Resistant E.coli in urine sample

Re: Resistant E.coli in urine sample

Rob Loxley — Tue, 04 Jan 2011 23:50:20 GMT

[quote user="David Beattie"]Has definitely got me thnking a bit more on what a lab actually means if it reports a bug as 'RESISTANT' to a given antibiotic. Totally depends how resistant it is and what levels of drug will reach that area, so I assume they have different cut-off values dependent on whether the sample I've sent is urine, skin pustule-contents or topical ear swab?[/quote]

Definitely with ear swabs coming back as FQ resistant pseudomonas it's still worth topical application of baytril as very high drug levels can be achieved and will often work.

Re: Resistant E.coli in urine sample

Anonymous — Tue, 04 Jan 2011 19:30:29 GMT

Thanks for ideas Sarah.

SG by refractometer was concentrated, would have to check records but pretty sure >1.035.

I'd thought I'd see if it cleared OK on antibiotics first and only look for an underlying cause if either this UTI recurred or another occurred. Wouldn't have thought of measuring fasting bile acids, so thanks for the suggestion - is this because PSS can be an underlying cause? Is hardly stunted, with a growth of about 3kg a week currently, so I'm not too suspicious presently of PSS.

Sent cysto results to two labs (different from first lab used for free-catch sample), with the main difference being both these labs considered it sensitive to cefalexin rather than resistant: here's the sensitivity report from an extremely helpful microbiologist at Abbey:

RESISTANT: TMPS, clindamycin, erythromycin, amox/clav, marbofloxacin, enrofloxacin, doxycycline, carbenicillin, piperacillin, ticarcillin, ticarcillin/clavulanate, gentamicin, tobramycin.

SENSITIVE: cephalexin, cefovecin, ceftazidime, cefpodoxime, fosfomycin, amikacin, imipenem

The obvious choice of treatment therefore appeared to be between cephalexin and cefovecin.

I've read conflicting reports on the use of cephalexin to treat E.coli, with a transcript by Dawn Merton Boothe, DVM, PhD, DACVIM, DACVCP, entitled "Antimicrobial Dosing Regimens: A Dynamic Challenge" at the ACVIM Forum 2009 (Auburn, AL, USA) reasoning against as follows:

"cephalexin, with a half‐life of 1.3 hr. At 25 mg/kg PO, 15 mcg/ml is achieved. ... For E coli, with an MIC 90 of 16 mcg/ml, not even one half‐life can lapse. Cephalexin should not be used to treat E coli."

Though the 15mcg/ml she refers to is the plasma drug concentration, it is generally thought (I think) that the concentration in the urine is probably 200 times this, which is possibly why Ettinger lists it as an appropriate choice of empirical treatment for a UTI while citing E.coli as the joint-favourite for most likely pathogen.

Idexx offer an MIC testing on culture (see http://www.idexx.co.uk/animalhealth/laboratory/mic/faq/), and gave an MIC=16mcg/ml for cefalexin (i.e. pretty standard for an E.coli).

I decided cefalexin was the most appropriate choice (though if it was not going to be effective at maintaining levels above the MIC for 50% of treatment time, then arguably cefovecin, despite being a 3rd generation cephalosporin, would be more appropriate?) and calculated a dosage as follows:

Urine peak drug concentration = 200 x plasma peak conc. = 200 x 15 = 3000mcg/ml

Half life = 1.5hrs; 7 half-lives (i.e. 10.5 hrs) before urine concs fall below MIC; twice daily dosing at this rate should be effective.

I actually decided to dose q8hrs as wanted to treat the vaginitis (which I'm still hoping will resolve once she has her first season...) also and thought better to err on side of higher dose?

In trying to use MIC value, I found main problem was lack of data or conflicting data. For instance, couldn't find any reliable data on what concentrations were reached in urine compared to plasma. Also datasheets variably report core data (e.g. 'Cephacare' reports a half-life of 2.5-3hrs, while 'Cephorum' reports 90mins).

Has definitely got me thnking a bit more on what a lab actually means if it reports a bug as 'RESISTANT' to a given antibiotic. Totally depends how resistant it is and what levels of drug will reach that area, so I assume they have different cut-off values dependent on whether the sample I've sent is urine, skin pustule-contents or topical ear swab?

Re: Resistant E.coli in urine sample

sarah mason — Mon, 03 Jan 2011 21:35:25 GMT

Do you have a SG on the urine? isostheuric urine would suggest an underlying problem. Might be worth doing a pre-bile acid on a dog with a history of this age with a history of pollakuria.

