Cell Wall Antibiotics Flashcards
Environment for metronidazole
Use
Anaerobic
Good for brain or abdomen
Environment for Aminoglycosides
Aerobic
“The Usual” AB treatment
Combo of extended spectrum penicillin, beta lactamase inhibitor, and vancomycin
General mechanisms of resistance
Enzyme inactivation, alteration of target site, altered bacterial membrane, efflux pumps, and environmental
What type of bacteria is resistant to almost all AB’s?
Carbapenem resistant enterobacteriacae
Most common in Klebsiella
Klebsiella producing carbapenemase (KPC)
New Delhi Metallo-beta-lactamase 1 (NDM)
What is mechanism of methicillin resistance?
Altered PBPs
Which bugs use efflux pumps?
Against which drugs?
Gram Neg and S pneumoniae
Tetracyclin, quinolones, and macrolides
4 families of beta lactams
penicillins, cephalosporins, carbapenems, and monobactams
Penicillins Type of killing Subtypes Resistance due to? Adverse rxns
Time-dependent killing (short half life)
Natural penicillins, aminopenicillins, Semi-synthetic penicillins, extended spectrum penicillins, penicillin / beta lactamase inhibitor combinations
Resistance caused by beta lactamase, changes in outer membrane porins, or altered PBPs
Advers rxns: rash, hypersensitivity, diarrhea, cytopenia, renal impairment.
Natural penicillins
Drugs
Spectrum
DOC for which conditions?
- Penicillin G Benzathine (IM) – Low concentrations over many weeks. Tx syphilis.
- Penicillin G (IV) – High serum concentrations. Tx endocarditis or brain abscess.
SPECTRUM
•Gram-positives: streptococci (DOC), most enterococci, most pneumococci, Peptostreptococcus, Listeria, Clostridia (gas gangrene, add clindamycin)
•Gram-negatives: Pasturella (caused by animal bites), Neisseria meningitidis
•Spirochetes: Treponema pallidum (syphilis), Borrelia species (Lyme disease)
•Periodontal infections
DOC for Streptococci and Syphillis
Aminopenicillins Comparison to natural penicillins Drugs Spectrum Resistance Use
Better Gram (-) coverage than natural penicillins.
•Amoxicillin (oral)
•Ampicillin (IV) – not on list
•Spectrum same as natural penicillins + some Gram Neg (E coli, Proteus mirablis, Haemophilus).
Does not work for bugs w/ beta-lactamase.
•Use – Upper and lower respiratory infections (pharyngitis, otitis, sinusitis, pneumonia), UTI, enterococcus, listeria, endocarditis prophylaxis for dental work
Semi-synthetic penicillins
Drugs
Use
Spectrum
Dicloxacillin (oral) – tx mild infections such as cellulitis
Oxacillin (IV) – tx more severe Staph infections such as endocarditis or osteomyelitis. Good CNS penetration
DOC for Staph (non-MRSA or MRSE). Treat bacteria w/ beta-lactamase properties, such as Staph aureus, which are resistant to natural penicillins.
•Spectrum – Narrow. Only used for Staph.
Penicillin / Beta-Lactamase Inhibitors Drugs Spectrum What if H influenzae does not make beta lactamase? Use
- Amoxicillin-clavulanic acid (oral) – Tx outpatient infections. Bites.
- Piperacillin-tazobactam (IV) – Tx nosocomial infections. Pseudomonas.
- Spectrum – Same as penicillin + beta-lactamase organisms: S aureus, E coli, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella, Bacteriodes, anaerobes
- 70% of H influenzae does NOT make beta-lactamase. Use amoxicillin.
- Use – Upper and lower respiratory tract infections, head / neck infections, SSTI’s (cellulitis), animal / human bites, intraabdominal infections, pseudomonas
Cephalosporins Type of killing Mechanism Resistance Adverse effects Which bugs do cephalosporins NOT work for? Which drugs do / do not enter CSF?
Time-dependent killing
Beta lactam inhibits cell wall synthesis
Resistance due to beta lactamase, changes in outer membrane porins, or altered PBP
Adverse Rxns - Few. Rash, cross-rxn w/ penicillin, diarrhea
Do NOT work for enterococci, Listeria, Chlamydia, or Mycoplasma
3rd gen (Ceftriaxone and Ceftazadime) and 4th ten (Cefepime) enter CSF. 1st and 2nd generation do not.
