Antimicrobial Chemotherapy
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1 2016 edition by Claudine El-Beyrouty, PharmD, BCPS Department of Pharmacy Thomas Jefferson University Hospital Brian Roslund, PharmD, BCPS, AQ-ID Department of Pharmacy Thomas Jefferson University Hospital Bhavik Shah, PharmD, BCPS, AAHIVP Department of Pharmacy Practice Jefferson College of Pharmacy Originally developed by: Gary K. Best, PhD Department of Pharmacology and Toxicology Medical College of Georgia Note to Instructors The POPS exercises are divided into seven sections: A. Introduction to the POPS System, introduction to and objectives of the clinical simulations, a pretest, and review topics B-E. Four different color-coded sections with pretest answers and the clinical problem F. Posttest G. Posttest answers For information on conducting the exercise, see the Instructor's Manual: Patient-Oriented Problem-Solving (POPS) System in Pharmacology.
2 Introduction to the Patient-Oriented Problem-Solving (POPS) System This is a Patient-Oriented Problem-Solving activity. The purposes are: 1. To help you learn how to apply your basic science knowledge to the solution of clinical problems. 2. To encourage you to locate information necessary for solving problems by using sources that will be available to you throughout your career. 3. To encourage you to work with your fellow students and thus: a. increase your ability to evaluate your colleagues' opinions, thought processes, and diagnoses; b. increase your communication skills; and c. increase your skills in interpersonal and interprofessional relations. This activity consists of five phases: First, you will review the attached set of learning objectives and complete the pretest on your own. In the second phase, you will use the pretest and the recommended review topics to guide your further study before you meet your group at the scheduled time. In the third phase, you will join three other students and review the pretest answers in an "open-book" discussion. In the fourth phase, the group will solve patient-oriented problems. Information exchange and group interaction are keys to the success of this phase. This process will allow you to teach your fellow students and, at the same time, learn from them. Finally, you will take a posttest, individually, which will enable you to assess your progress. 2
3 Introduction Infectious diseases remain one of the most common diagnoses in patients being managed in both the community and inpatient settings. Health care professionals should possess a solid knowledge base of the basic principles of antimicrobial chemotherapy, including the selection of empiric therapy based on likely pathogens for each disease state and de-escalation to definitive antimicrobial therapy based on microbiology results. Empiric Antimicrobial Therapy Empiric antibiotic therapy should be guided by the clinical presentation of the patient. Antibiotics should be selected with the intent to cover multiple possible pathogens commonly associated with the specific clinical syndrome. Clinicians should consider the following factors when selecting empiric antibiotic regimens: Differentiate between community acquired and hospital acquired infections. Consider the site of infection and the organisms most likely to be colonizing that site. Assess prior knowledge of bacteria known to colonize a given patient. Review the local bacterial resistance patterns or antibiograms. An antibiogram is a table of information which provides susceptibility patterns for each organism isolated in a healthcare environment. For each organism, the percentage of isolates sensitive to each antimicrobial drug is calculated. Use of Combination Antibiotic Therapy A combination of 2 or more antimicrobial agents is recommended in a few scenarios. When there is documented synergistic activity against a microorganism [e.g., beta lactams and aminoglycosides exhibit synergistic activity against gram-positive bacteria] When critically ill patients require empiric therapy before microbiological etiology can be confirmed Using a combination of antibiotics to extend the spectrum of activity (e.g., adding antibiotics with gram-positive or anaerobic activity to an antibiotic that provides gram-negative activity) Using two agents with activity against gram-negative bacilli, particularly Pseudomonas aeruginosa until antimicrobial susceptibilities are available To prevent the emergence of resistance (e.g., treatment of HIV, TB, HCV) Definitive Therapy and De-escalation Once microbiology results have identified the etiologic pathogen and susceptibility data are available (usually in 24-48hours), the antibiotic regimen should be changed to one with a narrower spectrum of activity (de-escalation). The benefits of de-escalation include: Avoidance of toxicity Prevention of the emergence of antimicrobial resistance in the community Reduced costs 3
4 Duration of Therapy Response to treatment of an infection should be assessed using clinical and microbiologic parameters. The antibiotic regimen should be utilized for the optimum duration of therapy suggested in clinical trials and national guidelines. Prolonged courses of antimicrobial agents can lead to negative consequences including: potential for adverse reactions, selection of antibioticresistant organisms, and high cost. This POPS unit was designed to give you practice in applying your knowledge of the pharmacology of antimicrobials to the management of four commonly encountered infectious diseases: Staphylococcus aureus bacteremia, bacterial meningitis, pneumonia, and urinary tract infections. 4
