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Amoxicillin Pharmacology - Muddy Waters Over Dosage Scheduled? To double dose or not?

Rybee

Bluelighter
Joined
May 29, 2013
Messages
1,305
Hi All, first of all I've had a fairly severe chest infection that's kept me up all night so have taken some Quetipaine, Morphine, Clonazolam, and Pregabalin to induce a strong sleep - I'm feeling quite faded and as such, my post may be a tad incoherent - really sorry for that, I do hope it's okay.

Background to Story
I had quite a severe chest infection come on w/c Monday 28th September and was p/x'd 500mg Amoxicillin TDS. I'm a bit of an antibiotic-phobe due the whole resilience epidemic and what not so decided to go without taking any to see if it just passed naturally. Reluctantly, I had to take the week off of work expecting to be fine to return by the end of last week (1st/2nd Oct). The Saturday just gone (4th) I was wheezing more than Lil Wayne and gasping for breath after walking up the stairs and generally losing my breath during normal conversation. This was also accompanied by a high fever which has got really quite bad over the last 48 hours and I'm now feeling horribly shit and have just been signed off of work for another week. Much to the annoyance of myself as I only have 8 weeks of my job left and don't want to be seen as a winding down sick-note/slacker, but also my local team of four (in HR covering ~1500 staff is quite a task). One colleague is on holiday and my doctor has signed me off work until w/c 12th Oct so they're only down to 2/4 people in office to battle away against all of our workloads.

So the jist of this story is that I need to get my chest infection cleared up ASAP (and have it NOT return) so that I can return to work and muck in and help reduce the workload that the two girls are picking up for the four of us, hopefully on Thursday/Friday. This morning my doctor prescribed me the same 5 day course of Amoxicillin (500mg TDS) that he prescribed to me last Monday.

I've read so many conflicting articles on antibiotics, and if I'm honest, they're one class of drug that scares me a little bit due to resilience - I think we're heading for a world-wide antibiotic resilience crisis quite soon. I've just cashed in my second prescription so have 30x500mg Amoxicillin's on hand for a 5 day course, and from a Pharmacological POV I need to know how much to take in order to really hit this bacterial infection this on the head ASAP not allow it to come back so that I can get back into action, hopefully attending work on Thursday and Friday to help out my team.

Now 'the obvious 8)' thing to do to help me get the best chance of a speedy recovery - and I say it like that, as I have no idea about antibiotics... is either one of four things IMO?

1) Just take 500mg TDS course for 5 days as generically directed and *hope* that is sufficient to really beat the fuck outta this infection with no chance of it returning - anyway, I guess the guidelines were drawn up my Doctors and Pharmacists alike, so as to be as effective as possible?

2) Just take 500mg TDS course for 5 days as generically directed, but then carry on by taking the second packet at another 500mg TDS course for a further 5 days to really ensure I've nailed the infection on the head and that it wont come back. I can't keep going back to work then pulling out then going back again like I was last week... it's really disruptive to my team.

3) Instead of following the generic 500mg TDS guidelines, double my dose to 1,00mg TDS. The thought being, that this would really 'hit the infection hard'. So take 1,000mg in the morning 1,000mg in the afternoon and 1,000mg in the evening for 5 days to finish the course, instead of 500mg in the morning, 500 in the afternoon and 500mg in the evening, just as I usually would anyway in the hope that the extra potent double-whammy dose of antibiotics for a short period of time would absolutely annihilate the infection, clear it up very quickly allow me to return to work on Thursday/Friday instead of next Monday/Tuesday. I know the team could really do with my support.

4) As Amoxicillin seems to have a half life of only ~60 minutes, I could stick to my 5 day course but instead of taking 500mg TDS I could take 500mg Q4H (six times daily, so, every 4 hours). This would allow me to squeeze in double the dose of antibiotics during my five day course but possibly reap some more rewards by spreading out the 6x500mg dose throughout the day and night every 4 hours and thus provide my blood stream with a highly concentrated and steady dose throughout the day and night.

As said, I really do apologise if these sound like stupid suggestions/questions but I did see a junior who kept having to refer to his handbook which didn't feel me with confidence - so I just had to trust his advise. Admittedly the pharmacological mechanisms of antibiotics are a whole now world to me, I don't know much about their use (apart from Gamma Positive and Gamma Negative antibiotics which I've just been reading about!)

So yeah please take it easy with me, and anything constructive to enable a quick but thorough recovery would be really, really appreciated.

I just want to get back to work and help my colleagues <3

Thanks Rybee xx
 
Well, in the first instance, the amoxicillin may not do anything at all, since you may have a viral, rather than bacterial, chest infection (typically bronchitis is viral and pneumonia bacterial). However hopefully your GP has done his/her best to determine that it's probably a pneumonia.

