Antimicrobial Stewardship Training

1. Antimicrobial Stewardship Training Part 1: Review of Basic Principles and Selected Antimicrobials By Keith Teelucksingh, PharmD Infectious Disease Pharmacist, Kaiser Permanente Vallejo With contributions by Linh Van, PharmD Infectious Disease Pharmacist, Kaiser Permanente Oakland This course is accepted by the California State Board of Pharmacy for 2.0 hours of credit. Provider #127: Accredited by CAPE Coursework expires: 1/1/2011

2. Antimicrobial Stewardship Training An Antimicrobial Stewardship program is a “an overarching program to change and direct antimicrobial use at a heath care institution.”1 A series of training programs have been developed to enhance pharmacists’ knowledge and expertise in providing antimicrobial stewardship at Kaiser Permanente hospitals. 1 MacDougall C, Polk R. Antimicrobial Stewardship Programs in Health Care Systems. Clin. Microbiol. Rev. Vol. 18 Oct 2005, p. 638-656

3. Antimicrobial Stewardship Training* Part 1: Review of Basic Principles and Selected Antimicrobials Provides core background information in three modules: • Microbiology Lab review • Antibiotic review • Allergy review See Notes

4. Module 1 (of 3): Microbiology Lab Review* Goal The goal of the Microbiology Lab Review module is to review and enhance pharmacists’ basic understanding of microbiology in the clinical setting.  See Notes

5. Objectives Upon completion of this module, the participant will be able to: • Differentiate between gram-positive and gram-negative bacteria and name pertinent species from each group. • Be able to interpret blood, urine, tissue and sputum culture results. • Define contamination and colonization. • Explain the purpose of urinalysis. • Be able to name some species of Coagulase-negative Staphylococcus (CoNS) and explain the significance of isolating CoNS from blood cultures.

6. Definitions * Infectious Disease: “an interaction with a microbe that causes damage to the host.”1 Pathogen: “any microorganism that has the capacity to cause disease.”1 Virulence: properties that enable a microorganism to establish itself on or within a host of a particular species and enhance its potential to cause disease. 1. Mandell, Bennett, & Dolin: Principles and Practice of Infectious Diseases, 6th Ed. See Notes

7. Definitions * Microbiology results will be reported similar to this See Notes

8. Definitions • Susceptible (S): implies that an infection due to the isolate may be appropriately treated with the dosage of antimicrobial agent recommended for that type of infection. • Only use an antibiotic that is reported as susceptible. • Intermediate (I): implies that an infection due to the isolate may be appropriately treated in body sites where the drugs are physiologically concentrated or when a high dosage of drug can be used (i.e., urinary tract).

9. Definitions Resistant (R): isolates that are not inhibited by the usually achievable concentrations of the agent with normal dosage schedules and/or fall in the range where specific microbial resistance mechanisms are likely (e.g., β-lactamases). Minimum inhibitory concentration (MIC): the lowest concentration of the antimicrobial agent that prevents visible growth after an incubation period. Breakpoint: discriminatory antimicrobial concentration used in the interpretation of results of susceptibility testing to define isolates as susceptible, intermediate or resistant. That is, the MIC where a bacteria goes from S to either I or R.

10. Gram Stain * • Can be performed on any body fluid • Only useful as preliminary guide – NOT definitive • Provides for rapid identification of presumed pathogen • Gram Positive (+) versus Gram negative (-) • Gives idea of morphology or arrangement of bacteria • cocci vs. rod • cluster, pairs, chain • Aids in selecting appropriate empiric antibiotic choices See Notes

11. Gram Stain * Application of series of dyes that affix to the peptidoglycan in bacterial cell wall: Purple Gram Positive Pink Gram Negative Bacteria isolated and colored with Gram stain. Gram-positive cocci, Staphylococcus aureus, from a lab culture. Gram-negative bacilli with a capsule, Klebsiella pneumoniae, from a pneumonia lung abscess (magnified 1,000×). See Notes

12. Bacterial Morphology * • Shapes • cocci = round • bacilli = rods • coccobacilli = ovoid • fusiform = pointed-end • Arrangements • single • pairs • clusters • chains See Notes

13. Microbiology: Common Pathogens * Gram-Positive Cocci Clusters Staphylococcus spp. Pairs or chains Streptococcus spp. including S. pneumoniae, S. viridans Enterococcus spp. Other species: Micrococcus spp. Staphylococcus aureus See Notes

14. Gram-Positive Bacilli (Rods) Diphtheroids: Corynebacterium spp. Proprionibacterium acnes Large, with spores: Clostridium spp (anaerobic) Bacillus spp Branching, beaded, rods: Nocardia spp. Actinomyces spp. Other Listeria spp. Lactobacillus spp. (vaginal flora) Microbiology: Common Pathogens Clostridium difficile

