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March 2008: VOLUME 1, NUMBER 9

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Update on New Antimicrobials

In this Issue...

In the past few years, several new antimicrobial agents have become available to treat a variety of infections. An understanding of the indications and side-effects of these new therapies as well as their advantages relative to older antimicrobial agents is important for all providers. In this issue, we review two new antibacterial agents (daptomycin and tigecycline), the echinocandin class of antifungal agents, the role of rifaximin in the treatment and prevention of travelers’ diarrhea, and retapamulin, a topical agent for minor skin infections such as impetigo.
THIS ISSUE
COMMENTARY from our Guest Author
DAPTOMYCIN FOR S. AUREUS BACTEREMIA AND RIGHT-SIDED ENDOCARDITIS
TIGECYCLINE FOR INTRA-ABDOMINAL, SKIN, SOFT TISSUE, AND MULTIDRUG-RESISTANT GRAM-NEGATIVE INFECTIONS
ECHINOCANDINS FOR INVASIVE CANDIDIASIS
RIFAXIMIN FOR PREVENTION OF TRAVELERS’ DIARRHEA
TOPICAL RETAPAMULIN FOR IMPETIGO AND INFECTED DERMATITIS
Course Directors

John G. Bartlett, MD
Professor of Medicine
Department of Medicine
The Johns Hopkins University
School of Medicine
Baltimore, MD

Paul G. Auwaerter, MD
Associate Professor of Medicine
Clinical Director
Division of Infectious Diseases
The Johns Hopkins University
School of Medicine
Baltimore, MD

Sara E. Cosgrove, MD, MS
Assistant Professor of Medicine
Division of Infectious Diseases
Director
Antibiotic Management Program
Associate Hospital Epidemiologist
The Johns Hopkins University
School of Medicine
Baltimore, MD
GUEST AUTHOR OF THE MONTH
Commentary & Reviews:
Sara E. Cosgrove, MD, MS
Assistant Professor of Medicine
Division of Infectious Diseases
Director
Antibiotic Management Program
Associate Hospital Epidemiologist
The Johns Hopkins University
School of Medicine
Baltimore, MD
Guest Faculty Disclosures

Sara E. Cosgrove, MD, MS has disclosed that she has received grants or research support from Merck and served on the Advisory Boards for Ortho-McNeil, Cadence Pharmaceuticals, and Theravance/Astellas.

Unlabeled/Unapproved Uses

The author has indicated that there will be reference to unlabeled or unapproved uses of the drug retapamulin in the presentation.

Program Directors' Disclosures
LEARNING OBJECTIVES
At the conclusion of this activity, participants should be able to:

Discuss with colleagues the indications for and side effects of two new antibiotics: daptomycin and tigecycline
Discuss with colleagues the indication for and side effects of the echinocandin class of antifungals
Discuss with colleagues the indications for two new non-systemic antimicrobial agents: rifaximin and retapamulin


Program Information
CME Info
Accreditation
Credit Designations
Intended Audience
Learning Objectives
Internet CME Policy
Faculty Disclosures
Disclaimer Statement

Length of Activity
1.0 hours Physicians

Expiration Date
February 27, 2010

Next Issue
March 27, 2008
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COMMENTARY
Daptomycin is a novel lipopeptide antibiotic with rapid bactericidal activity against Gram-positive organisms, particularly Staphylococcus aureus. It was initially FDA-approved for the treatment of skin and soft tissue infections at a dose of 4 mg/kg daily. The study by Fowler et al (reviewed herein) demonstrates that daptomycin at a dose of 6 mg/kg daily is not inferior to standard therapy, which is defined as antistaphylococcal penicillins or vancomycin, both with initially combined low-dose gentamicin, for the treatment of S. aureus bacteremia and right-sided endocarditis. While antistaphylococcal penicillins (eg, oxacillin and nafcillin) remain the antibiotics of first choice for methicillin-susceptible S. aureus (MSSA) bacteremia and endocarditis, daptomycin is a reasonable alternative to vancomycin for patients with MSSA bacteremia, severe penicillin allergy, or MRSA bacteremia. Its major limitations include an apparent propensity towards emergence of resistance during therapy of some deep-seated or poorly debrided infections, and the lack of information regarding efficacy and safety in patients with creatinine clearances below 30 ml per minute. Its major advantage is its once daily dosing.

