Minimum Inhibitory Concentrations before and after Antibacterial Treatment in Patients with Mycobacterium abscessus Pulmonary Disease.

The clinical importance of Mycobacterium abscessus (MABS) pulmonary disease has been increasing. However, there is still a lack of information about MIC distribution patterns and changes in clinical practice settings. The MIC results of rapidly growing mycobacteria isolated from 92 patients with nontuberculous mycobacterial pulmonary disease diagnosed from May 2019 to March 2021 were retrospectively analyzed. Most of the patients (86 patients; 93.5%) were infected with MABS; 46 with Mycobacterium abscessus subsp. abscessus (Mab), and 40 with Mycobacterium abscessus subsp. massiliense (Mma). Significant differences in susceptibility to clarithromycin (15.2% versus 80.0%, P < 0.001) and azithromycin (8.7% versus 62.5%, P < 0.001) were observed between Mab and Mma. Most isolates were susceptible to amikacin (80; 93.0%), and over half were susceptible to linezolid (48; 55.8%). Only one-quarter of isolates (22, 25.6%) were susceptible to imipenem, while more than half (56; 65.1%) had intermediate susceptibility. Fifty-one isolates (59.3%) had MIC values of less than 1 µg/mL for sitafloxacin, which were significantly higher than isolates for moxifloxacin (5; 5.8%), especially in Mab. Sixty-five (75.6%) isolates had MICs of less than 0.5 µg/mL to clofazimine. Two patients showed obvious MIC result changes: from susceptible to resistant to clarithromycin and from resistant to susceptible to amikacin and imipenem. In conclusion, MABS isolates were relatively susceptible to amikacin and linezolid, and clarithromycin and azithromycin were especially effective against Mma. In addition, sitafloxacin and clofazimine had low MICs and might be effective treatment agents. IMPORTANCE The MICs of isolates from 86 patients with Mycobacterium abscessus (MABS); 46 with Mycobacterium abscessus subsp. abscessus (Mab), and 40 with Mycobacterium abscessus subsp. massiliense (Mma) were retrospectively analyzed. The main findings are as follows: (i) Mma were significantly more susceptible to clarithromycin and azithromycin than Mab, and both subspecies tended to be more susceptible to clarithromycin than azithromycin. (ii) Most isolates were susceptible to amikacin (93.0%), and over half to linezolid (55.8%). (iii) Fifty-one isolates (59.3%) had MIC values of less than 1 µg/mL for sitafloxacin, and 65 (75.6%) had less than 0.5 µg/mL for clofazimine, which seems worth clinical investigating. (iv) Among nine cases analyzed chronological changes, only two patients showed obvious MIC result changes even after the long-term multidrug treatment. The present study revealed MICs of MABS clinical isolates before and after treatment in clinical settings, which could help develop future MABS treatments strategies.

Development of a latex particles-based lateral flow immunoassay for group determination of macrolide antibiotics in breast milk.

A lateral flow immunoassay (LFIA) using latex particles labeled with antibody to BSA-clarithromycin (CLA) was developed for the rapid simultaneous group determination of six macrolide antibiotics. Optimization of antigen spotting on the membrane and latex probe loading allowed improving visual detectability (vLOD) 100 times, which was 1, 1, 10, 10, 50, and 1000 ng/mL for CLA, roxithromycin, erythromycin, dirithromycin, azithromycin, and oleandomycin in buffer, respectively. The calculated limits of instrumental detection (cLOD) were respectively 0.12, 0.15, 1.4, 2.1, 2.4, and 3.3 ng/mL. To avoid a strong influence of breast milk of a very diverse and variable composition, a sample pretreatment is proposed. The six macrolides mentioned can be visually detected in breast milk after 20 min pretreatment at concentrations of 10-1000 ng/mL or instrumentally with cLOD of 4.0, 2.5, 30, 42, 42 and 180 ng/mL. The recovery rate from the spiked samples carried out using a strip scanner device ranged from 71 % to 110 %, and precision expressed as relative standard deviation was between 3-14 %. The described rapid on-site diagnostic assay format can be useful for monitoring the content of antibiotics in breast milk during macrolide treatment to ensure safe breastfeeding of infants.

