WEBVTT 1 00:00:00.080 --> 00:00:03.759 Imagine a patient comes into your clinic, right, their jaw 2 00:00:03.919 --> 00:00:06.679 is just it's swollen to the size of a grapefruit. 3 00:00:06.719 --> 00:00:10.199 Oh yeah, we've all seen it, right, It's inflamed, incredibly painful. 4 00:00:10.599 --> 00:00:12.599 So you admit them, You hook them up to an 5 00:00:12.599 --> 00:00:17.760 IV of the strongest, broadest spectrum antibiotics you have, and 6 00:00:17.800 --> 00:00:19.280 you wait for the swelling. 7 00:00:18.920 --> 00:00:21.519 To go down, and then it does absolutely nothing exactly. 8 00:00:21.559 --> 00:00:25.640 The infection just continues to rage. And why is that. 9 00:00:26.120 --> 00:00:28.760 It's because the most potent drug in the world is 10 00:00:28.879 --> 00:00:34.079 completely useless if the physical terrain like actually prevents it 11 00:00:34.119 --> 00:00:35.359 from reaching the bacteria. 12 00:00:35.520 --> 00:00:38.520 Yeah, you're hitting on honestly, one of the most frustrating 13 00:00:38.560 --> 00:00:41.399 realities in clinical practice. I mean, we train so hard 14 00:00:41.399 --> 00:00:43.320 to memorize which drug kills which. 15 00:00:43.200 --> 00:00:46.000 Bug, right, the classic matching gig exactly. 16 00:00:45.679 --> 00:00:49.840 But we often completely overlook the mechanical delivery system. We 17 00:00:49.880 --> 00:00:52.399 aren't treating a static, plastic model of a job. No, 18 00:00:52.520 --> 00:00:55.560 it's a living thing, right, It's a dynamic, highly compartmentalized 19 00:00:55.600 --> 00:01:00.000 biological system, and the rules of engagement they change entirely 20 00:01:00.399 --> 00:01:03.840 depending on the micro environment of that specific tissue, which. 21 00:01:03.640 --> 00:01:08.200 Is exactly why today's deep dive is custom tailored for you. 22 00:01:08.760 --> 00:01:11.879 So whether you're a dental student you know, prepping for clinicals, 23 00:01:11.879 --> 00:01:15.040 a young professional refining your habits, or just a self 24 00:01:15.079 --> 00:01:18.120 learner who wants to understand the why behind the protocols. 25 00:01:18.200 --> 00:01:20.560 Yeah, the mechanical why is so important. 26 00:01:20.200 --> 00:01:22.959 It really is. We are working through a massive stack 27 00:01:23.000 --> 00:01:26.640 of notes today from the fourteenth edition of Antibiotic. 28 00:01:26.159 --> 00:01:28.560 Essentials, edited by doctor Burke A. Kuna. 29 00:01:28.920 --> 00:01:31.439 That's the one and the mission today isn't just to 30 00:01:31.680 --> 00:01:33.359 like rattle off guideline lists. 31 00:01:33.439 --> 00:01:35.159 Yeah, that's what textbooks are for, right. 32 00:01:35.359 --> 00:01:40.560 We are extracting the core foundational tenets of rational antibiotic 33 00:01:40.680 --> 00:01:44.319 prescribing and mapping them directly onto head, neck, and oral infections. 34 00:01:44.400 --> 00:01:48.719 We're getting into the pharmacokinetics, the physiological barriers, and the 35 00:01:48.799 --> 00:01:52.840 really specific drug quirks that basically dictate success or failure 36 00:01:52.879 --> 00:01:53.560 in dentistry. 37 00:01:53.719 --> 00:01:55.680 So to understand those protocols, I mean, we really have 38 00:01:55.719 --> 00:01:57.359 to start with tissue penetration. 39 00:01:57.040 --> 00:02:00.560 Right, Yeah, absolutely. The textbook emphasizes this r and over, 40 00:02:00.920 --> 00:02:04.640 and antibiotics efficacy is strictly governed by its ability to 41 00:02:04.799 --> 00:02:09.240 literally physically achieve a therapeutic concentration at the side of 42 00:02:09.240 --> 00:02:12.000 the infection. It has to get there first, right, And 43 00:02:12.280 --> 00:02:16.520 in an acute infection like a rapidly spreading facial cellulitis, 44 00:02:17.080 --> 00:02:19.280 the body actually does a lot of the heavy lifting 45 00:02:19.319 --> 00:02:20.080 for the drug. 46 00:02:20.039 --> 00:02:27.080 Because the acute inflammatory response alters the vascular permeability precisely. 