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Pharmacokinetics of cefquinome in rainbow trout ( Oncorhynchus mykiss ) after intravascular, intraperitoneal, and oral administrations
Abstract
This study aimed to determine the pharmacokinetics and bioavailability of cefquinome in rainbow trout (Oncorhynchus mykiss) following intravascular (IV), intraperitoneal (IP), and oral (PO) administrations at 14 ± 1°C. In this study, three hundred and six clinically healthy rainbow trout (110–140 g) were used. The fish received single IV, IP, and PO injections of cefquinome at 10 mg/kg dose. The plasma concentrations of cefquinome were measured using HPLC‐UV and were evaluated using non‐compartmental analysis. Cefquinome was measured up to 96 h for PO route and 144 h for IV and IP routes in plasma. Following IV administration, t1/2ʎz, ClT, and Vdss were 18.85 h, 0.037 L/h/kg, and 0.84 L/kg, respectively. The Cmax of IP and PO routes was 9.75 and 1.64 μg/ml, respectively. The bioavailability following IP and PO administrations was 59.46% and 12.33%, respectively. Cefquinome at 10 mg/kg dose may maintain T > MIC above 40% at 72 and 96 h intervals, respectively, following the IP and IV routes for bacteria with MIC values of ≤2 μg/ml and at 24 h intervals following the PO route for bacteria with MIC value of ≤0.75 μg/ml. However, further studies are needed to determine in vitro and in vivo antibacterial efficacy and multiple dosage regimens of cefquinome against pathogens isolated from rainbow trout.
... Pharsight Corporation, Scientific Consulting Inc., North Carolina, USA). The pharmacokinetic calculation was conducted using non-compartmental analysis based on the mean concentration values at the sampling time, as different animals were employed for each sampling period [22,23]. For both groups, the Area Under the Curve (AUC), terminal elimination half-life (t 1/2ʎz ), total body clearance (CL/F), volume of distribution (V darea /F), and Mean Residence Time (MRT) were calculated. ...
Background
Antibiotics and bronchodilator drugs can be used together in respiratory distress caused by bacterial infections. Levofloxacin (LVX) and Salbutamol (SLB) can be used simultaneously in respiratory distress. However, there have been no investigations on how the concurrent use of SLB can affect the pharmacokinetics of LVX in rats.
Objective
The purpose of this study was to investigate the influence of SLB on the plasma and lung pharmacokinetics of LVX in rats.
Methods
A total of 132 rats were randomly assigned to two groups: LVX (n=66) and LVX+SLB (n=66). LVX (intraperitoneal) and SLB (oral) were administered to rats at doses of 50 and 3 mg/kg, respectively. The concentrations of LVX in the plasma and lungs were determined through the utilization of high-performance liquid chromatography along with UV. Pharmacokinetic parameters were assessed by non-compartmental analysis.
Results
The area under the curve from 0 to 16 h (AUC0−16), terminal elimination half-life, volume of distribution, total body clearance, and peak concentration of LVX in the plasma were 42.57 h*μg/mL, 2.32 h, 3.91 L/kg, 1.17 L/h/kg, and 23.96 μg/mL, respectively. There were no alterations observed in the plasma and lung pharmacokinetic parameters of LVX when co-administered with SLB. The AUC0−16 lung/AUC0−16 plasma ratios of LVX were 1.60 and 1.39 after administration alone and co-administration with SLB, respectively.
Conclusion
The concentration of LVX in lung tissue was higher than that in plasma. SLB administration to rats did not affect the plasma and lung pharmacokinetics and lung penetration ratio of LVX. There is a need to reveal the change in the pharmacokinetics of LVX after multiple administration of both drugs and after administration of SLB by different routes.
... each sampling time and averaged. Pharmacokinetic data of tolfenamic acid were calculated from the average plasma concentration at sampling times, as documented in previous studies(Corum et al., 2023;Durna Corum et al., 2022). The area under the concentration (AUC) versus time curve, AUC extrapolated from t last to ∞ in % of the total AUC (AUC extrap %), volume of distribution at steady state (V dss ), total body clearance (Cl T ), terminal elimination half-life (t 1/2λz ), mean residence time (MRT), mean absorption time (MAT = MRT IM,oral − MRT IV ) ...
Background
Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non‐steroidal anti‐inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties.
Objectives
The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C.
Methods
The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography–ultraviolet (UV) and pharmacokinetic parameters were assessed using non‐compartmental analysis.
Results
The elimination half‐life (t1/2ʎz) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent.
Conclusions
While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.
... Pharsight Corporation, Scientific Consulting Inc., North Carolina, USA). Because different animals were used at each sampling time, the pharmacokinetic calculation was determined by non-compartmental analysis of the mean concentration values at the sampling times for each sex in the group [27,28]. For both groups, the terminal elimination half-life (t1/2ʎz), area under the curve (AUC), mean residence time (MRT), total body clearance (CL/F) and volume of distribution (Vdarea/F) were calculated. ...
Abstract: Background: The simultaneous use of NSAIDs and antibiotics is recommended for bacterial dis�eases in human and veterinary medicine. Moxifloxacin (MFX) and dexketoprofen (DEX) can be used simul�taneously in bacterial infections. However, there are no studies on how the simultaneous use of DEX affects
the pharmacokinetics of MFX in rats.
Objectives: The aim of this study was to determine the effect of DEX on plasma and lung pharmacokinetics
of MFX in male and female rats.
Methods: A total of 132 rats were randomly divided into 2 groups: MFX (n=66, 33 males/33 females) and
MFX+DEX (n=66, 33 females/33 males). MFX at a dose of 20 mg/kg and DEX at a dose of 25 mg/kg were
administered intraperitoneally. Plasma and lung concentrations of MFX were determined using the high�performance liquid chromatography-UV and pharmacokinetic parameters were evaluated by non�compartmental analysis.
Results: Simultaneous administration of DEX increased the plasma and lung area under the curve from 0 to
8 h (AUC0-8) and peak concentration (Cmax) of MFX in rats, while it significantly decreased the total body
clearance (CL/F). When female and male rats were compared, significant differences were detected in
AUC0-8, Cmax, CL/F and volume of distribution. The AUC0-8lung/AUC0-8plasma ratios of MFX were calculated as
1.68 and 1.65 in female rats and 5.15 and 4.90 in male rats after single and combined use, respectively.
Conclusion: MFX was highly transferred to the lung tissue and this passage was remarkably higher in male
rats. However, DEX administration increased the plasma concentration of MFX in both male and female rats
but did not change its passage to the lung. However, there is a need for a more detailed investigation of the
difference in the pharmacokinetics of MFX in male and female rats.
... Pharmacokinetic non-compartmental analysis of OTC concentration-time data was analyzed using the WinNonlin 6.1.0.173 software (Pharsight Corporation, Scientific Consulting Inc., Raleigh, NC, USA). Pharmacokinetic parameters of OTC were calculated from the mean plasma concentration values collected at each sampling time, as reported in previous studies [20,21]. The pharmacokinetic parameters calculated included the area under the plasma concentration-time curve (AUC), AUC extrapolated from tlast to ∞ in % of the total AUC (AUC extrap %), volume of distribution at steady state (V dss = Cl T × MRT), apparent volume of distribution (V darea ), total body clearance (Cl T = Dose/AUC), terminal elimination half-life (t 1/2 ...
Simple Summary
Determination of the pharmacokinetics of oxytetracycline (OTC) at single and multiple oral doses revealed its long half-life, very low bioavailability, and strong accumulation in rainbow trout. The withdrawal time (WT) for the safe consumption of rainbow trout muscle+skin varied according to the guidelines set by regulatory authorities in different countries. This study improves the establishment of the optimal dosing regimen following OTC multiple administration and the determination of the appropriate WT for the safety of rainbow trout consumption.
