At the 41st Annual Meeting of the Infectious Diseases Society of America (IDSA), the global nature of infectious diseases was a recurring them. The opening plenary session featured a compelling presentation of the global challenges of HIV by Peter Piot, MD, from the United Nations.
Following his talk, Dr. Julie Gerberding, Director of the U.S. Centers for Disease Control and Prevention (CDC), emphasized that the world is shrinking: challenges in one geographic region more and more often become global problems. Severe acute respiratory syndrome (SARS), West Nile disease, and monkeypox are obvious examples of how disease can be spread globally by human travelers, animal migration, or importation, as well as by vector transport from one region to another. Dr. Gerberding described how the CDC has had to change its working model to respond rapidly to urgent threats from natural and manmade challenges, unlike in years past, when CDC dealt mainly with local or regional outbreaks. Throughout the conference, there were constant reminders that antibiotic policy in one area can affect microbial susceptibility in other areas, and that it is more and more important for organizations like CDC to continue developing methods for rapid detection of new infectious challenges, capacity for investigation into how these infectious threats occur, and how they can be diagnosed or prevented. This information also must be communicated rapidly to healthcare providers and the public so that appropriate actions can be promptly initiated. Electronic methods such as public health alerts, the IDSA's Emerging Infections network, and the International Society of Infectious Diseases' Promed are all examples of electronic approaches to sharing information rapidly by electronic modalities.
Emerging Rickettsial Diseases
For the 2003 Smadel Lecture, honoring Joseph Smadel, an early pioneer in rickettsial diseases, Didier Raoult, MD, from Marseille, France, addressed the topic of emerging rickettsial diseases and emphasized the importance of using new techniques to assess the relevance of microorganisms to human disease. In discussing rickettsial diseases in general, he emphasized that there is considerable overlap in clinical syndromes: some regions have more than 1 rickettsial species present, and the serologic tests are not highly specific in terms of distinguishing 1 rickettsial species from another. Thus, molecular techniques are probably becoming the tests of choice to make definitive diagnoses of the specific rickettsial species. He described the recent recognition of many new rickettsial species: 10 new species have been recognized and named since 1990.
Dr. Raoult spent some time comparing the clinical manifestations of Rickettsia conorii and Rickettsia africae that occur in southern Africa. He noted that, while we focus on Rocky Mountain spotted fever (Rickettsia rickettsiae) in the United States, there are probably more cases of R africae and R conorii imported by travelers than there are indigenous cases of Rocky Mountain spotted fever. Another note of importance for clinicians in the United States: R africae has been identified in the Caribbean. Thus, it is conceivable that this Rickettsia, which was probably imported into the Caribbean by livestock or birds, may become indigenous in North America since the appropriate tick vectors (Amblyomma) are present in parts of the United States.
Dr. Raoult described several other rickettsial diseases that clinicians often do not think about. Rickettsia felis, transmitted by cat fleas in North America, South America, and Western Europe, is a notable example. He described how some of these unusual rickettsial diseases can be associated with considerable long-term fatigue. He concluded that for many mysterious febrile diseases, and for some other syndromes that could be infectious, a trial of empiric doxycycline might not be such a bad idea, given the fact that most clinicians do not have access to rickettsial diagnostic laboratories. But, then again, we do not want to overuse or misuse antibiotics!
Tuberculosis and Other Mycobacterial Diseases
Tuberculosis was the topic of 2 symposia and numerous abstracts. Although there were only about 15,000 cases in the United States in 2002, clinicians are well aware of the worldwide impact that tuberculosis has, and of the potential for tuberculosis to yet again rise in incidence if we are not vigilant about prevention as well as diagnosis and therapy.
Several sessions emphasized the importance of this year's revised management guidelines cosponsored by CDC, IDSA, and the American Thoracic Society. Henry Blumberg, MD, from Emory University emphasized several important areas of emphasis in the new guidelines. Clinicians who treat tuberculosis must recognize that they are responsible for both choosing an appropriate regimen and for assuring that the regimen is successfully administered. Directly observed therapy (DOT) continues to be stressed. The importance of obtaining a sputum sample for mycobacterial culture after 2 months of therapy was pointed out: if the culture is positive at that point, treatment failure is likely, and the reasons for this poor response must be investigated (eg, are there issues of adherence, resistance, drug interactions, etc?). Dr. Blumberg stressed that the minimum duration of recommended regimens is 6 months in any situation. There are situations where longer regimens are recommended, such as in the case of a patient with cavitary disease and positive cultures after 2 months of therapy, or patients with HIV coinfection. If pyrazinamide cannot be used for the first 2 months (eg, due to hepatotoxicity), the minimum duration is 9 months. If rifamycin cannot be used, the minimum duration of therapy should be 12 months. Clinicians need to be familiar with these guidelines if they are going to treat tuberculosis; several of the tables in the document are especially helpful.