47 00:02:27.400 --> 00:02:31.439 You have this localized release of cytokine's histamines, you know, 48 00:02:31.479 --> 00:02:35.360 all those inflammatory mediators, and they cause vasodilation exactly, and 49 00:02:35.400 --> 00:02:38.599 the tight junctions between the endothelial cells that line the 50 00:02:38.599 --> 00:02:42.120 blood vessels they literally pull apart. Oh wow, Yeah, the 51 00:02:42.199 --> 00:02:46.800 vessels become leaky. And this increased microvascular permeability it allows 52 00:02:46.800 --> 00:02:50.199 the antibiotics circulating in the serum to just effortlessly pour 53 00:02:50.280 --> 00:02:53.000 into the interstitial fluid of the infected soft tissue. 54 00:02:53.039 --> 00:02:55.599 Okay, but the textbook draws a pretty hard line. When 55 00:02:55.599 --> 00:03:00.840 that acute cellulitis like organizes into a chronic, walled off abscess. 56 00:03:01.039 --> 00:03:02.639 Oh, it's a completely different ball game. 57 00:03:02.719 --> 00:03:05.039 The rules of tissue penetration completely invert. 58 00:03:05.639 --> 00:03:09.039 They do, because the anatomy of an abscess is fundamentally 59 00:03:09.080 --> 00:03:12.680 different from just inflamed tissue, and abscess is a highly 60 00:03:12.800 --> 00:03:17.759 organized capsule. It's full of necrotic tissue, fibrine, white blood cells, 61 00:03:17.800 --> 00:03:20.120 and just a massive bacterial. 62 00:03:19.560 --> 00:03:20.879 Load, just nasty mix. 63 00:03:21.039 --> 00:03:21.319 Yeah. 64 00:03:21.560 --> 00:03:26.599 But crucially, the interior of that capsule is a vascular 65 00:03:26.759 --> 00:03:30.199 meaning no blood flow exactly. There is zero capillary network 66 00:03:30.240 --> 00:03:32.199 feeding the center of that pus cavity. 67 00:03:32.439 --> 00:03:37.520 So, okay, trying to resolve a mature abscess with a 68 00:03:37.599 --> 00:03:42.439 systemic oral antibiotic, it's essentially like trying to deliver mail 69 00:03:42.520 --> 00:03:45.039 to a house in a neighborhood with no roads. 70 00:03:45.199 --> 00:03:46.240 That's a great way to put it. 71 00:03:46.319 --> 00:03:48.199 Like, it doesn't matter if you have the fastest mail 72 00:03:48.240 --> 00:03:50.520 truck or you know, a million letters, there's no physical 73 00:03:50.520 --> 00:03:52.599 path to the house. That delivery fails. You have to 74 00:03:52.599 --> 00:03:53.400 pave a rate first. 75 00:03:53.599 --> 00:03:58.159 That captures the mechanical reality perfectly. The text states definitively, 76 00:03:58.199 --> 00:04:02.520 and I mean definitively, that antibiotics cannot eradicate organisms from 77 00:04:02.560 --> 00:04:04.039 areas with impaired blood supply. 78 00:04:04.120 --> 00:04:06.840 This is just circulated right past it, right past the capsule. 79 00:04:06.879 --> 00:04:10.280 And this is why surgical intervention, you know, incision and 80 00:04:10.360 --> 00:04:13.800 drainage or I and D is an absolute, non negotiable 81 00:04:13.840 --> 00:04:15.400 prerequisite for a cure. 82 00:04:15.639 --> 00:04:17.040 You literally have to drain it. 83 00:04:17.160 --> 00:04:22.360 You must physically decompress the cavity and establish a drainage route. 84 00:04:22.639 --> 00:04:25.480 You have to alter the physical terrain before the systemic 85 00:04:25.519 --> 00:04:28.319 chemical therapy can even begin to do its job on 86 00:04:28.399 --> 00:04:30.439 the surrounding inflamed tissue. 87 00:04:30.519 --> 00:04:34.040 Okay, so that mechanical reality, it leads right into another 88 00:04:34.199 --> 00:04:38.160 trap the textbook highlights, which is this huge discrepancy between 89 00:04:38.199 --> 00:04:40.720 in vitro and in vivos susceptibility. 90 00:04:40.800 --> 00:04:42.759 Oh, this trips up so many people, right. 91 00:04:42.720 --> 00:04:46.000 Because a clinician sends a pulent sample from say, a 92 00:04:46.040 --> 00:04:50.199 periodontal pocket, to the microbiology lab, and the report comes 93 00:04:50.199 --> 00:04:53.519 back saying the bugs are susceptible to a specific. 94 00:04:53.079 --> 00:04:56.199 Antibiotic, and the immediate temptation is to just write the 95 00:04:56.240 --> 00:04:57.480 prescription exactly. 96 00:04:57.600 --> 00:04:59.360 You see, susceptible, You write the script. 97 00:04:59.399 --> 00:05:02.600 But relying surely on that lab report ignores everything we 98 00:05:02.720 --> 00:05:05.079 just talked about regarding tissue penetration. 99 00:05:04.839 --> 00:05:06.680 Because the lab isn't the human body. 100 00:05:06.800 --> 00:05:09.600 Right. In vitro testing, it happens in this highly controlled, 101 00:05:09.680 --> 00:05:13.639 standardized broth or aggar in a Petrie dish. The lab 102 00:05:13.720 --> 00:05:17.959 is simulating standard serum concentrations of the drug and the blood. 