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TetracyclinesTetracyclinesNew Uses for an Old Drug: Rebirth of the TetracyclinesTetracycline diffusion through bacterial cellulose—polyvinyl alcohol…Tetracycline Derivative Induces Lupus

Tetracycline antibiotics are the leading approved systemic treatments of moderate to severe inflammatory acne. Discovered decades ago as broad-spectrum systemic antibiotics, tetracyclines have been shown to be potent anti-acne agents. Paratek has utilized …

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TetracyclinesTetracyclinesNew Uses for an Old Drug: Rebirth of the TetracyclinesTetracycline diffusion through bacterial cellulose—polyvinyl alcohol…Tetracycline Derivative Induces Lupus

Tetracycline and doxycycline (long-acting tetracycline) have long been the antibiotics of choice for treating severe cholera in Bangladesh and in other parts of the world, except for young children and pregnant women (1,2). Furazolidone, erythromycin, trimethoprim-sulphamethoxazole, and chloramphenicol have also been effective in treating severe cholera caused by strains of V. cholerae susceptible to these agents (3).
During October 2004-December 2005, 953 (565 Ogawa and 388 Inaba) and 344 (197 Ogawa and 147 Inaba) strains of V. cholerae 01 isolated from cholera cases admitted to the Dhaka Hospital (urban area) and Matlab Hospital (rural area) of ICDDR,B respectively were examined for susceptibility to tetracycline, erythromycin, trimethoprim-sulphamethoxazole, furazolidone, and ciprofloxacin. Antimicrobial susceptibility was performed using the disc-diffusion technique on Mueller-Hinton agar (Difco, Detroit, Michigan, USA) with commercial discs (Oxoid, UK) and appropriate control strains (4).
Overall, 525 (55%), 420 (44%), 944 (99%), 948 (100%), and no strains from Dhaka and 186 (54%), 165 (48%), 332 (97%), 343 (100%), and no strains from Matlab were resistant to tetracycline, erythromycin, trimethoprim-sulphamethoxazole, furazolidone, and ciprofloxacin respectively. Prior to October 2004, most strains were resistant to trimethoprim-sulphamethoxazole and furazolidone but were uniformly sensitive to tetracycline, erythromycin, and ciprofloxacin.
The first multidrug-resistant strains of V. cholerae (strains resistant to furazolidone, trimethoprimsulphamethoxazole, tetracycline, and erythromycin) were observed in Matlab in October 2004 among the Ogawa serotype, and the isolation of such strains increased dramatically to reach 100% by February 2005. In Dhaka, the multidrug-resistant strains appeared one month later in November 2004 among both Ogawa (13%) and Inaba (5%) strains of V. cholerae, and by February 2005, all the Ogawa strains demonstrated the multidrug-resistant phenoytpe. By March 2005, nearly all the El Tor Ogawa isolates, 5 of 6 (83%) at the Matlab Hospital, and 43 of 45 (96%) at the Dhaka Hospital were multidrug-resistant. The figure shows the resistance patterns of V. cholerae in Dhaka and Matlab by month and site.
Based on the multidrug-resistant phenotype, it appeared that there were two or more clones of V. cholerae 01 in circulation at different time points, and we are in the process of understanding the clonality by subjecting representative strains to molecular typing analysis. We determined antimicrobial susceptibility using both disc-diffusion technique and E-test method.
In the absence of a reference zone size for V. cholerae resistance to erythromycin and azithromycin, we used the zone size for other organisms to determine the susceptibility (zone of inhibition [greater than or equal to]23 mm for erythromycin and [greater than or equal to]18 mm for azithromycin) of the V. cholerae strains to these drugs. Seventeen of the 35 (49%) V. cholerae strains were resistant to both erythromycin and azithromycin, while the remaining 18 (51%) strains were susceptible to both erythromycin and azithromycin. The strains resistant to erythromycin exhibited minimum inhibition concentrations (MICs) of 8 to 32[micro]g/mL, while the MIC of those susceptible to the drug ranged from 0.25 to 1 [micro]g/mL. The MIC of the strains resistant to azithromycin ranged from 0.75 to 3 [micro]g/mL, while the MIC of those susceptible to the drug was from 0.047 to 0.125 [micro]g/mL. These findings suggest that resistance to erythromycin could be a marker for resistance to azithromycin. Similarly, resistance to tetracycline is considered a proxy indicator for resistance to doxycycline (5). We have, for the first time, encountered this unique, multidrug-resistant pattern, including resistance to erythromycin, among V. cholerae O1 in Bangladesh.
[FIGURE OMITTED]
Throughout the period of this investigation, all isolates from Matlab and Dhaka were susceptible to ciprofloxacin. The MIC for ciprofloxacin was determined using E-test (AB-BIODISK, Sweden) with the zone size interpretive criteria for susceptibility corresponding to 0.06 [micro]g/mL (5). We noted a consistent increase in the median MIC of V. cholerae 01 strains isolated at the Dhaka Hospital over the years: 0.003 [micro]g/mL in 1994, 0.023 [micro]g/mL in 2001, and 0.38 to 0.5 [micro]g/mL in 2005 (6,7). In a recent study in adults infected with V. cholerae 01, we observed clinical success (resolution of diarrhoea by 48 hours of initiation of therapy) rate of 68% with 500-mg 12-hourly dose of ciprofloxacin for three days–a rate substantially lower than that observed with a single one-gramme dose of the drug in an earlier study (8).

