pradofloxacin and Cat-Diseases

Pradofloxacin is a novel third-generation oral veterinary fluoroquinolone with activity against Gram-positive aerobic bacteria and anaerobes (lower minimum inhibitory concentrations in vitro). It also has activity against other bacterial species, including Bartonella henselae, Pasteurella multocida, Bordetella bronchiseptica, extra-intestinal Escherichia coli, and some mycobacterial species. This review focuses on the current knowledge of the mechanism of action, adverse effects, clinical applications, and pharmacokinetic/pharmacodynamic properties of pradofloxacin in cats.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Cat Diseases; Cats; Fluoroquinolones

Pradofloxacin is a third-generation fluoroquinolone, licensed in the EU for use in a range of indications in the dog and cat and authorized more recently in the USA for one therapeutic indication (skin infections) in the cat. This review summarizes and appraises current knowledge on the physico-chemical, pharmacological [pharmacokinetics (PK) and pharmacodynamics (PD)], safety and therapeutic properties of pradofloxacin in the target species. Pradofloxacin contains two centres of asymmetry and is the pure SS enantiomer. After oral dosing of tablets (dog) or tablets and oral suspension (cat), maximum plasma concentrations (Cmax ) are achieved in less than 3.0 h, and terminal half-life is of the order of 5-10 h. Accumulation is slight or absent with once daily oral dosing. Free drug concentrations in plasma are in the range of 63-71% of total concentration. As for other fluoroquinolones, antibacterial activity is attributable to inhibition of bacterial replication at two sites, subunit A of topoisomerase II and topoisomerase IV. The antimicrobial spectrum includes gram-negative and gram-positive organisms, anaerobes, Mycoplasma spp. and some intracellular organisms (Rickettsia spp. and Mycobacterium spp.). The killing action is of the concentration-dependent type. Pradofloxacin has high potency (low MIC values) in comparison with first- and second-generation fluoroquinolones. Integration of in vivo PK and in vitro PD data provides values of Cmax /MIC and area under plasma concentration-time curve (AUC24 h )/MIC ratios predictive of good clinical efficacy against sensitive organisms, when administered at recommended dose rates. Clinical trial evaluation of pradofloxacin, in comparison with other authorized antimicrobial drugs, has demonstrated either noninferiority or superiority of pradofloxacin. Data indicating clinical and, in some instances, bacteriological cure have been reported: (i) in cats, for wound infections, abscesses, upper respiratory tract infections, conjunctivitis, feline infectious anaemia and lower urinary tract infections and (ii) in dogs, for wound infections, superficial and deep pyoderma, acute urinary tract infections and adjunctive treatment of infections of gingival and periodontal tissues. At clinical dose rates pradofloxacin was well tolerated in preclinical studies and in clinical trials. Among the advantages of pradofloxacin are (i) successful treatment of infections caused by strains resistant to some other fluoroquinolones, as

Topics: Animals; Anti-Bacterial Agents; Cat Diseases; Cats; Dog Diseases; Dogs; Fluoroquinolones

In humans with idiopathic pulmonary fibrosis (IPF), specific thoracic computed tomographic (CT) features in the correct clinical context may be used in lieu of histologic examination. Cats develop an IPF-like condition with similar features to humans. As few cats have invasive lung biopsies, CT has appeal as a surrogate diagnostic, showing features consistent with architectural remodeling supporting "end-stage lung".. A 1-year-old female spayed Domestic Shorthair cat presenting with progressive respiratory clinical signs and thoracic CT changes (reticular pattern, parenchymal bands, subpleural interstitial thickening, pleural fissure thickening, subpleural lines and regions of increased attenuation with traction bronchiectasis and architectural distortion) consistent with reports of IPF was given a grave prognosis for long-term survival. The cat was treated with prednisolone, fenbendazole, pradofloxacin and clindamycin. Five months later, while still receiving an anti-inflammatory dose of prednisolone, the cat was re-evaluated with owner-reported absent respiratory clinical signs. Thoracic CT demonstrated resolution of lung patterns consistent with fibrosis.. Fibrotic lung disease is irreversible. Despite this cat having compatible progressive respiratory signs and associated lung patterns on thoracic CT scan, these abnormalities resolved with non-specific therapy and time, negating the possibility of IPF. While the cause of the distinct CT lesions that ultimately resolved was not determined, infection was suspected. Experimental Toxocara cati infection shows overlapping CT features as this cat and is considered a treatable disease. Improvement of CT lesions months after experimental heartworm-associated respiratory disease in cats has been documented. Reversibility of lesions suggests inflammation rather than fibrosis was the cause of the thoracic CT lesions. This cat serves as a lesson that although thoracic CT has been advocated as a surrogate for histopathology in people with IPF, additional studies in cats are needed to integrate CT findings with signalment, other clinicopathologic features and therapeutic response before providing a diagnosis or prognosis of fibrotic lung disease.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents; Cat Diseases; Cats; Clindamycin; Female; Fenbendazole; Fluoroquinolones; Prednisolone; Pulmonary Fibrosis; Tomography, X-Ray Computed; Treatment Outcome

