Lecture 15: Antibiotics Part 1 Flashcards by Emily Wood

What color does a G+ bacteria stain?

Purple

Mnemonic:
(more Ps = more positive)

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What is the main shape of G+ bacteria?

Cocci

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What is the only coagulase positive Staphylococcus?

S. aureus

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What are the two types of paired/chained cocci?

Streptococcus
Enterococcus

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What is the more resistant Enterococcus?

E. faecium

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What are the two shapes of G- bacteria?

Cocci
Bacilli

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What 5 bacteria form the enterobacterales?

E. coli
Klebsiella spp.
Enterobacter spp.
Serratia spp.
Citrobacter spp.

AKA all lactose fermenters are enterobacterales.

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What are the 3 main enterobacterales?

E. coli
Klebsiella spp.
Enterobacter spp.

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What kind of bacteria is P. aeruginosa?

A non-lactose fermenter.
G- bacilli.

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What are the anaerobic bacteria?

G+:
Peptostreptococcus
Clostridium

G-:
Bacteroides spp.

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What are the 3 atypical bacteria?

Mycoplasma
Legionella
Chlamydophilia

Note:
Pneumonia is common from all 3 of these.

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What do penicillins and cephalosporins do for their mechanism?

Inhibition of cell wall synthesis.

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What does MRSA, VRE, ESBL, and CRE stand for?

MRSA: methicillin-resistant S. aureus

VRE: Vancomycin resistant enterococcus

ESBL: extended spectrum beta lactamase producing organism.

CRE: Carbapenem-resistant enterobacterales.

Note:
VRE and CRE are NOT THE SAME E.

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What is the different between narrow and broad spectrum abx?

Broad means multiple strain coverage.

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What is the difference between empiric and definitive therapy?

Empiric is not knowing what the specific organism is, but having a good idea.

Definitive is knowing what organism you’re going to treat.

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What is MIC?

Lowest concentration of an abx needed to INHIBIT growth of a bacteria.

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What does it mean when an abx is time-dependent?

The time spent above the MIC. AKA as long as you meet the MIC, it’s how long you stay above it, not the dosage itself.

Note:
Applies to many of the beta-lactamases, which are G- bacteria.

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What does it mean when an abx is dose-dependent?

Concentration dependent, aka the higher the dose, the higher the efficacy.

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What is meant by beta-lactamase bacteria?

A bacteria capable of producing an enzyme that can break apart beta-lactams.

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What ABX make beta lactams?

Penicillins
Cephalosporins
Carbapenems
Monobactams

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What ABX category is vancomycin?

Glycopeptide

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What ABX category is daptomycin?

Cyclic glycopeptide

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What ABX category ends in vancin?

Lipoglycopeptides

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What are all cell wall agents able to do to bacteria?

Kill them.

All agents are bactericidal.

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Describe the MOA of a beta-lactam.

Bind to penicillin-binding proteins in cell walls. Interrupts cell wall synthesis, resulting in bacterial cell lysis and death.

What kind of toxicity can ensue from beta-lactams in renal dysfunction?

CNS toxicity. Note: Most ABX are renally dosed as a result.

What kind of disturbance can ensue from oral beta-lactam use?

GI disturbances.

What drug interacts with all the beta-lactams? What does it do?

Probenicid. Increases serum concentration.

What is efficacy measured as?

Time above MIC (aka time-dependent)

What kind of agents usually use prolonged infusions?

Antipseudomonals.

What is the only natural pencillin?

The pencillins! Penicillin VK, G, G sodium, G benzathine, G procaine/benzathine.

Why is benzathine added to pencillin?

Prolongs half-life.

What is a unique clinical use of penicillin?

Syphilis treatment

What is the reaction that occurs from penicillin use? What kind of reaction relationship is it?

Jarisch-Herxheimer reaction. Time-related reaction.

What are the only two penicillins that do not require renal adjustments?

Nafcillin Oxacillin

What is MSSA?

