Access to MALDI-TOF does not improve clinical outcomes in the absence of an antimicrobial stewardship program. Antimicrobial stewardship technology is increasingly in vogue, but there are several papers now showing that rapid diagnostics don’t translate into better clinical outcomes unless you’re paying someone to look at the results and adjust antibiotics accordingly (i.e. you have an antibiotic stewardship program). Here’s another.
The authors examined clinical outcomes at a South Korean hospital without an ASP before and after the introduction of a MALDI-TOF rapid pathogen identification system to the microbiology lab. Records of patients who had bacteremia or fungemia from Oct-Dec 2012 (before) and Oct-Dec 2013 (after) were compared. As you’d expect, time to identification decreased from 86 to 64 hours. However, there were no associated statistically significant reductions in time to effective therapy (27 vs 23 hours), time to microbiologic cure (3.6 vs 3.7 days), length of ICU stay (17 vs 15 days), rate of recurrent infection (5% vs 3%) or mortality (18% vs 16%). Just goes to show that technology and data aren’t worth much in healthcare if you don’t have people who can use them appropriately.
The most cynical part of me wonders if adding rapid diagnostics to a hospital without a stewardship team might actually increase legal liability. Imagine a patient who dies of septic shock on inappropriate or delayed appropriate therapy with an overlooked rapid PCR resistance test result. Yikes! 30092780
Here’s a PCR panel for the microbiologic characterization of intrabdominal infections directly from patient samples. The Unyvero IAI cartridge is produced by Curetis GmbH, who provided the reagents and instruments for this study but with whom none of authors disclosed any financial relationships. Unyvero aims to provide PCR-based identification of a wide variety of pathogens associated with IAI, including Candida and Staphylococcus aureus, along with the presence of various resistance genes (e.g. mecA, vanA, CTX-M, KPC, MCR-1), all directly from clinical specimens such as ascites, aspirated pus, or surgical swab.
The authors collected 300 such samples from patients with suspected IAI from four European hospitals. The reference standard for identification was the hospital microbiology labs’ routine culture methods; concordant results were classified as true positives or negatives, and discordant results were refereed by performing DNA extraction, PCR and sequencing on the sample. Overall, the Unyvero cartridge exhibited 89.3% sensitivity and 99.5% specificity for pathogen identification; it was least sensitive for the detection of Enterococcus faecalis and Candida albicans (78% for each). Unyvero detected more pathogens than traditional culture; 40% of the samples identified as monomicrobial by culture were polymicrobial per Unyvero, with a large proportion of these being uncultured Bacteroides and Prevotella spp. The authors don’t report sensitivities and specificities for the Unyvero’s resistance gene detection because of variability in antimicrobial susceptibility testing, but they give NPVs for select resistance genes ranging from 84% (quinolone resistance gene qnrB) to 100% (mecA).
Finally, the authors report that Unyvero conferred significant reductions versus standard techniques in time to pathogen detection (22 vs 39 hours) and time to antimicrobial susceptibility testing (23 vs 64 hours). These numbers sound clinically meaningful… again, so long as someone is watching to use the results to guide antimicrobial prescribing. 30094522
And here is a study of the performance of the Accelerate Pheno system for rapid detection and susceptibility testing of gram-negative bloodstream infections. This platform combines fluorescent in situ hybridization (FISH) with automated microscopy to provide rapid pathogen identification and antimicrobial susceptibilities directly from positive blood culture bottles. In this study, the authors compared the speed and diagnostic utility of this system versus standard culture techniques in a prospective cohort of 104 positive blood cultures from a single French hospital. When susceptibility testing produced discrepant results, the authors performed broth microdilution assays as a reference standard. Accelerate Diagnostics (the company that makes this product) provided reagents and equipment for the study, but the authors disclosed no conflicts of interest.
Time to pathogen identification was lower using the Accelerate Pheno system (5 hours versus 24 hours), as was time to antimicrobial susceptibilities (11 hours versus 35 hours). The two methods agreed 96% of the time and 99% in monomicrobial bacteremias; in the four cases of disagreement, the Accelerate Pheno system missed a second pathogen representing <10% of the culturable bacteria in two cases, identified an additional pathogen not recovered on culture in one case, and misidentified an E. coli in one case.
Susceptibility testing via the Accelerate Pheno system was successful in 92% of isolates attempted and 98% of individual drug-antibiotic pairs. The 2% individual drug-bug testing failures occurred in cases of mixed cultures or when testing Enterobacteriales susceptibility to colistin or aminoglycosides. The two susceptibility testing methods agreed 94% of the time; Accelerate Pheno most often produced test results conflicting with the standard VITEK2 system in Pseudomonas aeruginosa (72% agreement) and with the beta-lactams cefepime, piperacillin-tazobactam, and ceftazidime (84%, 87%, and 88% agreements, respectively). The Accelerate system was particularly bad at determining Pseudomonas susceptibility to beta-lactams, (agreements of 78% for piperacillin-tazobactam, 56% for meropenem, 33% for cefepime, and 0% for ceftazidime).
To summarize, the Accelerate Pheno system looks like a reliable, rapid system for pathogen ID and rapid susceptibility testing, with a caveat that it is less reliable for some drugs in some organisms, and it has good potential to improve time to effective therapy as well as allow rapid de-escalation of broad-spectrum antimicrobials. Now, does it make sense to invest in one of these machines if your hospital has already bought the micro lab a MALDI-TOF and gram-negative and gram-positive antibiotic resistance PCR panels? There’s a question above my pay grade. 29808350