Re: Resistant E.coli in urine sample

Anonymous — Wed, 15 Dec 2010 20:46:55 GMT

Sounds like a clinical trial in the making

Good to hear from you, Ste - Merry Christmas to you, Rebs and Ruby

Re: Resistant E.coli in urine sample

Stephen Ashman — Wed, 15 Dec 2010 20:44:39 GMT

[quote user="David Beattie"]seems a little bit like labelling my watch as 'water-resistant' (splash some on and it's fine, but turn a hose on it and that's a different matter...). [/quote]

I can recommend the Casio Illuminator with electro luminescence, I am confident it would withstand the hose

Re: Resistant E.coli in urine sample

Anonymous — Wed, 15 Dec 2010 20:43:38 GMT

Cheers

The vaginal cytology pictures seem to have vanished, though - I thought I'd posted them along with the urine sediment. Perhaps was too much to upload to a post?

Re: Resistant E.coli in urine sample

Richard Fox — Wed, 15 Dec 2010 20:22:10 GMT

Wow - now that's a read at 8pm after 40 mins of cycling on my turbo

Nice piccies BTW - NL + rods + phagocytosis - can't get better than that

Glad Stephen was a help.

Re: Resistant E.coli in urine sample

Anonymous — Wed, 15 Dec 2010 20:05:58 GMT

Re: Resistant E.coli in urine sample

Anonymous — Wed, 15 Dec 2010 20:02:59 GMT

Thanks for suggestions and comments

Richard: Thanks for messages and support - spoke to Stephen this afternoon who was extremely helpful and dispatched some urine 1st class in post...

Laurence: Good point about the antibiotics concentrating in urine. This was part of what I was wondering about - labelling a bacteria as 'resistant' to a given antibiotic seems a little bit like labelling my watch as 'water-resistant' (splash some on and it's fine, but turn a hose on it and that's a different matter...). I was interested in getting in vitro MIC values with the culture and sensitivity report and then trying to be vaguely quantitative about what dose of antibiotic(s) to give based on this, and other factors. If we assume that marbofloxacin concentrations are 10 to 20-fold higher in urine than in plasma (say 10-fold), and pretended the MIC for the E.coli to be 0.06mcg/ml (this is apparently the MIC to marbofloxacin of 90% of E.coli isolates, but possibly not this one), we could make a semi-quantitative analysis as follows. For a concentration-dependent drug, we might typically want the plasma drug concentration (Cmax) to be 10 to 12 times the MIC; bearing in mind the urine concs 10x that of plasma, aiming for a plasma conc. of just 1xMIC would probably be sufficient (though obviously higher concs are prefarable). The 'Marbocyl' datasheet suggests that the plasma Cmax after oral dosing at 2mg/kg is 1.5mcg/ml, then one could be pretty happy that it should anihilate the bug. The problems with this method are pretty obvious: it might sound a bit scientific, but is only as good as the data - one needs an MIC value for the bug, an idea of what the effective concentrations in the tissue of interest are for a given dosing regimen etc. In this hypothetical case, there seem to be widely different estimations of the urinary conc of fluoroquinolones, with estimates of 'several hundred times' the plasma concentration also being given. It appears Idexx is the only lab in the UK to supply MIC values with culture and sensitivity testing, but I'm not sure what antibiotics this service operates for (with a suggestion that they use a human machine, so may not be specific vet ones).

Michael: re 'all or nothing' fluoroquinolone resistance (I gather from your post you mean by this that if resistant to one fluoroquinolone, then will be resistant to them all). Just pulled out a culture report from a Pseudomonas bug a while ago which was reported as sensitive to marbofloxacin and ciprofloxacin and resistant to enrofloxacin (as was the Proteus in the same culture). I had it in my head that enrofloxacin was 80% metabolised to ciprofloxacin in the dog (though can't find a reference to that now), so perhaps Baytril tablets would have been effective at a high enough dose. I think it's fair to say that if a sensitivity suggests resistance to one fluoroquinolone, then I would be a bit suspicious about some degree of resistance to others in the class also. Re cefpodoxime: I'm not sure precisely what 'generation' of cephalosporin this is, but am pretty convinced its inclusion in the sensitivity testing is to identify extended-spectrum beta-lactamase (ESBL) producing-bugs (requiring reporting, I think), rather than as an indication that I should be grabbing some off the shelf. The bug is quite possibly sensitive to 'Convenia' and that might actually be a decent choice of treatment (thanks for suggestion!), but I would prefer to confirm this sensitivity first. I don't actually have a bottle of Convenia to hand, so would have to order one specially (rightly or wrongly, I have a thing about giving a third generation cephalosporin where something else would suffice, like a 1st generation cephalosporin; indeed the licensing of the drug required the following on the datasheet, "It is prudent to reserve third generation cephalosporins for the treatment of clinical conditions, which have responded poorly, or are expected to respond poorly, to other classes of antibiotics or first generation cephalosporins. Use of the product should be based on susceptibility testing...", shame that seems to have been forgotten in the drug advertising *cough*) and it's reasonably pricey. Definitely better than considering a fluoroquinolone in a juvenile giant-breed bitch, I suspect. Blind cysto worked fine

Lucy: My reluctance to doing contrast cystography at this stage is on 2 accounts:

I didn't wish to pass a urinary catheter through a mucky vulva/vagina and introduce infection into the bladder on the off-chance that it wasn't actually there already.
I find this quite a hastle (and then the client finds it a hastle because I charge them for my hastle) and have no reason to believe that there is any underlying complicating reason at this stage.

