IDSA News - November 2008
Vol. 18 No. 11
(Print All Articles)

The IDSA Journal Club is on vacation.

The Journal Club will return in the next issue of IDSA News. Click here for last month's edition.

The Journal Club will return in the next issue of IDSA News. Click here for last month's edition.

ICAAC/IDSA Symposium Highlights Alternatives to Vancomycin

Mark Vogel
Vancomycin — usually used as a drug of last resort to treat infections caused by gram-positive bacteria — is increasingly being replaced by other agents because of the emergence of vancomycin-resistant organisms. Speakers at the 48th Annual ICAAC/ IDSA 46th Annual Meeting last month in Washington, D.C., talked about newer and investigational alternative agents, which may be used alone or in combination with vancomycin.

Vancomycin — usually used as a drug of last resort to treat infections caused by gram-positive bacteria — is increasingly being replaced by other agents because of the emergence of vancomycin-resistant organisms. Speakers at the 48th Annual ICAAC/ IDSA 46th Annual Meeting last month in Washington, D.C., talked about newer and investigational alternative agents, which may be used alone or in combination with vancomycin.

Daptomycin is useful against skin and soft-tissue infections, according to David Snydman, MD, of Tufts Medical Center in Boston. It is effective for the treatment of Staphylococcus aureus bacteremia (including MRSA), Streptococcus pyogenes, and endocarditis. There is promising data to support the use for vancomycin-resistant enterococcus (VRE) bacteremia and osteomyelitis. The drug is not indicated for pneumonia and should not be used for pulmonary infections.

Toxicity is not a major issue, Dr. Snydman said, but physicians should monitor creatine phosphokinase at all dosages, especially higher ones. The dosage can be as high as 10 mg/kg for 4 days instead of the standard 4 mg/kg for 8 days for skin and soft tissue infections, he suggested. Clinicians should be vigilant for resistance; there is documented emergence of resistance with S. aureus and VRE. Daptomycin can be used with other agents, but synergy is hard to predict. Data support the coadministration of rifampin, Dr. Snydman said, but use caution when administering with tobramycin. There are no drug interactions between daptomycin and the cytochrome P450 system.

Linezolid is indicated for skin infections (including MRSA) and pneumonia. It may be superior to vancomycin for ventilator-associated pneumonia (especially when caused by MRSA), according to Dilip Nathwani, MD, of the Ninewells Hospital Medical School in Dundee, Scotland. Recruitment is ongoing for a study of nosocomial pneumonia with suspected or proven MRSA. Dr. Nathwani also presented data showing linezolid performed better than vancomycin in treating complicated skin and skin structure infections.

Tigecycline is the first glycylcycline (a tetracycline analogue) agent; it has excellent in-vitro efficacy against gram-positive infections, said Yehuda Carmeli, MD, of the Tel Aviv Sourasky Medical Center in Israel. No resistance has been encountered yet, making tigecycline a good alternative to vancomycin in certain instances, Dr. Carmeli said. The agent is active against MRSA, VRE, and other gram-positive infections, some gram-negative ones (but not Pseudomonas and Proteus). Tigecycline is approved for soft-tissue infections and intra-abdominal infections and has been tested in pneumonia, but a comparative trial failed to show non-inferiority. The manufacturer withdrew application for a community-acquired pneumonia indication. Dr. Carmeli urged clinicians to use caution when using to treat sites not yet well studied, particularly lung infection.

Fusidic Acid can be a valuable adjunct for the treatment of serious Staphylococcus infections, said John D. Turnidge, MD, of Women’s and Children’s Hospital in North Adelaide, Australia. Fusidic acid is still used widely in many countries as a topical (e.g., for impetigo and pyoderma). Resistance for these indications has emerged and spread in Europe. Activity is largely retained against MRSA, though an optimal dosage has not been established. Oral or parenteral fusidic acid should always be used in combination with another agent for the treatment of MRSA, Dr. Turnidge said. Experts have expressed concern that fusidic acid should not be used for minor infections but instead reserved for MRSA. Limitations of fusidic acid include GI intolerability and a lack of major controlled prospective studies for serious infections.

Although these drugs represent two different classes, ceftobiprole and ceftaroline are both active against MRSA, gram-positive infections, and gram-negative infections. Both are being studied for soft-tissue infections, said David C. Hooper, MD, of Massachusetts General Hospital in Boston. Ceftobiprole is also being studied for treatment of pneumonia.

Investigational Glycopeptides differ from vancomycin in several respects. According to Dr. George M. Eliopoulous, MD, of the Beth Israel Deaconess Medical Center in Boston, they offer greater potency in vitro and less frequent dosing. Clinical positioning of these investigational agents (described below) with respect to vancomycin remains to be determined upon the approval of these drugs.

  • Dalbavancin shows promise for complicated skin and skin structure infections, including MRSA, but worldwide new drug applications were withdrawn in September. Additional Phase III multi-center studies are planned to provide additional data to support approval.
  • Telavancin also is being investigated for complicated skin and skin structure infections. In two trials of more than 1,800 patients, telavancin at 10 mg/kg once daily was marginally superior to vancomycin 1g every 12 hours. However, the drug was more promising for MRSA, where telavancin successfully treated the infection in 91 percent of patients versus 86 percent of those receiving vancomycin. Serious adverse events were more common with telavancin in this study, however (7 percent versus 4 percent).
  • Oritavancin has similar efficacy to vancomycin for the treatment of complicated skin and skin structure infections.

The pending approvals of telavancin and oritavancin in addition to the newer antibiotics expand physicians’ treatment options for gram-positive drug-resistant organisms. However, as IDSA and others have pointed out, there is still a pressing need for new compounds that are active against multi-resistant, gram-negative organisms.

Note: IDSA and the American Society of Health-System Pharmacists are developing new clinical practice guidelines on vancomycin, which will be available early next year.
 

