Antibiotics Flashcards
Antibiotics that are time dependent?
Beta Lactams:
Penicillins
Cephalosporins
Carbapenems
Antibiotics that are concentration dependent?
Fluoroquinilones
Aminoglycosides
Daptomycin
Macrolide
What does “cidal” mean?
- Defined as having a 2 log drop in your bacteria over a 24 hr period
- Beta lactams are categorized as these
4 categories of Beta Lactams
- Cephalosporins
- Penicillins
- Carbapenems
- Aztreonam
Penicillins
- Categories include natural, amino, anti-staph and extended spectrum with combo beta lactamase inhibitors
- Kill gram positives (MSSA)
- Work at the PBP on the peptidoglycan bacterial wall to cause apoptosis
- Primarily cidal drugs
- Generally have poor BA
3 major side effects of Penicillins
Hypersensitivities
Blood dyscrasias
Lower seizure threshold
T/F: When beta lactams can be given with continuous infusion they should be.
TRUE
T/F: GAS is completely susceptible to amoxicillin, ampicillin and penicillin
TRUE
Best way to administer penicillin?
Less drug and slow infusion allows you to reach better targets to treat your patients
What drug in combo with Penicillin will drastically increase Penicillin’s concentration in the body?
Probenecid
Ceftriaxone
- DOC for Strep pneumo
- IV only
- Treats diseases of the biliary tract because it is primarily biliary eliminated
- BAD drug to give in neonates can –> hyperbilirubinemia –> developmental delay
- May see calcium precipitation with this drug
- Normally given once daily unless meningitis (twice)
Third generation cephalosporins target?
Gram - bacteria
Fourth generation cephalosporins target?
Gram + and - bacteria (cefepime)
Fifth generation cephalosporins are important for?
Binding to the mutated site of the PBP site created by MRSA
Which drugs fit this description?
- Lumped under second generation cephalosporins but they also cover anaerobes
- Cephamycins
Cefotetan and Cefoxitin
Cephalosporin PEARLS
- Cephamycin’s have enhanced gram-negative anaerobic activity
- Third and fourth generation have enhanced CSF penetration (e.g. ceftriaxone, ceftaz, cefepime)
- Poor BA
Cephalosporins do NOT have activity against _______?
Enterococcus
Cephalosporins that can treat meningitis?
3rd and 4th generation
What 3 cephalosporins can be administered during dialysis?
Cefazolin, cefepime and perhaps ceftazidime
Ceftaroline
- 5th generation cephalosporin
- Activity vs. MRSA and gram-negatives
Two cephalosporins that should only be used with patients who have significant drug resistant infections.
Sometimes seen with CF and LVADS
Ceftazidime/Avibactam & Ceftolozane/Tazobactam
Mainly developed to treat gram negative bacterial infections
INCLUDE:
Imipenem/Cilastatin
Meropenem
Ertapenem
Doripenem
Carbapenems
PEARLS of Carbapenems
- IV only
- Worst offender of lowering the seizure threshold
- Lower the valproic acid level in your body drastically (DDI)
- Ertapenem has no pseudomonal activity
- Imipenem/Cilastatin duo may have better activity against gram positive bacterium
- Should be renally adjusted
How does Imipenem/Cilastin combo work?
Gives Imipenem a longer half life by inhibiting kidney enzymes!
Which carbapenem does not cover Pseudemonas?
Ertapenem
The beta lactamase inhibitors include:
- Clavulanic acid
- Tazobactam
- Sulbactam
- Avibactam
- Vaborbactam
Lone monobactam
Does not work AT ALL against gram + bacterium
Can give the drug inhaled for isolated pneumonia
Aztreonam
Aztreonam only treats which type of bacteria?
Gram -
Potential side effect for Azetreonam?
Transaminitis
There might be cross reactivity between aztreonam and ______ but otherwise, there is no cross-reactivity between aztreonam and beta lactams
Ceftazidime
First generation cephalosporin that is the “go to” oral Abx
Cephalexin
First generation cephalosporin that is the “go to” IV Abx
Cefadroxil
ABx that binds directly to the amino acid (Alanine) present on the bacterial cell wall of all gram positive bacteria, not the PBP
Does not have good activity to gram negative bugs
Acts against MRSA, strep and enterococcus
Cidal
Drug of choice against C diff and MRSA
AUC/MIC >400
Very high serum concentrations
Vancomycin
Targets of Vancomycin?
