8/28/19 Disclosure 2 E. Monee’ Carter-Griffin DNP, MA, RN, ACNP-BC Antibiotic has no financial relationships with commercial Review interests to disclose. Any unlaBeled and/or E. Monee’ Carter-Griffin, DNP, MA, RN, ACNP-BC unapproved uses of drugs or products will Be Associate Chair for Advanced Practice Nursing disclosed. University of Texas at Arlington, College of Nursing & Health Innovation Dallas Pulmonary & Critical Care, PA • Identify the general characteristics of • SusceptiBility à determine which antibiotics. antibiotics a bacteria is sensitive to • Discuss the mechanism of action, • à pharmacokinetics, and spectrum of activity MIC lowest concentration of drug that inhiBits growth of the Bacteria for the most common antiBiotic drug classes. Antibiotic Objectives • Identify commonly prescriBed antiBiotics • Trough à lowest concentration of within the drug classes including dosage Lingo drug in bloodstream range and indication for prescribing. – Collect prior to administration of • Identify special considerations for specific drug antibiotics and/or drug classes. • Peak à highest concentration of • Practice appropriate prescriBing for common drug in bloodstream bacterial infections. • Review Basic antiBiotic stewardship 3 4 principles. • Penicillins • Bactericidal or bacteriostatic • Cephalosporins • Narrow or Broad spectrum • Carbapenems General • Can elicit allergic responses Antibiotic • MonoBactam Characteristics • Affect normal Body flora Drug Classes • Macrolides • Fluoroquinolones • Sulfonamides • Tetracyclines 5 6 1 8/28/19 • Penicillins – Natural penicillins 8 – Aminopenicillins Penicillins Penicillins – Anti-staphylococcal penicillins • Mechanism of action àbactericidal à – Anti-pseudomonal penicillins interrupts cell wall synthesis 7 • Pharmacokinetics • Spectrum of Activity – Gram positive organisms Natural – Penicillin G à mostly given IM, But Natural • Streptococcus species (e.g. S. Penicillins one variation can Be given IV Penicillins pyogenes) • Poorly aBsorBed via PO • Some enterococcus species (e.g. E. faecalis) – Penicillin V à given PO Penicillin G Penicillin G • Staphylococci à only minority; most Penicillin V • Increased gastric acid staBility Penicillin V are resistant • Listeria monocytogenes – Gram negative organisms à limited – AnaeroBes • Bacteroides 9 10 • Fusobacterium species Drug Dosage Route Indication • Special Considerations Natural – Do not administer next to nerve or Penicillin G 1.2 – 2.4 MU IM Most commonly Penicillins artery benzathine used to treat Group A strep (e.g. – ProBenecid decreases renal Penicillin G procaine 2.4 MU x 1 dose IM pharyngitis), and Penicillin G clearance of penicillins. syphilis • Co-administration can be used to Penicillin V Penicillin G 12 – 24 MU daily IV increase concentration levels (parenteral) – Decrease parental dosage when CrCl Penicillin V 125-500 mg every 6- PO is less than 50 ml/min 8h – Allergy 11 12 2 8/28/19 Penicillins: • Pharmacokinetics – Amoxicillin +/- clavulanate à given 13 Beta-lactamase Inhibitors Aminopenicillins PO • StaBle in gastric acid Clavulanic acid (clavulanate) Amoxicillin • Best aBsorBed penicillin SulBactam Amoxicillin/Clavulanate – Ampicillin +/- sulbactam TazoBactam Ampicillin • Ampicillin can Be given PO, IM, or Ampicillin/Sulbactam IV • With the addition of the sulBactam can only Be given IM or IV 14 Penicillins: Drug Dosage Route Indication • Spectrum of Activity – Same activity as natural penicillins Aminopenicillins à susceptible gram-positive Amoxicillin (Amoxil) 250-500 mg every PO Sinusitis, 8h meningitis, organisms 500-875 mg BID susceptiBle UTIs, Amoxicillin – Improved gram-negative coverage Amoxicillin/ 250-500 mg every PO Soft skin infections Clavulanate 8h related to group A • Amoxicillin/Clavulanate Enterobacteriaceae (Augmentin) 875 mg every 12h strep, Otis media, pneumonia Ampicillin • H. pylori à used as part of multi- Ampicillin 250-500 mg every PO, IM, IV drug treatment 6h Ampicillin/Sulbactam • H. influenzae Ampicillin/ 1.5-3 g every 6h IM, IV 15 SulBactam (Unasyn) 16 Penicillins: • Special Considerations • Pharmacokinetics Anti- – Dicloxacillin à given PO – Of note, dosing of drugs with beta- staphylococcal Aminopenicillins lactamase inhibitors is Based on the • Delayed aBsorption when given amoxicillin or ampicillin NOT the Penicillins with meals – Nafcillin à given IM or IV Amoxicillin inhibitor. Dicloxacillin • Poor oral aBsorption Amoxicillin/Clavulanate – Decrease parental dosage when *Methicillin • CrCl is less than 50 ml/min Primarily metaBolized through the Ampicillin Nafcillin liver – MSSA coverage with Amoxicillin/ Ampicillin/Sulbactam Oxacillin – Oxacillin à given IM or IV Clavulanate but none with • Poor oral aBsorption Amoxicillin only 17 • Primarily metaBolized through