In the Ever-Evolving World of Infectious Disease, the Bottom Line Is Evidence Matters

When I teach infectious diseases (ID) to students in multiple health professions, I like to highlight how they are like a puzzle: Knowledge of the organisms that cause infections combined with knowledge of the pharmacology and spectrum of activity of antimicrobial agents leads to rational antibiotic choices. This is one of the areas of ID that I find most appealing because I am often in the scenario of having to choose agents for resistant infections based on in vitro data, pharmacokinetic/pharmacodynamic studies, logic, and—if I’m lucky—some retrospective studies. Although clinically interesting, this situation is not ideal. It is borne out of necessity, as resistant infections are difficult to study in controlled trials, and the epidemiology of antimicrobial resistance is constantly changing.

This issue of Contagion® will print shortly after the publication of a long-awaited clinical trial that was 5 years in the making. The MERINO trial tested the hypothesis that a β-lactamase inhibitor combination is noninferior to a carbapenem for the treatment of bacteremia caused by Enterobacteriaceae resistant to third-generation cephalosporins.¹ Previous retrospective studies examining the issue have had mixed results, and many clinicians have differing opinions. After screening over 1600 patients to find 391 to enroll, the investigators have an answer: Piperacillin/ tazobactam use was associated with higher mortality than meropenem.

This is a result that few in ID wanted to see because it can be used to justify (often correctly) more use of carbapenems, which in turn can lead to selection pressure encouraging the growth of carbapenem-resistant organisms. However, unpopularity does not lead to invalidity. The single-best-designed study examining empiric regimens for presumed extended-spectrum β-lactamase—producing bloodstream infections has concluded that carbapenems save lives.

ID practitioners were not the only group to receive an evidence-based wake-up call recently. The long-standing practice of using aspirin for primary prevention of cardiovascular events is being reevaluated after several recently published studies. More data in ID pharmacotherapy is emerging that reevaluates the need for intravenous therapy for several disease states, including endocarditis and osteomyelitis. As these and other prospective studies are reported, it is up to all of us in health care to evaluate the level of evidence in our own practices and continue to evolve, just like the organisms we work to treat.

This issue of Contagion® features the latest on the Zika virus, which although absent from the media headlines, has not disappeared from our lives and remains a concerning threat to those who live in tropical climates where the disease’s vector, the Aedes aegypti mosquito, is rampant. Keeping with the theme of zoonotic infections, we have included an interesting case study on Lyme neuroborreliosis presenting as syndrome of inappropriate secretion of antidiuretic hormone (SIADH), making it the fourth documented case of Lyme-induced SIADH. A couple of other items of interest in this issue include an article on the necessity of globalized antibiotic stewardship programs in the fight against antibiotic resistance, by Debra Goff, PharmD, FCCP, and colleagues as well as highlights and pitfalls of the Infectious Diseases Society of America and the American Thoracic Society guidelines for hospital-acquired and ventilator-associated pneumonia, by Lucia Rosé, PharmD, and Dana Byrne, MD, MSCE.

Continue to look for the latest infectious diseases news on our website and social media channels (@Contagion_Live on Twitter and Contagion Live on Facebook).

Jason C. Gallagher, PharmD, FCCP, FIDSA, BCPS

Editor-in-Chief

Contagion®

Dr. Gallagher is a clinical professor at Temple University School of Pharmacy and clinical pharmacy specialist in infectious diseases at Temple University Hospital, both in Philadelphia, Pennsylvania. He is also the director of the PGY2 Residency in Infectious Diseases Pharmacy at Temple.

REFERENCES:

1. Harris PNA, Tambyah PA, Lye DC, et al. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection and ceftriaxone resistance: a randomized clinical trial. JAMA. 2018;320(10):984-994. doi: 10.1001/jama.2018.12163.
2. Resistance Map. The Center for Disease Dynamics, Economics & Policy website. https://resistancemap.cddep.org/Antibiotic- Resistance.php. Accessed October 3, 2018.