Antibiotics Flashcards
Antibiotic Classes Gram Coverage? (Mnemonic)
“GLAM” - Effective against Gram Positive organisms
G:
Glycopeptides
Effective against Gram Positive organisms
L:
Lincosamides
Effective against Gram Positive organisms
A:
Ami(NO)glycosides - (NO)
Aminoglycosides
Effective against Gram Negative organisms
M:
Macrolides
Effective against Gram Positive organisms
Antibiotic Classes Gram Coverage? (Non Mnemonic)
NON-GLAM abx:
Effective against Gram Positive AND Negative organisms
Cephalosporins
Tetracyclines
Penicillins
Sulfonamides
Fluoroquinolones
Carbapenems
Antibiotic Classes Mechanism of Action? (Mnemonic Tutor)
“MALT” - Inhibit Protein Synthesis
M:
Macrolides
A:
Aminoglycosides
L:
Lincosamides
T:
Tetracyclines
Antibiotic Classes Mechanism of Action? (Mnemonic)
“Rated PG CoCO” - Inhibit Cell wall synthesis
P:
Penicillins
G:
Glycopeptides
C:
Cephalosporins
C:
Carbapenems
Antibiotics Mechanism of Action? (Non Mnemonic)
1- Sul(FO)namides - Inhibit (FO)late synthesis
Sulfonamides
2- Fluoro(QUIN)olones - Inhibit DNA synthesis - (QUIN)tuplets
Fluoroquinolones
How do antimicrobial drugs work?
Antimicrobial drugs work by killing bacteria or inhibiting their growth through various mechanisms, such as inhibiting cell wall synthesis, protein synthesis, nucleic acid synthesis, or metabolic pathways.
What are natural barriers to microbes?
Natural barriers include physical barriers (skin, mucous membranes), chemical barriers (stomach acid, antimicrobial peptides), and biological barriers (normal flora).
What are some additional factors that affect the ability to fight infection?
Factors include the immune status of the host, presence of chronic diseases, use of immunosuppressive medications, and presence of foreign bodies or comorbidities.
What are some considerations when selecting an antibiotic?
Considerations include the type of infection, causative pathogen, antibiotic susceptibility, patient allergies, potential side effects, drug interactions, and patient renal or hepatic function.
What is the difference between bactericidal and bacteriostatic antibiotics?
Bactericidal antibiotics kill bacteria, while bacteriostatic antibiotics inhibit bacterial growth, allowing the immune system to eliminate the bacteria.
What are adverse drug reactions?
Adverse drug reactions are unintended and harmful effects that occur at normal doses of a drug, including allergic reactions, toxicity, and interactions with other drugs.
What are opportunistic infections?
Opportunistic infections are caused by pathogens that take advantage of a weakened immune system or imbalanced normal flora.
What is the difference between true allergic reactions and sensitivities?
True allergic reactions involve an immune system response (e.g., anaphylaxis), while sensitivities may cause non-immune mediated reactions like nausea or rash.
What is Gram Positive Bacteria?
Usually cocci, sometimes rods
Thick Peptidoglycan layer
Sensitive to Beta Lactams
What is Gram Negative Bacteria
Usually rods, sometimes cocci
Thinner Peptidoglycan layer
External layer of Lipopolysaccharides that protects the peptidoglycan layer from Beta Lactam activity, so Gram Negative bacteria is more resistant to Beta Lactams
Produce Beta Lactamase that hydrolyze the Beta-Lactam ring of penicillins and cephalosporins, destroying their antibiotic activity
What Antibiotic classes affect Cell Wall Synthesis?
Beta-Lactams
Glycopeptides
What Antibiotic classes affect DNA Replication and Transcription?
Quinolones
What Antibiotic classes affect DNA-Dependent RNA Polymerase?
Fluoroquinolones*
*(Rifamycin)
What Antibiotic classes affect Folic Acid Antagonists?
Trimethoprim-sulfamethoxazole
What Antibiotic classes affect Protein Synthesis?
Aminoglycosides
Macrolides
Lincosamides (Streptogramins)
Tetracyclines
What Antibiotic classes affect Initiation of Protein Synthesis?
