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J Med Libr Assoc. Oct 2006; 94(4): 376–381.
PMCID: PMC1629446

Expert synthesis of the literature to support critical care decision makingFootnote icon for Electronic Content

Rebecca N. Jerome, MLIS, MPH, Assistant Director, Eskind Biomedical Library and Randolph A. Miller, MD, Donald A. B. and Mary M. Lindberg University Professor of Biomedical Informatics

INTRODUCTION

In this new column, the editorial team will address challenging situations in health sciences information provision. The column will provide narrative and insight from expert commentators drawn from librarianship, informatics, medicine, research, and other areas that inform the development of a given case situation. This feature will share commentary and practices for a variety of scenarios with the intention of prompting discussion of the issues facing health sciences librarianship as a developing profession and the development of potential solutions.

Health sciences librarians are increasingly being challenged to expand their skills in information retrieval and assessment into the clinical and other domains to foster the integration of evidence into decision making. The current column undertakes a complex clinical question drawn from the intensive care setting and explores the process of searching and synthesizing the evidence for application to a critical patient care decision. Coauthored by a clinical librarian and a clinician well versed in the fields of internal medicine and biomedical informatics, this case illustrates how clinical expertise and a detailed understanding of the literature can be applied. It has relevance to current and future potential directions for advanced development and application of librarian skill sets.

THE CLINICAL SETTING

You are a librarian collaborating with the clinical team in your hospital's intensive care unit (ICU). A sixty-four-year old male was admitted to the ICU ten days previously for respiratory failure and hepatic encephalopathy associated with advanced liver failure. He developed signs of possible ventilator-associated pneumonia and underwent bronchoscopy with bronchoalveolar lavage (BAL); the BAL fluid culture was positive for one of the Acinetobacter species. Antibiotic sensitivity testing indicated forty-eight hours later that his strain of Acinetobacter was resistant to the antibiotics commonly employed to treat bacterial pneumonia on the unit and to those recommended by recent practice guidelines [1]. This is a problem that the team has encountered in several patients over the last several months.

During morning rounds, the clinical team's discussion focuses on the best approach to treatment for this patient. The team's pharmacist recalls that an older antibiotic, colistin, was discussed as a possible option for such infections at a recent conference he attended. As this team's evidence consultant, you are charged with identifying quality information regarding the risks and benefits of using colistin for therapy in similar patients.

THE QUESTION

What is the evidence basis for the use of intravenous colistin for multidrug-resistant Acinetobacter infections in the adult, non-neutropenic, critical care population? Figure 1 provides a commentary on the significance of this question to the practice of critical care medicine.

Clinician commentary  Hospital-acquired pneumonia represents a clear and very real threat to patients receiving mechanical ventilation. The US Centers for Disease Control and Prevention (CDC) notes that the risk of this complication in patients ...

UNDERSTANDING THE CONCEPTS CONSTITUTING THE QUESTION

Before examining the literature related to this question, you should develop a basic understanding of related medical concepts to conduct a more efficient search of the literature. Developing a personal medical “knowledgebase” will increase your ability and proficiency in:

  • identifying the breadth of resources (databases, reference works, other electronic sources) that may contain information that will be relevant and useful for answering the question
  • selecting an appropriate assortment of controlled vocabulary and keyword terms describing these concepts
  • selecting the items (e.g., articles, Web documents, reference text excerpts) most relevant to the combination of topics and the context comprising the question
  • reading, interpreting, and summarizing the highest quality and most relevant items from the literature
  • discussing the results with the requestor(s) and addressing any follow-up questions that may arise

A number of resources are quickly and conveniently available for finding relevant background information on medical topics. MedlinePlus is often an excellent first stop, providing links to a variety of resources describing medical concepts such as those constituting the current question. Reference textbooks, general clinical electronic resources (e.g., UpToDate, MDConsult, eMedicine), and Web searches are also excellent ways to find additional information on a concept. Table 1 briefly defines the key concepts inherent in the current question, with example references that have provided source information for each definition.

