Please STOP CIPROFLOXACIN DIPS and other antibiotics

[Jay Hemdal]

Out of curiosity, why are you ok with PZQ?

You will read a lot about "Prazi resistant flukes". Indeed, in some aquariums, PZQ stops working after multiple doses. I had seen that myself, and at first attributed it to "acquired resistance". However, I noticed moving the fish to a new tank and treating them again worked! Years later, the researchers at Disney confirm that it is bacterial degradation of the PZQ, it becomes greater with every dose:

Praziquantel degradation in marine aquarium water

Praziquantel (PZQ) is a drug commonly utilized to treat both human schistosomiasis and some parasitic infections and infestations in animals. In the aquarium industry, PZQ can be administered in a “bath” to treat the presence of ectoparasites ...

www.ncbi.nlm.nih.gov

Jay

 

[Cell]

I'm finding several papers on PZQ resistance related to the treatment of schistosomiasis which is why I asked. But prazi resistant flukes would really stink for us reefers. I'm glad that wasn't the case.

 

[MnFish1]

I just want to add a little additional context. When cipro or another antibiotic is diluted as it is flushed or dumped down a drain, the concentration will drop to what is called “sub microbial”. Physicians / dentists commonly use doxycycline at submicrobial doses to reduce inflammation in periodontal disease or chronic inflammatory diseases of the skin like rosacea. It has been shown that these low doses do not confer resistance. There is no pressure on bacterial survival and therefore selection does not occur. So yes, though resistance is of great concern, unless we are concerned of resistant Mycobacterium marinum or Vibrio vulnificus, the limited use of cipro in tanks is a minor concern.

I believe you're incorrect. In fact - using lower than treatment doses could tend to promote resistance. There are many 'older' papers that suggest that resistance does not develop - however over time this has been re-thought. For example - patients with acne are asked to use something like benzoyl peroxide as well - to lessen the chance of resistance. I'm not aware of the word 'sub microbial doses'. I think you might mean sub-inhibitory or sub-bactericidal doses. (EDIT - I typed the word incorrectly. - sub microbial s a word. Additionally, there are many many many more bacterial types in a tank - besides vibrio and mycobacterium. The important issue you're missing is that bacterial resistance can be passed from bacteria of different species.

 

[alprazo]

Jay,

As always, the science in never absolute but as you read on in the article, resistance in this small sample size decreased in the treated group vs the placebo over 24 months. Defining resistance as organisms susceptible to a therapeutic dose. I'm sure you read the plethora of other articles that demonstrated no significant increase in resistance to submicrobial dosing. Now, more studies, preferable genomic studies sequencing for genetic resistance would be helpful, but to date the evidence strongly supports that the use of submicrobial doses of antibiotics does not confer resistance.

The logic makes sense too. A certain concentration is require to kill or at least inhibit the reproduction of a bacterium. Doxycycline in our case is bacteriostatic. If the concentration is below that level, there is no stress on the organism for survival, and natural selection does not take place. The submicobial dose for doxycycline in vivo for humans is 20mg BID. The lowest therapeutic dose is typically 50 mg BID. The dose of flushed doxycycline in the sewer likely nears homeopathic levels.

I fully understand the issues we face with antibiotic resistance and the want limit its use for those reasons but sometimes studies do not necessarily support the prevailing thought and pressures from society. I find it important that contrary information also be presented. This allows for informative debate and a greater understanding. Don't you love coming across an article that blows you away by knocking down and questions what you thought and considered to be a tested theory? One that disrupts the norm.

Anyway, thanks for the debate

 

[MnFish1]

The logic makes sense too. A certain concentration is require to kill or at least inhibit the reproduction of a bacterium. Doxycycline in our case is bacteriostatic. If the concentration is below that level, there is no stress on the organism for survival, and natural selection does not take place. The submicobial dose for doxycycline in vivo for humans is 20mg BID. The lowest therapeutic dose is typically 50 mg BID. The dose of flushed doxycycline in the sewer likely nears homeopathic levels.

