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Snapshots From 2010 IDSA

Louie, Ted MD

Infectious Diseases in Clinical Practice: March 2011 - Volume 19 - Issue 2 - p 80-82
doi: 10.1097/IPC.0b013e31820a545d
IDCP Snapshots

It is an impossible task to assemble a summary of IDSA, but I have chosen major themes that should prove useful to the majority of clinicians. The slides and audio are available on the Internet and can be purchased by logging onto

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Per Dr. Sarah Cosgrove, "Antibiotic stewardship (AS) refers to processes designed to measure and optimize the appropriate use of antimicrobials by selecting the appropriate agent, dose, duration of therapy and route of administration. The major objectives of antimicrobial stewardship are to achieve optimal clinical outcomes, to minimize toxicity and other adverse events, and to minimize the development of antimicrobial resistance. Antimicrobial stewardship may also reduce excessive costs attributable to inappropriate or unnecessary therapy, suboptimal outcomes, toxicity and other adverse events, and antimicrobial resistance."2

For the last 10 years, much data have accumulated to support the benefits of AS. In terms of patient safety, it has been shown that AS can decrease the incidence of Clostridium difficile-associated diarrhea.6 Antibiotic stewardship can also decrease antibiotic resistance. For example, Pseudomonas strains became more susceptible after AS was initiated.7 Finally, AS can significantly decrease antibiotic costs. Depending on many factors including the size of the hospital and the patient mix, the yearly cost savings can range from $140,000 to $300,0008,9 or more at larger institutions.

Implementing a new AS program involves careful planning, identifying the key members in your hospital to help with data gathering, and executing the plan. It requires "selling" the idea to the hospital administration, physicians, infection control committee, and pharmacy.5

For more information, please see the IDSA/SHEA guidelines of implementing AS by using the link

Also, log onto to view the AS page on the SHEA Web site.

Note: the CDC has shown increasing interest in AS. As methods of reimbursement change to reward quality rather than number of services provided, there is an opportunity for infectious disease physicians to become even more valued members of their hospital systems, by providing AS. At the 2010 IDSA, there were "Meet the Professor" sessions and a satellite symposium on AS, in addition to the above premeeting session. As developing such a program takes many hours of preparation, the best time to start would be immediately.

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1. Fishman N. Antimicrobial management: design, implementation, and efficacy. Premeeting session 1. No. 1 IDSA; 2010.

2. Cosgrove S. Driving change: why antimicrobial stewardship? Premeeting session 1. No. 2 IDSA; 2010.

3. Ohl C. Tailoring to your reality: effective strategies for designing a stewardship program. Premeeting session 1. No. 3 IDSA; 2010.

4. Septimus E. Components of a practical implementation approach: using a "driver diagram" for antimicrobial stewardship. Premeeting session 1. No. 4 IDSA; 2010.

5. Small R. Developing and delivering your business case for an antimicrobial stewardship program. Premeeting session 1. No. 5 IDSA; 2010.

6. Carling P, Fung T, Killion A, et al. Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years. Infect Control Hosp Epidemiol. 2003;24:699-706.

7. White AC, Atmar RL, Wilson J, et al. Effects of requiring prior authorization for selected antimicrobials: expenditures, susceptibilities, and clinical outcomes. Clin Infect Dis. 1997;25:230.

8. Fishman N. Antimicrobial stewardship. Am J Med. 2006;119:S53-S61.

9. LaRocco A. Concurrent antibiotic review programs-a role for infectious disease specialists at small community hospitals. Clin Infect Dis. 2003;37:74-83.

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The use of immunomodulatory agents (IAs) for inflammatory conditions, malignancies, and neurologic conditions has increased greatly. It has become apparent that IA increase the risk of certain infections. Rituximab, for example, increases the risk of hepatitis B reactivation, progressive multifocal leukoencephalopathy, and possibly increases the risk of Pneumocystis jiroveci pneumonia, atypical mycobacteria, and viruses including enterovirus and parvovirus B19.3

Although IAs are grouped together for convenience, their mechanisms of action are quite different. Etanercept, infliximab, and adalimumab, for example, are all tumor necrosis α inhibitors, but etanercept acts on the soluble p75 receptor, whereas infliximab and adalimumab are monoclonal antibodies. The risk of tuberculosis is significantly higher with the monoclonal antibodies.4

