tobramycin dose dogs

RE: tobramycin dose dogs

Beats — Tue, 29 Sep 2020 19:08:30 GMT

I'm going to have to rely on you reporting back to me from the Samsoc Autumn meeting, I'm afraid!

In the meantime, I'll speculate on what a "subclinical UTI" is..., but I'm assuming that if the owner has noticed signs that is not what is called "subclinical"? Is this the same as "incidental bacteriuria" (but if so then why were we looking at the urine sediment in the first place)?

I'm not sure I actually see "subclinical UTIs"?

[I'm also not sure I often see "uncomplicated UTI's" for that matter.]

I do have a few dogs with what I would term "chronic, untreated UTI's". One is a Boxer and the urine stinks to high heavens, but the owner is oblivious to this and generally reports no issues noted having gotten used to it (I think most owners would notice this dog...). He brings in a toxic vial of the urine every 3 months or so and I hold my nose and use it for teaching sediment analysis to the nursing or vet student before discussing what bin to put it in!

RE: tobramycin dose dogs

Sarah Keir — Tue, 29 Sep 2020 17:57:53 GMT

Come to the SAMSoc Autumn meeting and find out if you actually need to treat your subclinical UTI! You might be surprised at the answers!

RE: tobramycin dose dogs

Beats — Mon, 28 Sep 2020 19:59:02 GMT

Negative sediment (and culture) in January 2020.

Then bit of loss of follow-up, but no clinical signs until couple of weeks ago began with mild signs suggestive of cystitis again.

No uroliths present and pH6.5 quite respectable. Chains and clumps of cocci present, but not a lot of wbcs. Started on amoxicillin pending culture.

[I presume this is not a urease-producing organism predisposing to struvite, and therefore I did briefly consider leaving alone given few clinical signs, but thought given were some clinical signs and may predispose to further infection, or become more recalcitrant thus frustrating future treament, probably worth treating]

This was cysto culture (received 2 days after collection at lab, in plain tube):

10^4 - 10^5 cfu/ml Enterococcus spp.
Urine Antibacterial Activity	a NEGATIVE

	a This test determines whether antibacterials were detected in the sample.

MIC

MIC Testing

Isolate 1
Growth of:Enterococcus
Antibiotic                    Result                    MIC                    Sensitivity Range
---------------               -----------               ------                 ----------------------
Amoxicillin-Clavulanic acid   SENSITIVE                 <=2                    2     Ssrrr       32
Enrofloxacin                  SENSITIVE                 <=0.5                  0.5   Siir        4
Marbofloxacin                 SENSITIVE                 1                      0.5   sSirr       8
Doxycycline                   SENSITIVE                 1                      0.5   sSssir      16
Tetracycline                  SENSITIVE                 <=1                    1     Sssir       16
Nitrofurantoin                SENSITIVE                 <=16                   16    Ssirrr      512
Chloramphenicol               SENSITIVE                 8                      4     sSirr       64
Chlortetracycline             SENSITIVE                                         

Organism identified by MALDI-TOF.
Note: Generic antibiotics quoted. The choice of antibiotic and knowledge of any contraindications is the Veterinary Surgeons responsibility. MIC units expressed in ug/ml. Antibiotics without a MIC have been predicted using international guidelines.

Enterococci are tested against a targeted panel of antibiotics due to intrinsic resistance mechanisms found in this genus. They are naturally resistant to cefovecin, cephalexin, clindamycin, gentamicin and potentiated sulphonamides.

For more information on interpretation of MICs visit idexx.co.uk/files/microbiology-guide-interpreting-mic.pdf

I guess I'll find out when I phone the owner and check its urine sediment, but does anyone know if there's reason to believe would need to switch from amoxicillin [or why it is not tested as routine]?

[As an aside: Also why doxycycline, tetracycline, chlortetracycline all tested but not the oxytetracycline (one of the 3 drugs I actually regularly use for UTI's in dogs)? I'm assuming these give an idea of whether oxytet suitable, but it just seems quite random to test a urine culture to 3 different tetracyclines and not oxytet? Probably a good explanation if anyone knows it please share.]

PS - BSAVA Formulary has stuck with 9-14mg/kg q24hrs in 10th edition for dogs for those wondering if any change again with new edition, listed now for SC, IV or IM.

