Super Bugs and Wonder Drugs: Protecting the One While Respecting the Many Vicki Stringfellow, MSN, CPNP-AC/PC Werner Division of Pediatric Critical Care University of Kentucky Lexington, KY Disclosure Information I am a paid continuing education program associate for Pediatric Nursing Certification Board and the primary editor of continuing education modules. Please note: Antimicrobial therapy for the neonatal and immunocompromised patient populations is beyond the scope of this presentation. Objectives Identify antimicrobial agents used for prophylaxis against and treatment of selected infectious processes in the pediatric surgical patient and explain their mechanisms of action Describe antimicrobial resistance and relate the principles of antimicrobial stewardship to the pediatric surgical patient population Discuss current available guidelines related to the prevention and treatment of infection for specific surgical procedures 1
History Topical application of molded bread Ancient civilizations 1640 Lab work with molds 1870s - 1897 1928 Earliest penicillin treatment successes in humans 1930s- 1942 Mid 1940s -1960s Age of antibiotic resistance Present Treatment with mold in published work Alexander Fleming Widespread use of penicillin; Golden Age of antibiotic development; early acquired resistance Med Hist. 1986;30:42-56; Journal of Antimicrob Chemother. 2016;71:572-575; New York Times, 1999. Antibiotics Primary classes Penicillins Aminoglycosides Fluoroquinolones Cephalosporins Macrolides Tetracyclines Mechanisms of action Inhibition of cell wall synthesis Inhibition of protein synthesis Interference with cell membrane function Antimetabolite activities Inhibition of nucleic acid synthesis JNP. 2015:11(1):70-78. Resistance Intrinsic or acquired Mechanisms of resistance 1 Alteration of target binding sites or porin channels Efflux pumps and enzymes Most important contributor is antibiotic use 2 CDC reports: over 2 million illnesses and 23,000 deaths annually 2 1- JNP. 2015:11(1):70-78. 2- CDC: https://www.cdc.gov/drugresistance/about.html 2
# isolates Ampicillin Ceftriaxone Ceftaroline Meropenem Penicillin Clindamycin Linezolid Vancomycin 26th Annual Scientific Conference May 1-4, 2017 Hollywood, FL Susceptibility Reporting Minimum inhibitory concentration (MIC) The lowest concentration of an antibiotic that will inhibit growth of an organism in the laboratory Organism Method Amikacin susceptibility Ampicillin susceptibility Cefazolin susceptibility Cefepime susceptibility Klebsiella pneumoniae MIC (mcg/ml) < = 8 SUSCEPTIBLE > 16 RESISTANT < = 1 SUSCEPTIBLE < = 1 SUSCEPTIBLE Antibiograms Cumulative report of susceptibility and resistance Antibiotics (X Axis)/ Facility or Lab Identification Dates for Use of the Antibiogram Specific organisms (Y AXIS) Enterococcus faecalis 108 92 - - - 96 100 97 Oxacillin-resistant Staphylococcus 201 - - 100 0 87 97 100 aureus (MRSA) Oxacillin-sensitive Staphylococcus 171 - - - - - 95 100 100 aureus (MSSA) Staphylococcus epidermidis 81 - - - - - 50 100 100 Antibiotics for the Pediatric Surgical Patient Surgical site infection (SSI) 2% - 5% of inpatient surgeries 1 A 2013 review cited 1.8% for pediatric surgeries 2 Prophylaxis recommended for procedures with moderate or high infection rates, and when consequences of infection are likely to be serious 1 Factors associated with post-operative SSI 1 Number and virulence of microorganisms present; foreign matter in wound Host risk factors Surgical site; duration of procedure 1-2015 Red Book 2- Pediatrics 2013;132:e677-e688 3
Wound Classification and Prophylaxis Clean No inflammation, infection, or contamination; no entry into respiratory, alimentary or genitourinary tracts or oropharyngeal cavity Benefit of systemic antibiotic prophylaxis not justified unless risk for infection or consequences of infection is high Clean-contaminated Controlled entry into respiratory, alimentary or genitourinary tract Prophylaxis GI procedures when obstruction is present, child is receiving gastric acid suppression or has permanent foreign body; biliary tract obstruction Urinary tract procedures when bacteriuria or obstruction is present 2015 Red Book Wound Classification and Antibiotics Contaminated Previously sterile tissue with likely heavy bacterial contamination Prophylaxis for acute nonpurulent inflammation isolated within a viscus Empiric treatment if contamination has produced inflammation and infection Dirty and Infected Penetrating trauma over 4 hours, retained devitalized tissue, or existing infection or perforated viscera Empiric treatment 2015 Red Book Prophylaxis Recommendations Goals Prevent SSI and its related morbidity and mortality Reduce length of treatment and cost of care Result in no adverse effects Minimize adverse effects on microbial flora Recommendations address Indications Appropriate drug selection and dosage Preoperative timing and need for subsequent doses intraoperatively Duration of prophylaxis 2015 Red Book Med Lett Drugs Ther. 2016;58(1495):63-8. 4