(In other words: Blocks translocation of step in protein synthesis)
Oxazolidinones
Ex: Linezolid / ZYVOX
What are beta-lactams?
Beta-lactams are a class of antibiotics that include penicillins, cephalosporins, and carbapenems. They work by inhibiting bacterial cell wall synthesis.
What are the major classes of beta-lactams?
Penicillins
Cephalosporins
Carbapenems.
How do beta-lactams work?
Beta-lactams inhibit cell wall synthesis by binding to penicillin-binding proteins and disrupting the formation of the bacterial cell wall.
What is the role of penicillin-binding proteins in beta-lactam action?
Penicillin-binding proteins are involved in cross-linking peptidoglycan in bacterial cell walls; beta-lactams inhibit these proteins, leading to cell wall disruption.
How does the presence of beta-lactamase affect beta-lactam antibiotics?
Beta-lactamase enzymes hydrolyze the beta-lactam ring of these antibiotics, rendering them ineffective.
What are beta-lactamase inhibitors?
Beta-lactamase inhibitors are substances added to beta-lactam antibiotics to counteract the effects of beta-lactamase enzymes.
Like Clavulanic Acid (added to Amoxicillin)
and
Tazobactam (added to Piperacillin)
What are the 3 Types (not classes) of Penicillins?
1- Narrow-Spectrum Penicillins:
Resistant to Beta Lactamase, but restrict spectrum of activity
2- Aminopenicillins:
Have an added amino group that makes the molecule more hydrophilic so able to cross the Lipopolysaccharide layers easily. This makes Aminopenicillin have greater Gram Negative coverage
3- Broad-Spectrum Penicillins:
Modifications of Aminopenicillins with nitrogen and carbon atoms added. This increases range of sensitivity. Often coadministered with a Beta Lactamase Inhibitor
How is Penicillin excreted?
80% cleared by kidneys within 4 hours
So need consistent dosing to keep concentration of drug
Dose MUST be adjusted for patients with Renal Dysfunction
What are some examples of penicillins?
IMPORTANT:
- Penicillin G (IV)
- Penicillin V (PO) / Penicillin VK
Aminopenicillins:
IMPORTANT:
- Amoxicillin / Amoxil trimox
Aminopenicillins:
Other:
Ampicillin
Narrow-Spectrum:
Cloxacillin
Oxacillin
Nafcillin
Broad-Spectrum:
Piperacillin
Ticarcillin
What are the side effects of penicillins?
Hypersensitivity reactions (Maculopapular rash, urticarial rash, anaphylaxis)
Nausea, vomiting, diarrhea, stinging (when IV) and potential cross-reactivity with other beta-lactams.
What are the generations of cephalosporins and their examples?
1st Generation:
IMPORTANT 1st GEN:
- Cephalexin / Keflex
Other 1st gen:
Cefazolin / Ancef
Cefadroxil / Duricef
Cephalothin
Cephapirin
Cephradine
2nd Generation:
IMPORTANT 2nd GEN:
- Cefaclor / Ceclor
Other 2nd Gen:
Cefuroxime / Ceftin
Cefoxitin
Cefamandole
Cefmetazole
Cefonicid
Cefotetan
Cefprozil / Ceftin
Loracarbef / Lorabid
3rd Generation:
IMPORTANT 3rd GEN:
- Ceftriaxone / Rocephin
- Cefdinir / Omnicef
Other 3rd Gen:
Ceftazidime
Cefixime / Suprax
Cefditoren
Cefoperazone
Cefotaxime
Cefpodoxime / Vantin
Ceftibuten
Ceftizoxime
4th Generation:
Cefepime
How is cephalosporin excreted?
Renal excretion
Except Ceftriaxone (50% hepatic, 50% renal)
What does 3rd Generation of Cephalosporins have as a unique feature?
Good CNS penetration
Penetrate BBB (against bacterial meningitis)
What is the mechanism of action for cephalosporins?
Cephalosporins inhibit cell wall synthesis by binding to penicillin-binding proteins, similar to other beta-lactams.
