Effect of a bundle intervention on adherence to quality-of-care indicators and on clinical outcomes in patients with Staphylococcus aureus bacteraemia hospitalized in non-referral community hospitals.

BACKGROUND: Although a significant number of cases of Staphylococcus aureus bacteraemia (SAB) are managed at non-referral community hospitals, the impact of a bundle-of-care intervention in this setting has not yet been explored. METHODS: We performed a quasi-experimental before-after study with the implementation of a bundle of care for the management of SAB at five non-referral community hospitals and a tertiary care university hospital. Structured recommendations for the five indicators selected to assess quality of care were provided to investigators before the implementation of the bundle and monthly thereafter. Primary endpoints were adherence to the bundle intervention and treatment failure, defined as death or relapse at 90 days of follow-up. RESULTS: One hundred and seventy patients were included in the pre-intervention period and 103 in the intervention period. Patient characteristics were similar in both periods. Multivariate analysis controlling for potential confounders showed that performance of echocardiography was the only factor associated with improved adherence to the bundle in the intervention period (adjusted OR 2.13; 95% CI 1.13-4.02). Adherence to the bundle, performance of follow-up blood cultures, and adequate duration of antibiotic therapy for complicated SAB presented non-significant improvements. The intervention was not associated with a lower rate of 90 day treatment failure (OR 1.11; 95% CI 0.70-1.77). CONCLUSIONS: A bundle-of-care intervention for the management of SAB at non-referral community hospitals increased adherence to quality indicators, but did not significantly reduce rates of 90 day mortality or relapse.

Antimicrobial susceptibility of Rhodococcus equi strains isolated from foals in Chile.

Rhodococcus equi is responsible for foal pneumonia worldwide, with a significant economic impact on the production and breeding of horses. In Chile, the first case was reported in 2000, and since then, its incidence has been increasing. Distinctive characteristics of R. equi as an intracellular pathogen in macrophages, emergence of virulence plasmids encoding surface lipoprotein antigens, and appearance of antibiotic resistance against macrolides and rifampicin have significantly complicated the treatment of R. equi pneumonia in foals. Therefore, in vitro susceptibility studies of first-line and newer antibiotics against R. equi are the first step to establishing effective treatments and optimizing new therapeutic options. The aim of the present study is to determine the susceptibility profile of fourteen strains of R. equi isolated from foals in Chile to several antibiotics of the macrolide group including azithromycin, amikacin, tildipirosin and gamithromycin as well as others such as rifampicin, doxycycline and ceftiofur. Identification of R. equi in collected isolates from foals in Chile has been performed by CAMP test and PCR based on detecting of the gene encoding the 16 S rRNA. The presence of genes encoding virulence plasmids was also determined using PCR. Results obtained have demonstrated presence of virulent R. equi strains in Chile. In vitro susceptibility pattern to different antibiotics has shown better results for doxycycline and rifampicin similar to previous studies performed. Current macrolides have been evaluated in order to consider alternative treatment options in a context of emerging resistance to classic macrolides and rifampicin, obtaining better results with gamithromycin (MIC range of 0.125 to 128 mg/ml) than with tildipirosin (MIC range of 16 to 128 mg/ml). An adequate diagnosis of bacterial susceptibility based on antibiograms is necessary to treat the Rhodococcus equi infection in foals.

A novel liquid chromatography-fluorescence method for the determination of delafloxacin in human plasma.

