Bone biopsy in suspected osteomyelitis: Culture and histology matter

Diabetic foot ulcers and infections can lead to osteomyelitis, a potentially devastating infection in the bone.

WILLSIE/Getty Images

How much of a difference can osteomyelitis make to a patient’s prognosis? A 2014 commentary by Benjamin A. Lipsky, MD, a prominent expert in problems associated with diabetic patients’ feet who’s with the University of Washington, Seattle, hints at the potential toll: “Overall, about 20% of patients with a diabetic foot infection (and over 60% of those with severe infections) have underlying osteomyelitis, which dramatically increases the risk of lower-extremity amputation” (Diabetes Care. 2014 Mar;37[3]:593-5).

Diagnosis of osteomyelitis, which relies on a bone biopsy, is clearly important. But there’s a big gap in diagnostic findings depending on whether doctors request culture or histology results, according to a new study released at the 2018 scientific meeting of the American Diabetes Association (Diabetes. 2018 Jul. doi: 10.2337/db18-110-OR).

In an interview, lead author and podiatrist Peter A. Crisologo, DPM, of University of Texas Southwestern Medical Center, Dallas, explained the study findings and offered guidance for requesting bone biopsies in possible cases of osteomyelitis.

Q: What makes diagnosis and treatment of osteomyelitis unique?

A: In the foot, there’s not a lot of soft tissue between the outside world and your bone. If the wounds on the feet go deep enough, they can spread a bacterial infection to the bone. This changes how foot infections are treated.
 

If you have a skin infection, it requires 11-12 days of antibiotics. Things start ramping up once you start getting into the bone. You’re talking potential surgery and 6 weeks of antibiotics through IV treatments. This is why it’s really important that you get your diagnosis right.

A lot of people say “I’m going to do the safe thing” and treat a bone infection with an extended course of antibiotics.

That’s not necessarily safe. If you’re overdiagnosing – for example, you identify bacteria that’s just a contaminant – you could put a patient through 6 weeks of IV treatment along with the risks of a PICC (peripherally inserted central catheter ) line infection, complications from IV placement, and complications from the antibiotic.

Also, acute kidney injury develops in at least a third of the patients who undergo 6 weeks of antibiotics. That’s not to mention the cost of the visits and the labs you have to draw. But we don’t want to underdiagnose either. If osteomyelitis is underdiagnosed and then not treated, the infection can smolder and continue to progress and worsen.

Q: Your study looks at the bone biopsy. How does it fit into care of osteomyelitis in the diabetic foot?

A: A bone biopsy is the standard for diagnosis under the guidelines of the Infectious Diseases Society of America/International Working Group on the Diabetic Foot (Clin Infect Dis. 2012;54[12]:e132-73 ).
 

But beyond that, nobody says anything. Everyone has an operational definition of how a bone biopsy is interpreted, and there’s a need for a consensus on how a bone biopsy can be used to diagnose osteomyelitis.

You’ll get different percentages of your patients diagnosed with osteomyelitis. For example, someone may say the biopsy is only positive if the histology is positive, while another says the histology doesn’t matter if the culture is positive.

Q: Your study looks at histology and culture analyses. What do these reveal?

A: A traditional culture helps you identify the bacteria, as well as guide your treatment when it’s tested against antibiotics.
 

A traditional histology allows the pathologist to look under a microscope for signs of osteomyelitis: Do they see the right inflammatory cells, white cells, lymphocytes, combinations of cells? Does this look like an acute or chronic osteomyelitis?

Q: Why might it be wise to combine culture and histology analyses?

A: If you have bacteria that’s difficult to culture via traditional methods, it may be a bacteria that doesn’t grow well or easily. If you combine culture with histology, pathologists can look and say, “Your culture was negative but we see these other signs, so we feel this is osteomyelitis.”



Q: Your study examined 35 consecutive patients aged at least 21 years who had moderate or severe infections bone infections in the foot linked with type 1 diabetes (n = 4) or type 2 diabetes (n = 31).

The samples were analyzed via culture, histology, and culture/histology examinations. You also performed genetic sequencing (quantitative polymerase chain reaction targeting 16S rRNA). How does this test fit in to bone biopsies in the clinic?

A: That’s a newer method and not a standard of care treatment for the diabetic foot. This analysis looks at DNA that’s present, bypassing the analysis of difficult-to-grow bacteria.



Q: What did you discover?

A: In this study, histology had the lowest incidence of positively detecting osteomyelitis. (45.7%). The level increases when a culture is taken (68.6% vs. histology; P = .02).
 

Then it goes up when DNA is used because it’s catching everything (82.9%, P = .001 vs. histology and P = .31 vs. culture).