Gram + bacteria
MRSA
C. diff
Why does Vanco not have good activity against gram - bacterium?
The drug cannot fit through the channels of the double layered membrane
How is Vanco administered for C Diff?
Orally
2 ideal treatments for MSSA?
- anti Staph penicillins
- Cefazolin
ADEs of Vancomycin?
- Red Mans syndrome
- Thrombocytopenia
- Neutropenia
- Ototoxicity
- Nephrotoxicity
Vancomycin may have DDI with?
Aminoglycosides and Nephrotoxic Agents
Risk factors for nephrotoxicity while on Vancomycin include…
High doses
Obesity
Hypotension
Concurrent nephrotoxins
Concurrent beta lactams (piperacillin)
When dosing and monitoring Vancomycin you must take into account _______ dose and _______ dose
Loading and maintenance dose
you must ALSO take into account weight and renal function
- Used for efficacy, not so much toxicity
- 30 mins prior to 4th does
- Make sure patient is in steady state before ordering
- Done every week to two weeks after the initial monitoring is done because the patient maintains relatively stable concentrations
Trough concentrations
- Lipoglycopeptide
- IV
- Predominately gram positive
- Inhibits cross-linking and peptidoglycan formation (D-Ala-D-Ala) and causes membrane depolarization
- Highly protein bound
- Patient’s with bad kidneys did not have good results with this drug
- Chalky taste and foamy urine
- Decreases blood clotting
- Can be used for MRSA but not used over Vanc
- AUC/MIC
Telavancin
- 2nd generation lipoglycopeptides
- Treat staph and strep (MRSA)
- Long acting IV injections because of their very large half lives
- Used to treat osteomyelitis
Dalbavancin and Oritavancin
Has cidal activity except with enterococcus
Concentration dependent
Causes a membrane depolarization leading to an inhibition of DNA, RNA and protein synthesis
May cause musculoskeletal atrophy (statins may also increase CPK levels)
Weight based dosing
Do not use to treat any sort of pulm infection
Daptomycin
Route of administration for Daptomycin?
IV
What does Daptomycin treat?
Predominately gram positive including MRSA and VRE
NOT enterococcus
Daptomycin ADE?
May cause muscle toxicity with an increase in CPK
Daptomycin DDI?
Statins (might also increase CPK)
Work predominantly on gram negative bacterium because there are no holes on the gram positive membrane
Concentration dependent
Nephrotoxicity and ototoxicity
Very high PAE
Need to be cautious with this drug; therapeutic drug monitoring
Gram positive synergy (e.g. vanc)
Aminoglycosides
Aminoglycosides MOA?
Irreversible 30s subunit binding
Aminoglycosides- Why can we use/Why do we use?
Peak/MIC ration predictive of cidal activity
High peaks do not equal toxicity
Less nephrotoxicity
PAE
Less monitoring (once daily dosing)
Atypical pathogens?
Mycoplasma, Chlamydia, Legionella
Abx that work on atypcials?
Tetracyclines, Microlides and Fluoroquinilones
- Works against atypical pathogens (mycoplasma, chlamydia and legionella)
- Works against some gram negatives
- Limited with anaerobes
- STIs
- Strep pneumonia and staph areus
- Activity against C diff
Tetracyclines
Tetracycline MOA?
Works on the 30s ribosomal subunit; static
Tetracyclines used for treating S. aureus activity?
Doxycycline and Minocycline
Tetracycline ADE?
- GI dyspepsia
- Binding with multivalent cations
- Tooth discoloration
- Sun sensitivity
Minocycline: vertigo, discoloration, hepatitis, lupus, leukopenia, pericardial effusion
T/F: tetracyclines have really good tissue penetration but really poor serum concentrations
(Aka would not use to treat blood stream infections)
TRUE
Vancomycin-Resistant Enterococcal UTI’s
Doxy > Tetra > Mino
Tetracycline that treats SIADH (syndrome of inappropriate ADH secretion)
Demeclocycline
Tigecycline
- Tetracycline that binds to two sites on the ribosome
- Enhanced minocycline
- Broad spectrum but doesn’t work well in pts because it rapidly leaves blood stream and penetrates tissues greatly
- Rarely ever used
- Biliary excretion is the primary route of elim
- Been to work well with mycobacterium infections and severe C diff
The Tetracyclines include?