Delafloxacin is a novel fluoroquinolone antibiotic that was approved by the European Medicine Agency to treat bacterial infections of the skin and underlying tissues, and community-acquired pneumonia. Despite being in the market since 2019 in the European Union, there is no published liquid chromatography-fluorescence method for delafloxacin quantification in biological samples. A novel, rapid, and sensitive high-performance liquid chromatographic method was developed to determine delafloxacin in human plasma using its native fluorescence. Plasma delafloxacin concentrations were determined by reverse-phase chromatography with fluorescence detection at 405/450 nm of excitation/emission wavelengths. Delafloxacin was separated on a Kromasil C18 column 250 × 4.6 mm id, 5 µm using isocratic elution. The mobile phase was a mixture of 0.05% trifluoroacetic acid/acetonitrile (52/48). Retention times were 5.4 and 11.6 min for delafloxacin and valsartan (internal standard), respectively. Regression calibration curves were linear over the range of 0.1-2.5 µg/mL. The lower limit of detection was 0.05 µg/mL, and the lower limit of quantification was 0.1 µg/mL. Accuracy and precision were always <11%, and the limit of quantification was <16%. Mean recovery was 98.3%. This method can be applied to determine delafloxacin in human plasma and could be useful to perform pharmacokinetic studies.

Susceptibility of caprine mastitis pathogens to tildipirosin, gamithromycin, oxytetracycline, and danofloxacin: effect of serum on the in vitro potency of current macrolides.

Mastitis is a significant disease in dairy ruminants, causing economic losses to the livestock industry and severe risks to public health. Antibiotic therapy is one of the most crucial practices to treat mastitis, although the susceptibility of caprine mastitis pathogens to current antibiotics has not been tested under standard or modified incubation conditions. This work evaluated the in vitro activity of tildipirosin, gamithromycin, oxytetracycline, and danofloxacin against caprine mastitis pathogens incubated following standard conditions of Clinical and Laboratory Standards Institute (CLSI) and deviation method by 25% supplementation with goat serum. Mycoplasma agalactiae, Escherichia coli, Staphylococcus aureus, Streptococcus spp., and coagulase-negative Staphylococci (CNS) were isolated from dairy goats with mastitis in Spain. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution technique. The lowest MIC90 under standard conditions was obtained with danofloxacin for mastitis-causing pathogens. An exception was M. agalactiae, where danofloxacin and oxytetracycline obtained low values. However, after adding serum, gamithromycin showed the lowest MIC50 for S. aureus, Streptococcus spp., and CNS. The lowest MIC50 was obtained with all the antibiotics tested (< 0.125 µg/ml) against M. agalactiae. Supplementing with serum resulted in a significant variation in tildipirosin and gamithromycin MIC values for CNS, S. aureus, M. agalagtiae, and E. coli. In brief, the MIC for antibiotics used against mastitis should be determined under conditions closely resembling intramammary infections to obtain representative susceptibility patterns against mastitis pathogens. Caprine mastitis pathogens were broadly susceptible to danofloxacin under standard conditions. The potency of macrolides against caprine mastitis pathogens increases when serum is present in culture media.

A fast, cost-saving and sensitive method for determination of cefuroxime in plasma by HPLC with ultraviolet detection.

Cefuroxime (CFX) is a broad-spectrum second-generation cephalosporin and one of the best choices for antibiotic prophylaxis. However, when used in critically ill patients, it may present changes in its pharmacokinetic properties. Therefore, therapeutic drug monitoring of CFX is necessary for effective dosing strategies. A simple, rapid and sensitive liquid chromatographic method with UV detection was developed and validated for the quantification of CFX in plasma. The method involved a single-step precipitation of proteins with methanol and trifluoroacetic acid. Cefuroxime was analyzed on a Brisa LC2 C18 column in isocratic mode consisting of 0.1% trifluoroacetic acid in water and acetonitrile (75:25) with UV detection at a wavelength of 280 nm. The retention times of CFX and cephazolin (internal standard) were 9.8 and 7.4 min, respectively. The calibration curve was linear over a concentration range of 0.25-50 µg/ml. The limits of detection and quantification were 0.1 µg/ml and 0.25 µg/ml, respectively. The accuracy and precision were always <10%. The mean recovery was 93.52%. This fast and simple method could be applied in routine analysis and pharmacokinetic studies.

Pharmacokinetics of cefonicid in lactating goats after intravenous, intramuscular and subcutaneous administration, and after a long-acting formulation for subcutaneous administration.

