1 00:00:00,000 --> 00:00:12,260 Thanks for joining us again at the Canadian Breakpoint, a Canadian infectious diseases 2 00:00:12,260 --> 00:00:16,240 podcast by Canadian infectious diseases physicians. 3 00:00:16,240 --> 00:00:21,660 I'm Summer Stewart, back again with Dr. Rupeena Purewal, pediatric infectious diseases physician 4 00:00:21,660 --> 00:00:23,480 from Saskatoon. 5 00:00:23,480 --> 00:00:27,740 We're delighted to be welcoming you to the start of season three. 6 00:00:27,740 --> 00:00:30,960 Thank you so much for your support over the past two seasons. 7 00:00:30,960 --> 00:00:33,480 The response has been wonderfully positive. 8 00:00:33,480 --> 00:00:36,280 We have so much planned for 2024. 9 00:00:36,280 --> 00:00:42,000 In the first episode of this season, the Canadian Breakpoint welcomes back Dr. George Zhanel, 10 00:00:42,000 --> 00:00:48,040 medical microbiologist in Winnipeg and research director for CARA to expand on the clear registry 11 00:00:48,040 --> 00:00:51,400 and spotlight clear results for IV ceftobipral. 12 00:00:51,400 --> 00:00:52,400 Dr. Purewal. 13 00:00:52,400 --> 00:00:59,520 Hi, everyone. Welcome to another episode of our podcast, the Canadian Breakpoint. 14 00:00:59,520 --> 00:01:04,640 Today we are joined by Dr. George Zannell, as a microbiologist and pharmacologist who 15 00:01:04,640 --> 00:01:09,640 received his PhD in the Department of Medical Microbiology and Infectious Diseases at the 16 00:01:09,640 --> 00:01:15,680 Faculty of Medicine, University of Manitoba, and a doctor of clinical pharmacy at the University 17 00:01:15,680 --> 00:01:16,680 of Minnesota. 18 00:01:16,680 --> 00:01:21,120 He is presently professor and associate head in the Department of Medical Microbiology 19 00:01:21,120 --> 00:01:26,280 and Infectious Diseases, Max Reidy College of Medicine, and research director of the 20 00:01:26,280 --> 00:01:29,000 Canadian Antimicrobial Resistance Alliance. 21 00:01:29,000 --> 00:01:35,280 Dr. Zannell is the founding and chief editor of the Canadian Antimicrobial Resistance Alliance 22 00:01:35,280 --> 00:01:36,520 website www.can-r.com. 23 00:01:36,520 --> 00:01:45,320 Dr. Zannell has published over 1200 papers, chapters, and abstracts in the area of treatment 24 00:01:45,320 --> 00:01:47,320 and prevention of infectious diseases. 25 00:01:47,320 --> 00:01:53,920 He has presented over 1300 lectures as an invited speaker at international, national, 26 00:01:53,920 --> 00:01:58,360 and local meetings, speaking on the topics of antimicrobial resistance infections, as 27 00:01:58,360 --> 00:02:03,080 well as treatment and prevention of infectious diseases in Canada, United States, Central 28 00:02:03,080 --> 00:02:08,760 and Southern America, Western and Eastern Europe, including Russia, Australia, Southern 29 00:02:08,760 --> 00:02:11,760 and Northern Africa, the Middle East, and Asia. 30 00:02:11,760 --> 00:02:16,840 He has been extensively involved in the treatment guidelines for a variety of infections in 31 00:02:16,840 --> 00:02:19,160 Canada, the U.S., and internationally. 32 00:02:19,160 --> 00:02:24,400 Dr. Zannell has received or been nominated for more than 100 teaching awards, including 33 00:02:24,400 --> 00:02:29,720 the Canadian Association for Medical Education Merit Teaching Award in 2020. 34 00:02:29,720 --> 00:02:31,280 Congratulations, Dr. Zannell. 35 00:02:31,280 --> 00:02:36,160 Dr. Zannell is a member of the Who's Who in Medical Sciences Education. 36 00:02:36,160 --> 00:02:42,440 In 2022, he was elected as a fellow of the Canadian Academy of Health Sciences in recognition 37 00:02:42,440 --> 00:02:47,080 of sustained excellence in research and teaching within the health sciences. 38 00:02:47,080 --> 00:02:53,640 In 2023, Web of Science identified Dr. Zannell as one of the world's most influential researchers, 39 00:02:53,640 --> 00:02:59,840 selected among an elite group recognized for exceptional research influence, demonstrated 40 00:02:59,840 --> 00:03:06,060 by the production of multiple highly cited papers that rank in the top 1% by citations 41 00:03:06,060 --> 00:03:07,640 for field and year. 42 00:03:07,640 --> 00:03:15,040 Also, in 2022, Dr. Zannell received the Dr. Fred Ioki Career Achievement Award in recognition 43 00:03:15,040 --> 00:03:20,000 of a career of dedication and excellence in multiple domains of medical microbiology and 44 00:03:20,000 --> 00:03:27,560 infectious diseases, including research, education, clinical practice, service, and administration. 45 00:03:27,560 --> 00:03:38,160 All right, thank you, Dr. Zannell, for coming on another episode of our podcast, The Canadian 46 00:03:38,160 --> 00:03:39,160 Breakpoint. 47 00:03:39,160 --> 00:03:44,720 I think a lot of our listeners have heard you from our previous season in episode 6 48 00:03:44,720 --> 00:03:49,760 and then episode 10 as well, talking to us a little bit about the CLEAR registry. 