61. Nobbling the Nonfermentors: Acinetobacter Part 1

In this episode, Callum and Jame go over the second big family of nonfermentors, Acinetobacter. In part 1 we talk about the organisms themselves, risk factors, clinical syndromes and diagnostics before talking a little about treatment. 

In Part 2 (released next week) we’ll talk about Carbapenem-Resistant Acinetobacter Baumanii-calcoaceticus (CRAB), and resistance mechanisms in general. 

Chapters

• 0:00 Overview of Acinetobacter Infections
• 13:22 Options for Treating Acne Tabacta
• 18:46 Treatment Options for Acinetobacter Infections

Transcript

Overview of Acinetobacter Infections

Speaker 1 0:18

Hi everyone, welcome to the Idiots podcast that's infectious disease insight of two specialists. I'm James, that's Callum, and we're going to tell you everything you need to know about infectious disease.

Speaker 2 0:27

Soon. May the editing come to this continue the taser sun. One day, when the seer piece done, we'll take our leave and go.

Speaker 1 0:37

Callum. How are you doing?

Speaker 3 0:39

Oh, I don't have a pun ready.

Speaker 1 0:42

I have been looking forward to this, because I figured that this was the episode that was going to finally break you.

Speaker 3 0:48

The next episode is an easy pun.

Speaker 1 0:50

This one. Do you feel like somebody's torturing you by pouring concentrated acid all over your lower limbs? So you've got acid-nito, acid-nito. That reminds me Callum. This episode's an acetyl-battery, is it not?

Speaker 3 1:09

Oh, so bad.

Speaker 1 1:11

It is bad, but you had nothing. So I felt that I had to step in and also be thinking about it all week.

Speaker 3 1:15

You've been thinking about it all week.

Speaker 1 1:18

But these crap puns, just as with you, pop into my head and then I have to get them out. Any suggestions that that's why we started the podcast are scurrilous rumours which we'll not respond to.

Speaker 3 1:29

Just like source control. You have to get the pus out, we have to get the puns out.

Speaker 1 1:33

Just so, callum. So this is the second in our Noveling the Non-Fermenters mini-series, and we have previously talked about Pseudomonas and we did a quick introduction to the Non-Fermenters, which we are not going to go over again, but there's a sort of overview in the Prem notes that you can have a look at. The four big families that we're going to discuss are Pseudomonas, which we've discussed already, acid-nito-battery, stenotrophomonas and Berkholderia.

Speaker 3 2:03

They're like the four houses of Hogwarts, yeah exactly.

Speaker 1 2:06

There are a bunch of others which we've gone over before, but usually they are treated as Pseudomonas in the lab and are of limited importance. Let's say so, callum, why don't you tell us about Acid-nito-battery then?

Speaker 3 2:23

So Acid-nito-battery. So there's 32 species at the moment and of those, 15 of them cause human infection. And there is a whole other names. I think probably the one that you'd be most familiar with is Acid-nito-battery Balmani.

Speaker 1 2:41

Yeah, or specifically Acid-nito-battery, balmanii, calcoacetius complex, or ABC, which is now what everybody's trying to call this, and this is the thing that we're going to be talking about later on as well.

Speaker 3 2:58

So, and then there's a lot of other names which James put in the Prem notes. I don't know what they are. Should we read them out to you? Do people like us reading out back to your names in a big list?

Speaker 1 3:08

Maybe somebody in the recent feedback said that sometimes we make them sleepy. So perhaps as a cure for insomnia or a side gig as an ASMR podcast, perhaps we should go through these names. Well, I start.

Speaker 3 3:22

Okay, let's do it very quickly then.

Speaker 1 3:25

Bye Balmanii. Calcoacetius Hemolyticus Junii Jonsoniii.

Speaker 3 3:31

Lohofiii.

Speaker 1 3:32

Radioresistens.

Speaker 3 3:34

Bajoringriii.

Speaker 1 3:35

Berazinii.

Speaker 3 3:36

Gaelin Bergiii.