The single-dose disposition kinetics of cefonicid were determined in clinically normal lactating goats (n = 6) after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration of a conventional formulation, and after subcutaneous administration of a long-acting formulation (SC-LA). Cefonicid concentrations were determined by high performance liquid chromatography with ultraviolet detection. The concentration-time data were analysed by noncompartmental pharmacokinetic methods. Steady-state volume of distribution (Vss ) and clearance (Cl) of cefonicid after IV administration were 0.14 ± 0.03 L/kg and 0.51 ± 0.07 L/h·kg, respectively. Following IM, SC and SC-LA administration, cefonicid achieved maximum plasma concentrations of 14.46 ± 0.82, 11.98 ± 1.92 and 17.17 ± 2.45 mg/L at 0.26 ± 0.13, 0.42 ± 0.13 and 0.83 ± 0.20 hr, respectively. The absolute bioavailabilities after IM, SC and SC-LA routes were 75.34 ± 11.28%, 71.03 ± 19.14% and 102.84 ± 15.155%, respectively. After cefonicid analysis from milk samples, no concentrations were found above LOQ at any sampling time. From these data, cefonicid administered at 20 mg/kg each 12 hr after SC-LA could be effective to treat bacterial infections in lactating animals not affected by mastitis problems.

Pharmacokinetics of injectable marbofloxacin after intravenous and intramuscular administration in red-eared sliders (Trachemys scripta elegans).

Fluoroquinolone antibacterial drugs are currently used in reptilian medicine because of their broad spectrum of activity including the most frequent pathogens of these species. The disposition kinetics of marbofloxacin (MBX) at a single dose of 2 mg/kg were determined in healthy red-eared sliders after intravenous (IV) and intramuscular (IM) administration. The influence of renal portal system on the bioavailability of the drug was investigated by using forelimb and hindlimb as IM injection sites. Apparent volume of distribution at steady-state (Vss ) and systemic clearance (Cl) of marbofloxacin after IV administration were estimated to be 48.21 ± 5.42 ml/kg and 23.38 ± 2.90 ml/hr·kg, respectively. The absolute bioavailabilities after IM route were 45.96% (forelimb) and 52.09% (hindlimb). The lack of statistically significant differences in most of the pharmacokinetic parameters after the two IM injection sites suggests a negligible influence of renal portal system in clinical use of MBX, although the Cmax after IMfore administration is advantageous, having into account the concentration-dependent action of this antibiotic. The absence of visible adverse reactions in the animals and the advantageous pharmacokinetic properties suggest the possibility of its safe and effective clinical use in red-eared sliders.

Disposition kinetics and bioavailability of doxycycline after parenteral administrations in ewes.

Doxycycline is a tetracycline, which have been marketed in different species for treating infections caused by susceptible bacteria. There is limited information on the disposition kinetics of this drug in ewes and this antimicrobial may be useful against several sheep pathogens that are common causes of morbidity and economic loss. Therefore, the aim of this work was to establish the pharmacokinetics of doxycycline after intravenous (IV) and extravascular (subcutaneous (SC) and intramuscular (IM)) administrations in this species. A cross-over model was designed (n = 6). Doxycycline was dosed at 5 mg/kg for IV administration and 20 mg/kg for extravascular administrations. Non-compartmental pharmacokinetic methods were used to calculate plasma concentration-time data. The value of apparent volume of distribution (Vz) suggests a moderate distribution of this antibiotic in sheep, with a value of 0.84 L/kg. The maximum concentrations achieved after extravascular administrations (Cmax) were similar, with no significant differences between the two routes of administration (IM and SC). However, doxycycline absorption was slower after SC administration than after IM administration, taking twice as long to reach maximum plasma concentration (tmax). Bioavailabilities after extravascular routes of administration were low and after IM administration doxycycline caused lameness in all animals. Therefore, the SC administration showed a better profile with respect to pharmacokinetic properties and safety. Future studies on the susceptibility of isolated sheep pathogens to doxycycline are needed to establish appropriate dosing regimens.

