WEBVTT 00:00:00.000 --> 00:00:01.940 Welcome to the Deep Dive. We take the source 00:00:01.940 --> 00:00:03.859 material, you share the research, the reports, 00:00:04.019 --> 00:00:05.960 and really cut straight to the essential knowledge 00:00:05.960 --> 00:00:08.240 you need. Fast. Trying to get to the heart of 00:00:08.240 --> 00:00:11.419 it quickly. Exactly. Today, we're plunging into 00:00:11.419 --> 00:00:14.380 a really critical area of surgical practice, 00:00:14.820 --> 00:00:17.199 finding the best way to prevent infections during 00:00:17.199 --> 00:00:19.600 hip and knee replacement surgery. It's a major 00:00:19.600 --> 00:00:22.120 challenge. It is. And it involves this significant 00:00:22.120 --> 00:00:25.100 trade -off, doesn't it? How do you maximize protection 00:00:25.100 --> 00:00:28.039 against potentially devastating infections, but 00:00:28.039 --> 00:00:31.760 also carefully manage the risk of, well, serious 00:00:31.760 --> 00:00:33.880 drug side effects? Precisely. It's a constant 00:00:33.880 --> 00:00:36.500 balancing act in clinical practice. Today is 00:00:36.500 --> 00:00:39.219 a research paper. It's from the Royal National 00:00:39.219 --> 00:00:42.179 Orthopaedic Hospital NHS Trust, published on 00:00:42.179 --> 00:00:44.759 an official government website. It looks specifically 00:00:44.759 --> 00:00:47.460 at changing the antibiotic protocol used, you 00:00:47.460 --> 00:00:50.020 know, before and after surgery in primary joint 00:00:50.020 --> 00:00:52.659 replacement. Total joint arthroplasty, yes. And 00:00:52.659 --> 00:00:55.179 joining me is our expert guide, Prof. Mo Imam, 00:00:55.399 --> 00:00:58.780 to help us navigate these complex findings and 00:00:58.780 --> 00:01:01.280 understand what they really mean. Happy to be 00:01:01.280 --> 00:01:04.159 here. Preventing prosthetic joint infection, 00:01:04.459 --> 00:01:07.299 or PJI as we call it, is absolutely paramount 00:01:07.299 --> 00:01:09.599 in orthopedics. I can imagine. It's a complication 00:01:09.599 --> 00:01:11.980 that is truly devastating for the patient, and 00:01:11.980 --> 00:01:14.120 it presents enormous challenges for the healthcare 00:01:14.120 --> 00:01:17.680 system too. Choosing the right antibiotic prophylaxis 00:01:17.680 --> 00:01:20.000 isn't straightforward at all. It needs a careful 00:01:20.000 --> 00:01:23.099 balance of efficacy against those potential adverse 00:01:23.099 --> 00:01:25.819 effects. Exactly. And this study gives us some 00:01:25.819 --> 00:01:29.079 real world data on that very balance. So at this 00:01:29.079 --> 00:01:32.739 hospital, they changed their standard antibiotic 00:01:32.739 --> 00:01:35.200 regimen, what was the old approach, and what 00:01:35.200 --> 00:01:37.060 did they switch to, and crucially, what were 00:01:37.060 --> 00:01:38.859 they actually measuring, both the good and the 00:01:38.859 --> 00:01:41.120 bad, so to speak. Right, so the standard prophylaxis 00:01:41.120 --> 00:01:44.739 was initially cifroxam only, a three -dose regimen. 00:01:44.760 --> 00:01:47.400 Okay. They then switched, they moved to a single 00:01:47.400 --> 00:01:50.439 preoperative dose combining two drugs. Tegoplanin 00:01:50.439 --> 00:01:53.159 plus gentamicin. A combination therapy. Yes. 00:01:53.680 --> 00:01:55.780 And the main goal, of course, was trying to reduce 00:01:55.780 --> 00:01:58.200 the rate of prosthetic joint infection, PGI. 00:01:58.340 --> 00:02:01.340 Makes sense. On the flip side, the primary potential 00:02:01.340 --> 00:02:04.079 harm they were specifically tracking was acute 00:02:04.079 --> 00:02:07.319 kidney injury, AKI, which is a known risk associated 00:02:07.319 --> 00:02:10.060 with aminoglycosides. Gentamicin is one of those. 