Dr Kotton discussed infectious disease consultation before initiation of IA. A patient's relative risk of opportunistic infection will depend on his/her underlying condition, the specific immunosuppressive agent, and epidemiologic risk factors. It is mandatory to ask about epidemiologic risk factors (for diseases that can later be reactivated, such as strongyloidiasis, histoplasmosis, and, of course, tuberculosis). Either a PPD skin test or an interferon γ release assay should be done, as well as hepatitis B and C serologies. If no convincing history of varicella is obtained, varicella antibodies should be obtained. The presence of JC virus in the blood has not been shown to be useful in predicting risk for progressive multifocal leukoencephalopathy.5 Urine antigen may be used to screen for active histoplasma infection, but serologies are not considered helpful.

If the patient requires live vaccines such as MMR, varicella zoster, yellow fever, or oral typhoid, these should be given several weeks before the IA is initiated; they are contraindicated while on the IA. Some patients will require the hepatitis B immunization, in which case an accelerated schedule before the IA may be helpful. Patients with Strongyloides will require treatment, perhaps followed by periodic repeated treatment, while on IA. Those with latent tuberculosis infection will require at least 9 months isoniazid, and in selected circumstances such as those with extensive fibrosis on chest radiograph, may opt to treat longer. Those with active hepatitis B will need treatment as well.

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1. Kotton CN. How do I screen patients anticipating biologic agents? Session 28. No. 104. IDSA; 2010.

2. Winthrop, KL. Beyond TNF inhibition: the risks and rewards of biologic therapies. Session 28. No. 106a. IDSA; 2010.

3. Gea-Banagloche. Semin Hematol. 2010;47:187-198.

4. Dixon WG, Hyrich KL, Watson KD, et al. Extended report: drug specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy; results from the British Society for Rheumatology Biologics Register. Ann Rheum Dis. 2010;69:522-528.

5. Chen Y, Bord E, Tompkins T, et al. Asymptomatic reactivation of JC virus in patients treated with natalizumab. N Engl J Med. 2009;361:1067-1074.

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The US Food and Drug Administration has been responsible for defining the breakpoints of antibiotics against bacteria, yet it has become apparent that they have neither sufficient resources nor flexibility to revise them as needed. Clinical and Laboratory Standards Institute, a voluntary organization that strives to develop consensus guidelines on breakpoints, has been reviewing data for the last 8 years. Revision has become necessary because the original breakpoints were not based on clinical outcomes data, used different pharmacokinetic indices from the standards used today, and did not take into account the appearance of extended spectrum beta-lactamase (ESBL) gram-negatives.2,3

Dr Schreckenberger1 described a Klebsiella pneumoniae strain found by Vitek to be sensitive to cefepime, imipenem, and gentamicin yet resistant to ertapenem and tobramycin, which seemed inconsistent. The strain tested positive by the Hodge test, indicating presence of a carbapenemase (KPC), so it should have been reported as resistant to imipenem. By adjusting the breakpoints for imipenem from 4 or less to 1 or less, all KPC strains would have been reported as resistant to imipenem. There were also data presented that made an argument for lowering the breakpoints for pipericillin-tazobactam against Enterobacteriaceae and Pseudomonas.

Dr Ambrose4 reviewed break points for cephalosporins. He noted in animal model data that time over minimum inhibitory concentration (MIC), not the presence of ESBL, predicts efficacy. Patient outcome trials also supported this concept.5 As such, ESBL testing may be considered optional, provided the MIC breakpoints have true clinical correlation. These breakpoints have been revised for the carbapenems and the cephalosporins against the Enterobacteriaceae.6

Dr Weinstein3 reviewed other agents, as well as unusual organisms. With less commonly used antibiotics such as colistin, there is a paucity of useful data and often no defined breakpoint. For unusual bacteria such as nutritionally variant Streptococcus, breakpoint data will be provided in a new document starting January 2011.7 In clinical situations with resistant gram-negatives, unusual organisms, and novel agents, a consultation with the microbiology director will often be useful to help decide which antibiotic to choose.

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1. Schreckenberger P. Rationale for changing breakpoints: Pseudomonas and carbapenems. Session 61. No. 186. IDSA; 2010.

