Integrated Case-Based Learning 2 (Infectious Diseases) Lecture 1 PDF

PPP 408 Integrated Case Based Learning 2 Integrated Case-Based Learning 2 (Infectious Diseases) Amany El-Bassiouny, Pharm-D, PhD General rules Please silent your mobile phones No students will be allowed to enter the lecture hall after 10 minute...

PPP 408 Integrated Case Based Learning 2 Integrated Case-Based Learning 2 (Infectious Diseases) Amany El-Bassiouny, Pharm-D, PhD General rules Please silent your mobile phones No students will be allowed to enter the lecture hall after 10 minutes of starting Eating is not allowed in the lecture hall Interaction is required You are not allowed to record the lecture Course Lectures will be on Monday 10:30- 12:00 1:30 – 3:00 Overall course objectives The course will enable the students to implement clinical pharmacy tools to real case scenarios. The course will also enable students to detect drug related problems, screen for anticipated drug interactions. The course will advance students skills in managing complicated cases of infectious diseases & implementing evidence-based medicine using SOAP notes & appropriate clinical scores whenever required. The course will run as a capstone pharmacotherapy course integrating patient cases and drug information requested in a team-based collaboration. Course map Week 1 Lectures Establishing the presence Tutorials Revise information resources & 30 Sep 2 of an infection Prophylaxis of SSI Prophylaxis of SSI Grades 3 Special population Upper respiratory tract infection Midterm 30 grades 4 Practical pearls Pneumonia Practical 30 grades 5 Antimicrobial stewardship Meningitis Final 40 grades 6 Home parenteral therapy Practical quiz and PICC lines Bonus ?? 7 Midterm Infective endocarditis Bonus points 8 Viral and fungal infections Urinary Tract Infections Each correct answer = 1 point 9 Management of antimicrobial < 10 points → no bonus resistant Gram-negative Sepsis & Septic Shock 10-15 points → 1 grade infections 10 Management of bed sores Skin & Soft Tissue Infections 15-20 points → 1.5 grades 11 Vaccination (types, 20-25 points → 2 grades TB precautions, adverse effects) 25-30 points → 2.5 grades 12 Midterm 2 HIV >30 points → 3 grades 13 Opportunistic infections Final practical  PPP 408 Integrated Case Based Learning 2 Lecture 1 Establishing the presence of an infection Amany El-Bassiouny, Pharm-D, PhD Signs and symptoms Identifying the site of infection Determining the likely pathogen Antimicrobial therapy Monitoring the infection Objective Subjective Signs and symptoms of an infection Signs and symptoms of an infection General General condition Temperature White blood cell count Inflammatory markers Specific to site of infection 1. Signs and symptoms of an infection 1. Temperature: ≥ 38◦ ≤ 36◦ Afebrile 1. Signs and symptoms of an infection Temperature: Fever is a common manifestation of infection, with oral temperatures generally greater than 38°C. Some patients with overwhelming infection, however, may present with hypothermia with temperatures less than 36°C. Furthermore, patients with localized infections (e.g., uncomplicated urinary tract infection, chronic abscesses) may be afebrile. 1. Signs and symptoms of an infection WBCs 4000 -10000/ mm3 An increased WBC count is commonly observed with infection, particularly with bacterial pathogens. The WBC differential in patients with a bacterial infection often demonstrates a shift to the left owing to the bone marrow response to infection. Although infection is usually associated with an increased WBC, overwhelming sepsis can also be associated with a markedly decreased WBC count. In less acute infection (e.g., uncomplicated urinary tract infection, localized abscess), the WBC count may remain within the normal range because less bone marrow response would be anticipated. WBCs differential count demonstrates a shift to the left 1. Signs and symptoms of an infection Differential white cell count Neutrophils - 2500-8000 per mm3 (55-70%) Lymphocytes - 1000-4000 per mm3 (20–40%) Monocytes - 100-700 per mm3 (2–8%) Eosinophils - 50-500 per mm3 (1–4%) Basophils - 25-100 per mm3 (0.5-1%) 1. Signs and symptoms of an infection Neutrophilia Defined by an absolute neutrophilic count of more than 8000/µL. Neutrophilia occur in response to infection, chronic inflammation, stress, or drugs Certain infections (e.g., Clostridium difficile or tuberculosis in particular) are known to cause elevations in the WBC to greater than 30,000/µL in about one fourth of infected patients and may result in a leukemoid reaction, defined as a WBC of greater than 50,000/µL with a pronounced left shift. 