00:02:10.219 --> 00:02:12.800 OK. Let's unpack how they actually studied this 00:02:12.800 --> 00:02:14.800 change, then. What kind of approach did they 00:02:14.800 --> 00:02:17.219 take? How did they collect the data to compare 00:02:17.219 --> 00:02:19.879 these two regimens? Well, this was a retrospective 00:02:19.879 --> 00:02:22.500 study looking back at what happened. Using past 00:02:22.500 --> 00:02:25.319 records. Exactly. Comparing outcomes in two distinct 00:02:25.319 --> 00:02:28.300 time periods, but at the same hospital. They 00:02:28.300 --> 00:02:30.740 looked back at all patients undergoing primary 00:02:30.740 --> 00:02:33.639 hip and knee replacements. The pre -intervention 00:02:33.639 --> 00:02:36.360 group, that was patients from the 18 months before 00:02:36.360 --> 00:02:38.900 the antibiotic change. They have to see for oxy. 00:02:39.020 --> 00:02:41.560 Right. The post -intervention group were patients 00:02:41.560 --> 00:02:43.879 from the 18 months after the change. So they 00:02:43.879 --> 00:02:46.479 received the ticoplanin plus gentamicin. Got 00:02:46.479 --> 00:02:48.460 it. And how many patients are we talking about? 00:02:48.759 --> 00:02:51.479 They analyzed data from just under 2 ,000 patients 00:02:51.479 --> 00:02:54.580 in total, about 1 ,100 in the C. feroxan period 00:02:54.580 --> 00:02:58.400 and around 880 in the ticoplanin plus gentamicin 00:02:58.400 --> 00:03:01.300 period. And importantly, all the information 00:03:01.300 --> 00:03:03.860 came from routinely collected clinical records, 00:03:04.500 --> 00:03:07.819 real world data. And to ensure consistency, which 00:03:07.819 --> 00:03:11.039 is vital, They used standard, widely accepted 00:03:11.039 --> 00:03:14.280 definitions for the outcomes. The European Bone 00:03:14.280 --> 00:03:18.159 and Joint Infection Society criteria, EBJIS for 00:03:18.159 --> 00:03:21.360 diagnosing PJI. Right. And the kidney disease, 00:03:22.300 --> 00:03:26.360 improving global outcomes. KDIGO criteria for 00:03:26.360 --> 00:03:30.199 defining and staging AKI. So, established definitions, 00:03:30.500 --> 00:03:33.139 real -world results. Precisely. A pragmatic look 00:03:33.139 --> 00:03:36.080 at what happened after the change. That approach, 00:03:36.180 --> 00:03:38.580 using the hospital's own data, it feels very 00:03:38.580 --> 00:03:40.939 relevant. But whenever you compare groups from 00:03:40.939 --> 00:03:42.300 different times like this, you have to wonder 00:03:42.300 --> 00:03:44.199 if the patients were, well, truly comparable. 00:03:44.400 --> 00:03:46.479 Absolutely. Were there any significant differences 00:03:46.479 --> 00:03:49.280 between the group getting Siferoxim and the group 00:03:49.280 --> 00:03:52.020 getting the new combination? That's a very important 00:03:52.020 --> 00:03:53.460 point, and the authors definitely addressed it. 00:03:53.479 --> 00:03:55.599 They compared a whole range of baseline characteristics. 00:03:55.740 --> 00:03:59.509 Like what? Things like age, BMI. the ASA grade, 00:03:59.650 --> 00:04:01.629 which is a measure of overall health co -morbidities, 00:04:01.969 --> 00:04:03.669 how long the surgery took, whether it was a hip 00:04:03.669 --> 00:04:07.030 or knee. And for most of these, the groups were 00:04:07.030 --> 00:04:09.110 actually quite similar. But not identical. Not 00:04:09.110 --> 00:04:11.610 quite. There were two statistically significant 00:04:11.610 --> 00:04:14.530 differences they found. The Cifroxime group, 00:04:14.689 --> 00:04:16.949 the earlier group, had a higher proportion of 00:04:16.949 --> 00:04:20.470 female patients. and also more cemented arthroplasties. 00:04:20.930 --> 00:04:23.870 Ah, cemented versus uncemented, that can matter, 00:04:24.069 --> 00:04:26.370 can't it? It can sometimes influence risk profiles, 00:04:26.589 --> 00:04:29.250 yes. So because of these differences, sex and 00:04:29.250 --> 00:04:31.870 cement use, they couldn't just do a simple comparison 00:04:31.870 --> 00:04:35.029 of the raw numbers, they used statistical modeling. 00:04:35.800 --> 00:04:39.000 Cox regression analysis specifically. To adjust 00:04:39.000 --> 00:04:41.100 for those factors. Exactly. To adjust for the 00:04:41.100 --> 00:04:43.240 potential confounding effects of sex and cement 00:04:43.240 --> 00:04:45.959 use, which allows for a more sort of like -for 00:04:45.959 --> 00:04:48.540 -like comparison of the PGI risk that you can 00:04:48.540 --> 00:04:50.699 attribute to the antibiotic regimen itself. Good. 00:04:50.939 --> 00:04:52.860 So they tried to level the playing field statistically. 