2-Overview of Antibacterial Agents Flashcards
Name the four classes of beta-lactam antibiotics
Penicillins, cephalosporins, monobactams, carbapenems
How do beta-lactam antibiotics work?
Bind crosslinking (DAP) and transpeptidation enzymes to inhibit cell wall synthesis.
How do penicillins work?
beta-lactam activity inhibits cell wall synthesis Bind penicillin-binding proteins on cell wall = lysing enzymes
Name two ways bacteria have acquired resistance to penicillins
- production of beta-lactamase enzymes to destroy beta-lactam ring 2. Mutate PBPs to prevent binding
How are penicillins excreted?
Renally - remember they used to have soldiers drink urine of other soldiers on penicillins during shortage
What are the important adverse reactions to penicillins?
Hypersensitivity reactions with cross sensitivity between all penicillins
What is the treatment for syphilis?
Natural penicillins (G and V)
Name the four organisms that still respond to natural penicillin treatment
- streptococci (pyogenes and pneumoniae) 2. Nisseria meningitidis 3. Clostridium sp 4. Treponema pallidum (syphilis!!***)
Do aminopenicillins work via a time-dependent or concentration-dependent manner?
Time dependent- requires repeated administration
Name two examples of aminopenicillins
Ampicillin and amoxicillin
What organisms are aminopenicillins used for?
Upper respiratory tract pathogens:
- S. pyogenes
- S. pneumoniae
- Hemophilus influenza
- Enterococcus
community gram negative bacteria (E. Coli; proteus sp)
Do aminopenicillins have activity against Staphylococcus?
NO
Piperacillin (Class, Excretion, Uses, adverse effects)
Class: extended spectrum penicillin
Excretion: biliary tract
Uses: usu in combination with tazobactam (zosyn) **anti-pseudomonal
Adverse effects: Sodium overload Thrombocytopenia
Name anti-pseudomonal antibiotics
- Piperacillin (extended spectrum penicillin)
- Cetazimide (3rd generation cephalosporin)
- Cefepime (4th generation cephalosporin)
- Azetronam (monobactram)
- Doripenem, imipenem, meropenem (Carbapenems)
- Aminoglycosides (GNATS)
What organisms are treated with extended-spectrum penicillins?
NOT Staphylococcus
- Gram-negative bacteria
- Psudomonas aeruginosa
- Enterococcus
Name three Beta-lactamase inhibitors and their penicillin combination
- Cavulanic acid + amoxicillin = augmentin
- Sulbactam + ampicillin = Unasyn
- Tazobactam + piperacillin = Zosyn***
most widely used IV antibiotic in hospitals & gram +, gram -, & anaerobic activity
What is the method of action of beta-lactamase inhibitors? Do they have bactericidal effects?
Inhibit Beta-lactamase enzymes
NO bactericidal effect
Widen spectrum of penicillins to increase activity against Staphylococcus, gram -, and anaerobic bacteria
Name 2 penicilinase-resistant penicillins
- Nafcillin (can cause serum sickness rxn)
- Dicloxacillin
How does the spectrum of activity change for cephalosprin generations?
Start gram + then become more gram -
Which category of antibiotics do Cephalexin, Cephradine, and Cefadroxil belong to?
First generation cephalosporins (oral)
Cephalexin= used for community Staphyloccal and stretococcal infections
Cefazolin (Class, Administration, Uses)
- Class: 1st generation cephalosporin
- Administration: IV
-
Uses: gram positive
- Streptococcus sp & methicillin-sensitive Staphylococcus
- Used in hospitals for wound infections & surgical prophylaxis
- E. coli and Klebsiella sp
Cefuroxime and Cefoxitin belong to what category of antibiotics?
(Class and administration)
2nd generation Cephalosporins (Beta-lactam Abx)
Administration: IV
Cefoxitin (Class, Administration, Microbe)
- Class: 2nd generation Cephalosporin
- Administration: IV
- *Microbe**: anaerobic activity- abdominal and gynecologic infx
Cefuroxime, Cefaclor, and Cefprozil
(Class, administration, microbe)
- Class: 2nd generation Cephalosporins
- Administration: Oral
-
Microbes:
- gram negative bacteria: Klebsiella pneumoniae, Hemophilus influenzae, Moraxella catarrhalis
- Community acquired pnemonia, URI, otitis media
Cefotaxime and Ceftriaxone (Rocephin)
(Class, Administration, Microbe, Adverse rxn)
- Class: 3rd generation Cephalosporin
- Administration: IV
- Uses: cross BBB = useful for meningitis (“Ax to the head”)
- Adverse rxn: Disulfram-like reaction
Ceftazidime (Fortaz)
(Class, Administration, Use, Adverse reaction)
- Class: 3rd generation Cephalosporin
- Administration: IV
-
Microbe: only 3rd generation with anti-pseudomonas
- alternative to piperacillin
- Adverse rxn: Disulfram-like reaction
What are the general uses for 3rd generation Cephalosporins?
