Investigation on improvement of enantioseparation based on clindamycin phosphate by chiral deep eutectic solvents in capillary electrophoresis.

In this work, the potential synergetic effect between deep eutectic solvents and an antibiotic chiral selector (clindamycin phosphate) for enantioseparation was investigated in capillary electrophoresis. We synthesized a series of deep eutectic solvents with choline chloride as hydrogen bond acceptor and three α-hydroxyl acids (l-lactic acid, l-malic acid, and l-tartaric acid) as hydrogen bond donors. Compared to the single clindamycin phosphate separation system, significantly improved separations of model drugs were observed in several synergetic systems. Compared to deep eutectic solvents with a single hydrogen bond donor, deep eutectic solvents with mixed-type hydrogen bond donors were superior. The influences of several key parameters including the type and proportion of organic modifier, clindamycin phosphate concentrations, deep eutectic solvents concentrations, and buffer pH were investigated in detail. The mechanism of the enhanced separations in deep eutectic solvents systems was investigated by means of electroosmotic flow analysis, nuclear magnetic resonance analysis, and molecular modeling. It was the first time that the synergetic systems between deep eutectic solvents and antibiotic chiral selector were established in capillary electrophoresis, and these deep eutectic solvents were demonstrated to have a good synergetic effect with clindamycin phosphate for enantioseparation.

Injectable Platelet-Rich Fibrin as a Drug Carrier Increases the Antibacterial Susceptibility of Antibiotic-Clindamycin Phosphate.

The aim of this study was to investigate the change in clindamycin phosphate antibacterial properties against Gram-positive bacteria using the platelet-rich fibrin as a carrier matrix, and evaluate the changes in the antibiotic within the matrix. The antibacterial properties of CLP and its combination with PRF were tested in a microdilution test against reference cultures and clinical isolates of Staphylococcus aureus (S. aureus) or Staphylococcus epidermidis (S. epidermidis). Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM) analysis was done to evaluate the changes in the PRF_CLP matrix. Release kinetics of CLP was defined with ultra-performance liquid chromatography (UPLC). According to FTIR data, the use of PRF as a carrier for CLP ensured the structural changes in the CLP toward a more active form of clindamycin. A significant decrease in minimal bactericidal concentration values (from 1000 µg/mL to 62 µg/mL) against reference cultures and clinical isolates of S. aureus and S. epidermidis was observed for the CLP and PRF samples if compared to pure CLP solution. In vitro cell viability tests showed that PRF and PRF with CLP have higher cell viability than 70% after 24 h and 48 h time points. This article indicates that CLP in combination with PRF showed higher antibacterial activity against S. aureus and S. epidermidis compared to pure CLP solution. This modified PRF could be used as a novel method to increase drug delivery and efficacy, and to reduce the risk of postoperative infection.

Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug.

BACKGROUND: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).

Effect of Cedar (Ziziphus spina-christi) topical solution in mild to moderate acne vulgaris: a randomized clinical study.

BACKGROUND: Acne is the most prevalent skin disease in the world and antibiotics as its standard treatments have limited and also adverse effects. Cedar (Ziziphus spina-christi) has medicinal properties like antibacterial activity and is used topically for treatment of some kinds of skin problems in Persian medicine. The aim of this study was to evaluation the efficacy of topical cedar solution of acne vulgaris. METHODS: Eighty patients aged between 15-45 years with mild to moderate acne vulgaris were conducted in this randomized, double blind trial. The participants were allocated to receive the topical cedar solution plus clindamycin 1% or topical placebo plus 1% clindamycin solution for six weeks. Patients were evaluated at the beginning of the study, second, sixth and eighth weeks after intervention for the acne severity index (ASI) and total acne lesions counting (TLC). Data was analyzed by SPSS software with Mann-Whitney U test. RESULTS: From 105 subjects 68 people completed the study (33 persons in cedar group and 35 persons in placebo group). The mean and standard deviation of the age was 26.1 ± 7.5 years and 22 subjects (32.4%) were male. TLC and ASI in the sixth and eighth weeks in cedar group were significantly less than in placebo group (p < 0.001). Topical cedar solution had no serious side effects. CONCLUSION: The topical cedar solution plus clindamycin 1% was more effective and safe than placebo plus 1% clindamycin for the treatment of acne vulgaris.