Environmental Risk and Risk of Resistance Selection Due to Antimicrobials' Occurrence in Two Polish Wastewater Treatment Plants and Receiving Surface Water.

In this study, a screening of 26 selected antimicrobials using liquid chromatography coupled to a tandem mass spectrometry method in two Polish wastewater treatment plants and their receiving surface waters was provided. The highest average concentrations of metronidazole (7400 ng/L), ciprofloxacin (4300 ng/L), vancomycin (3200 ng/L), and sulfamethoxazole (3000 ng/L) were observed in influent of WWTP2. Ciprofloxacin and sulfamethoxazole were the most dominant antimicrobials in influent and effluent of both WWTPs. In the sludge samples the highest mean concentrations were found for ciprofloxacin (up to 28 µg/g) and norfloxacin (up to 5.3 µg/g). The removal efficiency of tested antimicrobials was found to be more than 50% for both WWTPs. However, the presence of antimicrobials influenced their concentrations in the receiving waters. The highest antimicrobial resistance risk was estimated in influent of WWTPs for azithromycin, ciprofloxacin, clarithromycin, metronidazole, and trimethoprim and in the sludge samples for the following antimicrobials: azithromycin, ciprofloxacin, clarithromycin, norfloxacin, trimethoprim, ofloxacin, and tetracycline. The high environmental risk for exposure to azithromycin, clarithromycin, and sulfamethoxazole to both cyanobacteria and eukaryotic species in effluents and/or receiving water was noted. Following the obtained results, we suggest extending the watch list of the Water Framework Directive for Union-wide monitoring with sulfamethoxazole.

Prioritised pharmaceuticals in German estuaries and coastal waters: Occurrence and environmental risk assessment.

In this study a target analysis approach with method detection limits down to 0.01 ng L-1 was developed in order to determine ultra-trace pharmaceuticals in seawater of the German coast and their estuaries. The selection of target analytes based on a prioritisation commissioned by the German Environmental Agency considering occurrence in German surface waters, production volumes and ecotoxicological data. Using ultra-high pressure liquid chromatography coupled to a triple quadrupole mass spectrometer equipped with an electrospray ionisation source 21 prioritised pharmaceuticals out of seven therapeutical classes (antibiotics, iodinated X-ray contrast media (ICM), analgesics, lipid reducers, antiepileptics, anticonvulsants, beta-blockers) have been detected in the low to medium ng L-1-range. The most frequently measured substance groups in the German Baltic Sea and German Bight are the ICM, represented by the non-ionic ICM iomeprol (German Bightmax: 207 ng L-1; Baltic Seamax: 34.5 ng L-1) and the ionic ICM amidotrizoic acid (German Bight: 86.9 ng L-1), respectively. The same pattern of substance distribution could be detected in the German Bight, the German Baltic Sea and their inflows with lower concentrations in the offshore region that are partly a result of dilution with marine water. Pharmaceuticals entering the estuaries and coastal regions are an environmental issue since data on the ecotoxicological effects on aquatic marine organisms is limited. Especially the antibiotics clarithromycin and sulfamethoxazole could be ecotoxicologically/environmentally critical.

Distribution and ecological risk of pharmaceuticals in surface water of the Yeongsan river, Republic of Korea.

This study examined the distribution of pharmaceuticals in Yeongsan River and at point sources (PSs) in the associated water system, and performed a risk assessment based on our findings. The samples included effluents collected from three sewage treatment plants (PS1, PS2, and PS3) and two industrial complexes (PS4 and PS5) as well as surface water collected from seven mainstreams and 11 tributaries of the river. The target pharmaceuticals were acetylsalicylic acid, carbamazepine, clarithromycin, naproxen, sulfamethazine, sulfamethoxazole, sulfathiazole, and trimethoprim, which were detected by liquid chromatography-tandem mass spectrometry. All pharmaceuticals except acetylsalicylic acid and sulfathiazole were found in PS1, PS2, and PS3 samples, whereas acetylsalicylic acid, carbamazepine, sulfamethazine, and sulfamethoxazole were found in PS4, most of the pharmaceuticals were not present in PS5. The rank order of pharmaceutical concentration in surface water was carbamazepine (97.2%, 0.2067 µg/L) > sulfamethoxazole (88.9%, 0.1132 µg/L) > naproxen (51.4%, 0.0516 µg/L) > clarithromycin (43.1%, 0.0427 µg/L). The distribution of pharmaceuticals in the Yeongsan River at PSs and non-PSs differed, and higher concentrations of human pharmaceuticals were detected in upstream and midstream areas whereas higher concentrations of animal pharmaceuticals were found downstream. Hazard quotients (HQs) evaluated at each sites based on mean concentration and 95% upper confidence limits (95% UCLs) were all less than one, indicating a low risk of toxicity. The findings of this study are expected to be useful for risk assessment of aquatic ecosystems.

