Academic literature on the topic 'Pradofloxacin'

ABSTRACT Collaborating veterinarians from five European countries collected subgingival bacterial samples from dogs exhibiting clinical periodontal disease. Sterile endodontic paper points were used for collection of the samples, which were transported to a central laboratory for susceptibility testing. Anaerobic bacteria were isolated and Porphyromonas and Prevotella isolates identified to the species level; susceptibility to pradofloxacin and metronidazole was determined using the CLSI agar dilution methodology. A total of 630 isolates, 310 of Porphyromonas spp. and 320 of Prevotella spp., were isolated. Pradofloxacin MIC data for all isolates were in the range of ≤0.016 to 1 μg/ml, the overall MIC50 was 0.062, and the overall MIC90 was 0.25 μg/ml. There were no differences in activity against Porphyromonas and Prevotella isolates or in the pradofloxacin susceptibility distributions from the different European countries. All isolates were within the wild-type distribution and were fully susceptible to pradofloxacin. Metronidazole was also highly active against these strains: 316 of 320 Prevotella strains (98.8%) and 309 of 310 Porphyromonas strains (99.7%) were susceptible (MICs of ≤8 μg/ml). However, three Prevotella strains had intermediate metronidazole susceptibility (MICs of 16 μg/ml), while one Prevotella and one Porphyromonas strain were metronidazole resistant (MICs of 128 and 256 μg/ml, respectively). Pradofloxacin, a novel broad-spectrum fluoroquinolone, demonstrates a high degree of antianaerobic activity against strains isolated from clinical cases of periodontal disease and shows activity against metronidazole-resistant isolates. The broad-spectrum activity of pradofloxacin makes it a suitable candidate for the treatment of periodontal disease in dogs.

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 5 mg/kg, q24 h for seven doses (11/13 cats; 85%), and pradofloxacin at 10 mg/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.

Urinary tract infections are common in dogs, necessitating antimicrobial therapy. We determined the speed and extent of in vitro killing of canine urinary tract infection pathogens by five antimicrobial agents (ampicillin, cephalexin, marbofloxacin, pradofloxacin, and trimethoprim/sulfamethoxazole) following the first 3 h of drug exposure. Minimum inhibitory and mutant prevention drug concentrations were determined for each strain. In vitro killing was determined by exposing bacteria to clinically relevant drug concentrations and recording the log10 reduction and percent kill in viable cells at timed intervals. Marbofloxacin and pradofloxacin killed more bacterial cells, and faster than other agents, depending on the time of sampling and drug concentration. Significant differences were seen between drugs for killing Escherichia coli, Proteus mirabilis, Enterococcus faecalis, and Staphylococcus pseudintermedius strains. At the maximum urine drug concentrations, significantly more E. coli cells were killed by marbofloxacin than by ampicillin (p < 0.0001), cephalexin (p < 0.0001), and TMP/SMX (p < 0.0001) and by pradofloxacin than by cephalexin (p < 0.0001) and TMP/SMX (p < 0.0001), following 5 min of drug exposure. Rapid killing of bacteria should inform thinking on drug selection for short course therapy for uncomplicated UTIs, without compromising patient care, and is consistent with appropriate antimicrobial use and stewardship principles.

AbstractThe aim of the study was to analyse the influence of enrofloxacin and pradofloxacin administered orally for 14 days on the ECG in dogs. The ECG was performed before and after a 14 day period of quinolone administration. There was an increase in the QTc and the TpTe interval in the group treated with quinolones. QTc was prolonged by 24 ms (p=0.001). The TpTe interval was shortened, on average, by 6.55 ms (p=0.048). In the group treated with enrofloxacin, QTc was prolonged by 16.27 ms (p=0.006) and the TpTe interval was shortened by 9.64 ms (p=0.050), the TpTe/QT index was reduced by 0.034 (p=0.050) on average. In dogs treated with pradofloxacin, QTc was prolonged by 21.55 ms (p=0.012) on average. The results suggest that a prolonged administration of quinolones can increase the risk of arrhythmias. Furthermore, different generations of these drugs increase this risk to various degrees. The study proved that second generation quinolones, such as enrofloxacin, significantly change the phase of depolarization and repolarization of the ventricles, at the same time increasing the risk of ventricular arrythmia. Pradofloxacin does not change the TpTe and TpTe/QT values, so it is safer in use.