Pharmacokinetics of Doxycycline in Plasma and Milk after Intravenous and Intramuscular Administration in Dairy Goats.

Doxycycline is a second-generation tetracycline, marketed in different species for treating infections caused by susceptible bacteria. Little information is available on the pharmacokinetics of doxycycline in lactating goats. The objective of this study was to establish the disposition kinetics of doxycycline after parenteral administration (intravenous and intramuscular) in dairy goats and its elimination in milk. A cross-over model was designed (n = 6). Doxycycline was dosed at 5 mg/kg for intravenous administration and 20 mg/kg for extravascular administrations. Noncompartmental pharmacokinetic methods were used to calculate plasma concentration-time data. The Vz value suggests a moderate distribution of this antibiotic in goats, with a value of 0.85 L/kg. A low bioavailability (F = 45.60%) of doxycycline following an intramuscular injection was observed, with all animals exhibiting signs of lameness. Doxycycline rapidly crossed the blood-milk barrier, but exposure to the antimicrobial and the concentrations reached in milk were lower than those obtained in plasma. Although PK/PD ratios may be low with the pharmacokinetic data obtained with this formulation of doxycycline, at this dose and route of administration, doxycycline after IM administration could be useful for infections by moderate or highly susceptible bacteria in the mammary gland of goats. However, it may be necessary to test different doses of doxycycline or other routes of administration to achieve better surrogate markers and to establish repeated dosing regimens and clinical efficacy.

Quantification and Determination of Stability of Tylvalosin in Pig Plasma by Ultra-High Liquid Chromatography with Ultraviolet Detection.

Tylvalosin (TV) is a macrolide antibiotic that is used for treating respiratory and enteric bacterial infections in swine and in poultry. In the coming years, the use of this drug will probably be widely studied in different species, but before its use in each veterinary species, macrolide analytical determination in various biological fluids is a pre-requisite step for the rational dose calculation of TV based on specific pharmacokinetic information. Its quantification is essential for detecting and avoiding the appearance of residues in animal products intended for human consumption. Therefore, a robust chromatographic method coupled with an ultraviolet detector was fully validated for the quantification of TV in pig plasma. A mixture (78:22) of (A) 0.3% formic acid in water and (B) acetonitrile was used as the mobile phase. TV and enrofloxacin (internal standard) were eluted at 14.1 and 5.9 min, respectively. Calibration curves ranged from 0.1 to 5 µg/mL. The accuracy and precision parameters for the quality controls were always <13.0%. Recovery ranged from 89.66 to 96.92%. The detection and quantification limits were found to be 0.05 µg/mL and 0.1 µg/mL, respectively. This method could be applied to develop pharmacokinetic studies.

Pharmacokinetics of tildipirosin in horses after intravenous and intramuscular administration and its potential muscle damage.

Tildipirosin is a novel semisynthetic macrolide antibiotic exclusively used in veterinary practice to treat respiratory infections. There are no pharmacokinetic or safety information available regarding the use of tildipirosin after intramuscular administration in horses. Thus, the objective of this work was to determine the disposition kinetics of tildipirosin after intravenous (IV) and intramuscular (IM) administration in horses and its potential muscle damage and cardiotoxicity. Six mature, Spanish-breed horses were used in a crossover study with a washout period of 30 days. Tildipirosin (18%) was administered at single doses by IV (2 mg/kg) and IM (4 mg/kg) routes. Tildipirosin plasma concentrations were determined by HPLC assay with ultraviolet detection. Muscle damage and inflammation were assessed by creatine kinase (CK) and haptoglobin (Hp), respectively. Creatine kinase myocardial band (CK-MB) and troponin (Tn) were used to evaluate cardiotoxicity. Tildipirosin in horses reached peak concentrations (Cmax = 1.13 µg/mL) at 0.60 h (tmax) after IM administration with an absolute bioavailability of 109.2%. Steady-state volume of distribution and clearance were 3.31 ± 0.57 L/kg and 0.22 ± 0.02 L/h/kg, respectively. Tildipirosin did not cause cardiotoxicity since CK-MB and Tn basal levels were not significantly different from those obtained after several days post-administration. Mild local reactions were observed after IM administration. This local inflammation was associated with mild myolysis (CK 239-837 UI/L), which was detectable for 48 h. In brief, tildipirosin could help to treat respiratory infections in horses because it showed extensive distribution, high bioavailability and did not provoke general adverse reactions.