Speaker 1 3:37

Nosokomialis Parvis, pityii, shindlerii, orsingii. There we go Right, and these are the 15 that have been noted to cause human infection, but by far and away the commonest is Astinita Balmanii, calcoacetius complex or ABC, and that's kind of what most of this episode is kind of based around. So where do you find them?

Speaker 3 4:06

Well, there's, like most of the sort of Pseudomonads, non-fermenters. They're environmental organisms. So they level a little bit of soil, they level a little bit of water. They cause infection through fomites as well, water fomites. So fomites are objects or materials which are likely to carry infection, so that can be clothes or furnishings, and they can also, if people have got wet skin they can be colonizing healthcare workers' skin in the infectious intensive care unit. So that's a potential risk person. Person transmission.

Speaker 1 4:42

But that really explains why they've got this preponderance for being in, and you know intensive care so the you know the, the risk factors for Astin's batter.

Speaker 1 4:53

It's, you know, prolonged hospital exposure, as that would be. It admissions, particularly stormy admissions, where you're you know you're sick and then you're getting better and then you get a sick again. Lots of lines. So opportunities for colonization and entry. Tpn Probably as a surrogate for you know, an unwell patient who's partially immunocompromised and heavy antibiotics use, particularly carbapenem use, yeah and that, but that's all for sort of hospital who would get it in the community very rarely.

Speaker 3 5:23

I don't know if I've ever really seen it.

Speaker 1 5:25

Well, this is actually much bigger problem as a pathogen in tropical regions when it's a very common cause of pneumonia. So one of my bosses was telling me that he was dealing with Astin to batch of pneumonia is in sort of Southeast Asia Kind of all the time, and yet you come north and then it's just doesn't seem to be as much of an issue.

Speaker 3 5:44

Yeah, the climate is so important. Um, so I guess if you're gonna get in community, it's particularly prevalent in, those are lung disease because you get sort of abnormal lung because it's wet.

Speaker 3 5:53

so particularly smokers, alcoholics, people, diabetes and you know, as James mentioned, tropical legions regions, yeah, although that said it's not a very pathogenic organism, so most of the time it's causing nosocomial illness, so infections acquired in the healthcare environment, and it's Not not something that you know. You see is a very, very long organism. It's more, you know, when people are immune compromised or their barriers gone. Yeah, so if you think about it, yeah.

Speaker 1 6:26

So if you think about a Alcoholic smoker who has uncontrolled diabetes, they've got, you know, bad lungs, sugar, e tissue and impaired immunity, and then all that can kind of Combined to predispose infection to, amongst other things, as a matter, what kind of clinical symptoms cause them?

Speaker 3 6:45

so it's mostly, you know, respiratory disease, lower respiratory tract infections. So ventilator associated pneumonia. Hospital acquired pneumonia and around 80% of the organisms are sort of drug resistance, difficult, difficult to treat and I think acinetobacter in general is difficult to treat anyway. Community acquired pneumonia in tropical regions and it can cause a tracheobronchitis in children.

Speaker 1 7:09

Yeah, I think that's a tropical thing as well.

Speaker 3 7:11

Yeah, don't quote me we'd recently talked about a cowty in a detail and you know that's plastic in the place where there shouldn't be plastic so it can cause cowty, nice, wet environment. See an S infections are particularly in the context of Prosthetic material like a vindicative access device or something like that, and in skins of tissue infections. So in patients with burns you get this sort of really abnormal skin. So a lot of sort of Gram negative organisms you know, including intrapeturalis but also including your non fermenters can can infect burns and that can be really problematic. And the real challenge of that is knowing like what's colonizing versus what's infecting. You've written here people inject drugs, so I guess you know if you're Breaking the skin barrier. I have to say I've never seen that. Maybe that's more of a tropical region thing as well.

Speaker 1 8:01

Well, maybe, but then I think also, if you're, if you're regularly Injecting into the groin and forming a tract and there's lots of groin organisms there, some of them can be gram negative and if you're not sterilizing your Injection materials, then they can be colonized or reusing them.

Speaker 3 8:19

even worse, they can be colonized with, amongst other things, ask me to battery guess if any infection it can lead on to bloodstream infection of atteremia, and that's usually from chest or in intravenous lines, and I think we've given a lot of sources there, but foreign, you know, by far the most common one is chest and line.

