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Mastitis is a common economically important disease of dairy buffaloes. Antibiotic resistance is the most cited reason behind the failure of clinical mastitis treatment in buffaloes. Selection of antibiotic after antibiotic sensitivity test is the key to avoid multidrug resistance (MDR) for mastitis therapy. Therefore, the present research work was carried out to evaluate efficacy of moxifloxacin and marbofloxacin in clinical mastitis in buffaloes based on the sensitivity against common mastitic bacteria in buffaloes. Total twenty clinical mastitis positive buffaloes were selected after screening of 129 lactating buffaloes by strip cup test and clinical signs, in and around Parbhani area. The selected buffaloes were divided into 2 groups, 10 animals in each. Group I was treated with injection Moxifloxacin @ 5 mg/kg BW IM for 5 days and group II received injection Marbofloxacin @ 2 mg/kg BW IM for 5 days. Supportive treatment was given in both groups as antihistaminic, multivitamins and NSAIDs. The clinical parameters like rectal temperature, heart rate and respiratory rate showed significant improvement in both the treatment groups. Haematolgical study showed significant improvement in TLC, neutrophil and lymphocyte count while apparent but non-significant improvement observed in Hb, PCV, basophil, eosinophil and monocyte count. The most frequent bacteria observed in mastitic samples were Staphylococcus aureus, followed by E. coli, Klesiella spp. and mixed bacterial infection. Marbofloxacin showed highest sensitivity to mastitis causing bacteria followed by Moxifloxacin, Enrofloxacin and Ciprofloxacin. The comparative efficacies in treatment groups were calculated on the basis of improvement in clinical signs, strip cup test and somatic cell count after treatment. Higher efficacy of Marbofloxacin was found (70%) as compared to Moxifloxacin (50%) for treatment of clinical mastitis. Hence, concluded that marbofloxacin could be appropriative antibiotic agent in the treatment of mastitis in buffalo. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the pharmacokinetics of marbofloxacin after intravenous (IV) administration of a single dose of 10 mg/kg to calves of different ages. The study was carried on 1‐ (n = 6), 2‐ (n = 6), and 4‐month‐old (n = 6) Montofon calves. Plasma concentrations of marbofloxacin were measured using HPLC, and pharmacokinetic data were calculated by non‐compartmental analysis. The elimination half‐life (t1/2ʎz), volume of distribution at steady state (Vdss), total clearance (ClT), and area under the concentration‐versus time curve (AUC0–∞) values of marbofloxacin in 1‐month‐old calves were 10.62 h, 1.03 L/kg, 0.08 L/h/kg, and 127.90 h*μg/mL, respectively. While the t1/2ʎz (from 10.62 to 3.36 h) and AUC0–∞ (from 127.90 to 47.35 h*μg/mL) decreased in parallel with the age of the calves, ClT (from 0.08 to 0.21 L/h/kg) increased. The Vdss of marbofloxacin was higher in 1‐ and 2‐month‐old calves compared to 4‐month‐old calves. After IV administration of marbofloxacin at a dose of 10 mg/kg, an ƒAUC0–24/MIC90 ratio of ≥ 125 was obtained for bacteria with MIC90 values of ≤ 0.60, ≤ 0.39 and ≤ 0.27 μg/mL in 1‐, 2‐, and 4‐month‐old calves, respectively. These results show that the antibacterial effect of marbofloxacin, which has concentration‐dependent activity, decreases due to age‐related pharmacokinetic changes and that the 10 mg/kg dose should be reviewed according to the MIC90 value of the bacteria. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTI), an adhesion and multiplication of bacterial uropathogens in the urogenital system, are one of the most important indications for antimicrobial use in veterinary medicine and contribute to the development of antimicrobial resistance. Previously, it was revealed that older cats with an average of 9.1 years old are most likely to develop UTI, however a contradicting investigation stated kittens and young adults are more likely to contract UTI. Along with the uprising of amoxicillin- and ampicillin-resistant uropathogens, the study aims to turn towards marbofloxacin reserve and to analyze their potency. Furthermore, the current study aims to enumerate and compare the number of uropathogens between age groups. Enumeration and identification of uropathgoens from urine samples of feline UTI patients were was conducted through the urine culture on EMB, MSA, and BHI medium followed by an IMViC test and inoculation to the Mueller-Hinton agar to observe the zone of inhibition. The investigation revealed that a higher number of younger cats and kittens were reported to have UTI and catheter-induced UTI with a higher number of uropathogens in the population. The uropathogens were further identified as Staphylococcus spp., Enterococcus spp., Enterobacter spp., Escherichia spp., and Klebsiella spp. Additionally, marbofloxacin was found to be effective in eliminating and inhibiting the growth of these uropathogens. In conclusion, younger cats were observed to be more prone to UTI of a diverse range of uropathogens, however, marbofloxacin may aid in the treatment of the cats as it has been proven to be most effective.

Abstract Background Antimicrobial resistance (AMR) is a global concern impacting both humans, animals and their environment. The use of oral antimicrobials in livestock, particularly in pigs, has been identified as a driver in the selection of AMR bacteria. The aim of the present study was to evaluate the effects of a single intramuscular (IM) dose of marbofloxacin (8 mg/kg) on Enterobacteriaceae and E. coli populations, as well as on fluoroquinolone resistance within the fecal microbiota of pigs. Twenty healthy pigs, 60-days old, were divided into two groups: a treated group (n = 13) and a control group (n = 7) and were monitored over a 28-day experimental period. Fecal samples were collected from all animals for the isolation of E. coli and Salmonella strains. The minimum inhibitory concentration (MIC) of marbofloxacin for the isolates recovered on MacConkey agar supplemented with 1 or 4 µg/mL of marbofloxacin and for some generic E. coli isolates (recovered from MacConkey agar not supplemented with marbofloxacin) was determined using the broth microdilution method. Genomic DNA was extracted from the confirmed bacterial strains and sequenced using the Sanger method to identify mutations in the quinolone resistance determining regions (QRDRs) of the gyrA and parC genes. Results The single IM administration of marbofloxacin resulted in a significant decrease in Enterobacteriaceae and E. coli fecal populations from days 1 to 3 post- treatment. No Salmonella isolates were detected in either group, and no marbofloxacin-resistant E. coli isolates were identified. The MIC of the selected generic E. coli strains (n = 100) showed an increase to up to 0.5 µg/mL between days 1 and 3 post-treatment but remained below the clinical breakpoint of marbofloxacin resistance (4 µg/mL). Sequencing of these isolates revealed no mutations in gyrA and parC genes. Conclusions The present study showed that this dosing regimen of marbofloxacin significantly decreases the fecal shedding of Enterobacteriaceae and E. coli populations in pigs, while limiting the selection of marbofloxacin-resistant E. coli isolates. These findings warrant validation in sick pigs to support the selective use of this antibiotic solely in cases of clinical disease, thereby minimizing the reliance on conventional (metaphylactic) group treatments in pigs.