Tigecycline is a novel bacteriostatic glycylcycline antibiotic derived from tetracyclines. It has a broad spectrum of activity against most strains of staphylococci and streptococci (including MRSA and vancomycin-resistant enterococci [VRE]), anaerobes, and many Gram-negative organisms (with the exception of Proteus spp and Pseudomonas aeruginosa). The studies by Babinchak et al and Ellis-Grosse et al, reviewed in this issue, support the efficacy of tigecycline for treatment of complicated intra-abdominal, skin, and soft tissue infections. The major drawbacks of the drug when used for its FDA-approved indications are its expense relative to other therapeutic alternatives and the high incidence of nausea and vomiting associated with its use. Caution should be exercised if tigecycline is used off-label for highly resistant Gram-negative infections, given reports of high failure rates for these pathogens.1 Although not currently FDA-approved for community-acquired pneumonia, tigecycline was found to be not inferior to levofloxacin. However, in data not yet published, tigecycline failed to meet the criteria for non-inferiority for treatment of hospital-associated and ventilator-associated pneumonia when compared to imipenem-cilastatin.

The echinocandins (caspofungin, mycafungin, and anidulafungin) are a novel class of intravenous antifungal agents with excellent fungicidal activity against Candida albicans and most other Candida species. The mean inhibitory concentration (MIC) of echinocandins for C. parapsilosis isolates tend to be higher than for other Candida species, and some experts recommend using caution when using echinocandins to treat C. parapsilosis. The newer echinocandins, mycafungin and anidulafungin, recently joined caspofungin as FDA-approved agents for the treatment of candidemia; there are no major differences between the three agents.2 The study by Reboli et al (reviewed herein) demonstrates that one of the agents, anidulafungin, was not inferior and perhaps superior to fluconazole for the treatment of invasive candidiasis. This latter observation is a matter of some controversy, given that fluconazole has been used successfully for many years for the treatment of candidemia, has the benefit of being relatively inexpensive, and available in a highly bioavailable oral formulation. Nonetheless, the sickest patients with candidemia should probably be treated initially with echinocandins, with a switch to fluconazole after the patients stabilize.

Rifaximin is an oral, but non-absorbed, derivative of rifamycin. It is FDA-approved for the treatment of non-invasive Escherichia coli-associated travelers’ diarrhea at a dose of 200 mg, 3 times daily, for 3 days. The study by DuPont et al, in this issue, shows that it is also effective for prevention of travelers’ diarrhea in Mexico. The advantage of rifaximin is that it provides a non-systemic antibiotic option for treatment and prevention of travelers’ diarrhea, although the cost of a longer course of therapy is considerable. However, rifaximin should not be used if there is concern for systemic infection in a traveler with diarrhea. Further, additional studies are needed to determine its efficacy in persons traveling to Asia.

Retapamulin is a novel antibiotic only available in topical formulation. It has activity against staphylococci (including MRSA) and streptococci and does not appear to have cross-resistance with other antibiotics, including mupirocin. It has been FDA-approved for treatment of impetigo due to MSSA or S. pyogenes based on a double-blind, randomized, placebo controlled study that included children ≥ 9 months (78%) and adults (22%).3 Patients with impetigo were randomized to receive retapamulin or placebo, both applied twice daily for 5 days. In the clinical per protocol population, retapamulin-treated patients had a 90% success rate versus a 36% success for placebo-treated patients at the end of therapy. A similar difference was seen at the follow-up visit 9 days after the end of treatment. In the study by Parish et al in this issue, retapamulin was also found to be effective therapy for secondarily infected dermatitis when compared to systemic antimicrobial therapy using oral cephalexin. The use of topical agents for minor skin infections allows for avoidance of systemic antimicrobial therapy, which can be associated with side effects and development of resistance.

The discovery and development of antibiotics is one of the success stories of modern medicine. Countless lives have been saved since the introduction of penicillin in the 1940's. However, the past decade has witnessed impressive increases in rates of resistance to antimicrobials in both the hospital and the community. Unfortunately, the discovery, testing, and FDA approval of novel antimicrobial agents has diminished dramatically during the same time period. Given these developments, appropriate use of currently available antimicrobial agents is increasingly important.


