What we know and what we don't know

IIn July, federal health officials told hospitals: Shortage of blood culture bottles That will continue until September.

Blood culture bottles are critical to diagnosing sepsis, a deadly infection of the bloodstream caused by a variety of bacteria. According to the Centers for Disease Control and Prevention, about half of U.S. labs get their bottles from a company called BD, which is a supplier that is experiencing shortages, and the shortages could have a major impact on patient care. Every hour that antibiotics are delayed in treating sepsis can cost Patient survival rate reduced by 7.6%.

But what are blood culture bottles, and what do we know about the shortage?

What are blood culture bottles used for?

If a doctor is concerned about sepsis, they may order a blood culture to check for infection, which involves taking a 10-milliliter sample of blood (the size of a ketchup packet) and adding it to a blood culture bottle containing a nutrient-rich medium that bacteria love to grow.

The bottle is then placed into a machine that incubates the blood mixture at a warm temperature, encouraging the growth of any bacteria present until the bottle turns cloudy, alerting a lab technician that the patient may have sepsis.

The bacteria-filled samples can then be subjected to a variety of stains, plate cultures, and PCR tests to determine exactly which bacterial strain is causing the infection and which antibiotic is best for the patient.

Blood cultures used to be done manually, but hospitals are now doing far more cultures and patients are more seriously ill and complicated, said Romney Humphreys, medical director of the microbiology lab at Vanderbilt University Medical Center. If the health system were to revert to manual cultures, technicians would have to visually check hundreds of samples for cloudiness, and could only do so about once every 12 hours. Humphreys called the prospect of going back to manual cultures “scary.”

After Humphries mentioned the manual process during her call with the CDC about the shortages, “I got emails from at least 20 people asking what the procedure was because they were worried that they might get to that stage,” she told STAT.

How long has this shortage been going on for?

BD told hospitals in late June to expect shortages and reduced bottle supplies.

Health officials said BD initially characterized the issue as temporary and not cause for alarm, but shipments to many countries fell sharply in the first week of July.

“We were told to expect about a 50% decrease,” said Sarah Olstadius, laboratory operations manager for Northeast Georgia Health System, a five-hospital health system. “What we've seen is more like a 70% decrease.”

“No matter how much we ordered, we never got anything. If we got anything, it was like five or 10 bottles, less than a case,” Humphreys said.

BD later determined that the shortage was more severe than initially thought. Now I say The company said in a statement that the issue is “more complicated than initially communicated by our supplier” but declined to provide further details.

Humphries worked with BD and was eventually able to get a direct shipment of 900 bottles a week, but Vanderbilt uses about 6,000 bottles a month, and she said that's still not enough.

Can I switch suppliers?

Switching suppliers is complicated. Part of the problem is that the equipment that analyzes the bottles only works with bottles of certain sizes and shapes, so labs can't easily switch to a different brand of bottles as they can with more common consumables like pipette tips or Petri dishes.

There are just three companies that manufacture these analyzers for laboratories in the U.S. Aside from a few laboratories that use Thermo Fisher, the rest of the industry is split between BD and the French company bioMérieux.

Switching from BD to another vendor would require hundreds of thousands of dollars in new equipment and weeks, possibly months, to install and validate the new system. Humphreys said Vanderbilt decided to change vendors, but bioMérieux has stopped accepting new customers because of supply shortages.

While bioMérieux doesn't expect its blood culture bottle supply will be affected, “we will not expediently pursue new business without first meeting the needs of our existing customers,” a company spokesperson told STAT in an email.

Is patient care currently being affected?

So far, very few.

The CDC and Food and Drug Administration are focusing on using best practices and promoting stewardship, such as bottle conservation. This includes reminding clinicians which patients need blood cultures and which don't, reducing just-in-case orders. Hospital officials told STAT that some systems are putting new rules into electronic health records to enforce stricter guidelines. Hospitals are also reexamining policies on how many samples to take and whether to do follow-up cultures, especially if the initial test is negative.

Representatives from health systems who spoke with STAT acknowledged that blood cultures are probably overused and that simply curbing orders could limit blood culture bottle usage and spare clinicians from having to make difficult patient care choices. But as hospitals implement more stringent measures, fewer cultures mean more infections are missed.

The worst-case scenario continues to plague clinicians: not using blood cultures to determine the appropriate course of treatment could result in prescribing the wrong antibiotic for a patient, delaying doctors' determination that a patient needs a stronger or different antibiotic, resulting in poorer outcomes and even death.

