Lecture 11 - Antibiotics I - Drugs that Weaken the Cell Wall

‭Classes of Antibiotics that Weaken the Cell Wall‬ ‭Beta-Lactam Antibiotics‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭ enicillins‬ P ‭Cephalosporins‬ ‭Carbapenems‬ ‭Monobactams‬ ‭Beta-Lactam Antibiotic Structure‬ ‭Bacterial Cell Wall‬ ‭Bacterial Growth‬ ‭●‬ ‭Involves breaking down and rebuilding the peptidoglycan layer‬ ‭Two Critical Enzymes‬ ‭Autolysins‬ ‭●‬ ‭Cleave the bonds in the cell wall, allowing growth and division‬ ‭●‬ ‭Activated by penicillin‬ ‭Transpeptidases‬ ‭●‬ ‭Build “bridges” back to give the cell wall its strength‬ ‭●‬ ‭Inhibited by penicillin‬ ‭Penicillin-Binding Proteins (PBPs)‬ ‭●‬ ‭Only expressed during growth‬ ‭○‬ ‭Penicillin cannot bind to a dormant bacteria‬ ‭●‬ ‭Binding sites for penicillins‬ ‭Penicillin‬ ‭›‬ ‭MOA‬ ‭●‬ ‭Disrupts the bacterial cell wall by:‬ ‭○‬ ‭Inhibiting transpeptidases‬ ‭○‬ ‭Activating autolysins‬ ‭●‬ ‭Leads to cell lysis and death (bactericidal)‬ ‭Penicillin Allergy‬ ‭‬ M ● ‭ ost common cause of drug allergy‬ ‭●‬ ‭Can be experienced without prior use of penicillin‬ ‭ ‬ ‭Exposure to penicillin in fungi or food‬ ○ ‭ ‬ ‭Reactions vary in time and severity‬ ● ‭○‬ ‭Time:‬ ‭■‬ ‭Immediate (2-30 mins)‬ ‭■‬ ‭Accelerated (1-72 hrs)‬ ‭■‬ ‭Delayed (days to weeks)‬ ‭○‬ ‭Severity:‬ ‭■‬ ‭Minor (ex. rash)‬ ‭■‬ ‭Severe (ex. anaphylaxis)‬ ‭Nursing Actions‬ ‭‬ S ● ‭ creen all patients for previous penicillin (PCN) allergies‬ ‭●‬ ‭Consider cross-sensitivity; if a patient has experienced a severe reaction to cephalosporin,‬ ‭avoid penicillin use as well, and vice versa‬ ‭●‬ ‭NKA: Observe for 30 minutes after injection‬ ‭○‬ ‭Signs of anaphylaxis include:‬ ‭■‬ ‭Rash/pruritus‬ ‭■‬ ‭Laryngeal edema‬ ‭■‬ ‭Wheezing‬ ‭■‬ ‭Severe hypotension‬ ‭●‬ ‭If anaphylaxis, epinephrine and respiratory‬ ‭support‬ ‭○‬ ‭Discontinue IV administration‬ ‭immediately and contact healthcare‬ ‭provider‬ ‭Categorizing Penicillin‬ ‭‬ N ● ‭ arrow-spectrum:‬‭Antibiotics that are active against‬‭a selective group of bacterial types‬ ‭●‬ ‭Broad-spectrum:‬‭Has a wide range of activity against‬‭gram-positive and some‬ ‭gram-negative organisms‬ ‭●‬ ‭Extended-spectrum:‬‭Affects gram-positive bacteria‬‭but has more extensive action‬ ‭against gram-negative bacteria due to a chemical modification‬ ‭●‬ ‭Resistance‬ ‭Bacterial Defense: Resistance to Penicillins‬ ‭‬ P ● ‭ revent penicillins from reaching their targets (PBPs)‬ ‭●‬ ‭Production of PBPs that have a low affinity for PCN (ex. MRSA)‬ ‭●‬ ‭Inactivation of PCN by bacterial enzymes [beta-lactamases] (ex. penicillinase)‬ ‭○‬ ‭Can be transferred from one bacterium to another (ex.