References

1. Anthony KB, Fishman NO, Linkin DR, Gasink LB, Edelstein PH, Lautenbach E. Clinical and microbiological outcomes of serious infections with multidrug-resistant gram-negative organisms treated with tigecycline. Clin Infect Dis. 2008; 46(4):567-570.
2. Sobel JD, Revankar SG. Echinocandins—First choice or first-line therapy for invasive candidiasis? N Engl J Med. 2007; 356:2525-2526.
3. Package insert, retapamulin (Altabax)


DAPTOMYCIN FOR S. AUREUS BACTEREMIA AND RIGHT-SIDED ENDOCARDITIS
Fowler VG, Boucher HW, Corey GR, et al, for the S. aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006; 355:653-665.

(For non-journal subscribers, an additional fee may apply for full text articles.)
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In an open-label randomized controlled trial, the authors studied adult patients with S. aureus bacteremia with or without endocarditis who were treated with either daptomycin (6 mg/kg daily) or standard therapy consisting of initial low-dose gentamicin plus either an antistaphylococcal penicillin or vancomycin. Patients were ineligible for enrollment if they had a creatinine clearance <30 ml per minute, osteomyelitis, potentially infected hardware, or pneumonia (daptomycin is inactivated by pulmonary surfactant and cannot be used to treat pneumonia). The primary outcome was treatment success 42 days after therapy was completed.

Two-hundred-thirty-five patients were included in the modified intent-to-treat analysis: 53 of the 120 (44%) patients who received daptomycin and 48 of 115 (42%) who received standard therapy were treatment successes. These results met the prespecified criteria for non-inferiority of daptomycin relative to standard therapy. Results were similar in the subgroups of patients with complicated bacteremia, right-sided endocarditis, and MRSA infection. Sixteen percent of patients who received daptomycin failed because of persisting or relapsing S. aureus infection, compared to 10% of patients who received standard therapy. Six of the patients in the daptomycin group had emergence of resistance to daptomycin and treatment failure; most of these patients had deep-seated and/or undrained foci of infection. Fifteen percent of patients who received standard therapy failed because of treatment-limiting adverse events, compared to 7% of patients who received daptomycin. Most of the additional failures in the standard therapy arm were attributable to renal adverse events, likely due to the fact that 93% of these patients received initial low dose gentamicin. Also of note is that all patients with left-sided endocarditis caused by MRSA, regardless of the agent that they received, failed therapy.

Daptomycin is not inferior to standard therapy for the treatment of S. aureus bacteremia and right-sided endocarditis. It should be used with caution in patients with deep-seated infections (such as epidural abscess) or undrained infections, given the risk of emergence of resistance to the drug. Although daptomycin is in general well tolerated, patients should be screened for muscle pain and have creatine kinase (CK) levels checked at least weekly, as myopathy is a rare side-effect of the drug. It should not be used to treat pneumonia because it is inactivated by pulmonary surfactant. Finally, daptomycin has not been studied in patients with creatinine clearances <30 ml per minute, including patients on dialysis; if used in this population, the dose is 6 mg/kg every other day, and patients should be monitored carefully for both evidence of treatment failure and myopathy.


TIGECYCLINE FOR INTRA-ABDOMINAL, SKIN, SOFT TISSUE, AND MULTIDRUG-RESISTANT GRAM-NEGATIVE INFECTIONS
Babinchak T, Ellis-Grosse E, Dartois N, et al. The efficacy and safety of tigecycline for the treatment of complicated intra-abdominal infection: analysis of pooled clinical trial data. Clin Infect Dis. 2005; 41:S354-S367.

(For non-journal subscribers, an additional fee may apply for full text articles.)
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Ellis-Grosse EJ, Babinchak T, Dartois N, et al. The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam. Clin Infect Dis. 2005; 41:S341-S353.

