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Infectious Disease I: Overview of Infectious Diseases

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1 Infectious Disease I: Overview of Infectious Diseases
Courses 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 infection Apply susceptibility data from an institution’s antibiogram in choosing presumptive antimicrobial therapy Select antimicrobial(s) of choice based on organism and infectious disease Design 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 allergy Discuss metabolic and host genetic variations that may affect antimicrobial therapy Explain key pharmacodynamic relationships to optimize antimicrobial dosing Recommend 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 therapy Formulate a monitoring plan to assess therapeutic response after initiation of antimicrobial therapy Evaluate issues including drug selection, host factors, and pathogen(s) in a patient lacking clinical response to antimicrobial therapy List clinical parameters to consider when switching from parenteral to oral therapy List clinical parameters to consider when switching from parenteral to oral therapy.

5 Required and Recommended Reading
Required Reading 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. Recommended Readings 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. Each one of the following patients is presenting with the same signs and symptoms consistent an infection.

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 mortality Antimicrobial 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 Each one of the following patients is presenting with the same signs and symptoms consistent with an infection, but may require vastly different antimicrobial therapies to treat the infection. A patient’s presenting signs and symptoms, past medical histories, allergies, recent antibiotic use, local resistance factors, and many more factors help determine the most appropriate therapy

8 Selection of Antimicrobial Agents (Slide 3 of 4)
Confirm the presence of infection Monitor therapeutic response Careful history and physical examination Clinical assessment Signs and symptoms Laboratory tests Predisposing factors Assessment of therapeutic failure Identification of the pathogen (see Chap. e24) Collection of infected material Stains Serologies Culture and sensitivity Selection of presumptive therapy considering every infected site Host factors Drug factors From AccessPharmacy: accesspharmacy.mhmedical.com, Copyright© McGraw-Hill Education. All rights reserved. Chapter 83. Antimicrobial Regimen Selection, Table 83-1 Systematic Approach for Selection of Antimicrobials Pharmacotherapy: A Pathophysiologic Approach, 9e, 2014 Joseph T. DiPiro, Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael Posey

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 superinfections Overuse 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 Infection Signs and Symptoms: Fever
Average normal body temperatures by site are defined as Oral: 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 rhythm An 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 noninfectious causes of fever Collagen vascular (autoimmune) disorders Malignancies/ cancer Medications / Drug induced fevers medications most often associated with drug-induced fever β-lactam antibiotics Anticonvulsants Allopurinol Hydralazine Nitrofurantoin Sulfonamides Phenothiazines hMethyldopa medications that can mask a fever Aspirin Acetaminophen NSAIDS Corticosteroids

11 Confirming the Presence of Infection Signs and Symptoms: White Blood Cell Count
Normal White Blood Cell (WBC) Count range: 4, ,000 cells/mm3 (4 × × 109/L) Infections will normally result in a leukocytosis (elevated WBC count) due to an increased production and mobilization of granulocytes and lymphocytes Patients may have an infection without a leukocytosis Patients may have a leukocytosis without an infection

12 Confirming the Presence of Infection Signs and Symptoms: Local Signs
Pain and inflammation Swelling Erythema Tenderness Purulent Drainage Examination of tissues and fluids Organ specific symptoms Pain and inflammation are common presenting signs and symptoms of infection. Clinicians should evaluate superficial infections and bone/joint infections for the presence of swelling, erythema, tenderness, purulent drainage, and pain. More deep-seated infections like meningitis, endocarditis, bacteremia, may require more organ specific evaluation. The course will discuss these techniques in future lectures.

13 Confirming the Presence of Infection Signs and Symptoms: Review
All three of the patients in the previous example are presenting with fever as a non-specific symptom of an infection Each of the patients has an elevated white blood cell count Patient # 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 infections Cough Increased mucous production Decreased lung sounds Looking at the three patient examples from earlier in the lecture, the non specific signs and symptoms of infection Fever and elevated WBC count are present. The more specific signs and symptoms for a respiratory infection are present. This would aid in the diagnosis of a respiratory infection. Had the patient example been cellulitis the fever and leukocytosis would most likely be present, but the patients would have pain, erythema, and inflammation at the site of the cellulitis instead of the respiratory signs and symptoms. The next step in the process is to attempt to identify the pathogen causing the infection