15. Common Bacteria and Classifications Adapted from Jeff Kuper, Pharm.D., BCPS See Notes

16. Gram-Negative Cocci Diplococci Pairs: Neisseria meningitidis Neisseria gonorrhea Other Acinetobacter spp. (technically a rod but can appear as cocci or bacilli) Microbiology: Common Pathogens Neisseria gonorrhoeae Acinetobacter baumannii

17. Gram-Negative Bacilli (Rods) Lactose fermenters Enterobacteriaceae (“enteric Gm -”) Serratia spp. Proteus spp. Enterobacter spp. Escherichia coli Citrobacter spp. Klebsiella spp. Nonfermenters Acinetobacter baumannii Pseudomonas aeruginosa Stenotrophomonas maltophilia Microbiology: Common Pathogens * Pseudomonas aeruginosa See Notes

18. Microbiology: Common Pathogens • Anaerobes • Gm + • Clostridium spp. (rods/bacilli) • Peptostreptococcus (cocci) • Gm - • Bacteroides spp. (rods/bacilli) • e.g. B. fragilis • Prevotella spp. (rods/bacilli) Clostridium difficile adhering to microvilli in the gut

19. Microbiology: Common Pathogens • Atypical bacteria • Mycoplasma pneumoniae • Legionella pneumophilia • Chlamydia pneumoniae • These bacteria are hard to culture on standard media, hence the name ‘atypical.’ • Commonly implicated in infections like community-acquired pneumonia (CAP). Legionella pneumophilia

20. *Program Learning* What type of bacteria is Bacteroides fragilis? How does the group of Enterobacteriaciae appear on gram stain? Name some atypical bacteria. What types of infections do atypical bacterial cause?

21. *Program Learning Answers* • What type of bacteria is Bacteroides fragilis? An anaerobic gram-negative rod. • How does the group of Enterobacteraciae appear on gram stain? Gram-negative and appear pink. • Name some atypical bacteria. What types of infections do atypical bacterial cause? Legionella pneumophilia, Chlamydia pneumoniae, Mycoplasma pneumoniae. These are mostly associated with community-acquired pneumonia.

22. The presence of bacteria on a body surface or mucous membrance without causing disease/infection. Upper respiratory tract (URT) – Strep. viridans, Candida spp Skin – S. epidermidis, Corynebacterium spp., S. aureus GI tract – E. coli, K. pneumoniae, Candida spp., Bacteroides spp. Urogential – Lactobacillus (vaginal flora) Colonization * S. epidermidis. CDC. See Notes

23. Colonization * See Notes • The presence of bacteria/organisms in a culture does not necessarily mean they are pathogenic. • It is up to the clinician to interpret the culture result and clinically correlate to the patient’s signs and symptoms.

24. Colonization • The following are considered sterile sites and are not prone to colonization: • Blood • Brain • Muscle • CSF • Synovial fluid

25. Contamination • An organism that is introduced at some point during the culturing process not related to or causing an infectious process. • Examples: Improperly prepped skin prior to venipuncture, drawn from ‘dirty’ IV line, poor lab technique  contamination on Petri dish). • Example: skin flora (S. epidermidis) being isolated in blood cultures.

26. Blood Cultures * • Definitive means of identifying most likely pathogens. • Most pathogens will grow within first 12–24 hours of collection (Candida, anaerobes may take longer). • Incubated for five days by laboratory. • Should be taken PRIOR to initiation of antibiotics. • Growth may be inhibited by antibiotics. See Notes

27. Blood Cultures * • Common contaminants: • Gm +cocci: Coagulase neg Staph (CoNS): S. epidermidis, S. hominis, S.capitis, S. warneri • Gm + rods: Corynebacterium spp., Micrococcus spp., Bacillus spp. (not anthracis) See Notes

28. Adapted from Jeff Kuper, Pharm.D., BCPS See Notes

29. Blood Cultures • The following should NEVER be considered contaminants: • Staphylococcus aureus • Gram – rods/bacilli • Candida spp.

30. Blood Cultures * So what’s the significance of isolating a Coagulase negative Staphylococcus spp. (CoNS) species from blood cultures? See Notes

31. Blood Cultures: Significance of CoNS • Assess how many blood cultures are positive vs. how many were drawn. • There should be a low suspicion for true infection if only one blood culture from multiple sets drawn around the same time period are positive for CoNS • There should be a low suspicion if only one culture is positive and cultures were drawn from separate sites (e.g., one from IV line, one from peripheral site). See next slide for more information.

