the anti-infectives, part i

All of the Anti-Infective Medications: 

All of the Anti- I nfective Medications Yikes! Science 355

How do these drugs kill micoorganism?: 

How do these drugs kill micoorganism ?

Basic Terminology: 

Basic Terminology Chemotherapy: using chemicals against invading organisms (bacteria, fungi, viruses) Antibiotic: a chemical produced by one microbe that has the ability to harm other microbes Antimicrobial: any agent (natural or not) that can kill or suppress microorganisms.

Our big goal is….: 

Our big goal is…. Selective toxicity: ability of the drug to injure the “bad” cell (or organism) without injuring or killing the “good” ones. Or in Jayme’s words: it’s not helpful to kill the host along with the bug. Main mechanisms of selective toxicity: Disruption of bacterial cell wall Inhibition of an enzyme unique to bacteria Disruption of bacterial protein synthesis

Classification of Antimicrobial Drugs: 

Classification of Antimicrobial Drugs Narrow versus broad Bacteriostatic vs. bactericidal (think homicidal) Mechanism of action Drugs that weaken the cell wall ( penicillins & cephalosporins ) Drugs that increase cell membrane permeability ( Amph B) Drugs that don’t let the cells synthesize protein (aminoglycosides) Drugs that don’t let the cells synthesize protein very well ( tetracyclines ) Drugs that disrupt synthesis of DNA or RNA (Ciprofloxacin) Drugs that disrupt biochemical reactions (trimethoprim and sulfanamides ) Drugs that suppress viral replication

A really important concept: 

A really important concept Resistance.. Use of antibiotics promotes the emergence of drug resistant microbes. Not good. Darwinian natural selection at work

How are antibiotics chosen?: 

How are antibiotics chosen? Emperic versus microbe identification Identify the infecting organism (if possible) Vaccinate Get catheters out Target the pathogen ID consults Antimicrobial control Use local data Treat infection not contamination Treat infection not colonization Just say no to vanco Stop when done Isolation Wash your hands!

Prophylactic use of Antimicrobials: 

Prophylactic use of Antimicrobials Surgery Bacterial endocarditis Neutropenia Other (UTI, STI, influenza)

Chapter 83: 

Chapter 83 Drugs That Weaken the Bacterial Cell Wall I: Penicillins

Penicillins: 

Penicillins Active against a variety of bacteria Direct toxicity – low Principal adverse effect – allergic reaction Beta-lactam ring in their structure Beta-lactam family – also includes cephalosporins, aztreonam, imipenem, meropenem, and ertapenem

The Penicillins: 

The Penicillins Class = “The penicillins ” Penicillin G as our prototype Potential problems Allergic reactions Pain (if IM) Sensory and motor dysfunction (IM) Neurotoxicity

Penicillins: 

Penicillins Mechanism of action Weaken the cell wall, causing bacteria to take up excessive water and rupture Active only against bacteria that are undergoing growth and division Bactericidal Bacterial resistance Inability of penicillins to reach their target Inactivation of penicillins by bacterial enzymes

Mechanisms of Bacterial Resistance: 

Mechanisms of Bacterial Resistance Three factors Inability of penicillins to reach their targets Inactivation of penicillins by bacterial enzymes Production of penicillin-binding proteins (PBPs) that have a low affinity for penicillins

Autobots vs Decepticons Beta Lactam Antibiotics Beta-lactamases: 

Autobots vs Decepticons Beta Lactam Antibiotics Beta-lactamases

Classification of Penicillins: 

Classification of Penicillins Narrow-spectrum penicillins Pencillinase-sensitive Narrow-spectrum penicillins Pencillinase-resistant Broad-spectrum penicillins Extended-spectrum penicillins

Penicillin G (Benzylpenicillin): 

Penicillin G (Benzylpenicillin) Bactericidal to a number of gram-positive and some gram-negative organisms Adverse effects Least toxic of all antibiotics Penicillins are the most common cause of drug allergy

Penicillin Allergy: 