Background: Antimicrobial resistance (AMR) is a global concern impacting both humans, animals and their environment. The use of oral antimicrobials in livestock, particularly in pigs, has been identified as a driver in the selection of AMR bacteria. The aim of the present study was to evaluate the effects of a single intramuscular (IM) dose of marbofloxacin (8 mg/kg) on Enterobacteriaceae and E. coli populations, as well as on fluoroquinolone resistance within the fecal microbiota of pigs. Twenty healthy pigs, 60-days old, were divided into two groups: a treated group (n = 13) and a control group (n = 7) and were monitored over a 28-day experimental period. Fecal samples were collected from all animals for the isolation of E. coli and Salmonella strains. The minimum inhibitory concentration (MIC) of marbofloxacin for the isolates recovered on MacConkey agar supplemented with 1 or 4 µg/mL of marbofloxacin and for some generic E. coli isolates (recovered from MacConkey agar not supplemented with marbofloxacin) was determined using the broth microdilution method. Genomic DNA was extracted from the confirmed bacterial strains and sequenced using the Sanger method to identify mutations in the quinolone resistance determining regions (QRDRs) of the gyrA and parC genes. Results: The single IM administration of marbofloxacin resulted in a significant decrease in Enterobacteriaceae and E. coli fecal populations from days 1 to 3 post- treatment. No Salmonella isolates were detected in either group, and no marbofloxacin-resistant E. coli isolates were identified. The MIC of the selected generic E. coli strains (n = 100) showed an increase to up to 0.5 µg/mL between days 1 and 3 post-treatment but remained below the clinical breakpoint of marbofloxacin resistance (4 µg/mL). Sequencing of these isolates revealed no mutations in gyrA and parC genes. Conclusions: The present study showed that this dosing regimen of marbofloxacin significantly decreases the fecal shedding of Enterobacteriaceae and E. coli populations in pigs, while limiting the selection of marbofloxacin-resistant E. coli isolates. These findings warrant validation in sick pigs to support the selective use of this antibiotic solely in cases of clinical disease, thereby minimizing the reliance on conventional (metaphylactic) group treatments in pigs. [ABSTRACT FROM AUTHOR]

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Abstract In this study, an evaluation was made of three treatments against feline leishmaniosis (FeL) and their impacts on the transmission of Leishmania infantum to its vector, Lutzomyia longipalpis. A cat with clinical signs of FeL was examined and L. infantum diagnosed. Subsequently, the cat was subjected to xenodiagnosis and L. infantum detected in the vectors. The cat was then treated with three different drugs and the clinical improvement and parasite transmissibility to the vector were evaluated. Promastigotes were observed in 21/52 female sandflies (40.38%) in a xenodiagnosis prior to the treatments. Clinical signs persisted after the first treatment with marbofloxacin, and the cat remained positive in serological, molecular, and parasitological tests. Therefore, the cat was treated with miltefosine but remained sick and tested positive. A second xenodiagnosis was performed a month after treatment with miltefosine, and promastigotes were observed in 5/9 females (55.55%). Lastly, the cat was treated with allopurinol, which led to good clinical improvement, but it remained positive, and a final xenodiagnosis revealed Leishmania in 2/29 (6.89%) females. The results showed that only treatment with allopurinol produced a good clinical response, but none of the treatments succeeded in eliminating L. infantum infection or preventing transmission to the vector.

The veterinary antibacterial Marbofloxacin (Marbo) is used in food-producing animals, including dairy cows, so the residues of this drug will be excreted through milk. This study was aimed to investigate a risk of developmental and neurobehavioral toxicity effects in newborn consumers exposed to the residues of this drug. To achieve this goal, suckling pups of rats were selected as a model. Four groups of female lactating rats (5 dams for each group – 8 pups per dams) were divided into (A,B,C,D) treated with Marbo (0 (control), 3, 6,9 mg/kg, i.m.) given once daily for 10 consecutive days (first nursing period) respectively. The exposure of suckling pups to the drug through milk in group (D) led to neurobehavioral toxicity effects represented in the occurrence of a significantly prolongation in both the time required to terminate the surface righting reflex on postnatal day (PND) 5 and the time of induction and duration of anesthesia by (ketamine and xylazine) on the (PND) 21 . the newborns in group (C) recorded a significantly prolongation of both in the period of appearance of pinna detachment and in induction and duration of anesthesia accompanied by a significantly decrease in numbers of squares crossed in open field activity test on the (PND) 21 .It could be conclude from our current study that there are risks of causing developmental and neurobehavioral toxic effects in newborn consumers exposed to Marbo residue in animal products such as milk. [ABSTRACT FROM AUTHOR]

A 3‐year‐old castrated male Jack Russell Terrier with a history of cholestatic hepatitis was presented with a non‐painful and non‐pruritic, subcutaneous nodule following vaccine injection. The dog was otherwise healthy. The nodule was surgically removed. Upon gross inspection, a firm, glistening and loculated tissue was seen within the panniculus. Histopathologically, extensive pyogranulomatous panniculitis was diagnosed, composed of variably sized lipocyst surrounded by neutrophils and an outer zone of foamy epithelioid macrophages, neutrophils and occasional Langhans form giant cells. Although histopathologic findings were most compatible with mycobacteriosis, other infectious and sterile conditions were considered differential diagnoses. Gram, acid‐fast and periodic acid Schiff staining were negative. However, PCR analyses for mycobacterial rpoB gene and sequencing revealed infection with Mycobacterium avium subsp. avium. Empirical treatment was avoided through the 3‐week course of histopathological and molecular investigations. Considering that there were no newly formed cutaneous masses, marbofloxacin (2 mg/kg, PO q24h) was administered for 2 weeks, and clarithromycin was avoided due to its potential cholestatic hepatitis adverse effects. Eight months following surgery, there are no new or relapsing cutaneous lesions or disease‐specific complications. This suggests that marbofloxacin monotherapy may be sufficient in immunocompetent dogs with early detection of localized cutaneous mycobacteriosis lacking lymph node or organ involvement. [ABSTRACT FROM AUTHOR]

To date, the pharmacokinetics of fluoroquinolones in estuarine crocodiles (Crocodylus porosus) have been reported for enrofloxacin but not for marbofloxacin (MBF), which is a broad‐spectrum antibiotic used only in veterinary medicine. This study investigated the pharmacokinetics of MBF after intramuscular administration at two difference dosages (2 and 4 mg/kg body weight) in estuarine crocodiles and estimated pharmacokinetic/pharmacodynamic (PK/PD) surrogate parameters for the optimization of dosage regimens. Ten treated estuarine crocodiles were divided into two groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at assigned times up to 168 h. MBF plasma samples were cleaned up using liquid–liquid extraction and analyzed using a validated high‐performance liquid chromatography method with fluorescence detection. A non‐compartment approach was used to fit the plasma concentration of MBF vs time curve for each crocodile. The plasma concentrations of MBF were quantifiable for up to 168 h in both groups. The elimination half‐life values of MBF were long (33.99 and 39.28 h for 2 and 4 mg/kg, respectively) with no significant differences between the groups. The average plasma protein binding of MBF was 30.85%. According to the surrogated PK/PD parameter (AUC0–24‐to‐MIC ratio >100–125), the 2 and 4 mg/kg dosing rates should be effective for bacteria with MIC values lower than 0.125 μg/mL and 0.35 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