Abstract
The aim of this study was to compare the pharmacokinetics of oxytetracycline (OTC) following single- (60 mg/kg) and multiple-dose oral administrations (60 mg/kg, every 24 h for 7 days) in rainbow trout. It also aimed to determine bioavailability after a single dose and tissue residues and withdrawal times after multiple doses. This study was carried out on 420 rainbow trout at 9 ± 0.8 °C. This study was carried out in two stages: single-dose (intravascular and oral) and multiple-dose treatment. The OTC concentrations in plasma and tissues were measured by high-performance liquid chromatography and analyzed by a non-compartmental method. The withdrawal time (WT) was estimated using the WT 1.4 software. OTC exhibited a long terminal elimination half-life (t1/2ʎz) after IV and oral administration. The oral bioavailability of OTC was very low (2.80%). In multiple-dose treatment, t1/2ʎz, the area under the plasma concentration–time curve and peak plasma concentration increased significantly after the last day compared to the first day. OTC showed strong accumulation after multiple doses with a value of 5.33. OTC concentrations were obtained in the order liver > kidney > muscle+skin > plasma. At 9 ± 0.8 °C, the WT calculated for muscle+skin was 56 days for Europe and 50 days for China, respectively. The t1/2ʎz (68.94 h) and time (68 h) above the 1 µg/mL MIC following a single OTC dose may support the extension of the 24 h dosing interval following multiple dosing. However, further studies are required to determine the optimal dosage regimen in multiple-dose OTC treatment in the treatment of infections caused by susceptible pathogens.
... Using the WinNonlin 6.1.0.173 software program (Pharsight Corporation, Scientific Consulting Inc., Sunnyvale, NC, USA), the plasma concentration-time curves of doxycycline were plotted. After oral administration, pharmacokinetic parameters were determined via non-compartmental analysis using mean plasma concentrations of doxycycline collected at each sampling time [25][26][27]. After the doxycycline administration, apparent volume of distribution (V darea /F), total body clearance (CL/F, area under the concentration-time curve (AUC), terminal elimination half-life (t 1/2Lz ), AUC extrapolated from t last to ∞ in % of the total AUC (AUC extrap %), and mean residence time (MRT) were determined. ...
The purpose of this study was to compare the pharmacokinetics, tissue residues, and withdrawal times of doxycycline after oral administration in rainbow trout reared at 10 and 17 °C. Fish received a 20 mg/kg oral dose of doxycycline after a single or 5-day administration. Six rainbow trout were used at each sampling time point for plasma and tissue samples, including liver, kidney, and muscle and skin. The doxycycline concentration in the samples was determined using high-performance liquid chromatography with ultraviolet detector. The pharmacokinetic data were evaluated by non-compartmental kinetic analysis. The WT 1.4 software program was used to estimate the withdrawal times. The increase of temperature from 10 to 17 °C shortened the elimination half-life from 41.72 to 28.87 h, increased the area under the concentration–time curve from 173.23 to 240.96 h * μg/mL, and increased the peak plasma concentration from 3.48 to 5.50 μg/mL. At 10 and 17 °C, the doxycycline concentration was obtained in liver > kidney > plasma > muscle and skin. According to the MRL values stated for muscle and skin in Europe and China (100 μg/kg) and in Japan (50 μg/kg), the withdrawal times of doxycycline at 10 and 17 °C were 35 and 31 days, respectively, for Europe and China and 43 and 35 days, respectively, for Japan. Since temperature significantly affected pharmacokinetic behavior and withdrawal times of doxycycline in rainbow trout, temperature-dependent dosing regimens and withdrawal times of doxycycline might be necessary.
... Plasma concentrations were presented as mean ± standard deviation (SD) values. PK parameters of ENR and CIP were calculated by the noncompartmental analysis using mean plasma concentration values collected at each sampling time after IV, IP, or PO administrations (Corum et al. 2018(Corum et al. , 2019bDurna Corum et al. 2022). The terminal elimination halflife (t 1/2kz ), mean residence time (MRT), area under the plasma concentration-time curve (AUC), total clearance (Cl T ), and volume of distribution at steady state (V dss ) were calculated. ...
The aim of the study was to investigate the plasma and muscle pharmacokinetic of enrofloxacin (ENR) and its active metabolite ciprofloxacin (CIP) in Nile tilapia (Oreochromis niloticus) following single intravascular (IV), intraperitoneal (IP), or oral (PO) administration at 30 ± 1 °C. In this study, 234 healthy Nile tilapia (120-150 g) were used. The fish received a single IV, IP, or PO treatment of ENR at a dose of 10 mg/kg. The plasma and muscle tissue concentrations of ENR and CIP were measured using high-performance liquid chromatography with fluorescence detection and were evaluated using non-compartmental analysis. The elimination half-life, volume of distribution at steady state, and total body clearance of ENR were 21.7 h, 2.69 L/kg, and 0.09 L/h/kg, respectively. The peak plasma concentrations of ENR after IP or PO administration were 6.11 and 4.21 µg/mL at 0.25 and 2 h, respectively. The bioavailability of ENR for IP or PO routes was 78% and 86%, respectively. AUC(0-120)muscle/AUC(0-120)plasma ratios following the IV, IP, or PO administrations were 1.43, 1.49, and 1.07, respectively. CIP was detected after all routes, but the AUC0-last ratios of CIP to ENR were <1.0% for plasma and muscle. ENR was detected up to 120 h following the IV, IP, or PO administrations. The long residence time of ENR after single IV, IP, or PO administration ensured the plasma concentration was ≥1 × MIC for bacteria with threshold MIC values of 0.92, 0.72, and 0.80 μg/mL over the whole 120 h observed. However, further studies are necessary to determine the optimum pharmacokinetic/pharmacodynamics data of ENR for the treatment of infections caused by susceptible bacteria in tilapia.
Deniz ürünleri üretimi, milyonlarca insana istihdam ve geçim sağlayan kritik bir küresel endüstridir. Sektördeki üretim teknolojilerinin yoğunlaşması, deniz ürünleri üretimindeki arz-talep açığını kapatmak için ortaya çıkmıştır, ancak potansiyel halk sağlığı tehditlerine ilişkin endişeler gündeme gelmiştir. Örneğin, su ürünleri yetiştiriciliği ortamlarında artan stok yoğunlukları balıklarda stresin artmasına yol açarak patojen çoğalmasına elverişli bir ortam yaratmıştır. Antibiyotikler balıklarda ve diğer hayvanlarda bakteriyel enfeksiyonların tedavisinde ve önlenmesinde yaygın olarak kullanılmaktadır. Ancak antibiyotiklerin insan ve hayvan sağlığına zararlı etki yapma riski bulunmaktadır. Balıklarda ve diğer su hayvanlarında, ayrıca su ortamında ve diğer ekolojik nişlerde antibiyotiklere dirençli bakterilerin ortaya çıkması, ilaca dirençli bakterilerin ve aktarılabilir direnç genlerinin rezervuarlarını oluşturmuştur. İnsan patojenlerindeki antimikrobiyal ajanlara karşı direnç, insan enfeksiyonları sırasında tedavi seçeneklerini ciddi şekilde sınırlandırmaktadır. Bu derleme, su ürünleri yetiştiriciliğinde yaygın olarak kullanılan antibiyotik türleri, antibiyotik uygulaması, antibiyotik test teknikleri ve su, balık ve sedimentteki antibiyotik direnci hakkındaki bilgileri bir araya getirmektedir. Antibiyotik direnciyle mücadelede karşılaşılan zorluklar, stratejiler ve kısıtlamaların yanı sıra su ürünleri yetiştiriciliğinde antibiyotik kullanımına yönelik beklentiler de tartışılmaktadır.