49 00:03:49,760 --> 00:03:55,320 And so just to remind our listeners, this is the Canadian Leadership on Antimicrobial 50 00:03:55,320 --> 00:03:57,720 Real-Life Usage Registry. 51 00:03:57,720 --> 00:04:02,040 And so without further ado, I do want Dr. Zannell to kind of introduce the CLEAR registry 52 00:04:02,040 --> 00:04:07,520 again, just give our listeners, and maybe we have some new listeners too this season, 53 00:04:07,520 --> 00:04:11,040 but it would be nice to see kind of, you know, what's changed, what's the ultimate purpose 54 00:04:11,040 --> 00:04:12,040 of this registry. 55 00:04:12,040 --> 00:04:16,680 Dr. Ipita, I'm delighted to be back and I thank you so much for the invitation. 56 00:04:16,680 --> 00:04:21,520 I've had lots of feedback from the prior podcast we've done. 57 00:04:21,520 --> 00:04:25,160 Colleagues across the country have been emailing me how when I start talking, they have a 58 00:04:25,160 --> 00:04:26,920 wonderful sleep. 59 00:04:26,920 --> 00:04:31,160 So they enjoy the podcast because George Zannell is teaching and they're sleeping. 60 00:04:31,160 --> 00:04:34,440 So I'm delighted to come back. 61 00:04:34,440 --> 00:04:36,720 You know, thank you to everyone who's part of CLEAR. 62 00:04:36,720 --> 00:04:38,580 We're going to be talking a lot about CLEAR. 63 00:04:38,580 --> 00:04:39,760 What is it? 64 00:04:39,760 --> 00:04:47,880 In brief, this is a national across Canada registry that really serves to capture data 65 00:04:47,880 --> 00:04:56,640 and then share data on how new IV antimicrobials are being used by clinicians in the Canadian 66 00:04:56,640 --> 00:04:58,600 setting across Canada. 67 00:04:58,600 --> 00:05:05,360 And the real purpose is to inform clinicians about why new IV antimicrobials are being 68 00:05:05,360 --> 00:05:11,720 used, how they're being used, are they working, what are the side effects in the Canadian 69 00:05:11,720 --> 00:05:14,200 context by Canadian clinicians. 70 00:05:14,200 --> 00:05:15,200 Yes. 71 00:05:15,200 --> 00:05:20,320 We've talked about this multiple times, but I'm just so grateful that this data exists. 72 00:05:20,320 --> 00:05:23,960 Today specifically, we're going to be talking about IV septobiprote. 73 00:05:23,960 --> 00:05:28,420 So we've done previous episodes on kind of the introduction of CLEAR registry when we 74 00:05:28,420 --> 00:05:31,280 had episode six in season two. 75 00:05:31,280 --> 00:05:35,440 So our listeners can tune into that if they just want to have the basics of the CLEAR 76 00:05:35,440 --> 00:05:40,400 registry, what medications are we looking at and what data we're collecting. 77 00:05:40,400 --> 00:05:46,520 And then our last episode of last season, we also went through IVOSFO, so IV fosfomycin, 78 00:05:46,520 --> 00:05:50,920 and really went through the indications and what the data was showing across the nation. 79 00:05:50,920 --> 00:05:54,600 So today we'll be focusing on IV septobiprote. 80 00:05:54,600 --> 00:05:59,800 And so specifically for septobiprote, Dr. Zanel, what specific data have you collected 81 00:05:59,800 --> 00:06:03,460 within the registry and what are our experiences? 82 00:06:03,460 --> 00:06:04,960 So thank you for that. 83 00:06:04,960 --> 00:06:11,720 As you've said, CLEAR has data on IV septobiprote, that's our focus today. 84 00:06:11,720 --> 00:06:17,920 But as a quick reminder to listeners, CLEAR is collecting data on intravenous fosfomycin, 85 00:06:17,920 --> 00:06:22,920 intravenous ceftolzentezo-bactam, and intravenous dalbovansin. 86 00:06:22,920 --> 00:06:25,100 So we've got a lot of good data out there. 87 00:06:25,100 --> 00:06:32,840 But specifically for IV septobiprote, in a nutshell, an overall summary, what clinicians 88 00:06:32,840 --> 00:06:39,720 are telling us in Canada is that they use this drug to treat on-label indications, meaning 89 00:06:39,720 --> 00:06:43,960 indications that are Health Canada approved, and there are only two, community-acquired 90 00:06:43,960 --> 00:06:48,340 bacterial pneumonia and hospital-acquired bacterial pneumonia. 91 00:06:48,340 --> 00:06:51,260 But they're using it a lot also off-label. 92 00:06:51,260 --> 00:06:54,800 And we'll talk about the indications that they're using it for. 93 00:06:54,800 --> 00:06:58,580 It is mostly being used as directed therapy. 94 00:06:58,580 --> 00:07:03,060 So we actually have a pathogen that we have grown. 95 00:07:03,060 --> 00:07:08,080 So we'll talk about it's being used to treat a variety of infections, but almost all the 96 00:07:08,080 --> 00:07:13,200 time they are documented MRSA infections. 