Pharmacokinetics of Tildipirosin in Plasma, Milk, and Somatic Cells Following Intravenous, Intramuscular, and Subcutaneous Administration in Dairy Goats.

Tildipirosin is a macrolide currently authorized for treating respiratory diseases in cattle and swine. The disposition kinetics of tildipirosin in plasma, milk, and somatic cells were investigated in dairy goats. Tildipirosin was administered at a single dose of 2 mg/kg by intravenous (IV) and 4 mg/kg by intramuscular (IM) and subcutaneous (SC) routes. Concentrations of tildipirosin were determined by an HPLC method with UV detection. Pharmacokinetic parameters were estimated by non-compartmental analysis. Muscle damage, cardiotoxicity, and inflammation were evaluated. After IV administration, the apparent volume of distribution in the steady state was 7.2 L/kg and clearance 0.64 L/h/kg. Plasma and milk half-lives were 6.2 and 58.3 h, respectively, indicating nine times longer persistence of tildipirosin in milk than in plasma. Moreover, if somatic cells are considered, persistence and exposure measured by the area under concentration-time curve (AUC) significantly exceeded those obtained in plasma. Similarly, longer half-lives in whole milk and somatic cells compared to plasma were observed after IM and SC administration. No adverse effects were observed. In brief, tildipirosin should be reserved for cases where other suitable antibiotics have been unsuccessful, discarding milk production of treated animals for at least 45 days or treating goats at the dry-off period.

Cephalosporin susceptibility of Staphylococcus aureus strains isolated from commercial rabbit and goats farms in Spain.

Antimicrobial drug resistance is an important problem that challenges veterinary clinicians to provide effective treatments without further spreading resistance to other animals and people. The most commonly used pharmacodynamic parameter to define potency of antimicrobial drugs is minimum inhibitory concentration (MIC). The aim of this study was to evaluate the antibiotic susceptibility of thirty-six strains of Staphylococcus aureus isolated from dairy goats with mastitis and rabbits with chronic staphylococcosis. Four cephalosporins were tested: cephalexin, cephalotin, cefonicid and ceftiofur. MIC tests were performed according to the microdilution broth method. The calculated values of sensitivity in goats and rabbits were 66.67% and 72.22% for cephalexin, 72.22 % and 94.44% for cefonicid, 77.78% and 94.44% for cephalotin and 77.78% and 100% for ceftiofur, respectively. For all antibiotics, MIC90 of S. aureus from rabbits were lower than MIC90 from goats. These data suggest that more antibiotics are used in goat milk production than in rabbit farming. According to MIC values obtained in this study, ceftiofur and cephalotin may be the best option for treating S. aureus infections in lactating goats. For rabbits, ceftiofur showed lowest MIC values, therefore, it could be an alternative to treatment the infections caused by S. aureus in this species.

Antimicrobial Resistance of Campylobacter jejuni, Escherichia coli and Enterococcus faecalis Commensal Isolates from Laying Hen Farms in Spain.

