Antibiotic overhaul - slow-acting antibiotics, and adds Atreyupan, a weak antibiotic

[Xhuis]

With first aid kits' infection removal capability now removed as of #23757, infections are much more commonly a death sentence early on. First aid kits are much more common than antibiotics, and now that antibiotics are the sole way to treat infections, there's very little an early survivor can do save for hoping they find antibiotics.

I don't want to just add a new item to cure infections, and feedback on the idea of restoring first aid kits' capabilities has been primarily negative, so this is a change I thought would help the game while retaining compromise and realism: Atreyupan, a fictional broad-spectrum antibiotic. Found with other common healing items like disinfectant and saline solution, it serves as a way to treat infections without removing them entirely.

Taking Atreyupan applies a hidden effect to you for 12 hours. While you have it, bites and infections progress two times slower; instead of increasing duration every turn, they do so two eight turns for the same amount. Natural recovery factor for both bites and infections is also increased by 100 for a player with Atreyupan in their body, as opposed to the base of 100 (+200 with the Infection Resistant trait.)

This means that, for a player who already has a bite or infection (which the Atreyupan can't remove entirely) they have more time available to them to try and find the necessary remedy, since after about 12 hours without help, they'll hit 60 constant pain, which more or less makes it impossible for them to fight.

Normal antibiotics have also been overhauled. If Atreyupan is a weak over-the-counter antibiotic, normal ones are strong, prescription-strength ones. Taking them adds a different effect to your system; this one slows infections by a factor of eight, and adds +200 to natural recovery chance.

Lastly, both Atreyupan and normal antibiotics show a message when taken while you have an infection and a dose isn't already in your system. This is to prevent players from downing the entire bottle at once due to the new mechanics not being immediately obvious.

tl;dr:

• Adds Atreyupan to the common drug list.
• Atreyupan comes with 5 charges, and each dose lasts 12 hours.
• Atreyupan halves the speed that bites and infections progress.
• Atreyupan can't cure bites or infections, only slow them down.
• Antibiotics are now slow-acting. Instead of an instant cure, they slow infection progression by a factor of eight, and add a substantial amount to the chance to recover naturally each turn.

[AMurkin]

Typo: Repplay.

[AMurkin]

Tabs

[AMurkin]

Excessive comma

[nexusmrsep]

Possible recipe idea: thyme oil + lard/tallow + container(glass jar? small plastic bottle?). Quantities to be considered.

[Xhuis]

Added a crafting recipe for innawoods. It uses survival 2 and needs first aid 1 - components are 3 thyme oil, 1 tallow, and 10 wild herbs.

[nexusmrsep]

Also consider adding a mortar and pestle as a tool to the recipe. You have to have something to mix/grind the ointment in.

[John-Candlebury]

Any reason why this isnt an extra function for the disinfectant?

I think the idea is good, but I'm not sure about needing a slightly different item unless its absolutely necessary

[Xhuis]

I'm not sure it could be done feasibly, as disinfectant's use_action is normal medicine. I suppose I could make it apply the effect as well, but I didn't know if that would be viewed as too powerful.

[Amariithynar]

Antibacterial ointment is just that, an antibacterial. This doesn't mean that it retards the growth of bacteria, but that it actively kills it. That was a bad change to begin with, as disinfectant and, by association, first aid kits, contain antibacterial compounds specifically to prevent infection from setting in, and cleaning a wound site to remove infection. Hard alcohol also serves a similar purpose, given alcohol's antiseptic properties as well (Antiseptics are basically just antibacterial+, in that they handle a wider range of microorganisms than just bacteria, including fungi, viruses, and protozoa, the latter of which the cause of malaria is a part of, for example). Fusidic acid is a common antibacterial ointment, and it is used to clear up most minor infections; otherwise a deep infection or a larger wound that is infected requires antibiotic tablets, or lancing and draining and constant washing of the wound, not just ointment. More info on Fusidic acid here: https://patient.info/medicine/fusidic-acid-for-skin-infections-fucidin and on wound infection here: https://patient.info/health/wound-infection

[Xhuis]

I agree, but in the PR I mentioned in the OP, the majority of people in the comments seemed to disagree with readdition of removing infections using first aid kits. This is my attempt at a compromise.

[Amariithynar]

I agree, but in the PR I mentioned in the OP, the majority of people in the comments seemed to disagree with readdition of removing infections using first aid kits. This is my attempt at a compromise.

Because they're full of crap and/or don't know what they're talking about, apparently. They are treating full-on ambulance and travel compact first aid kits as if they're the little like 1 dollar kits you can get at dollar stores and the like. I'll be putting up a post there shortly.

