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July/August 2010
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IDSA Journal Club

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

For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases.

Low CD4 Counts and Increased Risk for Cardiovascular Events in HIV Patients
Reviewed by Shireesha Dhanireddy, MD

Low CD4 counts (< 500 cells/ mm3) conferred an equivalent or greater risk for a cardiovascular event (CV) than traditional risk factors, such as tobacco use, in patients with HIV, according to a study in the August 15 issue of Clinical Infectious Diseases.

The observational cohort study included patients from 10 HIV-specialty clinics in the U.S. who were followed until a CV event, death, loss to follow-up, or the end of the study. The primary outcome of an event was defined as myocardial infarction, stroke, coronary artery disease, angina, or peripheral arterial disease. Patients were categorized at baseline using the Framingham 10-year cardiovascular risk (CVR) scale as either low risk, moderate risk, moderately high risk, or high risk.

Of the over 5,000 patients seen during the time period, more than 3,000 were excluded because data were unavailable to determine their baseline CV risk. Of the 2,005 patients analyzed, 148 experienced a CV event. Factors associated with higher rates included presence of traditional risk factors (smoking, diabetes, family history of premature CV disease, hypertension, low high-density lipoprotein [HDL] levels), having public or no health insurance, or a baseline CD4 count < 500  cells/mm3. The attributable risk of CV events for patients with low baseline CD4 counts was 25.6 percent, which is similar to the risk posed by smoking and dyslipidemia in this cohort. Antiretroviral therapy was overall associated with decreased incidence of CV events.

This study shows that low CD4 counts should be considered a risk factor when evaluating a patient’s cardiovascular risk. Another important finding was the absence of increased CV risk with antiretrovirals.

While the findings are striking, one major limitation is that many patients were excluded from the analysis for insufficient data to determine their baseline CV risk, which may have led to selection bias. Additional studies are needed to assess the effect of early HIV treatment on CV events.

(Lichtenstein et al. Clin Infect Dis. 2010;51:435–447.)

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Early Removal of Central Venous Catheters in Patients with Candidemia
Reviewed by Ed Dominguez, MD

When to remove a central venous catheter (CVC) in a patient with candidemia remains a debated question. Attempting to remove this ambiguity, a multi-center group of investigators retrospectively analyzed two prospective randomized clinical trials of antifungal therapy in such patients. Their findings are published in the August 1 issue of Clinical Infectious Diseases.

The authors evaluated the effects of early CVC removal at two time points (<24 hours and <48 hours) on six predefined outcomes: treatment success, 28-day and 42-day survival, rates of persistent and recurrent candidemia, and time to mycological eradication. Univariate and multivariate analyses were performed.

In the univariate analysis of these two studies (one comparing an echinocandin to liposomal amphotericin, the other comparing two echinocandins) the investigators found that early removal was indeed associated with higher treatment success and with increased survival at 28 and at 42 days. There was no significant improvement in the rates of persistent candidemia or recurrent candidemia. However, in the multivariate analysis, the benefit of early removal disappeared altogether.

Consequently, the authors conclude that early CVC removal was not associated with clinical benefit. It is important to note that this observation applies only to patients treated with an echinocandin (specifically micafungin and caspofungin) or with liposomal amphotericin B. Furthermore, since only 10 percent of the patients in the combined analysis were neutropenic, the findings are not applicable to this population.

The findings from this analysis call into question recommendations from two different IDSA practice guidelines (one for the management of candidiasis, and one for the diagnosis and management of catheter‐related infection) that recommend CVC withdrawal, when possible, once candidemia is documented. However, an accompanying editorial places the findings in perspective, noting that the lack of overlap in the authorship of the two guidelines suggests a consensus that strengthens the guideline recommendation. In addition, the authors of the editorial note that given the wide, 95 percent confidence intervals for the odds ratio for 28-day and 42-day survival in the multivariate analyses, one cannot rule out anywhere from a 67 percent to 75 percent improvement in survival with early removal.

While not statistically significant, such improvement would surely be clinically relevant. The debate will continue, barring a large prospective study, which is unlikely to be conducted. When the guidelines are revisited, this study will likely be part of the discussion.

(Nucci et al. Clin Infect Dis 2010;51:295-303 and Brass and Edwards. Clin Infect Dis 2010;51:304-306.)