00:04:53.639 --> 00:04:55.540 Right. Let's get to the core question then. The 00:04:55.540 --> 00:04:57.579 infection rates. How did the two antibiotics 00:04:57.579 --> 00:04:59.920 actually compare? This is where we see the potential 00:04:59.920 --> 00:05:02.180 benefit, presumably. Absolutely. And the results 00:05:02.180 --> 00:05:04.529 here were, well, pretty striding. OK. Across 00:05:04.529 --> 00:05:07.230 the entire group, nearly 2 ,000 patients followed 00:05:07.230 --> 00:05:11.730 for two years. The overall PGI rate was 1 .50%. 00:05:11.730 --> 00:05:14.709 So 30 patients in total. OK. Overall. But by 00:05:14.709 --> 00:05:16.709 group. That's where the difference shows up. 00:05:17.370 --> 00:05:19.389 The citroxine group, the ones on the older drug, 00:05:19.689 --> 00:05:24.110 had a PGI rate of 2 .24%. That's 25 infections 00:05:24.110 --> 00:05:26.310 out of about 1 ,100 patients. Right. Two and 00:05:26.310 --> 00:05:28.629 a quarter percent. Then. The ticoplanum plus 00:05:28.629 --> 00:05:32.930 gentamicin group, their PGI rate was just 0 .57%. 00:05:32.930 --> 00:05:37.350 0 .57. Yes. Only five infections out of 880 patients. 00:05:37.569 --> 00:05:40.050 Wow. That is a dramatic reduction just looking 00:05:40.050 --> 00:05:42.310 at the raw numbers. It is. A very noticeable 00:05:42.310 --> 00:05:44.949 drop in the observed infection rate. So after 00:05:44.949 --> 00:05:46.889 they did that statistical adjustment you mentioned 00:05:46.889 --> 00:05:49.009 for the differences in the groups, what was the 00:05:49.009 --> 00:05:51.550 estimated size of that risk reduction? Well, 00:05:51.730 --> 00:05:53.870 after adjusting for sex and cement use, the analysis 00:05:53.870 --> 00:05:55.829 showed that the ticoplankton -plustion -tambosin 00:05:55.829 --> 00:05:59.209 group had a 75 .2 % lower risk of developing 00:05:59.209 --> 00:06:02.649 PGI compared to the c -feroxime group. 75 % lower 00:06:02.649 --> 00:06:06.470 risk? Yes. The hazard ratio was .248. Okay, explain 00:06:06.470 --> 00:06:09.550 the hazard ratio a bit. What does .248 mean, 00:06:09.709 --> 00:06:12.009 practically? It means that patients getting the 00:06:12.009 --> 00:06:15.069 new combined regimen were, at any given time 00:06:15.069 --> 00:06:17.790 point during the follow -up, only about a quarter 00:06:17.790 --> 00:06:21.370 as likely to actually experience a PGI compared 00:06:21.370 --> 00:06:23.870 to those on ciferoxam, once you've accounted 00:06:23.870 --> 00:06:25.949 for those other factors like sex and cement type. 00:06:26.129 --> 00:06:28.209 Right. So a four -fold reduction in likelihood, 00:06:28.389 --> 00:06:31.189 roughly. Roughly, yes. And this difference was 00:06:31.189 --> 00:06:33.949 highly statistically significant. The P value 00:06:33.949 --> 00:06:37.569 is 0 .004. Very unlikely to be due to chance. 00:06:38.110 --> 00:06:41.509 A 75 % reduction is really substantial. Was this 00:06:41.509 --> 00:06:44.209 benefit seen across the board? for all types 00:06:44.209 --> 00:06:46.389 of infections or was it particularly effective 00:06:46.389 --> 00:06:49.050 against certain bacteria or maybe infections 00:06:49.050 --> 00:06:51.250 appearing at specific times after the surgery? 00:06:51.529 --> 00:06:53.670 That's a critical insight from the source actually. 00:06:53.790 --> 00:06:55.790 The risk reduction was, and I'm quoting here, 00:06:56.230 --> 00:06:58.990 most pronounced for early onset and delayed infections. 00:06:59.290 --> 00:07:01.250 So infections happening relatively soon after 00:07:01.250 --> 00:07:03.769 surgery or within the first year or so? Typically, 00:07:04.069 --> 00:07:06.430 yes. And specifically those caused by two groups 00:07:06.430 --> 00:07:09.310 of bacteria. coagulase -negative staphylococci 00:07:09.310 --> 00:07:12.329 connes, and sephiroxine -resistant enterobacteriaceae. 