Antimicrobials 2023 Narrated.pdf

Antimicrobials BETH QUAAS, DNP, APRN, CRNA Bacteria vs. Virus Bacteria Virus Single-cell living organism Genetic material surrounded by Larger protein coat Reproduce on own Smaller Antibiotics be...

Antimicrobials BETH QUAAS, DNP, APRN, CRNA Bacteria vs. Virus Bacteria Virus Single-cell living organism Genetic material surrounded by Larger protein coat Reproduce on own Smaller Antibiotics beneficial Use DNA of host to replicate Kills infected host cell and sets virus particles free Antibiotics NOT beneficial Vaccines reduce risk of becoming infected Benefits of Bacteria Breakdown Attack pathogens Release nitrogen Cyanobacteria nutrients into that would when they die produce O2 – Yay! substances the otherwise make us which is needed by body can use sick plants Fermentation to Breakdown of Mesophilic bacteria form some foods waste and Needed to make cause most human (cheese, yogurt, production of antibiotics infections and beer) chemicals thrive at 370 What doesn’t kill us makes us stronger Transformation of Use of antibiotics bacteria cause them to speeds up the process become more resistant of transformation to antibiotics Prevention is key: Warnings about the prescribing of Hand hygiene antibiotics have Clean food and water Vaccination decreased their use Safe sex and condom use Bacterial Cell Structure Bacterial cell Antibiotics Outer layers Osmotic Effect walls are rigid destroy cell wall no cholesterol 1 or 2? inside cell is ECF rushes in as in human Gram negative hyperosmotic and the cell cells has second draws water in explodes no elasticity outer bilayer no nucleus Types of Bacteria Spherical Cocci Can be either gram positive or negative Spherical shape Common examples: Gram positive Streptococcus Staphylococcus Gram negative N. gonorrhea N. meningitis Types of Bacteria Spiral Vibria, Spirillum, Spirochete Lyme disease, syphilis Types of Bacteria Rod-shaped Bacilli Gram positive, over time can become gram negative Gram positive Clostridium, Listeria Gram negative: E. coli, pseudomonas, Klebsiella Gram Stain Apply crystal violet to bacteria on slide – attaches to cell wall Gram positive: retain stain - appear purple Gram negative – lose stain after solvent applied - appear red Determines coverage needs for antibiotic choice Gram Positive vs. Gram Negative Bacterial Cell Membrane Gram Positive Bacteria Thick peptidoglycan outer layer NAG – N-glucosamine NAM - N-acetylmuramic acid Release exotoxins when cell wall is weakened and cell bursts DNA inside bacterial cells can move into intact cells and mutate to cause resistance Gram Positive Bacteria Cocci Bacilli Branched Filament Staphalococci Mycobacterium Actinomycetes Streptococci Corynebacterium Nocardi Pneumococci Clostridium enterococci Listeria Gram Negative Bacteria Thin peptidoglycan layer surrounded by phospholipid bilayer, outside lipopolysaccharides More difficult to kill because of second lipid bilayer Release endotoxins – body responds by engaging immune response Gram Negative Bacteria Gram Negative Bacteria Cocci Bacilli Spiral Gonococci E. Coli Treponemia Meningococci Klebsiella (Nisseria) Salmonella Shigella Proteus Pseudomonas Surgical Site Infections (SSI) Occur in up to 2-4% of surgical patients, 20% of HAI’s Directly related to surgery Nosocomial 3% mortality rate CMS requires reporting of SSIs – publicly disseminated Cost of SSI ˃ $1 billion 0-30 days postop or 90 days post prosthetic implant Incisional: staphylococcus aureus and staphylococcus epidermis Deep Tissue: gram negative rods and enterococci  CDC Surgical Wound Classification Clean Skin flora No signs of infection, respiratory, GI/GU not encountered Examples: diagnostic laparoscopy, CTR, etc. Clean-contaminated Examples: Abdominal, colorectal without leak, some GYN, lap chole, etc. Contaminated Open, accidental wounds, break in sterile technique