Atypical mycobacteria received attention in the poster sessions. Cutaneous lesions due to Mycobacterium abscessus or Mycobacterium chelonei were the topic of several presentations.
Mycobacteria inadvertently injected during acupuncture or various cosmetic procedures were reported. Elizabeth Phillips from Toronto, Ontario, Canada, followed up on 149 patients treated by an acupuncturist who had been identified as a potential source of cases. A total of 29 cases with compatible lesions were identified. Almost all patients were women who were immunocompetent. Interestingly, organisms could be cultured from only 6 of the patients, although 15 had granulomas on biopsy. The incubation period was 0.5-5.0 months. There had been reuse of needles, but no patient acquired hepatitis B, hepatitis C, or HIV. While it was conceivable that some of these lesions might have been caused by something other than M abscessus, the inability to identify the organism by culture or histology or polymerase chain reaction (PCR) in so many cases is revealing of the diagnostic challenges facing clinicians, and the need to consider empiric therapy when faced with compatible lesions that defy diagnosis.
In New York City, Reina Turcios, MD, and colleagues from CDC and the New York City Department of Health investigated 4 women who developed M abscessus infections following cosmetic injections. They found 13 confirmed cases and 12 suspected cases. The injections occurred in residential settings using non-FDA-approved substances injected by nonlicensed practitioners. Such illegal practice of medicine can impede a patient's willingness to provide an accurate history. In Chile, Carlos Perez, MD, and associates reported 51 cases of mycobacterial skin disease following cosmetic surgery: these were due to M abscessus or M chelonae. These reports remind clinicians to consider atypical mycobacteria when confronted with indolent skin lesions, and to pursue the possibility that they have resulted from some type of nonsterile injections.
Clinical Controversies: Debating New Agents and Approaches to Patient Care
This year, the IDSA meeting featured short, targeted, pro and con debates on a series of topics of special interest. These debates put the use of new drugs and new approaches into a practical perspective.
Activated Protein C for Septic Shock
Regarding the use of activated protein C (APC) for the therapy of septic shock, Dennis Maki, MD, from the University of Wisconsin emphasized that the pivotal licensing trial for APC showed a substantial survival benefit for the patient group as a whole. He stressed that this drug should be used, especially for patients at high risk of dying, and that its use was well worthwhile despite the considerable price ($8800) of this therapy. Peter Eichacker from the National Institutes of Health offered a rebuttal, pointing out that in postlicensing studies, APC has not been nearly as safe or effective as it had been in the licensing trial. He also pointed out that clinicians often do not heed the listed contraindications to its use. No consensus was reached, but 2 experienced intensivists showed that the jury is still out on where APC should fit into our therapeutic armamentarium, especially for patients who are not severely ill.
Influenza Prophylaxes
As influenza season approaches, and as concern continues that a pandemic may be in the offing in the next few years, the proper use of oseltamivir and zanamavir is an important issue. Fred Hayden, MD, from the University of Virginia and Arnold Monto, MD, from the University of Michigan addressed the issue of how to manage household contacts of an index case during an influenza A outbreak. They both agreed that a considerable amount of influenza is transmitted in the household, and that when a physician recognizes an influenza-like illness in a patient, the healthcare provider should consider prophylaxis for all unvaccinated household members. Dr. Monto would prescribe oseltamivir despite its cost, and despite the fact that nausea and vomiting can be troubling side effects, especially among children. Dr. Hayden preferred treating the index case with oseltamivir, but economizing by treating the household contacts with a cheaper alternative, namely rimantidine or amantadine (assuming that influenza B was unlikely, since these latter drugs are not active against influenza B). Both emphasized, however, that the best option is to immunize everyone at the outset of the influenza season.
Fluoroquinolones in Patients With Cardiac Arrhythmias
Paul Iannini, MD, from Danbury Hospital and Carleton Nibley, MD, a cardiologist from Oakland, debated whether fluoroquinolones can be used safely in patients with a history of cardiac arrhythmias. Both agreed that quinolones cause only a modest prolongation of the Q-T interval compared with other notorious drugs such as pentamidine, or certain drugs no longer on the market such as cisapride or terfenidine. They both agreed that the occurrence of torsade de pointes was extremely low, and that those rare cases that occurred were either in patients with congenital prolonged Q-T intervals or a history of dysrhythmias, or in patients receiving other drugs known to prolong the Q-T interval. Both agreed that healthcare providers need to be alert to such complications, and both agreed that obtaining a baseline ECG to measure the baseline Q-T interval would rarely be necessary. However, Dr. Nibley reminded the audience that in today's litigious society, any untoward arrhythmias that occurred and that might be linked to a prolonged QT interval were potential trouble for the treating physician.
