How do multiplex PCRs fair in the rapid diagnosis of viral respiratory infections? Quite well. The authors performed a meta-analyses of studies examining the diagnostic efficacy of the FilmArray, Verigene RV+, and Prodesse platforms for influenza A, influenza B, RSV, human metapneumovirus, and adenovirus. They identified 20 studies with a total 5510 patients. The area under the receiver operator curve (AUROC) was >0.98 for every virus except adenovirus, where the AUROC was 0.89. If you, like me, have only a tenuous grasp of the concept of AUROC, here is a nice primer; suffice it say that these PCR panels are excellent diagnostic tests for the viruses they identify. The three platforms were all highly sensitive for influenza A (sensitivities of 91%, 95%, and 95%, respectively). 29208560
A new strain of vancomycin-resistant Enterococcus faecium exhibits linezolid resistance not detected by standard automated susceptibility testing. This is a short report and I think it’s important, but don’t have much to say about it. The authors describe a cluster of linezolid-resistant VRE infections in liver and multiorgan transplant patients treated in a single ICU. Resistance to linezolid was not reliably detected by the VITEK2 system despite clinical failures with linezolid, and subsequent E testing showed resistance in every case. Whole genome sequencing revealed a novel mutation in the bacteria’s ribosomal RNA. Long story short – if you see a VRE infection that’s clinically failing linezolid despite the isolate being reported as sensitive, and it’s not clearly a source control issue, ask the lab to doublecheck the linezolid sensitivities. 30339217
Urine PCR may prove to be a good noninvasive test for Whipple’s Disease. Or rather, for Tropheryma whipplei. This is worth more than board trivia because it turns out that T. whipplei may be an important cause of culture-negative endocarditis. But in any case, the authors report that after noticing intact T. whipplei bacteria in a kidney biopsy from a patient with Whipple’s disease they decided to test the sensitivity of a urine PCR for the organism. They performed PCR on urine from 12 patients with newly diagnosed and untreated Whipple’s disease, 31 patients with treated disease, and 110 healthy volunteers. They found that the urine PCR was positive in 75% of the patients with untreated Whipple’s disease and negative in all of the controls, including 11 healthy carriers with T. whipplei in their stool. 30351371
Procalcitonin (PCT) facilitates the safe early discontinuation of antibiotics in patients with bacteremia. So concludes this meta-analysis of patient-level data from 13 clinical trials in respiratory infections and sepsis (n=523). The authors compared patients assigned to receive antibiotics based on PCT-guided algorithms versus those given antibiotics in accordance with standard care; the primary outcome of interest were antibiotic duration and 30-day mortality. The PCT algorithms were similar, recommending stopping antibiotics when PCT levels decreased below predetermined thresholds (<0.5 ug/L for the studies done in ICUs and <0.25 ug/L for the studies done elsewhere); adherence to the algorithms ranged from 46-100%.
The baseline characteristics of the groups were similar. Most bacteremias were due to either respiratory or urinary tract infections; 243 patients had gram-positive infections (mostly S. pneumoniae) and 196 patients had gram-negative infections (mostly E. coli). The mean initial PCT was 29.7 ug/L.
Antibiotic duration was significantly lower in the patients receiving PCT-guided algorithmic therapy (12.7 versus 15.6 days, difference 2.9 days; p=0.006). Subgroup analysis showed greater differences with pneumococcal bacteremia (difference 4.8 days; p for interaction=0.02); this should surprise no one, as by tradition bacteremic pneumococcal pneumonia has been safely treated using community-acquired pneumonia durations of therapy (i.e. 5-7 days). As for 30-day mortality, 17% of the patients in the PCT-guided algorithm group died versus 20% in the standard care group (OR 0.82; p=0.26; length of hospital and ICU stays were also similar between groups.
I have mixed feelings about the use of procalcitonin for antibiotic de-escalation. On the one hand, I fully support any intervention that gets actually doctors to stop prescribing antibiotics patients don’t need. On the other hand, increasing evidence suggests that many, perhaps most non-S. aureus bacteremias can be treated with less than the standard 10-14 days of therapy. If can we build a body of evidence to demonstrate that it’s usually safe to treat bacteremia with a week of antibiotics or less, and if we can actually change routine prescribing practice for bacteremia, will trending the procalcitonin for de-escalation still be a worthwhile use of antibiotic stewardship dollars? 30358811