Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study.

OBJECTIVES: An important clindamycin-rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration. METHODS: Patients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n = 20) or clindamycin-rifampicin combination therapy (n = 19). Patients received continuous IV clindamycin infusion for 2-6 weeks, followed by an oral regimen. Liquid chromatography-mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2 weeks of oral treatment. The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf = Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route. RESULTS: Comparing monotherapy with combination-therapy groups, the former's median steady-state concentration was two-fold higher after IV administration (8.49 versus 3.82 mg/L, p < 0.001) and its median AUC0-8h was 12 times higher after oral intake (37.7 versus 3.1 mg.h/L, p < 0.001). Riv, Rpo and Rf were 2.68, 18.8 and 7.0 respectively. CONCLUSION: The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin-rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion.

Simultaneous quantification of cefuroxime and clindamycin in human lumbar anulus fibrosus, nucleus pulposus and serum via UPLC-MS/MS.

BACKGROUND: This study aimed to develop a sensitive, accurate method for simultaneously quantifying cefuroxime and clindamycin in human serum, lumbar anulus fibrosus and nucleus pulposus. METHODS: Cefuroxime and clindamycin were quantified using ultra high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in multiple-reaction-monitoring mode on a triple-quadrupole AB Qtrap 5500 system in positive ion mode. Internal standards were D3-cefuroxime and D3,13C-clindamycin. Samples were pretreated by precipitating total protein. RESULTS: The method showed high sensitivity and good linearity over broad calibration ranges from 100 to 100 000 ng/mL for cefuroxime and 10 to 10 000 ng/mL for clindamycin in serum, and from 10 to 10 000 ng/mL for cefuroxime and 1 to 1 000 ng/mL for clindamycin in lumbar nucleus pulposus. In all sample types, correlation coefficients were greater than 0.99, intra- and inter-day precision (relative standard deviation) was less than 15%, and accuracy (relative error) was within 14% for both analytes. This method was effective at quantifying penetration of cefuroxime and clindamycin in patients undergoing oblique lumbar interbody fusion surgery. CONCLUSIONS: A very sensitive, specific method for simultaneous detection of cefuroxime and clindamycin has been developed for human lumbar anulus fibrosus, nucleus pulposus and serum samples.

Simultaneous determination of tazarotene, clindamycin phosphate and their active metabolites in Bama mini-pig skin by LC-MS/MS: Application to the development of a tazarotene/clindamycin phosphate cream.

Topical tazarotene combined with clindamycin phosphate can significantly improve the adherence and outcomes for the treatment of acne vulgaris than monotherapy, a novel tazarotene (0.05%)/clindamycin phosphate (1.2%) cream is thus developed. However, the pharmacokinetics and potential interaction of tazarotene and clindamycin phosphate in skin when formulated together remain unknown, which should be investigated to assess this novel cream. In the present work, a sensitive and rapid LC-MS/MS method for simultaneous determination of tazarotene, clindamycin phosphate and their active metabolites tazarotenic acid, clindamycin in Bama mini-pig skin was developed and reported for the first time. After pretreatment of the skin samples, the analytes were well separated on a Hypersil BDS C8 column (4.6 × 100 mm, 2.4 µm) using 0.2% (v/v) formic acid-0.1% (w/v) ammonium acetate water solution and acetonitrile as mobile phase in linear gradient elution. Quantification of tazarotene, clindamycin phosphate and their active metabolites tazarotenic acid, clindamycin was conducted under positive electrospray ionization mode using multiple reactions monitoring detection. The LC-MS/MS method was fully validated and then applied to the dermal pharmacokinetic study of the tazarotene/clindamycin phosphate cream. According to the obtained results, tazarotene and clindamycin phosphate did not have any drug-drug interaction when they were formulated together in the cream for topical application. Their absorption and metabolism features in the skin were also characterized, which can support the clinical medication regimen of tazarotene/clindamycin phosphate cream.

Safety, Tolerability, and Pharmacokinetics of Tazarotene Clindamycin Cream: A Single-Dose, 3-Period Crossover Study.