1. Signs and symptoms of an infection Lymphocytosis Defined by an increase in absolute lymphocyte count (ALC) to more than 4000 lymphocytes/microL in adult patients Viral infections: Epstein-Barr Virus (EBV): Cytomegalovirus (CMV) Human Immunodeficiency Virus (HIV), in acute phases Influenza, hepatitis, mumps, measles, rubella, and human T Lymphocytic virus type 1 (HTLV-1), adenovirus, Bacterial infections are mostly associated with neutrophilia and lymphopenia except: Bordetella Pertussis, Mycobacterial Tuberculosis Toxoplasma Gondii, Brucellosis, syphilis, malaria are also associated with lymphocytosis 1. Signs and symptoms of an infection Eosinophilia Defined by an absolute eosinophilic count of more than 400/µL. It is elevated in drug reactions, allergy, and asthma A variety of infections, particularly parasitic infections and, to a lesser degree, fungal infections can be associated with an increased number of circulating eosinophils. 1. Signs and symptoms of an infection Differential white cell count Neutrophilia: mostly bacterial Neutrophils - 2500-8000 per mm3 (55-70%) Lymphocytes - 1000-4000 per mm3 (20–40%) Lymphocytosis: mostly Monocytes - 100-700 per mm3 (2–8%) viral Eosinophils - 50-500 per mm3 (1–4%) Basophils - 25-100 per mm3 (0.5-1%) Eosinophilia: mostly parasitic 1. Signs and symptoms of an infection ESR, C-reactive protein, and procalcitonin Nonspecific tests that are commonly elevated in various inflammatory states, including infection. ESR: The rate at which red blood cells settle out when anticoagulated whole blood is allowed to stand is known as the erythrocyte sedimentation rate. (normal ≤ 20 mm/hr) CRP: C-reactive protein is an acute phase reactant (proinflammatory) with normal range < 3 mg/L The ESR, C-reactive protein, or procalcitonin can be used to follow the progression of infection; Signs and symptoms of an infection ESR, C-reactive protein, and procalcitonin Procalcitonin (PCT) is the peptide precursor of calcitonin, a hormone that is synthesized by the thyroid and involved in calcium homeostasis. The reference value for procalcitonin in adults is 0.25 ng/mL can indicate the presence of a bacterial infection. The synthesis of PCT can be increased up to 100 to 1000 fold due to circulating endotoxins or cytokines such as interleukin (IL)- 6 The ESR, C-reactive protein, or procalcitonin can be used to follow the progression of infection. 1. Signs and symptoms of an infection Localizing symptoms indicating site of infection: Chest: cough, sputum, shortness of breath Urinary tract: dysuria, urgency, flank pain Central nervous system: headache, meningism Biliary tract: upper abdominal pain, jaundice, vomiting Skin and soft tissue: signs of cellulitis, pain, tissue inflammation, pus, or subcutaneous air (crepitus). Blood stream: no obvious source. There is only an indwelling catheter, inflammation of the catheter insertion site 1. Signs and symptoms of an infection In severe cases (sepsis) Hypotension Tachycardia Hypoperfusion Oliguria, and organ dysfunction Mention 5 signs and symptoms of infection  Drugs that may interfere with infection diagnosis Corticosteroids may interfere with the diagnosis of an infection 1. Corticosteroids can reduce the febrile response. Thus, these corticosteroid-treated patients may be asymptomatic but at great risk for gram-negative septic shock. On the contrary corticosteroids may lead to falsely diagnose an infection because of the increase in WBCs induced by corticosteroids 2. Some drugs may cause aseptic meningitis (inflammation of the meniniges without an infection origin) such as NSAIDs, sulfonamides and some antiepileptics, corticosteroids especially after neurosurgical procedures. 2. Establishing the site of infection Site of infection can be easily detected from the signs and symptoms. Or may be masked ( in immunocompromised patients) and can be detected only by cultures. 3. Determining the likely pathogen History of the patient and comorbidities Site of infection Age Recent hospital admission Immune status Travel to an endemic region Isolation of the organism and susceptibility testing 3. Determining the likely pathogen Isolation of the organism and susceptibility testing Gram stain Acid fast Susceptibility testing Empirical therapy  Identified by acid Bacteria fast stain Gram Gram Gram positive negative neutral Aerobic Anaerobic Aerobic Anaerobic Atypical except Cocci Bacilli Cocci Bacilli Cocci Bacilli Bacilli some Mycob- acteria 3. Determining the likely pathogen Susceptibility testing Broth dilution Minimum inhibitory concentration (MIC) Disk diffusion AND/OR E test