Capillary electrophoresis with capacitively coupled contactless conductivity detection method development and validation for the determination of azithromycin, clarithromycin, and clindamycin.

A capillary electrophoresis with capacitively coupled contactless conductivity detection based method for the assay of azithromycin, clarithromycin and clindamycin was optimized and validated in this study. A buffer solution of 20 mM 2-(N-morpholino) ethane sulfonic acid, 40 mM l-histidine and 0.6 mM cetyltrimethylammonium bromide (pH 6.39) was used for the electrophoresis. An uncoated, bare-fused silica capillary (total length 60 cm, effective length 32 cm, 75 µm id) was used at 25°C. The sample was injected hydrodynamically at 0.5 psi for 5 s. The electrophoresis was conducted at 30 kV in reverse polarity for 6 min with 3 and 2 min of in-between sodium hydroxide (0.1 M) and background electrolyte rinsing, respectively. Ammonium acetate was used as internal standard. This simple and robust method showed reasonable limit of detection and limit of quantitation for azithromycin (0.0125/0.03 mg/mL), clarithromycin (0.017/0.03 mg/mL), and clindamycin (0.038/0.06 mg/mL), with good selectivity, precision both intraday (relative standard deviation ≤ 1.0%) and interday (relative standard deviation < 3.7%), linearity (R2  > 0.999) and recovery (99 - 101.7%). The method was successfully applied for the determination of azithromycin, clarithromycin and clindamycin in formulations.

Liquid Chromatographic-Chemometric Techniques for the Simultaneous HPLC Determination of Lansoprazole, Amoxicillin and Clarithromycin in Commercial Preparation.

Two multivariate calibration-prediction techniques, principal component regression (PCR) and partial least-squares regression (PLSR) were applied to the chromatographic multicomponent analysis of the drug containing lansoprazole (LAN), clarithromycin (CLA) and amoxicillin (AMO). Optimum chromatographic separation of LAN, CLA and AMO with atorvastatin as the internal standard (IS) was obtained by using Xterra® RP18 column 5 µm 4.6 × 250 mm2, and 25 mM ammonium chloride buffer prepared ammonium chloride, acetonitrile and bidistilled water (45:45:10 v/v) as the mobile phase at flow rate 1.0 mL/min. The high pressure liquid chromatography data sets consisting of the ratios of analyte peak areas to the IS peak area were obtained by using diode array detector detection at five wavelengths (205, 210, 215, 220 and 225 nm). LC-chemometric calibration for LAN, CLA and AMO were separately constructed by using the relationship between the peak-area ratio and training sets for each analyte. A series of synthetic solutions containing different concentrations of LAN, CLA and AMO were used to check the prediction ability of the PCR and PLS. Both of the two-chemometric methods in this study can be satisfactorily used for the quantitative analysis and for dissolutions tests of multicomponent commercial drug.

Selecting optimal columns for clarithromycin impurity analysis according to the quantitative relationship of hydrophobic subtraction model.

