoxazole)
Clinical Use
- UTI (treatment and prophylaxis)
- Respiratory tract infections
- PCP prophylaxis
- Abdominal infections
- Cellulitis
Sulfonamide ADE (7)
- Rash
- Photosensitivity
- Nephrotoxicity
- Obstructive uropathy
- Neutropenia
- Thrombocytopenia
- Hyperkalemia
Sulfamethoxazole/Trimethoprim (Bactrim®, Co-trimoxale®,SMX/TMP)
IV/PO information
Clinical Pearls (2); PCP dosing, allergies
- Only available in combination with trimethoprim
- Available as IV and PO
- IV has short stability and requires more frequent dosing
- PO dosing is typically q12
- Clinical Pearls
- PCP ppx dosing is TIW (FSS, MWF, etc)
- Watch for sulfa allergies
Fluoroquinolones
General and MOA
- Broad spectrum of activity against GNR
- Poor anti-anaerobic activity
- Mechanism of Action
- Bactericidal
- Inhibits topoisomerase IV and DNA gyrase
Fluoroquinolones
Spectrum of Activity (4)
- Broad spectrum of activity against GNR
- Variable Pseudomonal & Streptococcal activity
- Covers MSSA but not MRSA reliably
- E coli
Fluoroquinolones
Clinical Use
- Poor anti-anaerobic activity
- UTI
- STD
Fluoroquinolones
Available Agents
- Ciprofloxacin (CIPRO)
- IV/PO otic and optic suspension
- Best for pseduomonal activity
- Levofloxacin (Levaquin)
- IV/PO
- Moxifloxacin (Avelox)
- IV, PO
- Ofloxacin (ocular suspension)
Decision which FQ may be dictated by patient’s insurance
Fluoroquinolones ADE
- Photosensitivity
- Seizures(rare)
- Abdominal discomfort
- QTc interval prolongation
- CNS stimulation
- BBB for:
- Tendon ruptures
- Peripheral neuropathy
- CNS effects
FQs Clinical Pearls
- Ideal oral antibiotic if broad spectrum is needed
- Caution with BBB
- Watch for increasing rates of resistance
- Avoid in pregnancy and lactation
- Requires renal dose adjustment
- Polyvalent metallic cationic adsorptive interactions
- Avoid taking with foods and/or medications with metallic cautions
Tetracyclines
Mechanism of Action
- Bacteriostatic
- Inhibits 30s and 50s ribosomal subunits in susceptible bacteria
Tetracyclines
Spectrum of Activity
- Stenotrophamonas (minocycline)
- MSSA, MRSA
- Mycoplasma pneumonia
- Lots more…
Tetracyclines
CLinical Use
- Community-acquired respiratory tract infections
- STDs (chlamydia)
- Lime disease and Rickettsial diseases
- Malaria prophylaxis
- Acne
Tetracyclines
Available Agents
- (all have IV & PO formulations)
- Minocycline*
- Tetracycline
- Doxycycline *
* Used more orally than tetracycline
Tetracycline ADE
- Photosensitivity
- Abdominal discomfort
- Stained teeth (cosmetic)
- Absorption may be decreased with foods and metallic cations
Macrolides
Mechanism of Action
- Bacteriostatic
- Binds to 50s ribosomal subunit to inhibit RNA synthesis
Macrolides
Spectrum of Activity
- H. pylori
- Atypical pathogens
- Legionella
- Mycoplasma
- Chlamydia pneumoniae
Macrolides
Clinical Use
- Respiratory infections & community-acquired pneumonia
- Skin and soft tissue infections
- STDs
Macrolides
Available Agents
- Erythromycin (EES)
- Used largely in pediatric for pro-motility & enhance gastric emptying
- Causes QT prolongation
- Azithromycin
- Clarithromycin
Macrolides
ADE
- Abdominal discomfort
- Ototoxicity (rare)
- Taste disturbances
Macrolides
Clinical Pearls
- Erythromycin is used more for its intestinal pro-motility agent
- Decreased clearance of many drugs via CYP 450 inhibition
- Not seen with azithromycin
- Do not use clarithromycin during pregnancy
- Pregnancy category C
Clindamycin
Mechanism of Action
- Mechanism of Action
- Bacteriostatic
- Bacteriocidal
- Inhibits protein synthesis by binding to 50s ribosomal subunit
Clindamycin
Spectrum of Activity
Clinical Use
- Spectrum of Activity
- Aerobic GPCs
- MRSA & MSSA
- Anaerobic organisms
- Clinical Use
- Inhibits toxin release
- Cellulitis
Lincodamide ADE
- Abdominal discomfort
- Pseudomembranous colitis
- Taste!