Topics: Agglutination; Anemia; Animals; Anti-Bacterial Agents; Biopsy, Fine-Needle; Cat Diseases; Cats; Coombs Test; Erythrocytes; Female; Fluoroquinolones; Gene Rearrangement; Macrophages; Mycoplasma; Mycoplasma Infections; Phagocytosis; Receptors, Antigen, B-Cell; Receptors, Antigen, T-Cell; Spleen

In this study, 908 bacterial pathogens from defined infections of dogs and cats were tested for their susceptibility to the novel fluoroquinolone pradofloxacin, which was approved in 2011 for use in cats and dogs. Most of the bacteria tested (Staphylococcus aureus, Staphylococcus pseudintermedius, Escherichia coli, β-haemolytic streptococci, Pasteurella multocida and Bordetella bronchiseptica) exhibited low pradofloxacin MIC(90) values of ≤ 0.25 μg/ml. Solely Proteus spp. and Pseudomonas aeruginosa had higher MIC(90) values of ≥ 4 μg/ml. Only six (3.4%) of 177 S. pseudintermedius and 12 (5.3%) of 227 E. coli isolates showed pradofloxacin MICs of ≥ 2 μg/ml. Analysis of the quinolone resistance determining regions of the target genes identified double mutations in GyrA that resulted in amino acid exchanges S83L+D87N or S83L+D87Y and single or double mutations in ParC that resulted in amino acid exchanges S80I or S80I+E84G in all 12 E. coli isolates. The six S. pseudintermedius isolates exhibited amino acid exchanges S84L or E88K in GyrA and S80I in GrlA. Comparative analysis of the MICs of pradofloxacin and the MICs determined for enrofloxacin and its main metabolite ciprofloxacin, but also marbofloxacin, orbifloxacin, difloxacin and ibafloxacin was conducted for the target pathogens S. pseudintermedius, E. coli and P. multocida. This comparison confirmed that pradofloxacin MICs were significantly lower than those of the other tested fluoroquinolones.

Topics: Animals; Anti-Bacterial Agents; Cat Diseases; Cats; Dog Diseases; Dogs; Drug Resistance, Microbial; Fluoroquinolones; Gram-Negative Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Pets; Staphylococcus

Rapidly growing mycobacteria (RGM) and Nocardiae can cause severe or refractory infections in cats and dogs. Prolonged antibacterial therapy is required to cure these infections. As fluoroquinolones have been used in combination therapy for treating RGM infections, isolates from the Mycobacterium smegmatis cluster (n=64), Mycobacterium fortuitum cluster (n=17), and M. mageritense cluster (n=2), collected from feline and canine patients, underwent susceptibility testing to pradofloxacin. The MIC(50), MIC(90) and tentative epidemiological cut-off (ECOFF) values as determined by microbroth dilution susceptibility testing that inhibited growth of the M. smegmatis and M. fortuitum clusters were 0.063, 0.125 and ≤ 0.25; and 0.125, 0.250 and ≤ 1.0 μg/mL, respectively. E-Test results showed similar trends but MICs were lower than those for microbroth dilution. In summary, pradofloxacin demonstrated effective in vitro activity against RGM isolates. Additionally, veterinary isolates of Nocardia nova (n=18), Nocardia farcinica (n=3) and Nocardia cyriacigeorgica (n=1) underwent microbroth dilution testing to ciprofloxacin, enrofloxacin and pradofloxacin. The MIC(50) and MIC(90) of pradofloxacin, ciprofloxacin and enrofloxacin that inhibited growth of Nocardia nova isolates were 2 (4), 8 (16), 16 (32) μg/mL, respectively. The tentative ECOFF values for pradofloxacin and ciprofloxacin were 32 μg/mL and for enrofloxacin 64 μg/mL. The MIC or MIC range for the three N. farcinica isolates of pradofloxacin, ciprofloxacin and enrofloxacin were 0.25-0.5, 2 and 2 μg/mL and for the single N. cyriacigeorgica isolate were 1, 4 and 4 μg/mL, respectively. On the basis on these results, fluoroquinolones appear to have limited therapeutic potential for most Nocardia infections.

Topics: Animals; Anti-Bacterial Agents; Cat Diseases; Cats; Ciprofloxacin; Dog Diseases; Dogs; Enrofloxacin; Fluoroquinolones; Microbial Sensitivity Tests; Mycobacterium; Mycobacterium Infections; Nocardia; Nocardia Infections

Using Bartonella henselae isolates from cats and a human, the activity of pradofloxacin was compared with those of enrofloxacin and azithromycin. By Etest and disc diffusion assay, pradofloxacin showed greater antimicrobial activity than did other antibiotics. We conclude that pradofloxacin may prove useful for the treatment of B. henselae infections.

