Bactericidal Cell Wall Inhibitors Flashcards
Chemistry of bactericidal cell wall inhibitors?
Penicillins, cephalosporins, monolactams, and carbapenems all have b-lactam ring in the center. Some of these are inactivated if the ring is cleaved by B-lactamases.
monolactams and carbapenems are are reisistant to B-lactamases
What is used with penicillins and cephalosporins to inhibit b-lactamases?
Clavulanic acid binds and inhibits B-lactamase.
- augmentin is trade name for amoxicillin and clavulanic acid.
- Timentin is trade name for ticarcillin and clavulanic acid.
What results in higher serum levels of penicillin?
probenicid, it acts by competing with penicillin for the organic anion transport system which is primary route of penicillin excretion –> results in higher levels of penicillin in the serum.
Mechanism of Penicillin G?
B-lactam binds PBPs and inhibits cross linking of bacterial cell wall components
Spectrum of Penicillin G?
Gram postive cocci -> strep and staph
gram positive rods –> listeria and actinomyces
gram neg cocci -> Neisseria
most mouth anaerobes (clostridium)
***Not effective against gm - aerobes or B lactase producing organisms w/o conjugative therapy
- penicillinase sensitive
dosage forms:
IM, IV, PCN VK: oral (poor bioavailability)
DOC for which pathogens?
nonresistant staph and strep, N. meningitidis, B. anthracis, C. tetani, C, perfingens, Listeria, syphillis
Pharmokinetics of Penicillin G?
IV/IM for Penicillin G
PO for Pen V
Eliminated by kidneys
Side Effects of Pen G and V?
Hypersensitivity reactions, rare neurologic toxicity (seizures), Neutropenia, nephrotoxicity
MOA of B-lactams?
bactericidal –> bind to PBPs and inhibit transpeptidation which stops cross linking of polysaccharides and cell wall is destroyed and bacterial cell dies.
Classes of B-lactam compounds?
Penicillins, Cephalosporins, and B-lactamase inhibitors combined with PCN’s
Penicillin classifcation
Penicillin G
Antistaphlococcal PCNs: nafcillin, dicloxacillin, oxacillin, cloxacillin
Broad spectrum PCNs:
2nd generation: ampicillin, amoxicillin
3rd generation: carbenicillin, ticarcillin
4th generation: piperacillin
Combos with b-lactamase inhibitors
amoxacillin/potassium clavulanate= augmentin (PO)
ampicillin/sublactam=unasyn (IV)
Ticarcillin/potassium clavulanate= timentin
Piperacillin/tazobactam sodium= zosyn (sepsis)
General points of PCNs
All PCN’s should be given on an empty stomach except oral amoxicillin
Allergic rxns to one PCN are cross reactive to others, reactions can be urticarial to anaphylaxis to serum sickness
All abs can cause C. diff colitis
PCN G benzathine and PCN G procraine
IM forms: 1 injection lasts 10-12 days
used for strep and sometimes syphillis, gonorrhea now is resistant
IV form: meningitis and endocarditis
Usual dosage of PCN G
1-24 million units/day every 4-6 hours
erysipelas: IV 1-2 million units q 4-6 hours x 7-10 days
neurosyphilis: IV 18-24 million units q 4-6 hours x 10-14 days
Penicillin G safety
Preg Cat: B -> presumed safe
lactation: safe
Renal dosing: adj for creatine clearance adjust`
Adverse Reactions of PCN G
local: site reaction
significant reactions:
CNS -> coma, seizure
hematologic and oncologic: neutropenia, positive direct coombs test
Hypersensitivity: anaphylaxis, reaction, serum sickness
Renal: acute interstitial nephritis, renal tubular disease
Drug interactions of Penicillin G
BCG: used for TB - abx may diminish therapeutic effect of vaccine
methotrexate: PCNs may increase serum conc of metho
Probenecid: may increase serum conc of PCN
Tetracycline derivatives: may diminish effect of PCNs
Vit K antagonists (warfarin) - PCNs may enhance effect of Vit K antagonists -> monitor INR
OBCPs: pen may decrease OBCP efficacy
Penicillin VK
oral form -> 250-500 mg TID-QID
DOC for strep pharyngitis
AE’s: GI -> N/V/D
acute nephritis, convulsions, hemolytic anemia, positive coombs reaction
Antistaphyloccocal PCNs activity
activity: semisynth PCNs used for infection with B-lactamase producing staph, also used against PCN susceptible strep and pneumococci
**inactive against enterococci and methicillin resistant strains
Antistaphylococcal PCNs - drugs
Dicloxacillin, oxacillin and nafcillin (not affected by beta-lactamase enzyme)
Dosage forms of Antistaph PCNs
dicloxacillin: PO
Oxacillin: IM, IV
Nafcillin: IV
Antistaph PCNs safety
Preg Cat: B
lactation: unknown
No dosage adj needed for renal or hepatic disease
Adverse effects of Antistaph PCNs
GI (dicloxacillin)-> Nausea, diarrhea, abdominal pain
agranulocytosis, eosinophilia, hemolytic anemia, hepatotoxicity
Antistaph drug interactions
Aripiprazole: PCN may decrease concentration
Ca channel blockers: Nafcillin may increase metabolism
contraceptives: Nafcillin may increase metabolism of estrogens
BCG: may diminish effects of BCG
Methotrexate: may increase serum concentrations
Probenecid: may increase PCN serum concentration
Warfarin: may diminish effect
Broad spectrum PCNS
2nd gen: ampicillin, amoxicillin
3rd gen: carbenicillin, ticarcillin
4th gen: piperacillin
2nd gen PCNs uses
cover same as PCN G also E. coli, proteus marabilis, Salmonella, Shigella and H. influenzae,
Amox is better absorbed
uses: otitis, sinusitis, lower RTI
Amox combined with clay acid will expand coverage to gm +, gm - and anaerobic organisms
Safety of 2nd gen PCNs
Preg Cat: B,
Lacation: safe
Renal dosing: adjust if CrCl
Adverse effects of 2nd gen PCNs
CNS: agitation, anxiety, confusion, seizure
Hematologic: agranulocytosis, anemia, eosinophilia, hemo anemia
Renal: crystalluria
What will occur if 2nd gen PCN taken while infected with mono?