- Capsules can be opened and dissolved
Metronidazole
Mechanism of Action
Spectrum of Activity
- Mechanism of Action
- Bactericidal
- Interacts with DNA to cause a loss of helical DNA structure and strand breakage
- Spectrum of Activity
- Clostridium difficile colitis
- Anaerobic infections
- Protozoal infections
Metronidazole
Clinical Use
- STDs
- Bacterial overgrowth
Metronidazole
ADE
- Peripheral neuropathy
- Taste disturbances
- Disulfiram reaction
- Seizures (rare)
- Abdominal discomfort
Vancomycin
Mechanism of Action
Spectrum of Activity
- Mechanism of Action
- Slowly bactericidal
- Glycopeptide that Inhibits cell wall synthesis
- Spectrum of Activity
- Gram (+) organisms
- C. difficile
Vancomycin
Clinical Use
- Treatment of choice for MRSA
- Empiric therapy for pneumococcal meningitis
- Oral therapy for C. difficile colitis
- In place of penicillin in patients with a PCN allergy
Vancomycin
ADE
- Ototoxicity (rare)
- Nephrotoxicity
- (Red-man syndrome)
- Neutropenia
VANCO ADME
- Requires serum level monitoring for efficacy and safety
- Not orally absorbed
Linezolid
Mechanism of Action
- Bacteriostatic in vitro
- Bactericidal in vivo
- Inhibits cell wall synthesis
Linezolid
Clinical Use
- Vancomycin Resistant Enterococcus (VRE)
- Systemic oral GPC-specific product is needed
- Does not need renal adjustment
Linezolid
ADE
- Thrombocytopenia
- Peripheral neuropathy
- Optic neuropathy
- Lactic acidosis
Daptomycin
Mechanism of action
Spectrum of Activity
- Mechanism of Action
- Bactericidal
- Depolarizes cell wall
- Spectrum of Activity
- VRE
- MRSA
- VRSA
Daptomycin
Clinical USe
- Skin & soft tissue infections
- Endocarditis
- AVOID in pneumonia
Daptomycin
ADE
- CPK elevations
- Myopathies
- Avoid in combination with statins
- Azole Antifungal
- Mechanism of Action
- Inhibits ergosterol synthesis (main sterol in fungal cell wall) therefore prevents cell wall growth
Azole Antifungal
Available Agents
- Fluconazole
- Ketoconazole (used topically)
- Voriconazole
Azole Antifungal
Spectrum of Activity
- Fluconazole
- Voriconazole
- Fluconazole
- Candida
- Cyptococcus, blastomyces, etc.
- Voriconazole
- Candida species
- Aspergillus
- Mold
Azole Antifungal
Side effects
- Increase in LFTs
- Abdominal pain, N/V (general well tolerated)
- QT prolongation
- Specific to voriconazole:
- CNS hallucinations or visual disturbances
- Increased SCr
Azole Antifungal
Clinical Pearls
- Voriconazole requires therapeutic drug monitoring
- Major interaction with CYP enzymes
- CYP3A4 (strong inhibitor)
- CYP2C9 & CYP2C19 (moderate inhibitor)