Principles of antibiotic treatment in reproduction cases and xertes Flashcards
Case: Clinically ill dairy cow
T=39.5, P=80, R=25, anorexia, hypovolaemic, wobbly on her feet
Vaginal exam: nasty intrauterine odour,RFM present
1 day post partum, assisted delivery, dead calf
You decide she’s got clinical metritis (in cattle often caused by E.coli and a variety of anaerobic bacteria) and want to start antibiotic therapy.
1.List the factors that influence your choice of antibiotics
Additional questions wendelaw ould want to ask:
- Farm protocol? What the farm normally uses as an Abs?
- Known resistance?
- Level of current management? Like to know how accurate they are and good they are at giving the treatment/compliance, hygiene and cleanliness at farm, risk of secondary infection on the farm
- Any treatment thus far? ALWAYS ASK THIS. E.g If she’s already had pen-strep then would rather continue this for extra 2 days
My considerations:
- You need a systemic antibiotic, intrauterine antibiotic is not sufficient when the cow is clinically/systemically ill
- Check VMD product database: what is available (registered for metritis in cattle)
Compare antibiotic choices?

- We want to avoid fluroquinolones and 3 rd and 4 th gen cephalosporins (WHO)
- Withdrawal time is not a major decision maker as a truly ill cow milk would not go in bulk tank anyway.
- OTC: large volumes to give every 48 hours
- Price is considered depending on how profitable a milker she is
- TMPS not effective in a pus filled infected uterus
- Cefalexin: not a great gram –effect
Discuss decision making in this case with regards to antibiotic choice?
Decision making
- Skip cefquinome/marbofloxacin until you find a good reason
- avoid fluoroquinolones and 3rd/4th generation cephalosporins if we want to use antibiotics responsibly
- Skip TMPS as it does not work well in areas with lots of tissue debris.
- Skip cefalexin because you need good G+ & G-cover.
- Left with OTC, ceftiofurand amoxicillin

Discuss antibiotic decision making in this case further?
As you’re treating a severely ill animal, you don’t want to risk ab-resistance delaying cure, I would therefore probably skip OTC (VR paper Sheldon), in addition to potential resistance issues, the dose rate is massive and gives big lumps when admin IM, but cheap and you may want to find out for next time if resistance exists on farm.
Responsible AB use: prefer amoxicillin over a 3rd generation cephalosporin.
If animal is truly ill a 60h milk withdrawal will not be a major push from economics point of view, particularly when in first 5 days postpartum. However, 0 milk withdrawal is much easier to manage on a dairy farm (no risk of positive tank) and that with the smaller dose will make farmers prefer ceftiofur. Ceftiofuris 3rd gen cephalosporin though!

In this case as important as antibiotic choice…or sometimes even more important are the following:
- NSAIDs
- Fluids
- TLC (more specific, soft dry bedding, in/out with friends, access to food without competition, plenty food and water in front of them, warm enough)
- Enough access to feed if she is lame
- Remove RFM? If it can be drawn out without pressure yes if membrane is still attached don’t pull it out.
A huge number of factors underly the decisions made by vets in practice when selecting an antibiotic to use. When you are a new graduate it’s easy to be influenced by the pizza-wielding drug reps or what is nearest to grab, but you do need to bear some important factors in mind
First steps?
- Is the ‘problem’ infection?
- If so, bacterial, fungal, viral, mycoplasmal, parasitic or rickettsial?
- Likely organism involved and site?
- Do you need to confirm that or will you use empirical antibiotics?
- Does the infection warrant therapy?
- If so, with what?
Things to consider when trying to understand what kind of infection is it?
- You need to have a working understanding of what kind of pathogens are likely to occur in that site in that species. You should have had this information in your antibiotics lectures - it might be worth you making a list of the common pathogens and their characteristics which you can refer to.
- Whilst culture can be informative in certain circumstances, you often need an empirically chosen (ie best guess) antibiotic to cover the 5-7 days until you get the culture results back. In addition, in vitro sensitivity does not always correlate well with in vivo effectiveness. This may be because the bacteria you’re culturing are actually not the primary pathogen.
- Particularly for farm animal infection scenarios, such as BRD you will have a good idea of the likely pathogens involved in the secondary infection, and culture is not that useful in those situations. In other situations, it may be worth screening a group of cases for bacteriology, for example in mastitis cases.
What spectrum of activity do you need in an antibiotic how to choose?
- If you know what you are treating, the narrower the spectrum the better to avoid resistance. If you aren’t sure then a broad-spectrum choice might be better. Also, worth thinking about whether the drug works on a time or concentration dependent mode, which we’ll talk a bit about later.
- Again, worth thinking about making a list of these for the species you will be working with.
- Also remember that the MIC for penicillin is typically lower in susceptible organisms so it is not just about resistance, it is about efficacy; e.g. when treating Streptoccus infections, penicillin is an excellent choice.
Discuss Bacteriostatic vs bacteriocidal antibiotics?