New ARVs Offer Virologic Suppression in Most Patients

Mark Vogel
Newer antiretroviral (ARV) drugs in existing and novel classes are highly effective in treatment-experienced patients, but physicians must be careful to screen adequately for resistance patterns and sensitivity to agents, according to a session on state-of-the-art HIV care at the 48th Annual ICAAC/IDSA 46th Annual Meeting.

Newer antiretroviral (ARV) drugs in existing and novel classes are highly effective in treatment-experienced patients, but physicians must be careful to screen adequately for resistance patterns and sensitivity to agents, said Kimberly Y. Smith, MD, MPH, associate professor of medicine at Rush University Medical Center at a session on state-of-the-art HIV care at the 48th Annual ICAAC/IDSA 46th Annual Meeting in Washington, D.C., last month.

Recently approved ARVs offer virologic efficacy in multidrug-resistant patients, usually with minimal adverse events. Since few agents with demonstrated activity against multi-drug resistant virus are in the pipeline for the near future, Dr. Smith noted, “We need to get the most out of these new agents; thus, the most effective use of them requires strategic planning.”

The entry inhibitor maraviroc provides a good example of the importance of carefully selecting a drug regimen based on patient profiles. While physicians are aware that maraviroc can be very effective in patients with R5-tropic virus, some might not be aware that the less sensitive first-generation tropism assay (Trofile) was recently replaced by a more sensitive one (Trofile ES). Trofile ES is expected to do a better job of identifying patients with low levels of X4 virus who are not good candidates for treatment with maraviroc.

Dr. Smith highlighted a regimen including three recently approved drugs—the protease inhibitor darunavir (with ritonavir) plus non-nucleoside reverse-transcriptase inhibitor etravirine plus integrase inhibitor raltegravir—that resulted in high rates of viral suppression and recovery of CD4+ cells in highly treatment-experienced patients. Further studies investigating this combination are ongoing.

New Drugs for the Treatment-Naïve?

The success of new ARVs in treatment-experienced patients has some wondering whether the drugs, particularly from the new classes, are appropriate for treatment-naïve patients. Some are and some are not, reported Dr. Smith.

Maraviroc, in fact, was demonstrated to be less effective than efavirenz in the MERIT study, which was reported at the 2007 International AIDS Society (IAS) meeting. However, a poster presentation presented at the ICAAC/IDSA meeting suggested that maraviroc might have been more successful had the more sensitive tropism assay been available at the time.

Raltegravir has been shown to be as effective as efavirenz, reported Dr. Smith. A large phase III study comparing efavirenz to raltegravir (both in combination with fixed dose tenofovir plus emtricitabine) in treatment-naïve patients was presented by Lennox et al. at this year’s meeting. This study demonstrated high rates of viral suppression in subjects on both treatment arms of the study, with fewer side effects observed in the raltegravir-treated subjects.

Etravirine will like be used less often in treatment-naïve subjects due to its twice daily dosing.

Of the new agents, only darunavir is currently recommended for use in treatment-naïve patients. Once-daily dosing of this agent has been proven to be highly effective in this population, and long-term efficacy and tolerability are being studied. Both the U.S. Department of Health and Human Services and IAS-USA guidelines include darunavir among its protease-inhibitor treatment options, and the Food and Drug Administration has recently approved this agent for treatment-naïve patients.

Dr. Smith advised physicians to address adherence issues for all patients before initiating or switching therapy. However, for physicians switching patients from a failing regimen, she said, “Don’t wait too long, since additional mutations can accumulate that may affect the success of new agents.”

ID Physicians Can Increase Medicare Payments in 2009

Stephanie Cox
With fee schedule updates for 2009, plus incentive payments for e-prescribing and quality-measure reporting, physicians can increase their Medicare payments next year.

With a little extra initiative, physicians  may be able to receive more than a 5 percent Medicare pay boost for 2009, according to the 2009 Medicare Physician Fee Schedule.

For 2009, the fee schedule includes an incentive payment of 2 percent of total allowed charges for eligible professionals, including physicians, who successfully file electronic prescriptions for their Medicare patients. Physicians can earn another 2 percent incentive payment to report measures under the Physician Quality Reporting Initiative (PQRI). Both incentive payments are in addition to the fee schedule update Congress approved earlier this year that adds up to 4 percent for ID physicians. The new rates go into effect Jan. 1, 2009.

The Centers for Medicare and Medicaid Services (CMS) is encouraging physicians to e-prescribe in order to eliminate medication errors that result from the misreading of handwritten prescriptions. E-prescribing can also reduce out-of-pocket costs for beneficiaries because it facilitates communication between prescribers and pharmacies on lower-cost generic alternatives.

In order to qualify for the e-prescribing incentive bonus, physicians must have a system that:

  • generates a complete medication list through communication with patients’ pharmacies and benefit managers
  • provides decision-support tools for choosing appropriate medications
  • provides information on lower-cost, therapeutically-appropriate alternative medications and on adverse reactions by interfacing with formularies and/or tiered formularies.
  • provides information about patient eligibility and authorization requirements directly from patients’ Part D drug plans

Physicians can earn the incentive payment even if no medications were prescribed or if e-prescriptions for the drug are prohibited by law, such as in the case of controlled substances, as long as the proper code is included. 

In order to qualify for the e-prescribing incentive payment, professionals must generate at least 10 percent of their Part B charges in the outpatient setting and they must successfully e-prescribe at least 50 percent of the time during these situations.  

The new fee schedule also adopts changes to the PQRI program, including the addition of 52 new quality measures, for a total of 153, in areas including hepatitis vaccinations, HIV/AIDS, and wound care.

IDSA is analyzing these various payment incentives and will update information on our website that explains how ID physicians can participate in the PQRI and successfully e-prescirbe. Check http://www.idsociety.org/qualityimprovement.htm periodically for new information. Information on the PQRI program and the e-prescribing incentive is also available on the CMS website at http://www.cms.hhs.gov/pqri.

