Infectious Disease I: Overview of - PowerPoint Presentation

1. Infectious Disease I:Overview of Infectious DiseasesCourses in Therapeutics and Disease State Management

2. Learning Objectives (Slide 1 of 3)Recognize general signs, symptoms, laboratory, and microbiologic findings of a patient with an infectionApply susceptibility data from an institution’s antibiogram in choosing presumptive antimicrobial therapySelect antimicrobial(s) of choice based on organism and infectious diseaseDesign an appropriate antimicrobial regimen for a patient-based allergy profile, age, renal and liver function, concomitant disease states, and infection

3. Learning Objectives (Slide 2 of 3)Propose alternative antimicrobial therapy for a patient with a penicillin allergyDiscuss metabolic and host genetic variations that may affect antimicrobial therapyExplain key pharmacodynamic relationships to optimize antimicrobial dosingRecommend antimicrobial agents based on tissue or fluid penetration and site of infection

4. Learning Objectives (Slide 3 of 3)Debate advantages and disadvantages of using combination antimicrobial therapyFormulate a monitoring plan to assess therapeutic response after initiation of antimicrobial therapyEvaluate issues including drug selection, host factors, and pathogen(s) in a patient lacking clinical response to antimicrobial therapyList clinical parameters to consider when switching from parenteral to oral therapyList clinical parameters to consider when switching from parenteral to oral therapy.

5. Required and Recommended ReadingRequired ReadingLee GC, Burgess DS. Chapter 83. Antimicrobial Regimen Selection. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e.` New York, NY: McGraw-Hill; 2014.Recommended ReadingsLampiris HW, Maddix DS. Clinical Use of Antimicrobial Agents. In: Katzung BG, Trevor AJ. eds. Basic & Clinical Pharmacology, 13e. New York, NY: McGraw-Hill; 2015.Rybak MJ, Aeschlimann JR, LaPlante KL. eChapter 25. Laboratory Tests to Direct Antimicrobial Pharmacotherapy. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.

6. Selection of Antimicrobial Agents (Slide 1 of 4)Infectious diseases generally are acute, and a delay in antimicrobial therapy can result in serious morbidity or even mortalityAntimicrobial therapy must be initiated swiftly and appropriately in order to prevent serious complications from infectious process and the antimicrobial therapy itself

7. Selection of Antimicrobial Agents (Slide 2 of 4)Consider the following three patients:Patient # 1: A 35-year-old female presents to the emergency room with complaints of fever, cough, and increased green sputum production. She has decreased lung sounds at the bases of his lungs. She does not have a significant past medical history. She has received a 3-day course of levofloxacin for a urinary tract infection three weeks ago. A complete blood count with differential reveals an elevated white blood cell count of 11,000 cells/mm3 Patient # 2: A 45-year-old male presents to the emergency room with complaints of fever, cough, increased green sputum production. He has decreased lung sounds at the bases of his lungs. He has a past medical history significant for HTN, hypothyroid, and atrial fibrillation. He has not had any antibiotics in the past 6 months. A complete blood count with differential reveals an elevated white blood cell count of 14,000 cells/mm3 Patient # 3: 62-year-old male presents to the emergency room with complaints of fever, cough, increased sputum production. He has decreased lung sounds at the bases of his lungs. He has a past medical history of COPD, Diabetes, and HTN. He has not had any antibiotics in the past year. A complete blood count with differential reveals an elevated white blood cell count of 12,000 cells/mm3

8. Selection of Antimicrobial Agents (Slide 3 of 4)Confirm the presence of infectionCareful history and physical examinationSigns and symptomsPredisposing factorsIdentification of the pathogen (see Chap. e24)Collection of infected materialStainsSerologiesCulture and sensitivitySelection of presumptive therapy considering every infected siteHost factorsDrug factorsMonitor therapeutic responseClinical assessmentLaboratory testsAssessment of therapeutic failure

9. Selection of Antimicrobial Agents (Slide 4 of 4)Drawbacks to not following a systematic process include:Unnecessary use of broad-spectrum antimicrobial therapy that leads to widespread resistance and difficult-to-treat superinfectionsOveruse of more expensive or potentially more toxic antimicrobial agents Administration of antimicrobial agents to patients with infectious processes that are self-limiting (e.g. colds or viral gastritis)