Certainly, with the bitch probably having had a UTI from a young age, congenital anomalies may exist, or indeed complications like uroliths may have developed, but I would probably only go looking for these if, after treating the bacterial cystitis appropriately and waited for a season to see if that cleared the vaginitis, a problem was still evident.

Anyone else interested(!): Nice full bladder when came in today and took a cysto sample for C&S testing. Had rods in it, confirming that a bacterial cystitis is present. Vaginal cytology showed wbcs+++ and nucleated keratinocytes; few of wbcs had phagocytosed bacteria (mostly rods) [will try to upload photos down microscope just for fun]. Owners report that vagina less sticky and urination more normal and have maintained on TMPS while awaiting C&S results and coming up with new plan

Re: Resistant E.coli in urine sample

Lucy K — Wed, 15 Dec 2010 17:50:57 GMT

Would it be worth doing positive or double contrast cystography to view the integrity of the bladder, urethra and other retroperitoneal structures? I'm not suggesting this as an answer- just for my own education really!

Re: Resistant E.coli in urine sample

Michael Woodhouse — Wed, 15 Dec 2010 13:32:21 GMT

My understanding was susceptibility for the flouroquinolones was all or nothing and if resistant to one member of the group likely to be resistant to them all.

My take on cefpodoxime was it was an example of a 3rd generation cephlasporin, why not give it a shot of Convenia? If memory serves that's also 3rd gen.

I wouldn't worry too much about a cysto, If I do them blind I kennel for the morning, sedate last job before lunch and usually they have a palpable bladder. Have used the cow scanner, but usually go in blind. I have seen a number of u/s guided cystos miss that I don't worry too much.

Do remember TMPS and penicillins/cephlasporins concentrate in urine, meaning that the in vitro and in vivo sensitivities can vary.

Re: Resistant E.coli in urine sample

Laurence Webb — Tue, 14 Dec 2010 22:08:13 GMT

Yes, I'd be more believing that the culture is of significance as it's a pure growth, not a mixed bunch of bugs. Cysto is obviously the best way to find out but a catheterised sample would be useful, especially as you could combine it with some imaging.

IDEXX give sensitivity for antibiotics although in vitro sensitivity isn't always the same as in vivo especially as some antibiotics concentrate in the urine at very high levels

Re: Resistant E.coli in urine sample

Richard Fox — Tue, 14 Dec 2010 19:38:47 GMT

I though most cases of cystitis in bitches are due to gram -ve like proteus or E. coli as they are derived from faecal bacteria?

Re: Resistant E.coli in urine sample

Anonymous — Tue, 14 Dec 2010 17:51:22 GMT

Small juvenile vulva. Has very hairy bum and had D+ a month ago, so faecal contamination of vulva certainly a possibility (though there were wbcs+++ in free catch urine sediment, so some sort of inflammatory process somewhere between bladder and outside world, also sediment of reasonably fresh urine showed numerous rods on 2 separate occasions and owners did seem to have done reasonable job of collecting a 'decent' free-catch sample).

Thanks for suggestion

Rang owner just now who reports that the bitch puppy is not urinating as much since starting the TMPS and is no longer 'phantom' urinating as she calls it (was squatting after she had urinated and not passing anything on occasions). May be pure coincidence or wishful thinking, or perhaps 'resistance' is not absolute and high concentration achieved in urine is having some effect. Owner also feels that with hindsight has had pollakiuria since a pup and thinks the problem has been there since she had pup, I guess congenital anomalies aren't out of the question (though a straightforward UTI sounds more likely I think...)

Re: Resistant E.coli in urine sample

Hannah Wynne Richards — Tue, 14 Dec 2010 17:26:18 GMT

Pure growth E coli suggests faecal contamination-what's the vulval conformation like ?

Wynne

Re: Resistant E.coli in urine sample

Richard Fox — Tue, 14 Dec 2010 15:29:55 GMT

I just sent you a mail about further cultures but IIRC juvelile vaginitis is usually sterile or scanty growths of floral bacteria inc. coliforms and is usually mucoid to mucopurulent. How about a a catheter sample if you can't get a cysto? Have a conversation with our in house bacteriologist Stephen Steen (he's off today but in on Wed) about further culture and sens but also unless it is resistant to TMPS is something else occurring - urine dipstick/sedimet analysis/contrast bladder studies?