Speaker 1 8:39

I would say yeah, that's perhaps are the lion share of astne to better infections Micromoan engaged.

Speaker 3 8:55

So Gram stain of the astne to battery is a gram negative facilice. It can be gram variable. We think of gram staining as a, as a completely dichotomous thing, but there's probably a bit of a. You know this is more complicated than just gram, positive or negative?

Speaker 1 9:11

Yes, annoying levels of nuance, one might say.

Speaker 3 9:14

Yeah, like most things, once you more you learn the way to realize it's more complicated than you thought. And they're, and they're short and plump and cockle bacilli. So sometimes they're proper bacilli, sometimes are cockle bacilli, and so it's on your list of things to think about. When you see gram negative cockle bacilli, often they can have a capsule, the non-motile organism, so that differentiates it from some other organisms. So, like what we well, it's got the example like Legionella or Pseudomonas, they're oxidase negative. So when we think about non-fermenters in general, one of the main biochemical tests that are used is a really quick way to differentiate and we talked about the Pseudomonas is an oxidase test. So when you get an organism growing on a culture and you get a colony, you do an oxidase test and if it's oxidase positive you're usually thinking this is Pseudomonas and if it's oxidase negative you're usually thinking this isn't Pseudomonas. And the standards for microbiological investigation, the SMI it's got a really nice flow chart for that in their non-fermenter identification.

Speaker 1 10:22

Yeah, which I've got here, but I've also got like a list of the, you know, ox, boson, oxneve and ox variable organisms at the top in a hidden table. So yeah, so acetyl-tobacteran stenotrophomonas, so that oxidase negative, and Pseudomonas is almost always oxidase positive, and then bercralde area it varies. We'll talk about it in the relevant episode.

Speaker 3 10:44

It's catalyzed positive, the other thing to think about and it grows aerobically. On agar, just a side note catalyzed is an enzyme that a lot of organisms will use to sort of reduce oxygen free radicals. So kind of make sense of something's aerobically growing is usually catalyzed positive. Oh okay, I didn't know that. I wish, I wish there was some way, because it's something to feel like just to remember the biochemical test results of different organisms, and I find that really difficult unless you're in the lab doing the lab work all the time. I wish there was some way that you could be like, if you knew something about the organism, you could work it out from first principles. Maybe there's a way of doing that. What does it look like on the agar? So it's a yellow, grayish, white colony, often mucoid and hemolyticus. So I asked you to batch. Your hemolyticus Is hemolytic, so that makes sense. It's a homolysis, I presume.

Speaker 1 12:03

I can't remember, but it's the only one, so it's just a feature of that pretty small fry species.

Options for Treating Acne Tabacta

Speaker 3 12:10

The way you ideate it. So usually you sort of got your sample, which is probably going to be a respiratory tract sample and, let's face it, or it might be a blood culture from blood culture. It's going to be easy because you just be like oh, there's an organism, we're going to mold it off it from a respiratory tract. The difficulty is that you've got lots of organisms there so you're not going to mold it off every single thing you're seeing. You're trying to get the wheat from the chaff so you're going to do oxides test on it and you're going to do a gram stain and you're going to recognize it as a gram negative bacillus. That's oxides negative and you've got large numbers of growth on, say, a BAL. Thank you, I'll be over at the vagin and you probably send it off from Malditov. You can also do things like 16 SPCR or you can do a specific PCR for the gyro.

Speaker 1 12:55

B. Yeah, the G Y R B, and it's one of the DNA gyros Motifs. Yeah.

Speaker 3 13:01

And obviously you can do whole genome sequencing as well. If you're a plush with cash and just want to throw it away, so you're going to mold it off, aren't we? Or you could do other things like Malditov or APIs. There's lots of ways of doing this. I think most labs that will sort of mold it off in this. Yeah, so that's micro mode.

Speaker 1 13:21

I flew through that. We're flying through this episode.

Speaker 3 13:24

Yeah, well, what do you want to say about treatment?