10. Confirming the Presence of InfectionSigns and Symptoms: FeverAverage normal body temperatures by site are defined asOral: 36.7°C (98°F)- 37°C (98.6°F)Rectal: 37.3°C (99°F)- 37.6°C (99.6°F)Axillary: 36.1°C (97°F)- 36.4°C (97.6°F)Regulation of body temperature is a complex process, controlled by the hypothalamus, that follows a circadian rhythmAn elevation in temperature above the generally acceptable ranges is considered a hallmark of an infectious process Clinicians should be aware that there are many non-infectious origins for fever Medications can prevent a fever in patients with an infectious process

11. Confirming the Presence of InfectionSigns and Symptoms: White Blood Cell CountNormal White Blood Cell (WBC) Count range: 4,000 - 10,000 cells/mm3 (4 × 109 -10 × 109/L)Infections will normally result in a leukocytosis (elevated WBC count) due to an increased production and mobilization of granulocytes and lymphocytesPatients may have an infection without a leukocytosisPatients may have a leukocytosis without an infection

12. Confirming the Presence of InfectionSigns and Symptoms: Local SignsPain and inflammationSwellingErythemaTendernessPurulent DrainageExamination of tissues and fluidsOrgan specific symptoms

13. Confirming the Presence of InfectionSigns and Symptoms: ReviewAll three of the patients in the previous example are presenting with fever as a non-specific symptom of an infectionEach of the patients has an elevated white blood cell countPatient # 1: 11,000 cells/mm3 Patient # 2: 14,000 cells/mm3 Patient # 3: 12,000 cells/mm3 The following signs and symptoms are more organ specific to respiratory infectionsCoughIncreased mucous productionDecreased lung sounds

14. Identification of the PathogenLaboratory Tests: Gram’s StainOne of the initial tests completed on a specimen Differentiates between gram-positive and gram-negative organisms Describes the morphology of organismsThe Gram’s stain and morphology characteristics of the isolated organisms can be used to categorize stained the organisms into groupsRoutinely performed on Sputum Cerebral spinal fluidBlood Bronchial aspiratesUrineMucosal Scrapings

15. Identification of the PathogenLaboratory Tests: Evaluation and DirectionLink: Figure on Laboratory Tests to Direct Antimicrobial Pharmacotherapy

16. Identification of the PathogenLaboratory Tests: CultureIdentification of the infecting pathogen by culture is the most definitive method available for the diagnosis and treatment of infectionSamples of fluid or tissues collected from an infected patient will be used to inoculate several types of artificial growth media to identify the causative pathogenRoutinely performed on Blood Sputum Bronchial aspiratesUrineCerebral spinal fluidStoolJoint fluidWound or sinus drainage

17. Identification of the PathogenLaboratory Tests: Other TestsRapid Diagnostic TechnologiesCan have results within 15 minutes to 4 hoursGenomic testing methodologiesImmunologic AssaysRapid Strep TestRapid Influenza diagnostic testEnzyme-linked immunosorbent assay (ELISA) testsHybridization DNA ProbesPeptide nucleic acid fluorescence in situ hybridization (PNA-FISH) assayBranched DNA (bDNA) probe systemNucleic Acid Amplification Methodspolymerase chain reaction (PCR)Rapid PCR (rPCR)Mass spectrometry

18. Identification of the PathogenLaboratory Tests: Interpreting ResultsPositive results from a Gram stain and/or a culture do not always indicate an infectious processTrue pathogen vs. Contamination vs. Normal FloraGram-PositiveGram-NegativeCocciRodsCocciRodsOtherSkinStaphylococcus spp. (e.g., S. epidermidis), Streptococcus spp.Corynebacterium spp., Propionibacterium spp.Enteric bacilli (some sites), Acinetobacter spp. (Coccobacilli)OropharynxStreptococci—viridans group MicrococcusCorynebacterium spp.NeisseriaHaemophilus spp.SpirochetesGI tractEnterococcus spp., Peptostreptococcus spp.Lactobacillus, ClostridiumBacteroides spp., Enteric bacilli (E. coli, Klebsiella spp.)Genital tractStreptococcus spp., Staphylococcus spp.Lactobacillus, Corynebacterium spp.Enterobacteriacea, Prevotella spp., Candidia spp.Mycoplasma

