Latest / Deep Dive Ortho — Orthopaedic Surgery, AI & Digital Health Podcast. / Teicoplanin-Gentamicin vs. Cefuroxime: Prophylaxis in Joint Arthroplasty

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Teicoplanin-Gentamicin vs. Cefuroxime: Prophylaxis in Joint Arthroplasty · Deep Dive Ortho — Orthopaedic Surgery, AI & Digital Health Podcast.

• 0:00
  Welcome to the Deep Dive. We take the source
• 0:01
  material, you share the research, the reports,
• 0:04
  and really cut straight to the essential knowledge
• 0:05
  you need. Fast. Trying to get to the heart of
• 0:08
  it quickly. Exactly. Today, we're plunging into
• 0:11
  a really critical area of surgical practice,
• 0:14
  finding the best way to prevent infections during
• 0:17
  hip and knee replacement surgery. It's a major
• 0:19
  challenge. It is. And it involves this significant
• 0:22
  trade -off, doesn't it? How do you maximize protection
• 0:25
  against potentially devastating infections, but
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  also carefully manage the risk of, well, serious
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  drug side effects? Precisely. It's a constant
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  balancing act in clinical practice. Today is
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  a research paper. It's from the Royal National
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  Orthopaedic Hospital NHS Trust, published on
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  an official government website. It looks specifically
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  at changing the antibiotic protocol used, you
• 0:47
  know, before and after surgery in primary joint
• 0:50
  replacement. Total joint arthroplasty, yes. And
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  joining me is our expert guide, Prof. Mo Imam,
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  to help us navigate these complex findings and
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  understand what they really mean. Happy to be
• 1:01
  here. Preventing prosthetic joint infection,
• 1:04
  or PJI as we call it, is absolutely paramount
• 1:07
  in orthopedics. I can imagine. It's a complication
• 1:09
  that is truly devastating for the patient, and
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  it presents enormous challenges for the healthcare
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  system too. Choosing the right antibiotic prophylaxis
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  isn't straightforward at all. It needs a careful
• 1:20
  balance of efficacy against those potential adverse
• 1:23
  effects. Exactly. And this study gives us some
• 1:25
  real world data on that very balance. So at this
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  hospital, they changed their standard antibiotic
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  regimen, what was the old approach, and what
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  did they switch to, and crucially, what were
• 1:37
  they actually measuring, both the good and the
• 1:38
  bad, so to speak. Right, so the standard prophylaxis
• 1:41
  was initially cifroxam only, a three -dose regimen.
• 1:44
  Okay. They then switched, they moved to a single
• 1:47
  preoperative dose combining two drugs. Tegoplanin
• 1:50
  plus gentamicin. A combination therapy. Yes.
• 1:53
  And the main goal, of course, was trying to reduce
• 1:55
  the rate of prosthetic joint infection, PGI.
• 1:58
  Makes sense. On the flip side, the primary potential
• 2:01
  harm they were specifically tracking was acute
• 2:04
  kidney injury, AKI, which is a known risk associated
• 2:07
  with aminoglycosides. Gentamicin is one of those.
• 2:10
  OK. Let's unpack how they actually studied this
• 2:12
  change, then. What kind of approach did they
• 2:14
  take? How did they collect the data to compare
• 2:17
  these two regimens? Well, this was a retrospective
• 2:19
  study looking back at what happened. Using past
• 2:22
  records. Exactly. Comparing outcomes in two distinct
• 2:25
  time periods, but at the same hospital. They
• 2:28
  looked back at all patients undergoing primary
• 2:30
  hip and knee replacements. The pre -intervention
• 2:33
  group, that was patients from the 18 months before
• 2:36
  the antibiotic change. They have to see for oxy.
• 2:39
  Right. The post -intervention group were patients
• 2:41
  from the 18 months after the change. So they
• 2:43
  received the ticoplanin plus gentamicin. Got
• 2:46
  it. And how many patients are we talking about?