[The study also found that adding histology to culture or to genetic sequencing did not change positive findings.]

Q: Does the study suggest one approach is better than the others?

A: This paper doesn’t provide enough evidence to use one method over another. The main purpose was to raise the concern that diagnosis can change dramatically depending on how the gold standard of bone biopsy is interpreted.



Q: What were the pros and cons of the genetic sequencing approach?

A: When we use this approach, our positive diagnostic rate significantly increases. But there are also downsides. We don’t know whether the bacteria we see is alive or dead. We just know it was there. So are the patients truly positive? That’s a question we can’t answer.
 

Genetic sequencing also doesn’t tell us about susceptibilities to antibiotics.

Q: What is the take-home message here for physicians who may order bone biopsies?

A: The thing to do is request both traditional culture and traditional histology.
 

As far as DNA sequencing, that not something I’d recommend as a standard of care.

Q: Can you comment on cost and insurance coverage for these approaches?

A: As far as I know, genetic sequencing is not covered as it is not standard of care in the diabetic foot and is used mainly for research at this time.
 

Pathology and culture are standard of care when evaluating for osteomyelitis and should be a covered service. However, a patient should call their insurance company first prior to having the procedure done to see whether it is covered.

Q: What’s next for research in this area?

A: From here, the next step is bigger numbers: Increase the study size and look at this again. Also, we may be able to identify susceptibilities by identifying resistance within the DNA.



Dr. Crisologo and two other study authors report no relevant disclosures. One study author reported various disclosures including research support, consulting, and service on speakers' bureaus.
 

Diabetic foot ulcers and infections can lead to osteomyelitis, a potentially devastating infection in the bone.

WILLSIE/Getty Images

How much of a difference can osteomyelitis make to a patient’s prognosis? A 2014 commentary by Benjamin A. Lipsky, MD, a prominent expert in problems associated with diabetic patients’ feet who’s with the University of Washington, Seattle, hints at the potential toll: “Overall, about 20% of patients with a diabetic foot infection (and over 60% of those with severe infections) have underlying osteomyelitis, which dramatically increases the risk of lower-extremity amputation” (Diabetes Care. 2014 Mar;37[3]:593-5).

Diagnosis of osteomyelitis, which relies on a bone biopsy, is clearly important. But there’s a big gap in diagnostic findings depending on whether doctors request culture or histology results, according to a new study released at the 2018 scientific meeting of the American Diabetes Association (Diabetes. 2018 Jul. doi: 10.2337/db18-110-OR).

In an interview, lead author and podiatrist Peter A. Crisologo, DPM, of University of Texas Southwestern Medical Center, Dallas, explained the study findings and offered guidance for requesting bone biopsies in possible cases of osteomyelitis.

Q: What makes diagnosis and treatment of osteomyelitis unique?

A: In the foot, there’s not a lot of soft tissue between the outside world and your bone. If the wounds on the feet go deep enough, they can spread a bacterial infection to the bone. This changes how foot infections are treated.
 

If you have a skin infection, it requires 11-12 days of antibiotics. Things start ramping up once you start getting into the bone. You’re talking potential surgery and 6 weeks of antibiotics through IV treatments. This is why it’s really important that you get your diagnosis right.

A lot of people say “I’m going to do the safe thing” and treat a bone infection with an extended course of antibiotics.

That’s not necessarily safe. If you’re overdiagnosing – for example, you identify bacteria that’s just a contaminant – you could put a patient through 6 weeks of IV treatment along with the risks of a PICC (peripherally inserted central catheter ) line infection, complications from IV placement, and complications from the antibiotic.

Also, acute kidney injury develops in at least a third of the patients who undergo 6 weeks of antibiotics. That’s not to mention the cost of the visits and the labs you have to draw. But we don’t want to underdiagnose either. If osteomyelitis is underdiagnosed and then not treated, the infection can smolder and continue to progress and worsen.

Q: Your study looks at the bone biopsy. How does it fit into care of osteomyelitis in the diabetic foot?

A: A bone biopsy is the standard for diagnosis under the guidelines of the Infectious Diseases Society of America/International Working Group on the Diabetic Foot (Clin Infect Dis. 2012;54[12]:e132-73 ).
 

But beyond that, nobody says anything. Everyone has an operational definition of how a bone biopsy is interpreted, and there’s a need for a consensus on how a bone biopsy can be used to diagnose osteomyelitis.

You’ll get different percentages of your patients diagnosed with osteomyelitis. For example, someone may say the biopsy is only positive if the histology is positive, while another says the histology doesn’t matter if the culture is positive.