00:07:12.470 --> 00:07:15.069 Okay, connes and resistant enterobacteriaceae. 00:07:15.069 --> 00:07:17.209 Why those particularly? Well, it makes perfect 00:07:17.209 --> 00:07:20.250 sense when you look at the antibiotics. Sephiroxine, 00:07:20.290 --> 00:07:23.089 it's a second -generation cephalosporin. Its 00:07:23.089 --> 00:07:25.110 activity against many strains of connesse is 00:07:25.110 --> 00:07:27.670 limited, and it often has poor activity against 00:07:27.670 --> 00:07:30.370 enterobacteriaceae that have developed resistance 00:07:30.370 --> 00:07:33.550 mechanisms. So it had known weaknesses? Exactly. 00:07:33.800 --> 00:07:36.540 Tycoplanet, on the other hand, gives excellent 00:07:36.540 --> 00:07:39.680 coverage against gram -positive bacteria, including 00:07:39.680 --> 00:07:42.709 staph like connesse. And gentamisin provides 00:07:42.709 --> 00:07:44.730 strong coverage against many gram negatives, 00:07:45.009 --> 00:07:47.790 including most enterobacteriaceae. Ah, so the 00:07:47.790 --> 00:07:50.870 new combination directly targeted the bugs that 00:07:50.870 --> 00:07:53.649 the old drug wasn't hitting effectively. Precisely. 00:07:53.769 --> 00:07:56.050 It covered the gaps. And these are common causes 00:07:56.050 --> 00:07:59.069 of PGI. So the new combination addressed pathogens 00:07:59.069 --> 00:08:01.509 the previous single agent was less effective 00:08:01.509 --> 00:08:03.709 against. That's a really key point. It wasn't 00:08:03.709 --> 00:08:05.970 just a general improvement. It seems specifically 00:08:05.970 --> 00:08:08.370 effective where the previous antibiotic perhaps 00:08:08.370 --> 00:08:11.209 had a blind spot. So connecting this back, what's 00:08:11.209 --> 00:08:13.529 the main implication for why the infection rate 00:08:13.529 --> 00:08:15.850 dropped? The authors conclude that this change 00:08:15.850 --> 00:08:18.829 in the antibiotic prophylaxis is the most likely 00:08:18.829 --> 00:08:20.870 reason for the lower infection risk. Because 00:08:20.870 --> 00:08:24.529 of that better coverage? Primarily, yes. Better 00:08:24.529 --> 00:08:26.990 coverage of key pathogens often picked up around 00:08:26.990 --> 00:08:29.370 the time of surgery. And this was alongside the 00:08:29.370 --> 00:08:31.449 hospital maintaining consistent general infection 00:08:31.449 --> 00:08:34.269 prevention and control practices throughout both 00:08:34.269 --> 00:08:36.450 study periods. That's important too. Right, it 00:08:36.450 --> 00:08:38.409 wasn't just the drugs changing in isolation. 00:08:38.590 --> 00:08:40.789 No. It's also interesting they note this finding 00:08:40.789 --> 00:08:43.710 contrasts with some older studies, trials that 00:08:43.710 --> 00:08:46.490 didn't necessarily show one regimen being clearly 00:08:46.490 --> 00:08:48.870 better than another. Why might that be? The source 00:08:48.870 --> 00:08:51.129 suggests it might be because those older trials 00:08:51.129 --> 00:08:53.990 often compared regimens with only minor differences 00:08:53.990 --> 00:08:56.990 in their spectrum of activity, whereas this switch 00:08:56.990 --> 00:08:59.649 involved a much more substantial change in coverage, 00:09:00.350 --> 00:09:02.570 specifically targeting resistance patterns relevant 00:09:02.570 --> 00:09:06.070 to PJI. So a bigger change led to a bigger effect, 00:09:06.289 --> 00:09:08.570 potentially. Potentially. They also raised another 00:09:08.570 --> 00:09:11.809 possibility about ziferoxam dosing, particularly 00:09:11.809 --> 00:09:14.610 in obese patients. Flender dosing. Maybe. They 00:09:14.610 --> 00:09:17.710 noted that a really striking 96 % of the infections 00:09:17.710 --> 00:09:20.889 in the ziferoxam group occurred in obese patients, 00:09:21.629 --> 00:09:24.070 compared to only 40 % in the ticoplanin plus 00:09:24.070 --> 00:09:27.690 gentamicin group. 