The current study compared the safety, tolerability, and pharmacokinetics of the new compound pharmaceutical preparation tazarotene clindamycin cream, and 2 single pharmaceutical preparations, tazarotene cream and clindamycin phosphate gel. Twelve healthy volunteers were enrolled in this single-center, single-blind, 3-treatment, 3-period crossover, single-dose randomized study. An 800-cm2 area on volunteers' backs was evenly smeared with 1.6 g of the test preparation to form a film. Blood samples were collected at predetermined time points for pharmacokinetic analysis. Safety and tolerability were assessed via skin reaction evaluation and clinical laboratory tests. The incidences of skin reactions were 18.2% for tazarotene clindamycin cream, 25.0% for tazarotene cream, and 18.2% for clindamycin phosphate gel. There were no significant differences in safety or tolerability among the 3 groups. Erythema, desquamation, and pruritus occurred in 7 volunteers, but no burning or tingling occurred. All adverse events were mild and resolved spontaneously, and there were no severe adverse events. The respective maximum plasma concentrations of tazarotenic acid after local administration of tazarotene clindamycin cream and tazarotene cream were 11 ± 5 pg/mL and 18 ± 12 pg/mL, and the areas under the curve within 72 hours were 444 ± 341 pg · h/mL and 692 ± 462 pg · h/mL.

Targeted clindamycin delivery to pilosebaceous units by chitosan or hyaluronic acid nanoparticles for improved topical treatment of acne vulgaris.

We developed chitosan or hyaluronic acid nanoparticles to entrap clindamycin and evaluated for the first time the impact of these two polymeric nanosystems on the targeted drug delivery to the pilosebaceous units, considering the sebaceous characteristics of skin affected by acne. Chitosan and hyaluronic acid nanoparticles respectively presented diameters of 362 ± 19 nm and 417 ± 9 nm (PDI < 0.47), entrapped 42 % and 48 % of the clindamycin content (drug loading of 8.8 % and 0.5 %) and had opposite surface charges (+27.7 ± 0.9 mV and -30.2 ± 2.7 mV). Although only the hyaluronic acid nanoparticles showed increased deposition of the drug into the pilosebaceous structures, both nanoparticles revealed enhanced targeted delivery of clindamycin to these structures as compared to commercial formulation (53 ± 20 % and 77 ± 9% of the total drug that penetrated the skin was found on the pilosebaceous units from, respectively, chitosan and hyaluronic acid nanoparticles). Remarkably, the "targeting potential" of the nanoparticles was more pronounced when the skin was pretreated to simulate a sebaceous condition. In conclusion, both polymeric nanocarriers targeted drug delivery to the pilosebaceous structures at different extensions and, in the case of oily skin conditions, such targeting was increased.

Application of an LC-ESI-QTOF-MS method for evaluating clindamycin concentrations in plasma and prostate microdialysate of rats.

Clindamycin is used for infections caused by Gram-positive and Gram-negative anaerobic pathogens and Gram-positive aerobes. Propionibacterium acnes is an important opportunistic microorganism of the human skin and is related to prostatitis. An LC-electrospray ionization-quadrupole time-of-flight-MS method was validated for determining clindamycin concentrations in plasma and prostate microdialysate. Clindamycin separation was carried out on a C18 column at 0.5 mL/min. The mobile phase employed gradient elution of formic acid and methanol. A mass spectrometer was operated in positive electrospray ionization mode to monitor ion 425.1784 and 253.1152 for clindamycin and cimetidine (internal standard), respectively. Linearity was obtained at 0.5-10.0 µg/mL (plasma) and 0.05-1.0 µg/mL (microdialysate) with coefficients of determination ≥0.999. The intra- and inter-day precision (coefficient of variation - CV%) values were ≤13.83% and 12.51% for plasma, respectively, and ≤10.90% and 9.35% for microdialysate, respectively. The accuracy was between 90.82% and 108.25% for plasma, and 96.97% and 106.98% for microdialysate. The present method was fully validated and applied to investigate clindamycin concentrations in both plasma and prostate by microdialysis in Wistar rats (80 mg/kg, intravenous). Because the penetration of antibiotics into the prostate may be restricted, this method allows us to investigate the prostate concentrations of clindamycin for the first time.

Antibiotic route and duration of therapy for cellulitis: data extracted from a multi-center clinical trial.