The present study investigated the prospect of improvement in pharmacokinetic (PK) parameters of marbofloxacin due to alpha-1-monolaurin pre-treatment in broiler chickens. Two groups of broilers were administered a single oral dose of marbofloxacin (5.00 mg kg-1 body weight): Group-I without pre-treatment and Group-II with alpha-1-monolaurin pre-treatment (4.00 g kg-1 feed for 10 days). Blood sampling was done periodically for both groups and plasma marbofloxacin concentrations were determined using ultra-high performance liquid chromatography. Pharmacokinetic parameters using non-compartmental modelling approach were calculated with the PKSolver software. Statistical analysis revealed significant differences in plasma marbofloxacin concentrations between the two groups at 1, 2, and 24 hr. Group-II birds exhibited a higher mean maximum plasma concentration (2.43 µg mL-1) at an earlier time (Tmax: 1.38 hr) compared to Group-I. The plasma concentrations of marbofloxacin were maintained above 0.10 and 0.18 µg mL-1 up to 24 hr in Group-I and Group-II broilers, respectively. Significant differences were observed in PK parameters such as the area under the curve and total body clearance. The mean relative oral bioavailability of Group-II birds compared to Group-I was 119.61%. The findings of the study provided evidence of PK parameters enhancement of marbofloxacin in the alpha-1-monolaurin pre-treated group. The calculated PK-pharmacodynamic indices for marbofloxacin predicted clinical efficaciousness in the broiler chickens. [ABSTRACT FROM AUTHOR]

Marbofloxacin (MBX) is a 3rd generation fluoroquinolone specifically developed for animal health and is an approved antimicrobial agent for the cure of mastitis and respiratory diseases in cattle and swine. Ketoprofen (KTP) is a nonsteroidal anti-inflammatory drugs (NSAID) belonging to the aryl propionic acid group and is used in musculoskeletal inflammation and pain, abdominal pain and other inflammatory circumstances. The objective of this study is to investigate the impact of simultaneous administration of MBX and KTP on the coagulation and biochemical parameters in calves. In the study, 18 clinically healthy calves were randomly separated into 3 groups of six animals each. The first group of calves received a single dose of MBX at 8 mg/kg, the second group received MBX at 8 mg/kg along with concurrent KTP at 3 mg/kg and the third group received only KTP at 3 mg/kg dose. The drugs were administered via intramuscular (IM) injection in the neck region. Biochemical and coagulation parameters were evaluated using an automated analyzer and coagulation analyzer, respectively. The IM injection of MBX into calves significantly increased creatine kinase (CK) and lactate dehydrogenase (LDH) values, which may be related to muscle damage. This may limit the administration via IM route of MBX to calves. KTP increased the prothrombin time (PT) and activated partial thromboplastin time (aPTT) values but decreased the fibrinogen value. It can be stated that in alone MBX, and KTP administration and their combination, further investigations are required to determine the safety of drugs after repeated administrations and other administration routes in calves.

The fluoroquinolone antimicrobial agents, enrofloxacin and marbofloxacin, were US Food and Drug Administration (FDA) approved in the United States for use in dogs in 1988 and 1999, respectively. There have been many advances since then concerning the pharmacokinetic-pharmacodynamic (PK-PD) evaluation of fluoroquinolones, and there are data available on the susceptibility of targeted pathogens since the original approval. Using this information, the Clinical and Laboratory Standards Institute (CLSI) Veterinary Antimicrobial Susceptibility Testing Subcommittee (VAST) revised its antimicrobial susceptibility testing breakpoints. The previous breakpoints (used in older editions of CLSI standards) for enrofloxacin in dogs were susceptible (S), ≤ 0.5 µg/mL, intermediate (I) 1–2 µg/mL, and resistant (R) ≥ 4 µg/mL. The new breakpoints are S ≤ 0.06 µg/mL for a dose of 5 mg/kg, 0.12 µg/mL for a dose of 10 mg/kg, 0.25 µg/mL for a high dose of 20 mg/kg, and R ≥ 0.5 µg/mL. The breakpoints of 0.12 and 0.25 µg/mL represent a new susceptible-dose dependent (SDD) category. For marbofloxacin, previous breakpoints were S, ≤ 1 µg/mL, I 2 µg/mL, and R ≥ 4 µg/mL. The new breakpoints are S ≤ 0.12 µg/mL for a dose of 2.8 mg/kg, 0.25 µg/mL for a dose of 5.5 mg/kg (SDD), and R ≥ 0.5 µg/mL. The new breakpoints will be published in the next edition of CLSI-Vet01(S) and deviate considerably from the prior breakpoints. Laboratories are encouraged to revise their testing standards. These changes will likely reduce the unnecessary use of these fluoroquinolones in dogs. [ABSTRACT FROM AUTHOR]

Salmonella spp.; a major zoonotic pathogen worldwide could cause serious diseases that hinder the productivity in calf farms. This study discussed the antibacterial efficacy of the Marbofloxacin drug in calves affected with Salmonella spp. and how it impacted the animal body's haemato-biochemical changes. Salmonella spp. was isolated from diarrheic cases (18.8%) along with other bacteria which were also isolated in varying degrees. Salmonella isolates exhibited multiple serovars' identities. Also, they exhibited a multidrug resistant (MDR) pattern. Moreover, PCR approach confirmed both genotypic and phenotypic resistance traits of highly virulent MDR Salmonella isolates. In a trial to evaluate the anti-Salmonella effect of the Marbofloxacin drug, three groups of calves were divided; the first group (G1) was diarrheic without any drug administration, the second (G2) was diarrheic but intramuscularly administered with Marbofloxacin (2ml/50 Kg B.W.) while the control (healthy) group was (G3). The haemato-biochemical results of Salmonella infected group recorded significant increases in RBCs count, PCV, Hb, and leukocytes with marked neutrophilia, monocytosis, and lymphopenia. Moreover, high rates of AST, ALT, urea and creatinine were recorded as well as serum globulin (P<0.05) was extremely increased. Also, a high increase of serum potassium but with notably limited levels of both glucose and sodium was stated. Meanwhile, after treatment, all haemato-biochemical and mineral parameters in G2 were completely improved. In conclusion, the Marbofloxacin drug impacted positively on animal health and in vitro, it completely overcomes calf Salmonella infection which in turn enhances the growth curves of these animals and considerable financial profits. [ABSTRACT FROM AUTHOR]

Acute bacterial cholangiohepatitis of cats is a common disease associated with the inflammation of bile ducts and liver parenchyma, characterized by development of a pronounced hepatodepressive syndrome (hypoalbuminemia), cytolysis (increase in serum activity of alanine and asparagine transaminase), cholestasis (increase in serum concentration of bilirubin, cholesterol, activity of alkaline phosphatase and gamma-glutamyltranspeptidase), intoxication, dehydration, mesenchymal-inflammatory and pain syndromes. The aim of the research was to study the effectiveness of treatment for acute bacterial cholangiohepatitis in cats with average severity of the pathology course. According to inclusion and exclusion criteria, the study included a cohort of cats (n = 12) with acute bacterial cholangiohepatitis. Clinical, hematological, ultrasonographic, statistical methods of investigation were used in this work. For sick cats with medium severity form of cholangiohepatitis, when administered as a complex therapy the combination of marbofloxacin, metronidazole, ursodeoxycholic acid, cyancobolamine, tocopherol acetate, infusion therapy also had a good therapeutic effect, which was accompanied by improved clinical and laboratory performance. In the blood of cats with cholangiohepatitis, in the background of intensive therapy, there was a significant decrease in white blood cell count, erythrocyte sedimentation rate, and in serum, there was an increase in albumin concentration, reduction of creatinine, aminotransferase activity, alkaline phosphatase, gamma-glutamyltranspeptidase, lipase.

