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Resistance Wars IV. In the Trenches: Case Studies in the War on Resistance

  • Authors: John G. Bartlett, MD, Program Chair; Peter C. Appelbaum, MD, PhD; Henry F. Chambers, MD; Thomas M. File, Jr, MD, MSc, MACP; David L. Paterson, MD; Joseph S. Solomkin, MD
  • CME Released: 4/30/2010
  • Valid for credit through: 4/30/2011, 11:59 PM EST
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Target Audience and Goal Statement

This activity was developed for infectious disease specialists, pulmonologists, critical care physicians, surgeons, emergency medicine physicians, and clinical PharmDs.

The increasing prevalence of antimicrobial resistance is an issue of major concern to physicians as the presence of resistant pathogens complicates therapy, increases expense, and makes treatment failure more likely. Bacterial resistance to commonly used antimicrobial agents is a growing worldwide public health issue. New strains of resistant organisms are developing quickly and have resulted in challenging infections presenting in clinical practice. Resistance is recognized increasingly among organisms found in hospitals and the community, making the emergence and transmission of drug-resistant organisms a problem that affects all health care providers and facilities.

Antimicrobial-resistant infections have the potential to increase morbidity and mortality, prolong hospital stays, cause disease-related complications, and increase treatment-related costs. Preventing and controlling the emergence of resistance and outbreaks of infection is a priority for all clinicians, institutions, and agencies. Currently, new strategies, federal reforms, and pharmacologic approaches to prevent and treat antibiotic-resistant infectious diseases are under investigation. There is an expressed need from the community to understand these strategies and apply these principles to practice.

Upon completion of this activity, participants should be able to:

  1. Discuss the prevalence, risk factors, and potential consequences of serious bacterial infections in an era of resistance
  2. Recognize the current and emerging pathogens of significance found in nosocomial, community-acquired, and healthcare-associated infections
  3. Describe current and emerging strategies, guidelines, and recent reforms designed to improve outcomes in the management of infections
  4. Apply the principles of antimicrobial stewardship and empirical therapy in the clinical setting
  5. Understand treatment challenges for patients with pneumonia, intra-abdominal, and complicated skin and soft tissue infections
  6. Evaluate new and emerging pharmacologic strategies for the effective treatment of serious bacterial infections in an era of resistance


Penn State College of Medicine is committed to offering CME programs that promote improvements or quality in health care and are developed free of the control of commercial interests. Faculty and course directors have disclosed all relevant financial relationships with commercial companies, and Penn State has a process in place to resolve any conflict of interest. Penn State also requires that faculty disclose any discussion of off-label or investigational uses included in their presentations. Disclosure of a relationship is not intended to suggest or condone bias in a presentation, but is made to provide participants with information that might be of potential importance to their evaluation of a presentation.

Penn State College of Medicine and Rockpointe staff involved in the planning of this activity have no financial relationships with any commercial interests relevant to this activity.


  • John G. Bartlett, MD, Program Chair

    Professor of Medicine, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland


    Disclosure: John G. Bartlett, MD, has participated as a consultant/advisor for Johnson & Johnson and Pfizer Inc.

  • Peter C. Appelbaum, MD, PhD

    Professor of Pathology, Director of Clinical Microbiology, Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania


    Disclosure: Peter C. Appelbaum, MD, PhD, has received research grants from Achaogen Inc, Astellas Pharma Inc, AstraZeneca, Cempra Pharmaceuticals Inc, Cerexa Inc, Cubist Pharmaceuticals, Johnson & Johnson, Pfizer Inc, and Protez Pharmaceuticals.

  • Henry F. Chambers, MD

    Professor of Medicine, University of California, San Francisco, Chief, Division of Infectious Diseases, San Francisco General Hospital, San Francisco, California


    Disclosure: Henry F. Chambers, MD, has participated as a consultant/advisor for Johnson & Johnson, Pfizer Inc, and Astellas Pharma Inc. He has received research grants from Johnson & Johnson and Pfizer Inc and owns stock in Merck & Co. Inc.

  • Thomas M. File, Jr, MD, MSc, MACP

    Professor, Internal Medicine, Master Teacher, Head, Infectious Disease Section, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, Chief, Infectious Disease Section and Director HIV Research, Summa Health System, Akron, Ohio


    Disclosure: Thomas M. File, Jr, MD, MSc, MACP, has participated as a consultant/advisor and has received honoraria from Advanced Life Sciences, Astellas Pharma Inc/Theravance Inc, Cerexa Inc, Merck & Co. Inc, Nabriva Therapeutics, Ortho-NcNeil Inc, Oscient Pharmaceuticals, Pfizer Inc, Protez Pharmaceuticals, Schering-Plough, Targanta Therapeutics, and Wyeth Pharmaceuticals. He has received research grants from Boehringer Ingelheim, Cerexa Inc, Gilead Sciences, Ortho-McNeil, Inc, Pfizer Inc, Protez Pharmaceuticals, Rib-X Pharmaceuticals Inc, and Tibotec Therapeutics.

  • David L. Paterson, MD

    Professor, The University of Queensland Centre for Clinical Research, Infectious Diseases Unit, Royal Brisbane and Women's Hospital, Brisbane, Australia


    Disclosure: David L. Paterson, MD, is a member of the speakers' bureau for AstraZeneca, Johnson & Johnson, and Merck & Co. Inc. He is a consultant/advisor for Johnson & Johnson, and Pfizer Inc. He has received research grants from AstraZeneca.

