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November 2017
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.

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, FIDSA, in each issue of Clinical Infectious Diseases.

Is Vancomycin Plus a Beta-Lactam Better for Surgical Prophylaxis than Either Alone?
Reviewed by Christopher J. Graber, MD, MPH, FIDSA

The role of vancomycin in surgical antimicrobial prophylaxis is unclear. As compared to beta-lactam (including cephalosporin) agents, its primary advantage is its activity against methicillin-resistant Staphylococcus aureus (MRSA), while its disadvantages include prolonged time of administration that may make achieving appropriate serum levels at the time of incision more difficult, potential risk for nephrotoxicity, and lack of activity against Gram-negative pathogens. Combination prophylaxis with vancomycin plus beta-lactams has thus been suggested, but the efficacy of this approach remains unclear.

A recent paper published in PLOS Medicine retrospectively assessed the experience with combination therapy versus either vancomycin or a beta-lactam alone across a cohort of 70,101 surgical procedures throughout the Veterans Administration system from 2008 to 2013, 52,504 in which only a beta-lactam was given, 5,089 in which only vancomycin was given, and 12,508 in which a combination was given. The most common procedures were orthopedic (33,848) and cardiac (19,787). A total of 2,466 (3.5 percent) surgical site infections (SSIs) were observed; of 1,279 with a microbiology result, MRSA was isolated in 101 (7.9 percent), MSSA in 308 (24.1 percent), coagulase-negative staphylococci in 150 (12 percent), and Gram-negative enteric organisms in 512 (40 percent). Combination prophylaxis was associated with a lower incidence of SSI than single-agent prophylaxis only for cardiac surgery patients (adjusted risk ratio 0.61, 95 percent confidence interval [CI] 0.46-0.83). MRSA colonization was associated with a higher risk of SSI across all surgery types (RR 2.02, 95 percent CI 1.74-2.34). Point estimates of relative risk reduction were similar between MRSA-colonized and non-MRSA-colonized cardiac surgery patients (0.58 versus 0.61) but only statistically significant in the larger group of non-MRSA-colonized patients. Combination prophylaxis was associated with a higher overall rate of acute kidney injury (23.8 percent) versus vancomycin (20.8 percent) or beta-lactam (13.9 percent) alone. Risk for Clostridium difficile infection was similar across all prophylaxis regimens.

This paper highlights that combination prophylaxis may be of benefit in some situations (particularly with cardiac surgery) but is not without cost, at least with regard to acute kidney injury.

(Branch-Elliman et al. PLOS Med. 2017;14(7):e1002340.)

Higher Mortality With Higher Levels of CMV: Is It the Virus or the Treatment?
Reviewed by Erica Kaufman West, MD

The current strategy for allogeneic stem cell transplant (SCT) recipients is to provide preemptive antiviral therapy to prevent cytomegalovirus (CMV) end-organ disease. There has been some debate on the threshold at which to begin antiviral therapy, especially with the popularity of using CMV PCR assays. With some evidence showing that even low CMV DNA viral loads are associated with increased mortality, there is a need to evaluate what threshold should trigger antiviral therapy.

A recent article in Transplant Infectious Disease reported the results of a single-center retrospective study looking at CMV DNAemia and one-year overall mortality and non-relapse mortality in allo-SCT patients. There were 151 patients in Spain followed from 2010 to 2015. Viral loads were monitored at least once a week through day +100 for all patients. Treatment was with oral valganciclovir and IV ganciclovir, with IV foscarnet used as second-line therapy. Antiviral therapy was given for a minimum of two weeks, with longer therapy depending on CMV DNA results. Out of 151 patients, 109 had at least one episode of CMV DNAemia (72.2 percent). Antiviral therapy was required in 67 cases (61.5 percent). Only three patients had end-organ disease (one pneumonitis and two intestinal). The one-year overall mortality was 28.5 percent (n = 43), with 35 deaths due to causes other than relapse or progression of disease.

The risk of one-year overall mortality and non-relapse mortality was not increased in patients with low-level CMV DNAemia (< 1,500 copies/mL) and those with no documented CMV DNAemia. In those with CMV DNAemia > 1,500 copies/mL there was a significant increase in both outcomes. However, the peak level of CMV DNA viral load did not correlate with the risk of death nor did the duration of CMV DNAemia. One of the most striking findings was that about three-quarters of patients receiving ganciclovir had post-engraftment neutropenia, in contrast to only one-quarter of those not treated with antivirals. A study powered to differentiate whether it is the high CMV viral load or the effects of the antivirals is sorely needed, since antivirals without hematologic toxicity remain under investigation.

(Solano et al. Transpl Infect Dis. 2017;19:e12717.)

Quantifying Real Tuberculosis Risk with QuantiFERON: Is there a “Borderline” Category?
Reviewed by Nirav Patel, MD

Interferon-gamma release assays (IGRAs), including the QuantiFERON-TB Gold In-Tube (QFT) have been endorsed as a replacement for tuberculin skin testing (TST). However, after adoption of the QFT, there have been notable “conversions” to positive in previously TST serially negative individuals. The lack of a “borderline” category in QFT interpretation is thought to have contributed to these “positive” results, but there remains a concern about the natural history and prognosis of individuals listed as positive conversions.

A study in the Sept. 1, 2017, issue of the American Journal of Respiratory and Critical Care Medicine dramatically clarifies the actual risk of progression to active disease in individuals undergoing serial QFT testing. The investigators rigorously standardized the laboratory procedures surrounding the processing of QFT tests. Furthermore, they defined four categories:

  • Stringent non-converters (< 0.2 IU/mL TB Ag – nil at day 0, day 360, and 720)
  • Stringent persistent positives (> 0.7 IU/mL TB Ag – nil at day 0, 360, and 720)
  • Stringent converters (< 0.2 IU/mL TB Ag – nil at day 0 followed by > 0.7 IU/mL TB Ag – nil at day 360)
  • Uncertain converters (< 0.35 IU/mL TB Ag – nil at day 0 followed by a result ≥ 0.35 IU/mL TB Ag – nil at day 360 with at least one result within 0.2-0.7 IU/mL)

Stringent non-converters were noted to have 0.16 cases/100 person-years compared to stringent converters, who were noted to have 1.6 cases/100 person-years (P = 0.0003), and uncertain converters, who were noted to have 0.66 cases/100 person-years (P = 0.229).

Clearly, there remains ambiguity in the risk faced by uncertain converters, given the non-significant P-value. However, without a “borderline” category like the T-SPOT.TB assay, clinicians have created arbitrary thresholds in interpretation of QFT results without a true basis for risk adjudication. With this study, a more precise risk profile can be established to better interpret serial QFT results.

(Nemes et al. Am J Respir Crit Care Med. 2017 Sep 1;196(5):638-648.)

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:

October 15

  • Methicillin Resistance: Was Penicillin the Culprit?
  • Tolerant → Resistant
  • Case Vignette: Adenovirus Endotheliitis

October 1

  • Enterococci: How They Got That Way
  • Cerebrospinal Fluid Neutrophilic Pleocytosis in Viral Infections of the Central Nervous System: Does It Matter?
  • Antibiotic Resistance: The Potential Role of Bacteriophage “Superspreaders”
  • Case Vignette: Heater-Cooler Systems Strike Again—Left Ventricular Assist Device Infections With Mycobacterium Chimaera

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