1st Generation Cephalosporins
Drugs
Spectrum
Use
- Cephalexin (oral)
- Cefazolin (IV) – perioperative AB prophylaxis
- Spectrum – Gram Pos cocci including Strep and MSSA
- Use – SSTI from Strep and Staph. Perioperative AB prophylaxis
2nd Generation Cephalosporins
Unique feature
Drugs, spectrum, and uses
Only cephalosporin w/ anaerobic activity
•Cefuroxime group – Used for upper / lower respiratory infections
•Cefoxitin – same as 1st gen + anaerobes and some Gram Neg. Used for intra-abdominal / pelvic infections
3rd Generation Cephalosporins
Drugs w /uses and side effects
Spectrum
DOC for what?
•Ceftriaxone (IV) – long half life allows for once daily dosing. Good for gonorrhea. May cause biliary sludging w/ long term use. Used for seriuous infections such as meningitis, CAP, viridans strep endocarditis, intra-abdominal (need to add drug for anaerobes, such as metronidazole), UTIs.
•Ceftazadime (IV) – works against Pseudomonas
•Spectrum – Gram negative, Strep, N gonorrhoeae
DOC for gonorrhea
4th Generation Cephalosporins
Drugs w/ uses and side effects
Spectrum
- Cefepime – very broad spectrum. Tx serious nosocomial infections caused by Pseudomonas as well as febrile neutropenia. May cause mental status changes (be careful w/ elderly)
- Spectrum – Gram Pos and Neg including S aureus, Strep, GNR aerobes, Pseudomonas and ESBL (extended spectrum beta lactamase). Not MRSA or anaerobes.
5th Generation Cephalosporins
Drugs
Spectrum
Use
- Ceftaroline (IV) – only cephalosporin that treats MRSA (except CAP)
- Spectrum – Mainly Gram Pos. Some Gram Neg and anaerobes. MRSA, MRSE (coag-neg), strep.
- Use – SSTI’s, CAP (not MRSA for this)
Which class has broadest spectrum of all AB’s?
Carbapenems
Carbapenems Drugs Mechanism Reason they're so good Spectrum Resistance Adverse rxns
Meropenem
•Mechanism – inhibits cell wall synthesis (beta lactam). Time dependent killing.
•Reason they’re so good: molecules are small so can get through porins of Gram Neg, resistant to most beta-lactamases, and have high affinity for PBPs
•Spectrum – Most Gram Pos, Gram Neg (including ESBL), Pseudomonas, and anaerobes. Not MRSA, MRSE, Enterococcus faecium, C diff, Stenostrophomas, or Burkholderia
•Resistance – beta-lactamases, alterations in porins, changes in PBPs.
•Adverse effects – rash, hypersensitivity, cross-rxn w/ penicillins, seizures
Monobactam Drugs Mechanism Spectrum Resistance Adverse Rxns
Aztreonam
•Mechanism – inhibits cell wall synthesis (beta lactam). Time dependent killing.
•Spectrum – Aerobic Gram Neg Rods, such as Pseudomonas aeruginosa. Can be used in pxs allergic to penicillin or other beta-lactams.
•Resistance – beta-lactamases
•Adverse rxns – rash and hypersensitivity
Vancomycin Type of AB Mechanism Spectrum Resistance Uses Adverse Rxns
Glycopeptide
•Mechanism – Binds d-alanyl-D-alanine peptide precursor to prevent peptidoglycan polymerase / transpeptidation → autolysis. Slowly cidal (slower than beta-lactams). Time-dependent killing.
•Spectrum – Aerobic and anaerobic Gram Pos including MRSA, MRSE (Coag-Neg Staph), enterococci (not VRE), Strep, and corynebacteria.
•Resistance – Enterococcal resistance (VRE) due to peptidoglycan precursor w/ lower affinity for vancomycin. Some Staph aureus resistance as well (VRSA)
•Uses – IV form used for systemic infections. Oral form is not absorbed well in gut, which is good for C diff. MRSA, Coag-Neg Staph, Enterococcal infections that are resistant to ampicillin, P pneumoniae meningitis, penicillin allergy.
•Adverse rxns – neutropenia, renal impairment (monitor trough levels), ototoxicity, Red Man Syndrome
Daptomycin Type of AB Mechanism Dosing Spectrum Resistance Uses Adverse Rxns
Cyclic lipopeptide
•Mechanism – lipid portion inserts into cell membrane and causes rapid depolarization → protein inhibition and DNA synthesis inhibition → cell death (“blows up” cells). Concentration-dependent killing.
•Llong half life allows for once daily dosing (IV only).
•Spectrum – Gram (+). Does NOT work for CAP due to inactivation by pulmonary surfactant
•Resistance – some Staph aureus and E faecium. Does not work for CAP.
•Uses – Serious MRSA, VRE, Coag-Neg Staph, including bacteremia and endocarditis
•Adverse Rxns – Myopathy. Elevated CK.