Methicillin susceptible staph A

Why is Oxacillin preferred over Nafcillin?

Nafcillin has a higher incidence of acute interstitial nephritis.

What class are nafcillin, oxacillin, and dicloxacillin in?

Penicillinase-resistant Penicllins

What are the two aminopenicillins?

Amoxicillin Ampicillin Note: They start with A.

What specific bacteria are aminopenicillins used for?

Enterococcus spp. They are the drug of choice. Note: If it is VRE, they are generally resistant to penicillins as well.

What is the only extended spectrum penicillin?

Piperacillin No longer on market as a solo drug.

What is the bonus of having an ES penicillin over a regular one?

Additional G- coverage.

What was piperacillin originally intended for?

Antipseudomonal! AKA it works against P. aeruginosa.

What is a beta-lactamase inhibitor? Why is it clinically significant?

Prevents hydrolytic action on penicillin and binds directly to penicillin-bind proteins to increase abx activity. Note: Bacteria can make beta lactamases, which can cleave some abx and disable them.

What are the 3 beta-lactamase inhibitor combinations for penicillins?

Amoxicillin/clavulanic acid Ampicillin/sulbactam Piperacillin/tazobactam AKA the aminopenicillins and extended spectrum penicillin.

What does adding a beta-lactamase inhibitor do to an antibiotic's coverage?

Increased G- coverage Increase anaerobe coverage

Which beta-lactamase inhibitor combination can cover the acinetobacter spp?

Ampicillin/Sulbactam

What kind of antibiotic is a cephalosporin?

Beta-lactam abx

What generally happens as the cephalosporin generation increases?

Increased G- coverage Increased CNS penetration (aka able to treat meningitis)

If someone has a penicillin allergy, can I give a cephalosporin?

Yes (mostly) Cross-reactivity is only about 1%.

What are the 3 first-gen cephalosporins?

Cefazolin Cephalexin Cefadroxil

What are first-gen cephalosporins mainly used for?

MSSA

What penicillin do I use for more minor MSSA?

Oxacillin

What are the 2nd gen cephalosporins?

Cefotetan Cefoxitin Cefprozil Cefaclor Cefuroxime

Which 2nd gen cephalosporin can interact with warfarin?

Cefotetan Note: It has a MTT side chain.

What two 2nd gen cephalosporins have anaerobic activity?

Cefotetan Cefoxitin

What is cefuroxime usually used for?

Respiratory tract infections

What are the 3rd gen cephalosporins?

Cefdinir Cefpodoxime Cefixime Ceftriaxone Ceftazidime Cefotaxime

What is the only 3rd gen cephalosporin with antipseudomonal activity?

Ceftazidime

What is the only 3rd gen cephalosporin with POOR G+ activity?

Ceftazidime

What is the only 4th gen cephalosporin?

Cefepime

What is unique/significant about cefepime?

Antipseudomonal activity Acenitobacter spp. NO ANAEROBIC activity

What is the only MRSA-active cephalosporin?

Ceftaroline It is the only beta-lactam that works vs MRSA.

What is Ceftolozane/tazobactam used for?

DTR/MDR pseudomonas. Note: Requires 2x dosage if treating pneumonia.

What is ceftazidime/avibactam used for?

Mainly used for CRE Can be used on MDR pseudomonas.

What kind of cephalosporin is cefiderocol?

Siderophore cephalosporin Note: Chelates ferric ions and utilizes bacterial ion transport like a trojan horse.

What can cefiderocol be used on?

CREs P. aeruoginosa (not as preferred)

What are the 4 carbapenems?

Imipenem/cilastatin Meropenem Doripenem Ertapenem

Why is cilastatin added to imipenem?

To prevent breakdown.

What kind of spectrum do carbapenems cover?

Broad. Includes G+, G- and anaerobes.

What are the two preferred agents in the carbapenems?

Imipenem/cilastatin Meropenem

In what kind of bacteria are carbapenems the drug of choice?