What are contraindications of Cephalosporins?
ABSOLUTE CONTRAINDICATION:
Anaphylaxis to Penicillins
Nonanaphylactic allergy to penicillin is a relative contraindication
Cross-reactivity 1-10%
What are the common side effects of cephalosporins?
Hematologic effects - Neutropenia, granulocytopenia
Nephrotoxicity - Occasional Interstitial Nephritis
Pseudomembranous colitis - (Clostridium difficile) caused because the gut flora is wiped out, so C. diff can colonize it. This is more common with Broad Spectrum antibiotics
What is 1st Gen Cephalosporins good for?
Skin infections
Prophylactic antibiotics prior to surgery to prevent wound infection
What is 2nd Gen Cephalosporins good for?
Intra-abdominal infections
Okay for mild infections with Gram Negative
(But use 3rd gen for severe infections)
What is 3rd Gen Cephalosporins good for?
Severe infections in combination with another drug of a different class (Different MOA)
What is 4th Gen Cephalosporins good for?
reserved for severe Nosocomial infections
These have tendency to be resistant to multiple antibiotics, more severe infections, commonly due to Gram Negative
What are carbapenems and their examples?
Carbapenems are a class of beta-lactam antibiotics including:
IMPORTANT??:
Imipenem
Meropenem
Ertapenem / Ivanz
Doripenem
“Mira Dori y MI-Erta”
- Meropenem, Doripenem, Imipenem, Ertapenem
How are Carbapenems administered? Excreted? Dosage? Half-Life?
Administered by IV
Eliminated by kidneys
Imipenem is hydrolyzed by Renal Tubular Dipeptidase so always administered with Cilastatin which inhibits its breakdown
Meropenem and Ertapenem are not broken down so don’t need to add Cilostatin
Dose MUST be adjusted for patients with Renal Disease
Imipenem has higher risk of seizure for patients with Renal Dysfunction
Ertapenem has longer Half-Life and can be administered once daily
How do carbapenems differ from other beta-lactams?
“Big Guns”
Carbapenems are generally reserved for severe infections for patients very sick with bacteria that are more resistant to beta-lactamase.
Not 1st line treatment
What are Carbapenems contraindications?
Imipenem can cause seizures in 1.5% of patients
Should not be used in patient with seizure history
Other Carbapenems have replaced Imipenem
What are Carbapenems side effects?
Nausea
Vomiting
Fever
Neurotoxicity with Imipenem
But not with Meropenem or Ertapenem
What are glycopeptides and their examples?
IMPORTANT EXAMPLES:
- Vancomycin / Vancocin
Other examples:
Teicoplanin (Europe, not America)
Telavancin
What is the mechanism of action for glycopeptides?
Glycopeptides inhibit cell wall synthesis by binding to peptidoglycan precursors, preventing their incorporation into the cell wall.
What are Glycopeptides effective against?
Only Gram Positive bacteria
Because they target Peptidoglycan layer
What is Glycopeptides resistance?
Change to end of Amino Acid precursor can result in drug not binding to precursor
Excess cell wall production by bacteria
Biofilm production:
Staphylococcus epidermidis can produce a film that blocks penetration
What is Glycopeptides Half-Life? Absorption? Infection location and route? Excretion?
Vancomycin half-life is 6 hours
Glycopeptides are poorly absorbed from the GI Tract (this why used for C. diff)
If infection is anywhere else than GI Tract (like blood, soft tissues, heart, brain), then the drug needs to be administered via IV or IM
Renally cleared
MUST reduce frequency for patients with Renal Failure or Dysfunction
What are fluoroquinolones and their examples?
IMPORTANT EXAMPLE:
- Ciprofloxacin / Cipro
- Levofloxacin / Levaquin
- Moxifloxacin / Avelox
Other examples:
Norfloxacin
How do fluoroquinolones work?
Fluoroquinolones bind to and inhibit DNA gyrase and topoisomerase IV, preventing DNA replication and transcription.
DNA Gyrase in Gram Negative
Topoisomerase IV in Gram Positive
Bactericidal since DNA fragments accumulation kill bacteria
What is Resistance to Fluoroquinolones?