Management of Hepatitis C
Another "pro-con" debate focused on how to manage patients with acute hepatitis C (HCV), and revealed some interesting insights that may be counterintuitive for clinicians. Acute hepatitis C, defined as disease occurring within 3 months of infection, is often recognized in healthcare workers who are being followed post needle-stick injury, but can be seen in other settings where the likely exposure can be pinpointed. David Oldach, MD, from the University of Maryland laid out some basic facts. Patients with acute hepatitis C often resolve their infection spontaneously: in one study, 52% of 46 symptomatic patients cleared their viremia spontaneously, in contrast to 0 of 9 patients with asymptomatic disease. Treated patients have a high rate of response to interferon regimens. HCV-specific CD4 proliferative responses are important for response. Interestingly, these responses do not manifest until about 2-4 months postinfection, and begin to wane 4-6 months postinfection. Thus, to maximize response to therapy, he recommended that therapy not be given as soon as hepatitis C viremia is recognized. Rather, he would wait to see if viremia cleared spontaneously (eg, by 12 weeks), and would only institute this expensive, often difficult-to-tolerate regimen sometime between 2 and 4 months. He reviewed the limited data on various regimens. He recommended interferon alpha 5 million units daily for 24 weeks, although he recognized that pegylated interferon might be as good or better, and that his recommendations were based on his impressions rather than hard data.
Is a liver biopsy necessary for managing patients with hepatitis C? Ray Chung, MD, from Massachusetts General Hospital and Barbara McGovern, MD, from the New England Medical Center discussed this largely in the context of patients coinfected with HIV and hepatitis C. Both agreed that for most patients, there is no current imaging study or panel of serum markers that can indicate how much cirrhosis is present. Dr. Chung described the benefit of getting 2 biopsies, several years apart, in patients with mild disease in order to assess the rate of progression of their liver disease. Dr. McGovern agreed that biopsies were useful for determining when treatment could be deferred, and also advocated serial biopsies to determine the rate of fibrosis progression. Like many of the speakers, she is hopeful that more effective and better-tolerated drugs will be available in the future. Given the poor response of virus type 1 to current therapies, she would defer therapy if the patient had mild fibrosis. However, if the patient had type 2 or 3 virus, especially with a low viral load, she would be inclined to forgo biopsy and to treat with 48 weeks of interferon alpha plus ribavirin, since response rates with this regimen are robust enough to warrant subjecting the patient to the toxicities associated with this regimen. Several of the speakers in this and subsequent debates emphasized that if they did decide to treat, they would strongly consider stopping therapy in any patient who did not show at least a 2 log10 reduction in viral load at week 12 of therapy.
What New Drugs Should Be Added to the Formulary?
Finally, should new drugs coming into the market be added to the formulary? George Eliopoulos, MD, from Beth Israel Deaconess Medical Center and Chip Chambers, MD, from San Francisco General Hospital debated whether daptomycin really offers any advantages over linezolid. Daptomycin has bactericidal activity against staphylococci and streptococci, including methicillin-resistant staphylococci and vancomycin-resistant enterococci. Dr. Eliopoulos pointed out that we are seeing a few linezolid-resistant organisms, that linezolid is not bactericidal, and that some patients are intolerant of linezolid, so daptomycin is potentially useful for skin and soft-tissue infections. Dr. Chambers suggested that linezolid resistance is not that common, that we need to learn more about daptomycin's toxicity, and that, similar to linezolid, it is likely to be expensive. Dr. Chambers did not seriously doubt the utility of daptomycin but was not sure it needed to be on the formulary yet.
Bob Moellering, MD, from Beth Israel-Deaconness Hospital discussed the advantages of adding telithromycin to the formulary. Telithromycin is a once-daily ketalide that is likely to be approved soon and has better in vitro activity against pneumococci than the other available macrolides (azithromycin, clarithromycin, and erythromycin). It has been given to more than 4 million patients in 36 countries for the treatment of pharyngitis, sinusitis, bronchitis, and pneumonia. There has been very little toxicity overall, but there have been concerns about visual toxicities: these occurred in 0.6% of patients in the phase 3 trials and included blurred vision starting an hour after administration and lasting for 2 hours. Only 0.2% of patients stopped therapy, and the effects are transient. Dr. Moellering did not think these were reasons to be concerned about the drug's safety, and his bottom line was that this drug would provide an alternative to quinolones for therapy of respiratory infections likely due to pneumococci.