Speaker 1 13:26

Well, if you do want to treat this, you've got options, as long as this thing is not MDR and, as a reminder, 80% of them are MDR, the ones that are isolated from chest, but absolute vanilla acinetobacter should be sensitive to beta-lactam, in particular PIPTAZ, the third generation Keflasporans and the fourth gen, kefderechal, the Trojan horse and carbapenems, except Aertapenem. It's also sensitive to cell bactam. So this is we'll talk about this in detail later but ampicillin cell bactam is a beta-lactam beta-lactamase inhibitor combination and the subatom is part of the first generation of beta-lactamase inhibitors, called suicide inhibitors. So essentially they drown the beta-lactamase with substrate. They're the substrate and they get broken down at the expense of ampicillin. That leaves ampicillin able to target the organism.

Speaker 1 14:31

We've talked about this in the basics of beta-lactamase inhibitors episode, thank you. Solbactam actually has direct activity, particularly against Acne Tabacta. It targets one of the PVPs very precisely and that then means that solbactam itself can be used as the antibiotic to kill. So for years now people have been using Ampicillin solbactam not for the Ampicillin, because Ampicillin doesn't target Acne Tabacta, but for the solbactam, and there is a recent formulation called solbactam-derlabactam which we'll be going over later on.

Speaker 3 15:08

It'd be lovely if we could get those in the UK.

Speaker 1 15:10

Well, I know, but I think we'll probably be getting solbactam-derlabactam shot. You think, yeah, yeah, I think it's pretty needed. I think it's needed and the evidence behind it is pretty, but it's good to say nothing else that we're about to discuss.

Speaker 3 15:23

It just depends the drug company decides to put it forward for a license. But I like to.

Speaker 1 15:28

I think it's crossed In terms of other things that have activity against it. So some of the tetracycline do, doxocycline and minocycline. Aminoglycosides the resistance rates are really high Quinolones like Cypro and Levo, cotromoxazole and Colistin, and there are. What I've included in the show notes that people can take a look at is a table in which I've got all of the agents that we can use, including the UCAST and CLSI. Breakpoints were applicable, and I found a paper in which there was a breakdown of the kind of frequency of sensitivity of Acne-Tobacter to these agents. So, for example, ampestil and Solbactam, if you can use it it's great, but only about 36% of isolates are sensitive to it, so resistance rates are actually reasonably high, whereas, say, kefederkel, the Trojan horse, the sensitivities rates are about 90 to 96%, and so too, with Colistin. Of course there are issues with using Colistin for lung infections, which might mean that it's not particularly effective, and then there are some quirks of the particular agency. So CLSI always tends to have more break points than UCAST. Ucast are more circumspect, I guess you could say so. In particular, ucast doesn't have breakpoints for the third generation Custodian Sporins. It does for Kedefriger call. It's got a recognition of IE, which is interprets.

Treatment Options for Acinetobacter Infections

Speaker 1 17:15

Insufficient evidence. Insufficient evidence, yeah, where CLSI has SR breakpoints of 4 and 16, respectively. For Doropenem, ucast are recommending using it at higher doses all the time. So they have the S breakpoint set at point 001. And it doesn't have breakpoints for DoxaCyclin, whereas CLSI does their 4 and 16. Aravacyclin there's a Aravacyclin review paper for microbiological breakpoints which I'm referring to for all of the pseudomonads, but for UCAST it's got IE. Clsi don't have a breakpoint set yet, but the MIC 90 in that paper was one. So it is worth considering if your back is absolutely to a wall.

Speaker 3 18:01

Just explain MIC 90 quickly for people.

Speaker 1 18:03

So the MIC, the minimum inhibitory concentration we've mentioned before, it's the concentration on which visible growth has inhibited an omega or plate at 24 hours. The MIC 90 would do that to 90% of isolates. If you plate it out, an organism 100 times and then looked at if there was a zone of inhibition, you would hit that at least 90 out of 100 times. So you can get the MIC 50, which will do 50% of plated out isolates, and you can get the MIC 90. But I think the MIC 90 is what the breakpoints are actually based around. So that's that it's.