Mutation in genes that encode Type II Topoisomerase result in enzyme not being inhibited
Alteration in membrane Porins or Efflux Pumps that actively pump the drug out of the bacterial cell results in lower drug levels inside bacteria
What are common side effects of fluoroquinolones?
Generally well tolerated
Nausea, vomiting, diarrhea
Rare tendon ruptures (Achilles and shoulder) (unclear MOA)
What is Fluoroquinolones absorption? Excretion
Fluoroquinolones can enter human cells
Absorbed very well from gut
Makes easier transition from IV to Oral form
Most cleared Renally
Dose MAY be adjusted for patients with Renal Impairments
EXCEPTION is Moxifloxacin, which is cleared by Liver and is contraindicated in patients with Hepatic Failure
What are the contraindications for fluoroquinolones?
Pregnancy
Pediatric use (except otic/topical) for arthralgia and edema
Potential interactions with NSAIDs can make CNS toxicity and cause seizures
Theophylline (Fluoroquinolones will increase Theophylline).
What factors contribute to antibiotic resistance?
Factors include genetic mutations, changes in drug targets, production of drug-inactivating enzymes, and changes in drug permeability or efflux.
What is the role of beta-lactamase in resistance?
Beta-lactamase enzymes hydrolyze the beta-lactam ring, rendering beta-lactam antibiotics ineffective.
Why are carbapenems considered “big guns” in antibiotic treatment?
Carbapenems are used for severe infections and resistant organisms due to their broad-spectrum activity and resistance to many beta-lactamases.
- Oral Fluoroquinolones
Q: Are oral fluoroquinolones contraindicated in the pediatric population?
Yes, they are contraindicated in the pediatric population.
But Topical Fluoroquinolones are effective and safe
Approved for use in children and lack of Ototoxicity permits prolonged administration when necessary
Ofloxacin otic solution approved for Otitis Externa and Otitis Media with Perforated TM
Ciproflaxin otic suspension approved for Otitis Externa
Both can be used in patients 1+ year
- Topical Fluoroquinolones
Q: Are topical fluoroquinolones safe for children?
Yes, topical fluoroquinolones are effective and safe for use in children.
- Ofloxacin Otic Solution
Q: What conditions is Ofloxacin otic solution approved to treat?
Ofloxacin otic solution is approved for otitis externa and otitis media with a perforated tympanic membrane.
- Ciprofloxacin Otic Suspension
Q: What condition is Ciprofloxacin otic suspension approved to treat?
Ciprofloxacin otic suspension is approved for the treatment of otitis externa.
- Aminoglycosides - Examples
Q: Name three examples of aminoglycosides.
IMPORTANT EXAMPLE:
- Gentamicin (IV)
Other examples:
Tobramycin
Amikacin
Neomycin (only in creams and drops)
Streptomycin
Kanamycin
Paromomycin
- Aminoglycosides - Mechanism of Action
Q: How do aminoglycosides inhibit bacterial protein synthesis?
Aminoglycosides irreversibly bind to the 30S ribosomal subunit, causing misreading of mRNA at low concentrations and halting protein synthesis at higher concentrations.
- Aminoglycosides - Mechanisms of Resistance
Q: What are three mechanisms of resistance to aminoglycosides?
Ribosome alteration, decreased permeability, and inactivation by aminoglycoside modifying enzymes.
- Aminoglycosides - Absorption and Administration
Q: How are aminoglycosides typically administered and why?
They are usually administered IV due to poor penetration of biologic membrane, and poor GI absorption
EXCEPTION: Proximal Tubule of Kidneys
Accumulate in kidney cells and cause potential nephrotoxicity.
Tobramycin can also be inhaled.
There are topical drops for ears or eyes
Rapidly excreted by Glomerular Filtration of kidneys
Kidney function MUST be measured BEFORE and THROUGHT therapy
- Aminoglycosides - Side Effects
Q: What are common side effects and contraindications of aminoglycosides?