• 2:48
  They analyzed data from just under 2 ,000 patients
• 2:51
  in total, about 1 ,100 in the C. feroxan period
• 2:54
  and around 880 in the ticoplanin plus gentamicin
• 2:58
  period. And importantly, all the information
• 3:01
  came from routinely collected clinical records,
• 3:04
  real world data. And to ensure consistency, which
• 3:07
  is vital, They used standard, widely accepted
• 3:11
  definitions for the outcomes. The European Bone
• 3:14
  and Joint Infection Society criteria, EBJIS for
• 3:18
  diagnosing PJI. Right. And the kidney disease,
• 3:22
  improving global outcomes. KDIGO criteria for
• 3:26
  defining and staging AKI. So, established definitions,
• 3:30
  real -world results. Precisely. A pragmatic look
• 3:33
  at what happened after the change. That approach,
• 3:36
  using the hospital's own data, it feels very
• 3:38
  relevant. But whenever you compare groups from
• 3:40
  different times like this, you have to wonder
• 3:42
  if the patients were, well, truly comparable.
• 3:44
  Absolutely. Were there any significant differences
• 3:46
  between the group getting Siferoxim and the group
• 3:49
  getting the new combination? That's a very important
• 3:52
  point, and the authors definitely addressed it.
• 3:53
  They compared a whole range of baseline characteristics.
• 3:55
  Like what? Things like age, BMI. the ASA grade,
• 3:59
  which is a measure of overall health co -morbidities,
• 4:01
  how long the surgery took, whether it was a hip
• 4:03
  or knee. And for most of these, the groups were
• 4:07
  actually quite similar. But not identical. Not
• 4:09
  quite. There were two statistically significant
• 4:11
  differences they found. The Cifroxime group,
• 4:14
  the earlier group, had a higher proportion of
• 4:16
  female patients. and also more cemented arthroplasties.
• 4:20
  Ah, cemented versus uncemented, that can matter,
• 4:24
  can't it? It can sometimes influence risk profiles,
• 4:26
  yes. So because of these differences, sex and
• 4:29
  cement use, they couldn't just do a simple comparison
• 4:31
  of the raw numbers, they used statistical modeling.
• 4:35
  Cox regression analysis specifically. To adjust
• 4:39
  for those factors. Exactly. To adjust for the
• 4:41
  potential confounding effects of sex and cement
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  use, which allows for a more sort of like -for
• 4:45
  -like comparison of the PGI risk that you can
• 4:48
  attribute to the antibiotic regimen itself. Good.
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  So they tried to level the playing field statistically.
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  Right. Let's get to the core question then. The
• 4:55
  infection rates. How did the two antibiotics
• 4:57
  actually compare? This is where we see the potential
• 4:59
  benefit, presumably. Absolutely. And the results
• 5:02
  here were, well, pretty striding. OK. Across
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  the entire group, nearly 2 ,000 patients followed
• 5:07
  for two years. The overall PGI rate was 1 .50%.
• 5:11
  So 30 patients in total. OK. Overall. But by
• 5:14
  group. That's where the difference shows up.
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  The citroxine group, the ones on the older drug,
• 5:19
  had a PGI rate of 2 .24%. That's 25 infections
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  out of about 1 ,100 patients. Right. Two and
• 5:26
  a quarter percent. Then. The ticoplanum plus
• 5:28
  gentamicin group, their PGI rate was just 0 .57%.
• 5:32
  0 .57. Yes. Only five infections out of 880 patients.
• 5:37
  Wow. That is a dramatic reduction just looking
• 5:40
  at the raw numbers. It is. A very noticeable
• 5:42
  drop in the observed infection rate. So after
• 5:44
  they did that statistical adjustment you mentioned
• 5:46
  for the differences in the groups, what was the
• 5:49
  estimated size of that risk reduction? Well,
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  after adjusting for sex and cement use, the analysis
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  showed that the ticoplankton -plustion -tambosin
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  group had a 75 .2 % lower risk of developing
• 5:59
  PGI compared to the c -feroxime group. 75 % lower
• 6:02
  risk? Yes. The hazard ratio was .248. Okay, explain
• 6:06
  the hazard ratio a bit. What does .248 mean,
• 6:09
  practically? It means that patients getting the
• 6:12
  new combined regimen were, at any given time
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  point during the follow -up, only about a quarter
• 6:17
  as likely to actually experience a PGI compared
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  to those on ciferoxam, once you've accounted
• 6:23
  for those other factors like sex and cement type.