97 00:07:13,200 --> 00:07:19,960 So infections due to MRSA, usually we'll talk about that clinicians have regimens, they're 98 00:07:19,960 --> 00:07:27,800 using daptomycin or vancomycin, or potentially both, to treat documented MRSA infections. 99 00:07:27,800 --> 00:07:29,360 And patients are doing poorly. 100 00:07:29,360 --> 00:07:31,420 They're clinically failing. 101 00:07:31,420 --> 00:07:37,120 So clinicians are typically adding septobiprote to the daptomycin. 102 00:07:37,120 --> 00:07:43,960 They're adding septobiprote to the vanco, or they're adding septobiprote to dapto and 103 00:07:43,960 --> 00:07:45,480 vancomycin. 104 00:07:45,480 --> 00:07:53,680 And what we've seen is we have surprisingly very high microbiological eradication rates, 105 00:07:53,680 --> 00:07:55,480 high clinical cure rates. 106 00:07:55,480 --> 00:07:58,480 And then lastly, no surprise, it's a cephalosporin. 107 00:07:58,480 --> 00:08:02,120 It's a beta-lactam, typically very safe drugs. 108 00:08:02,120 --> 00:08:06,360 And this is a safe cephalosporin with very few side effects. 109 00:08:06,360 --> 00:08:11,400 Essentially, the only thing we've seen are a few episodes of hypersensitivity. 110 00:08:11,400 --> 00:08:14,360 No surprise, it has the beta-lactam nucleus. 111 00:08:14,360 --> 00:08:19,120 So all in all, some really great news for septobiprote in Canada. 112 00:08:19,120 --> 00:08:20,120 Okay. 113 00:08:20,120 --> 00:08:26,360 Yeah, and actually I've seen it recently on a lot of our susceptibility reporting come 114 00:08:26,360 --> 00:08:32,640 up because here where I'm practicing in Saskatchewan, we do have high MRSA rates. 115 00:08:32,640 --> 00:08:39,040 And a lot of times we're running into issues with higher MICs with vancomycin and other 116 00:08:39,040 --> 00:08:40,460 medications. 117 00:08:40,460 --> 00:08:45,320 And also practicing in the pediatric world, we don't have too much data on linesalid and 118 00:08:45,320 --> 00:08:48,240 daptomycin in terms of dothing and indications. 119 00:08:48,240 --> 00:08:54,280 And so it's nice to see that there is a beta-lactam because for us, pediatricians, beta-lactams 120 00:08:54,280 --> 00:09:00,340 are, and I think for prescribers in general, but beta-lactams are kind of our go-to drugs. 121 00:09:00,340 --> 00:09:05,840 And so it's nice to see that there's something else on the market for us in terms of MRSA 122 00:09:05,840 --> 00:09:06,840 management. 123 00:09:06,840 --> 00:09:10,800 And so you mentioned that most people are using it as combination therapy. 124 00:09:10,800 --> 00:09:16,600 Are there indications or have people had real life usage experience with using it as monotherapy 125 00:09:16,600 --> 00:09:18,520 in any states? 126 00:09:18,520 --> 00:09:19,520 Yes. 127 00:09:19,520 --> 00:09:21,320 So excellent points. 128 00:09:21,320 --> 00:09:24,720 And a quick thing you brought up was the pediatric side. 129 00:09:24,720 --> 00:09:29,480 I will say that the indications for this drug are in adults. 130 00:09:29,480 --> 00:09:35,920 However, clinicians in Canada, risk versus benefit, we've had several submissions of 131 00:09:35,920 --> 00:09:41,920 septobipril being used in children and it's showing that it was safe and effective. 132 00:09:41,920 --> 00:09:47,480 So the power of the clear registry is not what we think people are doing, but we actually 133 00:09:47,480 --> 00:09:49,840 find out what they're really doing. 134 00:09:49,840 --> 00:09:54,120 These are experts like you who are saying, look, in this case, risk versus benefit, I'm 135 00:09:54,120 --> 00:09:56,520 going to use the agent and it's working. 136 00:09:56,520 --> 00:10:03,440 What we've seen in Canada is the patients who are being treated are 94% of them are 137 00:10:03,440 --> 00:10:05,120 bacteremic. 138 00:10:05,120 --> 00:10:12,080 So the vast majority of them are bacteremic with MRSA, 30% of them are in the ICU. 139 00:10:12,080 --> 00:10:14,840 The other 70% are on the ward. 140 00:10:14,840 --> 00:10:21,720 The most common indication is endocarditis, but patients also being treated for hospital 141 00:10:21,720 --> 00:10:25,240 acquired bacterial pneumonia, community acquired pneumonia. 142 00:10:25,240 --> 00:10:32,120 A lot of patients with bone and joint infections, device related infections, central nervous 143 00:10:32,120 --> 00:10:38,880 system infections, complicated intra abdominal infections, complicated skin soft tissue infections. 144 00:10:38,880 --> 00:10:47,180 So a variety of infections, but virtually everyone is bacteremic and we've grown MRSA. 145 00:10:47,180 --> 00:10:52,280 So we have actually directed therapy against MRSA. 146 00:10:52,280 --> 00:10:59,360 And if we look at in terms of the combination therapy, so 25% of the time it's being used 147 00:10:59,360 --> 00:11:00,600 alone. 