19. Identification of the PathogenLaboratory Tests: Patient ExamplesLink: Algorithm on Laboratory Tests to Direct Antimicrobial PharmacotherapySputum gram stain results for the patients were as follows:Patient #1: Gram negative coccobacilli Patient #2: Gram positive cocci arranged in pairs Patient #3: No organism identified

20. Selection of Presumptive Therapy: Introduction After identifying the signs and symptoms of infection and attempting to identify a pathogen, empirical antimicrobial therapy may be initiated depending onDisease severity and acuityPatient specific factorsMedication related issuesNeed for multiple antimicrobial agentsEmpiric antimicrobial therapy is directed at organisms that are known to cause the infection Generally accepted drugs of first choice for specific infections are based on several factorsInfection Specific GuidelinesLocal antimicrobial susceptibility data via antibiograms

21. Selection of Presumptive Therapy: Patient Factors (Slide 1 of 3)AllergyCareful assessment of listed medication allergies and reactions must be completedAn “allergy” to a medication with a reaction of nausea is not an allergyPenicillin allergies are commonSerious reactions (anaphylaxis, laryngospasm, throat swelling) may prevent use of penicillin related compounds Patients with less serious reactions (rash) may be able to take penicillin related compounds under close supervision Age Certain infections are cause by different pathogens based on the patient’s ageMeningitisOsteomyelitis Certain medications cannot be processed appropriately in neonates due to underdeveloped hepatic and liver functionRenal function declines with age, which would cause decreased drug clearance in older patients

22. Selection of Presumptive Therapy: Patient Factors (Slide 2 of 3)Pregnancy Risk of harm to the fetus with teratogenic medicationsAltered pharmacokinetics in pregnant patientsIncreased intravascular volumeIncreased glomerular filtrationHigher hepatic clearance of medicationMetabolic or Genetic Variation Depending on the genetic variation could lead to increased or decreased drug metabolismCertain medications require screening for specific genetic variation prior to administration

23. Selection of Presumptive Therapy: Patient Factors (Slide 3 of 3)Organ DysfunctionDecreases in the renal and/or hepatic function of a patient can lead to accumulation of medicationsMedication specific recommendation should be followed when organ dysfunction is presentConcomitant Drugs/ Disease StatesAny antimicrobial agent should be screened against a patient’s past medical history and current medication list for drug disease and drug-drug interactions, respectivelyCertain disease states will predispose a patient to specific infections and/or pathogens

24. Selection of Presumptive Therapy Drug Factors: Pharmacokinetic and Pharmacodynamic Considerations Pharmacokinetics is used to describe how a medication is processed by the bodyArea under the curve (AUC)Maximum observed concentration (peak)Half life (t1/2)Pharmacodynamics describes the relationship between drug concentration and the effects on the microorganismAUC: Minimal inhibitory concentration (MIC) ratio (AUC:MIC ratio)Peak: MIC ratioTime (T) the concentration is above the MIC (T>MIC)Utilizing these tools has altered the methods employed to dose and administer medications

25. Selection of Presumptive Therapy: Drug FactorsTissue PenetrationAntimicrobial therapy must be able to get to the site of infection and be active once thereSerious infections are generally treated using intravenous antimicrobial therapyOutpatient treatment of less serious infectious diseases can be managed using oral medications Drug Toxicity Toxicities should be avoided at all costsCertain medications will require a risk vs. benefit analysis prior to starting therapy

26. Selection of Presumptive Therapy: Antimicrobial Regimen SelectionLink: Table on Antimicrobial Regimen Selection

27. Selection of Presumptive Therapy:Combination Antimicrobial TherapyBroadening the Spectrum of CoverageRequired for infections caused by multiple pathogensRequired for patients with two concurrent infections with different pathogensSynergismControversial data exists with the use of two antimicrobial agents with differing mechanism of action against a pathogenEndocarditis is often treated with a combination of an antimicrobial agent that targets the cell wall with an aminoglycoside. Preventing ResistanceCombining antimicrobials may decrease the development of bacterial resistance Frequently utilized in the treatment of tuberculosis

28. Selection of Presumptive Therapy:Disadvantages of Combination TherapyIncreased CostGreater risk of drug toxicitySuperinfection