Change is in the Air

Anne Gershon, MD, FIDSA

I am assuming the presidency of IDSA at a time when change is in the air. For nearly a year, the U.S. presidential candidates campaigned on platforms of change. The election has brought a new president and a shift in the balance of power in Congress, and there are sure to be many changes on the way.

One change we hope to see pertains to science policy. Over the past several years, the scientific community has spoken out repeatedly in favor of policies that are well-grounded in sound science, rather than ideology. IDSA and HIVMA have criticized abstinence-only sexuality education and we have supported needle-exchange programs for injecting drug users. Obama advisors are on record saying that science will play a more central role in decision-making in the new administration.

We hope science will take its rightful place in other issues important to public health, including vaccine safety and Lyme disease diagnosis and treatment. IDSA and HIVMA wrote to both presidential candidates during the campaign to encourage them to pursue science-based policies. We will continue to serve as a resource on these issues. We also will continue to advocate for improved funding for the National Institutes of Health and the Centers for Disease Control and Prevention, the cornerstones of our nation’s scientific research and public health endeavors. 

One area we hope does not change with the new presidency is the U.S. commitment to addressing the global HIV/AIDS epidemic. Despite our disagreements on some issues, we salute the Bush administration for its extraordinary leadership in this arena. The President’s Emergency Plan for AIDS Relief contributed to the remarkable improvements in access to HIV care among some of the world’s poorest people. In the current economic climate, there is a danger that politicians will lose the political will to commit to this program.

This makes another change all the more welcome: the opening of the new IDSA/HIVMA Infectious Diseases Center for Global Health Policy and Advocacy. Funded by the Bill & Melinda Gates Foundation, the Center will provide decision-makers with the best available evidence on what works and what needs to be done to control HIV and tuberculosis (TB). You recently received a survey about your involvement and interest in global HIV and TB. If you haven’t already done so, please take five minutes to fill it out. The new Center will derive its strength from the expertise and involvement of our members.

Another historic change took place this fall: For the first time in 11 years, the IDSA Annual Meeting and the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) were held together. Whether this was change for the better is up to you. ICAAC/IDSA drew nearly 16,000 people to Washington, DC for an exciting, content-rich joint meeting featuring timely updates and the latest in infectious diseases research. We are evaluating attendee feedback in order to help make a decision on future meetings. In the meantime, IDSA returns to its solo meeting next year in Philadelphia. We look forward to seeing you there.

In the midst of all this historic change, a number of things will stay the same. IDSA’s commitment to its members, to attracting the best and brightest to the specialty of infectious diseases, and to expanding our global reach remains strong. I look forward to serving as your president.


 

Antimicrobial Stewardship Programs, National Campaigns Curb Usage

Mark Vogel

Local antimicrobial stewardship programs and national public awareness campaigns both are effective means of reducing antibiotic use and resistance, according to speakers at the 48th Annual ICAAC/IDSA 46th Annual Meeting in Washington, D.C.

Antimicrobial stewardship — defined as a system of informatics, data collection, personnel, and policy/procedures that promote the optimal selection, dosing, and duration of therapy for antimicrobial agents — has been shown to limit the emergence and transmission of antimicrobial resistance when used in combination with infection control, said Christopher A. Ohl, MD, associate professor of medicine at Wake Forest University.

IDSA/SHEA Guidelines

In 2007, IDSA and SHEA published antimicrobial stewardship guidelines (Clin Infect Dis 2007; 44:159-77) to guide hospitals and other institutions in setting up comprehensive programs to cut antimicrobial use and lower resistance. “The key to a good program is to choose your name wisely and appeal to your base,” said Dr. Ohl. Program names containing the word “stewardship” appeal more than “control,” he said. Furthermore, it is imperative to demonstrate to the medical staff that the program is good for their patients. He suggested showing prescribers local antimicrobial-use data, which may surprise them.

Dr. Ohl described core elements of any successful program. They include a multidisciplinary team including an ID physician and a clinical pharmacist with ID training, as well as additional staff, including a clinical microbiologist, an information systems specialist, and an infection control professional. The team should develop a comprehensive program based on local antimicrobial use, local resistance patterns, and available resources.

The IDSA/SHEA guidelines recommend two core strategies that provide the foundation for an antimicrobial stewardship program. (These strategies are not mutually exclusive.) The two strategies are:

  • Prospective audit of antimicrobial use with direct interaction and feedback to the prescriber, performed by either an ID physician or a clinical pharmacist with ID training. The main disadvantage of this approach is that it is resource-intensive and prescribing changes are voluntary.
  • Formulary restriction and pre-authorization. Formulary restrictions can lead to immediate reductions in antimicrobial use and cost. The efficacy of pre-authorization is less clear, according to the guidelines, but may be useful in modulating antimicrobial use. Pre-authorizations are done by the ID physician or clinical pharmacist by pager or phone and usually result in a “mini-consult,” said Dr. Ohl. The disadvantage of this approach is that it could lead to inaccurate or misleading information from the prescriber or simply a switch to another antimicrobial agent that is not restricted or that does not require pre-authorization. Such approaches are also labor intensive and require nearly 24/7 support.

Supplemental interventions such as computerized order entry and clinical decision-making tools can be effective, added Dr. Ohl. One web-based clinical decision-support tool resulted in a $370,000 reduction in costs, an 11.6 percent reduction in doses, a 46 percent increase in user satisfaction, 40 percent fewer restricted antimicrobial-related phone calls, and an overall reduction in missed or delayed doses (Agwu et al. Clin Infect Dis 2008; 47:747-53).

National Campaigns

National antibiotic use campaigns are also an effective way to lower antimicrobial use and resistance. Herman Goossens, MD, of the University of Antwerp, Belgium, provided an overview of several European national public awareness campaigns, particularly Belgium’s program, which has been run every winter since 2000. Belgium spends 400,000 Euro every year on television ads, information booklets, posters, and Internet campaigns.