103 00:05:18.439 --> 00:05:21.959 But in vivo, you know, inside the living, breathing patient, 104 00:05:22.600 --> 00:05:25.839 the drug concentration in the serum almost never matches the 105 00:05:25.879 --> 00:05:29.360 concentration deep in the bone matrix or the cerebro spinal 106 00:05:29.399 --> 00:05:32.839 fluid or a necrotic periodontal pocket. 107 00:05:32.680 --> 00:05:35.720 So the lab just assumes a perfect delivery system it does. 108 00:05:36.079 --> 00:05:38.879 A drug might look like an absolute targeted missile strike 109 00:05:38.920 --> 00:05:41.240 in the Petrie dish, but if its molecular size, or 110 00:05:41.240 --> 00:05:44.879 its protein binding affinity or lipid solubility prevents it from 111 00:05:44.920 --> 00:05:47.319 penetrating the actual tissue you're targeting. 112 00:05:46.959 --> 00:05:47.560 It's going to fail. 113 00:05:47.560 --> 00:05:50.759 Clinically, it will completely fail. You always have to cross 114 00:05:50.800 --> 00:05:55.399 reference the lab susceptibility report with the known pharmacokinetic profile 115 00:05:55.519 --> 00:05:58.199 of the drug for that specific anatomical site. 116 00:05:58.240 --> 00:06:00.639 Man, that's wild. Well, let's talk about the actual mechanism 117 00:06:00.720 --> 00:06:03.839 of action once the drug does manage to reach the site. Sure, 118 00:06:04.040 --> 00:06:08.680 the text compares bactericidal drugs right, which actively induce bacterial 119 00:06:08.759 --> 00:06:13.920 cell death, with bacteriostatic drugs, which just inhibit replication processes 120 00:06:14.000 --> 00:06:15.160 like protein synthesis. 121 00:06:15.240 --> 00:06:16.920 Right, the killers versus the pausers. 122 00:06:17.199 --> 00:06:19.879 Yeah, And instinctively, as a patient or a doctor, it 123 00:06:19.920 --> 00:06:24.040 feels like we should always reach for the bacteriicityl you know, 124 00:06:24.079 --> 00:06:25.560 the actively destroying agent. 125 00:06:26.120 --> 00:06:30.560 Most clinicians have that exact instinct. But doctor Kuna's textbook 126 00:06:30.560 --> 00:06:35.120 clarifies that for the vast majority of routine infections, bactericidal 127 00:06:35.199 --> 00:06:39.920 and bacteriostatic antibiotics achieve clinical cure at the exact same rate. 128 00:06:40.199 --> 00:06:45.199 Wait, really, how does simply pausing bacterial replication achieve the 129 00:06:45.319 --> 00:06:48.319 same timeline as actively exploding. 130 00:06:47.879 --> 00:06:50.839 The cell wall Because the antibiotic isn't operating in a 131 00:06:50.920 --> 00:06:54.639 vacuum you know, ok, a bacteriostatic agent, it halts the 132 00:06:54.720 --> 00:06:58.279 exponential growth phase of the pathogen. It pins the bacteria 133 00:06:58.360 --> 00:07:00.600 down so they can't overwhelm the local tissue. 134 00:07:00.720 --> 00:07:01.879 Ah, I see, And at. 135 00:07:01.720 --> 00:07:05.240 That point, the host's own immune system, the neutrophils, the macrophages, 136 00:07:05.319 --> 00:07:08.680 they sweep through and figositize the static bacteria, clean up 137 00:07:08.680 --> 00:07:11.680 the mess exactly, they clear the infection. You are heavily 138 00:07:11.680 --> 00:07:14.879 relying on the patient's endogenous immune response, which. 139 00:07:14.680 --> 00:07:18.720 Means you only strictly require a bactericidal drug when the 140 00:07:18.720 --> 00:07:22.439 immune system, for whatever reason, cannot perform that sweep. 141 00:07:22.720 --> 00:07:25.160 You hit the nail on the head. The textbook lists 142 00:07:25.399 --> 00:07:30.439 very specific, very critical exceptions where bactericidal action is mandatory. 143 00:07:31.319 --> 00:07:34.839 One is endocarditis, because the heart valves actually lack a 144 00:07:34.879 --> 00:07:37.800 dedicated blood supply to deliver those white blood cells. 145 00:07:37.879 --> 00:07:38.519 Oh makes sense. 146 00:07:38.680 --> 00:07:42.160 Another is meningitis due to the immune privileged nature of 147 00:07:42.240 --> 00:07:49.079 the central nervous system. And finally, patients with profound febrel leukopenia. 148 00:07:48.519 --> 00:07:50.279 So patients without an immune system. 