Doxycycline, Tetracycline, Minocycline, Tigecycline
Tigecycline can be given in what situation?
ICU patients with severe drug resistance
Tigecycline ADE?
Profuse projectile vomiting
Tigecycline route of administration?
IV only
- Binding at the 23S and 50S ribosomal subunit
- Static activity and time dependent
- Oral and IV BA 100% (1:1)
- Good to use for vancomycin resistant bugs
- No renal adjustment
- Very high tissue penetration so it has never been clinically proven to be better than Vanco
Linezolid
Linezolid works against?
Gram positive, MRSA, VRE, Mycobacterium, C. Diff
Linezolid ADE?
- Hematologic (RBC,WBC and platelets)
- Peripheral neuropathies (weakness, numbness, pain in hands and feet)
- Arthralgia in hands and knees
- Optic neuritis
- May see drug drug interactions with SSRI’s because it is a MAO inhibitor; reduce SSRI to lowest effective dose
- Caution with tyramine containing foods; increase in BP
- Inhibits DNA gyrase and topoisomerase at the site of DNA replication
- 40% resistance of E coli
- Avoid use in “simple uncomplicated infections”
Fluoroquinilones
What do fluoroquinilones work against?
Gram +, gram -, pseudo, anaerobes, atypicals
ADE for fluoroquinilones?
Sun sensitivity, tendon rupture, Cipro Psychosis, dysglycemia, PN, QT prolong
- Not renally adjusted
- Activity against anaerobes
- Activity against atypical organisms
Moxifloxacin
- Does not have 1:1 BA like the other fluoroquinolones
- Has MRSA activity
Delafloxacin
The fluoroquinilones include?
Ciprofloxacin, Levofloxacin, Moxifloxacin, Delafloxacin
What 3 fluoroquinolones have pseudemomas activity?
Ciprofloxacin, Levofloxacin, and Delafloxacin
DNA gyrase is more common in which bugs?
Gram +
Topoisomerase is more common in which bugs?
Gram -
- Fluoroquinolone with higher topoisomerase activity in comparison to DNA gyrase
- Higher affinity for gram negative organisms
- DOES get into the lungs, it just doesn’t treat gram positive strep pneumo
Ciprofloxacin
The Macrolides include?
Azithromycin, Erythromycin, Clarithromycin
What is the MOA of macrolides?
Binding at 50s ribosomal subunit (dissociation of tRNA from ribosome)
What do macrolides cover?
Broad spectrum:
Atypical, strep, MSSA, STI, mycobacterium, Helicobacter Pylori
Because of their action on the ribosome, macrolides have a long half life, but….
This may breed resistance
ADE of macrolides?
- GI
- Dysgeusia
- Cardiotoxicity
Which macrolide does not have GI effects and why?
Azithromycin- does not bind to gastrin
Clarithromycin and Erythromycin both….
Inhibit 3A4
Therefore you see large increases in statin!
All Macrolides also have ________ properties
Anti inflammatory
Clindamycin is antagonistic with ________?
Macrolides
Clindamycin predominately treats?
Strep and Staph- including MRSA
Clindamycin BA?
Really good! Penetrates well into most body tissues except CSF
Time dependent killing
Biggest ADE for Clindamycin?
Severe diarrhea, high risk for C. Diff*
Clindamycin clinical uses with really bad staph and strep infections?
Clindamycin binds toxins and reduce toxin production of staph and strep
Recommended with limb or life threatening staph or GAS
Drug that interferes with human follic acid metabolism?
SMX/TMP
SMX and TMP treats?
MRSA, Gram +
SMX and TMP are the DOC for?
Nocardia and PJ
SMX/TMP ADE?
Bone marrow suppression (anemia)
Hyperkalemia
High serum Creatine
2 treatments for UTIs?
Fosfomycin
Nitrofurantoin
Side effects of Fosfomycin?
NONE works directly at the bladder and is exreted in the urine
DOC for invasive MSSA?
Nafcillin (or Oxacillin) and Cefazolin
Beta lactam that works against MRSA and why?
Ceftaroline- affinity for mutated site PBP 2a
DOC for MRSA?
Vancomycin