ESBLs

Which carbapenem has NO pseumondas or acinetobacter coverage?

Ertapenem

What kind of adverse effect should I be careful/monitor with carbapenem use?

Seizures, mainly with imipenem/cilastatin use. Note: 1% cross-reactivity with PCN allergy as well.

What abx can decrease valproic acid levels?

Carbapenems

What are the two carbapenem/beta-lactamase inhibitors?

Meropenem/vaborbactam Imipenem/relebactam

Why are carbapenem/beta-lactamase inhibitors used?

Used vs CRE. Imipenem/relebactam can be used vs CR pseudomonas. No added activity vs acinetobacters.

What abx falls under the monobactams?

Aztreonam

What is aztreonam used for?

G- only coverage. Antipseudomonal, but not vs acinetobacter. Note: Sometimes used in place of penicillin. Can cross-react with cefatizidime sometimes

What abx is a glycopeptide?

Vancomycin.

What is the MOA of vancomycin?

Blocks peptidoglycan synthesis, inhibiting bacterial cell wall synthesis.

What does vancomycin cover?

G+ (INCLUDING MRSA)

What is PO vanco used for?

C. Diff (must be PO, IV vanco does nothing to C. diff)

Why is vanco almost always given IV?

Extremely poor bioavailability if enterally.

What kind of reaction is a red-man syndrome?

Infusion reaction. It is a result of vancomycin being given too fast, not allergy.

What drugs can cause nephrotoxicity?

Piperacillin/bactam Vancomycin

Do I monitor trough or AUC/MIC ratio with vancomycin?

AUC/MIC ratio. (400-600 best)

What abx is a cyclic glycopeptide?

Daptomycin

What is the MOA of a cyclic glycopeptide?

Binds to components of cell membrane, causing rapid depolarization to inhibit DNA, RNA, and protein synthesis.

What is daptomycin used for?

G+ coverage, including MRSA. Also works vs VRE. It has a similar efficacy to vanco with better tolerance.

What is unique about daptomycin's PK?

Inactivated by pulmonary surfactant. AKA if the MRSA is in the lungs, it won't do anything.

What abx category is telavancin?

Lipoglycopeptide

What is the MOA of telavancin?

Inhibits cell-wall synthesis, blocking polymerization and cross-linking of peptidoglycan.

What is the coverage of telavancin?

G+ only, including MRSA.

When do I use telavancin?

Second-line for all indications.

What kind of adverse effects does telavancin have?

Increased SCr (less effective if CrCl < 50) Red man syndrome Artificially prolongs PT/INR, aPTT, factor Xa

What kind of drug interactions does telavancin have?

QT-prolongation

What kind of abx are dalbavancin and oritavancin?

Lipoglycopeptides

What is the MOA of dalbavancin and oritavancin?

Binds to cell wall peptidoglycan/precursors preventing cross-linking and interfering with cell wall synthesis.

When is oritavancin used?

Good against VREs.

What is unique about the PK of dalbavancin and oritavancin?

VERY LONG half-lives. Able to dose weekly or one time. Sometimes given 2 doses for 6 weeks. Currently in DOTS trial.

Which of the lipoglycopeptides has similar infusion reactions to vancomycin?

all 3! They can all have red man syndrome.

Which of the lipoglycopeptides has a similar rate of nephrotoxicity as vancomycin?

Dalbavancin

What do I need to be careful in terms of drug interactions with Oritavancin?

MAJOR CYP inducer and inhibitor. You cannot give IV unfractionated heparin for 5 days after giving oritavancin.

What are the cell membrane agents?

Colistin, polymixin E Polymixin B

What is the MOA of a cell membrane agent?

Damages cell membrane, allowing leakage of cell contents.

What spectrum are the cell membrane agents?

G- only. ONLY USED FOR MDR resistant organisms, such as P. aeruginosa and A. baumannii

What kind of toxicities can cell membrane agents cause?

Nephro Neuro