- gram (-) and gram (+) bacteria
- nosocomial infx, pneumonia, meningitis, advanced Lymes disease
- Ceftazidime = anti-pseudomonal
What is a common adverse rxn to 3rd generation Cephalosporins (Cefotaxime, Ceftriaxone, Ceftazidime, Cefixime, Cefpodoxime)?
Disulfram-like rxn: nausea, vomiting, palpitations if abx consumed with alcohol
Cefixime and Cefpodoxime (Class, Administration, Uses, Adverse rxn)
- Class: 3rd generation Cephalosporins
- Administration: Oral
-
Uses: gram (+) and gram (-) bacteria
- nosocomial infx, pneumonia, meningitis, advanced Lymes
- Adverse rxn: disulfram-like reaction
Cefepime (Class, Admin, Microbe)
- Class: 4th generation Cephalosporin
- Admin: IV
-
Microbes: resistant to chromosomal beta-lactamase enzymes
- Enterobacteriaceae
- Pseudomonas aeruginosa
- Penicillin-resistant Streptococcus pneumoniae
Ceftaroline (Class, Microbe)
- Class: 5th generation Cephalosporin
- Admin: IV
-
Microbe: MRSA infection (high affinit for PBP2a encoded by mecA gene in MRSA)
- similar to 3rd generation (gram+/-)
- NO pseudomonas or enterococcus
Azetronam (Class, Structure, Action, Other)
- Class: Monobactam
- Structure: monocyclic beta-lactam ring
-
Action: anti-psudomonal
- NO gram (+) activity
-
Other: no cross-sensitivity with penicillin or cephalosporin
- =useful for beta-lactam allergies
What is the first line choice for a patient with a gram (-) infection that is allergic to penicillins and cephalosporins?
Azetronam (monobactam with monocyclic beta-lactam ring)
Imipenem-cilistatin, Meropenem, Ertapenem, and Dripenem (class, administration, general uses, adverse effects)
- Class: Carbapenems
- Admin: IV
-
Uses: broad spectrum antibiotic for multi-resistant infections
- Polymicrobial and nosocomial infections
- Anti-pseudomonas except for Ertapenem
-
Adverse rxn
- Neurotoxic - seizures
- Superinfections (C. diff)
- High cost
- Cross-sensitivity with pencillin-allergic patiets
Why is cilistatin used with imipenem?
Cilistatin inhibits renal dihydropeptidase enzyme that would normally hydrolyze imipenem in the kidney
Which Carbapenem does NOT have activity against pseudomonas?
Ertapenem
Imipenem-cilistatin, Meropenem, and Doripenem DO
Doripenem has the most activity
Bacitracin (MOA, Microbe, Adverse Rxn)
- MOA: inhibitor of bacteria cell wall synthesis
-
Use: topical preparation for Streptococcus and Staphylococcus
- gram (+) bacteria only
- Adverse rxn: nephrotoxic if given systemically
Fosfomycin (Class, Microbe)
- Class: phosphonic antibiotic inhibiting peptidoglycan synthesis in urine
- Use: gram (-) UTI if resistant to sufla and fluoroquinolone abx
Nitrofurantoin (Use, adverse rxn, contraindications)
-
Uses: lower UTI
- bactericidal against E. coli, Enterococcus
- Adverse rxn: GI irritation, nausea, vomiting
-
Contraindications
- Elderly due to increased risk of pneumonitis and neuropathy
- renal failure
Vancomycin (Class, MOA, Admin, Use, Pharmacokinetics, Adverse Rxn)
- Class: glycopeptide w/ high molecular weight
- MOA: blocks transglycosylation to inhibit peptidoglycan elongation
-
Admin: mostly IV
- Oral for pseudomembranous colitis /C. diff colitis
- Use: MRSA *first line
-
Pharmacokinetics: renal excretion (proportional to creatinine clearance)
- Narrow therapeutic index
-
Adverse Rxn: Red man syndrome- massive histamine release if given too fast
- Ototoxicity
What is the first line choice for MRSA infection and how does that drug work?
Vancomycin - blocks elongation of peptidoglycan (transglycosylation)
What is Red Man Syndrome and what antibiotic is it associated with?
Massive histamine release caused by infusion of vacomycin that is too fast or too high of a dose
Daptomycin (Class, Admin, MOA, Microbe, Other)
- Class: cyclic lipopeptide
- Admin: IV
- MOA: inhibits cell membrane synthesis
- Microbe: gram (+) and vancomycin-resistant bacteria
- Other: Concentration-dependent activity
Colistin (Admin, Microbe, Adverse Rxn)
- Admin: IV
- Microbe: MDR resistant bacteria- CRE
- Adverse Rxn: Nephrotoxic
What are the 3 categories of bacterial protein synthesis inhibitors?