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.

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.

Population physiologically based modeling of pirlimycin milk concentrations in dairy cows.

Predictions of drug residues in milk are critical in food protection and are a major consideration in the economics of treatment of mastitis in dairy cows. Nonlinear mixed-effects modeling (NLME) has been advocated as a suitable pharmaco-statistical method for the study of drug residues in milk. Recent developments in physiologically based pharmacokinetic (PBPK) modeling of intramammary drugs allow the combination of a mechanistic description of milk pharmacokinetics with NLME methods. The PBPK model was applied to NLME analysis of a data set consisting of milk drug concentrations from 78 healthy cows and 117 with clinical mastitis. Pirlimycin milk pharmacokinetics were adequately described by the model across the range of observed concentrations. Mastitis was characterized by increased variance in milk production volume. Udder residual volume was larger in cows with 1, or 2 or greater diseased mammary glands than in the healthy cows. Low-producing cows had a greater risk of prolonged milk residues. With the exclusion of the low-production cows, the model predicted that healthy cows required a milk discard time 12 h longer than that indicated by the label, and the diseased cows 36 h longer than indicated by the label. More pirlimycin was systemically absorbed in the gram-positive infected compared with the gram-negative infected or healthy cows, suggesting a greater risk of violative meat residues in gram-positive infected cows. Using NLME and PBPK models, we identified factors associated with changes in pirlimycin milk residues that may affect food safety. This model extends the verification of a simple physiologically based framework for the study of intramammary drugs.

Formulation Optimization of Selective Laser Sintering 3D-Printed Tablets of Clindamycin Palmitate Hydrochloride by Response Surface Methodology.

The aims of the current study were to develop and evaluate clindamycin palmitate hydrochloride (CPH) 3D-printed tablets (printlets) manufactured by selective laser sintering (SLS). Optimization of the formulation was performed by studying the effect of formulation and process factors on critical quality attributes of the printlets. The independent factors studied were laser scanning speed, microcrystalline cellulose (MCC), and lactose monohydrate (LMH) concentration. The responses measured were printlets weight, hardness, disintegration time (DT), and dissolution in 30 min. The printlets were characterized for content uniformity, chemical interactions, crystallinity, drug distribution, morphology, and porosity. The laser scanning speed showed statistically significant effects on all the studied dependent responses (p < 0.05). MCC showed statistically significant effects on hardness, DT, and dissolution (p < 0.05), while LMH showed statistically significant effect on hardness and dissolution (p < 0.05). The model was validated by an independent formulation, and empirical values were in close agreement with model-predicted values. X-ray powder diffraction and differential scanning calorimetry data suggested a decrease in crystallinity of the LMH in the printlets. X-ray micro-CT scanning showed porous microstructure of the printlets with a porosity 24.4% and 31.1% for the printlets printed at 200 and 300 mm/s laser speed, respectively. In summary, the SLS method provides an opportunity to fabricate customized dosage forms as per patients' need.

The effect of intramammary pirlimycin hydrochloride on the fecal microbiome of early-lactation heifers.

