Cell Wall Inhibitors (Antibiotic I) Flashcards
What are the major ABX that function via inhibition of cell wall synthesis?
- Beta-lactams (Penicillins and Cephalosporins)
- Vancomycin
- Daptomycin
- Bacitracin
How do Penicillins function with respect to bacteria?
Bactericidal (Works best in rapidly proliferating organisms WITH cell wall)
Bind to Penicillin-Binding Proteins (PBPs) and inhibit transpeptidase (cross-linking of peptidoglycans → osmotically unstable membrane will rupture)
What are the three mechanisms of resistance in Penicillins?
- Inactivation by beta-lactamases (most common)
- Modification of PBP target
- Impaired penetration of drug to target PBP
What are the different sub-classifications of Penicillins?
- Natural Penicillins
- Aminopenicillins
- Penicillinase-Resistant Penicillins
- Antipseudonomal Penicillins
What are beta-lactamase inhibitors?
Considered “suicide inhibitors” → potent, irreversible inhibitors of most lactamase (extends the spectrum of ABX)
What ABX are considered Natural Penicillins? How is each PCN administered (if applicable)? [2]
- Penicillin V (PO)
- Penicillin G (IV, IM, Depot)
What ABX are considered Aminopenicillins? How is each PCN administered (if applicable)? [2]
- Amoxicillin (PO)
- Ampicillin (PO, IV)
What ABX are considered Penicillinase-Resistant Penicillins? How is each PCN administered (if applicable)? [5]
- Nafcillin (PO, IV)
- Oxacillin
- Dicloxacillin
- Methicillin (No longer available in the US)
- Cloxacillin (No longer available in the US)
What ABX are considered Antipseudomonal Penicillins?How is each PCN administered (if applicable)? [3]
- Piperacillin (IV)
- Ticarcillin (IV)
- Carbenicillin (IV)
What ABX are considered Beta-lactamase inhibitors? What PCN are each inhibitor used with (if applicable)? [3]
- Clavulanic acid (Adjunct TX: Amoxicillin, Ticarcillin)
- Sulbactam (Adjunct TX: Ampicillin)
- Tazobactam (Adjunct TX: Piperacillin)
What are MOAs and General Target of Natural Penicillins?
- Narrow spectrum
- Acid labile (PCN-G)
- Penicillinase sensitive
- Gram-positive cocci (Does not include Staphylococcus)
- Obligate anaerobes
- Some gram-negative (E. coli, H. influenzae, N. gonorrhoeae, Trepnema pallidium and suseptible Pseudomona spp.)
What are Natural Penicillins used to TX/Prophylaxis?
- Upper/Lower Respiratory Tract Infections
- Throat infection
- Skin infection
- GU tract infection
- PROPHYLAXIS Rheumatic fever, dental procedure (for those at risk of endocarditis, gonorrhoeae, syphilis exposure)
What are MOAs and Specific Target/Bacteria of Aminopenicillins?
PCN-G MOA + improved coverage of gram-negative cocci and Enterobacteriaceae
What are Aminopenicillins used to TX/Prophylaxis?
- URI (sinusitis, otitis)
- UTI (uncomplicated)
- Meningitis
- Salmonella infections (Not 1ST LINE)
No mentioned prophylactic measures
What are the MOAs and General Targets of Penicillinase-Resistant Penicillins?
- Also called “Antistaphylococcal Penicillins”
- Penicillinase resistant, narrow spectrum
- General Target: staphylococcal infections with high beta-lactamase production
- Not active against gram-negative or anaerobes
What is the name for Staphylococci spp. that are resistant to penicillinase-resistant penicillins?
MRSA (Methicillin Resistant Staphylococcus aureus)
What are Penicillinase-resistant penicillins used to TX/prophylaxis?
- Cellulitis
- Endocarditis
What are MOAs and Specific Target/Bacteria of Antipseudomonal penicillins?
- PCN-G MOA + greater gram negative coverage (including Pseudomonas spp.)
- Coverage: H. influenzae, Klebsiella sp.
- No coverage: Treponema palladium, Actinomyces spp.
What are the PK characteristics (Absorption, Distribution, Elimination) of Penicillins?
Absorption: Poor oral administration (food DEC absorption), IV preferred
Distribution: Widely distributed, poorly penetrate the eye, CNS (only when meninges are inflamed) and prostate
Elimination: Kidney unchanged (Antipseudomonal and naficillin→billary excretion)
How does Probenecid interact with penicillins?
Prevents active secretion of Penicillin into urine
What are important ADRs of Penicillins?
- Hypersensitivity reaction (could lead to analphylasis, Serum sickness interstitual nephritis, hemolytic anemia)
- GI effects (related to oral agents)
- Diarrhea
- Vaginal candidiasis (2ndary)
What are some important Drug interactions of Penicillins?
Bacteriostatic agents (i.e. tetracycline, aminoglycosides): DO NOT give concurrently
Warfarin: metabolism affected by anti-pseudomonal PCN
What are Cephalosporins?