Antimicrobial resistance (AMR) is a global threat for human and animal health. Few studies have been carried out in laying hens. We evaluated the antimicrobial susceptibility of commensal Campylobacter jejuni, Escherichia coli, and Enterococcus faecalis isolates in Spanish laying hens in 2018. The Minimum Inhibitory Concentration (MIC) was used to identify any AMR of the studied isolates by means of a broth microdilution method. C. jejuni was highly resistant to the B category antimicrobials, and 52% of the isolates were susceptible to all the antimicrobials tested. E. coli showed medium and high percentages of resistance to the B and A antibiotic categories, respectively, and 33.33% of the isolates were susceptible to all antimicrobials. The E. faecalis resistance to A category antimicrobials was variable, and 4.62% of the isolates were susceptible to all antimicrobials. In our work, novel data on AMR in laying hen commensal isolates in Spain is provided, and the AMR levels differ from those reported for poultry in the EU. A high resistance to key drugs for human medicine was found, representing a public health risk.

Pharmacokinetics and sedative effects of alfaxalone with or without dexmedetomidine in rabbits.

This study aimed to investigate the specific pharmacokinetic profile and effects of alfaxalone after intravenous (IV) and intramuscular (IM) administration to rabbits and evaluate the potential interaction with dexmedetomidine. The study design was a blinded, randomized crossover with a washout period of 2 weeks. Five New Zealand white rabbits were used. Each animal received single IV and IM injections of alfaxalone at a single dose of 5 mg/kg, and single IV and IM injections of alfaxalone (5 mg/kg) combined with dexmedetomidine (100 µg/kg) administered intramuscularly. Blood samples were collected at predetermined times and analysed by high-performance liquid chromatography. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation/anaesthesia scores were evaluated by a modified numerical rating scale. At pre-determined time points heart and respiratory rates were measured. Times to sternal recumbency and standing position during the recovery were recorded. Concentrations of alfaxalone alone were very similar (slighty smaller) to concentrations when alfaxalone was combined with dexmedetomidine, after both routes of administration. Dexmedetomidine enhanced and increase the duration of the sedative effects of alfaxalone. In conclusion, alfaxalone administered in rabbits provides rapid and smooth onset of sedation. After IV and IM injections of alfaxalone combined with dexmedetomidine, a longer MRT and a deeper and extended sedation have been obtained compared to alfaxalone alone. Consequently, alfaxalone alone or in combination with dexmedetomidine could be useful to achieve respectively moderate to deep sedation in rabbits.

Pharmacokinetics of Tildipirosin in Ewes after Intravenous, Intramuscular and Subcutaneous Administration.

A single-dose disposition kinetics for tildipirosin was evaluated in clinically healthy ewes (n = 6) after intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration of a commercial formulation. Tildipirosin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Plasma concentration-time data was calculated by non-compartmental pharmacokinetic methods. The apparent volume of distribution (Vz) of tildipirosin after IV administration was 5.36 ± 0.57 L/kg suggesting a wide distribution in tissues and inside the cells. The elimination half-life (t½λz) was 17.16 ± 2.25, 23.90 ± 6.99 and 43.19 ± 5.17 h after IV, IM and SC administration, respectively. Following IM administration, tildipirosin was rapidly absorbed (tmax = 0.62 ± 0.10 h) even to a greater extent than after SC administration. Time to reach peak concentration (tmax) and peak plasma concentrations (Cmax) differed significantly, but both parameters showed a more significant variability after SC than after IM administration. Bioavailabilities after extravascular administration were high (>70%). Therefore, given general adverse reactions that were not observed in any ewe and favourable pharmacokinetics, tildipirosin could be effective in treating bacterial infections in sheep.

Pharmacokinetics after intravenous, intramuscular and subcutaneous administration of moxifloxacin in sheep.

The disposition kinetics of moxifloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration was determined in sheep at a single dose of 5mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental (after IV, IM and SC administration) pharmacokinetic methods. Plasma concentrations of moxifloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (V(ss)) and clearance (Cl) of moxifloxacin after IV administration were 2.03+/-0.36L/kg and 0.39+/-0.04L/hkg, respectively. Following IM and SC administration, moxifloxacin achieved maximum plasma concentration of 1.66+/-0.62mg/L and 0.90+/-0.19mg/L at 2.25+/-0.88h and 3.25+/-1.17h, respectively. The absolute bioavailabilities after IM and SC routes were 96.12+/-32.70% and 102.20+/-23.76%, respectively. From these data (kinetic parameters and absence of adverse reactions) moxifloxacin may be a potentially useful antibiotic in sheep.