• 6:26
  Right. So a four -fold reduction in likelihood,
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  roughly. Roughly, yes. And this difference was
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  highly statistically significant. The P value
• 6:33
  is 0 .004. Very unlikely to be due to chance.
• 6:38
  A 75 % reduction is really substantial. Was this
• 6:41
  benefit seen across the board? for all types
• 6:44
  of infections or was it particularly effective
• 6:46
  against certain bacteria or maybe infections
• 6:49
  appearing at specific times after the surgery?
• 6:51
  That's a critical insight from the source actually.
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  The risk reduction was, and I'm quoting here,
• 6:56
  most pronounced for early onset and delayed infections.
• 6:59
  So infections happening relatively soon after
• 7:01
  surgery or within the first year or so? Typically,
• 7:04
  yes. And specifically those caused by two groups
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  of bacteria. coagulase -negative staphylococci
• 7:09
  connes, and sephiroxine -resistant enterobacteriaceae.
• 7:12
  Okay, connes and resistant enterobacteriaceae.
• 7:15
  Why those particularly? Well, it makes perfect
• 7:17
  sense when you look at the antibiotics. Sephiroxine,
• 7:20
  it's a second -generation cephalosporin. Its
• 7:23
  activity against many strains of connesse is
• 7:25
  limited, and it often has poor activity against
• 7:27
  enterobacteriaceae that have developed resistance
• 7:30
  mechanisms. So it had known weaknesses? Exactly.
• 7:33
  Tycoplanet, on the other hand, gives excellent
• 7:36
  coverage against gram -positive bacteria, including
• 7:39
  staph like connesse. And gentamisin provides
• 7:42
  strong coverage against many gram negatives,
• 7:45
  including most enterobacteriaceae. Ah, so the
• 7:47
  new combination directly targeted the bugs that
• 7:50
  the old drug wasn't hitting effectively. Precisely.
• 7:53
  It covered the gaps. And these are common causes
• 7:56
  of PGI. So the new combination addressed pathogens
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  the previous single agent was less effective
• 8:01
  against. That's a really key point. It wasn't
• 8:03
  just a general improvement. It seems specifically
• 8:05
  effective where the previous antibiotic perhaps
• 8:08
  had a blind spot. So connecting this back, what's
• 8:11
  the main implication for why the infection rate
• 8:13
  dropped? The authors conclude that this change
• 8:15
  in the antibiotic prophylaxis is the most likely
• 8:18
  reason for the lower infection risk. Because
• 8:20
  of that better coverage? Primarily, yes. Better
• 8:24
  coverage of key pathogens often picked up around
• 8:26
  the time of surgery. And this was alongside the
• 8:29
  hospital maintaining consistent general infection
• 8:31
  prevention and control practices throughout both
• 8:34
  study periods. That's important too. Right, it
• 8:36
  wasn't just the drugs changing in isolation.
• 8:38
  No. It's also interesting they note this finding
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  contrasts with some older studies, trials that
• 8:43
  didn't necessarily show one regimen being clearly
• 8:46
  better than another. Why might that be? The source
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  suggests it might be because those older trials
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  often compared regimens with only minor differences
• 8:53
  in their spectrum of activity, whereas this switch
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  involved a much more substantial change in coverage,
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  specifically targeting resistance patterns relevant
• 9:02
  to PJI. So a bigger change led to a bigger effect,
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  potentially. Potentially. They also raised another
• 9:08
  possibility about ziferoxam dosing, particularly
• 9:11
  in obese patients. Flender dosing. Maybe. They
• 9:14
  noted that a really striking 96 % of the infections
• 9:17
  in the ziferoxam group occurred in obese patients,
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  compared to only 40 % in the ticoplanin plus
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  gentamicin group. 96%. That's huge. It is. It
• 9:27
  highlights that maybe dose adequacy for certain
• 9:30
  patient groups. against specific bugs, could
• 9:33
  have played a role in the higher infection rate
• 9:35
  seen with Cifroxime in the study. Fascinating.