96%. That's huge. It is. It 00:09:27.690 --> 00:09:30.470 highlights that maybe dose adequacy for certain 00:09:30.470 --> 00:09:33.350 patient groups. against specific bugs, could 00:09:33.350 --> 00:09:35.929 have played a role in the higher infection rate 00:09:35.929 --> 00:09:38.590 seen with Cifroxime in the study. Fascinating. 00:09:38.730 --> 00:09:41.409 So a significant drop in infections likely due 00:09:41.409 --> 00:09:44.970 to better targeting of common and sometimes resistant 00:09:44.970 --> 00:09:48.289 pathogens. Okay, let's look at the other side 00:09:48.289 --> 00:09:50.110 of that balance sheet now, the potential harms. 00:09:50.250 --> 00:09:53.230 What about the acute kidney injury, the AKI? 00:09:53.289 --> 00:09:55.789 Yes, the AKI. As you'd perhaps anticipate with 00:09:55.789 --> 00:09:58.480 using an amyoglycoside like Tentamacin, the rate 00:09:58.480 --> 00:10:00.659 of AKI was higher in the group getting the combined 00:10:00.659 --> 00:10:03.179 regimen. How much higher? Well, the overall AKI 00:10:03.179 --> 00:10:05.299 rate across the whole study was just under 2%, 00:10:05.299 --> 00:10:08.879 1 .9%. In the Sviroxin group, it was low 0 .8%, 00:10:08.879 --> 00:10:11.700 only 9 patients. Okay. But in the take -a -plan 00:10:11.700 --> 00:10:13.820 and plus gentamicin group, it was significantly 00:10:13.820 --> 00:10:17.679 higher, 3 .3%. That's 29 patients. And that difference 00:10:17.679 --> 00:10:19.799 was statistically significant. Right. So a definite 00:10:19.799 --> 00:10:21.879 increase. But you mentioned earlier that AKI 00:10:21.879 --> 00:10:24.259 has different stages of severity based on those 00:10:24.259 --> 00:10:27.200 KDIGO criteria. Was this mostly severe kidney 00:10:27.200 --> 00:10:29.960 injury or milder cases? That's a crucial distinction. 00:10:30.059 --> 00:10:32.960 And the source is clear on this. The vast majority 00:10:32.960 --> 00:10:36.580 of the AKI cases, they saw 84 % of them, in fact, 00:10:36.759 --> 00:10:39.970 were stage one AKI. Stage one being the mildest 00:10:39.970 --> 00:10:42.389 form. Yes, the mildest form. And the rate of 00:10:42.389 --> 00:10:45.070 stage one AKI was significantly higher with the 00:10:45.070 --> 00:10:48.350 tekaplanin plus gentamisin. Three point zero 00:10:48.350 --> 00:10:51.110 percent versus only point five percent with sephiroxam. 00:10:51.309 --> 00:10:53.690 That drove the overall difference. OK, mostly 00:10:53.690 --> 00:10:56.820 stage one. What about more severe stages? Importantly, 00:10:56.960 --> 00:10:59.340 the study found no difference in the rate of 00:10:59.340 --> 00:11:02.120 stage 2 AKI between the groups. And critically, 00:11:02.600 --> 00:11:05.399 no patients developed stage 3 AKI, the most severe 00:11:05.399 --> 00:11:08.000 form, in either group. That's reassuring. Yes. 00:11:08.220 --> 00:11:10.899 And furthermore, no patients required renal replacement 00:11:10.899 --> 00:11:13.159 therodialysis for their kidney injury during 00:11:13.159 --> 00:11:15.940 the follow -up. So, more common, but generally 00:11:15.940 --> 00:11:18.360 less severe and seemingly reversible kidney issues. 00:11:18.500 --> 00:11:20.690 That's what this study found. And it's consistent 00:11:20.690 --> 00:11:22.970 with findings from some other studies using similar 00:11:22.970 --> 00:11:25.490 combined antibiotic regimens. An increase, but 00:11:25.490 --> 00:11:28.590 predominantly in mild AKI. Were there other significant 00:11:28.590 --> 00:11:31.289 potential harms discussed in the source? Yes, 00:11:31.570 --> 00:11:34.730 anaphylaxis. A severe allergic reaction. It was 00:11:34.730 --> 00:11:37.110 highlighted as a critical perioperative risk. 00:11:37.870 --> 00:11:40.009 And antibiotic -related anaphylaxis is certainly 00:11:40.009 --> 00:11:43.399 a known, though rare, concern. Right. The source 00:11:43.399 --> 00:11:45.960 references data from the UK's sixth National 00:11:45.960 --> 00:11:49.539 Audit Project, NAP6, which estimates anaphylaxis 00:11:49.539 --> 00:11:51.929 incidents during anesthesia. And what did that 00:11:51.929 --> 00:11:54.830 show for these drugs? Well, for the antibiotics 00:11:54.830 --> 00:11:57.929 