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December 2008
Vol. 18 No. 12
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IDSA Journal Club, December 2008

In this feature, a panel of IDSA members identifies and critiques important new studies that have a significant impact on the practice of infectious diseases medicine.

For more from Clinical Infectious Diseases and The Journal of Infectious Diseases, see the "In the IDSA Journals" section of IDSA News.

C. diff Rapid Tests Fall Short
By Khalil Ghanem, MD

Prevalence and pre-test probability of Clostridium difficile had a major impact on the ability of rapid diagnostic tests to accurately detect the infection, according to a review in the December issue of The Lancet Infectious Diseases. The authors recommend two-step screening using a rapid test followed by a confirmatory test on positive samples to maximize accuracy.

Diarrhea caused by C. difficile is common, and a new strain may cause more aggressive disease. The authors conducted a systematic review of the literature to determine the performance characteristics (sensitivity, specificity, positive predictive value) of commonly used rapid diagnostic tests for both Type A and B toxins that are produced by the organism. Due to significant heterogeneity in the studies reviewed, the authors were unable to use formal meta-analytic methods to calculate mean sensitivity and specificity estimates for these assays.

Overall, the performance measures for most of the assays studied were lower than the manufacturers’ values. None of the diagnostic tests achieved 100 percent sensitivity or specificity. Thus, negative results do not always rule out C. difficile colitis and positive results do not necessarily indicate true disease. As with all diagnostic tests, it is up to clinicians to interpret the results of these assays carefully: When the pre-test probability of C. difficile infection is moderate to high, a positive test is more likely to be a true positive. Repeat testing following a negative test may improve sensitivity. In settings where the pre-test probability is low, follow-up with a reference test can confirm a positive rapid test result. This additional step increases accuracy but is time-consuming and expensive. (Planche et al., Lancet ID. 2008;8:777-84.)

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Scoring HCAP to Improve Empiric Antibiotic Selection?
By Sara Cosgrove, MD, MS

A scoring system to better predict which patients with health care-associated pneumonia (HCAP) have infection caused by drug-resistant pathogens is proposed in a study published in the November 10 issue of the Archives of Internal Medicine.

Pneumonia patients with recent exposure to health care are more likely to have resistant pathogens. However, the authors note there are shortcomings in the criteria used to define HCAP in the recent American Thoracic Society/IDSA guidelines that may lead to the overuse of broad-spectrum antibiotics.

Investigators examined 639 patients with bacterial pneumonia. Patients were considered to have HCAP if they met at least one of the following criteria: hospitalization in the past 90 days, residence in a nursing home or long-term care facility, undergoing hemodialysis, or immunosuppression.  Patients had to have positive microbiology results suggesting pneumonia in order to be included.

The specificity of the HCAP definition was only 48.6 percent and misclassified one-third of patients. Not all risk factors conferred equivalent risk for infection with a resistant pathogen: 82 percent of patients with recent hospitalization had a resistant pathogen, compared to only 10 percent of patients on hemodialysis, 30 percent of nursing home patients, and 35 percent of immunosuppressed patients.

The authors created a scoring system that gives a patient 4 points for recent hospitalization, 3 points for nursing home residence, 2 points for hemodialysis, and 1 point for needing ICU care. Seventy-five percent of patients with a score of 6 or more had resistant pathogens, compared to 20 percent of patients with a score of 0-2. 

The scoring system is a good first step in guiding antimicrobial therapy in HCAP, but it must be viewed with caution as it is derived from data from a single site without split-sample or external validation.  It is also important to note that this study only looks at patients in whom a pathogen was detected in a disease that is notoriously difficult to diagnose microbiologically.  Both issues may limit the generalizability of the study.

 (Shorr et al., Arch Intern Med. 2008;168:2205-2210.)

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New Data on Age and HAART
by Sabrina Kendrick, MD

Time to virologic suppression after HAART initiation was shorter in older patients compared to younger patients, although CD4 response did not differ, according to a study published in the November 12 AIDS issue.

This retrospective analysis followed an observational cohort of HAART-naïve patients from an urban outpatient clinical setting. The cohort included 670 patients under 40 years old and 149 patients 50 or more years old.