Q: Your study looks at histology and culture analyses. What do these reveal?

A: A traditional culture helps you identify the bacteria, as well as guide your treatment when it’s tested against antibiotics.
 

A traditional histology allows the pathologist to look under a microscope for signs of osteomyelitis: Do they see the right inflammatory cells, white cells, lymphocytes, combinations of cells? Does this look like an acute or chronic osteomyelitis?

Q: Why might it be wise to combine culture and histology analyses?

A: If you have bacteria that’s difficult to culture via traditional methods, it may be a bacteria that doesn’t grow well or easily. If you combine culture with histology, pathologists can look and say, “Your culture was negative but we see these other signs, so we feel this is osteomyelitis.”



Q: Your study examined 35 consecutive patients aged at least 21 years who had moderate or severe infections bone infections in the foot linked with type 1 diabetes (n = 4) or type 2 diabetes (n = 31).

The samples were analyzed via culture, histology, and culture/histology examinations. You also performed genetic sequencing (quantitative polymerase chain reaction targeting 16S rRNA). How does this test fit in to bone biopsies in the clinic?

A: That’s a newer method and not a standard of care treatment for the diabetic foot. This analysis looks at DNA that’s present, bypassing the analysis of difficult-to-grow bacteria.



Q: What did you discover?

A: In this study, histology had the lowest incidence of positively detecting osteomyelitis. (45.7%). The level increases when a culture is taken (68.6% vs. histology; P = .02).
 

Then it goes up when DNA is used because it’s catching everything (82.9%, P = .001 vs. histology and P = .31 vs. culture).

[The study also found that adding histology to culture or to genetic sequencing did not change positive findings.]

Q: Does the study suggest one approach is better than the others?

A: This paper doesn’t provide enough evidence to use one method over another. The main purpose was to raise the concern that diagnosis can change dramatically depending on how the gold standard of bone biopsy is interpreted.



Q: What were the pros and cons of the genetic sequencing approach?

A: When we use this approach, our positive diagnostic rate significantly increases. But there are also downsides. We don’t know whether the bacteria we see is alive or dead. We just know it was there. So are the patients truly positive? That’s a question we can’t answer.
 

Genetic sequencing also doesn’t tell us about susceptibilities to antibiotics.

Q: What is the take-home message here for physicians who may order bone biopsies?

A: The thing to do is request both traditional culture and traditional histology.
 

As far as DNA sequencing, that not something I’d recommend as a standard of care.

Q: Can you comment on cost and insurance coverage for these approaches?

A: As far as I know, genetic sequencing is not covered as it is not standard of care in the diabetic foot and is used mainly for research at this time.
 

Pathology and culture are standard of care when evaluating for osteomyelitis and should be a covered service. However, a patient should call their insurance company first prior to having the procedure done to see whether it is covered.

Q: What’s next for research in this area?

A: From here, the next step is bigger numbers: Increase the study size and look at this again. Also, we may be able to identify susceptibilities by identifying resistance within the DNA.



Dr. Crisologo and two other study authors report no relevant disclosures. One study author reported various disclosures including research support, consulting, and service on speakers' bureaus.
 

Diabetic foot ulcers and infections can lead to osteomyelitis, a potentially devastating infection in the bone.

WILLSIE/Getty Images

How much of a difference can osteomyelitis make to a patient’s prognosis? A 2014 commentary by Benjamin A. Lipsky, MD, a prominent expert in problems associated with diabetic patients’ feet who’s with the University of Washington, Seattle, hints at the potential toll: “Overall, about 20% of patients with a diabetic foot infection (and over 60% of those with severe infections) have underlying osteomyelitis, which dramatically increases the risk of lower-extremity amputation” (Diabetes Care. 2014 Mar;37[3]:593-5).

Diagnosis of osteomyelitis, which relies on a bone biopsy, is clearly important. But there’s a big gap in diagnostic findings depending on whether doctors request culture or histology results, according to a new study released at the 2018 scientific meeting of the American Diabetes Association (Diabetes. 2018 Jul. doi: 10.2337/db18-110-OR).

In an interview, lead author and podiatrist Peter A. Crisologo, DPM, of University of Texas Southwestern Medical Center, Dallas, explained the study findings and offered guidance for requesting bone biopsies in possible cases of osteomyelitis.

Q: What makes diagnosis and treatment of osteomyelitis unique?

A: In the foot, there’s not a lot of soft tissue between the outside world and your bone. If the wounds on the feet go deep enough, they can spread a bacterial infection to the bone. This changes how foot infections are treated.
 