Pharmacokinetic study of marbofloxacin was carried out in healthy rabbits following intramuscular administrations @ 2.00 mg/kg body weight once daily for five days. A serial blood samples were collected on 1st and 5th day, i.e. at 2.5, 5, 10, 30, 45 min and then at 1, 2, 4, 6, 8, 10, 12 and 24 h after administration of marbofloxacin. Concentrations of the marbofloxacin in blood plasma were estimated by microbiological assay. Kinetic parameters were calculated by using one compartment open model. Apparently higher plasma concentrations of the drug appeared at all intervals from 2.5 min to 24 h on 5th day as compared to 1st day of marbofloxacin administration with significant differences at 10.0 min and 12 h only. The minimum therapeutic concentration (≥ 0.25 μg/mL) of marbofloxacin was maintained up to 12 h and all kinetic parameters differed non-significantly between 1st and 5th day of marbofloxacin administration. On the basis of present findings, a satisfactory dosage regimen of marbofloxacin @ 2.14 mg/kg body weight followed by 2.04 mg/kg body weight intramuscular route at 24 h intervals can be recommended to maintain the minimum therapeutic concentration (≥ 0.25 μg/mL) during the treatment of bacterial infections in rabbit. [ABSTRACT FROM AUTHOR]

Case summary: A 7.5-year-old neutered male Oriental Shorthair cat presented with an 8-month history of haematochezia, mucoid diarrhoea, tenesmus and vocalisation after a 4-year history of small bowel diarrhoea. Transabdominal ultrasonography confirmed diffuse colonic wall thickening and extensive ulceration and erythema after colonoscopy. Colonic histopathology confirmed periodic acid-Schiff positive macrophages, consistent with granulomatous colitis; Escherichia coli was cultured from colonic biopsy specimens. Fluorescent in situ hybridisation (FISH) identified intracellular E coli, and an 8-week oral course of marbofloxacin, a hydrolysed protein diet and a 5-day course of fenbendazole yielded a transient partial clinical remission of the colitis signs. A reported resolution in the small bowel signs was also reported. Colonoscopy was repeated 5 months later due to the recurrence of colitis signs. Histopathology was not consistent with granulomatous colitis supporting a complete remission; however, a chronic inflammatory enteropathy was confirmed with moderate lymphoplasmacytic, neutrophilic and eosinophilic colitis without a histiocytic component. E coli was again cultured from colonic biopsies with sensitivity to fluoroquinolones; FISH was positive for intracellular E coli. Clinical signs persisted despite a 2-week course of oral marbofloxacin. Relevance and novel information: E coli -associated granulomatous colitis is rare in cats. Colonic biopsy specimen culture is important to guide appropriate antibiotic therapy. Repeat histopathology, culture and FISH have not been previously reported after treatment of a cat with E coli -associated granulomatous colitis. Persistent clinical signs after treatment with oral marbofloxacin alongside a confirmed complete histologic remission support the presence of a concurrent chronic inflammatory enteropathy and pathology for the cat's ongoing colitis. [ABSTRACT FROM AUTHOR]

Marbofloxacin (MBX) is a 3rd generation fluoroquinolone specifically developed for animal health and is an approved antimicrobial agent for the cure of mastitis and respiratory diseases in cattle and swine. Ketoprofen (KTP) is a nonsteroidal anti-inflammatory drugs (NSAID) belonging to the aryl propionic acid group and is used in musculoskeletal inflammation and pain, abdominal pain and other inflammatory circumstances. The objective of this study is to investigate the impact of simultaneous administration of MBX and KTP on the coagulation and biochemical parameters in calves. In the study, 18 clinically healthy calves were randomly separated into 3 groups of six animals each. The first group of calves received a single dose of MBX at 8 mg/kg, the second group received MBX at 8 mg/kg along with concurrent KTP at 3 mg/kg and the third group received only KTP at 3 mg/kg dose. The drugs were administered via intramuscular (IM) injection in the neck region. Biochemical and coagulation parameters were evaluated using an automated analyzer and coagulation analyzer, respectively. The IM injection of MBX into calves significantly increased creatine kinase (CK) and lactate dehydrogenase (LDH) values, which may be related to muscle damage. This may limit the administration via IM route of MBX to calves. KTP increased the prothrombin time (PT) and activated partial thromboplastin time (aPTT) values but decreased the fibrinogen value. It can be stated that in alone MBX, and KTP administration and their combination, further investigations are required to determine the safety of drugs after repeated administrations and other administration routes in calves. [ABSTRACT FROM AUTHOR]

The present work introduced copper oxide nanoparticles as an efficient electrode modifier for sensitive adsorptive differential pulse voltammetric assaying of marbofloxacin (MRB) in pharmaceutical formulations and surface water samples. In the presence of sodium dodecyl sulphate (SDS) at pH 4.0, the marbofloxacin molecule was irreversibly oxidized at the electrode surface showing an anodic oxidation peak at 0.954 V. The electrode reaction mechanism was assumed as adsorption‐reaction controlled accompanied by the transferring of two electrons and proton exchange in agreement with the molecular orbital calculations performed on MRB molecule suggesting the oxidation of the amino group in the piperazinyl ring. At the optimized measuring conditions, the recorded peak heights were linearly correlated with the MRB concentration within the range from 6.67 to 360 ng mL−1, and the estimated LOD value was 2.2 ng mL−1. The integrated sensor showed a prolonged operational lifetime with good reproducibility of measurements. Based on the selectivity and sensitivity of the proposed method, MRB was successfully assayed in pharmaceutical formulations and surface water samples with mean average recoveries agreeable with the official method. [ABSTRACT FROM AUTHOR]

Marbofloxacin, a veterinary--exclusive antimicrobial drug of third--generation fluoroquinolone class, exhibits wide spectrum antimicrobial activity against Gram-negative as well as Gram-positive bacteria, and thus, is a promising agent to treat susceptible bacterial infections in poultry. Therefore, the present study was conducted to derive dosage regimen of marbofloxacin based on the results of intravenous and oral pharmacokinetic (PK) trial in sixteen healthy broiler chickens. Plasma concentrations of marbofloxacin were measured by optimized and in-house validated Ultra High Performance Liquid Chromatography (UHPLC) method. The PK parameters were calculated from plasma concentrations versus time data by non-compartmental analysis using 'PK Solver 2.0' software. Following oral administration of marbofloxacin at the dose rate of 5 mg/kg b.wt., the mean maximal plasma concentration (Cmax: 2.193 µg/ml) was achieved at 1.68 h. Marbofloxacin showed long half-life (6.03 h), high volume of distribution (2.64 L/kg) and good oral bioavailability (88.10 %). The average plasma concentration of marbofloxacin ≥ 0.32 µg/ mL was maintained upto 12 h and 0.10 µg/ mL at 24 h. Based on the values of PK-PD integrated indices, it is concluded that oral dose of marbofloxacin @ 5.0 mg/kg b.wt., to be repeated at 24 h, would be efficient to treat common bacterial pathogens of broiler chickens having MIC ≤ 0.12 μg/mL. [ABSTRACT FROM AUTHOR]

A simple, sensitive, and accurate chromatography (RP-HPLC) method for simultaneous estimation of Ciprofloxacin, Ofloxacin, and Marbofloxacin in their combined pharmaceutical dosage form or individually. The HPLC separation was achieved on a Hypersil (C18, 150 mm × 4.6 mm, 5 μm particle size) analytical column or equivalent. A mixture of triethanolamine (1 %), acetonitrile (80 %), and water was used as the mobile phase, with a flow rate of 1.2 mL /min and a detector wavelength of 280 nm at ambient temperature. In the HPLC method, the retention times of Ciprofloxacin, Ofloxacin, and Marbofloxacin were found to be 1.854, 2.480, and 4.688 min, respectively, and linearity was obtained in the range of 25–80 µg/mL for Ciprofloxacin, Ofloxacin, and Marbofloxacin. The correlation coefficient for the method was greater than 0.999. The RP-HPLC method validation parameter lay within its acceptance criteria as per the ICHq2 (R1) guideline. Hence, it can be successfully used for routine analysis of Ciprofloxacin, Ofloxacin, and Marbofloxacin in raw material or pharmaceutical dosage forms.