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  So a significant drop in infections likely due
• 9:41
  to better targeting of common and sometimes resistant
• 9:44
  pathogens. Okay, let's look at the other side
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  of that balance sheet now, the potential harms.
• 9:50
  What about the acute kidney injury, the AKI?
• 9:53
  Yes, the AKI. As you'd perhaps anticipate with
• 9:55
  using an amyoglycoside like Tentamacin, the rate
• 9:58
  of AKI was higher in the group getting the combined
• 10:00
  regimen. How much higher? Well, the overall AKI
• 10:03
  rate across the whole study was just under 2%,
• 10:05
  1 .9%. In the Sviroxin group, it was low 0 .8%,
• 10:08
  only 9 patients. Okay. But in the take -a -plan
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  and plus gentamicin group, it was significantly
• 10:13
  higher, 3 .3%. That's 29 patients. And that difference
• 10:17
  was statistically significant. Right. So a definite
• 10:19
  increase. But you mentioned earlier that AKI
• 10:21
  has different stages of severity based on those
• 10:24
  KDIGO criteria. Was this mostly severe kidney
• 10:27
  injury or milder cases? That's a crucial distinction.
• 10:30
  And the source is clear on this. The vast majority
• 10:32
  of the AKI cases, they saw 84 % of them, in fact,
• 10:36
  were stage one AKI. Stage one being the mildest
• 10:39
  form. Yes, the mildest form. And the rate of
• 10:42
  stage one AKI was significantly higher with the
• 10:45
  tekaplanin plus gentamisin. Three point zero
• 10:48
  percent versus only point five percent with sephiroxam.
• 10:51
  That drove the overall difference. OK, mostly
• 10:53
  stage one. What about more severe stages? Importantly,
• 10:56
  the study found no difference in the rate of
• 10:59
  stage 2 AKI between the groups. And critically,
• 11:02
  no patients developed stage 3 AKI, the most severe
• 11:05
  form, in either group. That's reassuring. Yes.
• 11:08
  And furthermore, no patients required renal replacement
• 11:10
  therodialysis for their kidney injury during
• 11:13
  the follow -up. So, more common, but generally
• 11:15
  less severe and seemingly reversible kidney issues.
• 11:18
  That's what this study found. And it's consistent
• 11:20
  with findings from some other studies using similar
• 11:22
  combined antibiotic regimens. An increase, but
• 11:25
  predominantly in mild AKI. Were there other significant
• 11:28
  potential harms discussed in the source? Yes,
• 11:31
  anaphylaxis. A severe allergic reaction. It was
• 11:34
  highlighted as a critical perioperative risk.
• 11:37
  And antibiotic -related anaphylaxis is certainly
• 11:40
  a known, though rare, concern. Right. The source
• 11:43
  references data from the UK's sixth National
• 11:45
  Audit Project, NAP6, which estimates anaphylaxis
• 11:49
  incidents during anesthesia. And what did that
• 11:51
  show for these drugs? Well, for the antibiotics
• 11:54
  we're discussing, NEP6 estimated incidences per
• 11:57
  100 ,000 procedures. Tycoplanin actually had
• 12:00
  a highest estimate at 16 .4. Compare that to
• 12:03
  sephiroxam at 0 .9 and gentamicin at 0 .6. So
• 12:07
  Tycoplanin potentially carries a higher background
• 12:10
  risk according to that national data. According
• 12:12
  to NEP6, yes. But what's particularly notable
• 12:15
  from the source, from this paper, is that their
• 12:17
  own observational data within their hospital
• 12:19
  suggested the actual rate for Tycoplan and anaphylaxis
• 12:22
  might be even higher. Really? Higher than the
• 12:24
  national estimate? Potentially up to three times
• 12:26
  higher than the NAP6 estimate. Your local data
• 12:29
  suggested a range between 1 in about 2100 and
• 12:31
  1 in about 1650 cases. Wow! That raises questions
• 12:35
  about under -reporting, perhaps. It does raise
• 12:37
  questions. The source does point out, though.