Even if they keep this stupid change, that doesn't mean that antibacterial ointment shouldn't be a proper antibacterial. This said, it definitely shouldn't be a binary, but follow the same treatment format where it slowly heals the infection, and further infectious attacks (those that can cause the "deep bite" effect) can introduce further infection vectors. It shouldn't just be a delay effect, though.

[kevingranade]

I don't think an ointment is the right approach, deep bites with foreign material require much more extensive care than a topical antibiotic.

I think the intermediate effect is worth doing though, how about having the same delaying effect, but change the description to be a (more common) over-the-counter antibiotic product?

I'd also be in favor of this buffing the natural recovery chance.

[Xhuis]

That could work. What should a name for it be - maybe just penicillin? I've got no idea which antibiotics in the real world are strong compared to others.

[DracoGriffin]

That could work. What should a name for it be - maybe just penicillin? I've got no idea which antibiotics in the real world are strong compared to others.

Penicillins aren't as useful as other groups/classes due to antibiotic overprescribing and misuse.

I'd suggest refactoring antibiotics into two categories --- broad and narrow-spectrum. Ignoring a lot of details, we'll just chalk broad-spectrum up to being a weaker, but more common alternative with narrow-spectrum being the current version of antibiotics (handwaving even knowing what type of infection it is, we're basically pretending the survivor somehow figured out the type of bacteria and the specific antibiotic needed -- using broad-spectrum inappropriately can actually make you more sick due to opportunistic [not to say narrow-spectrum can't either, but broad basically wipes out all your "good" current microbiota as well as more bacterial infections being resistant to broad-spectrums]).

[Xhuis]

Renamed from antibacterial ointment to amoxicillin, and updated the PR description to compromise. I also made some buffs due to its new status as a drug instead of a basic dermal cream; it now halts infection progression entirely, and comes with 5 charges. However, the effect isn't listed, and it has a health modifier of -5 due to being broad-spectrum.

The crafting recipe was also removed. I have no idea how amoxicillin is made in real life. Suggestions are welcome.

[Mecares]

Personally I like the stalling effect but dislike the 100% Protection from infection via bites, maybe half the risk but do not negate it completely. In a Zombie game getting bitten should have consequences.

[Amariithynar]

In a Zombie game getting bitten should have consequences.

As has been iterated repeatedly elsewhere, bites don't contain a T-Virus or anything. A bite infection is just a normal infection from a bite.

@Xhuis > https://pubchem.ncbi.nlm.nih.gov/compound/amoxicillin#section=Uses 6-Aminopenicillanic acid is a metabolite of penicillin v & penicillin g. D-4-Hydroxyphenylglycine seems to be one of those chemicals that is locked behind patents for processes; it can be found naturally in the latex of Euphorbia helioscopia, also known as "sun spurge", "madwoman's milk", umbrella milkweed", and "wart spurge". Unfortunately it's not naturally found in North America. It can also be isolated from vancomycin (itself a potent antibiotic) found in the soil bacteria Amycolatopsis orientalis; basically, amoxicillin isn't refinable given the access we have to raw materials and refinement processes. Penicillin, however, is, and easily so, most specifically with the variety of penicillin mold that comes from a cantaloupe, rather than from bread.

@DracoGriffin in the absence of an antibiotic, resistance is a trait that is selected against, not for, as such traits have their own costs to the bacteria, so resistant bacteria will quickly lose their resistance to penicillin in the Cataclysm, anyways. https://academic.oup.com/emph/article/2015/1/4/1795053 Even then, while there are plenty of bacteria that are resistant today, penicillin is still quite effective for a wide variety of infections still, and the mold is easily cultured, though not so easily rendered into a usable state. https://www.doomandbloom.net/making-penicillin-at-home/ we don't have a source of manganese in game, either, so either we'd have to add it, abstract it, or replace it, if we were to introduce penicillin.

Additionally, broad-spectrum antibiotics aren't broad-spectrum because they're weaker, they're broad-spectrum because they're stronger, and very flexible; when you're infected with something that the symptoms don't give a definite answer for, or it's a serious infection, they give you a broad-spectrum antibiotic. Narrow-spectrum antibiotics are such because they cover only a very limited method of addressing bacteria, by comparison; they either affect gram-negative or gram-positive bacteria only, which has its own uses in focusing in on one bacteria, but that's it; furthermore, the exact strain of the infection needs to be known for a narrow-spectrum antibiotic to be effective.