INTRODUCTION: Although cellulitis is a relatively common condition, there is uncertainty about the benefit of intravenous (IV) over oral (PO) antibiotic therapy, and the appropriate duration of treatment. METHODS: Data extracted from a clinical trial (NCT01876628) of antibiotic therapy for cellulitis were used to assess the association between the route of administration and duration of treatment, and clinical outcome. RESULTS: Of 323 patients with antibiotic data, 114 received some IV therapy. IV antibiotic therapy was preferred in those who had received antibiotics prior to trial entry (P < 0.001). Patients characterised as having more severe cellulitis (C-reactive protein > 100 mg/L, affected skin surface area > 5% or systemic inflammatory response syndrome score ≥ 1) were more likely to have had IV therapy. Those given only PO therapy were more likely to have improved at day 5 compared with those given at least a single dose of IV therapy (P = 0.015), and were as likely to be back to their normal activities at day 10 (P = 0.90), and day 30 (P = 0.86). There was no association between initial severity and the duration of antibiotic therapy given within the trial. There was no association between duration of antibiotic therapy and outcome as measured at day 10 and day 30. CONCLUSIONS: This study provides evidence that recovery is not associated with the route of antibiotic administration for patients with cellulitis of similar severity, or that a course length of > 5 days results in any additional benefit.

Pregnancy-related pharmacokinetics and antimicrobial prophylaxis during fetal surgery, cefazolin and clindamycin as examples.

Antimicrobial prophylaxis during surgery aims to prevent post-operative site infections. For fetal surgery, this includes the fetal and amniotic compartments. Both are deep compartments as drug equilibrium with maternal blood is achieved relatively late. Despite prophylaxis, chorio-amnionitis or endometritis following ex utero intrapartum treatment or fetoscopy occur in 4.13% and 1.45% respectively of the interventions. This review summarizes the observations on two commonly administered antimicrobials (cefazolin, clindamycin) for surgical prophylaxis during pregnancy, with emphasis on the deep compartments. For both compounds, antimicrobial exposure is on target when we consider the maternal and fetal plasma compartment. In contrast, amniotic fluid concentrations-time profiles display a delayed and much more blunted pattern, behaving as deep compartment. For cefazolin, there are data that document further dilution in the setting of polyhydramnios. Along this deep compartment concept, there is some accumulation during repeated administration, modeled for cefazolin and observed for clindamycin. The relative underexposure to antimicrobials in amniotic fluid may be reflected in the pattern of maternal-fetal complications after fetal surgery, and suggest that antimicrobial prophylaxis practices for fetal surgery should be reconsidered. Further studies should be designed by a multidisciplinary team (fetal surgeons, clinical pharmacologists and microbiologists) to facilitate efficient evaluation of antimicrobial prophylaxis.

First dose in neonates: pharmacokinetic bridging study from juvenile mice to neonates for drugs metabolized by CYP3A.

First dose prediction is challenging in neonates. Our objective in this proof-of-concept study was to perform a pharmacokinetic (PK) bridging study from juvenile mice to neonates for drugs metabolized by CYP3A. We selected midazolam and clindamycin as model drugs. We developed juvenile mice population PK models using NONMEM. The PK parameters of these two drugs in juvenile mice were used to bridge PK parameters in neonates using different correction methods. The bridging results were evaluated by the fold-error of 0.5- to 1.5-fold. Simple allometry with and without a correction factor for maximum lifespan potential could be used for a bridging of clearance (CL) and volume of distribution (Vd), respectively, from juvenile mice to neonates. Simulation results demonstrated that for midazolam, 100% of clinical studies for which both the predictive CL and Vd were within 0.5- to 1.5-fold of the observed. For clindamycin, 75% and 100% of clinical studies for which the predictive CL and Vd were within 0.5- to 1.5-fold of the observed. A PK bridging of drugs metabolized by CYP3A is feasible from juvenile mice to neonates. It could be a complement to the ADE and PBPK models to support the first dose in neonates.

A case of suspected antibiotic-associated encephalopathy in a patient undergoing long-term peritoneal dialysis.

A man undergoing long-term peritoneal dialysis who had no history of mental illness suffered psychosis and auditory hallucination 2 days after clindamycin was initiated at a single dose of 0.6 g per day for pulmonary infection. His mental symptoms disappeared after clindamycin was discontinued and peritoneal dialysis was strengthened. The patient's body temperature was mildly elevated the day before he was admitted to the hospital, and no abnormalities were observed on head and chest computed tomography imaging at admission, except for a slow rhythm on electroencephalogram. Many factors were involved in this case; antibiotic-related encephalopathy caused by clindamycin may be one factor. Physicians should carefully consider the use of antibiotics, especially in patients with end-stage renal disease.

Use of normalized prediction distribution errors for assessing population physiologically-based pharmacokinetic model adequacy.