Does this article explain it at all. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250919/

 

[MnFish1]

Jay,

As always, the science in never absolute but as you read on in the article, resistance in this small sample size decreased in the treated group vs the placebo over 24 months. Defining resistance as organisms susceptible to a therapeutic dose. I'm sure you read the plethora of other articles that demonstrated no significant increase in resistance to submicrobial dosing. Now, more studies, preferable genomic studies sequencing for genetic resistance would be helpful, but to date the evidence strongly supports that the use of submicrobial doses of antibiotics does not confer resistance.

The logic makes sense too. A certain concentration is require to kill or at least inhibit the reproduction of a bacterium. Doxycycline in our case is bacteriostatic. If the concentration is below that level, there is no stress on the organism for survival, and natural selection does not take place. The submicobial dose for doxycycline in vivo for humans is 20mg BID. The lowest therapeutic dose is typically 50 mg BID. The dose of flushed doxycycline in the sewer likely nears homeopathic levels.

I fully understand the issues we face with antibiotic resistance and the want limit its use for those reasons but sometimes studies do not necessarily support the prevailing thought and pressures from society. I find it important that contrary information also be presented. This allows for informative debate and a greater understanding. Don't you love coming across an article that blows you away by knocking down and questions what you thought and considered to be a tested theory? One that disrupts the norm.

Anyway, thanks for the debate

PS - this article also directly contradicts your theory as well: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913839/

 

[alprazo]

Does this article explain it at all. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9250919/

This article is quite informative and thorough. It fails however to support the argument of the OP and even directly states it "Antibiotic concentrations in wastewater have been reported ranging from ng L−1 to mg L−1, depending on the source: hospitals, urban wastewater, and/or WWTPs (Segura et al. 2009; Hughes et al. 2013). Despite their occurence, studies have not yet established the effect of antibiotic levels on bacteria in the environment,"
And the areas where they do cite, are from the discharge sites from the pharmaceutical manufacturing plants. That is a lot different than flushing a 10 gal tank with added copra down the drain.

 

[alprazo]

PS - this article also directly contradicts your theory as well: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913839/

As for this article, I completely agree with the authors argument. The MICs that have been developed are, for many factors, inadequate. It still doesn't support the argument that sub microbial (meaning that the concentration is below that to put stress on a bacterium) nano to pico mg/l of an antibiotic alters the resistance patterns in bacteria.

 

[alprazo]

I did find this article tough -its only one It argues against my reasoning and it has to do with laboratory conferred resistance increasing doubling time. https://pubmed.ncbi.nlm.nih.gov/21811410/
That said, it is one study and is quite limited. Many of their conclusions can be critically argued and possibly flawed. More research clearly needs to be done on this topic but at this point in time, IMO the evidence is lacking to support the OP post.

 

[MnFish1]

I did find this article tough -its only one It argues against my reasoning and it has to do with laboratory conferred resistance increasing doubling time. https://pubmed.ncbi.nlm.nih.gov/21811410/
That said, it is one study and is quite limited. Many of their conclusions can be critically argued and possibly flawed. More research clearly needs to be done on this topic but at this point in time, IMO the evidence is lacking to support the OP post.

I guess, one has to wonder why the WHO and multiple countries have banned the use of antibiotics without a professional's input (i.e. a prescription). Also - there are a couple of issues. Using sub microbial doses of antibiotics to treat a condition (a known condition - like acne or rosacea) is different than prophylactically choosing a broad spectrum antibiotic and using it as a dip without any known pathogen. Using an antibiotic to treat a bacterial infection on a fish is different than a randomly chosen treatment which also has no evidence behind it - right?.

 

[alprazo]

I agree with all of your points here. Responsible use is important. It’s a resource that we have and could ultimately lose. My point here was noting the lack of data to support the claim that treating fish or inverts for disease and dumping the water is harmful. To date that claim just can’t be supported. Empirical use for healthy fish would be a misuse in my opinion, and your right there are bacteria, other than the human pathogens I noted that could develop resistance.
I am thankful to R2R for not taking down my posts. On YouTube and other platforms a debate like this so often cannot occur.

 

[MnFish1]

I agree with all of your points here. Responsible use is important. It’s a resource that we have and could ultimately lose. My point here was noting the lack of data to support the claim that treating fish or inverts for disease and dumping the water is harmful. To date that claim just can’t be supported. Empirical use for healthy fish would be a misuse in my opinion, and your right there are bacteria, other than the human pathogens I noted that could develop resistance.
I am thankful to R2R for not taking down my posts. On YouTube and other platforms a debate like this so often cannot occur.