high % of patients have developed rash during therapy, don’t use in these patients
Drug interactions of 2nd gen PCNs
Allopurinol: may enhance risk of hypersensitivity rxn of PCN
BCG: diminish effect of BCG
methotrexate: may increase metho coc
tetracycline: may diminish effects of PCNs
Warfarin: PCNs may enhance effect
OCPs: PCNs may decrease efficacy
3rd generation PCNS, activity
carbenicillin and ticarcillin
activity: strep, enteric gram-neg bacilli (e. coli, klebsiella, pneumoniae, enterobacter cloacea, enterobacter aerogenes and proteus miriabilis), pseudomonas, and anaerobes
- IV only: std therapy as anti-pseudomonal med in hosp.
Piperacillin spectrum
derivative of ampicillin, covers same spectrum as 3rd generation, but more active against Klebsiella, enterococci and bacteroides
**piperacillin w/ tazobacatm (zosyn): broad spectrum, used for cellulitis, postpartem endometritis, peritonitis, comm-acquired pneumonia, nosocomial pneumonia
Good to know about PCNs
can cause bleeding problems
can cause nephritis
IN high doses can cause near complications and seizures
- common to see secondary infections such as vaginal candidiasis
B-lactamase inhibitors
clavulanic acid, sublactam, tazobactam
activity: inhibitors of many bacterial b-lactamases, inactivate ahminoglycosides
Use: only in comb with PCN -> PCN determines spectrum:
-intra-abdominal/gynecological infections
-skin and soft tissue infections
RTI, sinusitis, and lung abcesses
-Don’t have any antimicrobial activity by themselves.
Cephalosporins
as they progress from 1st to 3rd generation they increase in gm - coverage and lose gram positive coverage.
- well absorbed from GI tract, and food enhances absorption.
- allergic reactions are similar to PCNs (3-10% cross-reactivity)
Cephalosporins susceptibility to B-lactamases
are susceptible to B-lactamases
and they have similar SE’s as penicillin.
Most common 1st, 2nd and 3rd generation cephalosporins?
1st: cephalexin (keflex),
2nd: cefaclor (ceclor),
3rd: cefixime (suprax)
1st gen cephalosporins
cefadroxil=oldest,
cephalexin= keflex
cefazolin= Ancef (IV)
activity: good against gram +: strep and staph (not MRSA), some gram -, good against anaerobic cocci
SE: GI, allergic reactions, C. diff
Use of 1st gen cephalosporins
cephalexin: uncomplicated cellulitis
cefazolin: more complicated cellulitis or IV prophylaxis prior to surgery
2nd gen cephalosporins
cefaclor PO (more susceptible b-lactamase hydrolysis, not as useful), cefuroxime; IV, cefoxitin IV, cefotetan IV
activity: gram +, better gram - against klebsiellae, H. influenza, none against pseudomonas
Uses for 2nd gen cephalosporins
cefuroxime: sinusitis, otitis, RTI, comm acquired pneumonia (H. flu, K. pneumonia, and penicillin resistant pneumococci).
cefoxitin: anaerobic activity- prophylactic GI surgeries, peritonitis, and diverticulitis (active against gm - rods)
3rd gen cephalosporins
cefotaxime IV, ceftazidime IV, ceftriaxone
activity: expanded gram - against meningicoccus, citrobacter, b-lactamase strains of homophiles and neisseria
ceftazidime- active against pseudomonas
cefotaxime and ceftriaxone: cross blood/brain barrier
Use of 3rd gen cephalosporins
ceftriaxone and ceftotaxime: meningitis
empirical therapy for serious infections -> effective against PCN resistant strains pnemonococci
ceftriaxone: used to tx gonorrhea, lyme disease
SE: rash, N/V, LFTs, eosinophilia, HA
4th gen cephalosporins
cefepime IV
activity: gram + and -, including pseudomonas, staph aureus, strep pneuma, Haemphilus and Neisseria
4th gen cephalosporin use
penetrates BBB well -> meningitis, other serious infections and sepsis
sometimes used with amino glycoside w/ tx pseudomonas
SE: N/V/D, HA, rash
Cephalosporins points
1st gen: cephalexin and cefazolin still used a lot
2nd gen: tx otitis, sinusitis, and RTI (Ceftin)
3rd and 4th: DOC for gram - meningitis, good alt to aminogly.
need to watch for resistance strains -> combo therapy good for pseudomonas,
Ceftriaxone: DOC for gonorrhea
Ceftazidime: effective for pseudomonas meningitis
Carbapenems
Imipenem/cilastatin - better coverage than meropenem (IV(
activity: very resistant to cleavage (b-lactamase), effective against gram + (enterococcus faecalis, and listeria), gram - (H influenza, N gonorrhoaea, enterobacter, and pseudomonas), anaerobes (bactericides)
Carbapenem uses
meropenem= meningitis, intra-abdominal infections, resistant UTIs, pseudomonas, and w/ or w/o aminoglyc for neutropenic pt
SE: N/V/D, rashes,
imipenem: renal failure and seizures