The routine use of antibiotics in swine production can have unintended consequences, with antibiotic resistance genes sometimes leaking from waste lagoons into groundwater, according to new research from the University of Illinois.

Researchers report that some genes found in hog waste lagoons are transferred, “like batons,” from one bacterial species to another. This migration across species and into new environments sometimes dilutes, and sometimes amplifies, genes conferring antibiotic resistance, they say.

The new report, in the August issue of “Applied and Environmental Microbiology,” tracks the passage of tetracycline resistance genes from hog waste lagoons into groundwater wells at two Illinois swine facilities.

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TetracyclinesTetracyclinesNew Uses for an Old Drug: Rebirth of the TetracyclinesTetracycline diffusion through bacterial cellulose—polyvinyl alcohol…Tetracycline Derivative Induces Lupus

Tetracycline is widely used in swine production. It is injected into the animals to treat or prevent disease, and is often used as an additive in hog feed to boost the animals’ growth.

Its near-continuous use in some hog farms promotes the evolution of …

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TetracyclinesTetracyclinesNew Uses for an Old Drug: Rebirth of the TetracyclinesTetracycline diffusion through bacterial cellulose—polyvinyl alcohol…TETRACYCLINE FIBRE APPROVED IN EUROPE

The patients, all three of whom had metastatic cancer (two had prostate cancer and one had colon cancer), experienced phototoxic skin eruptions despite using sunblock and avoiding the sun. All tested positive for antinuclear antibodies, and two had elevated antihistone antibody levels. All experienced fever, and two had arthralgia, one with joint swelling.
The symptoms cleared within a few weeks of discontinuing COL-3 in two of the patients, but have been recurrent in the third. No new patients are being enrolled in the clinical trial at this time, the investigators said.
COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2008 Gale, Cengage Learning

Percentage of prescriptions
Minocycline 5.2%
Doxycycline 3.3%
Clobetasol 3.2%
Triamcinolone acetonide
topical 2.9%
Clindamycin topical 2.5%
Differin (adapalene) 2.3%
Fluocinonide 2.0%
Cephalexin 2.0%
BenzaClin 1.9%
(benzoyl peroxide/
clindamycin)
Tetracycline 1.8%

Source: Verispan

Note: Table made from bar graph.

COPYRIGHT 2007 International Medical News Group
COPYRIGHT 2008 Gale, Cengage Learning

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TetracyclinesTetracyclinesNew Uses for an Old Drug: Rebirth of the TetracyclinesTetracycline diffusion through bacterial cellulose—polyvinyl alcohol…Tetracycline Derivative Induces Lupus

The children had no adverse reactions to the presence of tetracycline-resistant bacteria, which were isolated from their normal oral microflora. Overall, 15 of the 18 children studied had tetracycline-resistant bacteria in their mouths at baseline, 6 months, and 12 months. The median percentages of 0.78%, 0.57%, and 0.62%, respectively, were not significantly different from one another. One hypothesis is that the children acquired tetracycline resistance from food, possibly from both meat and vegetable products. Tetracyclines have been used in animal husbandry and as pesticides in fruit production.
COPYRIGHT 2003 International Medical News Group
COPYRIGHT 2008 Gale, Cengage Learning

TetracyclinesTetracyclinesNew Uses for an Old Drug: Rebirth of the TetracyclinesTetracycline diffusion through bacterial cellulose—polyvinyl alcohol…Tetracycline Derivative Induces Lupus

> Warner Chilcott Ltd. has received FDA approval for a 150-mg strength of Doryx (doxycycline hyclate) delayed-release tablets. The drug, a tetracycline-class oral antibiotic indicated for adjunctive treatment of severe acne, contains enteric-coated pellets of doxycycline hyclate. The pellets do not release until they reach the small intestine, minimizing the gastrointestinal side effects most commonly associated with other doxycycline products.
COPYRIGHT 2008 Racher Press, Inc.
COPYRIGHT 2008 Gale, Cengage Learning

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TetracyclinesTetracyclinesNew Uses for an Old Drug: Rebirth of the TetracyclinesTetracycline diffusion through bacterial cellulose—polyvinyl alcohol…Tetracycline Derivative Induces Lupus