32. Blood Cultures: Significance of CoNS * • What disease state/infection being treated? • Patients with an indwelling central line, hemodialysis catheter may be more at risk of infection. • Patients with foreign material (especially cardiac), bone/joint infections may have positive blood cultures for CoNS. See Notes

33. Blood Cultures: Significance of CoNS * • What constitutional symptoms does the patient have? • Fever, leukocytosis • What type of patient? • Immunocompetent • Immunocompromised • Chemotherapy/meds • Disease state (advanced HIV) • Transplant • Neutropenic See Notes

34. Blood Cultures: Significance of CoNS • In general, a solitary peripheral blood culture positive for CoNS in an immunocompetent patient should be regarded as a contaminant if: • No other blood cultures drawn in a reasonable time frame are also growing CoNS. • The patient does not have prosthetic material present or does not have a central line/catheter. • If another source of infection is identified to account for the patient’s constitutional symptoms. • If patient has no signs or symptoms of infection.

35. Blood Cultures: Significance of CoNS Just as in any clinical situation where the case is not straightforward or there are questions: If ever in doubt, present case to ID physician.

36. Urine Culture * Urine samples are held for 24 hours by microbiology lab. Bacterial growth expressed as colony counts, i.e., >100,000 colony forming units (CFU). Should always have a corresponding urinalysis (UA) performed for microscopy. If >2 bacteria are isolated from a urine culture, the lab will not perform any further work-up on the specimen. See Notes

37. Urine Culture • Why perform a UA? • The examination of fluid microscopy allows for some differentiation between infection vs. colonization vs. contamination. • Infected fluid should have WBC, neutrophils or other inflammatory markers. • Uninfected fluids generally are devoid of these markers. • Keep in mind that immunocompromised patients may not be able to mount a strong enough immune response to produce these markers.

38. Urine Culture: Interpreting the UA • How many WBCs in urine? • How many epithelial/squamous cells present? • The lower the number, the ‘cleaner’ the sample (i.e., you can probably trust culture result). • The higher the number increases risk of contamination with colonizing flora (i.e., sample taken too early in the urine stream) • What amount of leukocyte esterase present? • Given as trace, small, moderate and large. • Found in certain WBC, sign of inflammation.

39. Tissue Culture • Preliminary report available at 24 hours, incubated for 72 hours total. • Lab will quantify growth of organism: rare, light, moderate and heavy. • Tissue sample is plated onto agar plate. • Quantification of growth on plate gives some idea of the bacterial burden of a sample.

40. Tissue Culture • These cultures can vary in quality: • Some may be superficial samples (i.e., more prone to contamination or colonization); others may be deep tissue samples or cultures from an operation (i.e., less likely to be contaminated or colonized). • The presence of cellulitis, pus, exposed bone can help distinguish true infection from contamination or colonization. • Read the MD note carefully and get some idea of what the area looks like, whether the MD thinks the area looks clinically infected or not.

41. Sputum Culture • Gram stain done initially by lab to assess quality of specimen. • If > 10 epithelial cells, sample is not worked up: • Sample not indicative of lower airway secretion. • May be prone to contamination. • Patients with pulmonary infection should have purulent sputum. • Presence of WBC on gram stain.

42. *Program Learning* Name some organisms that are commonly found on the skin. True or False: Coagulase positive Staphylococci growing from a blood culture should be considered a contaminant. Which microbes may take longer to grow out in blood cultures? True or False: It is common for CSF and synovial fluid to be colonized with bacteria.

43. *Program Learning Answers* • Name some organisms that are commonly found on the skin: S. epidermidis, S. aureus, Corynebacterium spp. • True or False: Coagulase positive Staphylococci growing from a blood culture should be considered a contaminant. False: CoNS are usually contaminants. Staphylococcus aureus is coagulase + and should never be considered a contaminant when isolated from the blood.

44. *Program Learning Answers* • Which microbes may take longer to grow out in blood cultures? Anaerobes and Candida spp. take longer to grow out in blood cultures. • True or False: It is common for CSF and synovial fluid to be colonized with bacteria. CSF and synovial fluid are considered sterile sites and are not commonly colonized.

45. References This concludes Module 1, the Microbiology Lab Review. Please proceed to Modules 2 and 3. Mandell, Bennett & Dolin. Principles and Practice of Infectious Disease. 7th ed. http://cl.kp.org (accessed Oct. 14, 2009). Kaiser Permanente Laboratory Manual – Information - Northern California. http://cl.kp.org (accessed Oct. 14, 2009). Mermel, L. et al. Clinical Practice Guidelines for the Diagnosis and Management of Intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49:1-45.