Principles of Infectious Diseases
Anas Bahnassi PhD
Pharmacotherapy of Infectious Diseases
Anas Bahnassi 2014
A Case-Based...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Clinical Pearls
• Although acute infection generally is associated ...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Clinical Pearls
• Isolation of an organism may reflect infection; h...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Approaching the Problem
Infection is
documented
Infection site
is i...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Establishing Infection:
• R.G., a 63-year-old, 70-kg man in the ICU...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Establishing Infection:
Physical examination reveals:
• Sinus tachy...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Establishing Infection:
• A chest radiograph demonstrates
bilateral...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Establishing Infection:
Laboratory Results
Anas Bahnassi 2014
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Establishing Infection:
Which of R.G.’s signs and symptoms are
cons...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Establishing Infection Severity:
Sepsis Cascade
Anas Bahnassi 2014
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Establishing Infection Severity:
What signs and symptoms manifested...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Establishing Infection Site:
What are the most likely sources of R....
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Determining the likely pathogen:
What are the most likely pathogens...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Susceptibility of the organism:
A Gram stain of R.G.’s tracheal asp...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Susceptibility of the organism:
In Vitro Antimicrobial Susceptibili...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Susceptibility of the organism:
Anas Bahnassi 2014
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Antimicrobial Toxicities:
Serratia marcescens grows from a culture ...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Antimicrobial Toxicities:
R.G. is empirically started on imipenem a...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Antimicrobial Cost of Therapy:
What factors should be included in c...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Antimicrobial Cost of Therapy:
What factors should be included in c...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Route of Administration:
Oral ciprofloxacin was considered for the ...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Antimicrobial Dosing:
What dose of IV ciprofloxacin should be given...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Pharmacokinetics and
Pharmacodynamics:
R.G.’s respiratory status re...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Pharmacokinetics and
Pharmacodynamics:
• β-Lactams, such as cefotax...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Once-Daily Dosing of
Aminoglycosides:
• As a result of PAE and othe...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Antimicrobial Protein Binding:
Ceftriaxone (Rocephin), rather than ...
PharmacotherapyofInfectiousDiseasesACase-BasedApproach
Pharmacotherapy:
Infectious Diseases:
Anas Bahnassi PhD
abahnassi@g...
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Principles of infectious diseases

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A case-based approach of the principles of infectious diseases. These principles are presented through a case with a discussion provided.

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Principles of infectious diseases

  1. 1. Principles of Infectious Diseases Anas Bahnassi PhD Pharmacotherapy of Infectious Diseases Anas Bahnassi 2014 A Case-Based Approach
  2. 2. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Clinical Pearls • Although acute infection generally is associated with an increased white blood cell count, fever, and localizing signs, these symptoms may be absent in less severe disease. • More severe infection, including sepsis, may be associated with hypotension, disseminated intravascular coagulation, and end- organ dysfunction. • Other disease states, particularly autoimmune disease and malignancy, may mimic infectious diseases. • Although it should be considered a diagnosis of exclusion, drug- induced fever should be ruled out, particularly in patients without other classic signs and symptoms of infection. • Site-specific signs and symptoms and host factors generally predict the most likely pathogens, and empirical antimicrobial therapy should be directed against these organisms. Anas Bahnassi 2014
  3. 3. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Clinical Pearls • Isolation of an organism may reflect infection; however, colonization and contamination must be ruled out to avoid unnecessary antimicrobial exposure. • Once the site of infection is confirmed and the likely pathogens are identified, antimicrobial toxicity and side effects, costs, site of infection, drug distribution, and route of administration must be considered before selection of therapy. • Antimicrobial dosing should reflect site of infection, route of elimination, and pharmacokinetics and pharmacodynamics. • Antimicrobial failure may be related to pharmacologic factors (inadequate dosing, insufficient penetration to the site of infection, and inadequate duration) and host factors (presence of prosthetic material, undrained focus of infection, and immune status). Anas Bahnassi 2014
  4. 4. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Approaching the Problem Infection is documented Infection site is identified Additional Lab tests requested Signs and Symptoms Organism Responsible Antimicrobial agent identified Dose and Duration Patient Size Infection site Route of Administra- tion Other factors Anas Bahnassi 2014