Flunixin's pharmacokinetics, bioavailability, and plasma protein binding were examined in rainbow trout. The experiment involved 252 rainbow trout ( Oncorhynchus mykiss ) maintained at 12 ± 0.6°C. Flunixin was administered to rainbow trout via intravascular (IV), intramuscular (IM), and oral routes at a dosage of 2.2 mg/kg. Plasma samples were collected at times 0 (control), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 h. High‐pressure liquid chromatography‐ultraviolet was employed to quantify flunixin concentrations. The elimination half‐life ( t 1/2ʎz ) for flunixin was 8.37 h for IV, 8.68 h for IM, and 8.76 h for oral. The t 1/2ʎz was similar between administration groups. The volume of distribution at a steady state and total body clearance were 55.81 mL/kg and 6.83 mL/h/kg, respectively, after IV administration. The mean peak plasma concentration was 6.24 ± 0.41 μg/mL at 4 h for oral administration and 13.98 ± 0.86 μg/mL at 2 h for IM administration. The in vitro protein binding ratio of flunixin in rainbow trout plasma was 96.34 ± 2.29%. The bioavailability of flunixin after oral (25.74%) administration was lower than that after IM (66.70%) administration. Thus, developing an oral pharmaceutical formulation that can be administered with feed and has high bioavailability could enhance the therapeutic effect.
Objective
The aim of this study was to determine the plasma pharmacokinetics of oxytetracycline (OTC) in rainbow trout ( Oncorhynchus mykiss ) of different body sizes.
Methods
The research was carried out on three groups as small (30–50 g), medium (90–110 g) and large (185–215 g) body sizes at 8 ± 0.5 °C. OTC was administered orally at a dose of 60 mg/kg to all groups. Blood samples were taken at 19 different sampling times until the 384 h after oxytetracycline administration. The plasma concentrations of OTC were measured using high pressure liquid chromatography-ultraviolet and pharmacokinetic parameters were evaluated using non-compartmental analysis.
Results
OTC was detected in small-body sized fish until the 336 h and in medium and large-body sized fish until the 384 h. The elimination half-life of OTC was 85.46, 87.24 and 86.98 h in the small, medium and large body size groups, respectively. The peak plasma concentration increased from 0.66 to 1.11 µg/mL, and the area under the plasma concentration-versus time curve from zero (0) h to infinity (∞) increased from 87.86 to 151.52 h*µg/mL, in tandem with the increase in fish body size. As fish body size increased, volume of distribution and total body clearance decreased.
Conclusion
These results show that the pharmacokinetics of OTC vary depending on fish size. Therefore, there is a need to reveal the pharmacodynamic activity of OTC in rainbow trout of different body sizes.
The bioavailability and pharmacokinetics in turkeys of cefquinome (CFQ), a broad-spectrum 4th-generation cephalosporin antibiotic, were explored after a single injection of 2 mg/kg body weight by intravenous (IV) and intramuscular (IM) routes. In a crossover design and 3-weeks washout interval, seven turkeys were assigned for this objective. Blood samples were collected prior to and at various time intervals following each administration. The concentration of CFQ in plasma was measured using HPLC with a UV detector set at 266 nm. For pharmacokinetic analysis, non-compartmental methods have been applied. Following IV administration, the elimination half-life (t1/2ʎz), distribution volume at steady state (Vdss), and total body clearance (Cltot) of CFQ were 1.55 h, 0.54 L/kg, and 0.32 L/h/kg, respectively. Following the IM administration, CFQ was speedily absorbed with an absorption half-life (t1/2ab) of 0.25 h, a maximum plasma concentration (Cmax) of 2.71 μg/mL, attained (Tmax) at 0.56 h. The bioavailability (F) and in vitro plasma protein binding of CFQ were 95.56% and 11.5%, respectively. Results indicated that CFQ was speedily absorbed with a considerable bioavailability after IM administration. In conclusion, CFQ has a favorable disposition in turkeys that can guide to estimate optimum dosage regimes and eventually lead to its usage to eradicate turkey’s susceptible bacterial infections.
The pharmacokinetic of enrofloxacin was investigated in brown trout (Salmo trutta) following oral administration of 10, 20, and 40 mg/kg doses at 11 ± 1.5 °C. Furthermore, MICs of enrofloxacin against Aeromonas hydrophila and A. sobria were determined. The plasma concentrations of enrofloxacin and ciprofloxacin were determined using HPLC–UV and analyzed by non-compartmental method. Following oral administration at dose of 10 mg/kg, total clearance (CL/F), area under the concentration–time curve (AUC0−∞) and peak plasma concentrations (Cmax) were 41.32 mL/h/kg, 242.02 h*μg/mL and 4.63 μg/mL, respectively. When compared to 10 mg/kg dose, the dose-normalized AUC0–∞ and Cmax were increased by 56.30% and 30.08%, respectively, while CL/F decreased by 38.4% at 40 mg/kg dose, suggesting the non-linearity. Ciprofloxacin was not detected in the all of plasma samples. The MIC values of enrofloxacin were ranged 0.0625–4 μg/mL for A. hydrophila and 0.0625–2 μg/mL for A. sobria. The oral administration of enrofloxacin at 10 (for 192 h) and 20 (for 240 h) mg/kg doses provided the AUC of enrofloxacin equal to 1.23 and 1.96-fold MICs, respectively, for A. hydrophila and A. sobria with the MIC90 values of 1 µg/mL. However, further researches are needed on the PK/PD study of enrofloxacin for the successful treatment of infections caused by A. hydrophila and A. sobria in brown trout.
The aim of this study was to determine the pharmacokinetics of carprofen following intravenous (IV), intramuscular (IM) and oral routes to rainbow trout (Oncorhynchus mykiss) broodstock at temperatures of 10 ± 1.5 °C. In this study, thirty-six healthy rainbow trout broodstock (body weight, 1.45 ± 0.30 kg) were used. The plasma concentrations of carprofen were determined using high-performance liquid chromatography and pharmacokinetic parameters were calculated using non-compartmental analysis. Carprofen was measured up to 192 h for IV route and 240 h for IM, and oral routes in plasma. The elimination half-life (t1/2λz) was 30.66, 46.11, and 41.08 h for IV, IM and oral routes, respectively. Carprofen for the IV route showed the total clearance of 0.02 L/h/kg and volume of distribution at steady state of 0.60 L/kg. For IM and oral routes, the peak plasma concentration (Cmax) was 3.96 and 2.52 μg/mL with the time to reach Cmax of 2 and 4 h, respectively. The bioavailability was 121.89% for IM route and 78.66% for oral route. The favorable pharmacokinetic properties such as the good bioavailability and long t1/2λz for IM and oral route of carprofen suggest the possibility of its effective use for the treatment of various conditions in broodstock.
Background:
Antimicrobial resistant bacteria are emerging biological contaminants of the environment. In aquatic ecosystems, they originate mainly from hospitals, livestock manure and private households sewage water, which could contain antimicrobial agents and resistant microorganisms. Aeromonas spp. occur ubiquitously in aquatic environments and they cause disease in fish. Motile aeromonads are also associated with human gastrointestinal and wound infections and fish can act as a transmission route of antimicrobial resistance (AMR) aeromonads to humans. The environmental ubiquity, the natural susceptibility to antimicrobials and the zoonotic potential of Aeromonas spp. make them optimal candidates for studying the AMR in aquatic ecosystems.