149 00:07:50.600 --> 00:07:53.560 Basically, yeah, if a patient doesn't have a functional white 150 00:07:53.600 --> 00:07:57.160 blood cell count, a bacteriostatic drug will just stall the 151 00:07:57.160 --> 00:08:00.079 infection until the pill bottle is empty, and then and 152 00:08:00.079 --> 00:08:02.279 the bacteria will simply resume replicating. 153 00:08:02.759 --> 00:08:06.439 For a standard dental infection in a healthy host, the 154 00:08:06.519 --> 00:08:10.279 distinction between cytyl and static is clinically. 155 00:08:09.879 --> 00:08:11.680 Irrelevant, completely irrelevant. 156 00:08:11.800 --> 00:08:14.439 Wow. Okay, knowing that opens up our options, which really 157 00:08:14.480 --> 00:08:17.720 brings us to the broader strategy of antibiotic selection and 158 00:08:18.360 --> 00:08:20.519 the looming threat of resistance. 159 00:08:20.040 --> 00:08:21.519 The big scary superbugs. 160 00:08:21.839 --> 00:08:22.040 Right. 161 00:08:22.800 --> 00:08:27.759 The text introduces this concept called resistance potential, and we 162 00:08:27.879 --> 00:08:32.759 tend to assume that writing any antibiotic prescription contributes equally 163 00:08:33.080 --> 00:08:35.000 to the global rise of superbugs. 164 00:08:35.240 --> 00:08:37.360 A lot of people think that, but the data actually 165 00:08:37.360 --> 00:08:41.159 shows that acquired resistance is highly drug specific. 166 00:08:41.440 --> 00:08:42.840 Oh interesting, Yeah. 167 00:08:42.639 --> 00:08:47.000 It's a critical distinction. Certain molecular structures inherently drive rapid 168 00:08:47.000 --> 00:08:50.240 resistance like which ones. Well, the book highlights a zittomycin, 169 00:08:50.399 --> 00:08:54.519 especially when used against Streptococcus pneumonia, as having a notoriously 170 00:08:54.559 --> 00:08:55.799 high resistance potential. 171 00:08:55.919 --> 00:08:57.919 Really, even if you don't overprescribe it. 172 00:08:58.080 --> 00:09:01.960 Even with conservative use, the bacteria rapidly acquire or upregulate 173 00:09:02.000 --> 00:09:04.600 these e flex pumps to literally just spit the drug 174 00:09:04.639 --> 00:09:07.639 back out of their cells, or they alter their ribosomal 175 00:09:07.759 --> 00:09:08.840 binding sites. 176 00:09:08.559 --> 00:09:11.120 So the drug just trains the bacteria to defeat it 177 00:09:11.360 --> 00:09:11.879 very quickly. 178 00:09:11.919 --> 00:09:12.159 Yes. 179 00:09:12.399 --> 00:09:16.600 Contrast that with something like doxycycline, which the TEFT categorizes 180 00:09:16.679 --> 00:09:18.240 having a low resistance potential. 181 00:09:18.600 --> 00:09:22.200 Right, I mean, despite decades of heavy widespread use and 182 00:09:22.320 --> 00:09:28.480 everything from acne to respiratory infections, bacteria really struggle to 183 00:09:28.519 --> 00:09:31.480 mount widespread systemic resistance to doxycycline. 184 00:09:31.639 --> 00:09:33.039 Why is that the. 185 00:09:33.000 --> 00:09:37.080 Structural hurdles required for the pathogen to bypass tenttracyclin inhibition 186 00:09:37.240 --> 00:09:38.799 are simply much much higher? 187 00:09:38.919 --> 00:09:39.240 Got it? 188 00:09:40.000 --> 00:09:42.480 So the clinical takeaway here is that when you're designing 189 00:09:42.480 --> 00:09:46.879 an empiric therapy regimen and two drugs offer equivalent coverage 190 00:09:46.879 --> 00:09:49.840 for your suspected bug, you always default to the one 191 00:09:49.919 --> 00:09:52.519 with the intrinsically lower resistance potential. 192 00:09:52.679 --> 00:09:55.000 Okay, that makes sense, But I want to push back 193 00:09:55.000 --> 00:09:57.039 on another strategic paradigm in the text. 194 00:09:57.200 --> 00:09:58.080 Okay, let's hear. 195 00:09:58.200 --> 00:10:00.720 Mono therapy versus common therapy. 196 00:10:00.879 --> 00:10:01.279 Ah. 197 00:10:01.360 --> 00:10:03.080 Yes, the book takes this. 198 00:10:03.159 --> 00:10:07.679 Aggressive stance that monotherapy is almost always preferred. But I mean, 199 00:10:07.720 --> 00:10:11.000 if we are facing a severe mixed flora oral infection, 200 00:10:11.440 --> 00:10:14.080 doesn't throwing two or three different mechanisms of action at 201 00:10:14.080 --> 00:10:16.039 the site guaranteed better coverage. 