(For non-journal subscribers, an additional fee may apply for full text articles.)
View journal abstract View full article
Babinchak et al pooled data from 2 doubled-blind, randomized controlled trials comparing tigecycline to parenteral imipenem-cilastatin for complicated intra-abdominal infections, defined as post-operative abscess, perforated appendix ± abscess, perforated diverticulitis ± abscess, complicated cholecystitis (with perforation, empyema, or gangrene), perforated gastric or duodenal ulcer, or small or large intestine perforation ± abscess. All patients were required to undergo a surgical procedure in addition to antibiotics. Antibiotics were given for 5 to 14 days. The primary endpoint was clinical response 12 – 42 days after therapy. Patients in the microbiologically-evaluable modified intent-to-treat population (n=1262) received a mean of 8 days of therapy. Clinical cure rates were 86% for both tigecycline and imipenem-cilastatin. Tigecycline therapy was more often associated with nausea (24% vs 19%) and vomiting (19% vs 14%).

Ellis-Grosse et al pooled data from 2 doubled-blind, randomized controlled trials comparing tigecycline to vancomycin plus aztreonam in hospitalized adults with complicated skin and skin structure infections that involved deep soft tissue, including cellulitis at least 10 cm in width or length, required surgery, or were associated with significant underlying disease such as diabetes, peripheral vascular disease, or venous insufficiency. Antibiotics were given up to 14 days. The primary endpoint was clinical response at the test-of-cure visit. Patients in the clinically-evaluable population (n=833) received a mean of 8 days of therapy. The most common diagnosis was deep tissue infection with cellulitis, occurring in two-thirds of patients. Only a small number of patients had MRSA infections. Clinical cure rates were 87% for tigecycline and 89% for vancomycin plus aztreonam. Tigecycline therapy was more often associated with nausea (35% vs 8%) and vomiting (20% vs 4%).

These studies supported FDA approval of tigecycline for skin and soft tissue infections and complicated intra-abdominal infections, and demonstrated that tigecycline is reasonable single-agent therapy for these infections, provided that there is not a strong suspicion for P. aeruginosa (given this agent’s lack of activity against that organism). Because tigecycline is a novel agent, there was initial excitement that it may be useful in the treatment of infections due to highly resistant Gram-negative organisms such as Acinetobacter baumanii; however, experience in this area has been disappointing. Tigecycline has low mean peak serum concentrations and poor urinary penetration, making it a suboptimal choice for bacteremia and urinary tract infections. Clinical failures have also been associated with higher pre-therapy MICs of implicated organisms, as well as with the emergence of resistance during therapy. Salvage therapy using tigecycline for multidrug-resistant Gram-negative infections and VRE infections should be done with caution and in consultation with an infectious diseases specialist.


ECHINOCANDINS FOR INVASIVE CANDIDIASIS
Reboli AC, Rotstein C, Pappas PG, et al, for the Anidulafungin Study Group. Anidulafungin versus fluconazole for invasive candidiasis. N Engl J Med. 2007:356:2472-2482.

(For non-journal subscribers, an additional fee may apply for full text articles.)
View journal abstract View full article
Reboli and colleagues performed a randomized, double-blind trial comparing anidulafungin with fluconazole for treatment of invasive candidiasis (either candidemia or Candida spp. isolated from a sterile site). Patients received anidulafungin or fluconazole (800 mg IV initially, then 400 mg daily) for 14 – 42 days, and could be switched to oral fluconazole after 10 days in both arms of the study. Patients were excluded if they had recent prophylactic azole therapy, endocarditis, osteomyelitis, meningitis, or C. krusei infection (the organism is intrinsically resistant to fluconazole). The primary endpoint was clinical and microbiological response at the end of IV therapy.

Two-hundred-forty-five patients were included in the modified intention-to-treat analysis. The majority of patients had candidemia (89%). Median duration of IV treatment was 14 days in the anidulafungin group and 11 days in the fluconazole group; median duration of oral fluconazole was 7 days in the anidulafungin group and 5 days in the fluconazole group. Ninety-six of 127 (76%) patients who received anidulafungin and 71 of 118 (60%) patients who received fluconazole had clinical and microbiological response at the end of IV therapy. These results met the prespecified criteria for non-inferiority of anidulafungin relative to fluconazole therapy; there was a significantly greater response rate in the anidulafungin group. Patients in the fluconazole group were more likely to have elevated transaminases relative to those in the anidualafungin group (7% vs 2%).