Lowell Young, MD, from the Kuzell Institute in San Francisco emphasized that telithromycin is only an oral agent; there is no intravenous form, and it is unlikely to be used in hospitals. He also pointed out that this has not been studied in children or in patients with severe pneumonia. He did not really express a "con" view, however. Thus, both agreed that this drug would be a safe and effective addition to our armamentarium of drugs for treating outpatient disease due to pneumococci, in addition to other pathogens covered by the macrolide-ketolide group.
Lionel Mandell, MD, from Hamilton, Ontario, discussed the need for gemifloxacin. Do we really need another respiratory fluoroquinolone? Gemifloxacin is by far the most active quinolone against pneumococci, Haemophilus, and atypical organisms among fluoroquinolones currently on the market, and its pharmacokinetics allow once-daily dosing. Dr. Mandell reviewed the clinical trials involving patients with respiratory infections and reported high efficacy and excellent tolerability. He strongly advocated using a drug with high activity to reduce the emergence of resistance, and for adding this agent to the antibiotic armamentarium. Although John Turnidge, MD, from North Adelaide, Australia, discussed some of the limitations of the new quinolones, it seemed persuasive that gemifloxacin was convenient, highly active, and could be used by those who believe that the highest ratio of area-under-the-curve to minimum inhibitory concentration should dictate the choice of agent. Clinicians should be cognizant, however, that this concept has not been substantiated clinically as a method to reduce emergence of resistance.
References
Piot P. The global AIDS epidemic: the greatest challenge to science and leadership in the new millennium. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 67.
Gerberding J. People protected . . . public health prepared. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 68.
Raoult D. Emerging rickettsial diseases. Program and abstracts of the 41st Annual Meeting of the Infectious Disease Society of America; October 9-12, 2003; San Diego, California. Abstract 481.
Kelly PJ, Fournier PE, Parola P, Raoult D. A survey for spotted fever group rickettsiae and ehrlichiae in Amblyomma variegatum from St. Kitts and Nevis. Am J Trop Med Hyg. 2003;69:58-59.
American Thoracic Society; CDC; Infectious Diseases Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52(RR-11):1-77.
Blumberg H. New treatment guidelines. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 441.
Phillips E, Tang P, Murray C. An outbreak of acupuncture-associated cutaneous Mycobacterium abscessus. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 845.
Turcios RM, Lash B, Yakrus M, et al. Outbreak of Mycobacterium abscessus soft tissue infections following cosmetic injections - New York City 2002. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 846.
Perez CM, Guzman AM, Garcia PC, et al. Outbreak of rapidly growing mycobacterial skin abscesses following cosmetic infections in Chile. Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 847.
Maki D. PRO: Activated protein C (Xigris): Do benefits justify the cost? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 44.
Eichacker P. CON: Activated protein C (Xigris): Do benefits justify the cost? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 45.
Hayden FG. CON: Oseltamivir for household contacts exposed to influenza: good practice or unnecessary risk? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 999.
Monto AS. PRO: Oseltamivir for household contacts exposed to influenza: good practice or unnecessary risk? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 998.
Iannini PB. PRO: Can fluoroquinolones be safely used in patients with cardiac dysrhythmias? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 1000.
Nibley CT. CON: Can fluoroquinolones be safely used in patients with cardiac dysrhythmias? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 1001.
Oldach D. What is the best management of a health care worker with acute hepatitis C? Should treatment be recommended? If so, when, with what, and for how long? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 430.
Chung R. How do you manage HIV infected persons with chronic hepatitis C? Program and abstracts of the 41st Annual Meeting of the Infectious Disease Society of America; October 9-12, 2003; San Diego, California. Abstract 431.
McGovern BH. How do you manage HIV infected persons with chronic hepatitis C? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 432.
Eliopoulous GM. PRO: Daptomycin: Do we need another anti-gram positive antibiotic? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 500.
Chambers HF. CON: Daptomycin: Do we need another anti-gram positive antibiotic? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 501.
Moellering RC. PRO: Telithromycin: Is there a need for a ketolide? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 502.
Young LS. CON: Telithromycin: Is there a need for a ketolide? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 503.
Mandell LA. PRO: Gemifloxacin and garenoxacin: Do we need more respiratory fluoroquinolones? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 504.
Turnidge JD. CON: Gemifloxacin and garenoxacin: Do we need more respiratory fluoroquinolones? Program and abstracts of the 41st Annual Meeting of the Infectious Diseases Society of America; October 9-12, 2003; San Diego, California. Abstract 505.