Examples: some GYN and colon procedures Dirty/Infected Infected wounds Example: ruptured appy Risk Factors for Surgical Site Infection (SSI) Extremes of age Poor Nutritional Status Obesity Diabetes Perioperative Glycemic Control PVD Tobacco Use – “teachable moment” any cessation will be beneficial Risk Factors for SSI con’t. Coexistent Infections Altered Immune Response Corticosteroid Therapy (not single dose for PONV) Preoperative Skin Prep (surgical scrub and hair removal) Length of Preoperative Hospitalization Surgical Technique and Duration of Procedure Facility CSP and OR Cleaning Process Risk Factors That Anesthesia Can Control SCIP measures (Surgical Care Improvement Project) Perioperative Glucose Control Beta Blocker Use Patient Temperature Preop warming was associated with a 64% decrease in SSI Control OR temp Use of warming devices (Preop, OR and PACU) Keep patient covered Hand Hygiene!!! Spot the touch points!  Glucose Control Hyperglycemia can increase the risk of SSI Preop HbA1C ˃ 7-8% R/T increased wound complications Monitor Monitor blood glucose Perioperative Treat Glucose Control Insulin as needed to maintain glucose less than 200 mg/dl IV route best in periop, sq not reliable if hypothermic, vasoconstricted, etc Not always necessary for minor procedures Maintain Maintain control Keep blood glucose below 200 mg/dl some sources say between 140-180 mg/dl (CT, colorectal) Effects of Stress on Glucose Control  Administration and Timing of Antibiotics Follow Surgeon’s orders (culture 1st?) Start IV antibiotics on time (dependent on incision) Antibiotic Best practice within 30-60 minutes of incision (or tourniquet) Vancomycin may need up to 120 minutes Administration Question patient about allergies prior to antibiotic May change surgeon’s preference if reactions are not as severe as stated May need to re-dose for long cases More effective if source of infection is removed Foreign body, infected artificial prosthesis, obstructed infectious cavity Bactericidal vs. Bacteriostatic Bactericidal Concentration-dependent killing Time-dependent killing Bacteriostatic Both efficacious in the destruction of infection Dependent on: Concentration of drug Reduction in bacterial density at a given dose Length of time to reach a decrease in bacterial density Allergy Review Anaphylaxis or adverse drug reaction? Allergic Reactions Anaphylaxis An antigen binds to an IgE antibody Do not give 1st generation cephalosporins if PCN allergy and pt. reports anaphylactic symptoms – SOB, swelling, CV collapse, ? hives Ask surgeon to order different antibiotic Adverse Drug Reaction Numerous reactions and side effects Question patient about previous symptoms regarding antibiotic allergy  Respiratory CV Skin Bronchospasm – Hypotension Flushing ↓ ETCO2 and Tachycardia Urticaria SaO2, ↑ PIP Arrhythmia Erythema / Cardiac arrest Stevens-Johnson Syndrome Anaphylaxis Presentation  Discontinue suspected agent ABCs Epi: 5-10 mcg for hypotension; 0.1-1.0 mg for CV collapse Intraop Hydration Anaphylaxis H1 antagonist: diphenhydramine 0.5 – 1.0 mg/kg IV Treatment H2 antagonist: ranitidine 50 mg IV or famotidine 20 mg IV Hydrocortisone 250 mg IV Albuterol Inhaler Vasopressin if needed to support BP Antibiotic Allergies Preop Question - What happens when you take X drug? Cross reactivity is low between 1st generation cephalosporins and penicillins -.0001 -.1% IgE mediated response to antibiotics is usually 30-60 minutes What antibiotic’s adverse effects can mimic anaphylaxis? Vancomycin  Comorbidities – renal/liver disease, immunosuppression, etc. Prior allergy or adverse drug effects Impaired elimination or detoxification Choice of Patient age Antibiotic Pregnancy Status Exposure to microbes – travel, family exposure, occupational exposure, etc.) Procedure type and contamination level (clean vs. contaminated)  Administered in 1910 to treat syphilis - Salvarsan 1st Antibiotic Paul Ehrlich was first scientist to detect bacteria by staining  Beta-lactams Time-dependent killing – exposure to minimum inhibitory concentration of target organism Antimicrobial Fluoroquinolines Effects on Concentration-dependent killing – must have high enough concentration of drug to overcome target organism Bacteria Vancomycin Works using both time- and concentration-dependent killing of target organisms Penicillin Structure  A thiazolidine ring connected to a Beta-lactam ring MOA – inhibit cell wall synthesis (transpeptidation reaction) Preop treatment for patients with congenital heart Penicillin disease or implants (TKA, THA, heart valves, etc.) Transient bacteremia seen with dental and surgical procedures Drug of choice for treatment of this group of infections: Pneumococcal Streptococcal Meningococcal  PCN Mechanism of Action Peptidoglycan consists of complex mesh of alternating amino sugars, NAM and NAG Penicillin Binding Protein (PBP) enzyme inhibits the interlinking of NAM and NAG Weakens cell wall  Penicillins Cephalosporins Beta-lactam antimicrobials that inhibit cell wall synthesis Carbapenems Monobactams Beta lactam MOA NAM and NAG are components of peptidoglycan “mesh” layer of bacteria Beta lactam antibiotics bind to PBP and interfere with transpeptidase cross-linking of NAM and NAG Inhibits cell wall synthesis Weakens bacterial cell wall and allows ECF to rush into hyperosmotic cytoplasm Bacterial cell explodes 1st Generation Penicillins Gram negative and positive Pen G, nafcillin, methicillin Pen G unable to cross inner cytoplasmic bilayer in gram negative cells destroys gram positive only Rapidly excreted by kidneys (except nafcillin) – 90% tubular secretion Caution in renal disease with low urine output Penicillin Formulations Pen G Susceptible to Beta-lactamases 10 million units = 16 mEq of K+ Caution in patients with renal disease (nephrotoxic), hyperkalemia Nafcillin Resistant to Beta-lactamases Absorption unpredictable – not used orally Highly protein bound Mostly cleared by biliary excretion – no dose adjustment needed in renal disease 2nd Generation Penicillins Ampicillin and amoxicillin Bacteriocidal against gram positive and negative Amoxicillin Absorbed better from GI tract than ampicillin Longer acting than ampicillin Ampicillin High renal excretion Highest incidence of rash (usually due to commercial prep, not allergy) 3rd Generation Penicillins Carbenicillin Must be given IV, Probenecid can Useful for organisms resistant to ampicillin not absorbed by GI increase plasma [C] tract by 50% Interferes with High sodium platelet aggregation content – caution in Bleeding time increased CHF patients Platelet count normal 4th Generation Penicillins Broadest Lower sodium Piperacillin spectrum of content than all PCNs carbenicillin  Used to treat gout Sulfonamide derivative Probenecid with Inhibits the renal tubular excretion of penicillins Penicillins Sometimes paired with penicillins to increase plasma levels Can also inhibit other drugs: Acetaminophen, lorazepam, ketoprofen, naproxen and rifampin Cephalosporin Structure Cephalosporins Cross reactivity with MOA- Inhibit Inhibited by Gram negative and PCN due to shared bacterial cell wall cephalosporinases positive beta-lactam ring synthesis (beta-lactamases) (rare) Inexpensive – CV, May see a positive Anaphylaxis reaction Can cause ortho, biliary, pelvic, Coombs’ test, but very low -.02% thrombophlebitis intraabdominal rarely see hemolysis procedures 1st Generation Cephalosporins Cefazolin (Ancef) Most widely used antibiotic in surgery Dose: Adult: 1-2 gm IV 50-120 kg; 3 gm IV if ˃ 120 kg Ped: 15-30 mg/kg IV Re-dose after 3-4 hours or significant blood loss (1500 cc Max dose: 6 gm in 24 hours Cephalexin (Keflex) Oral Do not use cefazolin if allergy to cephalexin  Cefuroxime (Ceftin) Effective in the treatment of meningitis – crosses into CSF Effective against H. influenzae 2nd Generation Cephalosporins Cefoxitin Resistant to cephalosporinases produced by gram negative bacteria Useful as treatment in gram negative bacterial infections  Cefotaxime (Claforin) and ceftriaxone (Rocephin) Enhanced resistance to B-lactamases 3rd Generation E. coli, Klebsiella, Proteus and H. influenzae Cephalosporins Can move into CSF and treat meningitis Ceftriaxone has the longest elimination ½ time of 3rd generations Highly effective against Neisseria and Haemophilus  Carbapenems Ertapenem, imipenem, meropenem High levels of imipenem can cause seizures (renal failure) Resistant to beta-lactamases produced by Enterobacter infections Other Beta- Excreted by kidneys -↓ dose in renal failure lactams Aztreonam Monocyclic beta-lactam ring Penetrates the CSF If allergy to PCN, this drug is well suited for pneumonia, meningitis and sepsis from gram negative bacteria Disadvantage – cause enterococcal superinfections Expensive Beta-lactamases Bacteria can produce beta-lactamases that can inactivate some beta-lactam antibiotics Hydrolyzes the beta-lactam ring faster than the drug can enter the cell There are hundreds of beta-lactamases Most common mechanism of resistance of the beta-lactam antibiotics Antibiotics with Beta-lactam Ring Beta-Lactamase Inhibitors Sulbactam, tazobactam and clavulanic acid Bind irreversibly to B-lactamase enzymes Inactivates these enzymes so that beta-lactam antibiotics can fight bacteria Extends the activity of the PCNs they are mixed with Combined with beta-lactam antibiotics in both oral and IV drugs  Gram negative coverage Synergistic effect when used in combination with other antimicrobials Gentamicin, streptomycin (limited use today), amikacin, neomycin Aminoglycosides Amikacin should not be used with PCNs – may antagonize PCN against enterococcus faecalis Neomycin – topical and oral, does not undergo systemic absorption Useful orally to decrease bacterial flora prior to GI surgery Extremely nephrotoxic, not given IV May prolong NMB Protein Synthesis Inhibitor MOA Aminoglycosides inhibit protein synthesis Irreversibly inhibits protein synthesis MALT: macrolides, aminoglycosides, licosamides, tetracyclines https://www.youtube.com/watch?v=INDIL9oms4g  Renal disease can increase elimination ½ time 20-40 fold Ototoxicity accentuated with furosemide and mannitol Nephrotoxicity Aminoglycosides Can cause renal tubular necrosis – usually reversible when Con’t. discontinued Skeletal muscle weakness Aminoglycosides can decrease the prejunctional release and sensitivity to ACh at the postsynaptic junction Calcium administration can decrease this effect Use with caution in patients with myasthenia gravis Can potentiate NMB Gentamycin Penetrates pleural, ascitic and synovial fluids when inflamed Plasma levels should be monitored to guide dosage Side effects run parallel with plasma [C] – decrease dose with renal disease Ototoxicity may present as nystagmus, vertigo, nausea, tinnitus, pressure in the ears Deafness can develop suddenly Glycopeptides Vancomycin MOA – inhibit cell wall synthesis Gram positive bacteria Treatment of choice for MRSA Severe staphylococcal infections Streptococcal or enterococcal endocarditis (if PCN or cephalosporin allergy) Used to treat C. difficile (oral and IV preparations can be used)  Dose – 10-15 mg/kg IV over 60-120 minutes Usually dosed every 12 Excreted by kidneys, 90% (reduce with renal hours unchanged in urine disease) Lab monitoring to Dose should be prevent ototoxicity and May potentiate completed prior to TQ or nephrotoxicity (especially succinylcholine NMB incision (realistic ?) if also receiving aminoglycosides) Vancomycin Vancomycin Con’t. Rapid infusion can lead Massive histamine Arterial hypoxemia to “Red Man Syndrome” release Unexpected decrease If flushing (or other Hypotension in SpO2 