14 Identification of the Pathogen Laboratory Tests: Gram’s Stain
One of the initial tests completed on a specimen Differentiates between gram-positive and gram-negative organisms Describes the morphology of organisms The Gram’s stain and morphology characteristics of the isolated organisms can be used to categorize stained the organisms into groups Routinely performed on Sputum Cerebral spinal fluid Blood Bronchial aspirates Urine Mucosal Scrapings Samples of infected body site fluids or tissues should be obtained if possible. Some samples may not be able to be obtained due to practicality. A needle aspiration of the sinus cavity would be helpful to identify the pathogen causing a sinusitis, but a patient may be hesitant to have a such an invasive procedure. McAdam AJ, Onderdonk AB. Laboratory Diagnosis of Infectious Diseases. In:Kasper D, Fauci A, Hauser S, Longo D, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 19e. 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.

15 Identification of the Pathogen Laboratory Tests: Evaluation and Direction
Link: Figure on Laboratory Tests to Direct Antimicrobial Pharmacotherapy 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.

16 Identification of the Pathogen Laboratory Tests: Culture
Identification of the infecting pathogen by culture is the most definitive method available for the diagnosis and treatment of infection Samples of fluid or tissues collected from an infected patient will be used to inoculate several types of artificial growth media to identify the causative pathogen Routinely performed on Blood Sputum Bronchial aspirates Urine Cerebral spinal fluid Stool Joint fluid Wound or sinus drainage 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.

17 Identification of the Pathogen Laboratory Tests: Other Tests
Rapid Diagnostic Technologies Can have results within 15 minutes to 4 hours Genomic testing methodologies Immunologic Assays Rapid Strep Test Rapid Influenza diagnostic test Enzyme-linked immunosorbent assay (ELISA) tests Hybridization DNA Probes Peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) assay Branched DNA (bDNA) probe system Nucleic Acid Amplification Methods polymerase chain reaction (PCR) Rapid PCR (rPCR) Mass spectrometry These are all newer and faster methods to identify specific pathogens in samples sent to the microbiology laboratory 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.

18 Identification of the Pathogen Laboratory Tests: Interpreting Results
Positive results from a Gram stain and/or a culture do not always indicate an infectious process True pathogen vs. Contamination vs. Normal Flora Gram-Positive Gram-Negative Cocci Rods Other Skin Staphylococcus spp. (e.g., S. epidermidis), Streptococcus spp. Corynebacterium spp., Propionibacterium spp. Enteric bacilli (some sites), Acinetobacter spp. (Coccobacilli) Oropharynx Streptococci—viridans group Micrococcus Corynebacterium spp. Neisseria Haemophilus spp. Spirochetes GI tract Enterococcus spp., Peptostreptococcus spp. Lactobacillus, Clostridium Bacteroides spp., Enteric bacilli (E. coli, Klebsiella spp.) Genital tract Streptococcus spp., Staphylococcus spp. Lactobacillus, Corynebacterium spp. Enterobacteriacea, Prevotella spp., Candidia spp. Mycoplasma A true pathogen is causing the infectious process at the site of infection A contaminate is a pathogen that is not causing the infectious process at the site of infection, but contaminated the sample sent to the laboratory Normal flora are pathogens that are normally at the site of infection, but are not causing the infection. See table for examples. From AccessPharmacy: accesspharmacy.mhmedical.com, Copyright© McGraw-Hill Education. All rights reserved. eChapter 25. Antimicrobial Regimen Selection, eTable 25-1 Examples of Normal Bacterial Flora Pharmacotherapy: A Pathophysiologic Approach, 9e, 2014 Joseph T. DiPiro, Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael Posey

19 Identification of the Pathogen Laboratory Tests: Patient Examples
Link: Algorithm on Laboratory Tests to Direct Antimicrobial Pharmacotherapy Sputum 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 Based on the gram stain results and the information in the algorithm, what are the most likely pathogens infecting the patients Patient #1: Gram negative coccobacilli Haemophilus influenza Moraxella catarrhalis Patient #2: Gram positive cocci arranged in pairs Streptococcus pneumoniae Patient #3: No organism identified Just because nothing was shown on gram stain does not mean that the patient is not infected. The patient could be infected with a pathogen that is not identifiable on gram stain