Sensitive, intermediate, resistant Broth dilution method Disk diffusion method E test 3. Determining the likely pathogen MIC notes MIC is only a measure of efficacy, outcomes are poorer with increasing MIC For example, vancomycin is said to be resistant when MIC>2mg/L In reality MIC was 0.5 mg/L ➔ treatment success rate was 62% MIC was 1 mg/L ➔ treatment success rate was 28% MIC was 2 mg/L ➔ treatment success rate was 11% 3. Determining the likely pathogen MIC notes MIC is specific for each organism and agent Antibiotic MIC Susceptibility Ampicillin/sulbactam 7 Susceptible Vancomycin 7 Intermediate Nitrofurantoin 20 Susceptible The MIC is interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines into susceptible, intermediate, or resistant We usually use a higher dose for intermediate strains. 3. Determining the likely pathogen 3. Determining the likely pathogen Susceptibility testing is well established for bacteria. As well as for candida and azoles. Susceptibility testing is not well established for amphotericin B or echinocandin antifungals Susceptibility testing for viral infections is more complicated. In some parts of the world, it is a standard part of HIV care process. Susceptibility testing of parasites especially malaria is done for research purposes to examine the presence of resistance in a certain region.  Which of the following is a qualitative susceptibility test? A. Broth dilution B. Disk diffusion C. E test 4. Antimicrobial therapy Antimicrobial therapy-disease progression timeline Prophylaxis Pre-emptive Empiric Definitive Suppressive No infection Infection Symptoms Pathogen Resolution isolation 4. Antimicrobial therapy Types and goals of antimicrobial therapy 1. prophylactic therapy Treating patients who are not yet infected or have not yet developed the disease. Goal is to prevent infection. Prophylaxis in general is not favorable because it may increase the resistance of microbes, but it is recommended is special groups. The prophylactic dose is usually smaller than the therapeutic dose.  4. Antimicrobial therapy Types and goals of antimicrobial therapy 1. prophylactic therapy (when is it needed?) Immunocompromised patients (HIV, or receiving immunosuppressants), where prophylaxis is targeted against certain organism. Chemoprophylaxis to prevent wound infection after surgical procedures. High risk groups for infective endocarditis undergoing invasive dental procedures ( a single dose of amoxicillin, macrolide or clindamycin) Post exposure prophylaxis( rifampin or ciprofloxacin for meningitis, macrolide for pertussis) 4. Antimicrobial therapy Types and goals of antimicrobial therapy 2. pre-emptive therapy In high-risk patients who have a laboratory evidence of infection but have not developed symptoms yet. 3. Empirical therapy In symptomatic patients in which the causative agent have not been yet identified and are at risk of developing life-threatening complications. Performing cultures is still mandatory to modify the antibiotics accordingly. Some infections are self-limiting and do not require antimicrobial therapy. Antimicrobial therapy Types and goals of antimicrobial therapy 4. Definitive therapy Based on the susceptibility test results Monotherapy for the shortest possible duration is preferred (exceptions) 5. Suppressive therapy Considered as secondary prophylaxis Usually in HIV & post transplant patients where treatment is given at lower doses to prevent relapse because the infection was not completely eradicated. 5. Monitoring the progression of an infection Clinical symptoms Temperature WBCs CRP and procalcitonin (In most studies, the reduction of PCT levels below 0.25–0.5 ng/mL, or an 80–90% decline from baseline led to antibiotic de-escalation.) Repeating cultures  5. Monitoring the infection A 64-year-old woman is admitted to the medical ICU with possible community-acquired pneumonia. The patient is initiated on ceftriaxone and azithromycin. Chest radiography reveals focal infiltrate. On admission, she is dyspneic with a respiratory rate of 33 breaths/minute. Her vital signs and laboratory values are as follows: blood pressure 90/50 mm Hg, heart rate 101 beats/minute, WBC 18 x 103 cells/mm3, and lactate 4.2 mmol/L.A procalcitonin result is 0.1 mcg/L. which is the most appropriate option, given the procalcitonin result? A. Continue all current antibiotics. B. Discontinue all antibiotics. C. Escalate antibiotics to piperacillin/tazobactam. D. Discontinue ceftriaxone only. Next time Do you think, a child who is about to perform a surgical operation to remove his tonsils (tonsillectomy) should administer an antibiotic?