2. Ambrose PG. Rationale for changing breakpoints: Enterobacteriaceae and cephalosporins. Session 61. No. 187. IDSA; 2010.

3. Weinstein M. Bad bugs without CLSI or FDA breakpoints: reasoning by analogy? Session 61. No. 188. IDSA; 2010.

4. Craig WA, Andes DR. Treatment of infections with ESBL-producing organisms: pharmacokinetic-pharmacodynamic considerations. Clin Microbiol Infect. 2005;11:10-17.

5. Craig WA, Bhavnani SM, Ambrose PG, et al. Evaluation of clinical outcome among patients with ESBL-producing Enterobacteriaceae treated with cephalosporin mono-therapy. ICAAC 2005, Abstract K-1291.

6. CSLI. Performance Standards for Antimicrobial Susceptibility Testing: Twentieth Informational Supplement (June 2010 Supplement). CSLI Document M100-S20-U. Wayne, PA: CSLI; 2010.

7. CSLI. Methods for Antimicrobial Dilution and Disk Susceptibility Testing of Infrequently Isolated or Fastidious Bacteria: Approved Guideline. CSLI document M45-A2. 2nd ed. Wayne, PA: CSLI; 2011.

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As it has been established that the efficacy of beta-lactams is based on time over MIC, some investigators have looked into extending the time of infusion, and interval between infusions, to improve efficacy. Lodise et al3 investigated 3.375 g intravenously for 30 minutes every 6 hours versus 3.375 g intravenously for 4 hours every 8 hours, for Pseudomonas infections. Clinical outcomes were improved with the extended infusion group, and significant cost savings were achieved. Those looking for a once-daily drug for home infusion might consider a continuous infusion of pipericillin-tazobactam (for normal renal function, 10.125 g as continuous fusion for 24 hours). A study investigating cefepime (2 g intravenously every 8 hours infused for 3 hours) showed that this high dose, when infused during a long period, improved the likelihood of achieving target concentrations for Pseudomonas aeruginosa in ventilator-associated pneumonia.4 Extended infusion of carbapenems may also display superior pharmacokinetics, particularly against gram-negative rods.

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1. Craig W. Session 34. No. 124a. IDSA; 2010.

2. Rodvold K. Session 34. No. 124b. IDSA: 2010.

3. Lodise T, Lomaestro B, Drusano G. Pipericillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended infusion dosing strategy. Clin Inf Dis. 2007;45:357-363.

4. Nicasio AM, Ariano RE, Zelenitsky SA, et al. Population pharmacokinetics of high-dosed, prolonged-infusion cefepime in adult critically ill patients with ventilator associated pneumonia. Antimicrob Agents Chemother. 2009;53:1476-1481.

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Fidaxomicin is from a class of drugs known as macrocyclics. It has a narrow spectrum of activity and is minimally active against Bacteroides. There is little systemic absorption and, thus, will achieve high colonic concentration.

In 2 randomized controlled trials in North America and Europe, fidaxomicin was studied against vancomycin for the treatment of Clostridium difficile-associated diarrhea. Initial response was equivalent in both drugs. There were more recurrences with vancomycin. Of the strains, 34% were typed as B1/NAP 1. There were no significant difference in adverse affects.1

In the follow-up oral presentation, data were presented in which 89 patients submitted serial stool samples, and the effect of vancomycin and fidaxomicin on the intestinal flora was measured. Fidaxomicin killed less of the native intestinal flora than vancomycin, although levels after treatment were not different. The expression of C. difficile toxin was also lower in the fidaxomicin group. The authors postulate that a more preserved microbial flora led to less expression of C. difficile toxin and thus less recurrence of disease.

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1. Crook D, Miller M, Louie T, et al. Efficacy and safety of fidaxomicin (FDX) vs vancomycin in Clostridium difficile infection in 2 randomized controlled trials with 1105 patients. Session 28, No. 1417. IDSA; 2010.

2. Louie T, Cannon K, Byrne B, et al. Fidaxomicin preserves the intestinal microbiome during and after treatment of C. difficile infection and reduces toxin re-expression and recurrence of CDI.

© 2011 Lippincott Williams & Wilkins, Inc.