• 12:39
  that administering Tycoplanin slowly, usually
• 12:42
  over 30 minutes, is the recommended practice.
• 12:45
  That helps minimize infusion -related reactions,
• 12:47
  which can sometimes mimic or contribute to anaphylaxis
• 12:51
  symptoms. This really brings us to the central
• 12:54
  question, doesn't it? You weigh that substantial
• 12:56
  reduction in devastating infections. Which are
• 12:59
  terrible for patients. Absolutely. Against the
• 13:02
  increase in mostly milder kidney issues and this
• 13:05
  potentially higher risk of a very serious, albeit
• 13:08
  still rare, allergic reaction like anaphylaxis,
• 13:11
  how do those benefits and harms actually stack
• 13:14
  up? How did the paper frame it? They provide
• 13:16
  a calculation, sort of a thought experiment,
• 13:18
  to help put this trade -off into perspective.
• 13:20
  based on treating 10 ,000 patients undergoing
• 13:22
  primary joint replacement. Okay, per 10 ,000
• 13:25
  surgeries. Switching from sepharoxin to tycoplan
• 13:27
  and plus gentamicin could lead to an estimated
• 13:30
  125 fewer PJIs over two years. That's 125 fewer
• 13:35
  major complications. Yes. However, it could also
• 13:38
  result in approximately 220 more stage 1 AKEIs.
• 13:41
  Okay, 220 more cases of mild kidney injury. Predominantly
• 13:44
  mild, yes. And using a combination of the NAP6
• 13:49
  data and their own higher local estimate for
• 13:51
  tico plane and risk, potentially five more cases
• 13:54
  of life -threatening anaphylaxis. Five more anaphylaxis
• 13:57
  events per 10 ,000. That's the estimate based
• 13:59
  on their data. and an AP6. So what's fascinating
• 14:03
  here is seeing that balance laid out with numbers
• 14:06
  derived from their real -world practice. It certainly
• 14:08
  is. It presents a very clear clinical decision
• 14:11
  point for hospitals and clinicians. Reducing
• 14:13
  one significant risk appears to come with increasing
• 14:16
  others, albeit potentially less severe ones in
• 14:19
  the case of AKI, but very severe in the case
• 14:21
  of anaphylaxis, even if rare. That really sharpens
• 14:24
  the perspective on the decision. Every medical
• 14:27
  intervention involves that risk -benefit analysis.
• 14:29
  What were the limitations of the study that the
• 14:31
  authors themselves acknowledged? Well, as is
• 14:34
  typical for a retrospective study, looking back
• 14:36
  in time, they noted several limitations. Such
• 14:38
  as? The inherent nature means you can't control
• 14:40
  all variables, like in a prospective trial. While
• 14:44
  they adjusted for those key differences like
• 14:47
  sex and cement use, They acknowledge that minor
• 14:50
  unmeasured differences in patient comorbidities
• 14:53
  or even maybe changes in the prevalence of certain
• 14:56
  bugs over the two time periods can't be entirely
• 14:59
  ruled out. Right. You can't control everything
• 15:01
  historically. Exactly. They also mentioned it's
• 15:04
  impossible to completely isolate the effect of
• 15:06
  the antibiotic change from other potential historical
• 15:09
  effects, maybe other subtle changes in practice
• 15:12
  at the hospital during that time. Although they
• 15:14
  did state that general infection prevention practices
• 15:17
  remain consistent. OK. And finally, the incidence
• 15:20
  of some very specific resistant bacteria, things
• 15:22
  like vancomycin -resistant enterococci VREA,
• 15:26
  was just too low on their data set to draw firm
• 15:28
  conclusions about the impact of the new regimen
• 15:31
  on those particular pathogens. Understood. So
• 15:34
  given these findings, the clear benefits and
• 15:36
  the clear risks, and acknowledging those limitations,
• 15:38
  what's the main takeaway message for professionals,
• 15:40
  say orthopedic surgeons or hospital pharmacists
• 15:43
  reviewing their own prophylaxis protocols? I
• 15:45
  think the key conclusion from this single -center
• 15:47
  observation study is pretty clear. The change
• 15:50
  to tycoplan and plus gentamisin was associated
• 15:53
  with a significant reduction in the overall rate
• 15:55
  of prosthetic joint infection. And particularly,
• 15:58
  it targeted those early and delayed infections
• 16:00
  caused by conness and sephiroxam -resistant enterobacteriaceae.