[DracoGriffin]

@DracoGriffin in the absence of an antibiotic, resistance is a trait that is selected against, not for, as such traits have their own costs to the bacteria, so resistant bacteria will quickly lose their resistance to penicillin in the Cataclysm, anyways. https://academic.oup.com/emph/article/2015/1/4/1795053 Even then, while there are plenty of bacteria that are resistant today, penicillin is still quite effective for a wide variety of infections still, and the mold is easily cultured, though not so easily rendered into a usable state. https://www.doomandbloom.net/making-penicillin-at-home/ we don't have a source of manganese in game, either, so either we'd have to add it, abstract it, or replace it, if we were to introduce penicillin.
Additionally, broad-spectrum antibiotics aren't broad-spectrum because they're weaker, they're broad-spectrum because they're stronger, and very flexible; when you're infected with something that the symptoms don't give a definite answer for, or it's a serious infection, they give you a broad-spectrum antibiotic. Narrow-spectrum antibiotics are such because they cover only a very limited method of addressing bacteria, by comparison; they either affect gram-negative or gram-positive bacteria only, which has its own uses in focusing in on one bacteria, but that's it; furthermore, the exact strain of the infection needs to be known for a narrow-spectrum antibiotic to be effective.

I'm not going to address this further than necessary as this will become a long diatribe resultant over nothing, especially when trying to hammer an incredibly complex subject into a very narrow hole.

Any naturally occurring antibiotic (like penicillin) will not be selected against, that doesn't even make sense. The more artificial ones, sure, that's quite plausible to a degree. However, I'm not going to postulate that significantly into a post-apoc world with unknown variable of survivors and other issues like how rampant disease may actually be considering zombies covered in who knows what amount of microbes and such. In addition to determine what the blob may or may not influence as well when in contact with bacteria, viruses, other vectors, and so on.

Secondly, there is penicillin (basically benzylpenicillin or Penicillin G) and then there is Penicillin (the antibiotic class). And following your link seems incredibly shady and not very trustworthy, and barring that information, it appears they are basically trying to synthesize Penicillin V. Either of which aren't readily prescribed in the US (again, we are discussing on a VERY BROAD level) --- although apparently in other countries they are, so becomes more of an epidemiological issue. So, penicillin you are referring to isn't very useful on a broad level (not to say it isn't used for extremely specific infections), although amoxicillin, which is in the Penicillin class, is a traditionally widely prescribed for a number of infections. Plainly speaking, any "natural" antibiotic would more than likely be highly ineffectual against foreign pathogens and really just end up destroying your own micro-fauna, and essentially making you sicker and weaker to fight off the prevalent infection.

Thirdly, I was using the term "weaker" in the sense that it isn't targeted --- broad-spectrum, as it says on the tin, attacks both gram-positive and gram-negative bacteria, including your own host bacteria that is generally beneficially. And just because it is broad, does not mean it is stronger, nor as useful as narrow-spectrum are --- the reason narrow-spectrum are generally not used is because it is extremely easy for bacteria to develop resistance for it so they are generally withheld unless absolutely necessary or administered in a setting that won't allow the antibiotic to be misused (that is, patients at home stopping or missing doses). Furthermore, there is a lot more testing required to identify bacteria strain and type in order to utilize narrow-spectrum, not because they are weaker or not as useful. Hence why most US physicians prescribe a broad-spectrum (because generally it will work, and if it doesn't, it's already a red flag to begin serious testing in preparation for narrow-spectrum). And all this in consideration of zombie bites and the wild amount of pathogens contained in their oral cavity... yeah, we can say broad-spectrum is a good choice from a realistic standpoint, but it doesn't always work and it also attacks your own microbiota on a broad scale, whereas we can handwave a bit and say hey, narrow-spectrum will work because it targets whatever prevalent organisms in zombie bites without too much harm to the host (although narrow-spectrum harm to host varies as well).

This is slightly cherry-picking, but I really don't want to have show article after article. Not to mention this is typically more for focused care, rather than general examination.

"Broad spectrum versus Narrow spectrum effectiveness"

Among children with acute respiratory tract infections, broad-spectrum antibiotics were not associated with better clinical or patient-centered outcomes compared with narrow-spectrum antibiotics, and were associated with higher rates of adverse events. These data support the use of narrow-spectrum antibiotics for most children with acute respiratory tract infections.

"Light background reading" for anyone interested.