It's a discussion. not. debate.

 

[Velcro]

I’ve been reefing twenty years and never needed it, nobody in my entire city of Lubbock ever needed it (I’m not in their homes to verify, per the reef meetings and online forum and pet stores where we traded actionable lore it was never ever even a thought) and I’ll never need it in the future. It’s possible to reef without it, because we have always done it that way. We aren’t restricted to certain anemones or sps, we can keep what we want.

Ive never seen it used at nano-reef.com either. I’m sure there has been a dose in the last few years, its the new trend for sure, but it’s not anything I’ve seen ever over there it’ll be highly isolated use if at all

Any doctor that prescribed it without a matched bacterial assessment is a quack. Nobody with credentials takes a guess with powerful antibiotics, having no idea at all if there’s another malady causing the issue, there could be twenty reasons an anemone doesn’t puff up.

what real doctors do is get a swab, plate it, grow the culture on agar for selection and for sure identify the target. they just don’t go get cipro, the doser of the year, they actually prescribe the matching antibiotic to the strain at hand. It has a set dose and sustain rate, which doesn’t exist for aquarium use only guesstimates guide aquarium use

I’ll also bet that was pre pandemic before supplies were at risk, but if it wasn’t, I can understand that too. Any doctor who prescribes a scrip for a powerful antibiotic off an aquarium picture has low standards. I once bought a scrip for testosterone in Acuna for ten bucks, at a bar, he was a real doctor no joke but I’m not sure his standards matched other doctors.

there are ways to change the approach to reefing where it is simply never needed and that’s the only way any of us should be reefing and researching and teaching others

You’re assuming that everyone that has a reef tank in your city has any interest in a reef club, your LFS or a local forum (they don’t). Your sample size isn’t what you think it is.

 

[brandon429]

Add to that reefing obsessively in forums for 22 yrs and here is the only place it’s repeat advocated, and I never read any articles on it until recently

it’s not an old practice for us, its a new shortcut

the only place you will read about peers who train each other on nonspecific target matches, guess doses of cipro, ignoring cdc guidelines on flippant use of antibiotics in general is in a reef forum or a reef builders article. The other day there was a post about a guys anemone here in the general forum that wouldn’t attach to his rocks and just tumbled around, I kept waiting for someone to prescribe him 500 mg cipro, and for the Xenia that wouldn’t open, and one of these days for someones cyano challenge when a reefer with spare cipro laying around sees it temporarily kills monerans in a reef tank

cipro dosing saves reefers from having to think and strategize, they’ll capitalize on its easy access for every whim soon, just watch. If it’s application causes an anemone to open up theyll buy it in droves / currently underway

 

[LadAShark]

Add to that reefing obsessively in forums for 22 yrs and here is the only place it’s repeat advocated, and I never read any articles on it until recently

it’s not an old practice for us, its a new shortcut

the only place you will read about peers who train each other on nonspecific target matches, guess doses of cipro, ignoring cdc guidelines on flippant use of antibiotics in general is in a reef forum or a reef builders article. The other day there was a post about a guys anemone here in the general forum that wouldn’t attach to his rocks and just tumbled around, I kept waiting for someone to prescribe him 500 mg cipro, and for the Xenia that wouldn’t open, and one of these days for someones cyano challenge when a reefer with spare cipro laying around sees it temporarily kills monerans in a reef tank

cipro dosing saves reefers from having to think and strategize, they’ll capitalize on its easy access for every whim soon, just watch. If it’s application causes an anemone to open up theyll buy it in droves / currently underway

Another thing people aren't considering is that the use of cipro without proper consideration will increase resistance to it in our aquariums themselves, and that could very well spread around the hobby, even if it doesn't spread to bacteria that infect humans.

As for antibiotic resistance in human pathogens, a lot of it is much more likely caused by improper use of antibiotics on humans. Many countries dispense it like candy. People take them for viral infections as well, and take them how they feel like.