The program’s impact and outcome measures both indicate success. Nearly half of the public surveyed remember the antibiotics campaign (television had the biggest impact); they remember the main message was “we use them too much” (38 percent) and “take them only if needed (25 percent). After the campaign, two-thirds agreed to use fewer antibiotics in agreement with their general physician (GP) versus 64 percent before the campaign. An astounding 100 percent of GPs surveyed remembered the campaign three months after it ended.

Antimicrobial resistance in several classes is down in Belgium. Drug-resistant Streptococcus pyogenes (obtained from throat cultures) decreased from 18 percent in 2002 to 2 percent in 2007, according to data from the University of Antwerp. Outpatient antibiotic use has decreased as well.

Dr. Goossens also pointed to a huge cost savings across European programs. For every 1 Euro invested, 8 Euro were saved.

“Strong joint public health, scientific, and political leadership in Europe results in the curbing of antibiotic use and resistance, both in community and hospitals, in an increasing number of countries,” concluded Dr. Goossens.

How to Treat MRSA? What Makes it Virulent?

Steve Baragona

Methicillin-resistant Staphylococcus aureus (MRSA) continues to develop resistance to a range of therapies, according an update on the epidemic at the 48th ICAAC/IDSA 46th Annual Meeting in October. In other developments updated at the session, Panton-Valentine leukocidin does not appear to be the primary virulence factor.

With nearly 100,000 invasive infections and 19,000 deaths each year, MRSA is “the epidemic of our time,” said Robert Daum, MD, of the University of Chicago Medical Center.

Community-associated (CA) MRSA, particularly the USA300 strain, has become the leading cause of emergency department visits for skin and soft tissue infections (SSTI) in most of the United States, and the rise of USA300 coincides with a sharp increase in SSTI hospitalizations, according to the Centers for Disease Control and Prevention’s Rachel Gorwitz, MD, MPH. The increasing incidence of MRSA community-acquired pneumonia is also becoming a serious concern. While most invasive MRSA infections are associated with health care, onset of infection predominantly occurs in the community, Dr. Gorwitz said.

The presence of Panton-Valentine leukocidin (PVL) is associated with epidemic MRSA strains and is a known virulence factor. However, Frank DeLeo, PhD, of the National Institute of Allergy and Infectious Diseases (NIAID), presented data suggesting PVL is not the primary virulence factor. Instead, a group of proteins called phenol-soluble modulin-like peptides (PSM), not PVL, appeared to promote severe SSTIs, pneumonia, and neutrophil lysis in animal models.

The primary management for CA-MRSA SSTIs is incision and drainage (I&D), Dr. Daum said. He noted that although most respondents to a recently published survey said they would add anti-MRSA antibiotics, there is very limited data on the efficacy of antibiotics for these infections. An NIAID-sponsored study is underway to provide some of the missing data. (IDSA urged NIAID to undertake a study like this one.)

Clindamycin is one of the top choices for empiric therapy of SSTIs, but reports of clindamycin-resistant MRSA are increasing. Some strains carry the erm gene that confers resistance to erythromycin and—sometimes—clindamycin. To assess clindamycin susceptibility, Dr. Daum strongly recommended performing a “D test,” which determines whether clindamycin resistance can be turned on. A positive D test generally—but not always—indicates clindamycin resistance. Before changing therapy, Dr. Daum advised, “Go to the patient’s bedside and see if they are already cured.”

For MRSA pneumonia, vancomycin remains the mainstay of treatment, Dr. Daum said.  But vancomycin has poor bacteriocidal activity, does not penetrate tissues well, and resistance is increasing. There are a few options beyond vancomycin, but all have serious shortcomings. Daptomycin is perhaps the next-best option, but elevates creatine phosphokinase levels. Linezolid has problems with hematologic toxicity, neuropathies, and lactic acidosis, especially with prolonged use. Daptomycin and tigecycline are not recommended for pediatric cases. There are reports of resistance to all these drugs. Drugs in clinical development all have serious shortcomings as well.

“I believe we need a Staphylococcus aureus vaccine,” Dr. Daum concluded. “I think the attack rate is high enough, and the antibiotic resistance problem demands it.”

ACIP Recommends Pneumococcal Vaccine for Cigarette Smokers

The federal Advisory Committee for Immunization Practices (ACIP) has added cigarette smokers ages 19-64 years to the list of people for whom pneumococcal vaccine is recommended, according to Samuel Katz, MD, FIDSA, IDSA’s liaison to ACIP.

This is the first time ACIP has recommended a vaccine specifically for smokers. The group also recommended that smokers undergo stop-smoking counseling. ACIP made the recommendation at its Oct. 22-23 meeting.

The Centers for Disease Control and Prevention (CDC) estimates that about one-fifth of U.S. adults smoke cigarettes. Cigarette smoking has bee identified as a major risk factor for pneumococcal disease, and the risk of pneumococcal disease increases with the longer one smokes and the number of cigarettes one has smoked. Population-based surveillance studies consistently report that smokers account for approximately half of otherwise healthy adults with invasive pneumococcal disease.

In June ACIP had recommended adding asthma to the list of indictions for giving the vaccine. ACIP may re-evaluate its recommendations in the future as new pneumococcal vaccines are licensed by the Food and Drug Administration (FDA).

Wyeth hopes to have approval for its new pneumococcal conjugate vaccine with 13 serotypes by mid-2009. In addition to the seven serotypes in the current conjugate vaccine, the new vaccine will have six new ones (1, 3, 5, 6A, 7F, 19A). Serotype 19A is of special note as it has become recognized more frequently in some locations and as a cause of invasive disease.

