These Are a Few of Our Favorite (Clinical Microbiology) Things!

Dec. 17, 2018

You've probably read a lot of scientific papers, and learned a lot of new information in the process. One of the great ways in which scientists, including clinical microbiologists, contribute to human advancement is by generating, and learning, new information. Some studies accomplish more than just generating new information: they change the way we think about a particular topic or the way that we practice our profession. Can you remember reading a study that had such an impact on your thinking or professional practice? I asked this question to ten clinical microbiologists, and here is what they had to say:


Peter Gilligan, Director of the Clinical Microbiology-Immunology Laboratories at the University of North Carolina Hospitals, selected the 1978 NEJM publication by John Bartlett and Andrew Onderdonk, et al., which first described toxin-producing C. difficile as the cause of antibiotic-associated pseudomembranous colitis,  as one of the publications that had the most impact on his career. Regarding why this study was important to him, Dr. Gilligan said:

 "Diarrheal diseases and especially C. difficile infection have been a career long interest of mine.  As a graduate student, I learned to do tissue culture cytotoxicity assays to study enterotoxigenic E. coli. As a fellow, I was able to apply this tool to develop a cytotoxicity assay for C. difficile at UNC in 1979.  I carried that tool with me to St. Christopher’s Hospital for Children where for 4 years between 1980-1984, I ran a C. difficile cytotoxicity assay reference lab service used by over 25 hospitals in Southeastern PA and Western NJ."  

That was a great, field-altering study, but I will admit I was hoping Professor Gilligan would submit a different NEJM article, one highlighting a virus outbreak on a remote Pacific Island where he may or may not have been stranded for three years before his clinical microbiology career.

Another paper on gut microbiota had a considerable impact on the approach to infectious diseases management for Colleen Kraft, the Medical Director of the Microbiology Laboratory at Emory University. She said:

"The published study that got me motivated to start the Emory fecal transplant program was presented in our Infectious Diseases seminar on March 2, 2012 by Dr. Cliff McDonald from CDC.  The study was published by Dr. David Relman and Dr. Les Dethlefsen. The thought that it took 6 months for the gut microbiota of healthy individuals who were receiving a short course of antibiotics to return back to baseline was very dramatic to me. This has motivated me to study how we can therapeutically repopulate the gut microbiome. While fecal transplant is a useful treatment, a surrogate that could be standardized would allow us to replant people’s “gut garden” after they have had antibiotics, and may be able to prevent infections such as C. difficile and other multi-drug resistant bacteria colonization."


Elitza Theel, the Director of the Infectious Diseases Serology Laboratory at the Mayo Clinic, chose a paper that made a big difference in her specialty area. She said:

"Changing diagnostic ‘dogma’ is challenging, and even more so when Lyme disease is thrown into the mix, so for me, one of the most impactful studies is by Branda and colleagues, published in Clinical Infectious Diseases (2011), which nicely showed improved performance of a modified, two-EIA based testing algorithm for detection of Lyme disease, as compared to the standard two-tiered testing algorithm, in place since 1995. There is undoubtedly a need for improved Lyme disease diagnostics, as the current standard testing algorithm, based on an initially reactive EIA (or rarely IFA) followed by supplemental IgM and IgG Western or immunoblot testing, is notoriously associated with insensitivity during acute infection and miss-interpretation of blot results (especially for IgM).  Building on previous findings, this publication is a diagnostic ‘game-changer’ of sorts, identifying an alternative and improved testing algorithm for Lyme disease, that has led to numerous subsequent studies evaluating two-EIA-based algorithms, which may collectively result in revision of the current Lyme disease testing guidelines.”


Jim Dunn, the Director of Medical Microbiology and Virology at Texas Children's Hospital, said that a study titled “Clinical and Financial Benefits of Rapid Detection of Respiratory Viruses: an Outcomes Study” had a big impact on his approach to clinical microbiology. He said:

“It was a paper published when I was doing my fellowship that really made me realize how much of an impact accurate and timely reporting from the lab can have on patient outcomes. It was from Joan Barenfanger’s lab. I was a virologist by training and spent a lot of time in that area during fellowship working on projects related to respiratory viruses and this reference was one I referred to often.”


Chris Doern, the Director of Clinical Microbiology at Virginia Commonwealth University, cites a study of the clinical impact of more rapid tests for ID and AST performed by his father, Gary Doern, in the early 1990’s. Chris said:

The study presented in this manuscript is elegant in its simplicity, and impressive in its scope and quality.  As an academic Clinical Microbiologist, the quality of the study design here is inspiring and it seeks to answer a very simple question, is faster better? In the midst of confirming what we all intuitively hope would be true, that is, that faster susceptibility testing improves patient care, an interesting question was raised for me: what impact does direct communication of results have on patient care? A unique element of the study design is that key results were telephoned to providers in both the control and the intervention arm of the study. And it begs the question, how much more would patient care be improved if we did this?”