Results:
The AMR patterns of 95 motile aeromonads isolated from freshwater fish during 2013 and 2016 were analyzed. All samples from fish came from farms and natural water bodies located in northern Italy, which is an area characterized by high anthropic impact on the environment. The isolates were biochemically identified as Aeromonas hydrophila, Aeromonas sobria or Aeromonas caviae and AMR was determined by the standard disk diffusion method. All isolates were resistant to cloxacillin, spiramycin and tilmicosin. High AMR frequencies (> 95%) were detected for tylosin, penicillin and sulfadiazine. AMR to danofloxacin, enrofloxacin, flumequine, ceftiofur, aminosidine, colistin, doxycycline, gentamicin, marbocyl and florfenicol was observed at low levels (< 10%). No AMR to cefquinome was found. Logistic regression showed several differences in antimicrobial activity between complexes. According to the source of aeromonads, only few differences in AMR between isolates from farmed and wild fish were observed.
Conclusions:
Our data revealed an increasing trend of AMR to neomycin and apramycin among Aeromonas isolates during the study period, while resistance to erythromycin, tetracycline and thiamphenicol decreased. All isolates were multidrug resistance (MDR), but A. caviae showed the highest number of MDR per isolate. In most isolates, various degrees of MDR were detected to macrolides, quinolones, fluoroquinolones, polymyxins and cephalosporins (third and fourth generations), which are listed, by the World Health Organisation, to be among the highest priority and critically important antimicrobials in human medicine. Our findings underlined that freshwater fish can act as potential source of MDR motile aeromonads. Due to their zoonotic potential, this can pose serious threat to human health.
Antimicrobial Drug Resistance in Fish Pathogens, Page 1 of 2
Abstract
Major concerns surround the use of antimicrobial agents in farm-raised fish, including the potential impacts these uses may have on the development of antimicrobial-resistant pathogens in fish and the aquatic environment. Currently, some antimicrobial agents commonly used in aquaculture are only partially effective against select fish pathogens due to the emergence of resistant bacteria. Although reports of ineffectiveness in aquaculture due to resistant pathogens are scarce in the literature, some have reported mass mortalities in Penaeus monodon larvae caused by Vibrio harveyi resistant to trimethoprim-sulfamethoxazole, chloramphenicol, erythromycin, and streptomycin. Genetic determinants of antimicrobial resistance have been described in aquaculture environments and are commonly found on mobile genetic elements which are recognized as the primary source of antimicrobial resistance for important fish pathogens. Indeed, resistance genes have been found on transferable plasmids and integrons in pathogenic bacterial species in the genera Aeromonas, Yersinia, Photobacterium, Edwardsiella, and Vibrio. Class 1 integrons and IncA/C plasmids have been widely identified in important fish pathogens (Aeromonas spp., Yersinia spp., Photobacterium spp., Edwardsiella spp., and Vibrio spp.) and are thought to play a major role in the transmission of antimicrobial resistance determinants in the aquatic environment. The identification of plasmids in terrestrial pathogens (Salmonella enterica serotypes, Escherichia coli, and others) which have considerable homology to plasmid backbone DNA from aquatic pathogens suggests that the plasmid profiles of fish pathogens are extremely plastic and mobile and constitute a considerable reservoir for antimicrobial resistance genes for pathogens in diverse environments.
As the human population increases there is an increasing reliance on aquaculture to supply a safe, reliable, and economic supply of food. Although food production is essential for a healthy population, an increasing threat to global human health is antimicrobial resistance. Extensive antibiotic resistant strains are now being detected; the spread of these strains could greatly reduce medical treatment options available and increase deaths from previously curable infections. Antibiotic resistance is widespread due in part to clinical overuse and misuse; however, the natural processes of horizontal gene transfer and mutation events that allow genetic exchange within microbial populations have been ongoing since ancient times. By their nature, aquaculture systems contain high numbers of diverse bacteria, which exist in combination with the current and past use of antibiotics, probiotics, prebiotics, and other treatment regimens—singularly or in combination. These systems have been designated as “genetic hotspots” for gene transfer. As our reliance on aquaculture grows, it is essential that we identify the sources and sinks of antimicrobial resistance, and monitor and analyse the transfer of antimicrobial resistance between the microbial community, the environment, and the farmed product, in order to better understand the implications to human and environmental health.
Enteric redmouth disease (ERM) is a serious septicemic bacterial disease of salmonid fish species. It is caused by Yersinia ruckeri, a Gram-negative rod-shaped enterobacterium. It has a wide host range, broad geographical distribution, and causes significant economic losses in the fish aquaculture industry. The disease gets its name from the subcutaneous hemorrhages, it can cause at the corners of the mouth and in gums and tongue. Other clinical signs include exophthalmia, darkening of the skin, splenomegaly and inflammation of the lower intestine with accumulation of thick yellow fluid. The bacterium enters the fish via the secondary gill lamellae and from there it spreads to the blood and internal organs. Y. ruckeri can be detected by conventional biochemical, serological and molecular methods. Its genome is 3.7 Mb with 3406-3530 coding sequences. Several important virulence factors of Y. ruckeri have been discovered, including haemolyin YhlA and metalloprotease Yrp1. Both non-specific and specific immune responses of fish during the course of Y. ruckeri infection have been well characterized. Several methods of vaccination have been developed for controlling both biotype 1 and biotype 2 Y. ruckeri strains in fish. This review summarizes the current state of knowledge regarding enteric redmouth disease and Y. ruckeri: diagnosis, genome, virulence factors, interaction with the host immune responses, and the development of vaccines against this pathogen.
Background:
In order to provide some basis for effective dosage regimens that optimize efficacy with respect to bacteriological and clinical cures, the in vivo activity of cefquinome against a clinical Escherichia coli (E.coli) strain (the minimum inhibitory concentration value for this strain equals to the MIC90 value of 0.25 μg/ml for 210 E.coli strains isolated from pigs) was investigated by using a piglet tissue-cage infection model. The aim was to elucidate the pharmacokinetic/pharmacodynamics (PK/PD) index associated with cefquinome efficacy, and then to identify the magnitude of the PK/PD parameter required for different degree of efficacy in clinical treatment.
Results:
Tissue-cage infection model was established in piglets, and then the animals received intramuscular injection of cefquinome twice a day for 3 days to create a range of different drug exposures. The tissue-cage fluid was collected at 1, 3, 6, 9 and 12 h after every drug administration for drug concentrationdetermination and bacteria counting. Different cefquinome regimens produced different percentages of time during that drug concentrations exceeded the MIC (%T > MIC), ranging from 0% to 100%. Cefquinome administration at 0.2, 0.4, 0.6, 0.8, 1, 2 and 4 mg/kg reduced the bacterial count (log10 CFU/mL) in tissue-cage fluid by -1.00 ± 0.32, -1.83 ± 0.08, -2.33 ± 0.04, -2.96 ± 0.16, -2.99 ± 0.16, -2.93 ± 0.11, -3.43 ± 0.18, respectively. The correlation coefficient of the PK/PD index with antibacterial effect of the drug was 0.90 for %T > MIC, 0.62 for AUC0-12/MIC, and 0.61 for Cmax/MIC, suggesting the most important PK/PD parameter was %T > MIC. A inhibitory form of sigmoid maximum effect (Emax) model was used to estimate %T > MIC, and the respective values required for continuous 1/6-log drop, 1/3-log drop and 1/2-log drop of the clinical E.coli count during each 12 h treatment period were 3.97%, 17.08% and 52.68%.
Conclusions:
The data derived from this study showed that cefquinome exhibited time-dependent killing profile. And from the results of the present study, it can be assumed that when %T > MIC reached 52.68%, cefquinome could be expected to be effective against a clinical E.coli strain for which the MIC value is below 0.128 μg/ml (3-log drop of bacteria count can be achieved after six successive administrations for 3 days).