148 00:11:00,600 --> 00:11:05,880 Patients are saying, okay, look, I've got MRSA, I'm treating endocarditis, I'm treating 149 00:11:05,880 --> 00:11:08,520 a pneumonia, treating a bone and joint. 150 00:11:08,520 --> 00:11:14,460 The vanco, the Daptomycin that the patients are on is not working. 151 00:11:14,460 --> 00:11:17,600 That's the most likely indication for ceftobiprol. 152 00:11:17,600 --> 00:11:20,040 The other agents are clinically failing. 153 00:11:20,040 --> 00:11:24,400 They'll stop vanco Dapto and use ceftobiprol alone. 154 00:11:24,400 --> 00:11:28,140 And the outcomes that we'll talk about are very, very, very good. 155 00:11:28,140 --> 00:11:34,440 But the majority of the time, 75% of the time they're saying, no, no, no, no, no. 156 00:11:34,440 --> 00:11:41,840 Yes I'm failing Dapto, yes I'm failing vanco, but I'm going to add on ceftobiprol because 157 00:11:41,840 --> 00:11:44,200 I'm worried, I'm clinically doing poorly. 158 00:11:44,200 --> 00:11:48,040 I've got bacteremia, I got endocarditis, I got a pneumonia, I got bone. 159 00:11:48,040 --> 00:11:53,200 I'm going to add on ceftobiprol and the drug is working. 160 00:11:53,200 --> 00:11:57,140 And interestingly now this is the Canadian experience, but then we reviewed the world 161 00:11:57,140 --> 00:11:58,140 literature. 162 00:11:58,140 --> 00:12:04,280 This is actually quite common of what is happening throughout European countries who've published 163 00:12:04,280 --> 00:12:08,720 a lot in Italy, in Spain, and in other countries. 164 00:12:08,720 --> 00:12:15,960 The same experience, ceftobiprol can be used alone and it works well, but frequently clinicians 165 00:12:15,960 --> 00:12:21,800 are adding it to vanco and Dapto when they have a documented MRSA infection. 166 00:12:21,800 --> 00:12:28,080 Okay, and so what dosage has been kind of reported in the clear registry in terms of 167 00:12:28,080 --> 00:12:32,400 all of those infections or does it vary based on the infection that we're treating? 168 00:12:32,400 --> 00:12:37,340 So it does vary, but I will say, and this is the great thing about the clear registry, 169 00:12:37,340 --> 00:12:42,920 you know, half of the data submitters are clinical pharmacists, half of the data submitters 170 00:12:42,920 --> 00:12:46,140 are infectious disease medical microbiologists. 171 00:12:46,140 --> 00:12:51,900 And what we've seen is that in every patient treated with intravenous ceftobiprol in Canada, 172 00:12:51,900 --> 00:12:57,620 it is clear that ID, micro and pharmacy are working together, customizing that dose based 173 00:12:57,620 --> 00:13:05,180 on renal function, but also the vast majority of patients actually get the pharmacodynamically 174 00:13:05,180 --> 00:13:12,600 optimized dose that's in the product monograph that is infusing it over two hours or more 175 00:13:12,600 --> 00:13:15,580 to maximize the time above the MIC. 176 00:13:15,580 --> 00:13:20,400 So the majority of clinicians are saying, okay, first of all, what's my renal function? 177 00:13:20,400 --> 00:13:25,740 And they'll customize it to the renal function, but then they're optimizing the pharmacodynamics 178 00:13:25,740 --> 00:13:27,860 by prolonging the infusion. 179 00:13:27,860 --> 00:13:34,340 So the most common dose is 500 milligrams every eight hours, and I'm talking in adults. 180 00:13:34,340 --> 00:13:41,100 However, we've seen a lot of dosing of 500 Q12 to 50 Q12 to 50 Q24. 181 00:13:41,100 --> 00:13:46,580 So depending on the renal function, but the majority of the time it's being optimized 182 00:13:46,580 --> 00:13:49,780 pharmacodynamically with prolonged infusion. 183 00:13:49,780 --> 00:13:50,780 That's good to know. 184 00:13:50,780 --> 00:13:51,780 Yeah. 185 00:13:51,780 --> 00:13:54,900 And so I think most of our listeners, if they're not pharmacists themselves, can reach out 186 00:13:54,900 --> 00:14:00,340 to their pharmacists and really get some support in terms of for this clinical indication, 187 00:14:00,340 --> 00:14:06,260 for this patient, what would be the best dose and regimen is what I'm hearing from that. 188 00:14:06,260 --> 00:14:12,020 So in terms of kind of switching gears to the micro data, do we have specific break 189 00:14:12,020 --> 00:14:16,900 points for septobipral that can be reported and what type of antimicrobial susceptibility 190 00:14:16,900 --> 00:14:18,780 testing our labs doing? 191 00:14:18,780 --> 00:14:21,020 So we do have break points. 192 00:14:21,020 --> 00:14:26,540 I will say that septobipral is not available in United States. 193 00:14:26,540 --> 00:14:29,500 They have seftarilene available, which is similar. 194 00:14:29,500 --> 00:14:35,220 We do not have seftarilene in Canada, but septobipral is available in the majority of 195 00:14:35,220 --> 00:14:36,500 European countries. 196 00:14:36,500 --> 00:14:39,460 And so we have UCAS break points. 