The purpose of this study was to determine the effect of intramammary pirlimycin on the fecal microbiome of dairy cattle. Primiparous heifers were enrolled and assigned to a treatment or control group at a ratio of 2:1. In part 1 of the study, treated heifers (T1) were given intramammary pirlimycin into one infected quarter once daily for 2 d at 24-h intervals, according to the label instructions. Control heifers received no treatment. In part 2 of the study, treated heifers (T2) were given intramammary pirlimycin into one infected quarter once daily for 8 d at 24-h intervals, according to the label instructions. All enrolled heifers (T1, T2, and control) had quarter-level milk samples aseptically collected for bacterial culture and fecal samples collected for 16S rRNA gene sequencing on d 0, 2, 7, 14, 21, and 28. Milk samples were plated on Columbia blood agar and incubated at 37°C for 24 h. Bacteria were identified using MALDI-TOF mass spectrometry. The DNA was extracted from feces using PowerFecal kits (Qiagen, Venlo, the Netherlands). The 16S rRNA gene amplicon library construction and sequencing was performed at the University of Missouri DNA Core facility. Testing for differences in fecal community composition was performed via one-way permutational multivariate ANOVA of Bray-Curtis and Jaccard similarities using Past 3.13 (https://folk.uio.no/ohammer/past/). Mean total count of operational taxonomic units and Chao1, Shannon, and Simpson α-diversity indices were determined and compared via t-test or Wilcoxon rank sum test. A treatment-dependent effect was present in the observed and predicted richness of feces from cows in the T1 group at d 2 posttreatment. Additionally, intramammary pirlimycin induced a significant change in the composition of the fecal microbiota by d 2 in the treated groups. Based on calculated intra-subject similarities, intramammary pirlimycin was associated with a significant acute change in the fecal microbiota of dairy heifers and that chance reversed when the antimicrobial exposure was brief, but sustained following longer exposure. Overall, intramammary pirlimycin administration affected the fecal microbiome of lactating dairy heifers. Further work is necessary to determine the effect of these changes on the heifer and the dairy environment as well as if treatment is influencing antimicrobial resistance among enteric and environmental bacteria.

Fate of pirlimycin and antibiotic resistance genes in dairy manure slurries in response to temperature and pH adjustment.

Quantifying the fate of antibiotics and antibiotic resistance genes (ARGs) in response to physicochemical factors during storage of manure slurries will aid in efforts to reduce the spread of resistance when manure is land-applied. The objectives of this study were to determine the effects of temperature (10, 35, and 55 °C) and initial pH (5, 7, 9, and 12) on the removal of pirlimycin and prevalence of ARGs during storage of dairy manure slurries. We collected and homogenized feces and urine from five lactating dairy cows treated with pirlimycin and prepared slurries by mixing manure and sterile water. Aliquots (200 mL) of slurry were transferred and incubated in 400 mL glass beakers under different temperatures (10, 35, and 55 °C) or initial pH (5, 7, 9, and 12). Pirlimycin concentration and abundances of 16S rRNA, mefA, tet(W), and cfxA as indicators of total bacteria and ARGs corresponding to macrolide, tetracycline, and ß-lactam resistance, respectively, were analyzed during manure incubation. The thermophilic environment (55 °C) increased the deconjugation and removal of pirlimycin, while the acidic shock at pH 5 increased deconjugation but inhibited removal of pirlimycin, suggesting that the chemical stability of pirlimycin could be affected by temperature and pH. The thermophilic environment decreased mefA relative abundance on day 7 and 28 (P = 0.02 and 0.04), which indicates that the bacteria that encoded mefA gene were not thermotolerant. Although mefA relative abundance was greater at the pH 9 shock than the rest of pH treatments on day 7 (P = 0.04), no significant pH effect was observed on day 28. The tet(W) abundance under initial pH 12 shock was less than other pH shocks on day 28 (P = 0.01), while no temperature effect was observed on day 28. There was no significant temperature and initial pH effect on cfxA abundance at any time point during incubation, implying that the bacteria that carrying cfxA gene are relatively insensitive to these environmental factors. Overall, directly raising temperature and pH can facilitate pirlimycin removal and decrease mefA and tet(W) relative abundances during storage of manure slurries.

Synthesis of a chiral ionic liquid, cholinium-clindamycin phosphate, as sole chiral selector in capillary electrophoresis.