This study demonstrates that an echinocandin – anidulafungin – is not inferior to fluconazole in the therapy of invasive candidiasis and is perhaps superior. Although MICs of fluconazole for C. glabrata tend to be higher that those for other Candida species, this did not seem to be a reason for the additional fluconazole failures in the study. Instead, the greatest difference was in outcomes of patients with C. albicans: 81% of anidulafungin patients had successful outcomes compared to 62% of fluconazole patients. Although this finding may be due to subtle differences in the two groups of patients (e.g. patients in the fluconazole arm had more non-candidemia infections, less frequent removal of central venous catheters, and there were more patients on immunosuppressive therapy), the result is striking. Most experts now recommend the use of echinocandins as first line therapy for patients with prior exposure to fluconazole and in critically ill patients, a recommendation supported by the results of this study. However, once a patient has had good clinical response and has stabilized, a switch to oral fluconazole remains a reasonable choice. Echinocandins do not penetrate well into the central nervous system; thus, a complete ophthalmologic exam to assess for endophthalmitis, recommended for all patients with candidemia, is of particular importance in echinocandin-treated patients


RIFAXIMIN FOR PREVENTION OF TRAVELERS’ DIARRHEA
DuPont HL, Jiang Z, Okhuysen PC, et al. A randomized, double-blind, placebo-controlled trial of rifaximin to prevent travelers’ diarrhea. Ann Intern Med. 2005; 142:805-812.

(For non-journal subscribers, an additional fee may apply for full text articles.)
View journal abstract View full article
DuPont et al performed a randomized, double-blind, placebo-controlled trial of rifaximin vs placebo for the prevention of travelers’ diarrhea in adults. Participants were US students attending classes in Guadalajara, Mexico, and living in local homes who presented to clinic with diarrhea. They were assigned to 1 of 4 treatment groups for 2 weeks: rifaximin 200 mg daily, rifaximin 200 mg twice daily, rifaximin 200 mg 3 times daily, or placebo 3 times daily. Participants kept a daily diary of symptoms and if they developed diarrhea, stool specimens were collected. The primary outcome measure was occurrence of diarrhea.

Two-hundred-ten patients were evaluable. Rates of diarrhea were similar in all 3 rifaximin arms and 23 of 156 (15%) of these patients experienced diarrhea. In contrast, 29 of 54 (54%) of placebo-treated patients had diarrhea. Rifaximin provided 72% protection against traveler’s diarrhea. Rifaximin also protected against mild diarrhea and non-diarrheal intestinal symptoms. No significant adverse events were noted in any study arm. The majority of stool isolates in all groups were enterotoxigenic E. coli. The MIC50 and MIC90 for coliform bacteria and Enterococcus spp were one dilution higher in the rifaximin groups than in the placebo groups.

This study demonstrates that rifaximin is beneficial for the prevention of travelers’ diarrhea. Given the immediate (~ 24 hours of incapacitation) and long-term (persistent irritable bowel symptoms in up to one-third of persons) consequences of travelers’ diarrhea, such preventive strategies may be reasonable. The advantage of rifaximin is that it is not absorbed and thus individuals are not put at risk for the toxicities associated with systemic antibiotic use, such as antibiotic resistance and antibiotic-associated diarrhea. However, the finding in this study that there were small increases in the MICs of rifaximin for stool flora deserves further attention. The authors of the study also point out that while the drug seems to prevent infections in Mexico, where most travelers’ diarrhea is caused by E. coli, its efficacy in Asia, where pathogens such as Shigella, Salmonella and Campylobacter species are more prevalent, has not been determined.


TOPICAL RETAPAMULIN FOR IMPETIGO AND INFECTED DERMATITIS
Parish LC, Jorizzo JL, Breton JJ, et al. Topical retapamulin ointment twice daily for 5 days versus oral cephalexin twice daily for 10 days in the treatment of secondarily infected dermatitis: results of a randomized controlled trial. J Am Acad Dermatol. 2006; 55:1003-1013.

(For non-journal subscribers, an additional fee may apply for full text articles.)
View journal abstract View full article
Parish et al performed a randomized, double-blind, double-dummy non-inferiority trial to compare topical retapamulin for 5 days to oral cephalexin twice a day for 10 days for the treatment of secondarily infected dermatitis to determine if retapamulin can be used in lieu of systemic antimicrobials. Patients (children ≥ 9 months and adults) had to have atopic dermatitis, psoriasis, or allergic contact dermatitis, plus evidence of secondary infection. The primary endpoint was the clinical response at follow-up 7-9 days after the end of therapy.