Contraindication:
Renal Dysfunction
Side Effects:
Ototoxicity
Caused by human mitochondrial ribosomes damaging hair cells of inner ear
Decrease hearing, tinnitus, vertigo
Nephrotoxicity
Drug accumulates in Proximal tubule cells
If creatinine levels rise, need stop drug IMMEDIATELY
Usually mild nephrotoxicity and reversible
Risk factors for renal adverse effects are HF, advanced age, and renal disease
- Lincosamides - Examples
Q: Name two lincosamides.
IMPORTANT:
- Clindamycin
Other example:
Lincomycin.
- Lincosamides - Mechanism of Action
Q: What is the mechanism of action of lincosamides?
Lincosamides inhibit protein synthesis by affecting ribosomal translation.
- Lincosamides - Mechanisms of Resistance
Q: What are some mechanisms of resistance to lincosamides?
Mutation of the ribosomal receptor site, enzymatic inactivation, and efflux pumps.
Resistance to Clindamycin usually implies cross-resistance to Macrolides
How are Lincosamides absorbed? Metabolized? Dose? Penetration?
Absorbed well orally
Metabolized by liver
Dose adjustment for severe Hepatic Dysfunction REQUIRED
Clindamycin penetrates bone and is effective for dental infections that may have bony involvement
What are Lincosamides Contraindications and Side Effects?
No contraindications
Side Effects:
High incidence of developing C. diff
- Tetracyclines - Examples
Q: Name three tetracyclines.
IMPORTANT EXAMPLES:
- Tetracycline
- Doxycycline / Oracea, Doryx
- Minocycline / Minocin
Other examples:
Demeclocycline
Tigecycline
- Tetracyclines - Mechanism of Action
Q: How do tetracyclines work?
They inhibit protein synthesis by binding to ribosomes and preventing the addition of amino acids.
Bacteriostatic, since they stop protein synthesis, but when drug level falls, protein synthesis starts again
- Tetracyclines - Resistance Mechanisms
Q: What are the main mechanisms of resistance to tetracyclines?
Efflux by Tetracycline specific pumps, ribosomal protection, and less common enzymatic inactivation.
How should Tetracyclines be taken? Excreted?
Calcium and Magnesium supplementation interferes with the effectiveness of Tetracyclines because they bind and inactivates them
Should take on empty stomach
All excreted in urine
Dose Adjustment for patients with Renal Impairments
- Tetracyclines - Contraindications
Q: What are the contraindications for tetracyclines?
Pregnancy, lactation, and children under 8 years old (except doxycycline).
What are Tetracyclines Side Effects?
GI: nausea, vomiting, diarrhea
Mottling of teeth: because bind to calcium can permanently stain developing teeth in children
Photosensitivity: resembles severe sunburn
Super infection: Wide Spectrum
Diabetes Insipidus
Liver damage: liver enzymes can be increased from drug
Kidney damage: rare, Acute Tubular Necrosis
Headache: Pseudo Tumor Cerebri (increased ICP)
- Doxycycline in Children
Q: Why is doxycycline used cautiously in children under 8 years old?
Due to potential for dental staining, but it’s used when benefits outweigh risks, especially for diseases like Lyme disease.
Between age 6-7 limited use
Only Doxycycline, since binds calcium to lesser extent than other Tetracyclines
- Macrolides - Examples
Q: Name three macrolides.
IMPORTANT:
- Erythromycin / Ery-tab
- Azithromycin / Zithromax, Z-pak
- Clarithromycin / Biaxin
- Macrolides - Mechanism of Action
Q: How do macrolides inhibit bacterial growth?
They inhibit protein synthesis by affecting ribosomal translation and can be bactericidal at high concentrations.
Erythromycin stimulates the Motilin receptors on GI smooth muscle, leading to increase forward transit of GI contents (helps with gastroparesis)
Clarithromycin and Azithromycin are commonly used for STI and Pneumonia
- Macrolides - Mechanisms of Resistance
Q: What are common mechanisms of resistance to macrolides?
Increased efflux by active pumps, production of esterase that hydrolyze Macrolides (more common in Gram Negative Enteric bacteria), and cross-resistance among macrolides.
What is Macrolides different features?