197 00:14:39,460 --> 00:14:45,980 Health Canada has adopted break points typically of one, two, four, less than or equal to one, 198 00:14:45,980 --> 00:14:51,400 S greater than or equal to four being R. But what we've seen in Canada, and I think this 199 00:14:51,400 --> 00:14:58,540 is because of our Can Ward study, Dr. We have a national surveillance study that we have 200 00:14:58,540 --> 00:15:00,540 been running since 2007. 201 00:15:00,540 --> 00:15:05,000 We partner with Health Canada, our friends in Winnipeg here across the street. 202 00:15:05,000 --> 00:15:09,820 And we have been testing septobipral for a very long time. 203 00:15:09,820 --> 00:15:15,300 We have never found an MRSA that's been resistant to septobipral in Canada. 204 00:15:15,300 --> 00:15:20,660 We've actually never found a staph aureus that's been resistant to septobipral in Canada. 205 00:15:20,660 --> 00:15:24,220 So I think clinicians are aware of that data. 206 00:15:24,220 --> 00:15:32,100 And with clear 70% of the time when clinicians are using septobipral in Canada to treat a 207 00:15:32,100 --> 00:15:37,700 documented MRSA infection, they do not even do susceptibility testing. 208 00:15:37,700 --> 00:15:44,340 You know, but a third of the time they do and they're using everything from e-test or 209 00:15:44,340 --> 00:15:47,420 discs and they're showing susceptibility. 210 00:15:47,420 --> 00:15:52,020 But the majority of the time clinicians are saying, look, I know that this staph aureus, 211 00:15:52,020 --> 00:15:54,900 I know that this MRSA will be susceptible. 212 00:15:54,900 --> 00:15:59,460 So they just started without doing susceptibility testing. 213 00:15:59,460 --> 00:16:02,700 And they're also adding it to Vanco or Dapto. 214 00:16:02,700 --> 00:16:10,140 So very rarely are clinicians using septobipral because there's actually documented resistance 215 00:16:10,140 --> 00:16:11,140 to Vanco or Dapto. 216 00:16:11,140 --> 00:16:17,800 Typically, you know, the MIC is one or maybe two or 0.5 to these agents, but they're clinically 217 00:16:17,800 --> 00:16:19,500 failing Vanco or Dapto. 218 00:16:19,500 --> 00:16:25,700 So they are adding the septobipral and there's good data that septobipral because it's a 219 00:16:25,700 --> 00:16:32,820 beta-lactam and inhibits penicillin binding proteins focusing on 1A1B3, but it actually 220 00:16:32,820 --> 00:16:39,900 interacts synergistically with vancomycin, which is more of a glycosylation inhibitor 221 00:16:39,900 --> 00:16:45,620 or Dapto, which is a membrane insertion inhibitor. 222 00:16:45,620 --> 00:16:47,160 So there's synergy. 223 00:16:47,160 --> 00:16:49,800 So they're saying, you know what, I don't need to do MIC testing. 224 00:16:49,800 --> 00:16:51,220 I know it'll be susceptible. 225 00:16:51,220 --> 00:16:56,580 Plus I'm using it as part of a combination regimen and I know I'm going to get synergy 226 00:16:56,580 --> 00:16:58,020 and it's working. 227 00:16:58,020 --> 00:17:02,220 And with it being a beta-lactam and us having so much experience with other beta-lactams, 228 00:17:02,220 --> 00:17:07,540 I think it makes it easier to kind of trust the penetration into certain tissues, especially 229 00:17:07,540 --> 00:17:12,940 with us, you know, like I deal with a lot of bone and joint infections with MRSA and 230 00:17:12,940 --> 00:17:14,920 including bacteremias. 231 00:17:14,920 --> 00:17:21,820 And oftentimes in the pediatric population we'll have low vanco troughs and I, you know, 232 00:17:21,820 --> 00:17:25,340 I'm not seeing clinical cure in that context. 233 00:17:25,340 --> 00:17:29,280 And so that's kind of when I resort to an agent like septobipral. 234 00:17:29,280 --> 00:17:32,940 You know, I'll say a couple of things there and this is, you know, a different podcast. 235 00:17:32,940 --> 00:17:35,740 Vancomycin as you know, is not a great drug. 236 00:17:35,740 --> 00:17:42,100 This was one of my first publications back in the mid 80s to show you how old I am. 237 00:17:42,100 --> 00:17:48,340 We reviewed the literature on Mississippi mud, which was isolated in 1956. 238 00:17:48,340 --> 00:17:49,580 It's not a great agent. 239 00:17:49,580 --> 00:17:56,100 We've lumped it as being bactericidal, but it is not nearly as bactericidal as adaptomycin 240 00:17:56,100 --> 00:17:59,740 or a penicillin or a cephalosporin or a carbapenem. 241 00:17:59,740 --> 00:18:04,820 This is a weekly bactericidal drug and we've kind of continued to use it. 242 00:18:04,820 --> 00:18:05,820 Why? 243 00:18:05,820 --> 00:18:06,820 It's cheap. 244 00:18:06,820 --> 00:18:12,660 We much rather use something that is more rapidly bactericidal like adaptomycin or a 245 00:18:12,660 --> 00:18:14,620 beta-lactam like septobipral. 