The major risk for antibiotic resistance in humans comes in 2 forms:
1) not properly eliminating the pathogen, leaving now antibiotic resistant selected pathogens
2) natural human bacteria develop antibiotic resistance, can occasionally become pathogenic, and can spread these genes to other bacteria (because bacteria can share dna in various ways)

Ultimately the improper disposal of antibiotics on the hobbyist end is unlikely to constitute a substantial selective pressure, as the doses we use are relatively low and infrequent, and the bacteria that get exposed to them will not be normal human pathogens much of the time. The bigger issue from this end is actually environmental stewardship. Widespread improper disposal of antibiotics stands to devastate the natural microbiome. This is a bigger problem than just our hobby.

In summation, it's not that likely that antibiotics we the hobbyists use will have a substantial effect on human pathogen abx resistance, given that it is both an incredibly low amount, and that society at large is releasing far higher quantities (approximately 50% of cipro taken is excreted in the urine unchanged, for example). But this does not free us of problems, as we are still having an impact on our hobby microbiomes (which inevitably is shared via frag swaps or whatnot) and also on the microbiomes we don't think about, like soil microbiomes.

Anyway, since everybody is so freaked out anyway, here's a simple solution: https://www.sciencedirect.com/science/article/abs/pii/S0045653513000738?via=ihub

Simply allowing ciprofloxacin to be exposed to the sun makes it degrade RAPIDLY. Here's what percentage of fluoroquinolones (including cipro) remain by time. It appears to follow psuedo first order kinetics under sunlight, at an extremely rapid rate at that. Thermal degradation/water degradation of ciprofloxacin is negligible to nonexistent, however just simply setting out the water used to sit in the sun for tens of minutes (we wouldn't want any molecules getting past, now would we?) would pretty much guarantee that no cipro is left in it.

So for those of you who thought cipro could be used in the light, think again. Even visible light without UV causes cipro to degrade to some extent.

 

[brandon429]

Ladashark anytime this thread is bumped i dread reading the posts but that's a rare sensible input I appreciate reading, excellent perspective wow

 

[MnFish1]

Another thing people aren't considering is that the use of cipro without proper consideration will increase resistance to it in our aquariums themselves, and that could very well spread around the hobby, even if it doesn't spread to bacteria that infect humans.

As for antibiotic resistance in human pathogens, a lot of it is much more likely caused by improper use of antibiotics on humans. Many countries dispense it like candy. People take them for viral infections as well, and take them how they feel like.

The major risk for antibiotic resistance in humans comes in 2 forms:
1) not properly eliminating the pathogen, leaving now antibiotic resistant selected pathogens
2) natural human bacteria develop antibiotic resistance, can occasionally become pathogenic, and can spread these genes to other bacteria (because bacteria can share dna in various ways)

Ultimately the improper disposal of antibiotics on the hobbyist end is unlikely to constitute a substantial selective pressure, as the doses we use are relatively low and infrequent, and the bacteria that get exposed to them will not be normal human pathogens much of the time. The bigger issue from this end is actually environmental stewardship. Widespread improper disposal of antibiotics stands to devastate the natural microbiome. This is a bigger problem than just our hobby.

In summation, it's not that likely that antibiotics we the hobbyists use will have a substantial effect on human pathogen abx resistance, given that it is both an incredibly low amount, and that society at large is releasing far higher quantities (approximately 50% of cipro taken is excreted in the urine unchanged, for example). But this does not free us of problems, as we are still having an impact on our hobby microbiomes (which inevitably is shared via frag swaps or whatnot) and also on the microbiomes we don't think about, like soil microbiomes.

Anyway, since everybody is so freaked out anyway, here's a simple solution: https://www.sciencedirect.com/science/article/abs/pii/S0045653513000738?via=ihub

Simply allowing ciprofloxacin to be exposed to the sun makes it degrade RAPIDLY. Here's what percentage of fluoroquinolones (including cipro) remain by time. It appears to follow psuedo first order kinetics under sunlight, at an extremely rapid rate at that. Thermal degradation/water degradation of ciprofloxacin is negligible to nonexistent, however just simply setting out the water used to sit in the sun for tens of minutes (we wouldn't want any molecules getting past, now would we?) would pretty much guarantee that no cipro is left in it.

So for those of you who thought cipro could be used in the light, think again. Even visible light without UV causes cipro to degrade to some extent.