the 18 – No pseudomonas coverage. liver 3 8/28/19 Anti- • Spectrum of Activity Drug Dosage Route Indication staphylococcal – Drug class also known as the Penicillins Penicillinase-Resistant Penicillins – Gram-positive organisms Dicloxacillin 125-500 mg every PO Drug of choice for 6h MSSA infections à Dicloxacillin • Staphylococcal species cellulitis, Nafcillin 0.5-2 g every 4-6h IV endocarditis, Nafcillin – MSSA* osteomyelitis, and bacteremia Oxacillin • Streptococcal species 0.5 g every 4-6h IM Oxacillin 0.25-2 g every 4-6h IM, IV 19 20 • Anti- • Special Considerations Anti- Pharmacokinetics – Piperacillin +/- tazoBactam à IV staphylococcal – No MRSA coverage pseudomonal Penicillins – Nafcillin tends to Be Better tolerated Penicillins • Piperacillin can also Be given IM – Oxacillin à drug-induced hepatitis • Piperacillin is NOT aBsorBed when Dicloxacillin • Usually reversiBle with discontinuation of Piperacillin given orally. the drug – Ticarcillin +/- clavulanate Nafcillin – Dose adjustments for Nafcillin and Piperacillin/tazobactam potassium à IV only Oxacillin Oxacillin for patients with severe hepatic Ticarcillin and renal dysfunction Ticarcillin/clavulanate potassium 21 22 • Anti- Spectrum of activity Drug Dosage Route Indication – Typically referred to the extended- pseudomonal spectrum penicillins Penicillins – Gram-positive activity Piperacillin (Pipracil) 3-4 g every 4-6h IV, IM Intra-abdominal infections, Piperacillin • Staph. and Strep. pneumonia, severe soft/skin and tissue Piperacillin/tazobactam • NO MRSA coverage. Piperacillin/tazoBactam 3.375-4.5 g every IV (Zosyn) 6-8h infections, sepsis, etc. Ticarcillin – Gram-negative activity Ticarcillin/clavulanate • Including Pseudomonas aeruginosa Ticarcillin +/- clavulanate 0.25-2 g every 4- IV potassium • Also has coverage against potassium (Timentin) 6h EnteroBacteriaceae. 23 24 – AnaeroBic coverage 4 8/28/19 • Special Considerations Anti- • Cephalosporins – Dosage considerations for patients – 1st Generation pseudomonal with renal dysfunction – 2nd Generation Penicillins • Elimination half-life can increase 2- fold in mild to moderate dysfunction – 3rd Generation Piperacillin to 6-fold in severe dysfunction Cephalosporins – 4th Generation – Use caution with Ticarcillin in patients Piperacillin/tazobactam – 5th Generation Ticarcillin with HF due to the high sodium load – High levels of Ticarcillin can increase Ticarcillin/clavulanate seizure risk in patients with seizure potassium disorders 25 26 Penicillins: • Pharmacokinetics st – Cefadroxil, Cephalexin, & 27 1 Generation Cephalosporins Cephradine à PO Cephalosporins • Rapidly aBsorBed from the GI tract • Mechanism of action àbactericidal à • Wide distriBution But do NOT cross interrupts cell wall synthesis Cefadroxil the Blood-brain-barrier Cefazolin – Cefazolin à IM, IV Cephalexin • Widely distriButed as well But poor Cephradine CSF penetration 28 Penicillins: • Spectrum of Activity Drug Dosage Route Indication st – Primarily active against gram- 1 Generation positive cocci. Cephalosporins Cefadroxil (Duricef) 1-2 g/daily in two PO Skin and soft tissue • Staphylococcus divided doses infections, respiratory Cefadroxil • Streptococcus Cefazolin (Ancef) 1-2g every 8h IM, IV infections, some UTIs, and otitis media Cefazolin • NO MRSA coverage. Cephalexin – Minor gram-negative activity Cephalexin (Keflex) 250-1000mg every PO 6-12h • E. coli Cephradine Cephradine (Velosef) 250-500mg every PO • H. influenzae 6-12h • Klebsiella 29 30 5 8/28/19 Penicillins: Penicillins: • Special Considerations • Pharmacokinetics – If cross-sensitivity reaction is to – Cefaclor & Cefprozil à PO 1st Generation 2nd Generation occur with a penicillin, it is most • Rapidly aBsorBed from the GI tract Cephalosporins likely to occur with 1st generation Cephalosporins • Cefaclor slowed aBsorption with cephalosporins. Cefadroxil Cefaclor food. • Cefadroxil • Cefprozil is not affected By food. Cefazolin Cefotetan – Cefazolin can cross the blood-brain- Cephalexin Cefoxitin – Cefotetan & Cefoxitin à IM, IV barrier in severe renal – Cefuroxime à PO, IM, IV Cephradine dysfunction/failure Cefprozil • Rapidly aBsorBed from the GI tract • Encephalopathy Cefuroxime 31 • Increased aBsorption when taken 32 • Seizures with food (PO form) Penicillins: • Spectrum of Activity Drug Dosage Route Indication – Gram-positive coverage 2nd Generation Cefaclor 250-500mg every PO Skin & soft tissue • 8h infections, UTIs, Staphylococcus respiratory tract Cephalosporins Cefotetan 1-2g every 12h IM, IV • Streptococcus infections Cefaclor – Extended gram-negative coverage Cefoxitin 1-2g every 6-8h IM, IV Cefotetan • Same as 1st generation but ADD Cefprozil 250-500mg every PO 12-24h Cefoxitin coverage against Neisseria, Proteus – AnaeroBic coverage Cefuroxime