The potential risk of occurrence of new diseases associated with the trade of live animals is well known. However, little importance is still given to the problematic of the dissemination of resistance genes that pass along with the animal trade. In this study we aimed to isolate Aeromonas spp. strains from water and skin of ornamental fish and test their resistance to antibiotics. The samples were collected from a national ornamental fish importer, with the intent of obtaining a collection of Aeromonas strains. The identifcation of the strains was made by gyrB and rpoD gene sequencing. A total of 288 strains grouped in seven different species - Aeromonas veronii, Aeromonas media, Aeromonas jandaei, Aeromonas hydrophila, Aeromonas caviae, Aeromonas culicicola, Aeromonas aquariorum, were isolated. The susceptibility profle was determined for 28 antibiotics commonly used. All the strains presented multi-resistance to the tested antibiotics. The antibiotic susceptibility profle to tetracycline, ticarcillin, carbenicillin, ampicillin and erythromycin revealed resistance levels of more than 80%. Few strains resistant to aztreonam and imipenem were identifed. On the other hand, all were sensitive to cefotaxime and cefepime. The results show that these Aeromonas spp. strains are potentially reservoirs of antibiotic resistance genes.
ABSTRACT: Antibiotic resistance and presence of the resistance genes were investigated in the bacteria isolated from water, sediment, and fish in trout farms. A total of 9 bacterial species, particularly Escherichia coli, were isolated from the water and sediment samples, and 12 species were isolated from fish. The antimicrobial test indicated the highest resistance against sulfamethoxazole and ampicillin in coliform bacteria, and against sulfamethoxazole, imipenem, and aztreonam in known pathogenic bacteria isolated from fish. The most effective antibiotics were rifampicin, chloramphenicol, and tetracycline. The multiple antibiotic resistance index was above the critical limit for almost all of the bacteria isolated. The most common antibiotic resistance gene was ampC, followed by tetA, sul2, blaCTX-M1, and blaTEM in the coliform bacteria. At least one resistance gene was found in 70.8% of the bacteria, and 66.6% of the bacteria had 2 or more resistance genes. Approximately 36.54% of the bacteria that contain plasmids were able to transfer them to other bacteria. The plasmid-mediated transferable resistance genes were ampC, blaCTX-M1, tetA, sul2, and blaTEM. These results indicate that the aquatic environment could play an important role in the development of antibiotic resistance and the dissemination of resistance genes among bacteria.
Cefquinome is a cephalosporin with broad-spectrum antibacterial activity, including activity against enteric Gram-negative
bacilli such as Escherichia coli. We utilized a neutropenic mouse model of colibacillosis to examine the pharmacodynamic (PD) characteristics of cefquinome,
as measured by organism number in homogenized thigh cultures after 24 h of therapy. Serum drug levels following 4-fold-escalating
single doses of cefquinome were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic
(PK) properties of cefquinome were linear over a dose range of 10 to 640 mg/kg of body weight. Serum half-lives ranged from
0.29 to 0.32 h. Dose fractionation studies over a 24-h dose range of 2.5 to 320 mg/kg were conducted every 3, 6, 12, or 24
h. Nonlinear regression analysis was used to determine which pharmacodynamic parameter best correlated with efficacy. The
free percentage of the dosing interval that the serum levels exceed the MIC (fT>MIC) was the PK-PD index that best correlated with efficacy (R2 = 73% for E. coli, compared with 13% for the maximum concentration of the free drug in serum [fCmax]/MIC and 45% for the free-drug area under the concentration-time curve from 0 to 24 h [fAUC0-24]/MIC). Subsequently, we employed a similar dosing strategy by using 4-fold-increasing total cefquinome doses administered
every 4 h to treat animals infected with four additional E. coli isolates. A sigmoid maximum-effect (Emax) model was used to estimate the magnitudes of the %fT>MIC associated with net bacterial stasis, a 1-log10 CFU reduction from baseline, and a 2-log10 CFU reduction from baseline; the corresponding values were 28.01% ± 2.27%, 37.23% ± 4.05%, and 51.69% ± 9.72%. The potent
bactericidal activity makes cefquinome an attractive option for the treatment of infections caused by E. coli.
Cefquinome is a cephalosporin with broad-spectrum antibacterial activity, including activity against Staphylococcus aureus. The objective of our study was to examine the in vivo activity of cefquinome against S. aureus strains by using a neutropenic mouse thigh infection model. Cefquinome kinetics and protein binding in infected neutropenic
mice were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In vivo postantibiotic effects (PAEs) were determined after a dose of 100 mg/kg of body weight in mice infected with S. aureus strain ATCC 29213. The animals were treated by subcutaneous injection of cefquinome at doses of 2.5 to 320 mg/kg of body
weight per day divided into 1, 2, 3, 6, or 12 doses over 24 h. Cefquinome exhibited time-dependent killing and produced in vivo PAEs at 2.9 h. The percentage of time that serum concentrations were above the MIC (%T>MIC) was the pharmacokinetic-pharmacodynamic (PK-PD) index that best described the efficacy of cefquinome. Subsequently, we employed
a similar dosing strategy by using increasing total cefquinome doses that increased 4-fold and were administered every 4 h
to treat animals infected with six additional S. aureus isolates. A sigmoid maximum effect (Emax) model was used to estimate the magnitudes of the ratios of the %T that the free-drug serum concentration exceeded the MIC (%T>fMIC) associated with net bacterial stasis, a 0.5-log10 CFU reduction from baseline, and a 1-log10 CFU reduction from baseline; the respective values were 30.28 to 36.84%, 34.38 to 46.70%, and 43.50 to 54.01%. The clear
PAEs and potent bactericidal activity make cefquinome an attractive option for the treatment of infections caused by S. aureus.
Aeromonas hydrophila, a ubiquitous, free-living, Gram-negative bacterium, is prevalent in aquatic habitats with cosmopolitan distribution; it is an opportunistic pathogen that has resulted in heavy mortalities in farmed and feral fishes. The traditional application of antibiotics and chemotherapy has been characterized by partial success in the management of diseases like motile aeromonad septicemia (MAS) and aeromonad-associated diseases like epizootic ulcerative syndrome (EUS). Application of antibiotics and chemotherapeutic drugs are necessary in the disease management though this practice has triggered the emergence of drug resistant strains in pathogens. Further resistance may be transferred to other related or unrelated bacteria; therefore, it is necessary to develop and screen new chemicals. Disease prevention by means of vaccination and immuno-stimulation of fish in aquaculture has been particularly successful against several bacterial diseases. For example, mono and multivalent vaccines have been developed against several bacterial diseases in fish. However, when new diseases and pathogens emerge from time to time, it would be difficult to develop such proactive strategies quickly. Recently, probiotics are widely used in aquaculture since they produce bacteriocins and other chemical compounds inhibiting the growth of pathogenic bacteria. Another emerging trend is medicinal plant research, which has increased the world over since herbs used in traditional medicine have little side effects are easily biodegradable and abundantly available in farm areas free of cost. Some herbals that wield potent antibacterial activity against shrimp and fish bacterial pathogens have a crucial role in disease management. Indeed, application of probiotics and herbals in aquaculture may also reduce cost of disease management by obviating the expenses incurred by the use of antibiotics, chemicals, and vaccinations in the future.