5 Learning Objectives When you have completed this booklet you should be able to: 1. Describe the epidemiological risk factors associated with infective endocarditis (IE) 2. Provide empiric antimicrobial recommendations for Staphylococcus aureus IE 3. Describe MIC creep and its impact on antimicrobial therapy 4. Provide definitive antimicrobial recommendations for IE 5. Provide empiric antibiotic recommendations for meningitis based on likely organism, patient and drug factors 6. Provide definitive antibiotic recommendations for meningitis based on culture and sensitivity data 7. List the most likely causes of bacterial pneumonia based on patient demographics, risk factors, and degree of healthcare exposure 8. Provide empiric antibiotic recommendations for pneumonia based on likely organism, patient and drug factors and provide definitive antibiotic recommendations based on culture and sensitivity data 9. Provide empiric antibiotic recommendations for urinary tract infections based on the likely organism, patient and drug factors 10. Provide definitive antibiotic recommendations for urinary tract infections based on culture and sensitivity data When you have become familiar with the learning objectives, please complete the pretest on the following page. 5
6 Pretest Instructions: To facilitate later discussion and review, please mark these pretest pages with your answers to the following questions. If your instructor has provided a separate form, mark your answers both on that form (being sure to fill in the identification section) and on these pages. Choose the one correct or most appropriate answer. If you do not know an answer leave the space blank. Do not guess. Health professionals who think they know something, but do not, can do real harm. Those who know they don't know something can get help. Don't be upset if you don't know all the answers. The purpose of the pretest and the objectives are to alert you to important concepts. The posttest will be similar in content to the pretest. 1. Which of the following antibiotics is not effective for Staphylococcus aureus infective endocarditis? A. vancomycin B. penicillin C. nafcillin D. daptomycin 2. Which of the following is the target site for cefazolin against Staphylococcus aureus? A. penicillin binding protein B. 30s ribosomal subunit C. DNA gyrase D. 50s ribosomal subunit 3. Which of the following antibiotics is associated with nephrotoxicity? A. cefazolin B. vancomyicn C. daptomycin D. linezolid 4. Which of the following antibiotics is useful to treat all of the following organisms: Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis? A. ceftazidime B. ceftriaxone C. penicillin G D. vancomycin 6
7 5. Which of the following antibiotics provides adequate penetration into the central nervous system for the treatment of bacterial meningitis? A. amoxicillin/clavulanic acid B. amikacin C. ceftriaxone D. clarithromycin 6. Which of the following antibiotics is useful to treat infections caused by Pseudomonas aeruginosa? A. azithromycin B. ceftriaxone C. moxifloxacin D. piperacillin-tazobactam E. vancomycin 7. Which of the following antibiotics has inadequate activity against Streptococcus pneumoniae, and as a result cannot be used for infections caused by it such as community-acquired pneumonia? A. azithromycin B. ceftriaxone C. ciprofloxacin D. moxifloxacin 8. Which of the following antibiotics should be avoided for the treatment of urinary tract infections due to inadequate excretion of the drug into urine? A. levofloxacin B. moxifloxacin C. nitrofurantoin D. sulfamethoxazole-trimethoprim E. tobramycin 9. Which of the following antibiotics achieves adequate concentrations in the kidney and can be used for pyelonephritis in addition to cystitis? A. fosfomycin B. nitrofurantoin C. sulfamethoxazole/trimethoprim 7
8 10. Which of the following antibiotics is considered the drug of choice for a urinary tract infection caused by organism that produces an extended-spectrum betalactamase? A. aztreonam B. cefazolin C. ceftriaxone D. ertapenem When you have completed the pretest, consult your study materials. Try to identify the correct answers and understand the concepts that make them correct. As a guideline for your studies, you may use the Learning Objectives. When your group meets, you will be responsible for explaining some of the answers. Please bring your materials to the group meeting. To prepare for the group meeting, which will be a problem-solving session, you should review the following topics: Pharmacology of Antimicrobials a. Spectrum of activity b. Pharmacokinetics c. Adverse Drug Effects Antimicrobial Chemotherapy Abbreviation Quick List Abbreviation Definition A&O x 3 Awake and oriented to person, place, and time Alk Phos Alkaline phosphatase ALT Alanine aminotransferase AST Aspartate aminotransferase b/l Bilateral BMP Basic metabolic panel BP Blood pressure BPM Beats per minute / breaths per minute BUN Blood urea nitrogen CAD Coronary artery disease CBC Complete blood count CNS Central nervous system CPK Creatinine phosphokinase CSF Cerebrospinal fluid CV Cardiovascular ESBL Extended spectrum beta lactamase EXT Extremities GI Gastrointestinal HEENT Head, eyes, ears, nose and throat Hgb Hemoglobin 8
9 Abbreviation HR HT HTN IE IV LFT LLE LP MI MIC MRSA N/V NKDA PCI PLT PMH PO RBC RR Scr T TBili UA UTI WBC WT Definition Heart rate Height Hypertension Infective endocarditis Intravenous Liver function test Left lower extremity Lumbar puncture Myocardial Infarction Minimum inhibitory concentration Methicillin resistant staphylococcus aureus Nausea/vomiting No known drug allergies Percutaneous coronary intervention Platelet Past medical history Orally, by mouth Red blood cell count Respiratory rate Serum creatinine Temperature Total bilirubin Urinalysis Urinary tract infection White blood cell count Weight 9
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