‘Know your panel’: Blood culture ID cautions

“This could be complicated by the fact that essentially all commercially available panels can have somewhat variable performance for polymicrobial cultures,” Dr. Butler-Wu said. “So typically, we are very conservative in our lab. Essentially, if you can’t see an identification by Gram stain, be very wary.” Pay attention to the positive results, she said, and look for unusual trends.

To illustrate the challenges associated with false-negative results, Dr. Butler-Wu presented the case of a 72-year-old male who presented to the emergency department with fever and abdominal pain (Fontana L, et al. J Clin Microbiol. 2019;57[1]:e00826-18). The patient had a medical history significant for colorectal cancer and had undergone several rounds of chemotherapy and a central hepatectomy with a hepaticojejunostomy. He also had a history of recurrent ascending cholangitis from a biliary stricture.

One month before admission to the ED, the patient had a biliary stent and a percutaneous drain placed. “He has frequently over his history presented with Gram-negative bacteremia that typically was E. coli or Klebsiella pneumoniae,” Dr. Butler-Wu said.

The patient was febrile on admission and cachectic, lethargic, and diaphoretic on exam. Deep palpation revealed a right, upper quadrant pain but no rebound tenderness.

“They were concerned about obstruction of his biliary drain,” she said. “They obtained blood cultures, and one of the two sets that were sent was positive for plump, enteric-looking Gram-negative rods.”

The laboratory used the Verigene BC-GN panel, “and the organism produced no identification by that panel but was subsequently identified as Klebsiella pneumoniae by MALDI-TOF-MS,” she said.

The mystery bug, she said, was K. variicola, part of the K. pneumoniae complex. “This is an interesting bug because, particularly by phenotypic methods, it’s often called Klebsiella pneumoniae, but bloodstream infections appear to have a higher mortality rate than other members of the Klebsiella pneumoniae complex.” One study found more than twice the mortality rate (29.4 percent versus 13.5 percent) compared with other members of the complex (Rodríguez-Medina N, et al. Emerg Microbes Infect. 2019;8[1]:973–988).

“There has also been an emergence of multidrug resistant strains among the Klebsiella variicola species,” Dr. Butler-Wu said. In several published papers, “it’s estimated that Klebsiella variicola may actually account for about 10 percent of bloodstream isolates that are identified as Klebsiella pneumoniae.”

That the Verigene Gram-negative panel was unable to detect K. variicola “was a significant issue,” she said, leading to false-negative results for this organism. “It’s important to know your panel and its limitations.”

A retrospective study performed over 15 months at Huntington Hospital in California found that six percent of 1,044 positive blood cultures were negative by the FilmArray BCID (Ny P, et al. J Clin Microbiol. 2019;57[5]:e01941-18).

Those BCID-negative blood cultures were then tested by standard phenotypic identification procedures using the BD Phoenix, and the results included many different anaerobic species, Dr. Butler-Wu said. Among the aerobic organisms the BD Phoenix identified were “quite a few coag-negative staph and a smattering of other organisms.”

“This mattered,” she said. When the authors looked at the time-to-effective therapy and mortality among these patients, they found that those whose blood cultures were positive for on-target organisms had better outcomes. Patients who had bloodstream infections with off-target organisms had lower rates of effective antimicrobial therapy, compared with patients who had on-target organisms, in terms of timeliness, she said.

“And, critically, they also observed a higher mortality rate among patients who had off-target bloodstream infections compared with on-target bloodstream infections”—26 percent versus eight percent.

“You can argue this means we need to, as they say, build a bigger boat,” Dr. Butler-Wu said, noting the latest generations of the Verigene BC-GN, ePlex BCID-GN, and FilmArray BCID and BCID2 panels have dramatically increased the number of organism targets.

But is the boat big enough? she asks, and then answers her own question: It may never be. Huang, et al., studied the ePlex BCID system, which Dr. Butler-Wu noted has the most comprehensive of the available panels. “And even with that, they were still observing six percent of isolates growing in blood culture that were not identified by these highly multiplexed panels” (Huang TD, et al. J Clin Microbiol. 2019;57[2]:e01597-18).

“You can never cover every possible organism,” Dr. Butler-Wu said, “but you can cover the majority of them.”

Dr. Butler-Wu would like to see a greater role for clinical microbiology in antimicrobial stewardship, citing two studies in particular. “They involved an antimicrobial stewardship pharmacist in micro rounds, and observed improved patient outcomes, improved time to effective antimicrobial therapy, and several other measures,” she said of the studies (Sapozhnikov J, et al. Am J Clin Pathol. 2021;155[3]:455–460; MacVane SH, et al. Open Forum Infect Dis. 2016;3[4]:ofw201).

But she understands the reality. “Long-term, daily involvement in antimicrobial stewardship pharmacy in microbiology rounds may not always be feasible,” Dr. Butler-Wu said. “Not all labs do microbiology rounds, and often clinical teams may be too busy to attend.”

She therefore proposes another option: targeted discussions focused on positive blood cultures with off-panel positive results. “They can be reviewed carefully by a microbiologist and that information provided back to the stewardship team.”

She asks: “Could there be greater involvement of clinical microbiology directors in interpreting Gram stain results in the context of these off-panel positive blood cultures? And is this a way to meet that gap, where we know we’ll never have panels that can catch absolutely everything, but we, through our own skills, can get a sense of what might be going on with the specimen and relay that information to our colleagues in stewardship?”

A meta-analysis (31 studies consisting of 5,920 patients) by Timbrook, et al., revealed that the odds ratio for mortality risk was significantly lower for patients who had undergone rapid blood culture identification (Timbrook TT, et al. Clin Infect Dis. 2017;64[1]:15–23).

“This includes detection of resistance markers in addition to the identification,” Dr. Butler-Wu added. “And a critical point for labs is that this benefit, in terms of reducing the odds ratio for mortality risk, was only observed [with] and appeared to be dependent on antimicrobial stewardship. There’s no point in doing rapid testing in a vacuum if it’s not combined with our ID pharmacy and stewardship colleagues. It’s going to be a waste of time and have minimal impact.”

“So rapid identification and timeliness of results matter, but only if you’re combining it by getting the results to the right people who can act on it.”

Dr. Butler-Wu concluded with a “shout-out” to the Gram stain: “The Gram stain is our very best friend. As clinical microbiologists, we have to balance what we can see versus what we can detect, know our panels, and relay that information effectively to our clinician colleagues.”

“You have to be ready for anything in the blood culture identification business,” she said.

Amy Carpenter Aquino is CAP TODAY senior editor.