Bacteriostatic
- Require animal’s own defence mechanism to aid pathogen removal - not good if immunocompromised.
- Act via interference with bacterial protein synthesis
Bacteriocidal
- Kills bacteria via interference with cell wall, ribosomes, DNA topoisomerases
- Don’t mix the two as they will inhibit each other
Discuss drug penetration of antibiotics?
- Where does your drug need to get to? Abscess walls, pus, pH, anaerobic environments all cause problems with getting the antibiotic to the site of infection, and may mean that an antibiotic which would be helpful for an infection in one location is not so good in a different location.
- For example, sulphonamides are inactivated in the presence of low pH tissue and tissue debris (pABA)
Discuss licensing with regards to antibiotics?
Is it licenced?
- Most of the older antibiotics are licensed for a wide-range of bacterial infections, and some of the newer antibiotics tend to have specific indications.
- Where can you get this information?
- Either from the datasheet in the box, or from the NOAH website or VMD product database
- You can search by species, drug name or ingredient…
Discuss rate and dosage of antibiotics?
-
Dose
- Bodyweight
- Formulation; beware trade names
- Minimum Inhibitory Concentration (MIC) - this is not the same as the Maximum Residue Limit (MRL)
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Rate of administration
- Is the drug concentration dependant or time dependant?
- Remember that there are differing withdrawal periods if you go off-label; and that standard withhold periods apply
- i.e. At least 7 and 28 days milk and meat
-
Toxicity and side effects?
- E.g. oxytetracycline may be an irritant to large animals and may discolour teeth in small animals under 6 months of age
What route can antibiotics go?
What route?
- Intravenous?
- Intramuscular?
- Subcutaneous?
- Intraperitoneal?
- Intramammary?
- Intra-occular?
- Per os?
- How to decide? Well, the route for which the drug has been licenced and is available is a good start. Then think about how easy it is for you/ the owner/ farmer to administer the drug by the different routes and how frequently it needs to be given. Also how well that drug will be absorbed; subcutaneous drugs are no good in a dehydrated animal, oral antibiotics are no good in an animal which is being sick.
Consider what is the withdrawal time of antibiotic?
- For food animals only. Variable between drugs and for the same drug through different routes. Typically, newer drugs tend to have a shorter withdrawal period than older ones.
- Remember that if you get this wrong in a dairy cow, a whole bulk tank might have to be discarded and you won’t be very popular.
- Make sure that the farmer knows the withdrawal period of the drugs given!
Discuss antibiotic cost?
- How much does it cost?
- Important for farmers, pet owning clients, and especially charity clinics such as the PDSA. More expensive doesn’t necessarily mean better….
- What mark-up is applied?
- Is it cheaper to dispense in bulk to avoid serial drug administration fees?
- Can you legally use a generic version/ cheaper form? Beware that they might not be licenced by the same routes, palatability may be different etc.
Consider how the owner can give the antibiotic?
Can the owner give the medication?
- Especially for the fractious cat, but also for the fell pony or cow in a massive field - there is no point dispensing a medication which the client cannot administer, so a long acting injection may be better if available.
- Remember that this is not just oral medication; if an ear is too sore for you to look down with an otoscope, there is little chance of the ear drops you prescribe getting to where you need them to go…
Compare choice factors for antibiotics choice in different species?

What would the consequences of blanket antibiotic resistance be?
The real implications of spreading drug resistance will be felt the world over, with developing countries and large emerging nations bearing the brunt of this problem. Routine surgeries and minor infections will become life- threatening once again and the hard won victories against infectious diseases of the last fifty years will be jeopardised. Hospital stays and expenses, for both public health care providers and for out of pocket payers will increase significantly. Drug resistant infections are already on the rise with numbers suggesting that up to 50,000 lives are lost each year to antibiotic-resistant infections in Europe and the US alone. Globally, at least 700,000 die each year of drug resistance in illnesses such as bacterial infections, malaria, HIV/AIDS or tuberculosis
“We have reached a critical point and must act now on a global scale to slow down antimicrobial resistance”; Professor Dame Sally Davies, UK Chief Medical Officer
Discuss primary and secondary pathogens in BRD?
- Primary pathogens
- Often viral (PI3, BRSV, IBR) with Gram negative organisms in early stages (e.g. Mannheimia)
- Secondary pathogens
- Gram positive opportunists in late stages (e.g. Trueperella)
Discuss therapeutic antibiotic treatment for BRD?
- Which calves do we treat?
- Early stages should be treated, when rectal temperature >39.0C
- False negatives?
- Calves that are missed for treatment, consequently have a poor response to treatment when started later on due to irreversible lung damage
- False positives?
- Chance of ‘unnecessary’ treatment, due to over-diagnosis when only based on a few clinical signs
What kind of antibiotic would we like in the ideal world?
- A broad spectrum antibiotic which is above the MIC for the pathogens involved
- Ideally an older drug to reduce resistance rates
- Bacteriocidal or bacteriostatic?