Currently employed methods for qualifying population physiologically-based pharmacokinetic (Pop-PBPK) model predictions of continuous outcomes (e.g., concentration-time data) fail to account for within-subject correlations and the presence of residual error. In this study, we propose a new method for evaluating Pop-PBPK model predictions that account for such features. The approach focuses on deriving Pop-PBPK-specific normalized prediction distribution errors (NPDE), a metric that is commonly used for population pharmacokinetic model validation. We describe specific methodological steps for computing NPDE for Pop-PBPK models and define three measures for evaluating model performance: mean of NPDE, goodness-of-fit plots, and the magnitude of residual error. Utility of the proposed evaluation approach was demonstrated using two simulation-based study designs (positive and negative control studies) as well as pharmacokinetic data from a real-world clinical trial. For the positive-control simulation study, where observations and model simulations were generated under the same Pop-PBPK model, the NPDE-based approach denoted a congruency between model predictions and observed data (mean of NPDE = - 0.01). In contrast, for the negative-control simulation study, where model simulations and observed data were generated under different Pop-PBPK models, the NPDE-based method asserted that model simulations and observed data were incongruent (mean of NPDE = - 0.29). When employed to evaluate a previously developed clindamycin PBPK model against prospectively collected plasma concentration data from 29 children, the NPDE-based method qualified the model predictions as successful (mean of NPDE = 0). However, when pediatric subpopulations (e.g., infants) were evaluated, the approach revealed potential biases that should be explored.

Recovery of cefazolin and clindamycin in in vitro pediatric CPB systems.

Cardiopulmonary bypass (CPB) is often necessary for congenital cardiac surgery, but CPB can alter drug pharmacokinetic parameters resulting in underdosing. Inadequate plasma levels of antibiotics could lead to postoperative infections with increased morbidity. The influence of pediatric CPB systems on cefazolin and clindamycin plasma levels is not known. We have measured plasma levels of cefazolin and clindamycin in in vitro pediatric CPB systems. We have tested three types of CPB systems. All systems were primed and spiked with clindamycin and cefazolin. Samples were taken at different time points to measure the recovery of cefazolin and clindamycin. Linear mixed model analyses were performed to assess if drug recovery was different between the type of CPB system and sampling time point. The experiments were conducted at a tertiary university hospital. 81 samples were analyzed. There was a significant difference in the recovery over time between CPB systems for cefazolin and clindamycin (P < .001). Cefazolin recovery after 180 minutes was 106% (95% CI: 91-123) for neonatal, 99% (95% CI: 85-115) for infant, and 77% (95% CI: 67-89) for pediatric systems. Clindamycin recovery after 180 minutes was 143% (95% CI: 116-177) for neonatal, 111% (95% CI: 89-137) for infant, and 120% (95% CI: 97-149) for pediatric systems. Clindamycin recovery after 180 minutes compared to the theoretical concentration was 0.4% for neonatal, 1.2% for infants, and 0.6% for pediatric systems. The recovery of cefazolin was high in the neonatal and infant CPB systems and moderate in the pediatric system. We found a large discrepancy between the theoretical and measured concentrations of clindamycin in all tested CPB systems.

Bioavailability testing of a newly developed clindamycin oral suspension in a pediatric porcine model.

Background: Clindamycin's bitter taste and odor is known to affect treatment adherence in children. Recently, a formulation of clindamycin HCl complexed with ion exchange resin IRP 69 was shown to mask the bitter taste. Because of the potential benefit of this formulation for children, a pilot study using a porcine model was conducted to evaluate its relative bioavailability. Methods: A randomized two-way crossover study design using six (n = 6) healthy male piglets 10-12 kg was used to evaluate the absorption profiles and pharmacokinetic parameters of clindamycin from the resinate complex formulation (Test) compared to a commercialized reference suspension. A dose of 15 mg/kg was administered orally by gastric gavage to each piglet followed by repeated blood sampling over 12 h. A wash-out period of 48 h occurred between treatments. Plasma concentration vs. time data was analyzed by non-compartmental analysis. Results: The mean relative bioavailability of clindamycin from the resinate formulation was 78.8%. A two-tailed, paired Student t test yielded a p < 0.05 for AUC∞ and Tmax parameters. A two one-sided test (TOST) suggested a difference in AUC∞ and Cmax for the Test formulation compared to the reference formulation according to the FDA's criteria for bioequivalence. Conclusion: The bioavailability of clindamycin from this novel oral formulation supports continued evaluation of the drug in humans for potential pediatric applications.