Three adult littermates were diagnosed with Brucella canis, two of which were diagnosed with discospondylitis. The first littermate, a 2-year-old spayed-female Labrador Retriever, was evaluated for progressive episodes of cervical pain, lethargy, reported circling to the right, and a right-sided head tilt. Magnetic resonance imaging (MRI) of the cervical spine revealed changes consistent with discospondylitis at C6-C7. MRI of the brain was unremarkable and cerebrospinal fluid analysis was declined. Brucella spp. was isolated from aerobic and Brucella blood cultures. PCR performed on the isolate identified Brucella canis and indirect fluorescent antibody (IFA) testing for Brucella canis also confirmed the species. Patient #1 was treated with doxycycline and marbofloxacin for 1 year. Clinical signs returned 2-years after diagnosis. Following the diagnosis of patient #1, a known littermate (patient #2) was tested for Brucella canis. Patient #2 was 2 years old and asymptomatic at the time of diagnosis. Aerobic and Brucella spp. cultures, PCR, and IFA were obtained and were diagnostic for Brucella canis. A 6-month course of marbofloxacin and doxycycline was implemented. The patient remained PCR positive following 4 months of treatment and repeat cultures were planned following 6 months of treatment; however, the patient was lost to follow-up. A third littermate (patient #3) was identified by the family of patient #1. Patient #3 was evaluated at 18 months of age for a 6-month history of progressive lumbosacral pain. Spinal radiographs revealed discospondylitis of the C3-C4, T12-T13, and L7-S1 vertebral endplates. Computed tomography (CT) of the lumbosacral spine was also consistent with discospondylitis at L7-S1. Brucella canis serologic testing consisting of rapid slide agglutination test, 2ME-rapid slide agglutination test, and cytoplasmic agar gel immunodiffusion was positive. Enrofloxacin was administered for 7 months and was discontinued thereafter based on radiographic evidence of healing and resolution of clinical signs. Although Brucella canis is not a rare disease in dogs, the documentation of two out of three adult littermates with associated discospondylitis is an interesting feature. In addition, this report highlights available diagnostic and treatment options, as each patient was managed differently based on clinical signs and the preference of the managing clinician.

Fluoroquinolone antibiotics are frequently used in human and veterinary medicine due to their spectrum and action. Marbofloxacin, last member of the flouroquinolone antibiotics, is used in many animal species. The aim of this research was to determine the lethal dose (LD)so and embryotoxic effects of marbofloxacin by administering to fertile chicken eggs. In the study, 210 fertile chicken eggs were used. Eggs were allowed to wait in an incubator for 7 days under optimal conditions. On the seventh day, 210 fertile chicken eggs were randomly divided into 7 equal groups. The first two groups were accepted as the control group. In the remaining 5 groups, 100, 50, 25, 12.5, and 6.25 mg/kg doses of marbofloxacin were injected, respectively, and the incubation period of 21 days was completed. At the end of the incubation period, eggs were opened, and the number of dead and live embryo and macroscopic findings were observed. In the study, both teratogenicity and embryotoxicity were detected depending on the dose. LD50 value was calculated as 43.3 and 43.8 mg/kg according to the probit and Karben-Behrens method, respectively. Normalized mortality rates acoording to Abbott formula at 100, 50 and 25 mg/kg doses were calculated as 100%, 74.7%, and 14.84%, respectively. At 12.5 and 6.25 doses, similar results with the control group were obtained. Consequently, it can be expressed that marbofloxacin may show teratogenic and/or embryotoxic effects in mammals concerning the dose and should be used carefully during pregnancy. [ABSTRACT FROM AUTHOR]

Mastitis is one of the economic diseases of the livestock industry, especially breeding dairy cows around the world. The most important bacterium that causes peripheral mastitis is Escherichia coli which can cause mild to severe mastitis. The Effect of antibiotics on mastitis caused by Escherichia coli is one of the dangers of the livestock industry. The aim of this study was to evaluate the efficacy of marbofloxacin as a new drug and compare it with the effects of enrofloxacin on grade I and II mastitis. In this study, 90 cows with mastitis grade I and II were identified and divided into three groups of control, anrofloxacin and marbofloxacin treatments. The cows were then treated and cows that had not been healed for up to 5 days were considered as untreated cows. In the present study 28 cows were treated with marbofloxacin and 24 cases were treated in the Enrofloxacin group and 2 in the control group. The results of statistical analysis showed that the effect of marbofloxacin was statistically significant compared to the two groups. It is recommended to use marbofloxacin as an effective drug in the treatment of mastitis in cows with mastitis I and II as compared to anrofloxacin.Conflict of interest: None declared.

Objectives: The level of resistance immediately prior to slaughter in food-producing animals is of great public health significance because of likely transmission of resistant bacteria via the food chain. Methods: Marbofloxacin was administered to goats at the dose of 2 mg/kg body weight by intramuscular route for 5 days. Faecal Escherichia coli population was monitored and examined for bacteriological procedures. DNA sequencing of gyrA and parC genes was performed to identify mutations at quinolone-resistance determining region, and interaction between marbofloxacin and GyrA was studied by in silico docking. E. coli isolates were screened for plasmid-mediated quinolone resistance genes qnrA, qnrB, qnrS, aac(6′)Ib-cr, qepA, oqxA and oqxB. Efflux pump-mediated resistance was evaluated by ethidium bromide assay, reduction in minimum inhibitory concentration (MIC) values in the presence of efflux pump inhibitors and relative expression of AcrAB-TolC efflux pump. Results: During the treatment period, emergence of marbofloxacin-resistant E. coli strains was observed in gut flora. Quinolone resistance determining regions (QRDRs) in gyrA identified amino acid codon mutations Ser83Leu and Asp87Asn, and Ser80Ile in parC. Docking analysis implied that marbofloxacin could not form strong complexes with mutated DNA-gyrase. A high prevalnce of PMQR genes, especially qnrS, was observed along with overexpression of AcrAB-TolC efflux pump. Conclusions: The study highlighted the high prevalence of transferable mechanisms of quinolone resistance and over expression of efflux pumps in marbofloxacin-resistant E. coli isolates apart from classic QRDR mutations. The present study recommends to consider the period of dominance of resistant commensals, being excreted by animals during the antimicrobial treatments, while formulating the withdrawal period for drugs, especially in food-producing animals.