Topics: Angiomatosis, Bacillary; Animals; Anti-Bacterial Agents; Azithromycin; Bartonella henselae; Cat Diseases; Cat-Scratch Disease; Cats; Enrofloxacin; Fluoroquinolones; Humans; Microbial Sensitivity Tests

Topics: Animals; Anti-Bacterial Agents; Azithromycin; Bacteremia; Bacterial Proteins; Bartonella henselae; Cat Diseases; Cats; DNA Gyrase; DNA Mutational Analysis; DNA, Bacterial; Drug Resistance, Bacterial; Enrofloxacin; Fluoroquinolones; Mutation; Polymerase Chain Reaction; RNA, Ribosomal, 23S; Sequence Analysis, DNA

To evaluate the efficacy of the fluoroquinolone pradofloxacin in the treatment of cats experimentally infected with Mycoplasma hemofelis.. 23 young adult specific-pathogen-free cats.. Cats were inoculated with M hemofelis from a chronically infected donor and assigned to 1 of 4 treatment groups: a doxycycline group, a low-dose-pradofloxacin group, a high-dose-pradofloxacin group, and an untreated control group. Treatment was initiated for 14 days when M hemofelis infection was detected via PCR assay and clinical signs of hemoplasmosis were present. Cats that had negative PCR assay results after treatment were administered a glucocorticoid and monitored via PCR assay for an additional 4 weeks.. All cats yielded positive results for M hemofelis via conventional PCR and quantitative PCR assays and developed anemia. The low-dose-pradofloxacin group had significantly lower M hemofelis copy numbers than the doxycycline group. Six cats treated with pradofloxacin yielded negative results during treatment. Of those cats, 4 yielded negative conventional PCR assay results and all yielded negative quantitative PCR assay results for M hemofelis 1 month after administration of high-dose glucocorticoids.. Pradofloxacin had anti-M hemofelis effects similar to those of doxycycline. In addition, pradofloxacin may be more effective at long-term M hemofelis organism clearance than doxycycline.

Topics: Anemia; Animals; Anti-Bacterial Agents; Blood Cell Count; Cat Diseases; Cats; DNA, Bacterial; Doxycycline; Female; Fluoroquinolones; Hematocrit; Male; Mycoplasma; Mycoplasma Infections; Polymerase Chain Reaction; Random Allocation; Specific Pathogen-Free Organisms

Forty humane society cats with suspected bacterial upper respiratory infections (URIs) were studied in order to compare amoxycillin and pradofloxacin for treatment of rhinitis and describe common pathogens. Nasal discharges were collected prior to random placement into one of three treatment groups. Cats failing to initially respond were crossed to the alternate drug. Drug toxicity was not noted. The organisms most frequently isolated or amplified pre-treatment were feline herpesvirus-1 (75%), Mycoplasma species (62.5%), Bordetella species (47.5%), Staphylococcus species (12.5%) and Streptococcus species (10.0%). No differences in clinical scores between groups over time were noted. Overall response rates for amoxycillin at 22 mg/kg, q12 h for seven doses (10/15 cats; 67%), pradofloxacin at 5mg/kg, q24 h for seven doses (11/13 cats; 85%), and pradofloxacin at 10mg/kg, q24 h for seven doses (11/12 cats; 92%) were not statistically significant. Results suggest that pradofloxacin can be a safe, efficacious therapy for some cats with suspected bacterial URI.

Topics: Animals; Anti-Bacterial Agents; Cat Diseases; Cats; Female; Fluoroquinolones; Male; Respiratory Tract Infections; Rhinitis; Treatment Outcome

To compare the intrinsic activity of pradofloxacin, a new fluoroquinolone developed for use in veterinary medicine, with other fluoroquinolones, against anaerobic bacteria isolated from dogs and cats.. One hundred and forty-one anaerobes were isolated from dogs and cats and comparative MICs of pradofloxacin, marbofloxacin, enrofloxacin, difloxacin and ibafloxacin were determined according to standardized agar dilution methodology.. Pradofloxacin exerted the greatest antibacterial activity followed by marbofloxacin, enrofloxacin, difloxacin and ibafloxacin. Based on the distinctly lower MIC(50), MIC(90) and mode MIC values, pradofloxacin exhibited a higher in vitro activity than any of the comparator fluoroquinolones.. Pradofloxacin, a novel third-generation fluoroquinolone, has broad-spectrum anti-anaerobe activity and offers utility as single-drug therapy for mixed aerobic/anaerobic infections.

Topics: Animals; Anti-Bacterial Agents; Bacteria, Anaerobic; Bacterial Infections; Cat Diseases; Cats; Dog Diseases; Dogs; Fluoroquinolones; Microbial Sensitivity Tests; Molecular Structure