symptoms) occurs, Facial and truncal Drug-induced decrease rate flushing ventilation/perfusion Cardiac Arrest mismatch May treat 1 hour preop with diphenhydramine (1mg/kg) or cimetidine (4mg/kg) Oxazolidinones Linezolid Inhibits bacterial protein synthesis by binding to 50S ribosomal unit Similar coverage as vancomycin 100% bioavailable – oral use Less incidence of Red Man syndrome than vanco Short term effects: nausea and hypoglycemia Long term effects: bone marrow suppression, peripheral and ocular neuropathy, serotonin syndrome if used with SSRIs Macrolides Erythromycin and azithromycin (Z-pack) Gram positive bacteria – strep, staph, H. influenzae, chlamydia Azithromycin Long ½ time – active 4-7 days after last dose Oral dosing – once/day for 5 days Macrolides Con’t. Erythromycin Advantage: useful if not able to take PCN or cephalosporins Disadvantages: GI upset (severe N/V), thrombophlebitis and tinnitus if IV form used, prolonged QT (torsades) Metabolized by CYP3A4 and CYP1A2 – may see increased levels if used with ketoconazole (inhibits CYP3A4) increased ventricular irritability with increased concentrations P450 enzyme inhibitor – can prolong metabolism of drugs that concurrently use this system for metabolism Lincosamides Clindamycin and lincomycin Inhibit protein synthesis of the 50S ribosomal subunit Metabolized to inactive compounds Decrease dose in severe liver disease Clindamycin Similar to erythromycin but covers more anaerobes Skeletal muscle weakness – prejunctional and postjunctional effects on NMJ Large doses can cause significant and prolonged NMB Not readily antagonized by calcium and anticholinesterase drugs Disadvantages – toxic, use only if other agents have failed causes severe pseudomembranous colitis discontinue use if patient has significant diarrhea Fluoroquinolones MOA – inhibits DNA synthesis of Gram negative and Effective for treatment of topoisomerase II and IV – Excreted by kidneys positive GI and GU infections bacteria unable to replicate Side effects – peripheral Not for routine use in FDA warning that this class neuropathy, psychosis, N/V, patients under 18 – has diarrhea, dizziness, insomnia, of drugs should be used if increased risk of tendonitis been shown to damage there are no alternatives and tendon rupture, muscle cartilage and cause weakness in MG arthropathy Fluoroquinolones Con’t. Ciprofloxacin Levofloxacin Moxifloxacin useful for many Used in GU Use only if no other systemic infections procedures options available Treatment of choice Side effects: for anthrax peripheral exposure neuropathy, SIADH, Can be used to treat liver failure, QT TB prolongation, psychotic reactions Antimycobacterials Used to treat tuberculosis Isoniazid CYP2D6 enzyme inhibitor Can cause drug-induced lupus and hepatitis CNS toxicity can be seen Rifampin CYP3A4 enzyme inducer (and others) – methadone, anticoagulants, anticonvulsants, benzodiazepines Harmless orange color to urine, sweat and tears Adverse effects – rash, thrombocytopenia, nephritis Teratogenicity Nitroimidazole Antimicrobials Dose: 500 mg – 1 gm IV Anaerobic gram (30 mg/kg/d) Metronidazole - negative bacilli and can also be used orally inhibits bacterial DNA Clostridium May be used to treat Useful for colorectal, non-severe C. diff, if Metabolized in liver, GYN and ENT vanco unavailable or excreted in urine procedures combined with vanco to treat severe cases Metronidazole Con’t. Side effects – dry mouth, headache, metallic taste and nausea Rare adverse effects: pancreatitis, CNS effects (ataxia, encephalopathy, seizures) Drug Interactions: Potentiates coumadin-like anticoagulants Phenytoin and phenobarbital accelerate clearance Cimetidine may prolong clearance May increase risk of Lithium toxicity EtOH may cause adverse reaction Metronidazole (Flagyl) Do Not Mix with EtOH ◦ Metronidazole inhibits the enzyme that breaks down alcohol ◦ Similar to