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May 2014
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Journal Club
May 2014

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.

Click here for the previous edition of Journal Club. 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.


Asymptomatic Bacteriuria Prior to Prosthetic Joint Implantation: Higher Infection Risk, but the Bugs Don’t Match

Reviewed by Christopher J. Graber, MD, MPH, FIDSA

Patients about to undergo prosthetic joint implantation are frequently screened and treated for bacteriuria based on the notion that patients with asymptomatic bacteriuria (ASB) are at higher risk for subsequent prosthetic joint infection (PJI), though this approach is not specifically endorsed by either the American Academy of Orthopaedic Surgeons or the Infectious Diseases Society of America. A new study published in Clinical Infectious Diseases addresses this practice.

Urine cultures were collected prior to 2,497 prosthetic joint surgeries across three institutions from the United Kingdom, Portugal, and Spain from 2010 to 2011, and the decision to prescribe an eight-day course of antibiotic was left to the discretion of the treating physician. ASB was found in 12 percent of surgery patients; risk factors for ASB included female sex, older age, obesity, and higher American Society of Anesthesiology (ASA) scores. PJI was diagnosed in 4.3 percent of ASB patients as compared to 1.4 percent of non-ASB patients (OR 3.23, p=0.001) but occurred with similar frequency among patients who were treated for ASB (3.9 percent) as compared to those who were not (4.7 percent).

While a significantly higher proportion of PJI in ASB patients were caused by Gram-negative organisms, there were no episodes where the ASB isolate correlated with the PJI isolate. In a multivariable model, postoperative urinary tract infection (UTI) also predicted subsequent PJI, though, as with ASB, postoperative UTI isolates were different from PJI isolates.

This study suggests patients with ASB are at higher risk for PJI (which may impact informed consent for what is typically an elective procedure) but that treatment of ASB prior to surgery does not seem to have benefit. Other strategies to reduce PJI risk in these patients (e.g., early discontinuation of Foley catheters, aggressive postoperative mobilization) deserve further study.

(Sousa et al. Clin Infect Dis. Advance Access, published online April 9, 2014.)

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Controlling Endemic, Drug-Resistant A. baumannii: The Role of Weekly Staff Emails in Sharing Infection Control Findings, Reducing Infections
Reviewed by Zeina Kanafani, MD, MS

Nosocomial outbreaks of infections due to drug-resistant Acinetobacter baumannii have been increasing in various medical centers worldwide. In some hospitals, epidemics that have not been controlled have persisted over time and become endemic.

An article in the May issue of the American Journal of Infection Control describes attempts by a 1,500-bed public hospital in Florida to reduce the spread of infections caused by carbapenem-resistant A. baumannii in an endemic situation. After using a bundle of interventions without success, including patient screening tests, weekly sampling of environmental surfaces, hand hygiene, and monthly multidisciplinary meetings, a steady decrease in the acquisition of new A. baumannii infections was achieved when the hospital used weekly staff emails to communicate the findings of surveillance cultures and their subsequent clinical significance.

According to this study, when the medical director of infection control sent comprehensive electronic weekly reports to physicians, nurses, and hospital leadership describing and analyzing the surveillance reports of A. baumannii for the previous week, a greater degree of feedback and accountability was created, and action plans were directly implemented.

The study analyzed a 42-month period of hospital data divided into three phases: periods before, during, and after the electronic communications. Weekly emails were sent only during the second period. Overall, the acquisition of new cases of A. baumanii decreased by 63 percent over the three phases of the study (from 5.13 ± 0.39 to 1.9 3± 0.23 per 10,000 patient-days, p < 0.0001). This effect was also reproducible in the medical and surgical ICUs, where infection rates with A. baumannii were higher.

The study authors conclude that mass electronic dissemination of results from the bundle of interventions to hospital staff was effective in reducing the rates of A. baumannii acquisition. The findings suggest that education, communication, feedback, and peer pressure are all important elements that can determine the behavior and attitude of health care workers.

(Munoz-Price et al. Am J Infect Control. 2014; 42(5):466-471.)

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Caspofungin for Prophylaxis: Benefits for High-Risk ICU Patients Lacking
Reviewed by Nirav Patel, MD


Echinocandins have been widely adopted in clinical practice due to potent activity, ease of dosing, and excellent tolerability. This has led to their overuse in unproven settings, which is even more concerning given recent reports of resistance developing in certain candidal species. In this context, researchers in the June 1 issue of Clinical Infectious Diseases ask an important question: Will caspofungin prophylaxis reduce the incidence of invasive candidiasis (IC) in high-risk critically ill patients compared to placebo?

Study patients included those who met the authors’ risk criteria: mechanical ventilation, central venous catheter, broad-spectrum antibiotics, parenteral nutrition, need for dialysis, major surgery, pancreatitis, steroid use, and use of other immunosuppressives. However, a number of important groups were excluded: those with neutropenia, AIDS, hepatic insufficiency, recent antifungal therapy, active invasive fungal infection, and those likely to die within 24 hours, among others. The multi-centered, randomized, blinded, placebo-controlled study was sponsored by Merck & Co.

Among approximately 16,000 patients who were screened, 222 met the study criteria and were randomized to receive either caspofungin (102) or placebo (84). Caspofungin was not more effective than placebo for prophylaxis of IC (proven/probable IC in 9.8 percent of patients receiving caspofungin compared to 16.7 percent receiving placebo, P=0.14). The authors also report analysis of a “preemptive approach,” which included patients who had IC at enrollment: proven/probable IC was found in 18.8 percent of these patients on caspofungin compared to 30.4 percent on placebo, P=0.04. The authors suggest that the underpowering of the study could account for these discrepancies.