If you have a skin infection, it requires 11-12 days of antibiotics. Things start ramping up once you start getting into the bone. You’re talking potential surgery and 6 weeks of antibiotics through IV treatments. This is why it’s really important that you get your diagnosis right.

A lot of people say “I’m going to do the safe thing” and treat a bone infection with an extended course of antibiotics.

That’s not necessarily safe. If you’re overdiagnosing – for example, you identify bacteria that’s just a contaminant – you could put a patient through 6 weeks of IV treatment along with the risks of a PICC (peripherally inserted central catheter ) line infection, complications from IV placement, and complications from the antibiotic.

Also, acute kidney injury develops in at least a third of the patients who undergo 6 weeks of antibiotics. That’s not to mention the cost of the visits and the labs you have to draw. But we don’t want to underdiagnose either. If osteomyelitis is underdiagnosed and then not treated, the infection can smolder and continue to progress and worsen.

Q: Your study looks at the bone biopsy. How does it fit into care of osteomyelitis in the diabetic foot?

A: A bone biopsy is the standard for diagnosis under the guidelines of the Infectious Diseases Society of America/International Working Group on the Diabetic Foot (Clin Infect Dis. 2012;54[12]:e132-73 ).
 

But beyond that, nobody says anything. Everyone has an operational definition of how a bone biopsy is interpreted, and there’s a need for a consensus on how a bone biopsy can be used to diagnose osteomyelitis.

You’ll get different percentages of your patients diagnosed with osteomyelitis. For example, someone may say the biopsy is only positive if the histology is positive, while another says the histology doesn’t matter if the culture is positive.

Q: Your study looks at histology and culture analyses. What do these reveal?

A: A traditional culture helps you identify the bacteria, as well as guide your treatment when it’s tested against antibiotics.
 

A traditional histology allows the pathologist to look under a microscope for signs of osteomyelitis: Do they see the right inflammatory cells, white cells, lymphocytes, combinations of cells? Does this look like an acute or chronic osteomyelitis?

Q: Why might it be wise to combine culture and histology analyses?

A: If you have bacteria that’s difficult to culture via traditional methods, it may be a bacteria that doesn’t grow well or easily. If you combine culture with histology, pathologists can look and say, “Your culture was negative but we see these other signs, so we feel this is osteomyelitis.”



Q: Your study examined 35 consecutive patients aged at least 21 years who had moderate or severe infections bone infections in the foot linked with type 1 diabetes (n = 4) or type 2 diabetes (n = 31).

The samples were analyzed via culture, histology, and culture/histology examinations. You also performed genetic sequencing (quantitative polymerase chain reaction targeting 16S rRNA). How does this test fit in to bone biopsies in the clinic?

A: That’s a newer method and not a standard of care treatment for the diabetic foot. This analysis looks at DNA that’s present, bypassing the analysis of difficult-to-grow bacteria.



Q: What did you discover?

A: In this study, histology had the lowest incidence of positively detecting osteomyelitis. (45.7%). The level increases when a culture is taken (68.6% vs. histology; P = .02).
 

Then it goes up when DNA is used because it’s catching everything (82.9%, P = .001 vs. histology and P = .31 vs. culture).

[The study also found that adding histology to culture or to genetic sequencing did not change positive findings.]

Q: Does the study suggest one approach is better than the others?

A: This paper doesn’t provide enough evidence to use one method over another. The main purpose was to raise the concern that diagnosis can change dramatically depending on how the gold standard of bone biopsy is interpreted.



Q: What were the pros and cons of the genetic sequencing approach?

A: When we use this approach, our positive diagnostic rate significantly increases. But there are also downsides. We don’t know whether the bacteria we see is alive or dead. We just know it was there. So are the patients truly positive? That’s a question we can’t answer.
 

Genetic sequencing also doesn’t tell us about susceptibilities to antibiotics.

Q: What is the take-home message here for physicians who may order bone biopsies?

A: The thing to do is request both traditional culture and traditional histology.
 

As far as DNA sequencing, that not something I’d recommend as a standard of care.

Q: Can you comment on cost and insurance coverage for these approaches?

A: As far as I know, genetic sequencing is not covered as it is not standard of care in the diabetic foot and is used mainly for research at this time.
 

Pathology and culture are standard of care when evaluating for osteomyelitis and should be a covered service. However, a patient should call their insurance company first prior to having the procedure done to see whether it is covered.

Q: What’s next for research in this area?

A: From here, the next step is bigger numbers: Increase the study size and look at this again. Also, we may be able to identify susceptibilities by identifying resistance within the DNA.



Dr. Crisologo and two other study authors report no relevant disclosures. One study author reported various disclosures including research support, consulting, and service on speakers' bureaus.