Four-hundred-seventy-six patients were in the per-protocol clinical population and returned for a follow-up visit; 275 of 320 (86%) of patients treated with retapamulin and 140 of 156 (90%) of patients treated with cephalexin had treatment success at the follow-up visit. Results were similar in the intent to treat analysis. Very few adverse events were reported that were felt to be related to the study medications. The majority of patients in both treatment groups reported that they preferred a topical therapy to an oral therapy (61% in the retapamulin arm and 57% in the cephalexin arm).

This study demonstrates that for patients with secondarily infected dermatitis, topical retapamulin for 5 days was not inferior to oral cephalexin for 10 days and that patients preferred topical therapy. In an era of increasing antimicrobial resistance, avoidance of systemic antimicrobials whenever possible is critically important and can be facilitated by the use of retapamulin and other topical treatment approaches. Recent attention to community-acquired MRSA skin infections has only heightened concern in patients and providers, and has presumably led to more systemic antimicrobial use, even for minor infections (such as impetigo and infected dermatitis) that in most cases do not require systemic antibiotic therapy. Although retapamulin is not FDA-approved for MRSA infections (only MSSA infections), it has in vitro activity against MRSA and would likely be adequate therapy for minor MRSA skin infections. Hopefully, additional studies will be performed to address its efficacy against MRSA.


CME INFORMATION
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The Johns Hopkins University School of Medicine is accredited by The Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
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Physicians
eNewsletter: The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

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To take the post-test for eInfections Review you will need to visit The Johns Hopkins University School of Medicine's CME website. If you have already registered for another Hopkins CME program at these sites, simply enter the requested information when prompted. Otherwise, complete the registration form to begin the testing process. A passing grade of 70% or higher on the post-test/evaluation is required to receive CME credit.
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The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity.
 Intended Audience — back to top
This activity has been developed for the Primary Care Physician, Internist, and Infectious Disease Specialist.
 Learning Objectives — back to top
At the conclusion of this activity, participants should be able to:

Discuss with colleagues the indications for and side effects of two new antibiotics: daptomycin and tigecycline
Discuss with colleagues the indication for and side effects of the echinocandin class of antifungals
Discuss with colleagues the indications for two new non-systemic antimicrobial agents: rifaximin and retapamulin
 Internet CME Policy — back to top
The Office of Continuing Medical Education (CME) at The Johns Hopkins University School of Medicine is committed to protect the privacy of its members and customers. The Johns Hopkins University SOM CME maintains its Internet site as an information resource and service for physicians, other health professionals and the public.

Continuing Medical Education at The Johns Hopkins University School of Medicine will keep your personal and credit information confidential when you participate in a CME Internet based program. Your information will never be given to anyone outside of The Johns Hopkins University School of Medicine's CME program. CME collects only the information necessary to provide you with the services that you request.
 Faculty Disclosure — back to top
As a provider accredited by The ACCME, it is the policy of The Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a provider has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Directors reported the following:

John G. Bartlett, MD has disclosed that he has served on the HIV Advisory Board for GlaxoSmithKline, Abbott, Bristol-Myers Squibb, Pfizer and Tibotec. He is also on the Policy Board for Johnson & Johnson.
Paul G. Auwaerter, MD has disclosed that he has served as a consultant for Novartis, Pfizer, Ortho-McNeil, Schering-Plough, and Genzyme. He is on the Speakers' Bureau for Schering-Plough and has also disclosed that he is a Stock Shareholder for Johnson & Johnson.
Sara E. Cosgrove, MD, MS has disclosed that she has received grants or research support from Merck and served on the Advisory Boards for Ortho-McNeil, Cadence Pharmaceuticals, and Theravance/Astellas.

Guest Author Disclosures
 Disclaimer Statement — back to top
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. Use of The Johns Hopkins University School of Medicine name implies review of educational format design and approach. Please review the complete prescribing information of specific drugs or combination of drugs, including indications, contraindications, warnings and adverse effects before administering pharmacologic therapy to patients.
© 2008 JHUSOM and eInfections Review

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