Clindamycin clearance during Cytosorb® hemoadsorption: A case report and pharmacokinetic study.

Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infections are rare but associated with very high mortality rates. We report the case of a 14-year-old patient with Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection and Influenza B pneumonia requiring veno-arterial extra-corporeal membrane oxygenator for refractory shock. In the absence of response to conventional therapy, we have inserted a Cytosorb® cartridge within the extra-corporeal membrane oxygenator circuit. A spectacular decrease in vasopressor requirements followed. Since clindamycin, a key component of Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus treatment, might be removed by Cytosorb® hemoadsorption, we have performed serial plasma concentrations measurements of the drug. Based on these measurements, we were able to develop a pharmacokinetic model incorporating variable plasma clearance. Patient's exposure was estimated before, during and after Cytosorb® hemoadsorption. According to this model, Cytosorb® hemoadsorption did not seem to result in significant clindamycin removal. Cytosorb® hemoadsorption during Panton-Valentine leucocidin producing methicillin-resistant Staphylococcus aureus infection appears safe and feasible and no adaptation of clindamycin dosage seems necessary.

Intervertebral disc penetration by antibiotics used prophylactically in spinal surgery: implications for the current standards and treatment of disc infections.

PURPOSE: The presence of Propionibacterium acnes in a substantial component of resected disc specimens obtained from patients undergoing discectomy or microdiscectomy has led to the suggestion that this prominent human skin and oral commensal may exacerbate the pathology of degenerative disc disease. This hypothesis, therefore, raises the exciting possibility that antibiotics could play an important role in treating this debilitating condition. To date, however, little information about antibiotic penetration into the intervertebral disc is available. METHODS: Intervertebral disc tissue obtained from 54 microdiscectomy patients given prophylactic cefazolin (n = 25), clindamycin (n = 17) or vancomycin (n = 12) was assayed by high-performance liquid chromatography, with cefaclor as an internal standard, to determine the concentration of antibiotic penetrating into the disc tissue. RESULTS: Intervertebral disc tissues from patients receiving the positively charged antibiotic clindamycin contained a significantly greater percentage of the antibacterial dose than the tissue from patients receiving negatively charged cefazolin (P < 0.0001) and vancomycin, which has a slight positive charge (P < 0.0001). CONCLUSION: Positively charged antibiotics appear more appropriate for future studies investigating potential options for the treatment of low-virulence disc infections. These slides can be retrieved under Electronic Supplementary Material.

Long-term clinical safety of clindamycin and rifampicin combination for the treatment of hidradenitis suppurativa. A Critically Appraised Topic.

CLINICAL QUESTION/SCENARIO: Can therapy with clindamycin and rifampicin be safely continued long term beyond the recommended 10-week course? BACKGROUND: Clindamycin and rifampicin are used in combination to treat hidradenitis suppurativa (HS). There is no data on the efficacy and safety of clindamycin/rifampicin combination therapy for HS beyond 10 weeks. METHODS: We identified the following major concerns that still lack a proper evidenced-based analysis: for rifampicin, drug-induced liver injury, interstitial nephritis, drug interaction and hepatic p450 3A4 enzyme induction; for clindamycin, the concern was community-acquired Clostridium difficile infection (CA-CDI); and experience with long-term treatment. Data sources were used as appropriate to answer the question. Systematic searches were used to assess the risk of CA-CDI and experience with long-term treatment with clindamycin. RESULTS/IDENTIFIED EVIDENCE: The risk for rifampicin-induced liver injury is highest in the first 6 weeks of treatment, whereas interstitial nephritis is primarily observed during intermittent treatment. Enzyme induction due to rifampicin is usually complete after about 2 weeks of treatment and reduces clindamycin blood levels by about 90%. Three meta-analyses identified antibiotic use as a risk factor for CA-CDI. Two of them assigned the highest risk to clindamycin. None of them stratified by length of treatment. There is extensive experience with rifampicin, primarily for the treatment of tuberculosis. Long-term experience with clindamycin is limited. DISCUSSION AND RECOMMENDATION FOR CLINICAL CARE: The analysed risks associated with a combination of clindamycin and rifampicin for hidradenitis suppurative cluster within the first 10 weeks. Treatment can be continued beyond 10 weeks, if clinically necessary.