In other news, ACIP:

  • Reviewed safety data on the new human papillomavirus (HPV) vaccine. More than 16 million doses of HPV vaccine have been distributed in the U.S. Syncope continues to be frequent among recipients, but investigations do not show any increased risk for thromboembolism, transverse myelitis, Guillain-Barre syndrome, or other adverse outcomes. As with all approved vaccines, CDC and FDA continue to monitor the safety.
  • Examined changes in rotavirus activity. Following widespread use of a new rotavirus vaccine, the 2007-2008 started 15 weeks later and was 12 weeks shorter than usual.
  • Reviewed safety data on the combined live measles, mumps, rubella, and varicella virus vaccine (MMRV).  Preliminary results have shown a 2-fold higher risk of febrile seizures during the two weeks after vaccination with MMRV, compared with simultaneous separate injections of measles, mumps, rubella (MMR) and varicella vaccines administered at the same visit. In June, ACIP withdrew its preference for combined MMRV over separate injections of MMR and varicella vaccines for the first dose and is awaiting further data on the second dose. However, since MMRV is not currently being distributed in the U.S. because of production problems, the issue is moot.
  • Received an update on influenza vaccine and antivirals. Virus isolates from the southern hemisphere demonstrate good matches with the 2008-2009 vaccine under current use. Increasing reports of H1N1 isolates resistant to oseltamivir range from 4 percent in Spain to 67 percent in Norway.

ACIP recommendations become official once approved by the Centers for Disease Control and Prevention and published in Morbidity and Mortality Weekly Report. For more information, see: http://www.cdc.gov/vaccines/recs/acip/.

In the IDSA Journals

Effect of Combination Antiretroviral Therapy on CD4 T Cell Count

Treatment options for HIV infection have evolved from nonboosted protease inhibitors (PIs) to nonnucleoside reverse-transcriptase inhibitors and boosted PI-based regimens, but the impact on immunologic recovery has remained uncertain. In a retrospective cohort study, the authors found that all three treatment strategies resulted in a similar recovery of the CD4 T cell count. (Khanna et al., Clin Infect Dis. 2008;47:1093-1101.)  

Combination Therapy or Monotherapy for Prosthetic Joint Infection?

Despite medical and surgical advances, the optimal treatment of prosthetic joint infections (PJI) remains a challenge, and the outcome remains poorly defined. In a retrospective cohort study, researchers analyzed data for all patients with enterococcal PJI over a 30-year period at a single institution. The outcomes of patients treated with a combination of vancomycin or β-lactam with an aminoglycoside were not significantly different from those of patients treated with monotherapy. (Helou et al., Clin Infect Dis. 2008;47:903-909.)  

Hospital Staffing and Health Care-associated Infections

In a review of studies of the relationship between nurse staffing variables and a patient's risk of developing a health care–associated infection, a significant correlation was found in 45 percent of the studies. The use of nonpermanent staff was associated with increased rates of hospital-associated infection. Float nurses and other temporary staff members may lack specific training, familiarity with procedures, and the relationships necessary for clear communication. (Stone et al., Clin Infect Dis. 2008;47:937-944.)

Bacteria Were Main Killers in Spanish Flu

Secondary bacterial pneumonia caused the vast majority of deaths in the 1918-19 influenza pandemic, according to a re-examination of autopsy samples and data. Pandemic influenza planning must target these infections as well as the primary viral infections, conclude the authors. (Morens et al., Journ Infect Dis. 2008;198:962-970; editorial commentary by McCullers, Journ Infect Dis. 2008;198:945-947.)

CXCR4 Emergence as Predictor of AIDS?

Emergence of CXCR4-utilizing HIV (X4) appears to contribute to T cell decline and progression to AIDS. A study of 67 HIV-infected patients found X4 tropism was more common in those who progressed to AIDS within 11 years of seroconversion and among those who experienced a decline in total T cell populations, compared to those who did not. Emergence of X4 viruses was seen at a median CD4 T cell count  of 475/µL in these patients, and occurred nearly a year before any T cell decline was noted. (Shepherd et al., J Infect Dis. 2008;198:1104-1112; editorial commentary by Burger and Hoover, J Infect Dis. 2008;198:1095-1097.)

HSV Reactivations Frequent but Brief

Asymptomatic reactivations of herpes simplex virus (HSV) 1 and 2 infection are more frequent, but briefer than previously thought, and are cleared rapidly. This study of 25 patients infected with HSV-2 and 18 HSV-1 patients observed an average rate of 18 reactivations per year, 81 percent of which were asymptomatic, and half of which lasted less than 12 hours. Rapid clearance strongly suggests involvement of the peripheral mucosal immune system. (Mark et al., J Infect Dis. 2008;198:1141-1149; editorial commentary by Mertz, J Infect Dis. 2008;198:1098-1100.)

For More in the Literature...

The IDSA Journal Club features brief summaries of key infectious diseases studies in the previous month’s major journals chosen by the IDSA Literature Review Panel. The Journal Club will return in the next issue of IDSA News.

In each issue of Clinical Infectious Diseases (CID), the “In This Issue” section highlights several important studies from that journal. (Click for November 1 or November 15.) For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of CID:

November 1:

  • Candida Endocarditis
  • Histoplasmosis and HIV Infection
  • Neutropenic Enterocolitis and Other Causes of Abdominal Pain in Neutropenic Patients
  • Herpes Simplex Suppression and HIV Infection

November 15:

  • Staphylococcus lugdunensis
  • Dental Bacteremia
  • The Right Time for Surgical Antibiotic Prophylaxis

EIN: When is it OK for TB Patients to Use TNF inhibitors?

Steve Baragona

An EIN member has been treating a patient for disseminated tuberculosis (TB) who also has recurring psoriasis. The patient has been taking combination TB drugs for four months and the last positive culture was more than three months prior. The patient’s dermatologist recommended treating the psoriasis with the TNF inhibitor etanercept (Enbrel), but the member is concerned about the implications for TB therapy. With the disease under control, the member is inclined to support the TNF-inhibitor treatment.