Older patients were more likely to be on nonnucleoside reverse transcriptase inhibitors (NNRTI) versus protease inhibitors (PI) than younger patients (42 percent vs. 29 percent), and had fewer AIDS-defining opportunistic infections (OIs) (22 percent vs. 31 percent). However, they had higher overall mortality (36 percent vs. 27 percent) and shorter survival (36.2 months vs. 58.5 months) than younger patients. AIDS-related deaths were similar between the two populations, which suggests younger patients had more non-fatal OIs than older patients. NNRTI-based regimens significantly increased the likelihood of virologic suppression.

This is one of the first studies to examine the effect of HAART regimen type on clinical response by age group. Limitations include the small sample size of older patients, which may account for the inability to detect immune response differences between the study populations. Duration of HIV infection, co-morbid conditions’ influence on disease progression, and mortality cause in relation to long-term HAART therapy outcomes in older HIV-infected patients are considerations for future studies. (Greenbaum et al., AIDS. 2008;22:2331-2339.)

Predictors of Change in Total Bone Mineral Density in HIV-infected Individuals

Bone mineral density (BMD) loss was greater in HIV patients using tenofovir or ddI compared to nonusers and was less in those using d4T or saquinavir in a study in the November 1 issue of JAIDS. CD4 count and viral load were not associated with changes in BMD. Higher body mass index and strength training were associated with less bone loss.

This longitudinal cohort of HIV-infected adults 18 years or older were followed for a median of 2.5 years.  A baseline measure of BMD before ART was conducted, and annual assessments with dual-energy X-ray absorptiometry, along with medical, dietary, and behavioral history were collected.

As HIV-infected patients live longer on ART, it is important to acknowledge the factors that may affect bone health in these individuals. Providers should encourage their patients to maintain adequate weight and nutritional status, while performing strength training exercises to decrease HIV-associated bone loss. (Jacobson et al., JAIDS. 2008;49:298-308.)

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Cohorting Thwarted by Respiratory Pathogen’s Environmental Reservoir
By Jason Weinberg, MD

Cohorting to prevent exposure to potentially infectious individuals was not sufficient to reduce rates of febrile respiratory illness (FRI) in a report in the November 15 edition of The Journal of Infectious Diseases.

In this study of more than 13,000 military recruits, units were classified as “closed” if they were not accepting new recruits after their initial formation, or “open” if they were accepting recruits returning from medical convalescence or other settings.  Rates of FRI were monitored for each type of unit over the first four weeks of recruit training. 

There was no statistically significant difference between rates of FRI in open and closed units.  However, units with larger populations tended to have higher FRI rates independent of their classification (i.e. open versus closed).  Viable adenovirus, the predominant cause of FRI in this population, was found in environmental samples obtained from housing units and medical clinics.  These results suggest that person-to-person spread was not the primary means of transmission.  Rather, environmental persistence of adenovirus is a likely reservoir that facilitates ongoing transmission and high rates of FRI in this setting.

This study only addressed adenovirus type 4, and its generalizability to other organisms such as other respiratory viruses, enteric viruses, and methicillin-resistant Staphylococcus aureus remains to be determined. Nonetheless, this study may help to shape policies and strategies to reduce environmental transmission of pathogens in daycares, long-term care facilities, dormitories, and similar settings.  This study reinforces the importance of environmental cleaning in reducing the rates of FRI.

And wash your hands, too.

(Broderick et al., J Infect Dis. 2008;198:1420-6.)

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Lower HPV Vaccine Cost Could Offset Barriers Raised by Promiscuity Concerns
By Melinda Pettigrew, PhD

Public perception that HPV vaccination increases sexual promiscuity may prevent HPV vaccination levels from reaching optimal targets, according to a study published in the December issue of the Proceedings of the National Academy of Sciences. But the study found lowering the cost of the vaccine can offset that effect.

The researchers applied game theory to explore how external factors such as a fear of increased promiscuity and vaccine cost influence equilibrium vaccination levels. Results from a survey of 326 U.S. adults showed that the majority of respondents believed that the risk of cervical cancer and genital warts are lower with the HPV vaccine. But survey respondents also reported that adolescent sexual activity would nearly double among those receiving the vaccine—an increase that the authors note has never been observed.

Cost also influenced the decision of whether to vaccinate. Even with financial assistance, the average family had to spend $181 for all three doses of vaccine when administrative fees, doctor’s office fees, and time lost from work were also considered. The authors estimated that a price reduction of $55 per dose would increase vaccination levels.

While mathematical models cannot predict behavior, study results indicate that clinicians should address parental concerns about increased promiscuity when encouraging parents to vaccinate their children. (Basu, S. et al., PNAS. 2008;19018–23.)

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