Penicillin Allergy Development of penicillin allergy Skin tests for penicillin allergy Management of patients with a history of penicillin allergy Assess for penicillin allergy in each patient who will be receiving penicillin If history of mild reaction – consider cephalosporin If history of anaphylaxis – avoid administration of penicillin or cephalosporins

Penicillin Allergy: 

Penicillin Allergy Types Immediate (reaction in 2 to 30 minutes) Accelerated (reaction in 1 to 72 hours) Late (reaction takes days or weeks to develop) Anaphylaxis Laryngeal edema Bronchoconstriction Severe hypotension

Penicillin Allergy: 

Penicillin Allergy Treatment Epinephrine Respiratory support Prevention – skin testing

Drug Interactions: 

Drug Interactions Aminoglycosides Penicillin V

Penicillinase-Resistant Penicillins: 

Penicillinase-Resistant Penicillins Available in the U.S. Nafcillin Oxacillin Dicloxacillin MRSA – methicillin-resistant Staphylococcus aureus

MRSA: 

MRSA A strain of staph that’s resistant to penicillins (not just Methicillin) and cephalosporins Vancomycin is the drug of choice for treatment Concern - ? Vancomycin resistant MRSA?

Broad-Spectrum Penicillins: 

Broad-Spectrum Penicillins Broad-spectrum penicillins (aminopenicillins) Ampicillin (Principen) Amoxicillin (Amoxil, DisperMox, Moxatag, Trimox) Adverse effects Rash Diarrhea

Extended-Spectrum Penicillins : 

Extended-Spectrum Penicillins Extended-spectrum penicillins (antipseudomonal penicillins) Ticarcillin (Ticar) One of the broadest antimicrobial spectra of all penicillins Risk of sodium overload – watch CHF patients closely Piperacillin Broad-spectrum, but penicillinase-sensitive

Penicillins Combinations: 

Penicillins Combinations Beta-lactamase inhibitors Clavulanic acid, tazobactam, sulbactam Extends antimicrobial spectrum when combined with penicillinase-sensitive antibiotics Ampicillin/sulbactam (Unasyn) Amoxicillin/clavulanic acid (Augmentin) Ticarcillin/clavulanic acid (Timentin) Piperacillin/tazobactam (Zosyn)

Chapter 84: 

Chapter 84 Drugs That Weaken the Bacterial Cell Wall II: Cephalosporins, Carbapenems, Vancomycin, Aztreonam, Teicoplanin and Fosfomycin

Cephalosporins: 

Cephalosporins Most widely used group of antibiotics Beta-lactam antibiotics Similar to penicillin structure Bactericidal Usually given parenterally Toxicity is low

Classification of Cephalosporins: 

Classification of Cephalosporins First generation Cefazolin ( Ancef ) Second generation Cefaclor ( Ceclor ) Third generation Cefoperazone ( Cefobid ) Fourth generation Cefepime ( Maxipime )

Cephalosporins: 

Cephalosporins Drug interactions Probenecid Alcohol Drugs that promote bleeding Calcium and ceftriaxone Adverse effects Allergy Bleeding Thrombophlebitis

Cephalosporins: 

Cephalosporins Therapeutic uses 19 cephalosporins currently used in U.S. First and second generation – rarely used for active infections Third generation Preferred therapy for several infections Highly active against gram-negative organisms Able to penetrate to CSF Fourth generation – yet to be established

Carbapenems: 

Carbapenems Beta-lactam antibiotics have an extremely broad antimicrobial spectrum with low toxicity Not active against MRSA Imipenem (Primaxin) Meropenem (Merrem IV) Ertapenem (Invanz) Doripenem (Doribax)

Vancomycin (Vancocin, Vancoled): 

Vancomycin (Vancocin, Vancoled) Action Inhibits cell wall synthesis Uses Severe infections only Methicillin-resistant Staphylococcus aureus or Staphylococcus epidermidis Oral dose used for Clostridium difficile if metronidazole was tried and found ineffective

Vancomycin (Vancocin, Vancoled): 

Vancomycin (Vancocin, Vancoled) Adverse effects Ototoxicity (reversible or permanent) Red man syndrome Thrombophlebitis (common) Thrombocytopenia (rare) Allergy