‬‭S. aureus‬‭)‬ ‭○‬ ‭Often gram-negative bacteria‬ ‭○‬ ‭Penicillinase-sensitive:‬‭Bacteria are more likely to be resistant‬ ‭Penicillins: 4 Major Types‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ ‭ arrow-spectrum, penicillinase-sensitive‬ N ‭Narrow-spectrum, penicillinase-resilient (antistaphylococcal penicillins)‬ ‭Broad-spectrum‬ ‭Extended-spectrum (antipseudomonals)‬ ‭Narrow Spectrum, Penicillinase Sensitive‬ ‭Prototype‬ ‭●‬ ‭Penicillin G‬ ‭●‬ ‭Penicillin V‬ ‭Indications‬ ‭●‬ ‭Most gram-positive (‬‭S. pneumonia‬‭)‬ ‭●‬ ‭Some gram-negative cocci (‬‭Neisseria gonorrhoeae‬‭)‬ ‭●‬ ‭Spirochetes (‬‭Treponema pallidum‬‭)‬ ‭Pharmacokinetics/Dynamics‬ ‭●‬ ‭Salts:‬‭4 types‬ ‭○‬ ‭Potassium, sodium, benzathine, procaine‬ ‭●‬ ‭Metabolism:‬‭Minimal‬ ‭●‬ ‭Excretion:‬‭Renal‬ ‭○‬ ‭Dosage adjustments based on renal failure patients‬ ‭●‬ ‭Administration:‬‭Parenteral‬ ‭○‬ ‭IM:‬‭Rates of absorption vary‬ ‭○‬ ‭IV:‬‭Only potassium or sodium salts‬ ‭Penicillin G‬ ‭●‬ ‭Adverse effects:‬ ‭○‬ ‭Allergic reaction‬ ‭○‬ ‭Pain at injection site‬ ‭○‬ ‭Risk for neurotoxicity if levels are high‬ ‭●‬ ‭Drug interactions:‬ ‭○‬ ‭Aminoglycosides‬‭(synergistic)‬ ‭○‬ ‭Often used together; penicillin allows aminioglycosides to reach intracellular sites‬ ‭○‬ ‭Inactivated by high concentrations of penicillin‬ ‭○‬ ‭Should be administered in separate IV lines with a flush in between‬ ‭Penicillin V‬ ‭●‬ ‭Only penicillin that can be administered‬‭orally‬ ‭●‬ ‭Stable against gastric acid‬ ‭Narrow-Spectrum, Penicillinase-Resilient (Antistaphylococcal Penicillins)‬ ‭Prototype‬ ‭●‬ ‭Nafcillin‬ ‭●‬ ‭Others: Oxacillin, dicloxacillin‬ ‭Indications‬ ‭●‬ ‭Penicillinase-producing staphylococcus‬ ‭○‬ ‭Ex.‬‭S. aureus‬ ‭●‬ ‭Does not work on MRSA‬ ‭Pharmacokinetics/Dynamics‬ ‭●‬ ‭Administration:‬‭IV only‬ ‭●‬ ‭Poor absorption if PO‬ ‭Adverse Effects‬ ‭●‬ ‭Allergic reaction‬ ‭Broad-Spectrum, Penicillinase-Sensitive‬ ‭Prototype‬ ‭●‬ ‭Amoxicillin‬ ‭●‬ ‭Other: Ampicillin‬ ‭Indications‬ ‭●‬ ‭Same spectrum as Penicillin G plus increased activity for gram negative bacteria‬ ‭○‬ ‭Ex.‬‭H. influenzae‬‭,‬‭E. coli‬‭,‬‭N. gonorrhea‬ ‭●‬ ‭Able to penetrate cell envelope of gram-negative bacteria‬ ‭●‬ ‭Ineffective against‬‭S‬‭.‬‭aureus‬‭due to production of‬‭beta-lactamases‬ ‭Pharmacokinetics/Dynamics‬ ‭●‬ ‭Administration:‬‭Oral (amoxicillin) or IV (ampicillin)‬ ‭●‬ ‭Excretion:‬‭Renal‬ ‭Adverse Effects‬ ‭●‬ ‭Most commonly rash or diarrhea‬ ‭Extended-Spectrum, Penicillinase-Sensitive (Antipseudomonals)‬ ‭Prototype‬ ‭●‬ ‭Piperacillin‬ ‭Indications‬ ‭●‬ ‭Pseudomonas aeruginosa‬‭,‬‭Enterobacter‬‭,‬‭Proteus‬‭,‬‭Klebsiella‬ ‭●‬ ‭Not‬‭staph‬‭due to susceptibility to beta-lactamases‬ ‭●‬ ‭Generally used in combination with other antibiotics‬ ‭○‬ ‭Ex. Augmentin, Unasyn, Timentin, Zosyn‬ ‭●‬ ‭Also synergistic