Carey-Ann Burnham, the Medical Director of Microbiology, Barnes Jewish Hospital (Washington University School of Medicine), highlights another study with Gary Doern as the corresponding author. She said:

“This study evaluated more than 500 episodes of clinically significant blood stream infection (BSI), and assessed the impact of reporting of microbiology results on antimicrobial management.  This study was conducted from 1999-2000, so rapid methods for ID and AST such as MALDI-TOF were not available at that time. This study demonstrated that for BSI, most antimicrobial interventions occurred at the time of phlebotomy, and the fewest interventions occurred at the time AST results were reported. In addition, the study demonstrated that notification of a positive blood culture Gram stain via telephone resulted in antimicrobial interventions.


For me, this study was meaningful and has a lasting impact for several reasons. One, it demonstrates the importance of active reporting (i.e. a telephone call) for clinical follow up of critical microbiology results. Second, this paper highlighted a clinical need for, drove my interest in, development and implementation of rapid microbiology methods for blood cultures, with the hope that by reducing the interval between the time blood cultures are collected and actionable AST results, our microbiology laboratory testing will have more impact on antimicrobial management of patients with blood stream infection.”


Eric Rosenbaum, the Medical Director of the University of Arkansas for Medical Sciences Clinical Microbiology Laboratory, cited an article that he shares the most with colleagues, residents, and fellows. It is "Challenges and Pitfalls of Morphologic Identification of Fungal Infections in Histologic and Cytologic Specimens" (AJCP, 2009) by Ankur Sangoi and Niaz Banaei at al.  He said:

“As a clinical microbiologist, I am frequently brought "fungal elements" on histologic section and cytologic preparation. This is a great article because it beautifully demonstrates the limits of something we thought we were much better at than we actually turned out to be (i.e. identifying, usually hyphae, on histologic and cytologic preparations).  It is good evidence to share with our clinical colleagues when they say ‘surely, you must be able to identify this organism’—well, surely not always!”


Alex McAdam, a microbiology comic graphic artist and satirist whose day job is Director of the Infectious Diseases Diagnostic Laboratory at Boston Children’s Hospital, said,

“I remember the first time I read ‘Application of Rejection Criteria for Stool Cultures for Bacterial Enteric Pathogens’ by Dr. Reller and colleagues at Duke. The paper described a process by which the laboratory leadership could assess the clinical value of a test and work with practitioners to reduce the use of tests which are very unlikely to improve patient care. There had been similar papers before and there have been many more since, but this was the first paper I read with a focus on the role of the clinical microbiologist in guiding care while conserving resources, and it has greatly affected my practice.”


Paul Luethy, Assistant Director of Microbiology at the University of Maryland Medical Center, highlights a study that brought a lot of attention in our field to sequencing technologies. The work performed by Charles Chiu’s group was half case report, and half launch pad. Dr. Luethy said: 

“This paper illustrates one of the first examples of utilizing next generation sequencing (NGS) technology for the unbiased detection of microorganisms causing disease. This report is significant to me because it revealed a new realm of possibilities for diagnosing infections that were either very difficult or impossible to diagnose before. Since publication in 2014, we have seen other groups follow suit with amazing applications of NGS technology (such as the Ivy et al. publication in JCM in 2018 on direct detection of prosthetic joint infection pathogens) in the field of clinical microbiology. I know I am not alone when I say that NGS-based diagnostics will significantly alter the practice of clinical microbiology in the not-to-distant future.”


As for me, I've read a lot of really good papers that have provided useful information and even changed the way I think about particular aspects of our field, but I will refer here to a study that spurred me into action. I remember reading this study from Dr. Robin Patel's group at the Mayo Clinic regarding the importance of blood culture volume on pathogen detection rates, and following up by reading many excellent papers on this topic from Dr. Melvin Weinstein and Dr. L. Barth Reller as well (including this one, and this one). I've been a bit of a crusader for more blood volume since then, and in my current position as a Lab Director, I've given presentations to various nursing and phlebotomy groups calling for more volume, altering our reports to collecting groups etc., with some encouraging returns. I've written previously on this blog about the importance of collecting sufficient volume of blood for detecting organisms causing bacteremia or fungemia, and I attribute all of this activity to the excellent publications cited above.


While some of most impactful articles describe new technologies, others are simply well-designed studies that may evaluate the impact of a test on the patient, detail the cost and clinical utility of the tests we offer, describe the value of picking up the phone to call providers with important results, analyze the process of specimen collection before specimens arrive in the laboratory, or evaluate the quality of our work—sometimes leading us to re-evaluate things we thought we were doing well. I’m thankful for the rich resources of published knowledge in our field, and I look forward to the next mind-changing article that comes out of the marriage of imagination and hard-work—perhaps from you!


If you have a favorite article that changed your perspective on an important topic in clinical microbiology, please tell us about it in the comments section below.