we're discussing, NEP6 estimated incidences per 00:11:57.929 --> 00:12:00.590 100 ,000 procedures. Tycoplanin actually had 00:12:00.590 --> 00:12:03.809 a highest estimate at 16 .4. Compare that to 00:12:03.809 --> 00:12:07.629 sephiroxam at 0 .9 and gentamicin at 0 .6. So 00:12:07.629 --> 00:12:10.009 Tycoplanin potentially carries a higher background 00:12:10.009 --> 00:12:12.289 risk according to that national data. According 00:12:12.289 --> 00:12:15.259 to NEP6, yes. But what's particularly notable 00:12:15.259 --> 00:12:17.679 from the source, from this paper, is that their 00:12:17.679 --> 00:12:19.539 own observational data within their hospital 00:12:19.539 --> 00:12:22.519 suggested the actual rate for Tycoplan and anaphylaxis 00:12:22.519 --> 00:12:24.940 might be even higher. Really? Higher than the 00:12:24.940 --> 00:12:26.759 national estimate? Potentially up to three times 00:12:26.759 --> 00:12:29.259 higher than the NAP6 estimate. Your local data 00:12:29.259 --> 00:12:31.960 suggested a range between 1 in about 2100 and 00:12:31.960 --> 00:12:35.000 1 in about 1650 cases. Wow! That raises questions 00:12:35.000 --> 00:12:37.299 about under -reporting, perhaps. It does raise 00:12:37.299 --> 00:12:39.559 questions. The source does point out, though. 00:12:39.740 --> 00:12:42.559 that administering Tycoplanin slowly, usually 00:12:42.559 --> 00:12:44.879 over 30 minutes, is the recommended practice. 00:12:45.379 --> 00:12:47.620 That helps minimize infusion -related reactions, 00:12:47.960 --> 00:12:51.879 which can sometimes mimic or contribute to anaphylaxis 00:12:51.879 --> 00:12:54.419 symptoms. This really brings us to the central 00:12:54.419 --> 00:12:56.940 question, doesn't it? You weigh that substantial 00:12:56.940 --> 00:12:59.639 reduction in devastating infections. Which are 00:12:59.639 --> 00:13:02.460 terrible for patients. Absolutely. Against the 00:13:02.460 --> 00:13:05.519 increase in mostly milder kidney issues and this 00:13:05.519 --> 00:13:08.299 potentially higher risk of a very serious, albeit 00:13:08.299 --> 00:13:11.179 still rare, allergic reaction like anaphylaxis, 00:13:11.500 --> 00:13:14.059 how do those benefits and harms actually stack 00:13:14.059 --> 00:13:16.200 up? How did the paper frame it? They provide 00:13:16.200 --> 00:13:17.879 a calculation, sort of a thought experiment, 00:13:18.200 --> 00:13:19.879 to help put this trade -off into perspective. 00:13:20.139 --> 00:13:22.539 based on treating 10 ,000 patients undergoing 00:13:22.539 --> 00:13:25.019 primary joint replacement. Okay, per 10 ,000 00:13:25.019 --> 00:13:27.559 surgeries. Switching from sepharoxin to tycoplan 00:13:27.559 --> 00:13:30.200 and plus gentamicin could lead to an estimated 00:13:30.200 --> 00:13:35.120 125 fewer PJIs over two years. That's 125 fewer 00:13:35.120 --> 00:13:38.200 major complications. Yes. However, it could also 00:13:38.200 --> 00:13:41.240 result in approximately 220 more stage 1 AKEIs. 00:13:41.440 --> 00:13:44.769 Okay, 220 more cases of mild kidney injury. Predominantly 00:13:44.769 --> 00:13:49.009 mild, yes. And using a combination of the NAP6 00:13:49.009 --> 00:13:51.690 data and their own higher local estimate for 00:13:51.690 --> 00:13:54.769 tico plane and risk, potentially five more cases 00:13:54.769 --> 00:13:57.710 of life -threatening anaphylaxis. Five more anaphylaxis 00:13:57.710 --> 00:13:59.970 events per 10 ,000. That's the estimate based 00:13:59.970 --> 00:14:03.090 on their data. and an AP6. So what's fascinating 00:14:03.090 --> 00:14:06.269 here is seeing that balance laid out with numbers 00:14:06.269 --> 00:14:08.370 derived from their real -world practice. It certainly 00:14:08.370 --> 00:14:11.029 is. It presents a very clear clinical decision 00:14:11.029 --> 00:14:13.889 point for hospitals and clinicians. Reducing 00:14:13.889 --> 00:14:16.509 one significant risk appears to come with increasing 00:14:16.509 --> 00:14:19.409 others, albeit potentially less severe ones in 00:14:19.409 --> 00:14:21.909 the case of AKI, but very severe in the case 00:14:21.909 --> 00:14:24.899 of anaphylaxis, even if rare. That really sharpens 00:14:24.899 --> 00:14:27.120 the perspective on the decision. Every medical 00:14:27.120 --> 00:14:29.460 intervention involves that risk -benefit analysis. 