A third-generation fluoroquinolone, pradofloxacin (PRA), is currently being developed to treat bacterial infections in dogs. The purpose of this study was to assess the clinical efficacy in 20 dogs affected with superficial and deep pyoderma. An initial aerobic skin culture was performed in dogs with superficial pyoderma; aerobic/anaerobic tissue culture was performed in dogs with deep pyoderma; and skin cytology and biopsies were obtained from all dogs. Pradofloxacin (approximately 3 mg/kg per os [PO]) was administered daily to all dogs. Clinical efficacy was recorded at 4 weeks for dogs with superficial pyoderma and at 3 and 6 weeks for dogs with deep pyoderma. At a mean dosage of 3.7 mg/kg PO once daily, PRA treatment resulted in an excellent to good clinical response within 3 to 6 weeks for all 20 dogs with superficial and deep pyoderma.

The study evaluated the Mutant Prevention Concentration (MPC) of Pradofloxacin on three Escherichia coli (E.coli) strains, 2 wildtypes and one first-step gyrA resistant mutant. We also measured the value of AUC (Under the Concentration)/MPC that prevents growth of resistant mutants. It is of importance to reach a concentration above MPC that prevent E.coli from developing resistance against the antibiotic.

We used an in vitro kinetic model where we added bacteria? and antibiotic. The culture flask was attached to a pump with an adjustable pump-speed. This made it possible to dilute the antibiotics in a satisfying elimination half-life (t1/2= 7 hours) pace. Samples were removed with a syringe at different times in the study. The samples where then cultured on agar- plates to enable counting of the viable colonies after incubation.

The optimal concentration to completely eradicate both E.coli wildtypes Nu14 and MG1655 with Pradofloxacin was Cmax ≥8 times MPC and AUC/MPC then became73. Additional experiments needs to be done on the resistant mutant LM378 before we can determine the optimal concentration. But results so far indicate that the concentration of Cmax would be about 8-12 timesMPC to completely eradicate that mutant.

Antimicrobials are not only considered as beneficial agents to human and animal health, but are also potentially harmful, both in terms of promoting antimicrobial resistance (AMR), and the potentially negative effects they may have on the gut microbiota. Focusing on these two major detrimental effects, this thesis aims to determine the frequency of AMR in companion animal pathogens isolated from Australia, as well as identify risk factors associated with infection my multidrug-resistant strains; and to describe the gut microbial community changes and other adverse effects in rabbits in response to administration of pradofloxacin, a new veterinary antimicrobial belonging to the critically important fluoroquinolone class. In the first nation-wide survey of AMR in companion animal pathogens, resistance to antimicrobials from more than ten different classes was described for a total 883 clinical Escherichia coli isolated from dogs (n=514), cats (n=341) and horses (n=28). Resistance to critically important antimicrobials not registered for use in animals (imipenem) was not detected in all clinical E. coli isolates. Resistance to amikacin, another critically important antimicrobial not registered for use in Australian animals, was low in dog and cat isolates (<2%) but moderately high in horse isolates (10.7%), reflecting its increased use in this species. Resistance to other third line antimicrobials such as third generation cephalosporins (3GC) and fluoroquinolones (FQN), was generally lower in cat isolates (3.8%-5%) compared with dog isolates (9.1%-10.9%) and horse isolates (25%-35.7%). A higher proportion of resistance was observed among the first and second line antimicrobials, ranging from 25%-100% for ampicillin and amoxicillin-clavulanic acid, mainly due to the new interpretation by veterinary-specific clinical breakpoints for dogs and cats which are much lower than human clinical breakpoints. The frequency of multidrug-resistant (MDR) E. coli was 18.1%, 11.7% and 42.9% in dog, cat and horse isolates respectively, which was positively associated with the chronicity of infection and prior antimicrobial treatment, in particular for urinary tract infections from dogs. Furthermore, among coagulase-positive staphylococci (CoPS) isolates from companion animals the frequency of methicillin-resistant Staphylococcus pseudintermedius (MRSP) and methicillin-resistant Staphylococcus aureus (MRSA) in the isolate collections was 11.8% (74/629) and 12.8% (15/117), respectively. Resistance to FQN in S. pseudintermedius ranged from 8.1%-8.8% and was highly associated with MRSP isolates from dogs (OR 287; 95%CI 91.2–1144.8). MRSA isolates were also co-resistant to FQN (OR 5.4, 95%CI 0.6–252.1), with a frequency ranging from 8.5%-11.8% of total S. aureus from dogs (n=47) and cats (n=14). By contrast MRSA isolates from horses, were most likely to be co- resistant to amikacin and rifampicin (OR 6.5, 95%CI 0.7–315.2) with a frequency of 9.4% of total S. aureus from horses (n=53). A risk factor analysis showed that MRSP isolates from dogs were significantly more likely in surgical site infections (SSI) and skin and soft tissue infections (SSTI), particularly if the animals had received prior antimicrobial treatment. Compared with other countries where similar studies have been undertaken, rates of AMR in E. coli, were generally lower. However, due to the abrupt emergence and spread of MRSP infections in Australia, rates of AMR in S. aureus and S. pseudintermedius were moderately higher. Faecal and gut microbiota profiling using V3-V4 16S rRNA gene Illumina MiSeq DNA sequence analysis confirmed that the veterinary fluoroquinolone pradofloxacin (which has a much broader spectrum of activity compared to earlier generations) had quite different effects on the microbial community in the rabbit stomach and caecum; compared to hard faeces, and soft faeces. Microbial richness and diversity decreased significantly in hard faeces at the end of the 3- day treatment but not in the lumen of the stomach and caecum. Pseudomonas spp. was depleted significantly in hard faeces while Anaeroplasma significantly diminished in the stomach and caecum. The abundance of several bacterial taxa from the Ruminococcaceae and Lachnospiraceae was significantly overrepresented in all samples. However, overproliferation of bacteria causing enteritis such as Clostridium spp. and coliforms was not detected in the two gut compartments nor hard and soft faeces. Further, we hypothesized that stomach microbiota would be less diverse compared with caecum microbiota but our data show that the stomach harboured higher levels of microbial diversity compared with the caecum, regardless of pradofloxacin treatment, most likely due to coprophagy. Although the short-term use of pradofloxacin appears safe in rabbits as we observed no clinically adverse effects, these results confirm that pradofloxacin did result in significant disturbance of the faecal microbial community and changes of metabolic functional diversity. In conclusion, the first nation-wide AMR survey provides an important snapshot of the current situation of AMR in companion animal pathogens in Australia. Further, this thesis underlined the public health (AMR) and individual health-related (dysbiosis) consequences which should increase the awareness of prudent use of antibiotics especially in animals and broadly in human medicine.
Thesis (Ph.D.) -- University of Adelaide, School of Animal & Veterinary Sciences, 2018