- Macrolides
- Tetracyclines
- Aminoglycosides
(4. Miscellaneous: Clindamycin, Linezolid & Mupirocin)
Macrolide antibiotics MOA
Reversibly bind to 50S ribosomal subunit
Macrolide antibiotics:
Uses & Bacterial susceptibility
- Bacteriostatic effect
- Upper & lower respiratory infections: activity against atypical bacteria causing pneumonia (Mycoplasma, Legionella & Chlamydophyla)
3. Chlamydia trachomatis STD infections
- Streptococcus & Staphylococcus
- Hemophilus Influenzae & Bordetella
- Penicillin-allergic patients
Name 3 Macrolide antibiotics.
mACErolides
- Azithromycin (Zithromax)
- Clarithromycin
- Erythromycin
Erythromycin
(class, MOA, adverse rxns, drug interactions)
- Class: Macrolide
- MOA: 50S ribosome inhibitor
- Adverse:
- Oral: abdominal pain & diarrhea (macrolides = motillin receptor agonists)
- IV: High doses can cause ototoxicity (Vancomycin also ototoxic) - Drug interactions: inhibits CYP450-3A4 (which metabolizes 50% of drugs), thus increases serum levels of statins, benzos, ca ch blockers, cyclosporines, etc.
Which antibacterial drug class acts as Motillin receptor agonists, thus causes diarrhea as an adverse effect?
Macrolides (Azitromycin, Clarithromycin & Erythromycin)
mACErolides
Clarithromycin (class, MOA, adverse, drug interactions)
Very similar to Erythromycin
- Class: Macrolides
- 50S ribosome inhibitor
- Adverse: Less GI effects than Erythro
- Drug interactions: stronger CYP450-3A4 inhibition than Erythro
Azithromycin
(class, MOA, adverse, drug interactions, benefits)
- Class: Macrolides
- MOA: 50S ribosome inhibitor
- Minimal adverse effects
- No drug interactions
- Other:
- Post-antibiotic effect (thus given 1/day for 3-5 days)
- Most popular, safest macrolide antibiotic
Tetracyclines
(MOA, bacterial susceptibility/uses, adverse & drug interactions)
- MOA: Reversibly bind 30S ribosomal subunit
- Bacterial susceptibility/Uses:
- Bacteriostatic
- Gram +/- bacteria,
- Lyme disease, Erlichiosis, Rocky Mountain Spotted Fever, Atypical pneumonia, Acne (w/ Minocycline) - Adverse:
- Discoloration of tooth enamel (children/fetus)
- Super infection: C. difficle = antibiotic-associated pseudomembranous collitis (also caused by Clindamycin)
- GI irritation, photosensitivity, hepatotoxicity w/ extended use - Drug interactions: Cheleating agent = binds cations (calcium) and prevents absorption (avoid w/ dairy/antacids)
Name 4 Tetracyclines
(& a fun fact about each!)
Tetra = 4; DMT (psychedelic) is fun!
- Doxycycline: Most popular tetracycline
- Fecal elimination = can use w/ renally impaired pts - Minocycline: Acne
- Tetracycline: Rarely used b/c low bioavailability/short half life
- Tigecycline: active against gram +/- & anaerobic bacteria
- Reserve for antibiotic-resistant infections (like MRSA)
Aminoglycosides
(MOA, bacterial susceptibility/uses, pharmacokinetics & adverse)
- MOA: irreversibly binds 30S ribosomal subunit
- Bacterial Susceptibility/Uses:
- Bactericidal
- Gram - (including Pseudomonas) - PK:
- Give high dose once b/c conc-dep effect
- Eliminated renally; accumulate in renal failure
- Narrow therapeutic index - Adverse:
- Nephrotoxic
- Ototoxic
- NMJ blocking
Name 5 Aminoglycosides
G-ANTS (gangsta ants, bruh)
- Gentamicin
- Amikacin
- Neomycin
- Tobramycin
- Streptomycin
Tobramycin (class, MOA, uses)
- Class: Aminoglycoside
- MOA: irreversibly bind 30S ribosomal subunit
- Uses: Inhaled form for Cystic Fibrosis Patients w/ Pseudomonas pneumoniae
Neomycin (class, MOA, uses & adverse)
- Class: Aminoglycoside
- MOA: irreversibly bind 30S ribosomal subunit
- Adverse: most toxic/never used as IV
- Uses:
- Topical formulas
- Oral form for prophylaxis before elective bowel surgery
- Recurrent GI infections
- Hepatic encephalopathy management (kills NH3 producing bacteria that worsen encephalopathy)
Streptomycin
(class, MOA, uses)
- Class: aminoglycoside
- MOA: irreversibly bind 30S subunit
- Uses: second line therapy for active tuberculosis
Clindamycin
(Class, MOA, Bacterial susceptibility/Uses, Adverse)
- Class: class of its own, baby
- MOA: binds 50S ribosomal subunit (like macrolides)
- Bacterial susceptibility/Uses:
- Bacteriostatic
- Anaerobic infections (Bacteroides fragilis & Clostridium perfringies)
- Streptococci, Staphylococci & Pneumocci
- Gram + infections in penicillin-alergic patients
- Newly discovered CA-MRSA
4. Adverse: - Primary cause of antibiotic-associated Pseudomembranous colitis (other is Tetracycline)
- Treatment: Vancomycin & Metrometazole
Linezolid
(Class, MOA, Bacterial susceptibility/Uses, Adverse)
- Class: class of its own
- MOA: unique activity against 50S ribosomal subunit
- Bacterial susceptibility/Uses:
- Bacteriostatic
- Reserved for multi-drug resistant bacteria (VRE/MRSA) - Adverse: Hematologic toxicity (thrombocytopenia/neutropenia)
Mupirocin
(class, MOA, uses)
- Class: of its own
- MOA: unrelated to other antibiotics (?)