00:14:29.840 --> 00:14:31.740 What were the limitations of the study that the 00:14:31.740 --> 00:14:34.039 authors themselves acknowledged? Well, as is 00:14:34.039 --> 00:14:36.279 typical for a retrospective study, looking back 00:14:36.279 --> 00:14:38.139 in time, they noted several limitations. Such 00:14:38.139 --> 00:14:40.519 as? The inherent nature means you can't control 00:14:40.519 --> 00:14:44.620 all variables, like in a prospective trial. While 00:14:44.620 --> 00:14:47.179 they adjusted for those key differences like 00:14:47.179 --> 00:14:50.519 sex and cement use, They acknowledge that minor 00:14:50.519 --> 00:14:53.259 unmeasured differences in patient comorbidities 00:14:53.259 --> 00:14:56.700 or even maybe changes in the prevalence of certain 00:14:56.700 --> 00:14:59.899 bugs over the two time periods can't be entirely 00:14:59.899 --> 00:15:01.700 ruled out. Right. You can't control everything 00:15:01.700 --> 00:15:04.320 historically. Exactly. They also mentioned it's 00:15:04.320 --> 00:15:06.779 impossible to completely isolate the effect of 00:15:06.779 --> 00:15:09.519 the antibiotic change from other potential historical 00:15:09.519 --> 00:15:12.299 effects, maybe other subtle changes in practice 00:15:12.299 --> 00:15:14.500 at the hospital during that time. Although they 00:15:14.500 --> 00:15:17.000 did state that general infection prevention practices 00:15:17.000 --> 00:15:20.200 remain consistent. OK. And finally, the incidence 00:15:20.200 --> 00:15:22.779 of some very specific resistant bacteria, things 00:15:22.779 --> 00:15:26.419 like vancomycin -resistant enterococci VREA, 00:15:26.419 --> 00:15:28.700 was just too low on their data set to draw firm 00:15:28.700 --> 00:15:31.000 conclusions about the impact of the new regimen 00:15:31.000 --> 00:15:34.019 on those particular pathogens. Understood. So 00:15:34.019 --> 00:15:36.080 given these findings, the clear benefits and 00:15:36.080 --> 00:15:38.039 the clear risks, and acknowledging those limitations, 00:15:38.179 --> 00:15:40.220 what's the main takeaway message for professionals, 00:15:40.779 --> 00:15:43.120 say orthopedic surgeons or hospital pharmacists 00:15:43.120 --> 00:15:45.559 reviewing their own prophylaxis protocols? I 00:15:45.559 --> 00:15:47.460 think the key conclusion from this single -center 00:15:47.460 --> 00:15:50.169 observation study is pretty clear. The change 00:15:50.169 --> 00:15:53.090 to tycoplan and plus gentamisin was associated 00:15:53.090 --> 00:15:55.149 with a significant reduction in the overall rate 00:15:55.149 --> 00:15:57.649 of prosthetic joint infection. And particularly, 00:15:58.029 --> 00:16:00.370 it targeted those early and delayed infections 00:16:00.370 --> 00:16:04.169 caused by conness and sephiroxam -resistant enterobacteriaceae. 00:16:04.509 --> 00:16:07.730 That seems key. What? But this benefit came with 00:16:07.730 --> 00:16:09.830 a statistically significant increase in acute 00:16:09.830 --> 00:16:13.090 kidney injury, mostly the milder stage one cases. 00:16:13.549 --> 00:16:16.330 And it requires very careful consideration. of 00:16:16.330 --> 00:16:18.850 the potentially increased risk of anaphylaxis, 00:16:19.129 --> 00:16:21.389 especially given the local risk estimate for 00:16:21.389 --> 00:16:23.070 take -a -plan and being higher than national 00:16:23.070 --> 00:16:25.929 figures. So the decision for other hospitals 00:16:25.929 --> 00:16:28.710 really involves carefully weighing these specific 00:16:28.710 --> 00:16:31.230 quantifiable benefits against these specific 00:16:31.230 --> 00:16:33.669 quantifiable harms, all within their own local 00:16:33.669 --> 00:16:36.009 context, their own patient population, their 00:16:36.009 --> 00:16:38.269 own resistance patterns. And linking this to 00:16:38.269 --> 00:16:40.409 the bigger picture, the source mentions the importance 00:16:40.409 --> 00:16:42.850 of prospective multicenter studies following 00:16:42.850 --> 00:16:45.029 this kind of single -center data. Why is that 00:16:45.029 --> 00:16:48.110 next step Well, prospective studies are really 00:16:48.110 --> 00:16:50.129 essential to confirm these findings in a more 00:16:50.129 --> 00:16:52.730 controlled environment, across multiple different 00:16:52.730 --> 00:16:54.549 centers, which would include varying patient 00:16:54.549 --> 00:16:57.389 populations and potentially different local bacterial 00:16:57.389 --> 00:16:59.549 resistance patterns. You get a broader view. 00:16:59.750 --> 00:17:02.779 Exactly. They can provide more robust data on 00:17:02.779 --> 00:17:06.599 less common outcomes, like severe AKI or anaphylaxis. 00:17:07.000 --> 00:17:09.700 And importantly, they offer a better opportunity 00:17:09.700 --> 00:17:12.359 to monitor the impact of these antibiotic changes 00:17:12.359 --> 00:17:15.759 on wider trends in antimicrobial resistance over 00:17:15.759 --> 00:17:18.859 time. Which is, of course, a major global health 00:17:18.859 --> 00:17:21.789 concern. So this study provides compelling real 00:17:21.789 --> 00:17:24.789 -world evidence from one place. Yes, strong observational 00:17:24.789 --> 00:17:27.589 evidence. But confirmation and broader applicability 00:17:27.589 --> 00:17:30.230 really need those larger prospective trials. 00:17:30.450 --> 00:17:32.869 That would be the ideal next step to inform wider 00:17:32.869 --> 00:17:35.369 practice changes confidently. Okay, so we've 00:17:35.369 --> 00:17:37.329 taken a deep dive into this really interesting 00:17:37.329 --> 00:17:40.069 study comparing two different antibiotic approaches 00:17:40.069 --> 00:17:42.710 for hip and knee replacements. We've seen that 00:17:42.710 --> 00:17:44.809 switching the regimen at this particular hospital 00:17:44.809 --> 00:17:48.109 led to a significant reduction in those dangerous 00:17:48.109 --> 00:17:51.250 prosthetic joint infections, especially hitting 00:17:51.250 --> 00:17:53.210 the bugs that the previous antibiotic struggled 00:17:53.210 --> 00:17:55.450 with. A clear benefit on the infection front. 00:17:55.589 --> 00:17:58.670 But we also saw that clear increase in kidney 00:17:58.670 --> 00:18:02.240 issues, mostly milder, thankfully, and that potentially 00:18:02.240 --> 00:18:05.799 higher risk of a severe allergic reaction anaphylaxis. 00:18:06.099 --> 00:18:09.400 The trade -off is very evident. This study powerfully 00:18:09.400 --> 00:18:12.180 illustrates that real -world balancing act, that 00:18:12.180 --> 00:18:13.880 trade -off that hospitals and clinicians have 00:18:13.880 --> 00:18:16.299 to navigate constantly when deciding on the best 00:18:16.299 --> 00:18:18.980 strategy to protect patients. If you found this 00:18:18.980 --> 00:18:21.220 deep dive valuable, it really helps other professionals 00:18:21.220 --> 00:18:23.339 discover these insights if you consider rating 00:18:23.339 --> 00:18:25.480 and sharing the show. Getting the knowledge out 00:18:25.480 --> 00:18:27.740 there. Indeed. Thanks for joining us for this 00:18:27.740 --> 00:18:30.039 deep dive. And just a final thought to leave 00:18:30.039 --> 00:18:33.259 you with. Thinking about the specific bacteria 00:18:33.259 --> 00:18:35.640 that this new regimen was particularly effective 00:18:35.640 --> 00:18:38.039 against those resistant to the previous antibiotic, 00:18:38.619 --> 00:18:41.619 does this study really hint that tailoring antibiotic 00:18:41.619 --> 00:18:44.039 prophylaxis strategies much more closely to local 00:18:44.039 --> 00:18:46.519 resistance patterns is perhaps the most impactful 00:18:46.519 --> 00:18:49.259 way forward, even if it means consciously accepting 00:18:49.259 --> 00:18:51.339 and managing different types of risks? Something 00:18:51.339 --> 00:18:53.500 to perhaps consider as you review protocols in 00:18:53.500 --> 00:18:54.299 your own clinical setting.