- Low dose volume, low dose frequency for ease of adminstration, to minimise stress of handling and to minimise labour input
- Subcutaneous route (pain?)
- Low cost
- Low meat and milk withdrawal
- A 3-wk old Holstein heifer calf with a 24 hour history of ocular and nasal discharge and coughing. On clinical examination, there are harsh lung sounds especially in the cranioventral lung fields and core temperature is 41C*
- Which of the following antibiotics would be your choice to treat the ill calf? We’ve called two answers correct; as with many of these antibiotic decision making exercises, there is often more than one appropriate answer…..
- TMPS
- Oxytetracycline
- Tilmicosin
- Florfenicol
- Tulathromycin
-
TMPS
- Duphatrim (TMPS) would need injecting every day (compliance, muscle damage (IM), handling/stress), and does not penetrate well into areas with pus/tissue debris, so may not be the best choice - try again.
-
Oxytetracycline
- Oxytetracycline would be appropriate in many respects (and is cheap!); Although there is evidence that resistance amongst calf pneumonia pathogens is relatively common (relative to other antibiotics), many farms find that they get good treatment outcomes; if this is the case then they should be encouraged to continue using oxytet.
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Tilmicosin
- Micotil has very similar properties to Draxxin (the other macrolide drug in this selection), except that it is cheaper. However, it has some important operator safety issues (check out the data sheet). It can only be administered by a veterinary surgeon (which might be important as further cases may require treating in the future, and this would often be done by dispensing product to the farmer). There is little reason to choose this over the other options. Micotil has now been superseded by other macrolides that persist for longer;e.g. gamithromycin, tildipirosin meaning it is less likely to chose Micotil over these other options
-
Florfenicol
- Nuflor has an appropriate (broad!) spectrum of activity for this indication. Although it has no label claim for activity against mycoplasmae in the UK, this has been added to the label in the USA, and there is evidence that florfenicol will cover these pathogens. A single treatment using the subcutaneous regime should give about four days of cover. If the patient was very near to slaughter weight, the long withdrawal period might be a problem (but this is not usually the case). Resistance is rare, and it’s not a compound which is used much in human medicine; good choice! Don’t forget adjunctive therapies too; NSAIDs are invaluable in cases like this.
-
Tulathromycin
- Although we might expect a macrolide like Draxxin to have a Gram-positive-biased spectrum of activity, Draxxin has label claims for Mannheimia haemolytica and pasteurellae. It also has an extremely long duration of activity (probably 10 days for most pathogens), which can be very important. If the patient was very near to slaughter weight, the long withdrawal period might be a problem (but this is not usually the case). Resistance is rare. However, although tulathromycin is not used in human medicine, macrolides are often considered as one of the next most important families after the currently promoted CIAs (3-4 Cephs and FQs) and we therefore aim to use them as a last resort
- Best combination – oxytetracycline and florfenicol
- A 4th parturition cow has gone down with mastitis at one of your top dairy farms and the farmer wants it sorted sharpish. You get there as soon as you can and find that it’s quite a severe case; she is sick with grade 3 mastitis and you suspect she has endotoxic shock.
- It’s almost impossible for you to know what bugs might be in her udder at the moment but you remember James Breen telling you that gram negatives were pretty high up on the list.
What are the important components of therapy when treating a severe mastitis?
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Antibiotics
- Antibiotics - definitely but for perhaps different reasons than you may expect ; there is limited evidence that cows with severe coliform mastitis are actually bacteraemic, so we have to question the role of antibiotic to treat the mastitis when clinical signs are driven by endotoxamia and pathogens in the udder are probably not viable. Instead we suggest systemic antibiotic is important because the cow is clinically unwell and we need to provide broad-spectrum cover against secondary infections. So not the be all and end all….but a difficult decision to leave them out entirely.
- NSAIDs
- NSAIDs are really important here to reduce inflammation and pyrexia +/- endotoxins, well done.
- Regular stripping of the quarter
- Stripping the quarter is very useful to reduce the LPS levels; remember to advise your farmers to do this
- Nursing care
- Ensuring that the cow has good access to food and water to include fluid therapy if needed, making her comfortable if she is down etc are almost as important as anything else here.
Best is a combination of all of the above!!
- A 4th parturition cow has gone down with mastitis at one of your top dairy farms and the farmer wants it sorted sharpish. You get there as soon as you can and find that it’s quite a severe case; she is sick with grade 3 mastitis and you suspect she has endotoxic shock.
- It’s almost impossible for you to know what bugs might be in her udder at the moment but you remember James Breen telling you that gram negatives were pretty high up on the list.
Will you give this cow a systemic antibiotic or an intra-mammary one?
- Intra-mammary
- No definite right answer here (you’ll be getting used to this by now…), and many people will use intra-mammary preparations, though our cattle vets typically wouldn’t. Just make sure that they are sufficiently broad spectrum
- Systemic
- Systemic antibiotics would be the choice of our farm vets.