Regarding the dosing, although the half-life is short, you have to understand that 500mg is a lot of amoxicillin. It's much more than is needed to inhibit the bacterial growth (what would be called the Minimum Inhibitory Concentration - MIC). Consequently, although the half-life is short, blood concentrations stay far above the MIC for a much more prolonged period thanks to the high starting dose. The TID dosing ensures that, over a 24-hr period, concentrations never fall below the MIC for a person of roughly average body mass.

Given the model employed, you can appreciate that increasing the dose is unlikely to inhibit the bacteria any more strongly since you're already far above the MIC.

The length of treatment is a valid point, however, but 5 days would usually be enough for the body's immune system to get on top of a typical pneumonia in an otherwise healthy (non immune-compromised) adult. Once the symptoms have been reduced and the amoxicillin stopped, it's unlikely to "come back" as the immune system by that point is already highly primed to kill the bug.

PS: If you would like to read a little more about the pharmacokinetic and pharmacodynamic model employed in antibiotic treatment, you could start here.
 
It would help to know if it is indeed pneumonia or acute bronchitis and where you are located. As CFC said bronchitis, asuming it isn't an acute exacerbation of chronic bronchitis is usually viral and self-limiting. Pneumonia can be viral as well, but bacterial infection is very common. Here in America macrolides, especially azithromycin have taken the place of amoxicillin as first line therapy because of a higher incidence of atypical pathogens not susceptible to amoxicillin, but that is not the case everywhere.

And typically 7-10 days has been the duration of therapy, but evidence shows 3-5 days may be sufficient.
 
Well, in the first instance, the amoxicillin may not do anything at all, since you may have a viral, rather than bacterial, chest infection (typically bronchitis is viral and pneumonia bacterial). However hopefully your GP has done his/her best to determine that it's probably a pneumonia.

Regarding the dosing, although the half-life is short, you have to understand that 500mg is a lot of amoxicillin. It's much more than is needed to inhibit the bacterial growth (what would be called the Minimum Inhibitory Concentration - MIC). Consequently, although the half-life is short, blood concentrations stay far above the MIC for a much more prolonged period thanks to the high starting dose. The TID dosing ensures that, over a 24-hr period, concentrations never fall below the MIC for a person of roughly average body mass.

Given the model employed, you can appreciate that increasing the dose is unlikely to inhibit the bacteria any more strongly since you're already far above the MIC.

The length of treatment is a valid point, however, but 5 days would usually be enough for the body's immune system to get on top of a typical pneumonia in an otherwise healthy (non immune-compromised) adult. Once the symptoms have been reduced and the amoxicillin stopped, it's unlikely to "come back" as the immune system by that point is already highly primed to kill the bug.

PS: If you would like to read a little more about the pharmacokinetic and pharmacodynamic model employed in antibiotic treatment, you could start here.

Well that's what put me off even more in the first place. I googled Amoxicillin chest infection and pretty much every article said don't bother taking them unless you have the phlegm cultured as the balance of probabilities would say that it's viral not bacterial an thus antibioitcs could do more harm than good. I did read up about the MIC thing which I found interesting, in my head, I just though it was better to keep it way above the MIC, than 'just above the MIC.

Thanks - I will give that article a read, seeing as I have nothing else to do other than stay in bed.
 
Yeah, I'd personally rather not take the antibiotics unless it had been cultured, also because of the harm caused to the GI flora. Sometimes you just have to accept you're ill and need to eat well and rest as much as possible.

Regarding the MIC, with B-Lactams like Amoxicillin they tend to inhibit cell wall biosynthesis, and thus the bactericidal activity is typically time-dependent rather than concentration-dependent. 500mg TID is still way above the MIC, and at a dose that causes few negative side-effects elsewhere in the body. Too high a dose can cause other issues (eg rashes, seizures etc) without accelerating outcomes.
 
If you take amoxicillin you should be taking probiotics, like yogurt with active cultures in it. As CFC said, it can really mess with your GI flora, and you want to keep that in balance so you get the most of the food you eat. (good nutrition helps a person heal quicker)

Also, did the doctor just diagnose you from symptoms? My stepdad had the same symptoms but ended up having congestive heart failure. Shortness of breath (breathing shallowly very quickly) fluid retention, phlegm, and a productive cough. His GP said he needed breathing treatments, but fortunately my Ma and I made him go to the hospital and get a chest x-ray. They kept him for three weeks.
 
If you are prescribed antibiotics, take them exactly as directed. Whether you feel like you need to or not, whether you get better or not. Don't modify the dosage, don't modify the frequency.

