In vitro killing of canine strains of Staphylococcus pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and pradofloxacin over a range of bacterial densities

Abstract

Background -Bacterial densities likely fluctuate during infection and may exceed the bacterial density used in susceptibility testing. As such, investigation of bacterial killing by antibiotics over a range of varying bacterial densities may provide important differences between compounds and could impact drug selection for therapy.Hypothesis/Objectives -To measure killing of clinical isolates of Staphylococcus pseudintermedius and Escherichia coli by cefazolin, cefovecin, doxycycline and pradofloxacin at clinically relevant (minimum inhibitory, mutant prevention, maximum serum and maximum tissue) drug concentrations against varying densities of bacteria.Methods and materials -Bacterial strains collected from dogs with urinary tract infections were studied. High bacterial densities ranging from 10 6 to 10 9 colony forming units (cfu)/mL were exposed to minimum inhibitory, mutant prevention, blood and tissue drug concentrations, and the percentages (log 10 ) of viable cells killed following 30 min, 1, 2, 4, 6, 12 and 24 h of drug exposure were quantified.Results -Doxycycline exhibited bacteriostatic properties with less killing than the other three agents. For example, at a 10 7 cfu/mL density of S. pseudintermedius, more cells were killed by pradofloxacin (P < 0.0001) and cefovecin (P = 0.0014) but not cefazolin when compared to doxycycline at the maximum serum drug concentration following 12 h of drug exposure.Conclusions and clinical importance -Differences were seen between some drugs in the speed and extent of bacterial killing; this could be clinically important and may impact drug selection and length of therapy.

Effectiveness of Biological Assays as an Alternative Method to Determine the Potency of Antibiotics: A Review

“…These values serve as a guide for dosing concentrations that can potentially reduce the amplification of bacterial subpopulations with reduced susceptibility to antimicrobials. The determination of MPC and MIC values provides valuable information regarding the effectiveness of these antibiotics against the specified pathogens [53]. Critical Concentration (Ccr) is the minimum concentration of an antibiotic that is required to prevent microbial growth and inhibit the concentration from reaching a specific critical point.…”

The Complex Diseases of Staphylococcus pseudintermedius in Canines: Where to Next?

“…When used in randomised clinical trials to treat dogs with superficial or deep pyoderma, cefovecin was shown to have a high clinical efficacy similar to previously used antibiotics, with only a small percentage of dogs showing adverse symptoms [ 88 ]. Although these results indicate that cefovecin is a safe and effective newly synthesised antimicrobial for veterinary use in particular geographical locations, the use of cefovecin is restricted only to use in cats and dogs where antibiotic sensitivity testing indicated use is required; therefore, additional research has focused on repurposing multiple human antibiotics for use in animals [ 89 , 90 , 91 ]. Many studies have tested the efficacy of various human antibiotics including nitrofurantoin, rifampicin, doxycycline, cefazolin and linezolid in the treatment of S. pseudintermedius infections in canines, mainly pyoderma, UTIs and surgical site infections [ 89 , 90 , 91 ].…”

“…Although these results indicate that cefovecin is a safe and effective newly synthesised antimicrobial for veterinary use in particular geographical locations, the use of cefovecin is restricted only to use in cats and dogs where antibiotic sensitivity testing indicated use is required; therefore, additional research has focused on repurposing multiple human antibiotics for use in animals [ 89 , 90 , 91 ]. Many studies have tested the efficacy of various human antibiotics including nitrofurantoin, rifampicin, doxycycline, cefazolin and linezolid in the treatment of S. pseudintermedius infections in canines, mainly pyoderma, UTIs and surgical site infections [ 89 , 90 , 91 ]. Whilst studies did show that the use of such human antibiotics was effective in vitro against clinical isolates or was able to treat the infection of interest in clinical trials, it is important to note that some of these antibiotics resulted in adverse side effects and possessed a short half-life in serum, therefore requiring frequent and repeated doses, which is known to increase resistance [ 89 , 90 , 91 ].…”

“…Many studies have tested the efficacy of various human antibiotics including nitrofurantoin, rifampicin, doxycycline, cefazolin and linezolid in the treatment of S. pseudintermedius infections in canines, mainly pyoderma, UTIs and surgical site infections [ 89 , 90 , 91 ]. Whilst studies did show that the use of such human antibiotics was effective in vitro against clinical isolates or was able to treat the infection of interest in clinical trials, it is important to note that some of these antibiotics resulted in adverse side effects and possessed a short half-life in serum, therefore requiring frequent and repeated doses, which is known to increase resistance [ 89 , 90 , 91 ]. Importantly, resistance was already noted against these tested antibiotics, either by the target strain, S. pseudintermedius , or associated species.…”

“…were isolated that were resistant to rifampicin [ 90 ]. The presence of resistance in the veterinary sector against human antibiotics is a major concern, as antibiotics such as nitrofurantoin, rifampicin, doxycycline and linezolid are essential in human medicine for the treatment of UTIs, tuberculosis in chemotherapy patients, chronic skin infections and pneumonia in humans, respectively; therefore, resistance would significantly impact the availability of treatment options in human medicine [ 89 , 90 , 91 ]. While alternative antibiotics may be effective in the treatment of S. pseudintermedius infections in dogs, particularly pyoderma, where other treatment options have failed, moving forward, the use of antibiotics intended for the treatment of human diseases may not be appropriate in veterinary medicine.…”