disulfiram (Antabuse) ◦ N/V, hypotension, tachycardia, headaches, flushing  Prevents bacterial protein synthesis by binding to 30s ribosomal subunit Doxycycline – not renally excreted Tetracyclines Adverse effects - N/V, diarrhea, photosensitive Avoid in pregnancy – cross placenta Liver and renal toxic Fetus can develop tooth discoloration, dysplasia and impaired bone growth Sulfonamides Gram negative and positive MOA – Inhibits folate synthesis in bacterial cells sulFOnamide = FOlate Often combined with trimethoprim or pyrimethamine Synergistic effect in inhibition of folate synthesis Metabolized in liver and excreted in urine Adverse reactions: fever, rash, S-J syndrome, N/V, diarrhea, photosensitivity, hematopoietic disturbances May precipitate in acid pH urine Sulfonamides Con’t. sulfamethoxazole/trimethoprim Clinical uses: GU, respiratory Increasing resistance to E. coli Trimethoprim inhibits creatinine secretion without effecting GFR – distinguish from sulfonamide nephrotoxicity silver sulfadiazine Used on burns – prevention of infection May slow wound healing Sulfa containing drugs: diuretics, diazoxide, sulfonylurea hypoglycemic agents Low risk of cross-sensitivity with allergic reactions Dosing Guidelines Special Considerations Pregnancy Teratogenic in early pregnancy Decreased antibiotic plasma levels Most antibiotics cross through the placenta and breast milk Immature liver function in fetus Elderly Physiologic changes with age can affect dosages Aminoglycosides and vancomycin may require altered doses Dosing Adjustments in Renal and Hepatic Impairment (Katzung, 2021)  aminoglycosides polymyxin B (irrigant) clindamycin Antibiotics affecting NMB lincomycin vancomycin Treatment: sugammadex, calcium IV, mixed reviews on neostigmine Drug Interactions with Antimicrobials Methotrexate Accumulation seen with penicillins, except amoxicillin Allopurinol Hypersensitivity syndrome with amoxicillin – usually seen with renal impairment Warfarin Potentiated by macrolides, metronidazole, trimethoprim-sulfa, ciprofloxacin Fluoroquinolones Ca++, Fe++, and Mg++ and carafate, decrease absorption, thereby concentration phenytoin and phenobarbital – P450 enzyme inducers Methicillin Resistant Staph. Aureus MRSA Preop screening – identify high-risk patients Mupirocin ointment eliminates colonization Can be applied a few days preop in high-risk or positive patients 1st line treatment: vancomycin Skin Preparations Chlorhexadine Chlorhexadine gluconate and 70% alcohol (Chloraprep) Disrupts bacterial cell membranes Destroys both gram positive and negative Reduces cutaneous skin flora Rapid acting Poor absorption Iodine Kills bacteria, viruses and spores Skin burns may occur in solutions above 7% Skin Preparations Con’t. Iodophors Povidone-iodine (Betadine) – least irritating for corneal prep Iodophor with alcohol (DuraPrep) Alcohols 70% ethyl alcohol kills 90% of skin flora Isopropyl alcohol - more bactericidal than ethyl alcohol Does not kill fungi or viruses Fire risk – must be completely dry prior to draping, avoid pooling Common Gram Positive and Negative Bacteria References Flood, P., Rathmell, J., Shafer, S. (2022) Stoelting’s Pharmacology and Physiology in Anesthetic Practice (6th ed.). Wolters Kluwer. Katzung, B., Vanderah, T. (2021). Basic and Clinical Pharmacology (15th ed.). McGraw Hill. th Barash, P., et.al. (2017). Clinical Anesthesia (8 ed.). Elsevier. Duggan, E., Carlson, K., Umpierrez, G: Perioperative hyperglycemia management: An update. Anesthesiology 2017; 126(3): 547-560 Surgical site infections. https://psnet.ahrq.gov/primer/surgical-site-infections What are bacteria and what do they do? https://www.medicalnewstoday.com/articles/157973?c=686732629097 Wald-Dickler, N., Holtom, P., Spellberg, B. (2018). Busting the myth of “Static vs Cidal”: A systemic literature review. Clinical Infectious Disease. 66(9), 1470-1474