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Update in Infectious Diseases: use and abuse of Antibiotics

Update in Infectious Diseases: use and abuse of Antibiotics. American College of Physicians Oklahoma Chapter October 14, 2011 Douglas A. Drevets MD, DTM&H Professor and Chief, Infectious Diseases OUHSC Staff Physician, VAMC Oklahoma City, OK. Learning Objectives & Seminar Outline.

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Update in Infectious Diseases: use and abuse of Antibiotics

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  1. Update in Infectious Diseases:use and abuse of Antibiotics American College of Physicians Oklahoma ChapterOctober 14, 2011 Douglas A. Drevets MD, DTM&H Professor and Chief, Infectious Diseases OUHSC Staff Physician, VAMC Oklahoma City, OK

  2. Learning Objectives & Seminar Outline 1. Review a case scenario that illustrates common issues in antibiotic use. 2. Review data regarding use / overuse of antibiotics and the emergence of antibiotic-resistant bacteria 2. Discuss the structure and positive impacts of antimicrobial stewardship programs. 3. Discuss local antimicrobial stewardship programs and the most frequent topics that they identify.

  3. Increasing Amounts of Antibiotic-Resistant Bacteria in Hospital Settings Wenzel, et al. Infect Control Hosp Epidemiol 2008; 29:1012-1018.

  4. NIH Talking Points About Antibiotics and Antimicrobial Resistance • Between 5 and 10 percent of all hospital patients develop an infection leading to an increase of about $5 billion in annual U.S. healthcare costs. • About 90,000 of these patients die each year as a result of their infection, up from 13,300 patient deaths in 1992. • People infected with antimicrobial-resistant organisms are more likely to have longer hospital stays and may require more complicated treatment. www.niaid.nih.gov/topics/antimicrobialresistance

  5. Case History 19 yr old F with brittle type I diabetes sought emergency medical attention for severe myalgias, chest pain, and weakness of 1 day duration. She noted shortness of breath with rapid breathing, and a vaginal discharge. Denied fever, chills, cough, abdominal pain, dysuria, etc. PMH Multiple admissions for DKA Recent admission to outside facility 1 week ago no drugs, alcohol or allergies PE BP 98/53, Hr 118, RR35, afebrile on admission Ill-appearing and in severe distress with Kussmal breathing Left upper extremity was swollen and erythematous Vaginal discharge was present

  6. Case History Continued • Key labs • Chemistries: Glucose 506, CO2 <5, Cr. 1.52, lactate 3.3 • ABG: pH 7.01 pCO2 11.2 pO2 86 • WBC: 47.9K, 80% segs, 4% bands • UA: 25-30 WBC/hpf, heavy bacteria, 5-10 hyaline and granular casts • Chest X-rays showed interstitial and patchy airspace opacities. • Initial clinical course • Rapidly developed high fever to 41C • Required intubation • Required multiple vasopressors • CXR -bilateral diffuse, patchy infiltrates with multiple, ill-defined nodular densities.

  7. Case History: Differential Diagnosis • DKA with shock • Initial differential diagnosis/possibilities • Sepsis/septic shock • UTI • Severe skin/soft tissue infection, e.g. necrotizing fasciitis • Nosocomial infection from prior hospitalization • ?PID/intra-abdominal infection • ARDS • Due to sepsis/septic emboli • Influenza • Nosocomial pneumonia from prior hospitalization

  8. Empiric Antimicrobial Treatment • Ciprofloxacin • Clindamycin • Doxycycline • Piperacillin/tazobactam • Vancomycin • Oseltamivir

  9. Hospital Course • Blood cultures grew MRSA • BAL showed >105 CFU/ml MRSA • Urine culture grew G. vaginalis • Ultrasound of left forearm showed cellulitis with a thrombosed antecubital vein. • Unifying diagnosis was MRSA sepsis possibly due to septic thrombophlebitis complicated by DKA and pneumonia/septic pulmonary emboli.

  10. Focused Antimicrobial Treatment • Most antimicrobials were stopped. • Antimicrobial therapy was directed at MRSA. • A bit of a twist • MRSA isolated from BAL had MIC to vancomycin of 2ug/ml • Vancomycin was stopped • Daptomycin + linezolid was started • Patient survived

  11. Key Antimicrobial Teaching Points • Drug resistant organism (MRSA) • Pharmacologic peculiarities of antibiotic • Daptomycin and the lung • Dose optimization based on renal function, organism, and location of infection • Vancomycin and MRSA pneumonia • Empiric therapy versus focused therapy • The need to change therapy even when the patient is improving

  12. Proper Antibiotic Use Is Just Like Proper Shark Fishing Good outcomes: Fish swims away Fisherman keeps fingers Happy fisherman Feeling proud of myself and quite manly ZZZZZZZZZZ Quiet fish Cayo Costa State Park, FL

  13. Proper Use Of Antibiotics • Good antibiotic choices • Infection is controlled and cured • Good outcomes • Patient does well • Lower risk of therapy related complications • Reduced risk of developing drug-resistant bacteria