202 00:10:16.120 --> 00:10:19.080 It definitely seems logical, right, Yeah, but it actually creates 203 00:10:19.159 --> 00:10:23.080 more problems than it solves. Outside of highly specific protocol 204 00:10:23.159 --> 00:10:28.600 driven exceptions like tuberculosis or HIV or certain crazy pseudomonal infections. 205 00:10:29.159 --> 00:10:33.120 Blindly stacking antibiotics does not prevent resistance. 206 00:10:33.279 --> 00:10:34.919 Wait really, what does it do then? 207 00:10:35.000 --> 00:10:38.360 Well, first, it drastically increases the risk of medication errors, 208 00:10:38.360 --> 00:10:41.240 and it compounds the likelihood of adverse side effects. 209 00:10:41.320 --> 00:10:42.840 Double the drugs, double the side. 210 00:10:42.639 --> 00:10:47.039 Effects exactly, But more importantly, you risk competitive antagonism. 211 00:10:47.440 --> 00:10:47.919 What's up? 212 00:10:48.240 --> 00:10:52.000 Okay? Imagine you prescribe a bacteria static drug that halts 213 00:10:52.240 --> 00:10:55.279 cellular processes right right, and at the same time, you 214 00:10:55.320 --> 00:10:59.120 prescribe a bactericidal beta lactum that relies on active cell 215 00:10:59.120 --> 00:11:02.320 wall synthesis to cause the cell to lise and explode. 216 00:11:02.519 --> 00:11:03.720 Oh, I see where this is going. 217 00:11:03.799 --> 00:11:06.759 Yeah, the static drug stops the cell from building its wall, 218 00:11:06.799 --> 00:11:09.360 which actually prevents the sidle drug from working. 219 00:11:09.480 --> 00:11:12.039 Wow, so you are paying double the financial cost to 220 00:11:12.080 --> 00:11:14.559 create chemical interference in the patient's own body. 221 00:11:14.679 --> 00:11:15.159 Exactly. 222 00:11:15.639 --> 00:11:20.080 Monotherapy using a single, appropriately targeted, broad enough agent is cleaner, 223 00:11:20.200 --> 00:11:23.399 it's safer, and it's far more cost effective. 224 00:11:23.240 --> 00:11:26.519 Which ties perfectly into what the textbook calls the most 225 00:11:26.639 --> 00:11:32.440 vital cost saving strategy in hospital medicine, the ived PO switch. 226 00:11:32.559 --> 00:11:34.919 The intravenous to oral switch, right, and. 227 00:11:35.039 --> 00:11:38.240 The data shows this switch saves roughly ten dollars per 228 00:11:38.279 --> 00:11:40.320 dose just in administration overhead. 229 00:11:40.480 --> 00:11:43.320 Yeah. The IV two being the saline flushes the nursing 230 00:11:43.399 --> 00:11:44.759 labor It adds up fast. 231 00:11:45.000 --> 00:11:48.399 But again, from a patient or even a young doctor's perspective, 232 00:11:48.960 --> 00:11:53.039 it feels like an IV drip is delivering a superior, 233 00:11:53.080 --> 00:11:54.480 stronger level of care. 234 00:11:54.679 --> 00:11:55.519 I get that feeling. 235 00:11:55.600 --> 00:11:55.919 I do. 236 00:11:56.080 --> 00:11:58.679 Like if a patient is admitted for a huge facial swelling, 237 00:11:58.960 --> 00:12:01.600 stepping them down to a feels like a massive downgrade. 238 00:12:01.600 --> 00:12:02.519 In therapy, it. 239 00:12:02.519 --> 00:12:06.799 Only feels like a downgrade if you misunderstand pharmacokinetics, specifically, 240 00:12:07.120 --> 00:12:11.360 oral bioavailability break that down force. So bioavailability is the 241 00:12:11.399 --> 00:12:15.080 exact fraction of the administered drug that survives the acidic stomach, 242 00:12:15.519 --> 00:12:19.840 passes through the intestinal mucosa, survives first pass metabolism in 243 00:12:19.879 --> 00:12:22.879 the lover, and successfully enters the systemic circulation. 244 00:12:23.039 --> 00:12:26.080 Okay, And an IVY drug is essentially one hundred percent 245 00:12:26.080 --> 00:12:27.919 bioavailable by definition. 246 00:12:27.600 --> 00:12:31.159 Correct because you bypass the gut and the liver entirely 247 00:12:31.200 --> 00:12:34.600 you're mainlining it. But the textbook points out that several 248 00:12:34.919 --> 00:12:40.000 highly relevant antibiotics in dentistry have exceptional oral bioavailability. Which 249 00:12:40.039 --> 00:12:45.840 ones we are talking about clindamycin, matronodozol, amoxicillin, and doxycycline. 250 00:12:45.960 --> 00:12:46.320 Okay. 251 00:12:46.919 --> 00:12:50.480 Their chemical structures allow them to absorb so efficiently across 252 00:12:50.519 --> 00:12:53.799 the GI tract that the serum concentrations achieved by taking 253 00:12:53.799 --> 00:12:57.279 them orally are nearly indistinguishable from an IV. 254 00:12:57.200 --> 00:13:00.480 Push seriously indistinguishable, pretty much identical. 