Part of why antibiotic resistance develops is people expose infectious organisms to a single dose of antibiotic and then abort therapy. If you take the whole course, whether you need it or not, you will prevent development of resistance.

500mg of amoxicillin 3-4x a day is more than enough to deal with bacterial infections. And amoxicillin is generally very well tolerated; side effects are minimal. Even though 500mg may seem like a large dose; it is neccesary to ensure your whole body becomes saturated with an inhibitory concentration of amox.

Again, it is absolutely key that you take antibiotics as directed. Do not double the dose, do not abort therapy. Take it exactly as directed. Let your doctor know if your symptoms do not improve within ~3 days. You do not need to modify the course of treatment; these drugs have been in active usage for more than 60 years now, and treatment is very routine.

Don't lose sleep about developing antibiotic resistance: amoxicillin is effectively a "silver bullet" when it is applied correctly.

Oh, by the way, don't pressure yourself to get back to work ASAP. If you are still sick when it comes time to return, don't go into work and contaminate everyone. Focus on getting better, focus on recovery. A good employer should be understanding of health issues anyway - if you are hacking and coughing up black sputum your work performance will suffer, obviously.

(Me personally: I would take antibiotics if you get the prescribed - the impact on gut flora is rather minimal for most people, compared with the misery of an active bacterial infection. A "rule of thumb" even though it may seem disgusting, is looking at the color of the sputum you cough up. If it's not clear to slightly yellow (e.g., green, brown, black, bright yellow) then it's a sign of bacterial proliferation. Waiting for a culture plate can take days, and usually the effect of antibiotic therapy is felt within 12 hours.)
 
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Finally someone said it. Thank you sekio.

In america we have this culture of working no matter what because most people cannot afford not to. So not only are you at work sick, but you risk taking out the other 2 workers. Just stay home! The quality of your work will suffer, and you might come back and everyone else is sick.

This was rampant in the restaurant business. No paid time off. No decent pay. You work sick, thats just what it is because noone could take the hit of a whole day of work missed in their paycheck.
 
I still say it comes down to the diagnosis. If the doctor simply did a physical exam with no tests, I probably would say dont take the amoxicillin. Even with the increase of resistant bacteria and guidlines on appropriate use of antimicrobials, old habits die hard and a script for an antibiotic is often written anyway.

I am a bit skeptical on the sputum color issue as well. While there is evidence that colored sputum does correlate to bacterial isolates, it is not decided if a presentation of cough with colored mucus benefits from antibiotics in acute bronchitis and other respiratory conditions. It is not really mentioned in the diagnostic criteria of even pneumonia but is still frequently asked by doctors which probably increases over prescribing.

But if you do decide to take them, then sekio is absolutely correct. Take as prescribed and finish the course. I too wouldnt worry about disturbing the GI flora as amoxicillin really isnt associated with C. Diff overgrowth much these days (historically it was though) and it may even lead to proliferation of gut bacteria is some cases. Being prescribed multiple antibiotics over a relatively short period of time is probably more of a risk to true disruption of intestinal microbes than a single agent, at normal doses and duration.
 
I'm sorry for the derail...

Kittycat or sekio. I have gotten the anti pneumonia shot. Does that protect me from both bacterial and viral? My immune system isn't that great, so I want to know what else I can do to keep from getting problems with my lungs. I used to get chronic bronchitis when I smoked. I no longer smoke.
 
The "pneumonia" vaccine is only effective against certain strains of pneumococcal bacteria that are common in causing bacterial pneumonia as well as other infections (skin infections being the most common). It doesnt provide protection against viral pneumonia.
 
Thank you Kitty Cat. Is there anything I can do to protect myself from viral pneumonia
 
Make sure you are up to date on your vaccines. Get a yearly flu shot as the influenza virus can cause pneumonia itself and is commonly occurs along with bacterial infections worsening symptoms. Obvious things like avoiding smoking and pollution, frequent hand washing, and avoiding sick people.

If you have a chronic disease, stick to your treatment ALWAYS. Vitamins and supplements dont hurt but wont prevent infection, just possibly boost your immune system.
 
Thank you so much. I have chronic hep c, stage four out of five...( the scale is from 0-4 ,0 being no fibrosis, and 4 being cirrhosis)

So I need to watch my immune system as my body is constantly struggling against that infection. I get a flu shot every year, and I was my hands like a maniac. I stopped carrying around Purell with me because it was making my hands raw.
 
No problem manboychef. Sorry to hear about your Hep C. Are you stable now or has it reached a level where liver transplantation is a real possibility? Have you tried the new meds (Sovaldi, Harvoni) or are you not a candidate for them?
 
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