Considerable information on the pharmacodynamics of β-lactams has accumulated in the past 20 years. In vitro, β-lactams demonstrate
time-dependent killing and variable postantibiotic effects. Animal models have shown that the time for which drug levels exceed
the minimum inhibitory concentration (MIC) correlates best with bacterial eradication, and this is now being borne out in
human studies. In investigations on osteomyelitis and endocarditis, trough serum inhibitory titers have generally correlated
better with cure than have peak titers, and studies that have analyzed outcomes in relation to the MIC for the infecting pathogen
have shown decreasing clinical efficacy with increasing MICs. One prospective study has shown that time above MIC correlated
better with time to pathogen eradication than did area under the curve. In some continuous-infusion studies, significantly
better outcomes were achieved with continuous infusion against susceptible bacteria or for patients with persistent, profound
neutropenia. With use of time above MIC as the predictor of efficacy, it is possible to reexamine current dosing schedules
critically.
The influence of temperature (10 degrees C and 20 degrees C) on pharmacokinetics and metabolism of sulphadimidine (SDM) in carp and trout was studied. At 20 degrees C a significantly lower level of distribution (Vdarea) and a significantly shorter elimination half-life (T(1/2)beta) was achieved in both species compared to the 10 degrees C level. In carp the body clearance parameter (ClB(SDM)) was significantly higher at 20 degrees C compared to the value at 10 degrees C, whereas for trout this parameter was in the same order of magnitude for both temperatures. N4-acetylsulphadimidine (N4-SDM) was the main metabolite of SDM in both species at the two temperature levels. The relative N4-SDM plasma percentage in carp was significantly higher at 20 degrees C than at 10 degrees C, whereas there was in trout no significant difference. In neither species was the peak plasma concentration of N4-SDM (Cmax(N4-SDM)) significantly different at two temperatures. The corresponding peak time of this metabolite (Tmax(N4-SDM)) was significantly shorter at 20 degrees C compared to 10 degrees C in both carp and trout. In carp at both temperatures, acetylation occurs to a greater extent than hydroxylation. Only the 6-hydroxymethyl-metabolite (SCH2OH) was detected in carp, at a significant different level at the two temperatures. Concentrations of hydroxy metabolites in trout were at the detection level of the HPLC-method (0.02-micrograms/ml). The glucuronide metabolite (SOH-gluc.) was not detected in either species at the two temperatures.
The pharmacokinetics and bioavailability of meloxicam were investigated after single intravascular (IV), intramuscular (IM), and oral dose of 1 mg/kg in rainbow trout broodstock at 11 ± 1.2°C. A total of 36 healthy rainbow trout (Oncorhynchus mykiss) broodstock weighing 1.40 ± 0.26 kg was used for the investigation. Plasma concentrations of meloxicam were measured with high-performance liquid chromatography-ultraviolet detection, and pharmacokinetic parameters were calculated by non-compartmental analysis. The elimination half-life for IV, IM, and oral routes was 3.63, 4.55, and 2.95 h, respectively. The IV route for meloxicam showed the total clearance of 0.05 L/h/kg and volume of distribution at a steady state of 0.20 L/kg. The peak plasma concentration was 2.97 μg/ml for the IM route and 0.84 μg/ml for the oral route. The bioavailability was 78.45% for the IM route and 21.48% for the oral route. Meloxicam following IM and oral administration displayed short t1/2ʎz. The short t1/2ʎz could be an advantage for the short-term use in acute conditions. The IM route with the good bioavailability can be preferred for the treatment of various conditions. However, developing new oral formulations with the good bioavailability for meloxicam is necessary to minimize stress and trauma through minimal handling in rainbow trout broodstock.
Cefquinome is the only fourth-generation cephalosporin used solely for veterinary applications. In this study, we established the wild-type cut-off (COWT) and pharmacokinetic/pharmacodynamic cut-off (COPD) of cefquinome against Escherichia coli and Staphylococcus aureus. A total of 210 E. coli and 160 S. aureus isolates were collected from pigs in Guangdong Province between 2014 and 2018. The minimum inhibitory concentrations (MICs) were determined using a microdilution broth method. MIC50 and MIC90 were 0.06 and 0.25 μg mL⁻¹ for E. coli and 0.5 and 1 μg mL⁻¹ for S. aureus, respectively. Statistical analysis and the ECOFFinder Program showed that the COWT for cefquinome against E. coli and S. aureus were 0.125 and 2 μg mL⁻¹, respectively. The resistance rates were 11.9% for E. coli and 6.25% for S. aureus. Based on a 5000-subject Monte Carlo simulation, the COPD value for cefquinome against E. coil and S. aureus was 0.25 μg mL⁻¹ under the recommended dose (2 mg kg⁻¹, twice a day for 3 days), confirming that infections caused by strains with MIC≤0.25 μg mL⁻¹ could be effectively treated. Following adjustment of the dosing regimen to 4.5 mg kg⁻¹, effective treatment (>90) was achieved for S. aureus infections with MIC90 1 μg mL⁻¹. This susceptibility breakpoint determination is significant for resistant surveillance and cefquinome dosage guidance against E. coli and S. aureus in pigs.
The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high‐performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half‐life (t1/2λz) 1.85 and 3.31 hr, area under the plasma concentration–time curve (AUC0–∞) 15.74 and 174 hr * μg/ml, volume of distribution at steady‐state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr−1 kg−1, respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 μg/ml, time to reach peak concentration 1 and 1.5 hr, t1/2λz 4.74 and 3.62 hr, and AUC0–∞ 22.75 and 147 hr * μg/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12‐hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of ≤0.5 and ≤4 μg/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.
The purpose of this study was to determine the pharmacokinetics of cefquinome (CFQ) following single and repeated subcutaneous (SC) administrations in sheep. Six clinically healthy, 1.5 ± 0.2 years sheep were used for the study. In pharmacokinetic study, the crossover design in three periods was performed. The withdrawal interval between the study periods was 15 days. In first period, CFQ (Cobactan, 2.5%) was administered by an intravenous (IV) bolus (3 sheep) and SC (3 sheep) injections at 2.5 mg/kg dose. In second period, the treatment administration was repeated via the opposite administration route. In third period, CFQ was administrated subcutane- ously to each sheep (n = 6) at a dose of 2.5 mg/kg q. 24 hr for 5 days. Plasma concen- trations of CFQ were measured using the HPLC-UV method. Pharmacokinetic parameters were calculated using non-compartmental methods. The elimination half-life and mean residence time of CFQ after the single SC administration were longer than IV administration (p < 0.05). Bioavailability (F%) of CFQ following the sin- gle SC administration was 123.51 ± 11.54%. The area under the curve (AUC0-∞) and peak concentration following repeated doses (last dose) were higher than those ob- served after the first dose (p < 0.05). CFQ accumulated after repeated SC doses. CFQ can be given via SC at a dose of 2.5 mg/kg every 24 hr for the treatment of infections caused by susceptible pathogens, which minimum inhibitory concentration is ≤1.0 μg/ ml in sheep.