Table thumbnail
Table 1 Brief concept definitions with references to introductory-level sources of information

EXPLORING THE LITERATURE

You find PubMed contains a number of useful citations for the current question, using search strategies that include the most important components. You may elect to begin with a focused search strategy using a combination of keywords and controlled vocabulary terms, such as

(colistin[mh] OR colistin[tiab] OR colistin[substance name] OR colistimethate[tiab] OR colistimethate[substance name]) AND (Acinetobacter[mh] OR Acinetobacter infections[mh] OR Acinetobacter[tiab]) AND (pneumonia[tiab] OR pneumonia[mh])

This strategy retrieves approximately twenty citations, making further limiting by study design or patient population unnecessary at this point. In the search results, you see articles discussing colistin use in specific patient populations, such as neutropenic patients and individuals with cystic fibrosis. Determining relevance of these items to the current patient requires you to revisit your “background” sources. Examining these two conditions via MedlinePlus, you note that each of these conditions represent a very specific, unique population within the broader critical care literature. Because of the unique character of each disease (frequent respiratory infections and progressive lung disease among cystic fibrosis patients, severely depressed immune systems in the neutropenic population), studies in these populations are unlikely to be generalizable to the overall critical care population.

Considering relevance to the clinical setting, you can also at this point exclude the purely molecular and genetic studies, as well as the animal studies, animal models, and in vitro explorations—these are also likely to lack direct applicability to this patient care situation. You are most interested in clinical studies (i.e., research in humans).

From this initial retrieval, you select four studies to examine further [1619]. These articles comprise clinical studies of the use of intravenous colistin to treat Acinetobacter infection, and all include patients with pneumonia as a primary type of infection treated with this regimen.

This focused search strategy also retrieves three review articles that seem to be relevant to the question [2022]. Review articles may serve as a complement to the primary data (i.e., actual clinical studies), with careful consideration of what the quality of the methods applied in preparing the reviews is and whether the review results are in line with what you are finding in the primary literature [23]. The Ferrara review [22], though being the most recent of the three and containing a good discussion of resistance in Gram-negative pneumonias, does not provide the amount of detail required to direct clinical actions that the other two reviews contain. These reviews may complement each other for the current question. Jain and Danziger [21] focus more on the question from the Acinetobacter multidrug resistance standpoint, including mention of other therapeutic strategies that the team may find useful should the colistin regimen be unsuccessful or unviable in the current case. The Falagas and Kasiakou review [20] considers colistin as a therapeutic agent for Gram-negative infections in general, providing a useful quick reference for dosage and adverse effects information, as well as commentary on other bacterial infections for which this agent may be useful.

Because multidrug resistance is also a problem with other Gram-negative nosocomial infections commonly seen in the ICU (e.g., Pseudomonas), you will also likely find it useful to browse broader search results, such as those returned by a more inclusive strategy:

(colistin[mh] OR colistin[tiab] OR colistin[substance name] OR colistimethate[tiab] OR colistimethate[substance name]) AND (Gram negative bacteria[majr] OR Gram negative bacterial infections[majr]) AND humans[mh]

When you examine these broader results, you find a systematic review that focuses on the toxicity of colistin and other agents from the polymyxin family that you select to examine further [24]. Because this reference is more recent than drug references are likely to be and is more systematic and comprehensive in nature than general drug references, it will be a useful item to include in the “packet” of information you are currently developing.

A number of studies address colistin use in patients with Pseudomonas or Enterobacter infections. Though these are not directly relevant to the current patient case, they may represent a potential source for future questions from the team, as resistance in these other Gram-negative infections is an important interest for the broader ICU patient population.

You also see a number of articles detailing the use of colistin as part of a selective decontamination regimen. Because this strategy, in which antibiotics are administered to eliminate bacteria colonizing the gastrointestinal tract, works to prevent infection rather than providing a therapeutic option once infection has been proved, these items can be disregarded.

In reviewing the results, you also notice that this agent has been used via delivery mechanisms other than the intravenous route noted by your clinical team (e.g., intrathecal [25] or inhaled [26] regimens). You note that few studies look at potential synergistic effects of combination therapy with colistin and rifampin or other antibiotics and that other antibiotic alternatives are examined in the literature for treatment of resistant bacterial infections. Though these related topics are perhaps not key for the current question, the team would likely find it useful to know that other administration strategies and alternative antibiotic regimens are available and may have some utility.

For a truly comprehensive search, you would follow up this search with an exploration of other resources that may contain information relevant to this question. Other resources that may be useful for this case include OLDMEDLINE, Web of Science, EMBASE, and BIOSIS Previews. For the purpose of this case, the study will stop here and begin looking at your initial selection of relevant items more closely.