with aminoglycosides‬ ‭Cephalosporins‬ ‭‬ R ● ‭ ecognized by “cef,” such as in‬‭cef‬‭triaxone,‬‭cef‬‭azolin,‬‭cef‬‭prozil‬ ‭●‬ ‭Like PCN in many ways:‬ ‭○‬ ‭Mechanism of action (MOA)‬ ‭○‬ ‭Beta-lactam ring structure‬ ‭○‬ ‭Bactericidal‬ ‭○‬ ‭Susceptible to beta-lactamases‬ ‭■‬ ‭Often made by gram-negative bacteria‬ ‭○‬ ‭Most are IV-administered‬ ‭○‬ ‭Most are eliminated by the kidneys‬ ‭○‬ ‭Potential for allergic rxns‬ ‭Five Generations of Cephalosporins‬ ‭Generation‬ ‭BBB‬ ‭Penetration‬ ‭Gram (+/-)‬ ‭Activity‬ ‭Risk of‬ ‭Superinfection‬ ‭-ase Resilient‬ ‭1st (‬‭cephalexin‬‭)‬ ‭None‬ ‭Mostly gm (+),‬ ‭few gm (-)‬ ‭Small‬ ‭Poor‬ ‭2nd (‬‭cefoxitin‬‭)‬ ‭Very little‬ ‭Mostly gm (+),‬ ‭some gm (-)‬ ‭Small‬ ‭Poor‬ ‭3rd (‬‭cefotaxime‬‭)‬ ‭Good‬ ‭Good coverage‬ ‭against both‬ ‭Moderate‬ ‭Better‬ ‭4th (‬‭cefepime‬‭)‬ ‭Good‬ ‭Similar to 3rd‬ ‭generation‬ ‭Moderate‬ ‭Better‬ ‭5th (‬‭ceftaroline‬‭)‬ ‭Similar to 3rd generation but active against MRSA‬ ‭Pharmacokinetics‬ ‭‬ A ● ‭ dministration:‬‭Often IM or IV‬ ‭●‬ ‭Not PO due to poor absorption‬ ‭Adverse Effects‬ ‭●‬ ‭Hypersensitivity reactions:‬ ‭○‬ ‭Delayed reaction: Maculopapular rash‬ ‭○‬ ‭Anaphylaxis is rare‬ ‭○‬ ‭Cross-sensitivity to PCN‬ ‭●‬ ‭Thrombophlebitis during IV admin → irritation and clot‬ ‭●‬ ‭Bleeding:‬‭Reduction in prothrombin time or bleeding‬‭time‬ ‭Drug Interactions‬ ‭●‬ ‭Alcohol:‬‭Cefazolin and cefotetan = disulfiram reaction‬ ‭○‬ ‭Can be fatal‬ ‭●‬ ‭Drugs that promote bleeding (ex. warfarin)‬ ‭Carbapenems‬ ‭●‬ ‭Extremely broad-spectrum‬ ‭Prototype‬ ‭●‬ ‭Imipenem (Primaxin)‬ ‭MOA‬ ‭‬ S ● ‭ imilar to PCN‬ ‭●‬ ‭Resistant to practically all beta-lactamases‬ ‭Indications‬ ‭‬ R ● ‭ eserved for mixed infections‬ ‭●‬ ‭Not MRSA‬ ‭Pharmacokinetics‬ ‭‬ A ● ‭ dministration:‬‭Parenteral‬ ‭●‬ ‭Excretion:‬‭Renal‬ ‭Adverse Effects‬ ‭‬ G ● ‭ I effects (N/V, diarrhea)‬ ‭●‬ ‭Hypersensitivity reaction:‬‭Some‬ ‭●‬ ‭Superinfections‬ ‭Question:‬‭Which of the following about superinfections‬‭is true?‬ ‭a.‬ ‭Superinfections are more common in patients treated with narrow-spectrum drugs.‬ ‭b.‬ ‭Superinfection is a new infection that appears during the course of treatment for a‬ ‭primary infection.‬ ‭c.‬ ‭Superinfections are caused by viruses.‬ ‭d.‬ ‭Superinfections are easy to treat.‬ ‭Clostridium Difficile‬‭Infection‬ ‭Superinfection‬ ‭●‬ O ‭ ccurs secondary to antibiotic treatment such as clindamycin, fluoroquinolones,‬ ‭penicillins, and cephalosporins‬ ‭Acquisition‬ ‭‬ ● ‭●‬ ‭●‬ ‭●‬ I‭ ngestion of spores‬ ‭Contaminated objects‬ ‭Patient/healthcare contact (hands)‬ ‭Can be a carrier‬ ‭S/S of Infection‬ ‭‬ A ● ‭ bdominal cramping, nausea, fever‬ ‭●‬ ‭Passage of three unformed stools in 24 hours‬ ‭●‬ ‭Positive‬‭C. diff‬‭test‬