- Adverse Consequences of Prolonged Antimicrobial Surgical Prophylaxis: Every Day Matters!
- A New Agent for Refractory or Resistant Cytomegalovirus Infections
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.
Reviewed by Christopher J. Graber, MD, MPH, FIDSA
Perioperative antimicrobial prophylaxis can reduce the incidence of subsequent surgical site infection (SSI). Discontinuation of this prophylaxis within 24 hours is currently recommended by national guidelines, but extension past this window is commonplace despite potential risk for adverse events.
A recent study in JAMA Surgery quantifies this risk by relying on data obtained from the nationwide VA Surgical Quality Improvement project, which employed manual review by a trained clinician of outcomes associated with approximately 80 percent of all VA surgical procedures from October 2008 through September 2013. Outcomes were available for 21,396 cardiac procedures, 38,675 orthopedic joint replacement procedures, 10,810 colorectal procedures, and 8,177 vascular procedures. Prophylaxis was extended past 24 hours in 26.8 percent, and this extension was not associated with reductions in SSI among any surgical category, though any use of vancomycin (alone or in combination) was associated with decreased SSI risk in cardiac procedures (adjusted odds ratio [aOR] 0.73). Adjusted odds of acute kidney injury (AKI) increased with each additional day of prophylaxis (1.03 for 24-48h, 1.22 for 48-72h, 1.82 for > 72h) as did the adjusted odds for C. difficile infection (1.08, 2.43, and 3.65, respectively). Inclusion of vancomycin in prophylaxis was also significantly associated with AKI, both in cardiac (aOR 1.17) and non-cardiac (aOR 1.21) procedures. C. difficile infections were also increased in patients who received non-β-lactam/vancomycin/aminoglycoside agents (aOR 1.53), most of which were clindamycin and fluoroquinolones.
While this study is limited by non-randomization of prophylaxis duration, it should nonetheless serve as a strong impetus for any antimicrobial stewardship or infection control program to work with their surgical colleagues to routinely enforce the reduction of the duration of perioperative antimicrobial prophylaxis to 24 hours or less.
Reviewed by Erica Kaufman West, MD
Refractory or resistant (RR) cytomegalovirus (CMV) infections plague both allogeneic hematopoietic stem cell transplant (HSCT) patients and solid organ transplant (SOT) patients. Novel agents are needed, due to resistance to ganciclovir, foscarnet, and cidofovir. Letermovir, which is approved for CMV prophylaxis in HSCT patients, has not been studied in patients with active disease.
A recent study in Clinical Infectious Diseases evaluated the use of maribavir in patients 12 years of age and older with CMV viremia ≥ 1,000 copies/mL where the CMV was RR to at least one CMV active agent. Patients were randomized to 400, 800, or 1,200 mg twice daily for up to 24 weeks, with a primary endpoint of undetectable CMV DNA (< 200 copies/mL) in two consecutive samples. Of the 120 subjects, 47 were HSCT recipients and 73 were SOT recipients.
In the intention-to-treat analysis, 67 percent of patients had undetectable CMV DNA by week 6, similar across doses. While this was the primary endpoint, it was interesting that of the 86 patients who achieved undetectable CMV DNA during the study, 30 had recurrent viremia with 25 of these occurring while on maribavir. Thirteen of 25 developed de novo UL97 mutations, which is known to confer resistance to maribavir. Thirty-four percent of patients discontinued the drug because of adverse events; the majority of these were because of CMV infections or disease. The authors did not include in the study with what these patients were eventually treated.
While maribavir seems to offer a good option for those with RR CMV infection, the development of resistance and the number of patients who developed infection or disease on treatment does leave ID physicians with continued questions.