Ch 24- PCN Flashcards
Antibiotics that contain Beta-lactam ring
Penicillin, Cephalosporins, Carbapenems, and monobactams
**Beta-lactam antibiotics are bactericidal
**Most effective against rapidly growing organisms forming cell walls
How does Penicillin work?
-6 aminopenicillanic-acid joined to the beta-lactam ring
-inhibit the biosynthesis of bacterial cell wall mucopeptide (peptidoglycan) ->wall weakened and lysis of the walls occur
**PBPs = transpeptidase, carboxypeptidase, and endopeptidase enzymes
What are the four PCN classes?
1) Penicillinase-sensitive or natural PCN (ex: Penicillin G-IV, Penicillin V-PO, Procaine, and Benzathine - IM)
2) aminopenciliins (ex: Ampicillin and amoxicillin)
3) Penicillinase-resistant or antistaphylococcal PCN (ex: Nafcillin, oxacillin, and dicloxacillin **most likely to cause hepatotoxicity)
4) Antipseudomonal or extended-spectrum PCN (ex: Piperacillin/tazobactam)
What are four types of natural PCN?
Penicillin V-oral
Penicillin G-IV
Procaine and Benzathine -IM (can cause cardiac arrest/death if given IV)
**treat aerobic, gram + Ex: S. pneumoniae, group A and B Strep, some Enterococcus strains, and some non-penicillinase-producing staphylococci.
Factors that lead to resistance against Penicillins
1) Inactivation by beta-lactamases
2) alteration in target PBPs on bacterial cell wall
3) alteration in the outer membrane of cell wall that decreases permeability to the site of action
**Beta-lactamase production is the most common
What are Beta-lactamases?
Enzymes such as penicillinases, cephalosporinases, and carbapenemases
**produced by S. auresus and Haemophilus species
**Inhibitors (clavulanate, sulbactam, and tazobactam)
How do Beta-lactamases inhibitors work?
Irreversibly inactivate beta-lactamases enzymes produced by bacteria, binding to their active site and protecting the antibiotic from inactivation
**E.coli, Klebsiella, and Enterobacter produce extended-spectrum beta-lactamases (ESBLs) spare only CARBAPENEMS
What is the problem with drug penetration?
Present only in gram (-), associated with cellular outer membrane
Oral Penicillin
Serum concentration do not rise proportionately with increased doses, higher than recommended doses cause GI distress and diarrhea
**dicloxacillin is the ONLY peniccilinase-resistant penicillin.
**Amoxicillin is more completely absorbed, and should always be used for oral
**PCN cross the placenta and enter breast milk
Excretion of PCN
-excreted primarily as unchanged drugs in the urine
**PROBENECID competes with PCN for secretion, will prolong half-life and raise the peak plasma [] of PCN -> toxicity in renal failure pts
-concurrent admin of oral probenecid and PCN to treat serious infection
Precautions with PCN
PCN are the most likely antibiotics to cause an allergic rx
**Piperacillin may induce hemorrhagic, Use with cautions with pts who have anemia, thrombocytopenia, granulocytopenia, or bone marrow depression
*Effects infants via breast milk, may cause diarrhea, candidiasis, or allergic response
ADRS with PCN
**Type I hypersensitive
PCN-resistant groups (Dicloxacillin, nafcillin, and oxacillin) most likely to cause hepatoxicity
**Piperacillin/tazobactam (ZOSYN) when combined with vancomycin lead to higher rate of nephrotoxicity
**high doses of procaine can cause transiet mental disturbances
**Use of broad-spectrum (Zosyn) or prolonged or repeat therapy with any broad-spectrum antibacterial may result in bacterial or fungal overgrowth.
**Food and acidic juices decreased oral absorption of PCN V and the PCN -resistant PCN
What are Cephalosporins?
-Beta-lactam antibiotics, structurally and chemically related to penicillins
**cefoxitin and cefotetan are cephamycin, but usually included with cephalosporins because of clinical and chemical similarity
-Inhibit mucopeptide synthesis in the bacterial cell wall, inhibit PBPs involved in crosslinking peptidoglycans in cell wall (similar to PCN)
First Generation Cephalosporins-Cefadroxil, Cefazolin, Cephalexin
-1st gen active against gram + cocci, including S. aureus and S. epidermidis (excluding methicillin-resistant strains) and most streptococci
**Enterococcus species are intrinsically resistant to cephalosporins
**Most beta-lactamases produced by Haemophilus and Moraxella affect first gen
Second Generation Cephalosporins-Cefaclor, Cefprozil, Cefotetan, Cefuroxime axetil, Cefdinir
-Cefaclor, cefprozil, and cefur
oxime
-against Gram + Cocci, including S. aureus and S. Epidermidis (excluding methicillin-resistant strains) with INCREASEd activity against H.influenzae
**Cephamycins (Cefotetan and cefoxitin) similar to first gen, and also have limited activity against anaerobes
Third Generation Cephalosporins-Cefixime, Cefotaxime, Cefpodoxime, Ceftibuten, Ceftriaxone, Cefepime
-Activity against streptococcal species, Streptococcus pneumoniae, MSSA, H.influenzae, Moraxella, N. gonorrhoeae, N.meningitidis, E.coli, Klebsiella, Proteus, and Salmonella.
**Cefdinir and cefpodoxime have the best gram + activity. IV : cefotaxime, ceftazidime (activity > gram -) , and ceftriaxone.
Resistance to Cephalosporins
-Most common mechanism of resistance that bacteria express against are
1)beta-lactamase production
2) altered target sites