Hydrophobic subtraction model (HSM) is widely applied to select columns of equivalent or different selectivity compared with a reference column, but its application in identifying optimal columns for specific separations of real samples is rare. In this work, a column selection method was proposed by firstly directly correlating separation selectivity of different pairs of solutes to column parameters based on the quantitative relationship of HSM and then selecting the optimal columns according to the predicted selectivity in consideration of the total separation of all critical pairs of solutes. Three critical pairs of solutes in clarithromycin impurity analysis were evaluated as examples. Starting with the analysis of clarithromycin impurities on 15 columns with different selectivities, ten optimal columns were finally identified for clarithromycin impurity analysis from the HSM column characterization database containing nearly 600 columns and two of them were validated with satisfactory separations for all critical peak pairs. The proposed methodology was also compared to the traditional column selection procedure based on calculations of scalar measures of the Euclidean distance between chromatographic columns. Results showed that our method provides an effective way to find the desired columns that may be overlooked by the traditional column selection due to selection of an inappropriate reference column or overestimation of column similarity, such as Fs introduced in HSM.

Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field.

The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1mgkg(-1) soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10mgkg(-1) macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1mgkg(-1) macrolides. Rapid mineralization of (14)C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance.

Analysis of Distribution of Ingredients in Commercially Available Clarithromycin Tablets Using Near-Infrared Chemical Imaging with Principal Component Analysis and Partial Least Squares.

The aim of this study was to evaluate pharmaceuticals using a near-infrared chemical imaging (NIR-CI) technique for visualizing the distribution of ingredients in solid dosage forms of commercially available clarithromycin tablets. The cross section of a tablet was measured using the NIR-CI system for evaluating the distribution of ingredients in the tablet. The chemical images were generated by performing multivariate analysis methods: principal component analysis (PCA) and partial least squares (PLS) with normalized near-infrared (NIR) spectral data. We gained spectral and distributional information related to clarithromycin, cornstarch, and magnesium stearate by using PCA analysis. On the basis of this information, the distribution images of these ingredients were generated using PLS analysis. The results of PCA analysis enabled us to analyze individual components by using PLS even if sufficient information on the products was not available. However, some ingredients such as binder could not be detected using NIR-CI, because their particle sizes were smaller than the pixel size (approximately 25×25×50 µm) and they were present in low concentrations. The combined analysis using both PCA and PLS with NIR-CI was useful to analyze the distribution of ingredients in a commercially available pharmaceutical even when sufficient information on the product is not available.

Suppressed Release of Clarithromycin from Tablets by Crystalline Phase Transition of Metastable Polymorph Form I.

The pharmaceutical properties of clarithromycin (CAM) tablets containing the metastable form I of crystalline CAM were investigated. Although the dissolution rate of form I was higher than that of stable form II, the release of CAM from form I tablet was delayed. Disintegration test and liquid penetration test showed that the disintegration of the tablet delayed because of the slow penetration of an external solution into form I tablet. Investigation by scanning electron microscopy revealed that the surface of form I tablet was covered with fine needle-shaped crystals following an exposure to the external solution. These crystals were identified as form IV crystals by powder X-ray diffraction. The phenomenon that CAM releases from tablet was inhibited by fine crystals spontaneously formed on the tablet surface could be applied to the design of sustained-release formulation systems with high CAM contents by minimizing the amount of functional excipients.

Group determination of 14-membered macrolide antibiotics and azithromycin using antibodies against common epitopes.

Erythromycin (ERY), clarithromycin (CLA), roxithromycin (ROX), and azithromycin (AZI) are macrolide antibiotics widely used in livestock and human medicine. Therefore, they are frequently found as pollutants in environmental water. A method based on indirect competitive enzyme-linked immunosorbent assay (ELISA) for group determination of these macrolides in foodstuffs, human biofluids, and water was developed. Carboxymethyloxime of clarithromycin (CMO-CLA) was synthesized and conjugated to bovine serum albumin (BSA) and gelatin to prepare immunogen and coating antigen with advantageous presentation of target epitopes, l-cladinose and d-desosamine, common for these analytes. Antibodies generated in rabbits were capable of recognizing ERY, CLA, and ROX as a group (100-150%), and AZI (12%) and did not cross-react with ERY degradants, which lack antibiotic activity. Assay displayed sensitivity of determination of 14-membered macrolides (IC50=0.13-0.2ng/ml) and low limit of detection (LOD) that was achieved at 0.02 to 0.03ng/ml. It allowed performing analysis of milk, muscle, eggs, bovine serum, water, human serum and urine, and avoiding matrix effect without special pretreatment using simple dilution with assay buffer. For 15-membered macrolide AZI, the corresponding characteristics were IC50=1.6ng/ml and LOD=0.14ng/ml. The recoveries of veterinary and human medicine macrolides from corresponding matrices were validated and found to be satisfactory.