Abstract Background While commercial poultry and captive birds are exposed to antimicrobials through direct medication, environmental pollution may result in contamination of wild birds. Fluoroquinolones are commonly used medications to treat severe avian bacterial infections; however, their adverse effects on birds remain understudied. Here, we examine toxicity of enrofloxacin and marbofloxacin during the egg incubation period using the chicken (Gallus Gallus domesticus) as a model avian species. Laboratory tests were based on eggs injected with 1, 10 and 100 μg of fluoroquinolones per 1 g of egg weight prior to the start of incubation and monitoring of chick blood biochemistry, reproductive parameters and heart rate during incubation. Results Eggs treated with fluoroquinolones displayed reduced hatchability due to embryonic mortality, particularly on day 13 of incubation. Total hatching success showed a similar pattern, with a significantly reduced hatchability in low and high exposure groups treated with both enrofloxacin and marbofloxacin. From 15 to 67% of chicks hatching in these groups exhibited joint deformities. Hatching one-day pre-term occurred with a prevalence of 31 to 70% in all groups treated with fluoroquinolones. Embryonic heart rate, measured on days 13 and 19 of incubation, increased in all enrofloxacin-treated groups and medium and high dose groups of marbofloxacin-treated eggs. Blood biochemistry of chicks sampled at hatch from medium dose groups showed hypoproteinaemia, decreased uric acid and increased triglycerides. Chicks from the enrofloxacin-treated group displayed mild hyperglycaemia and a two-fold rise in the blood urea nitrogen to uric acid ratio. Principal components analysis based on blood biochemistry clearly separated the control bird cluster from both enrofloxacin- and marbofloxacin-treated birds. Conclusions Fluoroquinolones induce complex adverse effects on avian embryonic development, considerably reducing the performance of incubated eggs and hatching chicks. Cardiotoxicity, which quickens embryonic heart rate, meant that the total number of heart beats required for embryogenesis was achieved earlier than in the standard incubation period, resulting in pre-term hatching. Our data suggest that enrofloxacin has a higher potential for adverse effects than marbofloxacin. To conclude, care should be taken to prevent exposure of reproducing birds and their eggs to fluoroquinolones.

To assess the toxicity of residual marbofloxacin from animal‐derived food, the interaction characteristics of marbofloxacin to bovine/human serum albumins (BSA/HSA) were explored using spectroscopic methods combined with molecular modelling. According to fluorescence spectra and time‐resolved fluorescence spectra measurements, quenching of BSA/HSA fluorescence induced by marbofloxacin was characterized as static quenching. A 1:1 ground‐state complex of marbofloxacin to BSA/HSA was formed with binding constant (Ka) 1.66 × 104/9.74 × 103 M−1 at 291 K. The location of marbofloxacin binding at site I within BSA/HSA was clarified by site marker competitive experiments. Molecular modelling demonstrated that the binding region for marbofloxacin to BSA and HSA were at site I with the lowest binding free energies of −22.86 and −21.60 kJ mol−1, respectively. Hydrogen bonds and van der Waals forces were dominantly involved in the spontaneous binding. Nonradiation energy transferred from BSA and HSA to marbofloxacin, due to the close distance (r0) between marbofloxacin and Trp residues of BSA (4.28 nm) and HSA (3.34 nm). As explained by circular dichroism (CD) spectra, an increased BSA/HSA α‐helix structure was observed after binding to marbofloxacin. Ultraviolet–visible (UV–vis) and Fourier transform infrared (FT‐IR) spectra suggested that conformation of the two proteins was altered by marbofloxacin. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Typhimurium, an intracellular pathogen, evades the host immune response mechanisms to cause gastroenteritis in animals and humans. After invading the host cells, the bacteria proliferate in Salmonella-containing vacuole (SCV) and escapes from antimicrobial therapy. Moreover, Salmonella Typhimurium develops resistance to various antimicrobials including, fluoroquinolones. Treating intracellular bacteria and combating drug resistance is essential to limit the infection rate. One way of overcoming these challenges is through combination therapy. In this study, Pyrogallol (PG), a polyphenol, is combined with marbofloxacin (MAR) to investigate its effect on Salmonella Typhimurium invasion and intracellular survival inhibition. The Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PG against Salmonella Typhimurium were 128 and 256 μg/mL, respectively. The lowest fractional inhibitory concentration (FIC) index for a combination of PG and MAR was 0.5. The gentamycin protection assay revealed that PG (30 μg/mL) alone and in combination with sub-MIC of MAR inhibited 72.75 and 76.18% of the invading bacteria in Caco-2 cells, respectively. Besides, the intracellular survival of Salmonella Typhimurium was reduced by 7.69 and 74.36% in treatment with PG alone and combined with sub-MIC of MAR, respectively, which was visualized by the confocal microscopy. PG has also shown to increase the intracellular accumulation of fluoroquinolone by 15.2 and 34.9% at 30 and 100 μg/mL concentration, respectively. Quantitative real-time PCR demonstrated PG suppressed the genetic expression of hilA, invF, sipB, and acrA by 14.6, 15.4, 13.6, and 36%, respectively. However, the downregulation of hilA, invF, sipB, and acrA increased to 80, 74.6, 78, and 70.1%, in combination with sub-MIC of MAR, respectively. Similarly, PG combined with MAR inhibited the expression of sdiA, srgE, and rck genes by 78.6, 62.8, and 61.8%, respectively. In conclusion, PG has shown antimicrobial activity against Salmonella Typhimurium alone and in combination with MAR. It also inhibited invasion and intracellular survival of the bacteria through downregulation of quorum sensing, invading virulence, and efflux pump genes. Hence, PG could be a potential antimicrobial candidate which could limit the intracellular survival and replication of Salmonella Typhimurium.

Abstract Background Porcine pleuropneumonia, caused by Actinobacillus pleuropneumoniae, is a bacterial respiratory disease of swine. Acute outbreaks of the disease are often accompanied by high mortality and economic losses. As severe cases of the disease frequently require parenteral antibiotic treatment of the animals, the efficacy of a single, high dose of marbofloxacin was compared to a three-time application of a dose of enrofloxacin under experimental conditions. Methods A blinded, controlled, randomized and blocked dose confirmation study was conducted to test the efficacy and safety of a single dose of 8 mg/kg marbofloxacin (160 mg/ml, Forcyl® Swine, Vetoquinol SA, France) to treat acute porcine pleuropneumonia after experimental aerosol inoculation of pigs with A. pleuropneumoniae serotype 2. The results were compared to a three consecutive day treatment of 2.5 mg/kg enrofloxacin and a mock (saline) treatment. Criteria for the assessment of efficacy were severity of lung lesions, bacteriological cure and the course of clinical disease after treatment. Results: Thirty six nursery pigs were divided into three treatment groups: marbofloxacin (T1), enrofloxacin (T2) and mock (T3). Statistically significant superiority (p

