Bacteria can develop resistance to antimicrobials and share that resistance, driving outbreaks of resistant bacteria all over the world. What they have in common is excessive or inappropriate antimicrobial usage.
The main uses of antimicrobials are in people, companion animals, and farm and food animals. Unless we take practical steps towards more limited, targeted use of antimicrobial agents, we will inevitably see more resistant, difficult-to-treat infections in our clinics.
Unfortunately, most prescribers believe that what they are doing is fine and that it is the other prescribers that are doing it wrong.
When Veterinary Antimicrobials are Prescribed
Veterinarians prescribe antimicrobials based on several factors:
- Knowledge of the patient history
- What has worked in the past for similar cases
- Changes in resistance over time
- Results of diagnostic tests
- Likely side effects
- Drug administration (PO, IV, IP)
- Drug specificity (narrow versus broad)
- Drug priority (reserving some antimicrobials for multiple resistant organisms)
Maybe veterinarians do not use a mathematical algorithm when determining prescribing practices, but these factors should all enter their minds.
Selecting Appropriate Antimicrobial Agents
Knowing that an infection is bacterial is just the first step. To predict which antimicrobial will work best, the doctor must harmonize the available information. Do we know if the bacteria are Gram-positive or negative? Rod or cocci? Do we know the genus? Or the resistance profile?
The more information you have, the better your choice of antimicrobial will be.
Some of these criteria may be known at varying confidence levels. For instance, a urinary tract infection (UTI) might have a significant chance of being E. coli and a smaller chance of being Staphylococcus, but it could still be any number of other bacteria.
A veterinarian’s choice of appropriate antimicrobial is based on the bacteria causing the infection. Antimicrobials are classified according to their spectrum of activity against the pathogens on which they are effective. Figure 1 provides a high-level overview of the two such classifications of antimicrobials which are narrow-spectrum or broad-spectrum that a veterinarian might select to treat a bacterial infection.
The Gram-negative Enterobacteriaceae (like E. coli, Klebsiella, Proteus, and Enterobacter), have a range of susceptibility to beta-lactams including easily treatable to being completely resistant to even the most potent carbapenems (although carbapenem resistance is currently rarely seen except in hospital settings). It is critical to know if penicillin (a simple beta-lactam) will work, if amoxicillin/clavulanate (a higher tier beta-lactam plus a beta-lactamase inhibitor) is needed, or if a different class of antimicrobials like trimethoprim-sulfamethoxazole (TMS) or a tetracycline is the better choice.
For many veterinarians, the first choice of antibiotic for a Gram-negative infection would be amoxicillin/clavulanate or TMS. Depending on how often penicillin resistance is present, using the beta-lactamase inhibitor may make sense, even though it is considered a higher tier course of treatment.
Using Veterinary Diagnostics to Improve Selection
When the veterinarian knows the exact organism and its resistance profile, decisions can be made more easily.
The standard practice for much of the 20th century was to send samples out to a lab for culture and sensitivity testing. There, bacteria were cultured and identified by visual inspection of the size and shape of colonies on different media. The cultured bacteria could also be grown on plates containing different antimicrobials to identify any resistance genes it carried.
Ruling in or ruling out bacterial infection should be done quickly, and preferably at a point of care situation such as a clinic or veterinarian’s office. This information allows the veterinarian to either prescribe antimicrobials or spend their time finding and treating the actual cause of the symptoms. The use of regional or national labs that require sending in samples can incur a delivery time which can increase the time it takes to identify the best antimicrobial.
Sometimes, needing to act before any results come back, the clinician is forced to prescribe an empirical antimicrobial. Choosing the wrong antimicrobial could result in the patient getting worse or dying, or it could lead to an increase in drug resistance.
In some cases, the patient may be on their second antimicrobial before laboratory results become known and the most appropriate antimicrobial can be prescribed.
Rapid Pathogen Identification with qPCR
Much like human diagnostics, modern veterinary clinics are beginning to investigate the use of automated qPCR analyzers to assist with rapid diagnoses of infectious diseases. These sophisticated yet automated analyzers check samples on-site for unique nucleic acids that identify pathogens and common resistance genes. The veterinarian may still have to consider other factors, such as the side-effects of each antimicrobial or whether they are considered higher value, but they will have more confidence in which pathogen they are targeting and which agents are effective against it.
Shortening the time of the diagnostic tests can drastically improve patient outcomes, avoid unnecessary drugs, and slow the spread of resistant bacteria.
Patient Compliance and Feedback
Once the patient is prescribed an antimicrobial, compliance and follow-up are important. Even if the patient begins to feel better, the complete course of treatment should be taken. Premature stoppage increases the chance of developing antimicrobial resistance.
If a patient is prescribed a broad-spectrum antimicrobial, then as the veterinarian gets more information from offsite laboratory results, they should try to move the patient to a more narrow spectrum antimicrobial. And if the patient does not improve, then it is possible the choice of antimicrobial needs to be adjusted. This can be a lengthy and costly process for the patient. On-site rapid testing could dramatically improve patient outcomes.
How Antimicrobial Resistance Spreads
Many patients may have symptoms caused by viral infections or organ dysfunction that might not have any immediate relief; there is an urge to offer the patient something to address their suffering, as empathy demands.
Antimicrobials are not what should be given. Prescribing antimicrobials should be reserved for when a diagnosis of a bacterial infection is made. The use of antibiotics can cause side effects either directly from the medication itself or indirectly by changing the gut biome (diarrhea or C. difficile infections) or the occurrence of resistance in the wild.
Whenever a patient is treated with an antimicrobial, we not only treat the infection, but we treat all of the organisms in the patient including their gut microbiome. If any of them have resistance, they will rapidly increase in abundance.
Many of these resistance mechanisms are spread through plasmids which can be shared among the different bacteria. Therefore recurrent infections are harder to treat; each time a course of antimicrobials is given there is a greater chance that the bacteria in the patient have mechanisms to resist that antimicrobial. The patient can also shed these bacteria into the environment, weakening the ability of the antimicrobials to work in the community.
Luckily, the mechanisms of resistance usually come with some cost to the bacteria. When growing for periods of time without antimicrobials, these mechanisms can be lost or the bacteria will be outcompeted by more efficient organisms.
As antimicrobial stewards, we want to reduce the proliferation of mechanisms of resistance. This means prescribing an appropriate antimicrobial when needed and not treating when appropriate.