  5. 5. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Establishing Infection: • R.G., a 63-year-old, 70-kg man in the ICU, underwent emergency resection of his large bowel. • Mechanically ventilated throughout his post-op course. • On day 20 of his hospital stay, R.G. suddenly becomes confused; BP drops to 70/30 mm Hg, HR of 130 b/min. • His extremities are cold to the touch, and he presents with circumoral pallor. • His temperature increases to 40◦, RR = 24/min. • Copious amounts of yellow-green secretions are suctioned from his endotracheal tube. Anas Bahnassi 2014
  6. 6. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Establishing Infection: Physical examination reveals: • Sinus tachycardia with no rubs or murmurs. • Rhonchi with decreased breath sounds are observed on auscultation. The abdomen is distended. R.G. complains of new abdominal pain. • No bowel sounds can be heard, and the stool is guaiac positive. • Urine output from the Foley catheter has been 10 mL/hour for the past 2 hours. • Erythema is noted around the central venous catheter. Anas Bahnassi 2014
  7. 7. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Establishing Infection: • A chest radiograph demonstrates bilateral lower lobe infiltrates, and urinalysis reveals >50 white blood cells/high power field (WBC/HPF), few casts, and a specific gravity of 1.015. Blood, endotracheal aspirate, • Urine cultures are pending. Anas Bahnassi 2014
  8. 8. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Establishing Infection: Laboratory Results Anas Bahnassi 2014
  9. 9. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Establishing Infection: Which of R.G.’s signs and symptoms are consistent with infection? • His WBC count (15,600/μL) is increased, and a “shift to the left” (bands, i.e., premature neutrophils) is observed on the differential. • R.G has fever which is a common manifestation for infection. • The bilateral lower lobe infiltrates on R.G.’s chest radiograph, • Presence of copious amounts of yellow- green secretions from his endotracheal tube, and the erythema surrounding his central venous catheter also are compatible with one or more infectious processes. Anas Bahnassi 2014
  10. 10. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Establishing Infection Severity: Sepsis Cascade Anas Bahnassi 2014
  11. 11. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Establishing Infection Severity: What signs and symptoms manifested by R.G. are consistent with a serious systemic infection? • Hemodynamic Changes. • Cardiac Output. • Systemic Vascular Resistance. • Cellular Changes. • Glucose Metabolism • Respiratory Changes. • Hematologic Changes. • Disseminated intravascular coagulation • Neurologic Changes. • Lethargy… • Fever. • Drug Effects. • Corticosteroids mask infection. Anas Bahnassi 2014
  12. 12. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Establishing Infection Site: What are the most likely sources of R.G.’s infection? R.G. has several possible sites of infection. • The copious production of yellow-green sputum, tachypnea, and the altered chest radiograph suggest pneumonia. • The abdominal pain, absent bowel sounds, and recent surgical procedure, however, suggest an intra-abdominal source. • The abnormal urinalysis (>50 WBC/HPF) and the erythema around the central venous catheter suggest urinary tract and catheter infections. Anas Bahnassi 2014
  13. 13. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Determining the likely pathogen: What are the most likely pathogens associated with R.G.’s infection(s)? • Bacterial pneumonia is caused by various pathogens, including: Streptococcus pneumoniae, Enterobacteriacae, and atypical pathogens (e.g., Legionella pneumophila) • Empirical antimicrobial therapy directed against all the above organisms is not necessary in all patients. • Community acquired pneumonia in normal hosts is generally associated with S. pneumoniae, Haemophilus influenza, and “atypical” bacterial pathogens. • In contrast, nosocomial (hospital, nursing home) pneumonia is associated with gram-negative bacilli (e.g., Escherichia coli, Klebsiella species, Enterobacter species, and Pseudomonas aeruginosa) and Staphylococcus aureus. Anas Bahnassi 2014
  14. 14. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Susceptibility of the organism: A Gram stain of R.G.’s tracheal aspirate shows gram-negative bacilli. What tests may assist with the identification of the pathogen(s)? • Culture and susceptibility testing (18-24h to complete) • Disk Diffusion (Agar). • Broth Dilution (Tubes). Anas Bahnassi 2014
  15. 15. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Susceptibility of the organism: In Vitro Antimicrobial Susceptibility: Aerobic Gram- Positive Cocci Anas Bahnassi 2014
  16. 16. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Susceptibility of the organism: Anas Bahnassi 2014
  17. 17. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Antimicrobial Toxicities: Serratia marcescens grows from a culture of R.G.’s endotracheal aspirate. How can it be determined whether an isolate represents a true bacterial infection versus colonization or contamination? • Culture results do not solely identify true • pathogens. • In R.G., the Serratia may be a pathogen, contaminant, or colonizer. • Considering the severity of R.G.’s illness and his associated respiratory symptoms, treatment directed against this pathogen is necessary. Anas Bahnassi 2014