Salmonella enterica serovar Typhimurium, an intracellular pathogen, evades the host immune response mechanisms to cause gastroenteritis in animals and humans. After invading the host cells, the bacteria proliferate in Salmonella -containing vacuole (SCV) and escapes from antimicrobial therapy. Moreover, Salmonella Typhimurium develops resistance to various antimicrobials including, fluoroquinolones. Treating intracellular bacteria and combating drug resistance is essential to limit the infection rate. One way of overcoming these challenges is through combination therapy. In this study, Pyrogallol (PG), a polyphenol, is combined with marbofloxacin (MAR) to investigate its effect on Salmonella Typhimurium invasion and intracellular survival inhibition. The Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PG against Salmonella Typhimurium were 128 and 256 μg/mL, respectively. The lowest fractional inhibitory concentration (FIC) index for a combination of PG and MAR was 0.5. The gentamycin protection assay revealed that PG (30 μg/mL) alone and in combination with sub-MIC of MAR inhibited 72.75 and 76.18% of the invading bacteria in Caco-2 cells, respectively. Besides, the intracellular survival of Salmonella Typhimurium was reduced by 7.69 and 74.36% in treatment with PG alone and combined with sub-MIC of MAR, respectively, which was visualized by the confocal microscopy. PG has also shown to increase the intracellular accumulation of fluoroquinolone by 15.2 and 34.9% at 30 and 100 μg/mL concentration, respectively. Quantitative real-time PCR demonstrated PG suppressed the genetic expression of hilA, invF, sipB , and acrA by 14.6, 15.4, 13.6, and 36%, respectively. However, the downregulation of hilA, invF, sipB , and acrA increased to 80, 74.6, 78, and 70.1%, in combination with sub-MIC of MAR, respectively. Similarly, PG combined with MAR inhibited the expression of sdiA, srgE , and rck genes by 78.6, 62.8, and 61.8%, respectively. In conclusion, PG has shown antimicrobial activity against Salmonella Typhimurium alone and in combination with MAR. It also inhibited invasion and intracellular survival of the bacteria through downregulation of quorum sensing, invading virulence, and efflux pump genes. Hence, PG could be a potential antimicrobial candidate which could limit the intracellular survival and replication of Salmonella Typhimurium. [ABSTRACT FROM AUTHOR]

Marbofloxacin (MBF) is a key class of synthetic fluoroquinolone antibiotic that is commonly used as a veterinary drug. However, excess residue of MBF in animal-derived food samples, such as milk, is harmful to consumers. In this study, 4 mAb against MBF, namely, M4E3, M7A6, M3C7, and M5C6, were produced. Indirect competitive (ic) ELISA revealed that the M4E3 exhibited the highest sensitivity with a half-maximal inhibitory concentration (IC 50) of 0.07 ng/mL and a limit of detection of 0.01 ng/mL for detection of MBF. The results of the cross-reactivity experiment revealed that the M4E3 could detect lomefloxacin, ofloxacin, fleroxacin, pefloxacin, danofloxacin, and enrofloxacin sensitively with IC 50 of 0.02, 0.07, 0.18, 0.27, 0.30, and 0.32 ng/mL, respectively. Meanwhile, a cross-reactivity experiment showed that the M4E3 had a crossover rate of more than 20% with these fluoroquinolone analogs. A weak crossover rate below 1.11% was observed with 14 other fluoroquinolone analogs. The recovery rate of MBF in milk ranged from 72.28% to 129.19%, which showed that the developed indirect competitive ELISA was effective in detecting MBF in milk. Furthermore, a visual colloidal gold-based immunochromatographic assay was developed for detecting MBF with a cut-off value of 1 ng/mL in both phosphate-buffered saline and a milk sample by using this mAb. Given this sensitive mAb, both indirect competitive ELISA and colloidal gold-based immunochromatographic assay could be effective screening tools for detection of MBF in milk. [ABSTRACT FROM AUTHOR]

The purpose of this study was to clarify the distribution of marbofloxacin (MBFX) within the bronchoalveolar region of pigs. Four clinically healthy pigs were intramuscularly injected with a single dose of MBFX (2 mg/kg). Samples of plasma and bronchoalveolar lavage fluid (BALF) were obtained for each pig at 0 (before administration), 3, 8 and 24 hr after administration of MBFX. As a result, the MBFX concentrations in pulmonary epithelial lining fluid (ELF) and in alveolar cells showed a similar pattern of concentrations during the experimental period. The MBFX concentrations both in ELF and alveolar cells were higher than in plasma. These results suggest that intramuscularly injected MBFX was well distributed in the bronchoalveolar region. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the influences of supportive therapy (ST) on the pharmacokinetics (PK) of marbofloxacin in lipopolysaccharide (LPS)‐induced endotoxemic sheep. Furthermore, minimum inhibitory concentration (MIC) of marbofloxacin against Escherichia coli, Mannheimia haemolytica, Pasteurella multocida, Klebsiella pneumoniae, Salmonella spp., and Staphylococcus aureus was determined. The study was performed using a three‐period cross PK design following a 15‐day washout period. In the first period, marbofloxacin (10 mg/kg) was administered by an intravenous (IV) injection. In the second and third periods, marbofloxacin was co‐administered with ST (lactated ringer + 5% dextrose + 0.45% sodium chloride, IV, 20 ml/kg, dexamethasone 0.5 mg/kg, SC) and ST + LPS (E. coli O55:B5, 10 µg/kg), respectively. Plasma marbofloxacin concentration was measured using HPLC‐UV. Following IV administration of marbofloxacin alone, the t1/2λz, AUC0–∞, ClT, and Vdss were 2.87 hr, 34.73 hr × µg/ml, 0.29 L hr−1 kg−1, and 0.87 L/kg, respectively. While no change was found in the MBX + ST group in terms of the PK parameters of marbofloxacin, it was determined that the ClT of marbofloxacin decreased, AUC0–∞ increased, and t1/2λz and MRT prolonged in the MBX + ST + LPS group. MIC values of marbofloxacin were 0.031 to >16 µg/ml for E. coli, 0.016 to >16 µg/ml for M. haemolytica, 0.016–1 µg/ml for P. multocida, 0.016–0.25 µg/ml for K. pneumoniae, 0.031–0.063 µg/ml for Salmonella spp., and 0.031–1 µg/ml for S. aureus. The study results show the necessity to make a dose adjustment of marbofloxacin following concomitant administration of ST in endotoxemic sheep. Also, the PK and pharmacodynamic effect of marbofloxacin needs to be determined in naturally infected septicemic sheep following concomitant administration of single and ST. [ABSTRACT FROM AUTHOR]