Why is there a shortage?

The company that supplies BD's plastic bottles is at fault, but when STAT asked for clarification, BD declined to say whether it was a raw material or manufacturing issue. The supplier's name was also not available. BD said in a statement that it is “working directly with our molded bottle raw material supplier to improve the efficiency and output of their production lines.”

BD sources its bottles from a single supplier in Indiana and told STAT that it has considered acquiring a second supplier, but that the bottle neck design and associated intellectual property pose a “barrier to adopting a second supplier.”

Chris Bedard, BD's vice president of microbiology, said in a July 15 call with the CDC that the shortage was specific to these bottles and did not affect other BD products.

When will the shortage end?

BD told STAT that it has a German glass bottle supplier online and expects to “realize improvements in supply in September 2024,” though hospital sources who spoke with STAT said BD has not said whether these supply improvements will occur in early or late September.

To CDC-sponsored conference call Bedard, speaking July 23 with the Infectious Diseases Society of America, said the use of glass vials is only temporary until supplies of plastic vials are restored.

What questions will physicians be asking regulators?

During the July 23 conference call, clinicians peppered FDA and other regulatory officials with questions about steps they should take, including whether it's OK to use near-expired or expired media, whether laboratories need to validate their procedures for new vials, and when follow-up cultures can be omitted.

The FDA referred many of these questions to the Centers for Medicare and Medicaid Services, which runs the federally regulated laboratory accreditation program. A CMS spokesperson told STAT that expired media can only be used if the manufacturer extends the expiration date (an FDA official said on a July 23 conference call that the agency is considering this), and that labs that have used glass vials in the past can use those validation studies when the new glass vials are introduced.

As part of List of quality measures Unlike the law, which dictates how hospitals are paid, Medicare rates hospitals based on the quality of their sepsis management, including blood cultures. Right now, clinicians told STAT they're not worried about not meeting Medicare's quality requirements, but it would be a problem if the bottles went missing altogether.

A CMS spokesperson said in an email to STAT that the agency is not currently tracking any issues with sepsis preparedness, but acknowledges that shortages could result in problems. “We will continue to monitor the situation and issue guidance accordingly if issues are identified,” the spokesperson said.

Sally Weiss, vice president of workforce policy and strategic initiatives for the Maine Hospital Association, is concerned about the lack of information about what hospitals should do if they run out of blood culture bottles. Current guidelines “don't really acknowledge that that could happen,” she said.

STAT asked the CDC what guidance it has for hospitals that may be running short of bottles. “This is a rapidly changing situation, and product availability varies widely by region,” a CDC spokesperson told STAT in an email. The spokesperson pointed to resources we've discussed in previous articles. CDC's call and notice The department said it was still trying to understand how staffing shortages were affecting health services.

How can I fix this?

The BD shortage is due to the company's reliance on a single supplier for plastic bottles, and the immediate solution is to diversify its sourcing, as bioMérieux has done, likely for similar reasons. Shortage of bioMérieux blood culture bottles In a statement to STAT in 2014, bioMérieux said it had multiple sources for raw materials, bottles and manufacturing, and was working with suppliers to secure supplies of plastic bottles.

More broadly, the proprietary nature of the analyzers means they're designed to fit only one type of bottle made by one manufacturer. Lab managers and hospital executives floated the idea of ​​standardizing the equipment to work with generic bottles or getting other companies to make generic versions of the proprietary bottles. Steve Dias, chief medical officer at MaineGeneral Health, said companies should be allowed to make money on their intellectual property, “but shouldn't they have some kind of backup in case something like this happens?”

While not cheap, “stretching out” all points in the supply chain — with manufacturers, distributors and hospitals all holding slightly more supply than they need — also allows for flexibility in times of crisis, said Nancy Foster, vice president of quality and safety policy at the American Hospital Association.

Linoj Samuel, chief of clinical microbiology at Henry Ford Health System in Detroit, said supply chain issues have popped up all the time and sparked a lot of discussion, especially since the pandemic began, but no one has really taken steps to solve them.

“What we need is a commitment from government, industry and other stakeholders to really step forward and build on some of these solutions and ideas and see what can be done,” he said. “It's a difficult and challenging problem. But if there were an easy solution, we'd probably do it. There aren't.”