It's too bad that the methods used were not viewable without purchasing the article. I would be interested in seeing the preparation used for the experiment. Though it's widely known that cipro degrades in light, its odd - when its given intravenously, I do not remember that its stored in an opaque container, certainly the tubing that it goes through is clear. if cipro was indeed degraded this quickly, intravenous cipro would not be effective, right - since it is given over 60 minutes. Additionally - its given (usually) IV and orally at the same dose.

Your other points make sense except - they are a little off the topic that the OP posted (although this thread has gone all over) - which was routine use of cipro/amoxicillin dips. I think the best point you made is that using cipro in a display tank is likely to cause widespread resistance to various bacteria within the tank- and this resistance can spread to others even in the absence of cipro. The bottom line - IMHO - there is no rationale for using Cipro, etc, as a prophylactic treatment/antibiotic. BTW - the same goes with metronidazole, kanamycin,neomycin, etc. If a person has a documented infection/symptoms that suggest a bacterial infection, and there is data out there that suggests the coral/fish/etc can be treated with it, to me thats a different ball game. BTW - same issue - fluconazole use for algae.

 

[LadAShark]

It's too bad that the methods used were not viewable without purchasing the article. I would be interested in seeing the preparation used for the experiment. Though it's widely known that cipro degrades in light, its odd - when its given intravenously, I do not remember that its stored in an opaque container, certainly the tubing that it goes through is clear. if cipro was indeed degraded this quickly, intravenous cipro would not be effective, right - since it is given over 60 minutes. Additionally - its given (usually) IV and orally at the same dose.

Your other points make sense except - they are a little off the topic that the OP posted (although this thread has gone all over) - which was routine use of cipro/amoxicillin dips. I think the best point you made is that using cipro in a display tank is likely to cause widespread resistance to various bacteria within the tank- and this resistance can spread to others even in the absence of cipro. The bottom line - IMHO - there is no rationale for using Cipro, etc, as a prophylactic treatment/antibiotic. BTW - the same goes with metronidazole, kanamycin,neomycin, etc. If a person has a documented infection/symptoms that suggest a bacterial infection, and there is data out there that suggests the coral/fish/etc can be treated with it, to me thats a different ball game. BTW - same issue - fluconazole use for algae.

Yes, cipro is given at the same dose roughly IV and orally, as it is absorbed readily and has something to the order of 70% bioavailability PO, unlike many drugs which undergo first pass metabolism with a sub 50% bioavailability PO.

The exposure to UVB and UVC as well as just far greater amounts of light in general could readily account for that. IV bags, tubing, and protective covers for them also exist, which also mitigate the breakdown. Furthermore IV bags contain fairly pure water, without much in the way of reactants to allow cipro to break down.

Judicious use of such medications is definitely necessary, however it's worth noting that the presence of other selective pressures can slow or prevent antibiotic resistance, namely diverse microbiomes. In addition, using narrow spectrum antibiotics also slows antibiotic resistance, and in a proper microbiome could potentially stop it. Here's a different interesting paper on this topic: https://www.nature.com/articles/s41396-019-0483-z
(This is also why protecting natural ecosystems is essential, disease is a much bigger problem when heterogeneity is lost and fewer species exist)

Just a tangent, of course. Ultimately we shouldn't be reaching for antibiotics quickly, when we do use antibiotics we must make sure we eliminate the problem pathogen, and then some. Just because we see symptoms stopping doesn't mean we are all clear, it's best to continue treatment just a little more after we begin to see recovery. This is both for the animal we're treating as well as to prevent any residual bacteria slipping through. But as you say, absolutely antibiotics should not be used prophylactically.

 

[MnFish1]

There is a bit more involved than just bacterial resistance when discussing the over use/prescribing of painkillers. I don't see anyone getting addicted to cipro. I would suggest researching the opiate epidemic.

Nor do you know what i do or do not have knowledge of.

Check out this link. You're right neither of us have any knowledge about the knowledge of the other person. https://www.medicalnewstoday.com/articles/197616

 

[Dutch_Mill]

I notice that people underestimate the overuse of antibiotics, and think that bacterial resistance is something out of a sci-fi movie. Not knowing that its something somewhat common and antibiotic resistant bacteria are present as we speak. If I had to bet on the next pandemic (god forbid) I think this is how it might start.
Thank you for sharing.

Pandemics tend to be viral, not bacterial.