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Infection Control Lapses at Ambulatory Surgical Centers
Reviewed by Rachel Simmons, MD

Ambulatory surgical centers (ASCs) have increased significantly over the last 10 years and have been the source of some well publicized outbreaks of health care-associated infections (HAIs). To assess compliance with basic infection control practices, the Centers for Medicare and Medicaid Services (CMS) conducted a voluntary audit of the infection control practices at 68 ASCs in three states (Maryland, Oklahoma, and North Carolina). The results appear in the June 9 issue of the Journal of the American Medical Association.  

Specially trained state surveyors conducted unannounced assessments that included a standard infection control audit tool and followed at least one patient from start to finish at the ASC. The audit tool focused on five areas: hand hygiene and use of personal protective equipment such as gloves, injection safety and medication handling, equipment processing, environmental cleaning, and handling of blood glucose monitoring equipment. 

Forty-six of the 68 centers (68 percent) had at least one lapse in infection control, and 12 (18 percent) had three or more lapses. More than 19 percent were observed to have lapses in hand hygiene and use of personal protective equipment such as gloves. In 28 percent of the ASCs, single-dose medications were used for more than one patient. Twenty-eight percent of the facilities also failed to properly reprocess their equipment. Forty-six percent did not appropriately handle blood glucose monitoring equipment. Ultimately, 39 (57 percent) of the 68 ASCs were cited for deficiencies in infection control. 

This pilot study suggests that routine infection control practices are lacking in ASCs.  With the prevalence of these centers, the related commentary notes that potentially millions of patients in the U.S. who undergo procedures at ASCs annually are needlessly placed at risk of HAIs.  These centers are now mandated by CMS to have infection control programs and should undergo regular self-audits to ensure and improve compliance with infection control guidelines.

(Schaefer et al. JAMA. 2010;303:2273-2279 and Barie. JAMA. 2010;303:2295-2297.)

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Is the “K” OK? Hyperkalemia with TMP-SMX in Older Patients Receiving Inhibitors of the Renin-Angiotensin System
Reviewed by Christopher J. Graber, MD, MPH

The risk of hospitalization for hyperkalemia among older adults receiving angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) was nearly seven times higher for patients prescribed trimethoprim-sulfamethoxazole (TMP-SMX) compared to other antibiotics commonly used for urinary tract infections. The estimated difference in risk, from an article in the June 28 issue of Archives of Internal Medicine, provides a helpful reminder to clinicians.

The authors reviewed the Ontario Drug Benefit Program to identify 439,677 local residents 66 years of age or older receiving an ACEI or ARB from April 1994 through March 2008.  Of this cohort, 371 were admitted to a hospital with the diagnosis of hyperkalemia within 14 days of receiving TMP-SMX (n=204), norfloxacin (n=20), ciprofloxacin (n=76), nitrofurantoin (n=18), or amoxicillin (n=49).  Comparing these patients to controls within the cohort who also received one of these antibiotics but were not admitted for hyperkalemia yielded an adjusted odds ratio of 6.7 for TMP-SMX being associated with hyperkalemia compared to amoxicillin.  Odds of hyperkalemia for all other antibiotics were similar to that of amoxicillin.

The overall rate of admission for hyperkalemia associated with TMP-SMX in this cohort was not directly reported but can roughly be calculated at 0.4 percent, since 11.6 percent of the cohort received at least one course of TMP-SMX during the study period (204/(439,677*0.116)).

The study is limited by lack of data regarding renal function, medication adherence, or other medications received, as well as reliance on ICD-9 coding for hyperkalemia on hospital admission rather than actual potassium levels. But the studyt does serve as a reminder to clinicians that hyperkalemia associated with TMP-SMX is much more common than with many other antibiotics, particularly in older patients receiving ACEIs or ARBs, and that close monitoring of such patients should be considered.  

(Antoniou T, et al. Arch Int Med 2010;170:1045-9)

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For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, MD, in each issue of Clinical Infectious Diseases:

August 1

  • Diagnosing Mumps: Don’t Be So Sure
  • Marseillevirus: A DNA Scavenger
  • Usutu: The Next Flavor of Flavivirus for the United States?

August 15

  • Bacterial Colonization of Implantable Cardiovascular Electronic Devices
  • Alkhurma Hemorrhagic Fever Virus: An Emerging Pathogen?

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