RE: tobramycin dose dogs

Beats — Fri, 03 Jan 2020 19:54:40 GMT

Follow-up:

Gave tobramycin at 4mg/kg SC q24hrs for 8 days at which point there were no signs of bacteria or wbcs - continued a further 3 days.

Re-cultured a week later (free-catch sample had copious rods in it again) - lab grew Enterococcus >10^5cfu/ml

MIC Testing

Isolate 1
Growth of:Enterococcus
Antibiotic                    Result                    MIC                    Sensitivity Range
---------------               -----------               ------                 ----------------------
Amoxycillin-Clavulanic acid   Resistant                                         
Enrofloxacin                  Intermediate              2                      0.5   siIr        4
Marbofloxacin                 Resistant                 >=4                    0.5   ssiRr       8
Doxycycline                   Resistant                                         
Tetracycline                  Resistant                 >=16                   1     sssiR       16
Nitrofurantoin                Intermediate              64                     16    ssIrrr      512
Chloramphenicol               SENSITIVE                 <=4                    4     Ssirr       64
Amoxicillin                   Resistant                                         

Organism identified by MALDI-TOF.
Note: Generic antibiotics quoted. The choice of antibiotic and knowledge of any contraindications is the Veterinary Surgeons responsibility. MIC units expressed in ug/ml. Antibiotics without a MIC have been predicted using international guidelines.

Enterococci are tested against a targeted panel of antibiotics due to intrinsic resistance mechanisms found in this genus. They are naturally resistant to cefovecin, cephalexin, clindamycin, gentamicin and potentiated sulphonamides.

I wondered if this was a contaminant and rods seen were Pseud back again, and started back on tobracmycin 4mg/kg SC.

3days later bacteria gone again and sediment clear. Did another 10 days of tobramycin and urine has been clear since including a cysto sample 2 weeks after antibiotics finished.

recommended D-mannose and high strength multi-probiotics
e.g.:
www.revital.co.uk/power-health-d-mannose-50gr-8903
0.2-0.4g d-mannose twice daily `Not sure conc of this preparation, but suggested quarter of human dose given twice daily would be rough guideline`
and
www.revital.co.uk/vivomixx-probiotic-450-billion-10sachets
third of sachet daily

Will continue to check urine monthly.

RE: tobramycin dose dogs

Sarah Keir — Wed, 02 Oct 2019 17:05:08 GMT

I love it that we are now aware of antibiotic stewardship but lets put this in perspective. I am a member of some international vet forums and every non-European country throws fluoroquinolones around like water, even for non-antibiotic diseases. It is getting very warring trying to educate but hopefully they will get the idea some point before we have no antibiotics left to use. Interestingly the USA is the worst culprit.

RE: tobramycin dose dogs

Michael Woodhouse — Mon, 30 Sep 2019 23:06:57 GMT

Cascade would dictate fluoroquinolone first. After that there is a horse licenced gentamicin. Personally it's not a place I'd go.

With that profile I'd reluctantly use marbofloxacin. Specifically licenced for UTIs, effective and safe. Personally I see that as justified use.

RE: tobramycin dose dogs

Beats — Mon, 30 Sep 2019 22:50:13 GMT

Thanks Michael, very open to any and all suggestions and thoughts on the case.

My thinking is:

Mainly I believe tobramycin to be less nephrotoxic than gentamicin in dogs (though that may be open to debate, and almost certainly will be dose-dependent: i.e. I guess comparing one to the other without stating at what dose is perhaps unfair). Also perhaps has slightly preferable activity versus pseudomonas compared to gentamicin. Both are probably at a similar pegging on the naughty list for antibacterial use?

Case is one with struvite stone removed 2 years ago and multiple new urine infections since. Most recently a pseudomonas with urolith formation again. Had planned to try to dissolve on s/d tins with antibiotics alongside, but reckon too much risk of pseudomonas beocming resistant while hiding out in the stone during 4-8 week dissolution, so am removing the urolith and planning on treating for 10-14days antibiotics (checking the urine after maybe 5 days), probably tobramycin at 4mg/kg q24hrs SC unless someone corrects me. The urine pH is 9 on a freshly collected cysto sample at time of culture few days ago. Reckon too big to do voiding hydropropulsion (and I'm rather too impatient for that generally...)