The accompanying editorial highlights a number of limitations, including the potential for under-diagnosis of IC based on the study definition, limitations associated with the authors’ risk criteria, no mention of β-1,3-D-glucan values, a confusing interpretation of the term “preemptive,” and the overall applicability to clinical practice given the low rate of screened patients who qualified to be enrolled (1.4 percent).

Given the widespread use of echinocandins in clinical practice, one hopes this study will serve to temper inappropriate enthusiasm and generate additional inquiry into the patients and settings where prophylaxis can actually yield tangible improvements in outcomes.

(Ostrosky-Zeichner et al. Clin Infect Dis. 2014;58(9):1219-1226.)

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 PICC-Related Bloodstream Infections: More Lumens, More Risk?
Reviewed by Manie Beheshti, MD


For various reasons, the use of peripherally inserted central catheters (PICCs) has gained considerable popularity in recent decades. Although the perception exists that rates of infection are reduced with PICCs compared to other central catheters, recent data casts doubt on this notion, prompting the need to better understand potential modifiable risk factors.

In the April issue of The American Journal of Medicine, researchers at the Veterans Affairs Medical Center in Ann Arbor, Michigan, report on their attempt to identify several specific patient, provider, and device-related factors that may contribute to PICC-associated bloodstream infections.

From 2009 to 2012 the investigators studied 966 consecutive PICCs accounting for nearly 27,000 catheter days. Fifty-eight (6 percent) PICC-associated bloodstream infections were identified (2.16 infections per 1,000 catheter days). PICC indications included IV antibiotics (52 percent), venous access (21 percent), parenteral nutrition (16 percent), and chemotherapy (11 percent). The most common attributable pathogens were coagulase-negative staphylococci (17 percent), Staphylococcus aureus (13 percent), and Candida species (11 percent).

On bivariate analysis, some of the significant factors were:
    • ICU status (HR: 3.80)
    • mechanical ventilation (HR: 4.30)
    • length of hospital stay (HR: 1.02)
    • PICC insertion in the ICU (HR: 3.79) or by interventional radiology (HR: 2.45)
    • two-lumen PICCs (HR: 5.29) and three-lumen PICCs (HR: 15.22)
    In their multivariate analysis, several factors maintained significant associations with PICC-related bloodstream infections:
    • ICU status (HR: 1.02)
    • length of hospital stay (HR: 1.02)
    • two-lumen PICCs (HR: 4.08)
    • three-lumen PICCs (HR: 8.52)
    Although limited by its homogenous patient population and retrospective design, this study helps identify some of the factors associated with PICC-related bloodstream infections. Perhaps most notable in this study was the increased risk of infection with more lumens, adding to prior data regarding increased infectious risk with multi-lumen PICCs. This study helps highlight some modifiable risk factors with regard to PICC-related infections.

    (Chopra et al. Am J Med. 2014;127:319-328.)

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     Accelerated Loss of Vaccine Seroprotection in HIV-Infected Individuals
    Reviewed by Brian R. Wood, MD

    Primary response to vaccination is diminished in HIV-infected individuals, especially those with advanced disease. Is long-term seroprotection also impaired? To answer this question, investigators conducted a systematic review of the literature, then constructed models of the decline in antibody level over time. They pooled the percentage of seroprotected patients at two and five years into a meta-analysis, which they describe in the April 15 issue of Clinical Infectious Diseases.

    The review yielded 54 prospective studies related to 13 different vaccine antigens. The meta-analysis produced several notable findings. Estimated seroprotection after primary response to hepatitis B vaccine was only 38 percent at two years and 17 percent at five years for adults. High-dose (40-mcg) vaccine did not improve long-term seroprotection as compared to standard dose. Seroprotection at five years after measles vaccination was meager (40 percent) in children vertically infected with HIV, but improved if antiretroviral therapy (ART) started before vaccination. Antibody levels after other vaccines (tetanus, polio, pertussis, pneumococcus, etc.) also vanished rapidly and generally fell below protective levels by five years. Seroprotection diminished more rapidly in those with low CD4 count or detectable viremia.  

    The authors conclude that duration of seroprotection after routine vaccination is shorter in HIV-infected individuals, and they suggest more frequent monitoring of antibody levels following vaccination (such as yearly rechecks of hepatitis B antibody level and every five-year rechecks of hepatitis A antibody after vaccination). However, the analysis is limited by several factors: The mean number of participants in the reviewed studies was only 40, clinical endpoints were not measured, cell-mediated immunity was not accounted for, and the presence of an anamnestic response was not measured. Therefore, the clinical significance of waning antibody titers is difficult to assess.

    The important message is that HIV-infected individuals have an impaired vaccine response, both short- and long-term, and booster schedules should not be based solely on data from HIV-uninfected persons. Additionally, long-term responses improve if HIV is well controlled on ART.

    (Kernéis et al. Clin Infect Dis. 2014;58(8):1130-9.)

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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:

    May 15

    • No Waiting! Rapid Detection of Inducible Resistance to Macrolides in Rapidly Growing Mycobacteria
    • Noncultivatable Bacteria on Vascular Catheters

    May 1

    • Visceral Leishmaniasis in Italy: Treatment With Liposomal Amphotericin B
    • Treatment of New World Mucosal Leishmaniasis With Liposomal Amphotericin B
    • Vancomycin Resistance in Group B Streptococci


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