Pharmacokinetics of marbofloxacin in loggerhead sea turtles (Caretta caretta) after single intravenous and intramuscular doses.

The disposition kinetics of marbofloxacin at a single dose of 2 mg/kg bodyweight were determined in a crossover trial with five clinically healthy loggerhead sea turtles (Caretta caretta) after i.v. and i.m. administration. Marbofloxacin plasma concentrations were determined by high-performance liquid chromatography (LOD/LOQ 0.05 microg/ml). Data were subjected to noncompartmental analysis. The integrated pharmacokinetic/pharmacodynamic variables showed that optimal area under the curve (AUC(0-24 h)): minimal inhibitory concentration (MIC) (>125) and Cmax: MIC (>8) ratios, as reported for concentration-dependent bactericidal antimicrobials (e.g., fluoroquinolones), were achievable with both a once daily i.v. or i.m. dose for microorganisms with MIC < or = 0.5 microg/ml, while a Cmax: MIC > 8 for MIC > or = 1 microg/ml was achievable only after the i.v. administration. The absence of adverse reactions in the animals after i.v. or i.m. administration of marbofloxacin and the favorable pharmacokinetic/pharmacodynamic properties after a single dose of 2 mg/kg suggest the possibility of its safe and effective clinical use in loggerhead sea turtles.

Pharmacokinetics of danofloxacin after single dose intravenous, intramuscular and subcutaneous administration to loggerhead turtles Caretta caretta.

The single-dose disposition kinetics of the antibiotic danofloxacin were determined in clinically normal loggerhead turtles (n = 6) after intravenous (IV), subcutaneous (SC) and intramuscular (IM) administration of 6 mg kg(-1) bodyweight. Danofloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. The concentration-time data were analyzed by non-compartmental kinetic methods. Steady-state volume of distribution, and total body clearance of danofloxacin after IV administration were estimated to be 1.02 +/- 0.17 1 kg(-1) and 0.11 +/- 0.01 1 h(-1) kg(-1), respectively. Following IM and SC administration, danofloxacin achieved maximum plasma concentrations of 10.25 +/- 4.59 and 10.35 +/- 4.45 mg l(-1) at 1.20 +/- 0.52 and 1.46 +/- 0.48 h, respectively. The absolute bioavailabilities after SC and IM routes were 98.72 +/- 11.73 and 104.81 +/- 14.97%, respectively. Danofloxacin shows a favourable pharmacokinetic profile in loggerhead turtles reflected by parameters such as a long half-life and a high bioavailability following a single dose of 6 mg kg(-1) by IM and SC routes; thus, it is likely that this treatment will be effective in loggerhead turtles with bacterial infections.

Tissue disposition of azithromycin after intravenous and intramuscular administration to rabbits.

Tissue disposition of azithromycin after intravenous (IV) or intramuscular (IM) injection at a single dose rate of 10mg/kg bodyweight were investigated in rabbits using a modified agar diffusion bioassay for determining tissue concentrations. The pharmacokinetic behaviour of azithromycin was characterized by low and sustained plasma concentrations but high and persistent tissue concentrations. Kinetic parameters indicated a high retention of the drug in peripheral compartments. The plasma half-lives after IV and IM administrations were similar being 21.8h and 23.1h, respectively, while the half-lives obtained in tissues after IV and IM administration were at least 1.4 and 1.9 times longer than in plasma, respectively. The highest tissue concentrations were found in bile, liver and spleen whereas the lowest ones were found in skeletal muscle (although they were higher than those in plasma). From the results of the single administration in this study an IM dosage regimen can be proposed that achieves minimum concentrations over 2mg/L in rabbits: three doses of 4-5mg/kg/day would provide suitable therapeutic concentrations in pulmonary tissues over seven days.