A respondent replies: “I know of no data to guide the choice as to when to resume anti-TNF therapy during the treatment of active TB. There is limited data to suggest that therapy of TB concurrent with etanercept administration started early during the TB treatment course might be safe (Wallis et al., AIDS 2004;18:257-264), but this was in a very small number (n=16) of HIV/TB co-infected patients. The issue deserves further study.”

The respondent continued, “CDC recommendations several years ago (Winthrop et al, Arthritis Rheum. 2005 Oct;52(10):2968-74) recommended waiting until anti-TB treatment was completed or in the very least, until the patient had been treated for 2 months, made clinical improvement, and was tolerating and adhering to a regimen to which their TB isolate was known to be sensitive. This recommendation was not driven by data, but rather because it seemed reasonable.”

“In the case outlined within this posting, it is probably reasonable to resume etanercept (Enbrel) if the patient meets the criteria above,” the respondent concluded.

As the use of anti-TNF and related agents increases, questions about management of the infectious complications associated with these drugs have also increased. Several questions related to the class of TNF-α antagonists have been posted to the EIN listserve recently. A 2007 EIN survey found that non-tuberculous mycobacterial infections, histoplasmosis, and invasive Staphylococcus aureus infections were all reported more frequently than was tuberculosis disease (Winthrop et al, Clin Infect Dis. 2008;46:1738-40). Clinicians should remain vigilant for mycobacterial infection and other types of serious infections that occur in patients using these agents. 

Drug Approvals, Recalls, Adverse Events Update

Rebecca Dotson

IDSA offers two e-mail services to help members stay informed of updates from the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). Recent alerts have included:

FDA Alerts:

No CDC alerts this month.

IDSA members can sign up for these services online. (You must be logged in to have access to this link.)

Infusion and Injection CPT Codes Changed

Several outpatient infusion coding and payment changes will take effect in 2009 that could impact the way ID practices code for drug administration services and bill for the drugs.

The current procedural terminology (CPT) infusion and injection codes for hydration and for non-chemotherapy therapeutic, prophylactic, or diagnostic drug administration have been renumbered.  The code changes, along with coding instructions and payment rates, are available on the IDSA website. (Login required). The changes take effect Jan. 1.

The codes were renumbered so that they would be adjacent to the chemotherapy administration codes in the 2009 CPT codebook for ease of reference to providers and their billing staff. There are no changes in the definitions.

Beginning in 2009, these infusion and injection codes are also available for hospitals and other inpatient facilities. Please refer to the CPT codebook for instructions on how to report these codes in inpatient settings.

Additional IVIG Payment Ends

In another change for 2009, the temporary payment Medicare offered physicians for infusing intravenous immune globulin (IVIG) has expired.

The Centers for Medicare and Medicaid Services (CMS) established a temporary G-code (G0332) for 2006-2008 to compensate physicians after supply shortages pushed the cost of IVIG over the Medicare reimbursement rate. CMS says the shortage has abated. IDSA continues to monitor the situation.

Finally, Medicare has postponed the competitive acquisition program for Part B drugs and biologicals. More information is available on the IDSA webiste.

2009 Clinical Practice Meeting in San Diego

Jeanna Ray

Online registration is now available for the  IDSA 2009 Clinical Practice Meeting.  This year’s meeting will take place on March 20 and 21 in San Diego and will feature valuable resources and practical strategies for clinicians in practice.

Featured Speakers:

  • Nancy Nielson, MD, PhD, president of the American Medical Association and an ID physician, will speak on Physician Quality Initiatives:  The Niche for ID Specialists.
  • William F. Jessee, MD, president and chief executive officer of the Medical Group Management Association, will speak on Health Care in 2009 and Beyond.
The 2009 meeting will include sessions on how to negotiate with private payers, address the challenges of human resources management, and improve billing and coding processes. Other topics include wound care clinic management and best practices, pay-for-performance and the electronic medical record, and the niche for ID specialists in quality improvement. The 2009 meeting will also feature plenty of break-out sessions so that attendees can tailor the meeting to their own interests.

More information is available online.

WHO Promotes “Three I’s” for HIV/TB Co-infection

Bill Black

The World Health Organization (WHO) is calling for a worldwide focus on “Three I’s” for the prevention and treatment of tuberculosis (TB) in people living with HIV: isoniazid preventive treatment (IPT), intensified case finding (ICF) for active TB, and TB infection control (IC).

In recent years, as many lower-income countries have greatly expanded their HIV programs, they have found themselves confronting another, related threat: a dramatic rise in the number of persons infected with both HIV and TB. In 2008 alone, an estimated 230,000 people living with HIV will die as a result of TB, or some 630 persons every day.

WHO has created the Three I’s strategy in response. All three approaches have proved to be effective. Isoniazid prophylaxis can reduce the risk of TB for people living with HIV by between 33 and 62 percent. Intensifying efforts to find TB cases is important because while screening and diagnosing TB in people living with HIV can be difficult, once cases are found, TB can be cured. And infection control is key to preventing the spread of TB to vulnerable patients, health care workers, and the broader community.

“None of those things is very new and sexy, but what we think is new and sexy is actually that the three are being thought up together and as part of HIV care and treatment,” said Reuben M. Granich, MD, MPH, of WHO’s HIV/AIDS Department, at the 39th Union World Conference on Lung Health in Paris in October.

To scale-up the Three I’s worldwide in 2009, WHO plans to issue a screening algorithm and a single set of guidelines on intensified case finding and preventive treatment. WHO also separately plans to issue new guidelines for infection control in 2009.

Increased advocacy efforts involving other international institutions, policymakers, community organizations, and activists will be central to the WHO efforts, according to Dr. Granich.

Slides of Dr. Granich’s talk and others from the conference are available  online. (For Dr. Granich’s talk, see “Global Progress Report On Scale-Up Of The Three I’s.”)