Modulation of microenvironmental pH and utilization of alkalizers in crystalline solid dispersion for enhanced solubility and stability of clarithromicin.

Clarithromycin (CAM) is known to be poorly water-soluble and acid-labile drug. Various alkalizers such as MgO, Na2CO3, Na2HPO4 and NaHCO3 were utilized to modulate the microenvironmental pH (pHM) and to improve the low stability and solubility of CAM in a crystalline-solid dispersion system (CSD). Polyvinylpyrrolidone (PVP K-30) and hydroxypropylmethylcellulose (HPMC) 4000-based CSDs containing alkalizers were prepared by cosolvent precipitation followed by evaporation process. The dried-CSDs mixed with microcrystalline cellulose, 2% croscarmellose sodium, and 1% magnesium stearate was then directly compressed into tablet. A dissolution test was carried out in 900 mL of pH 5.0 buffer solutions at 37 °C with a 50 rpm paddle speed. pHM, surface morphology, and structural behaviors were investigated. The dissolution rates of CAM in CSD containing alkalizers were improved. The drug in CSD remained crystalline as observed by differential scanning calorimetry and powder X-ray diffraction. Scanning electron microscopy revealed nearly identical images regardless of the sorts and amounts of carriers. PVP-based CSD tablet without alkalizer showed greater drug release, while HPMC-based CSD tablet without alkalizer retarded drug release due to its greater swelling capability. However, when the alkalizers were added in CSD tablet, the drug release was sharply increased. NaHCO3 induced the most rapid drug release while MgO retarded drug dissolution. Alkalizers in CSD also could maintain the pHM of the tablet above pH 5 under acidic conditions. The use of pH modifiers in CSDs could provide a useful method to improve the dissolution rate and stability of CAM via modulation of pHM without changing drug crystallinity.

Environmental risk assessment of selected pharmaceuticals in Turkey.

In this study, environmental risks of selected pharmaceuticals were investigated to assess potential hazards. Ciprofloxacin, Clarithromycin, Cefuroxime axetil, antibiotics, Benzalkoniuman antiseptic, Paracetamol, an analgesic, and Naproxen, an anti-inflammatory, were selected due to their high rate of usage in Turkey. Ciprofloxacin was found to have the highest risk due to its high PEC/PNEC ratio (28.636). Benzalkonium, Paracetamol and Clarithromycin have a potential to cause environmental hazards. The biodegradation and biological concentration factors (BCF) of the drugs were also determined using EPA/STWIN and EPA/BCFWIN programs. The results illustrated that these pharmaceuticals are nonbiodegradable in wastewater treatment plants. The BCFs of Benzalkonium and Clarithromycin were found to be very high, 70.790 L/kg and 56.490 L/kg, respectively. It was suggested that alternative treatment methods other than biological ones should be investigated for these pharmaceuticals because of their low biodegradability. Also, unnecessary use of antibiotics is supposed to be discouraged to reduce environmental hazards.

Survey of the occurrence of pharmaceuticals in Spanish finished drinking waters.

Fifty samples of finished drinking waters (FDWs) from Spain covering 12 million inhabitants were tested for 53 pharmaceuticals pertaining to 12 different Anatomical Therapeutic Chemical (ATC) classification system codes. The studied compounds are a combination of most commonly consumed pharmaceuticals with other barely reported in the literature. Five compounds, azithromycin, clarithromycin, erythromycin, sulfamethoxazole, and ibuprofen were tentatively identified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) in some samples (2 to 15 %), but only ibuprofen and azithromycin could be confirmed when analyzed by liquid chromatography-high-resolution mass spectrometry (LC-HRMS) with a quadrupole-Orbitrap instrument. Concentration levels of ibuprofen in the positive samples ranged from 12 to 17 ng/L (n = 6) while for azithromycin values from 5 to 9.5 ng/L (n = 3) were found. Ibuprofen fragmentation behaviour in different mass spectrometry instrument configurations (triple quadrupole, quadrupole-ion trap, and quadrupole-Orbitrap) was evaluated.

