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Why Do Antibiotics Fail? A Veterinary Perspective

Andreia Garcês 1,2,3*
1 INNO Veterinary Laboratory, R. Cândido de Sousa 15, 4710-503 Braga, Portugal
2 Cooperativa de Ensino Superior Politécnico e Universitário, CRL -CESPU, R. Central Dada Gandra, 1317, 4585-116 Gandra, Portugal
3 CITAB University of Trás-os-Montes and Alto Douro, Quinta de Prados 5000-801, Vila Real, Portugal
* Corresponding author: Andreia Garcês, INNO Veterinary Laboratory, R. Cândido de Sousa 15, 4710-503 Braga, Portugal. Email:



In both human and veterinary medicine, the failure of apparently appropriate antimicrobial therapy is a common and often exasperating clinical problem. Many factors are associated with the failure of antibiotic therapy, including an incorrect diagnosis of infectious disease, selection of the inappropriate antibiotic, and incorrect dosage. To achieve the best results, bacteriological diagnostics in the laboratory should be made. Even though the in-vitro antimicrobial susceptibility testing guides the potentially suitable antimicrobials, the in-vitro susceptibility obtained is not always the best in-vivo. The clinician should be aware of other factors, including biofilm-forming bacteria, physicochemical conditions at the site of infection (such as perfusion rate, oxygen partial pressure, and pH value), or immunosuppression of the patient can lead to failure of the treatment. This review summarized the main factors associated with antibiotic failure in a veterinarian practice. In a world where the animal and human resistance to an antibiotic is rising every year, rational and efficient use of antibiotic therapy is of utmost importance. It is essential to continue with the education of veterinary practitioners in all aspects of antimicrobial resistance and treatment to improve future treatments and have a more rational use of antibiotics to reduce antibiotic resistance in animals and humans.

1. Introduction

According to the World Health Organisation, European Medicines Agency, Committee for Medicinal Products for Veterinary Use, and other agencies, there is a worldwide misuse and overuse of antimicrobials in veterinary and human medicine that are leading to the increase of resistant bacteria worldwide 1–3.
Bacterial infections are a large percentage of the cases admitted to veterinary clinics. Therefore, optimization and rational use of antibacterial therapy are necessary to reduce the selection of resistant bacteria2. Veterinary practitioners must consider a variety of factors to prescribe antibiotic therapy, such as the severity of the disease, the etiological agent, drugs available on the market, additional therapeutic interventions, or symptomatic add-on therapy2. The clinical first must identify if it is indeed a disease caused by infectious etiology. In the case of infection, animals usually present different symptoms, such as fever, leucocytosis, increased fibrinogen, and discopondylosis1–3.

If present any of these criteria a correct laboratory diagnosis and subsequent antimicrobial susceptibility testing (AST) are important to achieve a good outcome. It is not classified as an infection, a preventive antibiotic therapy is only suitable in cases of strong suspicion of contamination or yearly infection1,4. In human medicine, the “90/60 rule” is based on the analysis that about 90% of bacterial infections respond positively to antimicrobial therapy if the antibiotic has been classified as “susceptible” in vitro tests 3. In veterinary, this rule is not confirmed due to a low number of observations, so there are some limitations 2. Treatment failure is usually detected by objective clinical criteria4. When the empirical antibiotic therapy fails, it is necessary to consider microbiological results, and if the first-line therapy chosen was inappropriate, the antibiotic should be changed immediately 4. Sometimes the antibiotic treatment seems to be falling because the response is not immediate. Some patients can only show signs of response within 24-48 hours after the beginning of the treatment5.

2. Inappropriate diagnosis of bacterial infections

2.1. Non-infectious disease that mimics infection

Some non-infectious diseases mimic infections because the organisms of vertebrates have a limited number of responses to aggression. For example, in a systematic inflammation (non-infectious) the patient presents a rise in the temperature, heart rate, respiratory, and white blood cell count. These parameters also are present in clinical cases of infection, such as sepsis5. Several pathologies mimic symptoms of infectious diseases. Some examples are vasculitis, malignant hyperthermia, drug hypersensitivity, or adrenal insufficiency5.

2.2. Untreatable Infectious diseases with antibiotics

Although considered infectious, viral, mycotic, and toxin-induced infections, these diseases should not be treated with antibiotic therapy6. Inappropriate diagnosis leads to the treatment with antibiotic therapy, which in some cases appears to be working because some agents, such as azithromycin have anti-inflammatory activity5. Unusual pathogens, such as Rickettsia, do not respond to the standard antibiotics used in clinic6.

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