  14. Improper Antibiotic Use Is Like Shark Fishing Gone Wrong Maybe this was a bad idea? Concerned fisherman Just a little closer…. Frisky fish High potential for bad outcome: Fish looses temper Fisherman loses body part Cayo Costa State Park, FL

  15. Improper Use Of Antibiotics • Poor antibiotic choices • Infection • Gets worse • Slow to respond • Not cured • Higher risk of bad outcomes • Patient does not well • Relapse of infection • Higher risk of therapy related complications • Higher risk of developing drug-resistant bacteria

  16. Effect Of Antibiotics On Microbial Ecosystems Green = susceptible Red = resistant ABX Courtesy of Chris Gentry, Pharm. D.

  17. Know When To Say When

  18. Association Of Vancomycin Use With VRE Kim NJ et al. JID 1999;179:163

  19. Association of Carbapenam Use with Imipenam-Resistance P. aeruginosa r = 0.41, p = .004 (Pearson correlation coefficient) Gould et al. ICHE 2006;27:923-5

  20. Antimicrobial-Resistant Bacteria in Primary Care • Meta-analysis of 24 studies • 22/24 involved symptomatic patients • 2/24 relied on healthy volunteers • 19/24 were observational • 5/19 – randomized trials • Analyzed time –dependent emergence of drug-resistant bacteria in: • Urine • Respiratory tract Costelloe, C. et al. BMJ 340:c2096, 2010.

  21. Meta-Analysis: Key findings • Bacterial resistance to the prescribed antibiotic develops routinely • The effect is greatest in the month immediately after treatment • The effect wanes, but may persist up to 12 months • Longer duration and multiple courses were associated with higher rates of resistance • This is important as primary care is responsible for the majority of antibiotic use in humans Costelloe, C. et al. BMJ 340:c2096, 2010.

  22. Association Between Drug-Resistant Organisms and Poor Clinical Outcomes • MRSA • Mortality risk associated with MRSA bacteremiarelative to MSSA bacteremia: OR: 1.93; p < 0.001.1 • Mortality of MRSA infections was higher than MSSA: relative risk [RR]: 1.7 (1.3–2.4).2 • Drug-resistant tuberculosis • Mortality riskof patients with TB: RR of death was 4.68 (2.02–10.8) –fold greater for MDR vs. drug susceptible TB. 1. Cosgrove et al., Clin. Infect. Dis.36:53–59 , 2003. 2. Shurland et al. Infect. Control Hosp. Epidemiol.28:273–279, 2007. 3. Quy, Int. J. Tuberc. Lung Dis. 10:45–51 , 2006.

  23. Impact of Carbapenem Resistance on Mortality Caused by K. pneumoniae p<0.001 Resistant p<0.001 Susceptible OR 3.71 (1.97-7.01) OR 4.5 (2.16-9.35) Patel G et al. Infect Control Hosp Epidemiol 2008;29:1099-1106

  24. Direct Link Between Antibiotic Use and a Particular Infection • The preceding data suggest poor outcomes con be associated with drug-resistant bacteria. • This could be due to • Delay of “active “ antimicrobial therapy • Change in bacterial virulence • Poor efficacy of alternative antimicrobials • It has been difficult to link in hospital abx use to outcomes. • Use of C. difficileinfection as a marker.

  25. Linking Antibiotic Useage to C. difficileInfection in a Teaching Hospital • A retrospective cohort study conducted from 1 January to 31 December 2005 among hospitalized patients 18 years or older receiving 2 or more days of antibiotics. • 10,154 hospitalizations for 7,792 unique patients • 241 cases of CDI • Detection of C. difficile toxin in a diarrheal stool sample within 60d. • Eliminated cases diagnosed pre-hospitalization or 2 d after admission. • Quantified antimicrobial use/exposure • Controlled for co-morbidities that might change risk of CDI. Stevens et al. Clin. Infect. Dis. 53:42, 2011

  26. Cumulative Antibiotic Exposures and the Risk of C. difficile Infection

  27. Association of Antibiotic Classes with C. difficileInfection

  28. One’s Own Role in Antimicrobial Resistance Depends on Their Point of View A Survey of Faculty and Resident Physicians Attitudes, Perceptions, and Knowledge About Antibiotics Abbo et al. Infection Control and Hospital Epidemiol. 32:714-8, 2011.

  29. “I Am A Better Than Average Driver” Abbo et al. Infection Control and Hospital Epidemiol. 32:714-8, 2011.

  30. A Modicum of Knowledge Assessment Abbo et al. Infection Control and Hospital Epidemiol. 32:714-8, 2011.

  31. Strategies To Combat Antimicrobial Resistance • Reduce antibiotic exposure • Healthcare • Agricultural • Public awareness campaigns (CDC) • Get Smart About Antibiotics Week November 14-20, 2011 • Education of healthcare providers • Focused attention on inpatient use • Antimicrobial Stewardship Programs

  32. IDSA/SHEA Supplemental Elements of Antimicrobial Stewardship Programs Rapp et al . A hospital pharmacist’s guide to antimicrobial stewardship programs, Cited in Septimus et al. Clin. Inf. Dis. 53:S8, 2011.