A cross-sectional investigation of the quality of selected medicines in Cambodia in 2010.

BACKGROUND: Access to good-quality medicines in many countries is largely hindered by the rampant circulation of spurious/falsely labeled/falsified/counterfeit (SFFC) and substandard medicines. In 2006, the Ministry of Health of Cambodia, in collaboration with Kanazawa University, Japan, initiated a project to combat SFFC medicines. METHODS: To assess the quality of medicines and prevalence of SFFC medicines among selected products, a cross-sectional survey was carried out in Cambodia. Cefixime, omeprazole, co-trimoxazole, clarithromycin, and sildenafil were selected as candidate medicines. These medicines were purchased from private community drug outlets in the capital, Phnom Penh, and Svay Rieng and Kandal provinces through a stratified random sampling scheme in July 2010. RESULTS: In total, 325 medicine samples were collected from 111 drug outlets. Non-licensed outlets were more commonly encountered in rural than in urban areas (p < 0.01). Of all the samples, 93.5% were registered and 80% were foreign products. Samples without registration numbers were found more frequently among foreign-manufactured products than in domestic ones (p < 0.01). According to pharmacopeial analytical results, 14.5%, 4.6%, and 24.6% of the samples were unacceptable in quantity, content uniformity, and dissolution test, respectively. All the ultimately unacceptable samples in the content uniformity tests were of foreign origin. Following authenticity investigations conducted with the respective manufacturers and medicine regulatory authorities, an unregistered product of cefixime collected from a pharmacy was confirmed as an SFFC medicine. However, the sample was acceptable in quantity, content uniformity, and dissolution test. CONCLUSIONS: The results of this survey indicate that medicine counterfeiting is not limited to essential medicines in Cambodia: newer-generation medicines are also targeted. Concerted efforts by both domestic and foreign manufacturers, wholesalers, retailers, and regulatory authorities should help improve the quality of medicines.

Occurrence, distribution and partitioning of nonionic surfactants and pharmaceuticals in the urbanized Long Island Sound Estuary (NY).

This work deals with the environmental distribution of nonionic surfactants (nonylphenol and alcohol ethoxylates), their metabolites (NP, nonylphenol; NPEC, nonylphenol ethoxycarboxylates; and PEG, polyethylene glycols) and a selection of 64 pharmaceuticals in the Long Island Sound (LIS) Estuary which receives important sewage discharges from New York City (NYC). Most target compounds were efficiently removed (>95%) in one wastewater treatment plant monitored, with the exception of NPEC and some specific drugs (e.g., hydrochlorothiazide). Concentrations of surfactants (1.4-4.5 µg L(-1)) and pharmaceuticals (0.1-0.3 µg L(-1)) in seawater were influenced by tides and sampling depth, consistent with salinity differences. Surfactants levels in suspended solids samples were higher than 1 µg g(-1), whereas only most hydrophobic or positively charged pharmaceuticals could be found (e.g., tamoxifen, clarithromycin). Maximum levels of target compounds in LIS sediments (PEG at highest concentrations, 2.8 µg g(-1)) were measured nearest NYC, sharply decreasing with distance from major sewage inputs.

Evaluation of subgingivally delivered 0.5% clarithromycin as an adjunct to nonsurgical mechanotherapy in the management of chronic periodontitis: a short-term double blinded randomized control trial.

OBJECTIVE: As the risk involved with systemic antimicrobials (high doses, microbial resistance, adverse reactions, etc.) restricts their use and local delivery of antimicrobials into periodontal pockets improves periodontal health, this study was designed to investigate the effects of subgingivally delivered clarithromycin (CLM; 0.5%) as an adjunct to nonsurgical mechanotherapy in chronic periodontitis subjects. METHODS: Ninety-eight patients were categorized into two treatment groups: scaling and root planing (SRP) plus 0.5% CLM (test; group 1) and SRP plus placebo (control; group 2). Clinical parameters included gingival index (GI), sulcus bleeding index (SBI), plaque index (PI), probing depth (PD), and periodontal attachment level (PAL), recorded at 4, 8 and 12 weeks. The concentration of 0.5% CLM in gingival fluid was estimated by reverse-phase high pressure liquid chromatography. anova, the chi-square test and the Scatterthwaite test were used for statistical analysis. RESULTS: Patients treated with SRP + CLM showed enhanced reductions in GI, SBI, and PD, and gains in PAL (P < 0.001) over time, as compared with the placebo group. However, no statistically significant differences were noted for PI. The mean concentration of CLM was detected in gingival crevicular fluid for up to 7 weeks, fulfilling the conditions for a controlled-release device. CONCLUSION: Adjunctive use of 0.5% CLM as a controlled drug delivery system enhanced the clinical outcome up to 3 months.