The group of tetracyclines, especially tetracycline, oxytetracycline, and chrlortetracycline, are widely used to treat human illness, in veterinary practice, and as feed additives. Because of the increased awareness among consumers, there is growing demand for faster and more sensitive methods for determination of tetracycline, especially in biological matrixes (Figure 1).
Due to the widespread use of tetracyclines, the literature on the analysis of these compounds is fairly extensive and includes methods for the extraction and analysis in various matrixes, e.g., animal tissues, urine, plasma, feces, water, and soil. In recent years, several methods for the determination of tetracyclines in human plasma have been based on liquid chromatography (LC). The methods have all used reversed-phase separation with UV and fluorescence detection. A few methods based on LC/mass spectrometric (MS) determination of tetracycline in human plasma have been published (1-4).
Bioanalytical methods used for the quantitative determination of drugs and their metabolites in biological samples are the key determinants in generating reproducible and reliable data, which, in turn, are used in the evaluation and interpretation of bioavailability, bioequivalence, and pharmacokinetic findings. It is essential to use well-characterized and fully validated analytical methods to yield reliable results which can be interpreted satisfactorily. Bioanalytical method validation includes all the experimental procedures and documentation which demonstrate that a particular method used for quantitative measurement of analytes is reliable and suitable for the intended analytical applications. Fundamental parameters that require determination are linearity, accuracy, precision, specificity, and stability (5, 6).
LC coupled with MS detection has been used for both identification and quantitation of drugs at low concentrations in raw materials, various pharmaceutical formulations, and biological matrixes, due to the improved sensitivity and specificity of this technique. Moreover, as a consequence of mass selectivity, it was expected that the time for method development and sample turnover could be significantly reduced. However, matrix ion suppression requires that most of the biological matrix constituents be removed before LC/MS/MS analysis, making sample preparation a time-consuming step in the development of an LC/MS/MS procedure (7-12).
Despite the advances in the development of highly efficient analytic instrumentation for the end point determination of analytes in biological matrixes, sample pretreatment is still necessary to extract the analyte of interest. This can be performed using solid-phase extraction (SPE), liquid-liquid extraction (LLE), or protein precipitation methods. SPE is used to increase the reproducibility and decrease the volume of organic solvents needed in comparison to LLE. However, traditional offline SPE needs either relatively large volumes of plasma or organic solvents for the elution of the analyte from the solid phase, so that concentration of the extract before injection in the LC/MS/MS system is usually necessary. In contrast, the protein precipitation method requires smaller amounts of plasma, does not need concentration of extracts before injection, and requires a shorter sample preparation time.
[FIGURE 1 OMITTED]
The aim of the present work was to develop and validate a sensitive and fast LC/MS/MS method for determination of tetracycline in human plasma, improving the current published procedures, in order to support human clinical studies, and to demonstrate the applicability of the method for the quantitation of tetracycline in bioequivalence studies.
Experimental
Chemicals and Reagents
Tetracycline chloridrate reference standard was purchased from Brazilian Pharmacopeia (Santa Maria, Brazil) and oxytetracycline was purchased from Sigma (St. Louis, MO). Tablets containing 500 mg tetracycline were obtained from Prati, Donaduzzi & Cia Ltda (Toledo, Brazil) and Parenzyme[R] from Medley (Sao Paulo, Brazil) within their shelf-life period. HPLC grade acetonitrile, methanol, formic, and acetic acid were purchased from Tedia (Fairfield, OH). Ammonium acetate and trichloroacetic acid were purchased from Merck (Darmstadt, Germany). All chemicals used were of pharmaceutical or special analytical grade. For all the analyses, ultrapure water (Gehaka, Sao Paulo, Brazil) filtered through a 0.22 [micro]m membrane filter was used.

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Please avoid every type of Vitamin a derivative either topical or oral. Medications such as Isotretinoin, which is one of the favorites of acne medicines, should be strictly avoided. Other topicals containing tretinoin, tazarotene and other Vitamin A derivatives should be strictly avoided. Please do not use any topical skin care product before asking your doctor. Please avoid any oral medication after talking to your doctor. Many OTC skin care products contain Vitamin A derivatives. Please avoid all such products.

Please avoid antibiotics from the group of tetracycline such as tetracycline, doxycycline etc. They may damage the fetus or breast-feeding child. No antibiotic should be taken innocently.

Please avoid any hormone preparation that you may be using for your acne. Many hormones such as estrogen and other anti androgen hormones can damage the fetus and also get passed to the breast-feeding child. Avoid as many medicines as possible. Avoid all skin care and makeup products. Get everything certified by your doctor, if you are planning to get pregnant, or are pregnant or breast feeding your child.

This article is only for informative purposes. This article is not intended to be a medical advise and it is not a substitute for professional medical advice. Please consult your doctor for your medical concerns. Please follow any tip given in this article only after consulting your doctor. The author is not liable for any outcome or damage resulting from information obtained from this article.