Speaker 3 18:39

you know well I want to comment on things You're talking. I sat patiently waiting for you to finish.

Speaker 1 18:45

You did the whole first half of the episode. No, I didn't.

Speaker 3 18:48

Fine, what do you want to ask? I want to say well. First I want to say the table is lovely, well done. Oh, thank you, I think it's really easy to read and it's, I'm going to use it. So thanks for helping me.

Speaker 1 19:01

Well, what I've been doing lately Kalma's and the listeners might as well hear this too is that I've been building the prep notes now in the ocean so that hopefully they're a bit more useful to the listener than the old Word documents. And it's also easy, if you're looking at it, to grab images and tables off and you can put them into your own notes if you need to. But yeah, hopefully they're of some use to people.

Speaker 3 19:30

So can we get Solbatsum at the moment in the UK? Just know.

Speaker 1 19:33

So it's not the B&F Callum which makes me think that we can't get a hold of it. So at the very least it would be off-license, because if it's not the B&F it doesn't have a license in the UK. But like all things, like plasmison and like other weird and wonderful antimicrobials, if you need it you can get it. It's just that it's a historical thing. The UK is addicted to Coam-Mozsa-Clav and Pepero-Silentazobactam. There's not really been much of a use case for Tymentin, which is to Sarsil and Chlivalonic Acid, or Ampsiline-Sulbactam until recently, and I think that as we're encountering more and more NDR infections, in particular Gram-negative infections, in particular non-fermenters, in particular Acneetabacter, the lack of access to Sulbactam has become more and more of a problem. But that should be shortly being rectified if the UK knows what's good for it.

Speaker 3 20:34

And so another question so I guess this is a big question is all very well looking at this table and it's a bit, you know, having it a bit difficult with UCAS in terms of they're not giving breakpoints for a lot of things now and that's not particularly helpful, if you know. I guess it is scientifically sound but it's not very useful for your jobbing microbiologist. So if we had a patient who presents with Acneetabacter infection let's say it's a FAP and it was not multi-drug resistant, it wasn't MDR we had all the options. What's our like? Go to, you know, first line treatment like what we're going to be giving routinely I'm thinking Piptaz although I find that a bit tricky because UCAS don't give a breakpoint. So then I'd have to go to CLSI.

Speaker 1 21:23

Well, I mean, if it's nice to you, they may well already be on Piptaz, but because there's no breakpoint issue by UCAS, no lab will report Piptaz sensitivity. If you ask and you insist, they may report PKP.

Speaker 3 21:39

Well, we do some sensitivity reporting by CLSI in our lab.

Speaker 1 21:43

Yeah, yeah, and some labs may take the decision to do that, usually out of desperation, because UCAS haven't seen fit to offer anything. But you know, like if you're just going by this table you'll probably get a breakpoint for one of the carbapenems probably imapenem, mcquinlone or two and amnibalicicide, colostin and cauterine. So of all of those I would probably go to Coltrim. Leave of Loxacin and meropenem.

Speaker 3 22:14

Yeah, and obviously we're trying to avoid you know, certainly locally we try very hard to avoid to use as little carbapenems as possible, just to try and stop driving antibiotics in the ICU and driving it Because we said they're all one of the biggest risk factors for getting Acne to Bacter infections is the use of carbapenems.

Speaker 1 22:36

And it's an environmental organism.

Speaker 3 22:38

I mean know that when people are given antibiotics, they excrete that antibiotic in their urine and their sweat and their stool because it's all over the environment. So the more carbapenems you're using, the more we're going to get Acne to Bacter another you know difficult to treat organisms. And then we're saying like, oh, but how do you treat this? You give carpet. So you get to this vicious cycle of giving more carpenters, getting more infections, etc.

Speaker 1 23:03

Yeah, well, I mean the. But then when you're looking at the rest of the things that that you cast would say are safety, use, you know amygl oxides for, for lung infections, certainly you wouldn't want to use it on its own and there have been recent changes to the breakpoints which mean that they, you know they wouldn't really consider them or constant be to be ideal the. You know, lung penetrance of Amygl oxides is about a third. So if you've got, you know, tobor, bisoner or gentomycin and you're getting a Cmax over M, I see if maybe eight to ten times you'll be getting two to three times in the lung tissue, that's not bad, you'll still be getting some kill. But will you be getting enough to rely on it as your soul, you know, as your soul agent?