Reduction of clarithromycin and sulfamethoxazole-resistant Enterococcus by pilot-scale solar-driven Fenton oxidation.

The presence of pathogenic antibiotic-resistant bacteria in aquatic environments has become a health threat in the last few years. Their presence has increased due to the presence of antibiotics in wastewater effluents, which are not efficiently removed by conventional wastewater treatments. As a result there is a need to study the possible ways of removal of the mixtures of antibiotics present in wastewater effluents and the antibiotic-resistant bacteria, which may also spread the antibiotic resistance genes to other bacterial populations. In this study the degradation of a mixture of antibiotics i.e. sulfamethoxazole and clarithromycin, the disinfection of total enterococci and the removal of those resistant to: a) sulfamethoxazole, b) clarithromycin and c) to both antibiotics have been examined, along with the toxicity of the whole effluent mixture after treatment to the luminescent aquatic bacterium Vibrio fischeri. Solar Fenton treatment (natural solar driven oxidation) using Fenton reagent doses of 50 mg L(-1) of hydrogen peroxide and 5 mg L(-1) of Fe(3+) in a pilot-scale compound parabolic collector plant was used to examine the disinfection and antibiotic resistance removal efficiency in different aqueous matrices, namely distilled water, simulated and real wastewater effluents. There was a faster complete removal of enterococci and of antibiotics in all aqueous matrices by applying solar Fenton when compared to photolytic treatment of the matrices. Sulfamethoxazole was more efficiently degraded than clarithromycin in all three aqueous matrices (95% removal of sulfamethoxazole and 70% removal of clarithromycin in real wastewater). The antibiotic resistance of enterococci towards both antibiotics exhibited a 5-log reduction with solar Fenton in real wastewater effluent. Also after solar Fenton treatment, there were 10 times more antibiotic-resistant enterococci in the presence of sulfamethoxazole than in the presence of clarithromycin. Finally, the toxicity of the treated wastewater to V. fischeri remained very low throughout the treatment time.

Periodontal tissue and serum concentration of clarithromycin after systemic administration in patients affected by chronic periodontitis.

BACKGROUND: During the past two decades, dentists and microbiologists have relied on periodontal antibiotic therapy in the management of periodontitis. This association has accumulated and strengthened exponentially. Macrolides attain high therapeutic concentrations in infected tissue, so they are potentially a good choice for inhibiting invasive periodontal pathogens. Clarithromycin accumulates in phagocytes, monocytes, fibroblasts, polymorphonuclear cells, macrophages, and lymphocytes. These cells are more numerous at inflamed sites, so it is reasonable to expect clarithromycin levels to be higher in periodontally diseased sites. This study determines the distribution profile of clarithromycin in the gingiva of patients with periodontitis compared to serum after systemic administration of clarithromycin. METHODS: Twenty patients (14 males and six females, aged 25 to 45 years) with chronic periodontitis were enrolled in the study. Gingival index and plaque index were recorded at baseline and 3 days after administration of 500 mg clarithromycin, twice daily, for 3 days. Intravenous blood and biopsy of periodontal tissue samples were taken on the third day. These samples were analyzed for detection of clarithromycin concentration using high-performance liquid chromatography. RESULTS: Approximately 6 hours after the last dose of clarithromycin, mean clarithromycin concentrations in serum and periodontal tissue were 0.465 µg/mL and 2.61 µg/g, respectively, and the difference was statistically significant. CONCLUSIONS: Clarithromycin can attain higher levels in gingiva than serum of patients with periodontitis. This distribution profile of clarithromycin can thus be advantageous in the management of periodontal lesions.