Recently, in separation science, ionic liquids (ILs) have been commonly used as modifiers for buffer solutions, dynamic coating solutions, or coating solutions on carriers in capillary electrophoresis. However, only several papers have reported the use of chiral ILs as the sole chiral selector. In this paper, a chiral ionic liquid, cholinium-clindamycin phosphate (Ch-CP), was synthesized and employed as a sole chiral selector in capillary electrophoresis (CE). A series of parameters affecting the separation were optimized, including chiral selector concentration, buffer pH, proportion of organic modifier, as well as the applied voltage. Under the optimal conditions, compared to clindamycin phosphate (CP), the IL selector showed better enantioseparation capability and improved peak shapes for five racemic drugs. In addition, Molecular docking program Autodock was employed to elucidate the chiral recognition mechanism of Ch-CP, the computing results conformed to the experimental results.

Evaluation of an ionic liquid chiral selector based on clindamycin phosphate in capillary electrophoresis.

Recently, increasing attention has been given to the research on chiral ionic liquids (CILs) in chiral separation field; however, only a few literatures focus on the exploration of CILs as the sole chiral selector. In this study, an ionic liquid chiral selector based on antibiotic, namely tetramethylammonium clindamycin phosphate (TMA-CP), was originally synthesized and subsequently utilized for enantioseparation in capillary electrophoresis (CE). Remarkably improved separations of eight racemic analytes were achieved in TMA-CP system in contrast to the clindamycin phosphate (CP) system. The optimal separation conditions were determinated by systematic experiments on several crucial parameters including the type and proportion of organic modifier, CIL concentration, buffer pH, and applied voltage. Additionally, molecular modeling with AutoDock was applied to probe into the chiral recognition mechanism of the ionic liquid chiral selectors, which well corresponded with the experimental results. It is the first time that antibiotic-based ionic liquid was exploited as favorable sole chiral selector in CE, and this strategy has paved a new way for development of novel ionic liquids chiral selectors based on antibiotics. Graphical abstract.

Staphylococcus aureus related to bovine mastitis in Switzerland: Clonal diversity, virulence gene profiles, and antimicrobial resistance of isolates collected throughout 2017.

Staphylococcus aureus can be associated with subclinical, acute, chronic, and toxic cases of bovine intramammary infections, leading to considerable financial losses for the dairy industry in Switzerland and worldwide. In addition, milk products are one of the most common food categories implicated in staphylococcal food poisoning in humans. Detailed information on the population structure, as well as the virulence and resistance characteristics of Staph. aureus originating from bovine mastitis milk is needed to allow for source attribution and risk assessment of Staph. aureus in a food poisoning context and to improve therapeutic approaches in cattle. Our objective was to assess the population structure, phenotypic resistance patterns, and virulence and resistance gene profiles of Staph. aureus isolates from bovine mastitis milk in Switzerland. To this end, 58 Staph. aureus strains were characterized. The DNA microarray was used to test for the presence or absence of virulence and resistance genes. In addition, minimum inhibitory concentrations of various antimicrobial agents were determined by microdilution. To assess the population structure of the isolates, we determined clonal complexes (CC) using DNA microarray hybridization profiles and performed multilocus sequence typing and spa typing. The strains were assigned to 7 clonal complexes, 10 sequence types, and 11 spa types, with CC705 (43%), CC97 (33%), and CC20 (12%) representing the most common lineages and t529 (43%) and t267 (21%) representing the most common spa types. Only 1 isolate was assigned to CC8, a clonal lineage linked to high within-herd prevalence of mastitis. A total of 14% (n = 8) of strains were classified as resistant to penicillin, and 1 strain each was classified as oxacillin and pirlimycin resistant. Although no clinical breakpoints are available for the combination of kanamycin/cefalexin, growth of all strains was inhibited by the lowest combination of kanamycin/cefalexin concentrations tested (4 µg/mL of kanamycin and 0.4 µg/mL of cefalexin). One strain assigned to CC20, ST389, and t2094 exhibited resistance to penicillin, oxacillin, and pirlimycin as well as intermediate susceptibility to erythromycin and high minimum inhibitory concentration for several antimicrobial agents, for which no breakpoints were available.