- Uses:
- Topical preparations for Staphylococcal infections
- Nasal formulation reserved for MRSA
- Impetigo (streptococci/staphylococci)
Fluoroquinolones
(MOA, Bacterial susceptibility/Uses, Adverse, Drug interactions)
- MOA: DNA gyrase/topoisomerase inhibitors
- Bacterial susceptibility/Uses:
- Bactericidal against
- Most gram (-), gram (+) (3rd gen) & Atypical bacteria
- Complicated UTI & prostatitis
- Adverse:
- Arthropathy (avoid in children/pregnancy) = Achilles tendon rupture
- Neurotoxic @ high doses - Drug interactions:
- Oral dose inhibited by cations (Ca2+, Mg2+, Fe, Zn)
- Inhibits caffeine/theophylline metabolism
Name two 2nd generation Fluoroquinolones
(& their uses)
- Ciprofloxacin: only quinolone w/ anti-Pseudomonas aeruginosa
- Norfloxacin: UTI infections
Name three 3rd generation Fluoroquinolones
(Bacterial susceptibility/use, metabolization)
“Respiratory fluoroquinolones” + (LGM)
Bacterial Susceptibility/Uses:
- Gram (-)
- Atypical bacteria (respiratory infections)
- Multidrug-resistant Streptococci pneumoniae
1. Levofloxacin (renal elimination)
2. Gemifloxacin (hepatic metabolism: don’t use for UTI)
2. Moxifloxacin (hepatic metabolism: don’t use for UTI) - Better anaerobic activity than Levofloxacin
Trimethoprim-Sulfamethoxazole
(MOA, Bacterial susceptibility/Uses)
aka Bactrim, TMP-SMX or Cotrimoxazol
- MOA: “Sequential inhibition”
- Sulfonamides: inhibit DHF synthesis (via substituting as PABA)
- Trimethoprim: inhibit Folate reductase (DHF -> THF rxn) - Bacterial Susceptibility/Uses:
- Most gram (+)/(-) including CA-MRSA
- Nocardia, Pneumocytis jiroveci = AIDS pts
- Primary drug for UTI
- Secondary drug for upper/lower respiratory tract infections, sepsis, meningitis, travelers diarrhea, typhoid, cholera
Trimethoprim-Sulfamethoxazole (Bactrium)
(Adverse, Drug interactions)
- Adverse:
- Hypersensitivity rxn to SMX (Stevens-Johnson syndrome & Exfoliative dermatitis)
- High doses (P. jiroveci in AIDS) = thrombocytopenia, neutropenia, allergic rxns & hyperkalemia - Drug interactions:
- Sulfa drugs = CYP inhibitors: increase serum levels/toxicity of warfarin, phenytoin & oral sulfonylureas (for DM)
Metronidazole (Flagyl)
(MOA, uses, adverse)
- MOA: Disrupts DNA helical structure
- Uses:
- Antibacterial + Antiprotozoal
- THE best drug for anaerobic bacteria (including C. difficile colitis) - Adverse:
- Disulfiram-like effect (avoid alcohol)
FDA Categories for Drug Use in Prenancy
A, B, C, D, X
A = research shows no risk to human fetus
B = animal studies no risk; animals studies show risk, but preg women no risk
C = no available studies; animal studies show risk, but no women trials (most common category)
D = fetal risk, but benefits outweigh risks
X = definite fetal risk; outweighs benefits