255 00:13:00.559 --> 00:13:03.320 So if a patient has a functioning gut, keeping them 256 00:13:03.360 --> 00:13:06.679 on a peripheral IV line is just exposing them to 257 00:13:06.720 --> 00:13:10.320 the risk of like phlebitis or a line infection for 258 00:13:10.600 --> 00:13:14.919 zero added benefit. Exactly once a patient demonstrates clinical improvement 259 00:13:14.919 --> 00:13:17.919 and their hemodynamically stable, usually within forty eight to seventy 260 00:13:17.960 --> 00:13:21.399 two hours. Maintaining IVY access for these specific drugs is 261 00:13:21.440 --> 00:13:22.799 basically medical. 262 00:13:22.399 --> 00:13:24.000 Theater, medical feed or wax. 263 00:13:24.120 --> 00:13:26.919 It's not medical science. The switch to oral therapy should 264 00:13:26.960 --> 00:13:27.559 be immediate. 265 00:13:27.720 --> 00:13:31.039 Okay, Let's apply that specific strategy to the actual pathogens 266 00:13:31.039 --> 00:13:32.279 we face in the oral cavity. 267 00:13:32.360 --> 00:13:32.879 Let's do it. 268 00:13:33.039 --> 00:13:36.200 Doctor Kuna's text breaks down impyic therapy regimens for severe 269 00:13:36.279 --> 00:13:38.039 dental infections, and. 270 00:13:37.960 --> 00:13:39.320 The usual suspects here. 271 00:13:39.200 --> 00:13:43.960 Are oral anaerobes which thrive in the deep oxygen depleted 272 00:13:44.039 --> 00:13:47.240 periodental pockets, and oral stryptococcy right. 273 00:13:47.159 --> 00:13:48.679 The classic dental dugs. 274 00:13:48.840 --> 00:13:51.399 So if that patient is hospitalized with the severe facial 275 00:13:51.440 --> 00:13:54.840 space infection, what is the initial IV therapy targeting those 276 00:13:54.879 --> 00:13:55.840 specific bugs. 277 00:13:56.039 --> 00:13:59.919 The standard textbook recommendation is clindamycin at six hundred milligram 278 00:14:00.200 --> 00:14:04.320 thavi every eight hours, or a broad spectrum combination like 279 00:14:04.559 --> 00:14:06.200 piper ascyllintiso buctum. 280 00:14:06.480 --> 00:14:09.080 Let's focus on clindamycin for a second. Why is it 281 00:14:09.480 --> 00:14:12.200 historically such a powerhouse for dental stuff. 282 00:14:12.320 --> 00:14:15.279 It really comes down to its unique tissue penetration and 283 00:14:15.320 --> 00:14:18.960 its mechanism of action. How so Well, clindamycin is highly. 284 00:14:18.679 --> 00:14:20.440 Lipophilic, meaning it likes fat. 285 00:14:20.559 --> 00:14:23.639 Right, it easily crosses lipid cell membranes, which allows it 286 00:14:23.639 --> 00:14:26.919 to penetrate deeply into bone matrix and necrotic soft tissue 287 00:14:27.159 --> 00:14:29.559 where vascularity is super compromise. 288 00:14:29.639 --> 00:14:31.320 Well, that's perfect for dental abscesses. 289 00:14:31.440 --> 00:14:33.759 It is, and once it's inside, it binds to the 290 00:14:33.759 --> 00:14:38.080 fifty s ribosomal subunit of the anaerobic bacteria, rapidly shutting 291 00:14:38.120 --> 00:14:43.039 down protein synthesis. It absolutely decimates the oral anaerobic populations 292 00:14:43.039 --> 00:14:45.559 that drive those deep fascil space infections. 293 00:14:45.639 --> 00:14:48.679 And when that hospitized patient stabilizes and we apply that 294 00:14:48.879 --> 00:14:52.399 IV to PO switch, what is the step down therapy. 295 00:14:52.240 --> 00:14:56.120 You utilize that near perfect bioavailability we talked about. They 296 00:14:56.200 --> 00:14:59.639 step down to clindamycin three hundred milligrams orly every eight 297 00:14:59.679 --> 00:15:03.200 hours for two weeks. Alternatively, if the initial IV therapy 298 00:15:03.320 --> 00:15:06.759 was a beta lactam, they switched to a maxiicellin clavulin eate. 299 00:15:06.840 --> 00:15:08.720 It's augmentin right at bugmenton and. 300 00:15:08.759 --> 00:15:10.600 A dose of eight hundred and seven hundred five one 301 00:15:10.639 --> 00:15:13.679 hundred and twenty five milligrams orally every twelve hours. 302 00:15:13.759 --> 00:15:17.440 Nice, okay, But beyond the deep tissue bacterial infections, the 303 00:15:17.559 --> 00:15:20.799 oral cavity is also a battleground for viral, fungal and 304 00:15:20.799 --> 00:15:21.840 spear shehed pathogens. 