246 00:18:14,620 --> 00:18:20,660 Well, we've literally used it just because it's cheap, but the synergy part is something 247 00:18:20,660 --> 00:18:24,220 that is important in terms of the beta-lactam. 248 00:18:24,220 --> 00:18:29,460 You know, the great thing about cephalosporin, septobipral being one is clinicians like you 249 00:18:29,460 --> 00:18:32,480 consider it to be one of the safest drugs in the world, right? 250 00:18:32,480 --> 00:18:39,260 If you're not going to be one of the ones who drops dead anaphylaxis, one in 80,000 251 00:18:39,260 --> 00:18:43,340 that drops dead of anaphylaxis, these are the safest drugs in the world, whether it's 252 00:18:43,340 --> 00:18:48,220 in pregnancy, whether it's in lactation, whether it's in the very young, whether it's in the 253 00:18:48,220 --> 00:18:53,700 very old, the critically ill, these are proven safe drugs and so clinicians like you like 254 00:18:53,700 --> 00:18:54,700 to use them. 255 00:18:54,700 --> 00:18:55,700 Yeah. 256 00:18:55,700 --> 00:19:01,020 And that being said, I guess like in the registry, have people mentioned any side effects like 257 00:19:01,020 --> 00:19:05,140 outside of I would say like beta-lactam induced neutropenia? 258 00:19:05,140 --> 00:19:09,460 That would probably be probably the most common thing that I would see clinically when I use 259 00:19:09,460 --> 00:19:13,620 beta-lactams, but are there any side effects that have been reported? 260 00:19:13,620 --> 00:19:18,700 So they have reported side effects and I want to go back to talking about the types of patients, 261 00:19:18,700 --> 00:19:24,220 the majority are bacteremic, you know, a third are in the ICU so they're critically ill. 262 00:19:24,220 --> 00:19:33,780 In terms of is it working, we've shown 94% microbiological success, which is really astonishing 263 00:19:33,780 --> 00:19:39,580 considering these patients have documented MRSA, a lot of endocarditis, their bacteremic, 264 00:19:39,580 --> 00:19:46,700 their failing vanco and dapto, clinically 85% success rates, you know, patients getting 265 00:19:46,700 --> 00:19:49,580 better, which is what you're really interested in. 266 00:19:49,580 --> 00:19:55,280 And in that setting, the vast majority have had no side effects whatsoever. 267 00:19:55,280 --> 00:20:02,960 So really sick people, bacteremic, endocarditis, bone and joint, pneumonia, MRSA, failing vanco 268 00:20:02,960 --> 00:20:09,080 dapto, clinically they're doing well, and the vast majority no side effects whatsoever. 269 00:20:09,080 --> 00:20:16,340 We have seen a little bit of hypersensitivity, you know, this is typically our rashes, et 270 00:20:16,340 --> 00:20:17,380 cetera. 271 00:20:17,380 --> 00:20:24,180 In only one of those cases have Canadian clinicians told us the drug had to be discontinued. 272 00:20:24,180 --> 00:20:29,700 We had one patient who had hypersensitivity and had blisters and the clinician said we're 273 00:20:29,700 --> 00:20:35,260 going to have to stop the drug and go to a different therapeutic category. 274 00:20:35,260 --> 00:20:39,660 But you know, we're getting close to 100 patients here and clinicians are telling us this is 275 00:20:39,660 --> 00:20:42,300 an unbelievably safe drug. 276 00:20:42,300 --> 00:20:48,000 The only thing they've seen is a little bit of hypersensitivity, but in only one patient 277 00:20:48,000 --> 00:20:50,660 did it lead to stopping the drug. 278 00:20:50,660 --> 00:20:54,860 You know, I always focus on, okay, you've got a side effect, but was it bad enough to 279 00:20:54,860 --> 00:20:55,860 stop? 280 00:20:55,860 --> 00:20:59,900 No, the majority of the time, even if there's a side effect like hypersensitivity, they 281 00:20:59,900 --> 00:21:00,900 continue. 282 00:21:00,900 --> 00:21:06,620 So a lot of good news here, the drug is working and despite treating really sick people, very, 283 00:21:06,620 --> 00:21:10,740 very few side effects, which is what you would expect with a cephalospora. 284 00:21:10,740 --> 00:21:12,740 I agree. 285 00:21:12,740 --> 00:21:16,900 And then being part of the beta-lactam, we already know that they're good drugs, they 286 00:21:16,900 --> 00:21:21,820 work well and you know, rarely we run into severe side effects. 287 00:21:21,820 --> 00:21:23,880 So that's fantastic. 288 00:21:23,880 --> 00:21:28,580 And so in terms of, we already mentioned kind of the outcomes for our patients, which is 289 00:21:28,580 --> 00:21:33,300 fantastic for this drug, which I'm actually grateful to hear because you know, there's 290 00:21:33,300 --> 00:21:39,180 a lot of times when you're, as a clinician, it's very stressful when there's MRSA and 291 00:21:39,180 --> 00:21:44,260 you don't have your patients not doing very well because we know that MRSA causes serious 292 00:21:44,260 --> 00:21:47,260 infections or patients are very, very sick. 293 00:21:47,260 --> 00:21:48,740 They can have very poor outcomes. 