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 [16
]. 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 [20
]. 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.