  18. 18. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Antimicrobial Toxicities: R.G. is empirically started on imipenem and gentamicin. In review of his patient records, R.G. has no known allergies. Are there equally effective, less toxic options for this patient? • Adverse Effects and Toxicities: • Allergies… • Concomitant Disease States: • Older patients with hearing deficits are poor candidates for potentially ototoxic aminoglycoside therapy. • Diabetic or kidney transplant patients with candidemia may be better treated with fluconazole or an echinocandin rather than nephrotoxic amphotericin B products Anas Bahnassi 2014
  19. 19. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Antimicrobial Cost of Therapy: What factors should be included in calculating the cost of R.G.’s antimicrobial therapy? • Determining the true cost of antimicrobial therapy is complex. • Acquisition cost, IV bags, infusion controllers, and labor must be incorporated into the analysis. • Although they are difficult to estimate, other costs, including antibiotic toxicity and failure of therapy, also should be included. Anas Bahnassi 2014
  20. 20. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Antimicrobial Cost of Therapy: What factors should be included in calculating the cost of R.G.’s antimicrobial therapy? • Determining the true cost of antimicrobial therapy is complex. • Acquisition cost, IV bags, infusion controllers, and labor must be incorporated into the analysis. • Although they are difficult to estimate, other costs, including antibiotic toxicity and failure of therapy, also should be included. Anas Bahnassi 2014
  21. 21. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Route of Administration: Oral ciprofloxacin was considered for the treatment of R.G.’s presumed Serratia pneumonia, but the IV route was prescribed. Why is the oral administration of ciprofloxacin reasonable (or unreasonable) in R.G.? • In septic patients,” blood flow often is shunted away from the mesentery and extremities, resulting in unreliable oral or muscular bioavailability. • Hemodynamically unstable patients should always receive antimicrobials by the IV route to ensure therapeutic antimicrobial levels. • Drug interactions with oral agents can result in subtherapeutic serum concentrations (e.g., reduced bioavailability associated with concomitant quinolone and antacid administration and the decreased absorption of itraconazole with[PPI] therapy). Anas Bahnassi 2014
  22. 22. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Antimicrobial Dosing: What dose of IV ciprofloxacin should be given to R.G.? What factors must be taken into account in determining a proper antimicrobial dose? • Patient Age. • Site of Infection. • Anatomic and physiologic barriers. • Fever and Inoculum effect. • Route of Elimination • Creatinine Clearance. Anas Bahnassi 2014
  23. 23. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Pharmacokinetics and Pharmacodynamics: R.G.’s respiratory status remains unchanged; thus, the ciprofloxacin is discontinued and cefotaxime and gentamicin are started empirically. The use of a constant IV infusion of cefotaxime is being considered in R.G. In addition, the use of single daily dosing of gentamicin is being discussed. What is the rationale for these approaches, and would either be advantageous for R.G.? Anas Bahnassi 2014
  24. 24. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Pharmacokinetics and Pharmacodynamics: • β-Lactams, such as cefotaxime, are not associated with increased bacterial killing with increasing drug concentrations but of the duration of time the AB is kept above MIC. • The efficacy of quinolone antimicrobials appears to correlate with the peak plasma concentration to MIC ratio or (AUC) to MIC ratio. • Gentamycin has been administered q 8 -12 hrs to achieve peak serum of 5-8 g/mL to ensure efficacy in the treatment of serious gram-ve infection. • Gentamicin troughs >2mcg/mL have been associated with an increased risk for nephrotoxicity, • Several antimicrobials (e.g., aminoglycosides) have been associated with a pharmacodynamic phenomenon known as a postantibiotic effect (PAE). PAE is delayed regrowth of bacteria after exposure to an antibiotic. Anas Bahnassi 2014
  25. 25. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Once-Daily Dosing of Aminoglycosides: • As a result of PAE and other pharmacodynamic factors, certain antimicrobials may be dosed less frequently. • Higher doses less frequently should provide the same advantages. • Single daily dosing of aminoglycosides has been investigated primarily in patients with normal renal function, and few critically ill patients have been treated with this nontraditional regimen. • Thus, patients in septic shock are less clear candidates for once-daily dosing. Anas Bahnassi 2014
  26. 26. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Antimicrobial Protein Binding: Ceftriaxone (Rocephin), rather than cefotaxime (Claforan), is being considered for the treatment of R.G.’s infection. Ceftriaxone is more highly protein bound than cefotaxime. Why is protein binding important in the selection of therapy? • Free (i.e., unbound) rather than total drug levels are best correlated with antimicrobial activity. • Although ceftriaxone is 85% to 90% protein bound, the free concentrations probably remain far above the MIC of the Serratia. • Therefore, protein-binding considerations are unlikely to be important in the treatment of R.G.’s infection. Anas Bahnassi 2014
  27. 27. PharmacotherapyofInfectiousDiseasesACase-BasedApproach Pharmacotherapy: Infectious Diseases: Anas Bahnassi PhD abahnassi@gmail.com http://www.twitter.com/abpharm http://www.facebook.com/pharmaprof http://www.linkedin.com/in/abahnassi Anas Bahnassi 2014
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