294 00:21:48,740 --> 00:21:54,800 And so to know that we have another drug on the market that's available to us is fantastic. 295 00:21:54,800 --> 00:22:00,620 So in terms of accessibility, so I know like this probably very center by center, but is 296 00:22:00,620 --> 00:22:07,060 septobiprl on formulary in a lot of provinces or is this a health Canada approved drug that 297 00:22:07,060 --> 00:22:10,180 we have to get special access for? 298 00:22:10,180 --> 00:22:15,820 Health Canada approved and the majority of hospitals have it on the formulary. 299 00:22:15,820 --> 00:22:18,180 It's available for you to use. 300 00:22:18,180 --> 00:22:21,620 You know, I talk to clinicians a lot about special access drugs. 301 00:22:21,620 --> 00:22:25,620 I'm delighted to say this is not a special access drug. 302 00:22:25,620 --> 00:22:29,820 Special access drugs work well in Canada for these chronic conditions that you're going 303 00:22:29,820 --> 00:22:32,880 to have for weeks, months, years. 304 00:22:32,880 --> 00:22:37,800 Special access clinicians have told us over and over is a disaster for clinicians like 305 00:22:37,800 --> 00:22:43,500 you who are treating a patient with an acute infectious disease, where ideally if you choose 306 00:22:43,500 --> 00:22:49,660 to use the drug, you want to use it within an hour or two, not wait five days or 10 days. 307 00:22:49,660 --> 00:22:55,300 So I'm delighted to say this is health Canada approved is on the majority of hospital formularies 308 00:22:55,300 --> 00:23:00,300 and it's available to be used right off the shelf, which is very, very good. 309 00:23:00,300 --> 00:23:01,300 Okay. 310 00:23:01,300 --> 00:23:02,660 That's great to hear. 311 00:23:02,660 --> 00:23:07,060 And so for our listeners, you know, in the past we've talked a little bit about the data 312 00:23:07,060 --> 00:23:10,880 that you've presented and where to find this data. 313 00:23:10,880 --> 00:23:15,060 And so for septobiprl specifically, I think you mentioned that there's more than a hundred 314 00:23:15,060 --> 00:23:17,460 experiences that you've looked at. 315 00:23:17,460 --> 00:23:22,700 And so where can some of our listeners reach out to see some of the resources or some of 316 00:23:22,700 --> 00:23:24,500 this published data? 317 00:23:24,500 --> 00:23:33,020 Our general clear vision has been that every IV antimicrobial, every new one that comes 318 00:23:33,020 --> 00:23:41,040 onto the clear registry, we will define its use and share the data with all clinicians 319 00:23:41,040 --> 00:23:46,720 in Canada who are clear participants for septobiprl no different. 320 00:23:46,720 --> 00:23:51,460 My vision is that it's on the clear registry for maximum two to three years. 321 00:23:51,460 --> 00:23:55,300 And then three years later, clinicians know all about the drug. 322 00:23:55,300 --> 00:23:58,860 It moves off the registry and we move on now and you drugs. 323 00:23:58,860 --> 00:24:04,980 So our typical plan is, and this is what we've done with septobiprl is once we hit about 324 00:24:04,980 --> 00:24:08,940 20 ish or 30 patients, we present an amy poster. 325 00:24:08,940 --> 00:24:13,940 And we did that with septobiprl in 2022. 326 00:24:13,940 --> 00:24:19,980 Once we hit 50 patients, we published a paper in the journal of global antimicrobial resistance 327 00:24:19,980 --> 00:24:21,820 in 2022. 328 00:24:21,820 --> 00:24:28,540 And then once we hit more than that 50, 60, we had a second amy poster, which we presented 329 00:24:28,540 --> 00:24:30,300 in 2022. 330 00:24:30,300 --> 00:24:36,340 Now that we're approaching a hundred patients, I would like people to continue to hit that 331 00:24:36,340 --> 00:24:39,060 clear link and get us over a hundred. 332 00:24:39,060 --> 00:24:44,900 We've committed to writing our third and final amy poster for this December of 2023. 333 00:24:44,900 --> 00:24:50,580 We'll present that poster in the new year in Vancouver. 334 00:24:50,580 --> 00:24:56,260 And then once we get over a hundred, we will write the final paper and that'll be the final 335 00:24:56,260 --> 00:25:01,520 chapter of how is septobiprl being used in Canada. 336 00:25:01,520 --> 00:25:09,940 And so I'm hoping perhaps by mid 2024, we will wrap up septobiprl and clear with the 337 00:25:09,940 --> 00:25:16,300 poster at amy in 2024 and then the publication in mid 2024. 338 00:25:16,300 --> 00:25:21,260 And then we'll move on to another agent, but please keep hitting that link, whether it's 339 00:25:21,260 --> 00:25:27,400 septobiprl, you know, whether it's a subtols, ain't taso, Dalva Vance and or IV phospho. 340 00:25:27,400 --> 00:25:29,300 We really need all your help. 341 00:25:29,300 --> 00:25:30,780 Thank you so much for doing that. 342 00:25:30,780 --> 00:25:31,780 Fantastic. 