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 on Disease severity and acuity Patient specific factors Medication related issues Need for multiple antimicrobial agents Empiric 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 factors Infection Specific Guidelines Local antimicrobial susceptibility data via antibiograms

21 Selection of Presumptive Therapy: Patient Factors (Slide 1 of 3)
Allergy Careful assessment of listed medication allergies and reactions must be completed An “allergy” to a medication with a reaction of nausea is not an allergy Penicillin allergies are common Serious 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 age Meningitis Osteomyelitis Certain medications cannot be processed appropriately in neonates due to underdeveloped hepatic and liver function Renal function declines with age, which would cause decreased drug clearance in older patients In order for any antimicrobial therapy to treat an infection, it must go through the patient first. This makes patient specific factors extremely important in the selection of empirical antimicrobial therapy. The perfect antimicrobial medication to treat an infection could be contraindicated in a patient with an allergy to the antimicrobial therapy or pre existing disease state that would worsen with the selected medication.

22 Selection of Presumptive Therapy: Patient Factors (Slide 2 of 3)
Pregnancy Risk of harm to the fetus with teratogenic medications Altered pharmacokinetics in pregnant patients Increased intravascular volume Increased glomerular filtration Higher hepatic clearance of medication Metabolic or Genetic Variation Depending on the genetic variation could lead to increased or decreased drug metabolism Certain medications require screening for specific genetic variation prior to administration Penicillins, cephalosporins, and aminoglycosides are cleared from the peripheral circulation more rapidly during pregnancy. The net result is that maternal serum antimicrobial concentrations can be as much as 50% lower during this period than in the nonpregnant state. Increased dosages of certain compounds might be necessary to achieve therapeutic levels during late pregnancy. patients who are phenotypically slow acetylators of isoniazid are at greater risk for peripheral neuropathy. Patients with severe deficiency of glucose-6-phosphate dehydrogenase can develop significant hemolysis when exposed to certain medications The antiretroviral drug abacavir, which is associated with a severe hypersensitivity reaction, consisting of fever, rash, abdominal pain, and respiratory distress. This risk has been associated with the presence of a human leukocyte antigenalleleHLA-B*5701. Routine screening for the presence of this allele before initiating treatment with abacavir is a recommendation in the current HIV treatment guidelines.

23 Selection of Presumptive Therapy: Patient Factors (Slide 3 of 3)
Organ Dysfunction Decreases in the renal and/or hepatic function of a patient can lead to accumulation of medications Medication specific recommendation should be followed when organ dysfunction is present Concomitant Drugs/ Disease States Any antimicrobial agent should be screened against a patient’s past medical history and current medication list for drug disease and drug- drug interactions, respectively Certain disease states will predispose a patient to specific infections and/or pathogens Two agents that have similar adverse effect profiles could cause an increase risk for adverse effects. Aminoglycosides and loop diuretics both individually can cause ototoxicity. The risk for ototoxicity increase when used together. Diabetic patients are at a high risk for soft tissue infection of the lower extremities due to decrease perfusion and sensation. Patients with immune system deficiencies are at risk for a wider variety of infections than patients with normal immune function.

24 Selection of Presumptive Therapy Drug Factors: Pharmacokinetic and Pharmacodynamic Considerations
Pharmacokinetics is used to describe how a medication is processed by the body Area under the curve (AUC) Maximum observed concentration (peak) Half life (t1/2) Pharmacodynamics describes the relationship between drug concentration and the effects on the microorganism AUC: Minimal inhibitory concentration (MIC) ratio (AUC:MIC ratio) Peak: MIC ratio Time (T) the concentration is above the MIC (T>MIC) Utilizing these tools has altered the methods employed to dose and administer medications Concentration dependent medications are best described using Peak:MIC Time dependent medications are best described using T>MIC Aminogylcosides exhibit concentration dependent bactericidal effects best described using Peak:MIC ratio. This led to the discovers of “Once Daily” or “Extended Interval” aminoglycoside dosing. Aminoglycoside used to be administered as a small dose multiple times a day. This type of dosing leads to improved T>MIC, but does not maximize the Peak:MIC parameters. This lead researchers to give one large dose of an aminoglycoside once a day. This approach causes a high initial concentration of aminoglycoside in the patient, which leads to improved penetration into the pathogens.