29. Selection of Presumptive Therapy:Patient Examples (Slide 1 of 3)Patient #1: 35-year-old female (not pregnant)PMH: not significantCurrent Medications: nonePast medications: levofloxacinAllergies: nonePossible bacteria for community acquired pneumonia: Streptococcus pneumoniaMycoplasma pneumonia*Haemophilus influenza *Chlamydophila pneumoniaGram stain: Gram negative coccobacilli *

30. Selection of Presumptive Therapy:Patient Examples (Slide 2 of 3)Patient #2: 45-year-old male PMH: Hypertension, hypothyroidism, atrial fibrillationCurrent Medications: levothyroxine, lisinopril, warfarin, Past medications: no recent antibioticsAllergies: tetracycline (upset stomach)Possible bacteria for community acquired pneumonia: Streptococcus pneumonia*Mycoplasma pneumoniaHaemophilus influenza Chlamydophila pneumoniaGram stain: Gram positive cocci arranged in pairs *

31. Selection of Presumptive Therapy:Patient Examples (Slide 3 of 3)Patient #3: 62-year-old male PMH: COPD, Diabetes, and HypertensionCurrent Medications: tiotropium , albuterol, valsartan, metformin, insulin Past medications: no recent antibioticsAllergies: nonePossible bacteria for community acquired pneumonia: Haemophilus influenzaePseudomonas aeruginosaLegionella speciesStreptococcus pneumoniaMorexella cararrhalisChlamydophila pneumonia Different pathogens due to history of COPDGram stain: No organism identified

32. Monitoring Therapeutic Response: IntroductionPatient should be monitored for clinical improvements for two to three days following the initiation of antimicrobial therapyDecrease in signs and symptoms of infectionAbsence of feversCorrection of WBC countPatients that fail to respond to therapy should be reevaluated closely

33. Monitoring Therapeutic Response:Switching from IV to Oral TherapyPatients with an overall clinical improvement should be considered to be switched from parenteral to oral antimicrobial therapyPatients should meet the following criteriaLack of fever for 8 to 24 hoursDecreased WBC countHave a functioning Gastrointestinal tractOral antimicrobial therapy should have excellent oral bioavailability and activity against the suspected or isolated pathogen

34. Monitoring Therapeutic Response:Failure of Antimicrobial TherapyDrug SelectionInappropriate Drug SelectionIncorrect dosageIncorrect routePoor penetration into the site of infectionPatient FactorsImmunosuppression Need for surgical intervention to control source of infectionMicroorganismsIntrinsic resistanceAcquired Resistance Alteration in the target siteChange in membrane permeabilityEfflux pumpDrug inactivation

35. AntibiogramsInstitutional differences in pathogen susceptibilityAn antibiogram is a periodic summary of antimicrobial susceptibilities of local bacterial isolates submitted to the hospital's clinical microbiology laboratoryThe information in the antibiogram aid clinicians in the empiric selection of antimicrobial therapies.

36. Antibiograms: Example

37. Antimicrobial StewardshipMultidisciplinary team that ensures appropriate and judicious use of antimicrobial therapy in an institutionMake formulary recommendationsRestrict antimicrobial therapies to infectious disease specialists

38. Common BacteriaLink: List of Drugs of Choice, First Choice, Alternative(s)

39. SummaryConfirm the presence of infectionNonspecific signs and symptoms of infectionFeverWBC countPain and inflammationSite specific symptoms Identify of the pathogenGram StainCultureRapid testSelect empiric antimicrobial therapy based on suspected infection, patient, medication factors, and local resistanceMonitoring therapeutic responseImprovement of signs and symptomsConsider changing patient from parenteral to oral therapy

40. References Lee GC, Burgess DS. Chapter 83. Antimicrobial Regimen Selection. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e.` New York, NY: McGraw-Hill; 2014.Lampiris HW, Maddix DS. Clinical Use of Antimicrobial Agents. In: Katzung BG, Trevor AJ. eds. Basic & Clinical Pharmacology, 13e. New York, NY: McGraw-Hill; 2015.Rybak MJ, Aeschlimann JR, LaPlante KL. eChapter 25. Laboratory Tests to Direct Antimicrobial Pharmacotherapy. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9e. New York, NY: McGraw-Hill; 2014.