IM Subspecialists Lend Support to Adult Immunization

Diana Olson

The American College of Physicians (ACP), IDSA, and 17 other internal medicine subspecialty societies are asking their members to take a more active role in discussing and reviewing their adult patients’ vaccination status and in administering recommended vaccines.

IDSA played a pivotal role in encouraging ACP and the other societies to adopt a new policy statement outlining their support for adult immunization. The statement was announced earlier this month.

The Centers for Disease Control and Prevention (CDC) estimates that about 95 percent of vaccine-preventable diseases occur in adults. Each year, hundreds of thousands of adults are hospitalized and more than 46,000 adults die because of vaccine-preventable diseases or their complications. Costs associated with treatment run in the billions.

Adult Uptake of New Vaccines

2.1%:

Adults ages 18-64 who received diphtheria-tetanus-pertussis

1.9%:

Adults ages 60 and older who received zoster (shingles)

10%:

Women ages 18-26 who received human papillomavirus

Adult Uptake of Influenza Vaccine, 2007

37%:

High-risk individuals age 18-49

42%:

Individuals age 50-64

69%:

Individuals age 65 and older

Source: Centers for Disease Control and Prevention

While immunization rates among children are high, uptake rates for adults fall significantly short of public health targets. Adult vaccination rates range from 26 to 69 percent, depending on the vaccine and the specific target group. For newer vaccines, the rates are even lower. (See box.)

“Thanks to immunization, most children in this country never suffer from vaccine-preventable diseases. That’s not true for their parents or grandparents,” said William Schaffner, MD, FIDSA, chair of IDSA’s Immunization Work Group. “Every year, thousands of adults get sick, miss work, are hospitalized, and many die because of vaccine-preventable diseases.”

“It is crucial for physicians—internists, family physicians, and subspecialists who provide primary and preventive care services for patients, especially those with chronic diseases—to discuss and review their adult patients’ vaccination status and either vaccinate them or provide a referral for recommended vaccines,” said Jeffrey P. Harris, MD, FACP, president of ACP.

The ACP/IDSA statement also notes that physicians and their staff should be up to date on their own recommended immunizations, particularly their annual flu vaccinations.

ACP and IDSA plan to work with the other subspecialty societies toward facilitating access to tools and resources to help physicians encourage adult immunization--such as simple screening tools (see the Immunization Action Coalition’s patient checklist at www.immunize.org/catg.d/p4036.pdf), software for physicians offices, improved insurance coverage, and better payment for vaccines and their administration.

For its part, IDSA plans to survey its members in the near future about their practices and opinions regarding immunizing adults. “We hope IDSA members will respond to this survey and be very candid in their answers,” said Dr. Schaffner. “We have a huge potential to improve public health, but first we need to fully understand why more adults aren’t being immunized.”

Dr. Schaffner acknowledges that cost is one factor. Many new vaccines are expensive, and more than 40 million individuals in the U.S. do not have health insurance coverage. For those who do, coverage of vaccines is not always adequate.

For more information, see the adult immunization section of the IDSA website. The ACP/IDSA Joint Statement of Medical Societies Regarding Vaccination by Physicians can be found there, as well as IDSA’s 2007 policy principles on adult immunization, , with specific steps to strengthen adult immunization coverage. The American Medical Association recently lent its support to the concepts outlined in IDSA’s 2007 document.

FDA Advisory Groups Warn Against Home Stockpiling of Antivirals for Pandemic Flu

Two advisory committees to the Food and Drug Administration (FDA) have recommended against home stockpiling of antivirals in preparation for pandemic influenza following a meeting in which  IDSA and other medical societies outlined their concerns.

The committees were reviewing proposals from two drug companies--GlaxoSmithKline and Roche—to develop products called MedKits consisting of the companies’ influenza antiviral drugs and patient instructions. Each of the MedKits would contain enough medication to use for either treatment (5-day course, twice daily) or prophylaxis (10-day course, once daily). The companies developed their proposals in response to a request from the Department of Health and Human Services (HHS).

At a joint meeting of FDA’s Antiviral Drugs and Nonprescription Drugs Advisory Committees on Oct. 29, IDSA and other medical societies expressed their reservations about the proposals.  “Every policy carries potential risks and benefits,” said Luciana Borio, MD, of IDSA’s National and Global Public Health Committee. “This policy introduces an uncertain time-lag between acquisition of prescription and drug-taking, and therefore introduces uncertainties regarding the risks and benefits, making this proposal particularly difficult to evaluate. An adequate science base is needed to inform this calculation.”

To understand the benefits, Dr. Borio said, more information is needed about the correct dosing and duration for the treatment of severe influenza--an important proxy for pandemic flu. “We might only learn that information once a pandemic occurs,” she said. At that point it would be difficult to get appropriate advice to individuals who have stockpiled the treatments in advance.

Other concerns include the difficulty for patients to assess when to start a prophylactic course and the possibility of drug resistance. Dr. Borio asked the committees, “Is it wise for the government to promote family purchase of a therapeutic of uncertain benefit, which might potentially be rendered ineffective due to changing susceptibility of influenza viruses, and which carries a limited shelf-life?”

Finally, she noted, the policy wouldn’t alleviate the need for public health stockpiles.

On a related front, IDSA has continued to express concerns to HHS about home stockpiling of antibiotics for a potential anthrax attack, including the importance of evaluating home stockpiling strategies and exploring other options for rapid access.

Seasonal and Pandemic Influenza 2008 Monograph Now Available

Stephanie Cox

A CME-certified monograph based on the proceedings of the Seasonal and Pandemic Influenza 2008 meeting is now available online. This monograph is intended for those who are involved in caring for patients at risk for or with seasonal or avian influenza, or those who are involved in research or policy decisions that will lead to improvements in influenza prevention or treatment.