25 Selection of Presumptive Therapy: Drug Factors
Tissue Penetration Antimicrobial therapy must be able to get to the site of infection and be active once there Serious infections are generally treated using intravenous antimicrobial therapy Outpatient treatment of less serious infectious diseases can be managed using oral medications Drug Toxicity Toxicities should be avoided at all costs Certain medications will require a risk vs. benefit analysis prior to starting therapy The central nervous system (CNS) is a body site with well defined tissue penetration for multiple antimicrobials. Ceftriaxone dosed at 1g or 2g IV daily will lead sub-therapeutic levels in the CNS during the treatment of meningitis. Ceftriaxone must be dosed at least 2 gm IV every 12 hours to get an appropriate drug concentration into the CNS Daptomycin is able to treat skin and soft tissue infections caused by Staphylococcus aureus throughout the body, but not in the lungs. This is due to the fact daptomycin is broken down in the lungs by surfactants. An example of risk vs. benefit is the decision to use isoniazid prophylactically to prevent tuberculosis. Because the hepatotoxicity of isoniazid increases in frequency with age, older persons (>45 years of age) who are candidates for isoniazid prophylaxis (positive skin test) must have additional risk factors for tuberculosis to balance the potential toxic effects.

26 Selection of Presumptive Therapy: Antimicrobial Regimen Selection
Link: Table on Antimicrobial Regimen Selection

27 Selection of Presumptive Therapy: Combination Antimicrobial Therapy
Broadening the Spectrum of Coverage Required for infections caused by multiple pathogens Required for patients with two concurrent infections with different pathogens Synergism Controversial data exists with the use of two antimicrobial agents with differing mechanism of action against a pathogen Endocarditis is often treated with a combination of an antimicrobial agent that targets the cell wall with an aminoglycoside. Preventing Resistance Combining antimicrobials may decrease the development of bacterial resistance Frequently utilized in the treatment of tuberculosis Empiric coverage of community acquired pneumonia may require two antibacterial agents, one that covers typical pathogens and one that covers atypical pathogens. Amoxicillin plus azithromycin Pelvic infections in female patients often require two antibiotics. One antibiotic will have aerobic gram negative bacteria coverage. The other antibiotic will have activity against anaerobic bacteria. Aminoglycoside plus metronidazole A patient could have a pneumonia caused by Staphylococcus aureus and a urinary tract infection caused by a E. coli

28 Selection of Presumptive Therapy: Disadvantages of Combination Therapy
Increased Cost Greater risk of drug toxicity Superinfection

29 Selection of Presumptive Therapy: Patient Examples (Slide 1 of 3)
35-year-old female (not pregnant) PMH: not significant Current Medications: none Past medications: levofloxacin Allergies: none Possible bacteria for community acquired pneumonia: Streptococcus pneumonia Mycoplasma pneumonia* Haemophilus influenza * Chlamydophila pneumonia Gram stain: Gram negative coccobacilli * This patient is young without much of a past medical history. Therefore the suspicion for decreased renal or hepatic function is low, though it could be confirmed with laboratory testing. She has no allergies She has no past medical history listed, including genetic or metabolic variations She does not take any medications that may interact with an antimicrobial agent The recent use of antibiotics may place the patient at risk for having a resistant bacteria. The choices of antibacterial agent will not be restricted due to the few patient specific factors.

30 Selection of Presumptive Therapy: Patient Examples (Slide 2 of 3)
Patient #2: 45-year-old male PMH: Hypertension, hypothyroidism, atrial fibrillation Current Medications: levothyroxine, lisinopril, warfarin, Past medications: no recent antibiotics Allergies: tetracycline (upset stomach) Possible bacteria for community acquired pneumonia: Streptococcus pneumonia* Mycoplasma pneumonia Haemophilus influenza Chlamydophila pneumonia Gram stain: Gram positive cocci arranged in pairs * This patient is older than the last patient with a past medical history. Therefore the suspicion for decreased renal or hepatic function is higher, and could be confirmed with laboratory testing. He has an allergy to tetracycline, but it is not a true allergy (upset stomach) He has a past medical history listed, but no genetic or metabolic variations. Hypertension may be worsened by medications with a high sodium content. Warfarin is notorious for drug interactions. The antimicrobial therapy selected should avoid drug interactions with the patients current medications No recent use of antibiotics may place the patient at a lower risk for having a resistant bacteria. The choices of antibacterial agent will be restricted due to the few patient specific factors.

