Rational Use of Antibiotics

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Published on December 22, 2008

Author: nsal

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Rational Use of Antibiotics in the Shelter & Spay/Neuter Clinic : Rational Use of Antibiotics in the Shelter & Spay/Neuter Clinic Dr. Stephanie Janeczko October 18, 2008 Summary & Overview : Summary & Overview Importance of appropriate use Basic principles of pharmacokinetics & pharmacodynamics Types of antibiotics Drug selection Avoiding inappropriate use to minimize resistance Case examples of appropriate therapy Using antibiotics the right way : Using antibiotics the right way Most commonly prescribed Most commonly misused Treatment failure Increased cost Prolonged holding times Poor reputation Development of antimicrobial resistance Using antibiotics the right way : Using antibiotics the right way Adverse effects do occur Lack of overt problems or complications does not mean they don’t happen! In our patients In the population Using antibiotics the right way : Using antibiotics the right way Adverse effects do occur Lack of overt problems or complications does not mean they don’t happen! In our patients In the population Slide 6: “It can’t hurt and it might help” should not be the reason you are prescribing antibiotics! The Basic Concepts : The Basic Concepts Pharmacokinetics what the body does to a drug Pharmacodynamics what the drug does to a body Cmax - Maximum Plasma Drug Concentration MIC - Minimum Inhibitory Concentration AUC - Area Under the Curve Minimum Inhibitory Concentration : Minimum Inhibitory Concentration Determined by serial tube dilutions - lowest concentration of drug that prevents visible growth of an isolate More Important Concepts : More Important Concepts MIC is specific to that particular bacterial isolate and that particular drug Cmax or some multiple thereof must be maintained at or above the MIC for some portion of the day Some drugs also have a post-antibiotic effect Categorizing Antibiotics : Categorizing Antibiotics Time-dependent antibiotics – beta lactams, macrolides, lincosamides Most important parameter: t > MIC Maintain drug concentration above MIC most of the time Concentration-dependent antibiotics – fluoroquinolones, aminoglycosides, metronidazole Most important parameter: Cmax:MIC ratio or AUC:MIC ratio Achieve higher plasma drug concentrations Categorize based on PK/PD parameters rather than bacteriostatic and bactericidal classifications: Categorizing Antibiotics : Categorizing Antibiotics Time-dependent antibiotics – beta lactams, macrolides, lincosamides Most important parameter: t > MIC Maintain drug concentration above MIC most of the time Concentration-dependent antibiotics – fluoroquinolones, aminoglycosides, metronidazole Most important parameter: Cmax:MIC ratio or AUC:MIC ratio Achieve higher plasma drug concentrations Categorize based on PK/PD parameters rather than bacteriostatic and bactericidal classifications: Antibiotic Selection : Antibiotic Selection First things first! Is there an indication for antibiotic therapy in this patient? Delay appropriate treatment Waste of resources Development of resistance Antibiotic Selection : Antibiotic Selection Yes we need antibiotics. Now where is the infection? Make an educated guess on type of bacteria present May influence drug selection Prostate, eye, CNS May influence duration of treatment Guides sample collection Antibiotic Selection : Antibiotic Selection I know where the infection is! What bacteria are most likely to be found in that location? Sample collection for culture & sensitivity or cytologic evaluation Antibiotic Selection : Antibiotic Selection I know what bacteria are likely to be causing the problem. What antibiotics are most likely to be effective against this bacteria? Based on historical sensitivity data Becoming less and less reliable Any factors that might affect this? Previous antibiotic therapy DO NOT play antibiotic roulette! Volume of distribution, local factors Antibiotic Selection : Antibiotic Selection By what route do I want to give this antibiotic? What dose and for how long? Dictated by patient & drug Compliance, convenience, cost Some guesswork involved Any factors that might affect this? Acute vs. chronic infections Immunosuppression Culture & Sensitivity Testing : Culture & Sensitivity Testing Ideal for guiding appropriate therapy Better for picking which drugs NOT to use BUT – of limited practicality Expense Turnaround time Inherent limitations Isolated organisms In vitro results Consider for: Particularly unusual case Treatment failures Population-level problems Interpreting Sensitivity Results : Interpreting Sensitivity Results Compare MIC of that isolate to breakpoint MIC for that drug Breakpoint MIC = highest drug concentration likely to be achieved in a patient with recommended dosing Using Sensitivity Results : Using Sensitivity Results One drug may be considered representative of that category Not necessarily true! In general - avoid drugs with resistant or intermediate designations More likely to promote resistance More likely to have treatment