Preparation and evaluation of clindamycin phosphate loaded chitosan/alginate polyelectrolyte complex film as mucoadhesive drug delivery system for periodontal therapy.

In this study, Clindamycin phosphate loaded adhesive polyelectrolyte complex films for local periodontal therapy were prepared with alginate and chitosan. The thickness, drug content, structure, swelling, adhesion and in vitro drug release with release kinetics of formulations were evaluated. The effects of the varying concentration and molecular weight of polymers used and the volume of the polymer solutions on the characteristics of the films were investigated. Increasing the concentration of sodium alginate in total content of polymer mixture caused to higher adhesiveness. Chitosan molecular weight also affected to adhesiveness of complex films. The release rate of drug and release kinetics was affected from the complexation. The best complexation was obtained with the three times higher concentration and volume of alginate in combination with low molecular weight chitosan. Thus polyelectrolyte films that have delayed release together with high swelling ability and adhesiveness and high drug content were formed. Due to the heterogeneous structure of complex film, the release profiles of the formulations fitted to the anomalous transport mechanism. 3D structure of the drug loaded complex film was analyzed by Micro-CT imaging in this study and it was showed that using this method would be very advantageous for further studies about the investigation of complexation than the other imaging methods in order to determine the volume and the size of the formed complexes within the structure at the same time.

Development and validation of a simple chromatographic method for simultaneous determination of clindamycin phosphate and rifampicin in skin permeation studies.

Rifampicin (RIF) and clindamycin phosphate (CDM) are the main drugs currently used in combination to treat severe infectious diseases in hair follicles. This work describes a simple, rapid and sensitive method for simultaneous analysis of RIF and CDM in the different skin layers using high performance liquid chromatography (HPLC). The efficient chromatographic separation of CDM and RIF was succeeded using a C18 column (150 mm x 4.6 mm, 5 µm) with gradient elution using a mobile phase composed of 0.01 M phosphoric acid and methanol at a flow rate of 1 mL min-1. Determinations were performed using UV-vis detector at 200 nm and 238 nm for CDM and RIF, respectively. The method was precise, accurate and linear (r2 > 0.999) with regression curve in the concentration range from 0.5 to 20.0 µg mL-1 and recovery rates from the skin layers higher than 85%. The retention times for CDM and RIF were approximately 7.4 and 12.2 min, respectively. The presence of skin components did not interfere with the analysis. The validated method was therefore appropriate for quantification of both CDM and RIF and thus may be feasible to be used in skin permeation studies.

Fate of Pirlimycin and Antibiotic-Resistant Fecal Coliforms in Field Plots Amended with Dairy Manure or Compost during Vegetable Cultivation.

Identification of agricultural practices that mitigate the environmental dissemination of antibiotics is a key need in reducing the prevalence of antibiotic-resistant bacteria of human health concern. Here, we aimed to compare the effects of crop (lettuce [ L.] or radish [ L.]), soil amendment type (inorganic fertilizer, raw dairy manure, composted dairy manure, or no amendment), and prior antibiotic use history (no antibiotics during previous lactation cycles vs. manure mixed from cows administered pirlimycin or cephapirin) of manure-derived amendments on the incidence of culturable antibiotic-resistant fecal coliforms in agricultural soils through a controlled field-plot experiment. Antibiotic-resistant culturable fecal coliforms were recoverable from soils across all treatments immediately after application, although persistence throughout the experiment varied by antibiotic class and time. The magnitude of observed coliform counts differed by soil amendment type. Compost-amended soils had the highest levels of cephalosporin-resistant fecal coliforms, regardless of whether the cows from which the manure was derived were administered antibiotics. Samples from control plots or those treated with inorganic fertilizer trended toward lower counts of resistant coliforms, although these differences were not statistically significant. No statistical differences were observed between soils that grew leafy (lettuce) versus rooted (radish) crops. Only pirlimycin was detectable past amendment application in raw manure-amended soils, dissipating 12 to 25% by Day 28. Consequently, no quantifiable correlations between coliform count and antibiotic magnitude could be identified. This study demonstrates that antibiotic-resistant fecal coliforms can become elevated in soils receiving manure-derived amendments, but that a variety of factors likely contribute to their long-term persistence under typical field conditions.