SUMMARIZING THE INDIVIDUAL REFERENCES FOR THE TEAM'S QUICK REFERENCE

While it is useful to summarize the reviews in narrative format (discussed further in the next section), the individual studies are perhaps more suited to summarization in a tabular format. Table 2 provides an example of applying this format to summarize one of the selected articles. An online version of the table is available in Word format (Table 2 supplement), so that you may apply this template to summarizing the other clinical studies selected for this question as a practice exercise.

Table thumbnail
Table 2 Summarizing the individual articles

OVERALL STATE OF THE LITERATURE: THE BOTTOM LINE

You have now selected and summarized a group of references that represent the highest quality and most relevant data from the literature. It is now time to think about the most effective way to share this information with the clinical team.

Given your fairly in-depth understanding of the related literature at this point in the process, you can leverage this insight in an “executive summary” to introduce your more detailed description of each item. This will provide an overview to the clinical team that captures the general state of the literature on the topic: the quality and currency of available evidence, relevance to the question and any discrepancies between the literature and the specific context of the question at hand, areas of consensus and disagreement in published research and opinion, and any “gaps” in the literature (i.e., aspects of the question that currently available data fails to address).

This summary involves derivation of the “essence of the literature.” It may be useful to think of this section as detailing what you would say if you wanted to characterize the literature for this question if asked in conversation.

So, by reflecting on the key points of what you have read and the understanding you have gained regarding use of colistin for Acinetobacter infections, topics come to mind that you would want to include in the summary document:

  • a brief description of the antibiotic and the rationale behind the recent resurgence of interest in this agent
  • comments on the types of infections colistin can treat, particularly the sensitivity of Acinetobacter to this therapeutic agent
  • brief commentary on the review articles you selected to address this question that incorporates key points from and about each article; comments should put each article into context, highlighting strengths and weaknesses of methods used and results
  • sentence characterizing the study designs and population sizes represented in each study
  • commentary on the range of dosages used and durations of therapy represented in the selected literature
  • a note describing nephrotoxicity and neurotoxicity as potential serious adverse effects associated with this agent, including strategies for detecting and managing these complications
  • mention of the other administration routes (intrathecal, inhaled/aerosolized) for colistin
  • commentary on other therapeutic strategies for Acinetobacter infection recently explored by clinical researchers as potential alternatives of interest; the team should acquaint itself with alternative approaches to colistin should the patient not tolerate colistin therapy due to nephrotoxicity or other side effects or if the patient's infection does not respond to colistin

Figure 2 provides an example of what the end product of this final summarization product may look like.

Sample statement describing the overall state of the literature The use of colistin and its derivatives for treatment of Acinetobacter ventilator-associated pneumonia  Colistin is an older antibiotic in the polymyxin family. Renewed attention ...

CONCLUDING REMARKS

As the evidence consultant to the team, you have developed and applied your expertise in searching and synthesizing the biomedical literature to provide evidence to inform the clinicians as they determine a course of action for this patient.

The background knowledge that you have gained over the course of addressing this question as well as your understanding of the patient case have allowed you to sift through up to several hundred references, narrowing the results to a small group of key citations. Your summary of the carefully selected, most relevant studies and your commentary on the overall state of the literature will facilitate the team's understanding of the available evidence and help them to apply these results to the current patient. In addition, you have found additional evidence in the literature to provide the team with suggestions for therapeutic alternatives should colistin fail or cause significant side effects in this patient. The product of your efforts provides the clinicians with a focused and directly actionable information base to use in caring for this patient and for similar patients in the future. Your actions make you a valuable and valued expert member of this team!

Supplementary Material

Table 2 supplement:

Footnotes

Editor's note: This column will be curated by Rebecca Jerome. The editors will invite other experts to contribute cases and welcome ideas for useful topics to appear in this feature. The case studies will also be supplemented by an online forum for further discussion of the scenarios and facets of the strategies for addressing these information-related challenges. The commentary and discussion of results for this case were updated on June 19, 2006. We invite your commentary on this case online at jmlacasestudies.blogspot.com.

Footnote icon for Electronic Content

Supplemental electronic content is included with this paper on PubMed Central.

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