Temperature-dependent pharmacokinetics (PK) have rarely been reported in tilapia despite there are popularly cultured worldwide, ranging from tropical to temperate climates. The present study aims to investigate the PK characteristics of florfenicol (FF) in Nile tilapia at 3 temperature levels (24, 28, and 32 °C) after single intravenous (IV) and oral (PO) dose of 15 mg/kg to evaluate the effects of temperature on PK. The serum concentrations of FF were analyzed by HPLC-UV method and PK characteristics were analyzed by 2-compartmental model. It was revealed that temperature has profound influences on certain PK parameters. The results from both IV and PO experiments were generally similar. Increasing water temperature from 24 to 32 °C led to significantly increased elimination rate constant (β) from 0.056 to 0.095 1/h and shortened elimination half-life (t1/2β) from 12–13 h to 7–8 h. The absorption half-life (t1/2Ka) were decreased from 2.28 to 1.18 h as well as the maximum serum concentration (Cmax) from 23.14 to 16.71 μg/mL and time to reach Cmax (Tmax) from 1.40 to 0.75 h. The area under the serum concentration-time curves (AUC) were reduced by half while the clearances were doubled and the volume of distributions (Vd) were significantly increased. Our results also demonstrated that for FF in Nile tilapia the temperature coefficient (Q10) values could be applied to predict the CL and β at a specific temperature with high accuracy (94–116%). The temperature-sensitive PK parameters such as the increase in Ka, Vd, and β significantly affected the serum concentrations and its overall exposure (AUC), thereby could potentially implicate that proper dosing regimen should take water temperature into consideration. The study highlighted the possibility of water temperature effect on therapeutic outcome of FF used in tilapia and likely other cichlids.
Plasma and muscle pharmacokinetics of danofloxacin were investigated after 10 mg/kg intravenous (IV, caudal vein) and intramuscular (IM, right epaxial muscles) administrations in 168 healthy brown trout (Salmo trutta fario) at 10°C–13°C. High-performance liquid chromatography was used to determine its plasma and muscle concentrations. Pharmacokinetic parameters were analysed with a non-compartmental model. After IV administration, elimination half-life (t1/2ʎz), area under the concentration–time curve (AUC0–∞), mean residence time (MRT0–∞), volume of distribution at steady state, total body clearance in plasma and AUCMuscle/AUCPlasma ratio were 22.22 h, 140.66 h*µg/mL, 23.15 h, 2.28 L/kg, 0.07 L/h/kg and 3.79, respectively. After IM administration, t1/2ʎz, AUC0–∞, MRT0–∞, peak concentration (Cmax), time to reach Cmax, bioavailability in plasma and AUCMuscle/AUCPlasma ratio were 28.28 h, 84.39 h*µg/mL, 37.31 h, 4.79 µg/mL, 1 h, 59.99% and 8.46, respectively. Danofloxacin exhibited long t1/2ʎz and good bioavailability after IM administration. Therefore, 10 mg/kg IM administration of danofloxacin in brown trout can provide AUC0–24/MIC of > 125 and Cmax/MIC of > 10 to treat diseases caused by susceptible bacteria with ≤ 0.336 µg/mL MIC.
Ceftriaxone (CTX) is a third-generation cephalosporin that has proven to be effective in the treatment of infections caused by a wide range of gram- positive and gram-negative microorganisms. This study aimed to determine the plasma and muscle pharmacokinetics of CTX after its administration via the intravenous (IV) and intramuscular (IM) routes to brown trout (Salmo trutta fario) at temperatures of 10°C–13°C. In total, 140 healthy brown trout (body weight, 245 ± 38 g) were used. The brown trout received single IV and IM injections of CTX at 25 mg/kg. The IV doses were injected into the caudal vein, whereas the IM doses were injected into the right epaxial muscles. The plasma and muscle tissue concentrations of CTX were measured using high- performance liquid chromatography. Pharmacokinetic parameters were calculated using noncompartmental methods. Following the IV administration of CTX, the elimination half-life (t1/2ʎz), volume of distribution at steady state, total body clearance, and area under the concentration–time curve (AUC0–72) in plasma were 5.83 h, 0.09 L/kg, 0.02 L/h/kg, and 1079.46 h*μg/mL, respectively. After the IM administration of CTX, plasma t1/2ʎz, peak plasma concentration (Cmax), time to reach Cmax, and bioavailability were 22.78 h, 87.92 μg/mL, 0.5 h, and 27.19%, respectively. The AUCMuscle/AUCPlasma ratio following the IV administration was 0.02 and that following the IM administration was 0.04. CTX exhibited low bioavailability and prolonged t1/2ʎz after the IM administration. The prolonged t1/2ʎz of CTX could thus be beneficial in brown trout. Nevertheless, future studies that aim to determine the clinical efficacy and pharmacokinetics after repeated administration of CTX are warranted.
The pharmacokinetics (PK) of cefquinome (CEQ) was studied in crucian carp (Carassius auratus gibelio) after single oral, intramuscular (i.m.), and intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight and following incubation in a 5 mg/L bath for 5 hr at 25°C. The plasma concentration of CEQ was determined using high‐performance liquid chromatography (HPLC). PK parameters were calculated based on mean CEQ concentration using WinNonlin 6.1 software. The disposition of CEQ following oral, i.m., or i.p. administration was best described by a two‐compartment open model with first‐order absorption. After oral, i.m., and i.p. administration, the maximum plasma concentration (Cmax) values were 1.52, 40.53, and 67.87 μg/ml obtained at 0.25, 0.23, and 0.35 hr, respectively, while the elimination half‐life (T1/2β) values were 4.68, 7.39, and 6.88 hr, respectively; the area under the concentration–time curve (AUC) values were 8.61, 339.11, and 495.06 μg hr/ml, respectively. No CEQ was detected in the plasma after bath incubation. Therapeutic blood concentrations of CEQ can be achieved in the crucian carp following i.m. and i.p. administration at a dosage of 10 mg/kg once every 2 days.
The pharmacokinetics of cefquinome was studied in plasma after a single dose (10 mg/kg) of intramuscular (i.m.) or intraperitoneal (i.p.) administration to tilapia (Oreochromis niloticus) in freshwater at 30 °C. Ten fish per sampling point were examined after treatment. The data were fitted to two-compartment open models following both routes of administration. The estimates of total body clearance (CL/F), volume of distribution (Vd/F), and absorption half-life (T1/2ka ) were 0.049 and 0.037 L/h/kg, 0.41 and 0.33 L/kg, and 0.028 and 0.035 h following i.m. and i.p. administration, respectively. After i.m. injection, the elimination half-life (T1⁄2β ) was calculated to be 5.81 h, the maximum plasma concentration (Cmax ) to be 49.40 μg/mL, the time to peak plasma cefquinome concentration (Tmax ) to be 0.14 h, and the area under the plasma concentration-time curve (AUC) to be 204.6 μg h/mL. Following i.p. administration, the corresponding estimates were 6.05 h, 44.39 μg/mL, 0.17 h and 267.8 μg h/mL. The minimum inhibitory concentrations of cefquinome, determined for 30 strains of Streptococcus agalactiae isolated from diseased tilapia, ranged from 0.015 to 0.12 μg/mL. Results from these studies support that 10 mg cefquinome/kg body weight daily could be expected to control tilapia bacterial pathogens inhibited in vitro by a minimal inhibitory concentration value of ≤2 μg/mL.
© 2015 John Wiley & Sons Ltd.
Important antibiotics in human medicine have been used for many decades in animal agriculture for growth promotion and disease treatment. Several publications have linked antibiotic resistance development and spread with animal production. Aquaculture, the newest and fastest growing food production sector, may promote similar or new resistance mechanisms. This review of 650+ papers from diverse sources examines parallels and differences between land-based agriculture of swine, beef, and poultry and aquaculture. Among three key findings was, first, that of 51 antibiotics commonly used in aquaculture and agriculture, 39 (or 76%) are also of importance in human medicine; furthermore, six classes of antibiotics commonly used in both agriculture and aquaculture are also included on the World Health Organization's (WHO) list of critically important/highly important/important antimicrobials. Second, various zoonotic pathogens isolated from meat and seafood were observed to feature resistance to multiple antibiotics on the WHO list, irrespective of their origin in either agriculture or aquaculture. Third, the data show that resistant bacteria isolated from both aquaculture and agriculture share the same resistance mechanisms, indicating that aquaculture is contributing to the same resistance issues established by terrestrial agriculture. More transparency in data collection and reporting is needed so the risks and benefits of antibiotic usage can be adequately assessed.