- Class of Beta-lactam drugs, chemically similar to PCN with respect to MOA and toxicity
- possess dihydrothiazine ring → INC resistant to beta lactamases
- Bactericidal
- Classified in 5 generations
What ABX are considered 1st Generation Cephalosporins? How are the ABX administered (if applicable)? [3]
- Cefazolin (IV)
- Cephalexin (PO)
- Cefadroxil (PO)
Only class that has “ph” instead of “f” in name
What ABX are considered 2nd Generation Cephalosporins? What added coverages does each ABX have (Gram-negative vs. Anaerobic)? How are the ABX administered (if applicable)?
- Added Gram-negative coverage
- Cefuroxime (IV, PO)
- Cefaclor (IV, PO)
- Cefporzil (IV, PO)
- Added anaerobic coverage
- Cefotetan (IV)
- Cefoxitin (IV)
What are ABX are considered 3rd Generation Cephalosporins? How are ABX administered (if applicable)? [8]
- Cefpodoxime (PO)
- Cefdinir (PO)
- Cefixime (PO)
- Cefditoren (PO)
- Cefibuten (PO)
- Cefotaxime (IV, IM)
- Ceftriaxone (IV, IM)
- Ceftazidime (IV)
What are ABX are considered 4th Generation Cephalosporin? How are the ABX administered (if applicable)? [1]
- Cefepime (IV, IM)
What are ABX are considered 5th Generation Cephalosporins? How are ABX administered (if applicable)? [2]
- Ceftaroline fosamil (IV)
- Ceftolozane (IV)
What are the three mechanisms of resistance with Cephalosporins?
- Mutation in PBP
- Production of Beta-lactamases
- Alteration in cell-membrane porins in gram-negative organ
What are the MOAs and General Target/Bacterias of 1st Generation Cephalosporins?
Similiar MOA to Penicillinase-Resistant (Anti-staph) PCN and Aminopenicillins
General Target:
- Aerobic Gram-positive
- Above diaphragm anaerobes
- Community acquired Gram-negative
What are 1st Generation Cephalosporins used to TX/Prophylaxis?
GRAM-POSITIVE (patients who can’t take PCN)
- Septic arthritis (adults)
- Skin infections
- Acute otitis media
- Pharyngitis
- PROPHYLAXIS: Clean surgeries, UTI
How does 2nd Generation Cephalosporin compare to 1st Generation coverage?
Somewhat less Gram-positive coverage than 1st Gen, but significantly greater Gram-negative coverage
What is significant about the spectrum of 3rd Generation Cephalosporins?
- Expanded Gram-negative coverage
- Penetration of BBB
What are extra-defining features Ceftriaxone, Cefotaxime, Ceftazidime? (3rd generation Cephalosporins)
Long Half-Life
- Ceftriaxone (IV, IM)
- Cefotaxime (IV, IM)
INC Anti-pseudomonal coverage
- Ceftazidime (IV)
What are 3rd Generation Cephalosporins used to TX/Prophylaxis?
1st LINE TX:
- Meningitis
- Pneumonia (Children and Adults)
- Sepsis
- Peritonitis
Additional TX:
- UTI
- Skin infections
- Osteomyelitis
- Neisseria gonorrheae
What are MOAs and General Target/Bacterias of 4th Generation Cephalosporins?
Good activity against all gram bacteria including anaerobic coverage (P. aerugnosa, H. influenzae**, N. Meningitidis, N. gonorrheae; Enterobacteriaceae resistant to other Cephalosporins)
What are 4th Generation Cephalosporins used to TX/Prophylaxis?
- Intra-abdominal infections
- Respiratory tract infections
- Skin infections
What is important to know pertaining to 5th generation cephalosporins?
- Activity against MRSA
- TX complicated skin and intra-abdominal infections including CAP
- Expensive (rarely used)
What are the PK characteristics (Absorption, Distribution, Elimination) of Cephalosporins?
Absorption: PO rapidly absorbed, variable effects with food
Distribution: Extensive (2nd, 3rd, 4th Gen can cross BBB; think long half-life for 3rd Gen)
Elimination: Kidneys (most)
What are General ADRs/Drug interactions associated with Cephalosporins?
Hypersensitivity: Similar to PCN, allergic reaction (rare; S/Sx rash, fever, eosinophilia, hives)
Superinfection: Resistant organisms/fungi may proliferate
GI effects: N/V/D (well tolerated)
Blood Dyscrasias (will resolve w/ DC drug): Eosinophilia, Thrombocytopenia, Leukopenia
DRUG INTERACTION:
- Probenecid (INC serum levels of co-administered Cephalosporin)
- Warfarin (INC effects; Cefotetan, Cefazolin, Cefoxitin, Ceftriaxone)
What specific ADRs are associated with Ceftriaxone? (3rd Generation Cephalosporin)
- Cholestasis
- DRUG INTERACTION: INC effects of Warfarin
What specific ADRs are associated with Cefotetan? (2nd Generation Cephalosporin, added anaerobic coverage)
Methylthiotetrazole side chains induce disulfiram-like reaction with EtOH ingestion
What are Monobactams?