Introdução: A hemossiderose caracteriza-se pela deposição acentuada de ferro, chamado hemossiderina nos tecidos. A etiologia dessa doença é hemorrágica ou hemolítica, podendo ser causadas por anemia hemolítica imunomediada, resultando assim na deposição de hemossiderina nos tecidos, podendo ou não, danificá-los. Objetivo: O presente resumo tem como objetivo relatar a etiologia da hemossiderose. Materiais e Métodos: Foi atendido na clínica veterinária um felino, fêmea, SRD, 3 kg, de 4 anos. Apresentando êmese, anorexia e descarga serosa nasocular. No exame físico, foi detectada apatia, mucosas ictéricas, juntamente com a da confirmação da presença do herpesvírus felino 1, agente da rinotraqueíte felina. Além disso, o felino apresentou uma possível lipidose hepática, devido ao longo período de inapetência, causada pela rinotraqueíte. O animal foi internado. O tratamento consistiu em alimentação facilitada e antibioticoterapia com pradofloxacina em suspensão 25 mg/dia por 5 dias. Em 4 dias, após recaída, foi realizada transfusão sanguínea de 40 ml de sangue total. O animal apresentou melhora e recebeu alta. Um mês após, o animal retornou apresentando anasarca. Solicitado hemograma e bioquímico, foi observada anemia normocítica normocrômica, trombocitose, leucocitose linfocítica, proteínas totais baixas e hipoalbuminemia. Como tratamento da hepatopatia, foi utilizado amoxicilina com clavulanato de potássio 12,5 mg/kg/dia por via oral, durante 20 dias; S-Adenosil-Metionina 100 mg/dia por via oral, durante 30 dias. Em relação a anasarca, foi prescrita furosemida 12 mg/kg/dia, espironolactona 12 mg/kg/dia e 12 mg/kg/dia de hidroclorotiazida, até melhora no quadro do paciente. Em um mês, foram refeitos o perfil bioquímico e o hemograma. Nos quais, verificou-se melhora na albumina e do hematócrito, leuco e plaquetograma. Diante disso, os tutores autorizaram a biópsia e histopatologia hepática. Resultados: No histopatológico foi encontrado acúmulo de pigmento granular marrom acastanhado no citoplasma de macrófagos. O diagnóstico foi dado como hemossiderose multifocal moderada. Conclusão: Conclui-se que a hemossiderose foi resultante da anemia hemolítica, pelas alterações hepáticas, aumentando assim a deposição de ferro nos tecidos por consequência tanto da lise das hemácias transfundidas, quanto das hemácias próprias do animal. Do mesmo modo a anasarca decorreu da hepatopatia e hipoalbuminemia, resultando na diminuição da pressão oncótica dos vasos, extravasando líquido para os tecidos.