Enteric red-mouth disease, caused by Yersinia ruckeri, is an important disease in rainbow trout aquaculture. Antimicrobial agents are frequently used in aquaculture, thereby causing a selective pressure on bacteria from aquatic organisms under which they may develop resistance to antimicrobial agents. In this study, the distribution of minimal inhibitory concentrations (MICs) of antimicrobial agents for 83 clinical and non-clinical epidemiologically unrelated Y. ruckeri isolates from north west Germany was determined. Antimicrobial susceptibility was conducted by broth microdilution at 22±2°C for 24, 28 and 48h. Incubation for 24h at 22±2°C appeared to be suitable for susceptibility testing of Y. ruckeri. In contrast to other antimicrobial agents tested, enrofloxacin and nalidixic acid showed a bimodal distribution of MICs, with one subpopulation showing lower MICs for enrofloxacin (0.008-0.015μg/mL) and nalidixic acid (0.25-0.5μg/mL) and another subpopulation exhibiting elevated MICs of 0.06-0.25 and 8-64μg/mL, respectively. Isolates showing elevated MICs revealed single amino acid substitutions in the quinolone resistance-determining region (QRDR) of the GyrA protein at positions 83 (Ser83-Arg or -Ile) or 87 (Asn87-Tyr), which raised the MIC values 8- to 32-fold for enrofloxacin or 32- to 128-fold for nalidixic acid. An isolate showing elevated MICs for sulfonamides and trimethoprim harbored a ∼8.9kb plasmid, which carried the genes sul2, strB and a dfrA14 gene cassette integrated into the strA gene. These observations showed that Y. ruckeri isolates were able to develop mutations that reduce their susceptibility to (fluoro)quinolones and to acquire plasmid-borne resistance genes.
Antibiotics are very useful additions to any fishhealth manager’s toolbox, but they are only tools and not “magic bullets.” The ability of antibiotics to help eliminate a fish disease depends on a number of factors. This document is Circular 84, one of a series from the Department of Fisheries and Aquatic Sciences, Florida Cooperative Extension Service, Institute of Food and Agricultural Sciences, University of Florida. Published January 2003. CIR 84/FA084: Use of Antibiotics in Ornamental Fish Aquaculture (ufl.edu)
The objectives of the study were to determine the chemical constituents of rainbow trout (Salmo gairdneri) during the first 14 months of life, to study the effects of starvation on the body composition of trout, and to measure organ weights during the first 14 months of life.
Body fat and protein content as a percentage of body weight increased with age, the water content declined, and the ash content remained constant during the first 14 months of life. There were no significant differences in body composition between immature male and female rainbow trout. Total body ions as a proportion of ash content decreased until the 10th month and then began to increase. During starvation, fat was used as the primary source of energy while water and ash content increased and protein content remained constant as a percentage of body weight.
The gall bladder, liver, and air bladder remained relatively constant as a percentage of body weight during the first year of life. As body weight increased, the relative weight of brain, heart, and digestive system decreased while the gonad and spleen weight increased.
A pharmacokinetic study of oxytetracycline (OTC) following an intravascular administration (40 mg/kg) was carried out in sea bass, Dicentrarchus labrax (110 g), at 13.5 and 22 °C water temperature. Blood, muscle and liver samples were taken at 1, 2, 4, 8, 16, 32, 64 and 128 h post-injection. The plasma data were conformed to a two-compartment model. The kinetic profile of the drug was found to be temperature dependent. The absorption half-life (t1/2α) of OTC was 0.98 and 0.192 h at 13.5 and 22 °C, respectively, whereas the elimination half-time (t1/2β) of the drug was 69 h at 13.5 °C and 9.65 h at 22 °C. The apparent volume of distribution of the drug at steady state [Vd(ss)] was 5.62 l/kg at 13.5 °C and 2.59 l/kg at 22 °C. The mean residence time (MRT) of OTC was found to be 37.7 h at 22 °C and 71 h at 13.5 °C. The total clearance of the drug (CLT) was calculated to be 73.5 and 68.7 ml/kg/h at 13.5 and 22 °C, respectively.Liver levels indicated higher OTC values than respective muscle levels at all time points and for both temperatures. The elimination of OTC from tissues tested was faster at the high temperature, whereas the drug was eliminated faster from liver compared to muscle when comparisons are made at the same temperature.
Cefquinome is a new injectable aminothiazolyl cephalosporin derivative. It is stable against chromosomally and plasmid-encoded
beta-lactamases and has a broad antibacterial spectrum. Staphylococcus aureus, streptococci, Pseudomonas aeruginosa, and members
of the family Enterobacteriaceae (Escherichia coli, Salmonella spp., Klebsiella spp., Enterobacter spp., Citrobacter spp.,
and Serratia marcescens) are inhibited at low concentrations. Cefquinome is also active against many strains of methicillin-resistant
staphylococci and enterococci. Its in vitro activity against gram-negative anaerobes is very limited. The high in vitro activity
of cefquinome is reflected by its high in vivo efficacy against experimental septicemia due to different gram-positive and
gram-negative bacteria. We studied the pharmacokinetic properties of cefquinome in mice, dogs, pigs, and calves. After single
parenteral administrations, cefquinome displayed high peak levels, declining with half-lives of about 0.5, 0.9, 1.2, and 1.3
h, respectively. The areas under the concentration-time curve determined for dogs and mice showed linear correlations to the
given doses. In dogs the urinary recovery was more than 70% within 24 h of dosing.
The absorption and elimination of cefquinome in serum and tissues of coho salmon were studied. The study was performed in freshwater at 10°C with fish weighing 100 ± 5g (mean and standard deviation). Single doses of 5, 10 and 20 mg/kg were administered intraperitoneally to 30 fish for each dose. The maximum concentration occurred in the following order; kidney and liver > serum > muscle > brain. The pharmacokinetic analysis and predictive withdrawal times were calculated using only the dose of 20 mg/kg body weight. The peak cefquinome concentrations (Cmax) in serum (3.35 ± 0.45 μg/ml) and muscle (2.87 ± 0.53 μg/g) were achieved at 12h. In the brain, the Cmax was 2.18 μg/g at 6h. The halflives (t 1 / 2 ) in serum, muscle, brain, liver and kidney were 20.56, 8.93, 9.35, 113.61 and 119.48 h, respectively. With the detection limit of 0.015 μg/g for the cefquinome, the predicted withdrawal time with 95% confidence for muscle tissue was 104.2 h at 10 °C for the 20 mg/kg dose.
The results suggest that cefquinome could be efficacious and safe for the consumer in treating bacterial diseases of coho salmon in fresh water. Nevertheless, future studies are required in order to determine an adequate dose with the corresponding withdrawal times.
Cefquinome. Summary report. EMEA/MRL/005/95. European Agency for the Evaluation of Medicinal Products London UK
- Cvmp
EMEA/MRL/883/03-FINAL. European Agency for the Evaluation of Medicinal Products London UK
- Cvmp
The State of World Fisheries and Aquaculture 2020
- Fao
FAO. (2020). The State of World Fisheries and Aquaculture 2020.
Sustainability in Action. Rome: FAO. https://www.fao.org/3/ca922
9en/ca922 9en.pdf
Practical pharmacology for the pharmacy technician
- J B Sakai
Sakai, J. B. (2009). Practical pharmacology for the pharmacy technician (1st
ed., pp. 27-40). Lippincott Williams & Wilkins.
Committee for Medicinal Products for Human Use
EMA. (2011). Committee for Medicinal Products for Human Use (CHMP);