343 00:25:31,780 --> 00:25:35,940 And I think, I mean, all of us, I mean, the more submitters we have, the more data we 344 00:25:35,940 --> 00:25:41,100 have, the easier it is for us clinicians as well, because we then have more and more real 345 00:25:41,100 --> 00:25:42,100 life experience. 346 00:25:42,100 --> 00:25:44,400 So thank you so much, Dr. Zanell. 347 00:25:44,400 --> 00:25:49,460 It's always a pleasure having you on the podcast and especially talking about some of these 348 00:25:49,460 --> 00:25:54,560 newer agents that we don't have that much information about, and we don't have Canadian 349 00:25:54,560 --> 00:25:57,520 based information outside of clear registry. 350 00:25:57,520 --> 00:26:02,860 So it's fantastic that we have a resource like this and it's fantastic that, you know, 351 00:26:02,860 --> 00:26:05,460 our listeners can reach out to your registry. 352 00:26:05,460 --> 00:26:10,340 They could submit cases, they can be involved in this and like we've mentioned previously. 353 00:26:10,340 --> 00:26:16,180 And so we really, really appreciate all the support that you've given to our podcast. 354 00:26:16,180 --> 00:26:19,940 And thank you so much again for such an educational conversation. 355 00:26:19,940 --> 00:26:27,500 Dr. Rupia, two quick thank yous first to the clear participants and for the podcast listeners 356 00:26:27,500 --> 00:26:32,180 who don't know, you can just Google George Zanell and you'll find my email, send me an 357 00:26:32,180 --> 00:26:35,620 email, say I want to be a clear participant and it's free. 358 00:26:35,620 --> 00:26:37,940 What do you get for that every two, three months? 359 00:26:37,940 --> 00:26:43,480 I send all the clear participants, all of the slides of the new agents, how they're 360 00:26:43,480 --> 00:26:44,480 being used. 361 00:26:44,480 --> 00:26:48,980 So you keep up with your colleagues knowing how these agents are being used, but we also 362 00:26:48,980 --> 00:26:49,980 send you the links. 363 00:26:49,980 --> 00:26:54,220 And if you are motivated and you've treated a patient or have treated or will treat a 364 00:26:54,220 --> 00:26:59,060 patient with one of the drugs on the registry, just hit that link and in three minutes, point, 365 00:26:59,060 --> 00:27:02,340 click, point, click, and you are done entering the data. 366 00:27:02,340 --> 00:27:08,340 So we've got 400 participants, half of them are AMI members, half are CSHP members, half 367 00:27:08,340 --> 00:27:11,500 ID, micro, half clinical pharmacy. 368 00:27:11,500 --> 00:27:16,100 And I'm very thankful for everything that they do, all clear participants. 369 00:27:16,100 --> 00:27:18,060 And lastly, thank you to you. 370 00:27:18,060 --> 00:27:20,860 For me, it's an honor to be part of your podcast. 371 00:27:20,860 --> 00:27:23,020 I know people, I see them running down the street. 372 00:27:23,020 --> 00:27:27,620 They've got earbuds in, I know what they're listening to, they're listening to what they 373 00:27:27,620 --> 00:27:28,660 are podcasting. 374 00:27:28,660 --> 00:27:29,660 Let's hope so. 375 00:27:29,660 --> 00:27:37,020 I think we've had a lot of support and success based on the last few seasons that we've done. 376 00:27:37,020 --> 00:27:43,740 And so we hope to continue to provide more educational information. 377 00:27:43,740 --> 00:27:48,500 And I always like to tell everybody that the podcast is really designed for informational 378 00:27:48,500 --> 00:27:55,140 and educational purposes and it's never to endorse a product or an idea or an agent. 379 00:27:55,140 --> 00:28:00,340 And really, I think it's important for us to get together in our community of learners 380 00:28:00,340 --> 00:28:04,940 and to continue learning through interfaces such as the podcast. 381 00:28:04,940 --> 00:28:06,420 So it's fantastic. 382 00:28:06,420 --> 00:28:10,260 It's honestly a lot of support from our listeners and a lot of support from our guests. 383 00:28:10,260 --> 00:28:11,900 So we really appreciate it. 384 00:28:11,900 --> 00:28:12,900 Thank you so much. 385 00:28:12,900 --> 00:28:13,900 Thanks. 386 00:28:13,900 --> 00:28:14,900 Take care. 387 00:28:14,900 --> 00:28:18,940 Thank you, Dr. Rapina and Dr. Zanel for this valuable review. 388 00:28:18,940 --> 00:28:29,380 To join the CLEAR registry, email drzanel at ggzanel, z-h-a-n-e-l, at pcsinternet.ca. 389 00:28:29,380 --> 00:28:31,540 Links are in the episode description. 390 00:28:31,540 --> 00:28:33,460 Have a topic suggestion? 391 00:28:33,460 --> 00:28:40,180 Email us at thecanadianbreakpoint at gmail.com and follow us on ex, formerly Twitter, at 392 00:28:40,180 --> 00:28:41,500 CA Breakpoint. 393 00:28:41,500 --> 00:28:49,420 See you again soon at the Canadian Breakpoint.