31 Selection of Presumptive Therapy: Patient Examples (Slide 3 of 3)
Patient #3: 62-year-old male PMH: COPD, Diabetes, and Hypertension Current Medications: tiotropium , albuterol, valsartan, metformin, insulin Past medications: no recent antibiotics Allergies: none Possible bacteria for community acquired pneumonia: Haemophilus influenzae Pseudomonas aeruginosa Legionella species Streptococcus pneumonia Morexella cararrhalis Chlamydophila pneumonia Different pathogens due to history of COPD Gram stain: No organism identified This patient is older than the last patient with a past medical history. Therefore the suspicion for decreased renal or hepatic function is higher, and could be confirmed with laboratory testing. He has no allergies He has a past medical history listed, but no genetic or metabolic variations. Hypertension may be worsened by medications with a high sodium content. Diabetes may be worsened during an acute infection due to increase release of stress hormones. No recent use of antibiotics may place the patient at a lower risk for having a resistant bacteria. This patient has COPD which changes the typical bacteria that cause Community Acquire Pneumonia seen in normal patients The choices of antibacterial agent will be restricted due to the few patient specific factors.

32 Monitoring Therapeutic Response: Introduction
Patient should be monitored for clinical improvements for two to three days following the initiation of antimicrobial therapy Decrease in signs and symptoms of infection Absence of fevers Correction of WBC count Patients that fail to respond to therapy should be reevaluated closely

33 Monitoring Therapeutic Response: Switching from IV to Oral Therapy
Patients with an overall clinical improvement should be considered to be switched from parenteral to oral antimicrobial therapy Patients should meet the following criteria Lack of fever for 8 to 24 hours Decreased WBC count Have a functioning Gastrointestinal tract Oral antimicrobial therapy should have excellent oral bioavailability and activity against the suspected or isolated pathogen Drugs that exhibit excellent oral bioavailability when compared with IV formulations include ciprofloxacin, clindamycin, doxycycline, levofloxacin, metronidazole, moxifloxacin, linezolid, and trimethoprim–sulfamethoxazole.

34 Monitoring Therapeutic Response: Failure of Antimicrobial Therapy
Drug Selection Inappropriate Drug Selection Incorrect dosage Incorrect route Poor penetration into the site of infection Patient Factors Immunosuppression Need for surgical intervention to control source of infection Microorganisms Intrinsic resistance Acquired Resistance Alteration in the target site Change in membrane permeability Efflux pump Drug inactivation Malabsorption of a drug product because of GI disease (such as a short-bowel syndrome) or a drug interaction (such as complexation of fluoroquinolones with multivalent cations resulting in reduced absorption) can lead to potentially sub-therapeutic serum concentrations Patients with necrotizing fasciitis require surgical debridement (and sometimes amputation) of infected tissue with antimicrobial therapy to cure the patient.

35 Antibiograms Institutional differences in pathogen susceptibility
An antibiogram is a periodic summary of antimicrobial susceptibilities of local bacterial isolates submitted to the hospital's clinical microbiology laboratory The information in the antibiogram aid clinicians in the empiric selection of antimicrobial therapies. All culture and sensitivity results in a specific institution are compiled to evaluate for local resistance patterns

36 Antibiograms: Example
The antibiogram lists the pathogen, the number of isolates of that pathogen, and the percentage of the isolates that were susceptible to the tested antimicrobial therapies

37 Antimicrobial Stewardship
Multidisciplinary team that ensures appropriate and judicious use of antimicrobial therapy in an institution Make formulary recommendations Restrict antimicrobial therapies to infectious disease specialists

38 Link: List of Drugs of Choice, First Choice, Alternative(s)
Common Bacteria Link: List of Drugs of Choice, First Choice, Alternative(s)

39 Summary Confirm the presence of infection Identify of the pathogen
Nonspecific signs and symptoms of infection Fever WBC count Pain and inflammation Site specific symptoms Identify of the pathogen Gram Stain Culture Rapid test Select empiric antimicrobial therapy based on suspected infection, patient, medication factors, and local resistance Monitoring therapeutic response Improvement of signs and symptoms Consider 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.


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