One of the most dangerous places for an infection to occur is in the bloodstream. Septicemia, when microbes are present in the blood, not only allows bacteria access to other internal organs through the highway of our circulatory system, but also can cause a massive inflammatory response, leading to septic shock. Conditions that increase risk of bloodstream infections, such as invasive surgery or implantation of an indwelling device, are carefully monitored and are sometimes accompanied by prophylactic antimicrobial drugs to prevent this very serious condition.
In the unfortunate case where an infection does occur, timing is everything. The quicker physicians can diagnose the invasive microbial species, the faster the patient can be given the most effective therapy. That is the reasoning behind a new meta-analysis of bloodstream infection diagnostic practices, now published in Clinical Microbiology Reviews.
Traditional diagnostic assays – which not only identify the microbe but also its antibiotic susceptibility profile – can take up to 48 hours to produce a result (sometimes longer). While scientists are hard at work to produce more accurate, extremely fast assays using technology such as mass spectroscopy, there are technologies already available that can help hasten diagnosis. The panel of experts convened to compare results across studies to make best-practice recommendations to save precious hours during patient diagnosis. They compared three different practices in their review:
- Rapid molecular techniques with additional direct communication to clinicians
- Rapid molecular techniques without additional direct communication (communicated only by electronic medical record)
- Rapid phenotypic techniques with additional direct communication to clinicians
Rapid molecular techniques included PCR and peptide nucleic acid fluorescent in situ hybridization (PNA-FISH), while rapid phenotypic techniques included tube coagulase and penicillin binding protein 2a (PBP2a) assays, thermonuclease testing, the BioMérieux Vitek 2 system, and the API 20E bacterial identification system.
Comparing only patient studies, the panel found 1820 relevant studies that fit the initial inclusion criteria. These were whittled down to a mere 16 studies by increasing the stringency of the criteria to include only well-controlled experiments with high-quality statistical analyses. The small number of studies was not enough for the panel to make strong recommendations on any one technique over the other, but they noted several aspects of each of the practices.
- The rapid molecular test without additional direct communication showed an improvement over traditional techniques, but only when one of the four studies comparing this method was excluded.
- The rapid molecular test with additional direct communication showed only moderate evidence for increased treatment timeliness, in part because of the quality of the five eligible studies.
- The rapid phenotypic test with additional direct contact showed mixed results in speeding diagnostics, with two of four studies demonstrating a positive effect and the remaining two demonstrating no effect.
One important conclusion that the panel was able to make was a reduction in mortality. Over 70,000 patients suffer hospital-acquired bloodstream infections annually in the U.S., and delays in infection diagnosis can lead to increased patient stays and even death. There was a significant reduction in mortality associated with rapid molecular testing with additional direct communication (see figure, right). This makes sense, as a physician can immediately call the hospital to change a patient’s medications upon receiving diagnostic news. If that same physician waits to check the patient’s records at the end of the day (or even a few hours later), the patient may have lost a few precious hours still fighting without proper therapy.
As with the urine sample collection and storage guidelines, one of the most important issues raised by this meta-study was the lack of consistency between studies. To facilitate better analyses in the future, the panel created guidelines for experimental design elements that will allow more decisive conclusions in future reviews by standardizing across studies.
-- Julie Wolf