failures Exceptions exist Using Sensitivity Results : Using Sensitivity Results Select drugs designated as susceptible. Consider: MIC furthest away from the breakpoint MIC Narrow-spectrum Compliance with dosing regimen Ability to give multiple doses a day Safety of higher doses Margin of safety Cost effective Cytologic evaluation : Cytologic evaluation Don’t underestimate the value of cytology! Morphology Gram stain Type of inflammatory cells Empiric selection of antibiotics : Empiric selection of antibiotics Selection of an antibiotic without identifying the causative organism & its susceptibility pattern Essentially playing the odds using your best guesses Most likely pathogens Historical susceptibilities Works better in some cases than others Empiric selection of antibiotics : Empiric selection of antibiotics TARGET - The Antimicrobial Reference Guide to Effective Treatment, 3rd Edition by David Aucoin Makes selecting the appropriate antimicrobial and dose for the most probable pathogen at each location a simpler process Ranks the efficacy of 24 antimicrobials against 13 of the most common pathogens Select the most cost-effective antimicrobial and dosage for maximum efficacy Formulary section Prophylactic Antibiotics for Surgery : Prophylactic Antibiotics for Surgery Routine spays & neuters Other procedures Antibiotics will not make up for poor surgical technique! Prophylactic Antibiotics for Surgery : Prophylactic Antibiotics for Surgery Prevent bacterial infection as a result of potential contamination If they will be effective, they must be: effective against the likely contaminants present at the site at the time of contamination Some degree of contamination is likely but infection is unlikely Degree of contamination Virulence of the bacteria Strength of host defenses Tissue health and integrity Prophylactic Antibiotics for Surgery : Prophylactic Antibiotics for Surgery Post-op infection risk factors: Prolonged duration of surgery/anesthesia Traumatic tissue handling Lack of aseptic technique, dirty surgical field Multiple people in sx suite Some indications: Prolonged sx times > 90 min Prosthesis Severely infected or traumatized tissues Prophylactic Antibiotics for Surgery : Prophylactic Antibiotics for Surgery Neither needed nor recommended for routine spays and neuters Minimal chance of contamination Short duration Excellent surgeons! Therapeutic antibiotics for surgical cases A different story altogether! Slide 31: Prophylactic antibiotics will not make up for poor surgical technique. They are not a substitute for aseptic technique, gentle tissue handling, and short anesthetic and surgical times. Antimicrobial Resistance : Antimicrobial Resistance Biggest unseen problem relating to antibiotic usage Both human and animal health Eventually impacts individual patient care Take appropriate steps to minimize development of resistance Antimicrobial Resistance : Antimicrobial Resistance Biggest unseen problem relating to antibiotic usage Both human and animal health Eventually impacts individual patient care Take appropriate steps to minimize development of resistance Antimicrobial Resistance : Antimicrobial Resistance Key point: selection pressure for resistant organisms to survive and replicate Risk factors for resistance – previous antibiotic treatment Inappropriately low dose Prolonged period of time Inherent vs. Acquired Mycoplasma & beta lactams MDR Salmonella spp. Acquired Resistance : Acquired Resistance Bacteria have different mechanisms Enzymes to destroy the drug Efflux pumps Modification of target site Change in porin size or number Development of Resistance : Development of Resistance Common to have >1 type of resistance Can be transmitted rapidly Many mechanisms not specific to drug class May lead to development of MDR strains of numerous species GI normal flora Development of Resistance : Development of Resistance Chromosomal mutations “First-step” mutations usually cause low-level resistance Multiple mutations can cause greater resistance Bacteria may get a competitive advantage Plasmid transmission Extrachromosomal pieces of DNA Occurs within & across species Requires only a single event – rapid and complete Avoiding Resistance : Avoiding Resistance Only use antibiotics when a bacterial infection exists! Choose as narrow-spectrum a drug as possible Select a dose the will ensure adequate drug concentrations at the site of infection High enough to prevent “first-step” mutations Maintain t > MIC at 70% or greater Cmax:MIC ratio > 8-10, AUC:MIC ratio 125-250 Don’t play antibiotic roulette! : Don’t play antibiotic roulette! Lulu – 10mo F/S DSH presented for chronic URI Treated by the shelter with multiple rounds of antibiotics: Clavamox Doxycycline Clavamox Clindamycin Baytril Azithromycin Deep nasal swab C&S: multi-drug resistant Pseudomonas aeruginosa Slide 40: Treat the infection right the first time – the right drug, at the right dose, for the right amount of time. Dead bugs don’t mutate! Optimizing Antibiotic Therapy : Optimizing Antibiotic Therapy Give an appropriate dose that will kill the bacteria and minimize the development of