  33. Outcomes for Patients Treated With Aminoglycosides or Vancomycin in Hospitals With and Without a Pharmacist-led ASP Bond et al. Am J Health Syst. Pharm 62:1596, 2005.

  34. Clinical and Economic Outcomes in Surgical Patients in Hospitals With and Without a Pharmacist-led ASP Bond et al. Am J Health Syst. Pharm 64:1935-42, 2007.

  35. Examples of Local Antimicrobial Stewardship Programs • OUMC and the VAMC • Both programs include a mix of administrative and clinical duties. • Formulary restriction • Review of antibiotics • Recommendations communicated with primary team • Clinical outcomes @ VAMC • Analysis of patents before and after Antimicrobial Stewardship Program • Length of stay 13.2 days versus 10.8 days (p <0.0001) • Mortality 8.28% versus 6.61% (p <0.007) Gentry et al. Am J Health Syst. Pharm 57:268-74, 2000.

  36. Antimicrobial Stewardship at OUMC • Joint effort between OUMC Inpatient Pharmacy and Infectious Diseases • Computer-distance (Meditech) review of all adult inpatients on antibiotics. • Age, gender, weight, renal function and diet • Cultures • Drug levels (vancomycin, aminoglycoside) • Additional information available • Communication to primary team • Written recommendations placed in chart – do not become part of the official record. • Occasional phone call • ID consult is recommended in select cases

  37. Most Common Antibiotic Streamlining Issues at OUMC

  38. Typical Antimicrobial Recommendations Make an IV to PO switch • Antibiotics that have good-to-excellent oral bioavailability • Acyclovir, valacyclovir & valgancyclovir • Azithromycin • Fluoroquinolones • Fluconazole/voriconazole • Metronidazole • Linezolid • Rifampin • Trimethoprim-sulfamethoxazole • Need to make sure that the gut works • Beware of divalent cations.

  39. Typical Antimicrobial Recommendations Change the dose of i.v. antibiotics • Gentamicin • Wrong - 80 mg iv q 8hrs regardless of CrCl, age, body weight or type of infection • Right dose depends on several factors • Dose according to type of infection and role of antibiotic • Synergy for Gram positive requires lower levels • Therapy for Gram negative requires higher levels • CrCl • Varies with age and body weight • Generally use single dose if possible • Follow trough levels (<1.0)

  40. Typical Antimicrobial Recommendations Change the dose of i.v. antibiotics • Vancomycin • Wrong - 1 gm iv q 12hrs regardless of CrCL, age, body weight or type of infection • Right – • CrCl is critical • Varies with age and body weight • Young people have much higher CrCl and need larger doses • Follow trough levels • (15.0 – 20.0 ug/ml) for severe MRSA infection/pneumonia • Rybak et al. Am J Health-Syst Pharm. 2009; 66:82-98. • Generally use multiple daily doses in the setting of normal renal function • Generally use intermittent dosing in renal failure • Avoid q18hr or q36hr dosing

  41. Typical Antimicrobial Recommendations Changes an antibiotic combinations that is unnecessary or not helpful • Piperacillin/tazobactam + metronidazole • Metronidazole or clindamycin are often used for anaerobic activity. • In this case pip-tazo (or imipenam, meropenam, etc.) already provide better anaerobic activity that do either metronidazole or clindamycin. • Metronidazole is potentially useful if C. difficile colitis, giardiasis, or amoebic liver abscess are in the differential diagnosis.

  42. Typical Antimicrobial Recommendations Changes an antibiotic combinations that is unnecessary or not helpful –part II • Aztreonam + 3rd gen cephalosporin • Aztreonam is a semi-synthetic b-lactam known as a mono-bactam. • Works by binding penicillin-binding protein 3 • Same R1 and R2 groups as ceftazidime Aztreonam • Cephalosporins are b-lactam antibiotics based on a hetero-cyclic cepham nucleus. • Work by binding a variety of penicillin-binding proteins • Because these drugs have the similar/same mechanism of action, there is little benefit to this combination. Cepham nucleus

  43. Pharmacologic Missteps • Daptomycin and the lung • Drug is bound and inactivated by surfactant. • Moxifloxacin and urine • Moxifloxacin is poorly excreted in the urine • Most drugs and the CNS • Higher amounts are necessary

  44. Conclusions • Drug resistant bacteria are a major health hazard • Proper use of antibiotics is important for: • Optimal patient outcomes • Prevention of antibiotic resistance • Benefits of antimicrobial stewardship programs include: • Improve antibiotic selection and utilization • Improve patent outcomes • Effect cost savings

  45. Thanks For Your Attention 9’2” Lemon shark Indian Pass, Port St. Joe, FL

  46. Wishing You A Good Antibiotic Outcome Shark swims away

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