20% – Proportion of people that are persistent carriers of S. aureus52
$3 billion – Annual healthcare costs associated with MRSA in US62
19,000 – Deaths per year caused by MRSA in the US62
61% – Vancomycin (52) resistance rate of E. faecium in the US5
40% – S. pneumoniae strains resistant to penicillin75,76
50% – Chance of contracting C. difficile with > 4 week hospital stays80
1.3 million – Worldwide deaths caused by TB per year90
$483,000 – Average cost of XDR-TB treatment92–93
30% – Increase in carbapenem resistant A. baumannii strains from 1995–2004129
30% – Quinolone resistance rate for Enterobacter138
700,000 – N. gonnorhoeae infections in the US per year3,4
15.5% – HAI incidence rate in developing countries144

[Inglonias]

I like this change, but I think you need to make it more clear that this doesn't cure infections on its own.

"A broad-spectrum antibiotic used in treatment of infections. Typically used to supplement the immune system's natural defense, but probably won't cure them on its own."

[Xhuis]

Holy wall of text. I thought only doctors did that.

@Inglonias Fair point.

[Xhuis]

Tweaked the effects a lil' more.

• Healthiness is now -2, from -5.
• Recovery factor increase is also applied to bites, and bites won't progress into infections.
• No longer protects from new bites.
• Changed the description.

[kevingranade]

Good catch updating the existing antibiotic description as well 👍
Maybe actually call out that it immediately cures infections?

[Amariithynar]

@nexusmrsep As I said, about the only thing that you wouldn't really be able to easily synthesize (but technically could) are the quatrenary ammonium compounds... but they aren't even all that effective as disinfectants. https://www.sciencedirect.com/topics/neuroscience/quaternary-ammonium-compounds They're long-term-storage stable, and are generally low on the toxicity scale, so carelessness doesn't matter as much if someone sods up with quats-and-alcohol solutions; though it is highly toxic to waterborne life. https://www.education.nh.gov/instruction/school_health/documents/disinfectants.pdf There's a catagory beyond disinfectant known as sterilants, but chemical sterilants exhibit serious human toxicity as well, and are only used in very specific circumstances- none of which involve application to living beings; they're used exclusively to sterilize lab equipment, for example, though an autoclave steam-heating equipment works just as well and is safer.

[kevingranade]

@Xhuis just focus on the existing version, everyone else is getting way off in the weeds. I don't have time to evaluate whether I agree with their overall proposal, but your changes are definitely an improvement.

I'm not against having a strong antibiotic and a weak antibiotic, but they should both work over time, now that we have that feature working, that's how they should work in general.

If theres a strong and a weak version, the version you have now is the strong version, it has something like a 90% chance of curing a bite with a single dose, and probably a 99%+ chance with multiple doses.

For the actual weak version, it would probably work to cut both effects (progress delay and recovery chance boost) roughly in half, but I haven't run any numbers.

My goal would be something like a 90% recovery rate with one dose and a 99%+ recovery rate with a full course for the strong antibiotic, and 60%/80% for the weak antibiotic.

[Xhuis]

That should be it.

• Normal antibiotics now slow infections by a factor of eight and add a large amount (+200) to normal recovery chance. As they were previously a guaranteed cure, having them serve the same purpose seems well to me.
• Atreyupan now slows infections by half and adds a good amount (+100) to normal recovery chance.
• Added a message when taking both kinds of medicine if they aren't in your system and you have an infection, to prevent people downing the whole bottle due to the new mechanics not being immediately obvious.
• Buffed Atreyupan spawn rates, as some playtesting showed that they weren't as common as I intended them to be. They should be findable in about one every 5-6 houses, if my guessing is correct.

I'm thinking about adding another instant-acting antibiotic in the form of some sort of experimental medicine found in labs, but that's for another PR if I do.

[DracoGriffin]

has_effect ( has extra space here to remove --> has_effect(

[DracoGriffin]

has_effect ( has extra space here to remove --> has_effect(

[Xhuis]

This should be ready, unless there's anything that needs to be changed?

[ZhilkinSerg]

} else if { should go on single line.

[ZhilkinSerg]

} else if { should go on single line.

[ZhilkinSerg]

} else if { should go on single line.

[ZhilkinSerg]

} else if { should go on single line.

[ZhilkinSerg]

} else if { should go on single line.

[ZhilkinSerg]

There are still some astyle regressions in player_hardcoded_effects.cpp and iuse.cpp.

[ZhilkinSerg]

[ZhilkinSerg]

@Xhuis, you've had a couple of conflicts and also missing whitespace, which broke astyle, so I've fixed this for you before mergetesting.

[Xhuis]

Thank you, I appreciate that. I'm still not very good at C++, and I'm having to fix code styling errors in most of my PRs, but I'm slowly adjusting.