After completing this CME activity, participants will be able to:

  • identify groups at risk for morbidity and mortality from seasonal influenza infection
  • describe the global spread of seasonal and pandemic influenza, including the role of animal hosts
  • list pharmacologic and non-pharmacologic interventions to control seasonal and pandemic influenza
  • discuss the recommendations for vaccination of the U.S. population, reasons for current usage rates, and strategies to improve uptake
  • summarize current data on efficacy, safety, and resistance of antivirals for seasonal influenza
  • report the global and U.S. status of social and biomedical interventions to prevent or manage an influenza pandemic

This program is approved for a maximum of 2.5 AMA PRA Category 1 Credits™. 

Visit fluinfo.idsociety.org to access the CME-certified monograph and learn about seasonal and pandemic influenza.

How to Claim CME Credit from ICAAC/IDSA

Steve Baragona

If you attended the 48th Annual ICAAC/IDSA 46th Annual Meeting this October, you can claim CME credit through the Joint Meeting web site, www.icaacidsa2008.org.  Follow the link under “Claiming Your Statement of Credit.” You will need to log in using your last name and the ZIP code you used to register for the meeting. 

Welcome, New IDSA Members!

Members

Akpaka, Patrick, MD
Alejandria, Marissa, MD
Allende, Maria, MD
Al-Nakib, Widad, MD
Clax, Pamela, DPM
Cooperstock, Michael, MD
Felton, Mark, PhD, BSN, DTM & H, MB, MRCP, MSc
Ghide, Solomon, MD
Guardo, Monica, MD
Hammond, Abdulrahman, MD
Heyderman, Robert, DTM&H, MBBS, PhD
Kaplan, Nachum, PhD
Labischinski, Harald, PhD
Levi, Marilyn, MD
Mehta, Geeta, MD, MBBS, MPH
Papadopoulos, Antonios, MD
Romano-Mazzotti, Luis, MD
Seki, Masafumi, MD
Sherwood, Edward, MD
Solante, Rontgene, MD
Tarr, Philip, MD
Turner, Paul, MD
Van Vaerenbergh, Kristien, MD, PhD
Zeigler, Dustin, PharmD

Associate

Abreu, William, MD
Abudher, Abdulhafid, MD
Airemen, Susan
Al-Sulaiti, Ghada, MBBS
Arbeter, Allan, MD
Astry, Calvin, PhD
Azad, Shahnaz, MD
Bonnet, Eric, MD
Boreyko, John, PharmD
Breuer, Judy, MD
Catanzaro, Andrew, MD
Crosby, Cynthia
De Farias, Alessandro
de la Rosa Zamboni, Daniela, MD
De Mendonca Melo, Mariana, MD
Diaz-Mitoma, Francisco, MD, PhD
Dunn, Jeanne
Durrant, Ian, PhD
Egami, Yoriko, MD
Enani, Mushira, MBBS
England, Leslie, MD
Enrique, Silvia
Farley, Jason
Finney, James, PhD
Fisher, Neil, MD
Florez, Jorge, MD
Foster, Charles, MD
Franka, Ezzadin, MD, PhD
Frosch, Anne, MD, MPH
Garcia, Liza, MD
Garcia, Hermes, MD
Gler, Maria, MD
Grady-Letendre, Norah, MSN
Gupta, Vineet, MBBS
Gutkind, Gabriel, PhD
Hamour, Abu Obeida, MD
Hernandez, Anny, MD
Hildreth, Stephen
Horban, Andrzej, MD, PhD
Irani, Paurus
Karunakaran, Kumudhini, MD
Khan, Sabih, PhD
Kozlov, Roman, MD, PhD
Landry, Monique, MD
Lima, Maria, PhD
Matti, Pamela, MD
Moniot-Ville, Nathalie, MD
Mooka, Busi, MD
Moore, Kathy, PA-C
Morales, Arturo, PhD
Nemeri, Omer, MD
Nicogossian, Arnauld
Nino-Oberto, Sandra, MD
Obsioma, Maria, MD
Park, Sueun, MD
Park, Tae-ho, PhD
Pasternak, Jacyr, PhD
Pasumbal, Edwin, MD
Pearson, Andrew, MD
Perenboom, Roos, MD, PhD
Ramiro, Jane, MD
Rank, Douglas, MD
Raymundo-Tayzon, Maria, MD
Rizk, Hussein, MD, BCh
Rosario, Amanuel, MD
Royero, Cristina, MD
Salazar Giraldo, Beatriz
Sepulveda Arzola, Gladys, MD
Shariati, Nasser, MD
Shoemaker, Susan, PhD
Sikkema, Craig
Smith, Ronald, RPh
Starling, Carlos, MD
Straus, Don
Sutopo, Bambang, MD, DTM&H
Tecalero, Jose, MD
Van Utterbeeck, Martine, MD
Vasileios, Papastamopoulos, MD
Villar, Luis, MD
Went, Gregory, PhD
Wilhelm, Jan
Wortzman, David, MD
Yassin, Mohamed, MD
Yicenia, Brito, MD

Members-in-Training

Agrawal, Aarti, MD
Aldoo, Christian, MD
Berry, Stephen, MD
Brown, Claire, MD
Capraro, Ilavia, MD
Chak, Azfar, MD
Christoff, Jennifer, MD
Chua, Joel, MD
Fana, Cruz, MD
Ghosh, Niladri, MBBS
Goolsby, Tiffany, PharmD
Hawkinson, Dana, MD
Herbert, Courtney, MD
Hingwe, Ameet, MD
Hou, Cindy, DO
Kwan, Candice, MD
Lin, Htein, MD
Marty, Aileen, MD
Mirembe, Justine, MD
Nicolescu, Ioan, MD
Qamar, Fozia, MD
Saleeb, Paul, MD
Sebunya, Robert, MD, MB, ChB
Sharma, Saarika, MA, MD
Wolfe, Cameron, MD

In Memoriam

Alford, Charles, MD
Weller, Thomas, MD