Clindamycin phosphate 1.2%/benzoyl peroxide 3% fixed-dose combination gel versus topical combination therapy of adapalene 0.1% gel and clindamycin phosphate 1.2% gel in the treatment of acne vulgaris in Japanese patients: A multicenter, randomized, investigator-blind, parallel-group study.

Adapalene 0.1% (ADA) with clindamycin phosphate 1.2% (CLNP; ADA + CLNP) and the fixed-dose combination containing CLNP and benzoyl peroxide 3% (CLNP/BPO 3%) are strongly recommended for the early treatment of acne vulgaris in Japan. Here, we compare the early efficacy and safety of CLNP/BPO 3% with Japanese standard topical use of ADA + CLNP in the treatment of acne vulgaris. In this phase IV, multicenter study, 351 patients were randomized to receive CLNP/BPO 3% or ADA + CLNP for 12 weeks. The primary end-point was percentage change from baseline in total lesion (TL) counts at week 2. Secondary end-points included the percentage change from baseline in TL, inflammatory and non-inflammatory lesion (IL and non-IL) counts, Investigator's Static Global Assessment (ISGA), quality of life (QoL [Skindex-16]) and patient preference. Local tolerability scores and adverse events were also recorded. CLNP/BPO 3% provided a significantly greater percentage reduction from baseline in TL compared with ADA + CLNP at week 2, and week 4. Compared with ADA + CLNP, CLNP/BPO 3% was superior at reducing IL (but not non-IL) over weeks 2-12, was more effective at improving patient QoL and ISGA, and scored higher in patient-preference assessments. Both treatments were well tolerated; adverse drug reactions occurred more frequently in patients receiving ADA + CLNP (37%) than in those receiving CLNP/BPO 3% (17%). In conclusion, CLNP/BPO 3% showed greater efficacy for the early treatment of acne vulgaris in Japan, with a more favorable safety profile compared with ADA + CLNP.

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.

Early-lactation extended pirlimycin therapy against naturally acquired Staphylococcus aureus intramammary infections in heifers: A randomized controlled trial.

The primary objective of the current study was to evaluate cure rate following an early-lactation extended intramammary pirlimycin treatment on heifers naturally infected by Staphylococcus aureus. The secondary objective was to assess Petrifilm Staph Express (3M Microbiology, St. Paul, MN) count plate characteristics when used in a protocol for early-lactation detection of infected quarters in heifers. Milk samples were collected from heifers (n = 946) in the first few days following calving (mean = 5 d). Heifers with laboratory-confirmed S. aureus intramammary infection (n = 72) were randomly allocated into 2 groups. The treatment group (n = 54 quarters from 38 heifers) received an intramammary infusion of 50 mg of pirlimycin once per day for 8 consecutive days in infected quarters. The control group (n = 44 quarters from 34 heifers) did not receive any treatment. Treatment success was defined as having negative culture results for S. aureus in all 3 post-treatment quarter milk samples collected on d 17, 24, and 31 post-treatment. Treatment group mammary quarters showed a statistically significant higher cure rate (64.8%) compared with the control group (34.1%). A total of 38% of quarters identified as S. aureus-positive using the Petrifilm Staph Express count plate were in fact identified as non-aureus staphylococci on routine laboratory-based bacteriological culture. The current study demonstrates that a higher cure rate for S. aureus IMI can be achieved in dairy heifers if an extended treatment protocol is put in place soon after calving. Use of Petrifilm Staph Express count plate for identification of S. aureus-infected heifers could lead to unnecessary treatments because of false-positive results.