Prophylaxis Recommendations Antimicrobial agent selected based on most likely pathogens and their susceptibilities, and safety and efficacy of the agent Dosage weight-based up to the usual adult dose Dose administered 60 minutes prior to surgical incision, or within 120 minutes for vancomycin or fluoroquinolones Subsequent doses administered if the procedure time exceeds two half-lives of the agent, or if there is excessive blood loss Prophylaxis continues 24 hours following the procedure 2015 Red Book Am J Health-Syst Pharm. 2013; 70:195-283 Agents: Cefazolin (Ancef) First generation cephalosporin, inhibits cell wall synthesis 1,2 Active against most staphylococci, streptococci, and enteric Gramnegative enterococci 1,2 Recommended for most procedures 1 Gastric, biliary tract, thoracic, vascular, neurosurgical, orthopedic, cardiac Traumatic wounds (excluding bites) Typical dose is 30 mg/kg (adult/maximum dose 2 grams) 1,2 Half life: neonates 3-5 hours; adult 1.5-2.5 hours; repeat doses at 4 hours 1,2 1-2015 Red Book 2- Lexicomp Pediatric & Neonatal Dosage Handbook, 2016 Agents: Vancomycin (Vancocin) Glycopeptide; inhibits cell wall synthesis 1,2 Routine use NOT recommended 1 Consider for 1 High risk of methicillin-resistant Staphylococcus aureus (MRSA) Children with known colonization or previous infection with MRSA High community rates of MRSA infection Dose 15 mg/kg; multiple dosing considerations 1,2 Half-life varies by age 2 ; repeat doses not given 1-2015 Red Book 2- Lexicomp Pediatric & Neonatal Dosage Handbook, 2016 5
Prophylaxis for Colorectal Procedures Coverage against enteric gram-negative bacilli, enterococci, and anaerobic organisms 2015 Red Book recommendations Cefoxitin Metronidazole plus gentamicin Cefazolin plus metronidazole Clindamycin plus gentamicin or ciprofloxacin 2016 Medical Letter and 2013 American Society of Hospital Pharmacists recommendations also include Ampicillin/sulbactam Ertapenem (Invanz) Agents for Colorectal Procedures Ampicillin/Sulbactam (Unasyn) Penicillin and beta lactamase inhibitor, interferes with cell wall synthesis 1 Active against Escherichia coli, Enterococcus faecalis, and Bacteroides fragilis 1 Typical dose 50mg/kg 1 (adult/maximum dose 3 grams) 2,3 Half-life mean 0.7-0.9 hours (1-12 years) 1 ; repeat dose at 2 hours 3 Metronidazole (Flagyl) Antibiotic and antiprotozoal, inhibits protein synthesis 1 Active against most obligate anaerobes, including Bacteroides, and Fusobacterium species 1 Typical dose 15 mg/kg 1 (adult/maximum dose 500 mg) 2,3 Half life 6-10 hours (child/ adolescent) 1 ; no repeat dose 3 1- Lexicomp Handbook, 2016 2- Med Lett Drugs Ther. 2016;58(1495):63-8 3- Am J Health-Syst Pharm. 2013; 70:195-283 Agents for Colorectal Procedures Cefoxitin (Mefoxin) Second generation cephalosporin, inhibits cell wall synthesis 1 Active against Escherichia coli and Bacteroides species 1 Typical dose 40mg/kg 1 (adult/maximum dose 2 grams) 2,3 Half-life infants 1.4 hours, adults 45-60 minutes 1 ; repeat dose at 2 hours 3 Clindamycin (Cleocin) Lincosamide, inhibits protein synthesis 1 Active against Clostridium perfringens, Peptostreptococcus and Fusobacterium species 1 Typical dose 10 mg/kg 1 (adult/maximum dose 900 mg) 2,3 Half life 2-3 hours 1 ; repeat dose at 6 hours 3 1- Lexicomp Handbook, 2016 2- Med Lett Drugs Ther. 2016;58(1495):63-8 3- Am J Health-Syst Pharm. 2013; 70:195-283 6
