Minocycline positive

Fig. 1. Tetracycline (1) and its derivatives chlortetracycline (7-chlorotetracycline) (2) oxytetracycline (5-hydroxytetracycline) (3), demeclocycline (6-demethyl-7-chlorotetracycline) (4) methacycline (6-demethyl-6-deoxy-5-hydroxy-6-methylenetetracycline) (5) doxycycline (6a-deoxy-5-hydroxytetracycline) (6) and minocycline (6-demethy1-6-deoxy-7-dimethy1 amino tetracycline) (7). Substituents at positions not specifically...

Thiatetracyclines contain a sulphur atom at position 6 in the molecule. One derivative, thiacycline, is more active than minocycline against tetracycline-resistant bacteria. Despite toxicity problems affecting its possible clinical use, thiacycline could be the starting point in the development of a new range of important tetracycline-type antibiotics. 

A generalized pustular eruption was reported in a patient with acne treated with minocycline (28). Skin prick tests with minocycline were positive at 48 hours. 

Immunoallergic reactions have been reported with minocycline and include lupus-like syndrome, autoimmune hepatitis, eosinophilic pneumonia, hypersensitivity syndrome, a serum sickness-like illness (29), and Sweet s syndrome (SEDA-21, 262) (SEDA-22, 271). Over 60 minocycline-induced cases of lupus-like syndrome and 24 cases of minocycline-induced autoimmune hepatitis were found in a review of the literature (30). In 13 patients, both disorders co-existed. These patients had symmetrical polyarthralgia/polyarthritis, raised liver enzymes, and positive antinuclear antibodies they were also generally antihistone-negative, and only two patients had p-ANCA antibodies. Minocycline-related lupus can also occur in adolescents (31). 

According to the authors, the patient fulfilled all the criteria for a diagnosis of drug-induced lupus-like syndrome, that is no history of lupus erythematosus before minocycline therapy, the presence of antinuclear antibodies, at least one clinical feature of lupus erythematosus, and prompt recovery after withdrawal of minocycline. She also had positive antihistone antibodies, compatible with drug-induced lupus-like syndrome. 

Three adolescents taking therapeutic doses of minocycline for 12-20 months met the 1993 International Autoimmune Hepatitis Group criteria for autoimmune hepatitis. All had hypogammaglobulinemia and positive antinuclear antibody and antismooth muscle antibody titers. Two underwent liver biopsy that showed severe chronic lymphoplasmocytic inflammation, necrosis, and fibrosis. All other causes of liver disease were excluded. One patient had resolution of symptoms after withdrawal of the drug, while two required immunosuppressive therapy. 

Two cases of biopsy-proven cutaneous polyarteritis nodosa with positive perinuclear antineutrophilic cytoplasmic antibodies have been reported with long-term use of minocycline for acne vulgaris (50-100 mg/day for 44 months and 100 mg/day for 65 months) (52). In one of the cases, involvement was not restricted to medium-size vessels alone. In both cases the vasculitis disappeared after a short course of prednisone (40 mg/day) and withdrawal of minocycline. Rechallenge was not performed. P-ANCA is usually found in microscopic poly angiitis, a vasculitis of smaller arteries, and its significance in polyarteritis nodosa is not clear. 

Fig. 13.6 Structural modifications at the 9 position of the tetracycline antibiotic minocycline conferring increased stability against resistance mechanisms.

Tetracyclines including semi-synthetic derivatives like doxycycline and minocycline are offering a wide range of antimicrobial activity against Gram-positive, Gramnegative bacteria and even some protozoa infections. 

To demonstrate this application, we used the BacTiter-Glo Assay to screen some LOP AC compounds (Rack 8, enzyme inhibitors, total of 80 compounds) for antimicrobial activity against S. aureus. The results were shown in Fig. 2. All positive controls of standard antibiotics (boxed points) and three LOPAC compounds (circled points) exhibited significant anti-S. aureus activity. The three LOPAC hits were D6 emodin Dll sanguinarine chloride and H7 minocycline. Their anti-5, aureus activities were reported in the literature previously. ... 

Numerous drugs have been associated with the development of vasculitis (ten Holder et al. 2002 Cuellar 2002). For example propylthiouracil is associated with cutaneous, renal, and pulmonary vascultis aUopurinol is associated with cutaneous, renal, and hepatic vasculitis hydralazine is associated with cutaneous, renal, and pulmonary vascultis and isotretinoin is associated with cutaneous, renal, pulmonary, and gastrointestinal vascultis (Cuellar 2002 ten Holder et al. 2002). Systemic polyarteritis nodosa, a vasculitis with involvement of small- and mediumsized renal arteries, has been described following minocycline use (Cuellar 2002). Patients may present with hematuria, proteinuria, reduced renal function, and hypertension. Hydralazine, propylthiouracil, aUopurinol, and peniciUamine have been implicated in the development of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis (Choi et al. 2000). Patients exposed to these drugs... 

Fawcett and Pepys (1976) reported the case of a patient who developed immediate bronchospasm and an urticarial reaction after ingestion of a commercial combination of three tetracyclines no reactions could be elicited by oral challenge with the different tetracyclines, tartrazine, or the blue coating of the drug, whereas a provocation test with the commercial preparation was positive. Other clinical patterns, such as fixed drug eruptions (Kandil 1969 Delaney 1970 Csonka et al. 1971 Brown 1974 Shimizu and Shimao 1977 Pasricha and Shukla 1979), vascular purpura (Schoenfeld 1964) and a picture similar to systemic lupus erythematosus (SLE) (Sulkowski and Haserick 1964) have also been described. Contact dermatitis seems to be a very rare complication it was, however, observed after contact with oxytetracycline (Dohn 1962 Bojs and Moller 1974) and minocycline. In the latter case subsequent oral therapy with the same drug was followed by a systemic reaction and the sensitivity was confirmed by epicutaneous tests (Shelley and Heaton 1973). 

A 70-year-old woman developed a fever, asymmetrical paresthesia, numbness in her limbs, and right foot drop after taking oral minocycline lOOmg/day for 8 months. There was a positive antinuclear antibody, and a nerve conduction study showed abnormahties... 

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