Axithromycin: distributed intra cellularly so long Half-Life (can be once daily)
Liver metabolized but not enzyme inhibitor
Erythromycin and Clarithromycin are significant CYP450 enzyme inhibitors and are liver metabolized, drug interactions should be monitored
Erythromycin is unstable in gastric acid, but Azithromycin and Clarithromycin are stable in gastric acid
Azithromycin has long duration of action, 5-day oral once daily is adequate
- Oxazolidinones - Examples
Q: Name an example of an oxazolidinone.
Linezolid / ZYVOX
They are weak Monoamine Oxidase Inhibitors (MAOI)
- Oxazolidinones - Mechanism of Action
Q: What is the mechanism of action for oxazolidinones?
They block the translocation step in protein synthesis and are bacteriostatic.
- Oxazolidinones - Side Effects
Q: What are serious but rare side effects of oxazolidinones?
SERIOUS but RARE
Serotonin syndrome (for pt who take drugs that increase Serotonin in brain, SSRI most comonly, antidepressant)
Hyperlactatemia, metabolic acidosis, nerve damage, and bone marrow suppression (mild reversible in 4 weeks after stop).
- Sulfonamides - Examples
Q: Name three sulfonamides.
IMPORTANT:
- Sulfamethoxazole
- Silver Sulfadiazine
- Sulfacetamide (topical)
- Trimethoprim (non sulfa)
Others:
Sulfadiazine
Sulfanilamide
Sulfacytine
Sulfamethizole
Pyrimethamine (non sulfa)
IMPORTANT COMBINATION:
- Sulfamethoxazole/Trimethoprim / Bactrim, Septra
- Sulfonamides - Mechanism of Action
Q: How do sulfonamides work?
They inhibit folate synthesis, and trimethoprim is often combined with sulfonamides for enhanced efficacy.
- Sulfonamides - Mechanisms of Resistance
Q: What are the mechanisms of resistance to sulfonamides?
Overproduction of PABA (p-aminobenzoic acid), enzyme mutations (reduced affinity for sulfas), and reduced drug levels inside the cell.
What is Sulfonamides metabolism? excretion? dose?
Sulfonamides metabolized by liver
Excreted by kidney
Dose adjustment for pt with Advanced Renal Dysfunction
What is Sulfonamides side effects? Contraindications?
Side Effects:
Steven-Johnson Syndrome - rare life threatening hypersensitivity involving skin and mucous membranes
Hemolytic anemia
Aplastic anemia
Granulocytopenia
Thrombocytopenia
Kernicterus (increase free Bilirubin and Jaundice in newborn)
Contraindication:
Allergy to Sulfa antibiotics
G6PD deficiency (Glucose-6 Phosphate Dehydrogenase Deficiency)
What are common uses for Sulfonamides?
UTI
Respiratory infections: Community Acquired Pneumonia
PJP (Pneumocystic Jiroveci) Prophylaxis
Topical to prevent infection in burns and severe blistering diseases of skin
- Metronidazole - Examples
Q: Name an example of a metronidazole formulation.
IMPORTANT:
- Metronidazole / Flagyl
Different formulations available, depending on what treating
Oral
Vaginal Gel (Bacterial Vaginosis)
«<Flagyl>>>
Topical (Metrogel to treat Rosacea)</Flagyl>
- Metronidazole - Mechanism of Action
Q: What type of bacteria is metronidazole effective against?
It is effective against anaerobic bacteria and protozoa.
What is Metronidazole route and metabolism? Dose?
Metronidazole oral and complete absorption
Metabolized by liver
Dose adjustment for Liver Metabolism
- Metronidazole - Side Effects
Q: What are some side effects of metronidazole?
Nausea, metallic taste, CNS toxicity (rare as Ataxia, Encephalopathy, or seizure)
Rare:
Neutropenia, pancreatitis, peripheral neuropathy, and hepatitis.
- Metronidazole - Contraindications
Q: What should metronidazole not be taken with?
Alcohol (due to Disulfiram reaction)
Can lead to severe nausea and vomiting
Contraindicated in pregnancy (causes tumor growth and crosses readily to placenta)