• 16:04
  That seems key. What? But this benefit came with
• 16:07
  a statistically significant increase in acute
• 16:09
  kidney injury, mostly the milder stage one cases.
• 16:13
  And it requires very careful consideration. of
• 16:16
  the potentially increased risk of anaphylaxis,
• 16:19
  especially given the local risk estimate for
• 16:21
  take -a -plan and being higher than national
• 16:23
  figures. So the decision for other hospitals
• 16:25
  really involves carefully weighing these specific
• 16:28
  quantifiable benefits against these specific
• 16:31
  quantifiable harms, all within their own local
• 16:33
  context, their own patient population, their
• 16:36
  own resistance patterns. And linking this to
• 16:38
  the bigger picture, the source mentions the importance
• 16:40
  of prospective multicenter studies following
• 16:42
  this kind of single -center data. Why is that
• 16:45
  next step Well, prospective studies are really
• 16:48
  essential to confirm these findings in a more
• 16:50
  controlled environment, across multiple different
• 16:52
  centers, which would include varying patient
• 16:54
  populations and potentially different local bacterial
• 16:57
  resistance patterns. You get a broader view.
• 16:59
  Exactly. They can provide more robust data on
• 17:02
  less common outcomes, like severe AKI or anaphylaxis.
• 17:07
  And importantly, they offer a better opportunity
• 17:09
  to monitor the impact of these antibiotic changes
• 17:12
  on wider trends in antimicrobial resistance over
• 17:15
  time. Which is, of course, a major global health
• 17:18
  concern. So this study provides compelling real
• 17:21
  -world evidence from one place. Yes, strong observational
• 17:24
  evidence. But confirmation and broader applicability
• 17:27
  really need those larger prospective trials.
• 17:30
  That would be the ideal next step to inform wider
• 17:32
  practice changes confidently. Okay, so we've
• 17:35
  taken a deep dive into this really interesting
• 17:37
  study comparing two different antibiotic approaches
• 17:40
  for hip and knee replacements. We've seen that
• 17:42
  switching the regimen at this particular hospital
• 17:44
  led to a significant reduction in those dangerous
• 17:48
  prosthetic joint infections, especially hitting
• 17:51
  the bugs that the previous antibiotic struggled
• 17:53
  with. A clear benefit on the infection front.
• 17:55
  But we also saw that clear increase in kidney
• 17:58
  issues, mostly milder, thankfully, and that potentially
• 18:02
  higher risk of a severe allergic reaction anaphylaxis.
• 18:06
  The trade -off is very evident. This study powerfully
• 18:09
  illustrates that real -world balancing act, that
• 18:12
  trade -off that hospitals and clinicians have
• 18:13
  to navigate constantly when deciding on the best
• 18:16
  strategy to protect patients. If you found this
• 18:18
  deep dive valuable, it really helps other professionals
• 18:21
  discover these insights if you consider rating
• 18:23
  and sharing the show. Getting the knowledge out
• 18:25
  there. Indeed. Thanks for joining us for this
• 18:27
  deep dive. And just a final thought to leave
• 18:30
  you with. Thinking about the specific bacteria
• 18:33
  that this new regimen was particularly effective
• 18:35
  against those resistant to the previous antibiotic,
• 18:38
  does this study really hint that tailoring antibiotic
• 18:41
  prophylaxis strategies much more closely to local
• 18:44
  resistance patterns is perhaps the most impactful
• 18:46
  way forward, even if it means consciously accepting
• 18:49
  and managing different types of risks? Something
• 18:51
  to perhaps consider as you review protocols in
• 18:53
  your own clinical setting.