Sample Type	PLAIN
Urine Culture	> 10^5 cfu/ml Pseudomonas aeruginosa.
Urine Antibacterial Activity	a NEGATIVE

MIC Testing

Isolate 1
Growth of:Pseudomonas aeruginosa
Antibiotic                    Result                    MIC                    Sensitivity Range
---------------               -----------               ------                 ----------------------
Amikacin                      SENSITIVE                 <=2                    2     Ssssir      64
Gentamicin                    SENSITIVE                 <=1                    1     Sssir       16
Enrofloxacin                  SENSITIVE                 0.5                    0.12  ssSiir      4
Marbofloxacin                 SENSITIVE                 <=0.5                  0.5   Ssir        4


So fluroquinolone would be alternative option. I try to avoid their use generally (don't think I've 
ever used for a urinary infection but I might have and don't remember),
and would have concerns about rapid in vivo development of resistanfce given the MIC for enro, but 
I may be wrong on that. 
Also Have got into this mess due to last bug being treated with cefovecin and reckon
 that the narrower the antibiotic the better in this case - no need here to be wiping out the cocci on the perivulval skin etc. 
Also injectable aminoglycoside probably less 
induced resistance than oral fluoroquinolone in gut flora.

RE: tobramycin dose dogs

Michael Woodhouse — Mon, 30 Sep 2019 22:05:56 GMT

May I ask why? Is it the only thing that the sensitivity profile shows will be effective?

Never considered its use in animals.

RE: tobramycin dose dogs

Beats — Mon, 30 Sep 2019 20:52:26 GMT

Trying to answer my own question, but in case of interest or someone searches here again, I did a bit of digging and think the lower dose range sounds safer (and I presume likely effective for pseudomonas UTI) as adverse renal effects appear to be dose-related such as:

"Dogs: A study using 4 dogs for each daily intramuscular dose was carried out for 28 days. The appearance, behaviour, hematology, and blood chemistry were unaffected by doses of 3.75 to 15 mg/kg. Histologic examination of the tissue revealed that a slight renal injury, as evidenced by the finding of a mild regeneration of the cortical tubular epithelium, had occurred at the upper dose. In a further study with 4 dogs, a daily dose of 30 mg/kg was tolerated for 2 weeks with no apparent ill effects; but thereafter, anorexia, weight loss, hypoactivity and a general CNS depression were noted. Two animals were killed during the fourth week because of morbidity. Renal tubular necrosis accompanied by regeneration of the tubular epithelium was noted in all animals of the 30 mg/kg group. Dogs had a reduced tolerance for tobramycin dosage regimens of longer duration. In a study using 2 dogs/sex/dose for 90 days, a daily intramuscular dose of 3.75 or 7.5 mg/kg of tobramycin caused no changes in appearance, behaviour or body weight, but 2 of 4 dogs on the 7.5 mg/kg dose had a mild degree of renal cortical tubular epithelial regeneration or a mild reparative nephrosis. A daily dose of 15 mg/kg of tobramycin was well tolerated by 2 of 4 dogs. The other 2 dogs of this group had marked appetite suppression, weight loss and marked elevations in BUN and SGOT. One of these dogs became deaf on Day 49. This dog also showed evidence of tobramycin accumulation. A mild to moderate reparative nephrosis and inflammatory reactions at the injection sites represented the only histologic evidence of injury. The daily intravenous administration of 7.5, 15 or 30 mg/kg of tobramycin for 2 dogs/sex/dose over 14 days caused no changes in appearance or behaviour except for a single emetic episode in one dog of the 30 mg/kg group. Blood serum concentrations of tobramycin one hour after intravenous injection were similar to those found one hour after intramuscular administration. The hematologic and blood chemistry parameters were not altered significantly. A slight to moderate proteinuria was detected in one or two dogs of each dosage regimen, and a slight glucosuria occurred in one animal of the 15 mg/kg group. There was no histologic evidence of tissue injury. It seems probable, however, on the basis of the results of intramuscular administration of similar doses, that renal injury would occur with more prolonged intravenous dosage."

from https://www.sandoz.ca/sites/www.sandoz.ca/files/Tobramycin%20Ophtalmic%20Solution%20Product%20Monograph.pdf