305 00:15:21.919 --> 00:15:23.399 So definitely it's a jungle in there. 306 00:15:23.440 --> 00:15:26.639 And the text differentiates treatment from mouth ulcers and vesicles 307 00:15:26.639 --> 00:15:28.159 based heavily on the etiology. 308 00:15:28.399 --> 00:15:31.879 The differential diagnosis is critical here because the mechanisms of 309 00:15:31.919 --> 00:15:35.559 the treatments are completely divergent. Like if the vesicles are 310 00:15:35.639 --> 00:15:40.840 viral specifically herpie simplex virus or HSV, the textbook points 311 00:15:40.879 --> 00:15:41.679 to a cyclover. 312 00:15:41.919 --> 00:15:45.600 I've always wondered about this. How does a cyclover specifically 313 00:15:45.639 --> 00:15:50.360 target the virus without destroying the host's own cellular replication? 314 00:15:50.639 --> 00:15:53.519 A cyclover is honestly an incredibly elegant drug. 315 00:15:53.639 --> 00:15:54.279 How does it work. 316 00:15:54.399 --> 00:15:57.240 It's a nucleoside analog, but it is administered in an 317 00:15:57.320 --> 00:15:58.159 inactive form. 318 00:15:58.279 --> 00:15:59.240 Okay, it only. 319 00:15:59.159 --> 00:16:03.360 Becomes activation when it encounters thymidine kinase. And that's an 320 00:16:03.480 --> 00:16:07.279 enzyme produced specifically by the herpes virus, not by human cells. 321 00:16:07.480 --> 00:16:09.000 Oh wow, So it's like a sleeper agent. 322 00:16:09.279 --> 00:16:12.919 Exactly once the viral enzyme activates it, the drug incorporates 323 00:16:12.960 --> 00:16:16.480 itself into the replicating viral DNA strand, and because it 324 00:16:16.559 --> 00:16:19.559 lacks a crucial chemical attachment point, it acts as a 325 00:16:19.639 --> 00:16:21.000 chain terminator. 326 00:16:20.600 --> 00:16:21.440 So it breaks the chain. 327 00:16:21.559 --> 00:16:24.919 The viral DNA polymerase literally cannot add the next link. 328 00:16:25.279 --> 00:16:29.000 Viral replication halts completely and the healthy human cells are 329 00:16:29.080 --> 00:16:30.440 left completely untouched. 330 00:16:30.679 --> 00:16:34.080 That is fascinating, but I mean, if the oral ulcers 331 00:16:34.159 --> 00:16:38.519 are bacterial, like the severe punched out lesions caused by 332 00:16:38.639 --> 00:16:43.159 spirit shates in Vincent's angina, you know, trenchmouthl cycle over 333 00:16:43.200 --> 00:16:44.240 does absolutely. 334 00:16:43.879 --> 00:16:46.559 Nothing, nothing at all. For spiro shades, the treatment of 335 00:16:46.679 --> 00:16:51.080 choice remains penicillin G. The classic yep spara shavs have 336 00:16:51.120 --> 00:16:55.559 a unique highly sensitive cell wall architecture. The beta lactum 337 00:16:55.639 --> 00:16:59.200 ring of penicillin G aggressively binds to the penicillin binding 338 00:16:59.200 --> 00:16:59.919 proteins on. 339 00:16:59.840 --> 00:17:01.799 The spira shape and that breaks the wall. 340 00:17:01.919 --> 00:17:05.640 It inhibits the cross linking of their peptidoglicin layer. The 341 00:17:05.680 --> 00:17:10.039 cell wall loses its structural integrity and osmotic pressure basically 342 00:17:10.039 --> 00:17:11.799 causes the bacteria to rise and die. 343 00:17:11.880 --> 00:17:14.680 Okay, So that's viral and spira shase rounding out the 344 00:17:14.720 --> 00:17:20.799 mucosal infections we have oropharyngeal candidiasis to rush. Right. Fungal overgrowth, yes. 345 00:17:20.720 --> 00:17:25.200 Driven by candida albicins. And this frequently occurs in immunocompromised 346 00:17:25.200 --> 00:17:27.960 patients or in patients who have recently completed a course 347 00:17:27.960 --> 00:17:30.559 of heavy broad spectrum antibiotics because. 348 00:17:30.279 --> 00:17:32.759 The antibiotics wiped out their normal bacterial. 349 00:17:32.279 --> 00:17:35.400 Flora exactly, eliminating a competition for the yeast. So the 350 00:17:35.440 --> 00:17:36.359 yeast just takes over. 351 00:17:36.759 --> 00:17:40.680 And the treatment options here are clotrimosoal troches which just 352 00:17:40.720 --> 00:17:43.599 dissolve locally in the mouth, or A nine stat and 353 00:17:43.640 --> 00:17:47.400 swish and swallow, or systemI fluconazole correct and these work 354 00:17:47.440 --> 00:17:49.279 by targeting or gostral. 