  • Joseph S. Solomkin, MD

    Professor of Surgery, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio


    Disclosure: Joseph S. Solomkin, MD, is a member of the speakers' bureau for Schering-Plough. He has participated as a consultant/advisor for Bayer Corporation, Johnson & Johnson, Merck & Co. Inc, and Schering-Plough. He has received research grants from Pfizer Inc.

  • P. Susan Jordan, PharmD

    Scientific Writer


    Disclosure: P. Susan Jordan, PharmD, reports no financial relationships with any commercial interests relative to this activity.

Accreditation Statements

    For Physicians

  • This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Penn State College of Medicine and Rockpointe®. Penn State College of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

    Penn State College of Medicine designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

    Participation should take approximately 1 hour.

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For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]

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This activity is designed to be completed within the time designated on the title page; physicians should claim only those credits that reflect the time actually spent in the activity. To successfully earn credit, participants must complete the activity online during the valid credit period that is noted on the title page.

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Resistance Wars IV. In the Trenches: Case Studies in the War on Resistance

Authors: John G. Bartlett, MD, Program Chair; Peter C. Appelbaum, MD, PhD; Henry F. Chambers, MD; Thomas M. File, Jr, MD, MSc, MACP; David L. Paterson, MD; Joseph S. Solomkin, MDFaculty and Disclosures

CME Released: 4/30/2010

Valid for credit through: 4/30/2011, 11:59 PM EST


This CME activity is based on a combination of the slides and lectures presented by the faculty at the satellite symposium Resistance Wars IV. In the Trenches: Case Studies in the War on Resistance, which took place on both September 13, 2009, at the Moscone Center in San Francisco, California, during the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and on October 29, 2009, at the Pennsylvania Convention Center, in Philadelphia, Pennsylvania, during the 47th Annual Meeting of the Infectious Diseases Society of America (IDSA).


The prevalence of antimicrobial resistance is on the increase. The first organism to demonstrate resistance was Staphylococcus aureus, first to penicillin in the 1940s, followed by methicillin resistance in the 1960s, and vancomycin resistance in the mid-1990s.[1] The increase in antimicrobial resistance rates and the steady decline in the development of antimicrobial agents (from 16 between 1983 and 1987 to 4 from 2003 to 2007) clearly demonstrate the need for clinical strategies to combat widespread resistance.[2]

The development of antimicrobial resistance by S aureus illustrates the importance of resistance: once a resistance mechanism develops, it spreads and evolves over time. More than 90% of strains of S aureus are now resistant to penicillin[3,4]; methicillin-resistant S aureus (MRSA) strains have become endemic in hospitals worldwide since the 1980s,[3,5] and vancomycin-intermediate S aureus (VISA) and heteroresistant VISA (hVISA) are now associated with treatment failures.[6] Because surveillance of hVISA is neither routine nor standardized, it is likely underreported and likely determined by reduced clinical efficacy to vancomycin.[6,7] One study that used the Macro Etest found that the incidence of hVISA rose from 2.2% of all MRSA isolates collected from 1986 to 1993 to 8.3% of isolates collected from 2003 to 2007 and that hVISA increased with increasing vancomycin minimum inhibitory concentration (MIC).[6] Recently, vancomycin-resistant S aureus strains (VRSA) with the vanA gene were reported (Detroit, Michigan; Hershey, Pennsylvania; New York, New York).[3,8] VanA-acquired variants have the facility to transform unstable, low-level vancomycin resistance into endemic antimicrobial resistance with overuse of vancomycin.[3] The MIC susceptibility breakpoint for hVISA strains may be lower than that currently accepted for vancomycin.

Surveillance is necessary to monitor trends in resistance at various levels (hospital, regional, state, national) and to provide susceptibility patterns to guide treatment decisions.[9] Inappropriate/inadequate antimicrobial treatment due to resistance increases costs and mortality.[9] In a study of 6056 patients, the odds ratio of dying while hospitalized was 3.58 (95% confidence interval, 2.53-5.06) in patients whose initial antimicrobial therapy was inappropriate compared with those who had successful therapy (Table 1).[10] Selection of adequate antimicrobial treatment for VISA is complicated by limitations of available agents, such as toxicity (eg, quinupristin/dalfopristin, linezolid), higher MIC for many VISA strains (eg, daptomycin), and lack of clinical experience (eg, telavancin).[7]

The case studies that follow highlight treatment challenges and apply the principles for selecting appropriate empiric therapy and antimicrobial stewardship in an era of resistance.

Ventilator-Associated Pneumonia

Data from 2002 estimated that pneumonia accounts for approximately 25% of hospital-acquired infections in intensive care unit (ICU) patients (100,689 of 394,288 infections) and approximately 36% of deaths from hospital-acquired infections (35,967 of 98,987 deaths).[11] Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), in particular, are becoming increasingly more difficult to treat as there are no new agents in development for the causative gram-negative pathogens.

Case Presentation

A.P. is a 52-year-old male ICU patient who develops fever and pulmonary infiltrates while on a ventilator 5 days postsurgery for a ruptured diverticular abscess. Findings from the medical examination show the following: temperature, 38.5°C; blood pressure (BP), 130/90 mm Hg; pulse, 110 beats/min; respirations, 22 breaths/min; and bilateral rales and rhonchi in the lungs. Laboratory findings include the following: white blood cell count is 18,000 cells/mm3, chest x-ray shows new infiltrates, endotracheal aspirate shows moderately purulent secretions.