A highly efficient electrochemical platform was constructed for sensitive determination of MAR using zirconium-based metal-organic framework/nitrogen-doped graphene nanocomposites. [Display omitted] • An efficient electrochemical platform for determination of marbofloxacin. • UiO-66/NG demonstrated remarkable catalytic toward marbofloxacin. • A wide linear range (0.01–10 μM), low LOD (2 nM) and good stability (2 week). • High sensitivity in the detection of marbofloxacin in water and milk samples. Improper and persistent use of marbofloxacin (MAR) is prone to produce residues that deteriorate the surrounding environment and endanger our health. Hence, it is urgent to stablish a facile and efficient detection technique for the detection of MAR. Herein, a highly efficient electrochemical platform was constructed for sensitive determination of MAR using zirconium-based metal–organic framework (UiO-66)/nitrogen-doped graphene (NG) nanocomposites (UiO-66/NG). The surface morphology, crystalline phase, elemental composition, and electrochemical behavior of UiO-66/NG were characterized by various spectroscopic and electrochemical techniques. Owing to the synergistic interaction of UiO-66 MOFs and NG nanosheets, the UiO-66/NG exhibited remarkable catalytic activity for MAR oxidation. As consequently, the UiO-66/NG demonstrated a wide linear response range (0.01 − 10 μM), high sensitivity (1.80 μM μA−1 cm−2) and low detection limit (0.002 μM). The proposed UiO-66/NG/GCE demonstrated robust voltammetric responses even in the presence of excess potential interfering species and retained stable response signals for at least two weeks. More importantly, the proposed UiO-66/NG/GCE displayed highly consistent sensitivity toward MAR detection in both aquaculture water and milk matrices and PBS buffer, and achieved accurate and sensitive detection of MAR with good recovery. Together with its low cost and facile operation, the UiO-66/NG/GCE shows great prospects for trace detection of MAR from complex matrices. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus (S. aureus) is an important pathogen that causes clinical mastitis in goats and produces infections difficult to cure. Different antimicrobials as fluoroquinolones have been used against S. aureus. However, the studies developed to evaluate the bacterial drug interaction only have used the MIC as a single reference point with artificial growth media. The aims of this study were to describe the effect of marbofloxacin on S. aureus isolated from mastitis goats’ milk by different approaches as the minimum inhibitory and bactericidal concentrations (MIC and MBC) in cation adjusted Mueller–Hinton broth (CAMHB), serum and milk of goats at two inoculum sizes of 105 and 108 CFU/mL, the determination and analysis of the time kill curves (TKC) by non-linear mixed effect models in each growth medium and inoculum size, as well as the estimation of their pharmacokinetics/pharmacodynamics (PK/PD) cutoff values. The results obtained indicate that MIC values were higher and increases 2,4-fold in serum and 3,6-fold in milk at high inoculum, as well as the EC50 values determined by each pharmacodynamics model. Finally, the PK/PD cutoff values defined as fAUC24/MIC ratios to achieve clinical efficacy were highly dependent on inoculum and growth medium, with median values of 60–180, especially at high inoculum in milk, suggesting that further studies are necessary to evaluate and optimize the best therapeutic strategies for treating S. aureus in lactating goats.

Coagulase-negative staphylococci are main pathogens that produce goat mastitis. Marbofloxacin is a third-generation fluoroquinolone approved for treat mastitis in animals. The objectives of this study were: (i) to determine the pharmacokinetics of marbofloxacin (10 mg/kg/24 h) in serum and milk administered intramuscularly for five days in goats with mastitis induced by coagulase-negative staphylococci; (ii) to characterize the concentration–effect relationship of marbofloxacin against coagulase-negative staphylococci in Mueller Hinton broth and goat milk; (iii) to determine AUC/MIC cutoff values of marbofloxacin, and (iv) to perform a PK/PD analysis to evaluate the efficacy of the dose regimen for the treatment of goat mastitis produced by coagulase-negative staphylococci. Marbofloxacin presented context-sensitive pharmacokinetics, influenced by the evolution of the disease, which decreased marbofloxacin disposition in serum and milk. Marbofloxacin showed a median (95% CI) fAUC/MIC values for MIC of 0.4 and 0.8 µg/mL of 26.66 (22.26–36.64) and 32.28 (26.57–48.35) related with −2 log10CFU/mL reduction; and 32.26 (24.81–81.50) and 41.39 (29.38–128.01) for −3 log10CFU/mL reduction in Mueller Hinton broth. For milk, −2 log10CFU/mL reduction was achieved with 41.48 (35.29–58.73) and 51.91 (39.09–131.63), and −3 log10CFU/mL reduction with 51.04 (41.6–82.1) and 65.65 (46.68–210.16). The proposed dose regimen was adequate for the treatment of goat mastitis produced by coagulase-negative staphylococci, resulting in microbiological and clinical cure of all animals. The animal model used in this study provided important pharmacokinetic information about the effect of the infection on the pharmacokinetics of marbofloxacin. Pharmacodynamic modeling showed that fAUC/MIC cutoff values were higher in goat milk compared with Mueller Hinton broth.

The purpose of this study was to evaluate the differences in the disposition and plasma pharmacokinetic behavior of marbofloxacin (MAR) in broiler chickens at different seasons. Chicken broilers (n = 345) were used, in lots of 5 individuals, divided into 6 groups depending on the way of administration, intravenous or oral (dose 2 mg/kg) and the test period. Post-administration plasma samples were obtained at different times, intravenously (0.08 to 24 hours) and orally (0.25 to 120 hours). A liquid-liquid extraction of MAR was performed by high-performance liquid chromatography (HPLC) with a fluorescent detector. The plasma concentrations obtained at the different sampling times of each season, were analyzed with ANOVA and pharmacokinetic analysis was conducted with the PK Solution 2.0 software. The concentration of marbofloxacin in plasma was significantly lower in winter and summer than in spring, with MAR being detected in winter up to 72 hours post-application, coinciding with the differences in MAR pharmacokinetics parameters with increase in the average residence time (MRT) is 9.4 hours in winter. Increased clearance MAR in summer (7.5 ml/min/kg) coincides with MRT 6.3 hours. Finally, the oral bioavailability of MAR is lower in summer and winter (86 ± 1.7% and 78 ± 3.1%) than in spring (94 ± 5.2 %). There are differences in the disposition and plasma pharmacokinetic behavior of MAR applied orally in broiler chickens, coinciding with the physiological changes in the thermoregulation of birds, considering its correct therapeutic management and contributing to provide safe food for human consumption.

Abstract Background Bacterial pneumonia in pigs occurs widely and requires antimicrobial therapy. It is commonly caused by the pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida. Marbofloxacin is an antimicrobial drug of the fluoroquinolone class, licensed for use against these organisms in the pig. In recent years there have been major developments in dosage schedule design, based on integration and modelling of pharmacokinetic (PK) and pharmacodynamic (PD) data, with the objective of optimising efficacy and minimising the emergence of resistance. From in vitro time-kill curves in pig serum, PK/PD breakpoint Area under the curve (AUC) 24h /minimum inhibitory concentration (MIC) values were determined and used in conjunction with published PK, serum protein binding data and MIC distributions to predict dosages based on Monte Carlo simulation (MCS). Results For three levels of inhibition of growth, bacteriostasis and 3 and 4log10 reductions in bacterial count, mean AUC24h/MIC values were 20.9, 45.2 and 71.7 h, respectively, for P. multocida and 32.4, 48.7 and 55.5 h for A. pleuropneumoniae. Based on these breakpoint values, doses for each pathogen were predicted for several clinical scenarios: (1) bacteriostatic and bactericidal levels of kill; (2) 50 and 90% target attainment rates (TAR); and (3) single dosing and daily dosing at steady state. MCS for 90% TAR predicted single doses to achieve bacteriostatic and bactericidal actions over 48 h of 0.44 and 0.95 mg/kg (P. multocida) and 0.28 and 0.66 mg/kg (A. pleuropneumoniae). For daily doses at steady state, and 90% TAR bacteriostatic and bactericidal actions, dosages of 0.28 and 0.59 mg/kg (P. multocida) and 0.22 and 0.39 mg/kg (A. pleuropneumoniae) were required for pigs aged 12 weeks. Doses were also predicted for pigs aged 16 and 27 weeks. Conclusions PK/PD modelling with MCS approaches to dose determination demonstrates the possibility of tailoring clinical dose rates to a range of bacterial kill end-points.