Speaker 1 23:50

I'm not sure that I would. You know, and I I'm on record as being team amygl oxides. I'm not even sure that I would want to do that. And then ditto for colostin with bells on because it's, you know, it's crap at getting into the lungs but it's great at getting into your kidneys and causing fail. So I'm gonna go like sides are very polarly charged, they've got high polar charge and so that means that they're difficult crossing some barriers. But I'm gonna look into Penetrance into alveolar fluid and we'll do an episode on it later. That sounds good.

Speaker 2 24:23

Yeah so anyway.

Speaker 1 24:25

So yeah, well, I'm looking at the rest of it. You know ditto for colostin, so then really, it's just kind of you know you're drawn by default to Koltram Cypro and a carbon-pennum.

Speaker 3 24:35

And it has to be Cypro high dose.

Speaker 1 24:38

Well, sorry, not Cypro. Sorry meant levoflosses.

Speaker 3 24:41

Oh, I see, so do you use levoflossin over Cypro for Acinetobacter?

Speaker 2 24:46

I.

Speaker 1 24:47

Would. I think it's particularly an intensive care patients. You can make the argument that you know once you've gone broad spectrum. Why not? Why? Why not try and minimize the amount of antibiotics you need? Do you know what I mean? So like if you're using Cypro? I don't think you would really want to use Cypro on its own. You probably want something with a bit of grand positive cover.

Speaker 3 25:12

Well, I don't know, if you've got a VAP and you grow an organism on BAL and that's the only thing that you've got, you could, I'm not sure.

Speaker 1 25:19

Moving from I'm not sure moving from levot-cypro I would count as targeted therapy. I think that's a bit of a stretch, yeah.

Speaker 3 25:26

I don't know, I don't, I just I guess comes on to side effect profile. Yeah.

Speaker 1 25:30

Well, I think that in terms of side effect profile and tendon toxicity and C diff risk, there's not much difference between the two. The only difference is you're also covering streptococci.

Speaker 3 25:41

We need to definitely do a deep dive into quinolones and that's gonna come up soon, a feature drug episode. And I particularly want to ask a lot of questions about delafloxism because that's come up a couple of times recently.

Speaker 1 25:52

I'm gonna have to deep dive into nailing. I'm fine, I'll do it. I'll do it for you, for you.

Speaker 3 26:00

I'll do it. There'll be some red ale in it for when you come to Edinburgh, and Okay, so, so we've got a bit of an idea about you know the approach if you've got a sort of quite a sensitive Acne to back. Yeah, are you happy, cal? I'm ecstatic.

Speaker 1 26:14

Good, now throw all that out of the window, because this is an absurdly resistant organism and we're all doomed.

Speaker 3 26:19

Oh that's, that's a real shame. I I wish they would just all say sensitive, to be honest, but that seems hopelessly unrealistic. So I guess you'll need to come back and join us for the next episode where we're gonna talk through the resistance mechanisms and how to manage the crab in the room. So that's the carbopenum resistant Acne to batch or Bauma, and I calcose eticus complex.

Speaker 1 26:51

Stay tuned for next week's episode where Cal finally pronounces it correctly on the first go.

Speaker 3 26:55

Thank you for listening to the idiots podcast, the UK's premier infectious disease podcast. We are supported by the British Infection Association, but they do not have creative control over the episode content, so please don't blame them if we get something wrong. Questions, comments, suggestions. Why don't?

Speaker 1 27:11

you send them into idiots podcasting at gmailcom. Have a five star review in your pocket, cal, and I would love to have it. Please drop it in your podcast player of choice. We tweet at the idiots underscore pod and if you want to donate to support the show, there's a link to do so in the description. But until next time, I'm James and Callum. See you there Now that the episode's done.

Speaker 2 27:28

We hope you learn and had lots of fun. So go forth and treat people with some of what you now know.