Prevention of Infective Endocarditis Congenital heart disease; selected orthopedic procedures; selected dental procedures 1 Coverage against skin flora, oral flora, GI/GU tract flora specific to procedure Regimens (parenteral) Ampicillin 50 mg/kg (adult dose 2 grams) 1 Cefazolin 30 mg/kg 1 / 50 mg/kg 2 (adult dose 1 gram) Ceftriaxone 50 mg/kg (adult dose 1 gram) 1 Clindamycin 20 mg/kg (adult dose 600 mg) 2 1-2015 Red Book 2- Circulation. 2007;116:1736-1754 Prophylaxis for Urinary Tract Procedures Recommended for urinary tract surgery or instrumentation in the presence of bacteriuria or obstructive uropathy Coverage for enteric Gram-negative bacilli and enterococci 2015 Red Book recommendations Ampicillin 50 mg/kg + gentamicin 2 mg/kg (or) Cefazolin 30 mg/kg 2016 Medical Letter and 2013 American Society of Hospital Pharmacists recommendations also include Ciprofloxacin or trimethoprim/sulfamethoxazole; Cefazolin for open or laparoscopic procedures Agents for Urinary Tract Procedures Gentamicin Aminoglycoside, interferes with protein synthesis 1 Wide gram-negative activity: Enterobacter, Klebsiella, Proteus species; Escherichia coli and Pseudomonas aeruginosa 1 Typical dose 2.5 mg/kg 1 (adult dose 5 mg/kg with weight specifications) 2,3 Half life decreases with age 1 ; no repeat dose 3 Ampicillin Penicillin, inhibits cell wall synthesis 1 Active against non-penicillinase producing strains of Escherichia coli, and Proteus mirabilis Typical dose 50mg/kg 1 (adult/maximum dose 3 grams) 2,3 Half-life 1-1.8 hours (children and adults) 1 ; repeat dose at 2 hours 3 1- Lexicomp Handbook, 2016 2- Med Lett Drugs Ther. 2016;58(1495):63-8 3- Am J Health-Syst Pharm. 2013; 70:195-283 7
Empiric Therapy for Appendicitis Appendicitis Provide coverage for enteric gram-negative bacilli, enterococci, and anaerobes (Bacteroides species) Agents Carbapenems: imipenem, meropenem or ertapenem Combination drugs: piperacillin-tazobactam or ticarcillin-clavulanate Cephalosporins: cefotaxime, ceftriaxone, ceftazidime, cefepime Severe beta-lactam allergy: ciprofloxacin plus metronidazole or an aminoglycoside-based regimen Clin Infect Dis. 2010;50(2):133-64 Empiric Therapy for Empyema Empyema Provide coverage for Streptococcus pneumoniae Agents Third-generation cephalosporins: ceftriaxone or cefotaxime Vancomycin or clindamycin in addition if characteristics of Staphylococcus aureus are present Duration of therapy related to adequacy of drainage; 2-4 weeks common, or approximately 10 days after resolution of fever Clin Infect Dis. 2011;53(7):e25-e76 Therapy for Clostridium difficile Disclaimer: AAP guideline on C. difficile in infants and children, which is referenced in the 2015 Red Book, was retired in late 2016. Clostridium difficile Discontinue precipitating antimicrobial agents For symptomatic children, antimicrobial therapy recommended Initial treatment, mild to moderate diarrhea and first relapse Metronidazole orally Severe disease Vancomyin enterally or as an enema (not effective IV) Metronidazole orally or IV may be used as well 2015 Red Book 8
Empiric Therapy for HAIs* *HAI Healthcare-associated infections Initial therapy always based on clinical factors Central line-associated bloodstream infection Provide coverage for skin flora and Gram-negatives 1 Initial therapy usually includes vancomyin paired with a second agent 2 Catheter-associated urinary tract infection Provide coverage for periurethral and perirectal flora 1 Initial therapy choices include extended spectrum penicillins or thirdgeneration cephalosporins 1- Infect Control Hosp Epidemiol. 2016;37(11):1288-1301 2- Pediatr Infect Dis J.2013;32(8): 905-910 Tips for New Prescribers Utilize references; a few examples include Drugs@FDA - https://www.accessdata.fda.gov/scripts/cder/daf/ FDA Pediatric Labeling Information Databasehttps://www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?sd=labelingdatabase Lexicomp Pediatric and Neonatal Dosage Handbook Prescribers Digital Reference http://www.pdr.net/home Monthly Prescribing Reference http://www.empr.com/ Be familiar with state rules and regulations and institutional credentialing Network! State professional organization as well as national organizations Institutional/ organizational committees Seek out and work with pharmacists and discharge planners Continuing Education Resources Always verify the credit offered is acceptable to your licensing or certifying body Sources and examples Conferences: APSNA, NAPNAP; state and local professional organizations Local universities with nursing programs Journals: Journal of Pediatric Surgical Nursing, Journal of Pediatric Health Care The Journal for Nurse Practitioners, Pediatric Annals, Neonatal Network, Advances in Neonatal Care, Pediatrics in Review Online modules: Healio (Education/CME) http://www.healio.com/ Pediatric Nursing Certification Board (Modules/CE) https://www.pncb.org/ National Certification Corporation (Continuing Ed) https://www.nccwebsite.org/ 9
Questions? THANK YOU! 10