resistance t > MIC for at least 60-70% of the dosing interval More frequent dosing +/- higher doses to add a half-life Cmax:MIC of 8-10 or a AUC:MIC > 100-125 Higher doses +/- more frequent doses to increase AUC Optimizing Antibiotic Therapy : Optimizing Antibiotic Therapy Bacteriostatic vs. bactericidal levels Oral vs. parenteral administration Remember – need adequate drug concentrations at the site of infection Capillary tight junctions Poor blood supply Intracellular infections Inflammatory cells and debris Optimizing Antibiotic Therapy : Optimizing Antibiotic Therapy Hemodynamic changes Dehydration, shock, fluid therapy Renal or hepatic disease Age? Older – may have a higher percentage of body fat Neonates - higher percentage of body water, decreased drug protein binding Optimizing Antibiotic Therapy : Optimizing Antibiotic Therapy Consider combination therapy Improve the spectrum of activity Helpful or even necessary with polymicrobial infections Shorter duration of treatment may be possible Reduced risk of adverse drug reactions Synergistic combinations – drugs work on different targets or through sequential pathways Beta lactam & fluoroquinolone Beta lactam & aminoglycoside Avoid antagonist combinations Chloramphenicol & erythromycin Tetracycline & fluoroquinolones Optimizing Antibiotic Therapy : Optimizing Antibiotic Therapy Remember: antibiotic + patient ? cure if you don’t take all the factors into consideration Host factors Drug factors Bacterial factors Case Example - Pyometra : Case Example - Pyometra “Roxanne” 6 year old intact female (overweight!) Rottweiler Case Example - Pyometra : Case Example - Pyometra Step 1 – Do I need an antibiotic? Step 2 – Where is the infection? Step 3 – What organisms are likely to be found in this location? E. Coli Occasionally other gram negatives, Streps, or Staph intermedius Case Example - Pyometra : Case Example - Pyometra Step 4 – What antibiotics are those organisms most likely to be sensitive to? Aminoglycosides, potentiated sulfas, fluoroquinolones, some beta lactams (better at higher doses) Case Example - Pyometra : Case Example - Pyometra Step 4 – What antibiotics are those organisms most likely to be sensitive to? Aminoglycosides, potentiated sulfas, fluoroquinolones, some beta lactams (better at higher doses) Step 5 – What route of administration and at what dose do I need to give this antibiotic? Oral administration for 14 days following surgery Clavamox at 30 mg/kg po BID Cephalexin at 30 mg/kg po TID TMS at 30 mg/kg po SID Enrofloxacin at 10mg/kg po SID Case Example - Pyoderma : Case Example - Pyoderma “Freckles” 5 month old intact female Pit mix Generalized demedicosis! Case Example - Pyoderma : Case Example - Pyoderma Step 1 – Do I need an antibiotic? Step 2 – Where is the infection? Step 3 – What organisms are likely to be found in this location? Superficial vs. deep pyoderma Staph intermedius, E. Coli, Proteus, Pseudomonas But if you wanted more information to convince yourself… Case Example - Pyoderma : Case Example - Pyoderma Step 4 – What antibiotics are those organisms most likely to be sensitive to? Gram positive cocci = Staph intermedius Cephalosporins, aminoglycosides, fluoroquinolones all excellent choices Cephalexin most practical – safe, cost-effective, narrow spectrum Case Example - Pyoderma : Case Example - Pyoderma Step 4 – What antibiotics are those organisms most likely to be sensitive to? Gram positive cocci = Staph intermedius Cephalosporins, aminoglycosides, fluoroquinolones all excellent choices Cephalexin most practical – safe, cost-effective, narrow spectrum Step 5 – What route of administration and at what dose do I need to give this antibiotic? Oral dosing should be sufficient, most convenient Cephalexin at 22mg/kg po BID for 1-2 weeks past clinical cure Case Example - URI : Case Example - URI “Calliope” 8mo F DSH Sneezing, nasal discharge Case Example - URI : Case Example - URI Step 1 – Do I need an antibiotic? Step 2 – Where is the infection? Step 3 – What organisms are likely to be found in this location? Good question! Primary viral infections Secondary bacterial infections Pseudomonas, Pasturella, Strep, Mycoplasma spp. Case Example - URI : Case Example - URI Step 4 – What antibiotics are those organisms most likely to be sensitive to? Really depends a lot on what bacteria is present Most common options include beta lactams, fluoroquinolones, doxycycline Step 5 – What route of administration and at what dose do I need to give this antibiotic? Doxycycline at 10mg/kg po BID for 10-14 days NEVER dry pill a cat with doxycycline ? esophageal strictures Final Summary : Final Summary Antibiotic use is not without consequence Antimicrobial resistance is real and will affect all of us Limit antibiotics for those cases that really need them Prophylactic use is not needed or recommended for routine S/N Think through the clinical case to decide on drugs and dosages – likely pathogens and historical sensitivities should guide empiric choices Slide 58: Any Questions? Slide 59: Dr. Stephanie Janeczko (607) 253-3857 sdj7@cornell.edu

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