Sensitive analytical method to quantify clindamycin in plasma and microdialysate samples: Application in a preclinical pharmacokinetic study.

Clindamycin is widely used in antimicrobial prophylaxis to prevent surgical site infections. Adequate subcutaneous free tissue concentrations should reach therapeutic levels, which have to be maintained throughout the surgical procedure for antibiotic prophylaxis to be efficient. A method was developed and validated using high performance liquid chromatography coupled to a mass spectrometry to determine clindamycin concentrations in two biological matrices: plasma, for drug monitoring, and subcutaneous microdialysate, to determine free concentrations at the incision site. Gradient separation of clindamycin was carried out using a reverse phase C18 column eluted with a mixture of mobile phases (1% formic acid in water and 1% formic acid in acetonitrile). The monitored transitions were m/z 425.3 > 377.3 for clindamycin, and m/z 407 > 359 for lincomycin, used as the internal standard for plasma samples. Linearity was reached in the 0.5-100 µg/mL range for plasma and 25-1000 ng/mL for microdialysate samples. The method was selective, precise, and accurate, and was successfully employed in a preliminary pharmacokinetics study to investigate plasma and subcutaneous clindamycin penetration, determined by microdialysis, after intravenous administration of a 50 mg/kg dose to Wistar rats.

Effect of composting and soil type on dissipation of veterinary antibiotics in land-applied manures.

The objective of this study was to determine the fate of commonly used veterinary antibiotics in their naturally excreted form when manure-based amendments are applied to soil. Beef cattle were administered sulfamethazine, tylosin, and chlortetracycline and dairy cows were treated with pirlimycin. The resulting manure was composted for 42 d under static or turned conditions and applied at agronomic N rates to sandy, silt, and silty clay loam soils and compared with amendment with corresponding raw manures in sacrificial microcosms over a 120-day period. Antibiotic dissipation in the raw manure-amended soils followed bi-phasic first order kinetics. The first phase half-lives for sulfamethazine, tylosin, chlortetracycline, and pirlimycin ranged from 6.0 to 18, 2.7 to 3.7, 23 to 25, and 5.5-8.2 d, respectively. During the second phase, dissipation of sulfamethazine was negligible, while the half-lives for tylosin, chlortetracycline, and pirlimycin ranged from 41 to 44, 75 to 144, and 87-142 d, respectively. By contrast, antibiotic dissipation in the compost-amended soils followed single-phase first order kinetics with negligible dissipation of sulfamethazine and half-lives of tylosin and chlortetracycline ranging from 15 to 16 and 49-104 d, respectively. Pirlimycin was below the detection limit in the compost-amended soils. After incubating 120 d, antibiotics in compost-amended soils (up to 3.1 µg kg-1) were significantly lower than in manure-amended soils (up to 19 µg kg-1, p < .0001), with no major effect of soil type on the dissipation. Risk assessment suggested that composting can reduce antibiotic resistance selection potential in manure-amended soils.

Dosing antibiotics in neonates: review of the pharmacokinetic data.

Antibiotics are often used in neonates despite the absence of relevant dosing information in drug labels. For neonatal dosing, clinicians must extrapolate data from studies for adults and older children, who have strikingly different physiologies. As a result, dosing extrapolation can lead to increased toxicity or efficacy failures in neonates. Driven by these differences and recent legislation mandating the study of drugs in children and neonates, an increasing number of pharmacokinetic studies of antibiotics are being performed in neonates. These studies have led to new dosing recommendations with particular consideration for neonate body size and maturation. Herein, we highlight the available pharmacokinetic data for commonly used systemic antibiotics in neonates.

Pharmacokinetics of intravenous clindamycin phosphate in captive Bennett's wallabies (Macropus rufogriseus).

This study was designed to investigate the pharmacokinetics of clindamycin, a lincosamide antibiotic, in Bennett's wallabies. The pharmacokinetic properties of a single intravenous (IV) dose of clindamycin were determined in six wallabies. A single 20-min IV infusion of 20 mg/kg of clindamycin was administered, followed by blood collection prior to, and up to 12 hr after clindamycin administration. Plasma clindamycin concentrations were determined by high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. Pharmacokinetic variables were calculated using a two-compartment model with first order elimination which best fit the data. The mean volume of distribution at steady-state, distribution half-life, and elimination half-life were 898.25 ml/kg, 0.16 hr, 1.79 hr, respectively. No adverse effects were noted after IV administration.