355 00:17:48.839 --> 00:17:53.200 Right, you got it. Human cell membranes rely on cholesterol, 356 00:17:53.279 --> 00:17:56.680 but fungal cell membranes rely on or gostol verstability. 357 00:17:56.880 --> 00:17:58.079 Ah, that's the difference. 358 00:17:58.279 --> 00:18:02.279 Yeah. These anti fingal agents either bind directly to ergostrol 359 00:18:02.480 --> 00:18:06.079 or inhibit its synthesis, which tears microscopic holes in the 360 00:18:06.079 --> 00:18:10.119 fungal cell membrane, causing the cellular contents to just leak out. 361 00:18:10.319 --> 00:18:12.880 So for anyone taking notes, you basically have three main 362 00:18:13.160 --> 00:18:18.160 oral battlegrounds. The deep bacterial infections requiring clindamycin, the viral 363 00:18:18.240 --> 00:18:22.160 or spirashet ulcers, and the fungal overgrowths like thrush. 364 00:18:22.200 --> 00:18:23.559 That's a great way to categorize it. 365 00:18:23.799 --> 00:18:26.440 There's one more throat area condition we need to cover, though, 366 00:18:26.480 --> 00:18:31.000 because it highlights a massive prescribing trap, pharyngitis right strep throat. 367 00:18:31.559 --> 00:18:35.680 For true group A streptococcal pharyngitis, the textbook actually prefers 368 00:18:35.720 --> 00:18:39.160 a moxocillin over standard penicillin just for better GI absorption. 369 00:18:39.359 --> 00:18:41.359 It's much easier for the patient to tolerate. 370 00:18:41.720 --> 00:18:45.039 But what happens if the clinician misdiagnoses the sore throat? 371 00:18:45.960 --> 00:18:50.039 What if the patient actually has infectious mononucleosis caused by 372 00:18:50.079 --> 00:18:54.480 the epstein bar virus and the clinician prescribes a moxacillin anyway. 373 00:18:54.319 --> 00:18:56.519 You trigger a spectacular adverse event. 374 00:18:56.680 --> 00:18:57.400 It's bad, right. 375 00:18:57.480 --> 00:19:00.599 If you introduce a moxocillin into a system actively fighting 376 00:19:00.640 --> 00:19:04.400 the epstein bar virus, nearly ninety percent of those patients 377 00:19:04.440 --> 00:19:09.799 will erupt in a massive, intensely itchy, full body maculopopular rash. 378 00:19:09.960 --> 00:19:13.440 Ninety percent, And it looks exactly like a severe drug allergy. Right. 379 00:19:13.640 --> 00:19:16.559 The patient usually ends up in the er convinced they're 380 00:19:16.599 --> 00:19:17.799 going into anaphylaxis. 381 00:19:17.920 --> 00:19:20.880 It perfectly mimics an allergy, but it's fundamentally different. This 382 00:19:20.960 --> 00:19:25.440 is not a true ig mediated life threatening type one hypersensitivity. 383 00:19:25.519 --> 00:19:26.079 What is it? Then? 384 00:19:26.279 --> 00:19:30.599 It's a delayed immune complex mediated reaction. The epstein bar 385 00:19:30.680 --> 00:19:34.920 virus basically hyperstimulates the patient's immune system, altering how it 386 00:19:34.960 --> 00:19:38.920 recognizes the immoxicillin molecule, so it gets confused exactly. The 387 00:19:38.920 --> 00:19:41.599 immune system suddenly views the drug as a target, leading 388 00:19:41.599 --> 00:19:46.240 to widespread cutaneous inflammation. The patient isn't permanently allergic to ammoxicillin, 389 00:19:46.279 --> 00:19:49.880 They're just experiencing a transient virus induced immune confusion. 390 00:19:50.079 --> 00:19:55.319 Wow. That epstein bar rash perfectly illustrates the danger of 391 00:19:55.359 --> 00:19:58.559 treating a symptom or like a lab test rather than 392 00:19:58.640 --> 00:20:02.519 understanding the underlying real of the microbiome, absolutely which brings 393 00:20:02.599 --> 00:20:05.599 us directly to the textbook's golden rule. This is perhaps 394 00:20:05.599 --> 00:20:07.839 the most critical takeaway for any clinician listening. 395 00:20:08.079 --> 00:20:10.519 Do not use antibiotics to treat colonization. 396 00:20:10.720 --> 00:20:13.680 It's the bedrock of infectious disease stewardship, isn't it. 397 00:20:13.680 --> 00:20:16.799 It really is the human oral cavity, the gut, the skin. 398 00:20:17.680 --> 00:20:20.799 They are not sterile environments lilion clothes. No, they are 399 00:20:20.839 --> 00:20:23.759 teeming with billions of bacteria that make up your normal, 400 00:20:23.960 --> 00:20:29.440 healthy flora. These organisms are colonizers. They occupy physical space 401 00:20:29.480 --> 00:20:33.599