EDITORIAL ESPANOL:

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Hola amigos DERMAGICOS, el tema de hoy LA MINOCICLINA, lo bueno la malo y feo de este antibiótico. Quien iba a pensar hace unos años, que este popular medicamento iba a tener efectos beneficiosos sobre enfermedades como la lepra, esclerodermia, pénfigo, pioderma gangrenoso, penfigoide, papilomatosis reticulada y otras más. Estas 49 referencias nos ilustran bien el tema. 

Y les pregunto,, realmente la minociclina se esta usando en la lepra en nuestros países, ??? 

Dras: Ana Rita y Maria Alejandra Jimenez (Venezuela), bienvenidas a DERMAGIC 

próxima edición: Colagenosis: LA MORFEA 

Saludos,,,

Dr. José Lapenta R.,,,

 EDITORIAL ENGLISH:

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Hello DERMAGICS, friends the topic of today THE MINOCICLINA, the good thing the bad and ugly of this antibiotic. Who will have thought for some years that this popular medication will have beneficial effects on illnesses like the leprosy, scleroderma, pemphigus, gangrenous pyoderma, pemphigoid, reticulated papillomatosis and other but. This 49 references illustrate us well the topic. 

And do I ask you, really the minociclina is it using in the leprosy in our countries??? 

Dr: Ana Rita and Maria Alejandra Jimenez (Venezuela), welcome to DERMAGIC 

Next edition: THE MORPHEA (LOCALIZED SCLERODERMA)

Greetings,,,

Dr. José Lapenta R. 

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DERMAGIC/EXPRESS(45)

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LA MINOCICLINA: LO BUENO LO MALO Y LO FEO

THE MINOCYCLINE: THE GOOD, THE BAD, AND THE UGLY.

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()()()()()()()()()()()()LO BUENO () THE GOOD ()()()()()()()()()()()()()() 

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1.) Superior antibacterial action and reduced incidence of bacterial

resistance in minocycline compared to tetracycline-treated acne patients. 

2.) Tetracycline-resistant propionibacteria from acne patients are

cross-resistant to doxycycline, but sensitive to minocycline. 

3.) Research letters : Minocycline in early diffuse scleroderma

4.) Minocycline in lepromatous leprosy. 

5.) Efficacy of minocycline in single dose and at 100 mg twice daily for

lepromatous leprosy. 

6.) Field trial on efficacy of supervised monthly dose of 600 mg rifampin,

400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first

results. 

7.) Bactericidal activity of a single-dose combination of ofloxacin plus

minocycline, with or without rifampin, against Mycobacterium leprae in mice

and in lepromatous patients. 

8.) Efficacy of single dose multidrug therapy for the treatment of

single-lesion paucibacillary leprosy. Single-lesion Multicentre Trial Group. 

9.) Bactericidal activity of single dose of clarithromycin plus

minocycline, with or without ofloxacin, against Mycobacterium leprae in

patients. 

10.) WHO Expert Committee on Leprosy. 

11.) Experimental evaluation of possible new short-term drug regimens for

treatment of multibacillary leprosy. 

12.) Powerful bactericidal activities of clarithromycin and minocycline

against Mycobacterium leprae in lepromatous leprosy. 

13.) Minocycline is a useful adjuvant therapy for pemphigus. 

14.) Confluent and reticulated papillomatosis: response to minocycline. 

15.) Minocycline treatment for confluent and reticulated papillomatosis. 

16.) No detection of Borrelia burgdorferi-specific DNA in erythema migrans

lesions after minocycline treatment. 

17.) Minimizing cicatricial pemphigoid orodynia with minocycline. 

18.) Response of atypical bullous pyoderma gangrenosum to oral minocycline

hydrochloride and topical steroids. 

19.) Blastomycosis-like pyoderma--report of a case responsive to

combination therapy utilizing minocycline and carbon dioxide laser

debridement. 

20.) A sporotrichoid-like Mycobacterium kansasii infection of the skin

treated with minocycline hydrochloride. 

21.) Primary lymphocutaneous nocardiosis due to Nocardia otitidiscaviarum:

the first case report from Japan. 

22.) Minocycline treatment of pulmonary nocardiosis. 

23.) Minocycline in rheumatoid arthritis. A 48-week, double-blind, 

placebo-controlled trial. MIRA Trial Group [see comments] 

24.) Minocycline prevents the decrease in bone mineral density and

trabecular bone in ovariectomized aged rats. 

25.) Minocycline and cefotaxime in the treatment of experimental murine

Vibrio vulnificus infection. 

26.) The role of minocycline in the treatment of intracranial 9L glioma. 

27.) Evaluation of the long-term efficacy and safety of locally-applied

minocycline in adult periodontitis patients. 

28.) Clinical and microbiological effects of minocycline-loaded

microcapsules in adult periodontitis. 

29.) The broad-spectrum activity and efficacy of catheters coated with

minocycline and rifampin. 

30.) Symptomatic hepatic cysts: treatment with single-shot injection of

minocycline hydrochloride. 

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()()()(()()()()()()()()( LO MALO () THE BAD ()()()()()()()()()()()()()()

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31.) Minocycline induced autoimmune hepatitis and systemic lupus

erythematosus-like syndrome [see comments] 

32.) Minocycline and Lupuslike Syndrome in Acne Patients 

33.) Minocycline-induced lupus. 

34.) Minocycline related lupus. 

35.) Acute hepatitis and drug-related lupus induced by minocycline treatment. 

36.) Minocycline-induced pneumonitis with bilateral hilar lymphadenopathy

and pleural effusion. 

37.) Comparative safety of tetracycline, minocycline, and doxycycline. 

38.) Serious adverse reactions induced by minocycline. Report of 13

patients and review of the literature. 

39.) [Side effects of minocycline in the treatment of acne vulgaris] 

40.) Serious dermatologic reactions in children. 

41.) Serum sickness-like syndrome associated with minocycline therapy. 

42.) Minocycline-induced loss of potassium from erythrocytes:

identification of a family with an augmented response. 

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()()()()()()()()()()()()()() LO FEO () THE UGLY ()()()()()()()()()()()()

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43.) Minocycline-induced hyperpigmentation in leprosy. 

44.) Psoriatic arthritis and minocycline induced autoantibodies.

45.) Minocycline hydrochloride hyperpigmentation complicating treatment of

pyoderma gangrenosum. 

46.) Minocycline-induced oral pigmentation. 

47.) Nodular hyperplasia, black thyroid, and chronic minocycline ingestion

in a teenager. 

48.) Black bones following long-term minocycline treatment. 

49.) Pigmented postacne osteoma cutis in a patient treated with

minocycline: report and review of the literature. 

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()()()()()()()()()()()()LO BUENO () THE GOOD ()()()()()()()()()()()()()() 

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1.) Superior antibacterial action and reduced incidence of bacterial

resistance in minocycline compared to tetracycline-treated acne patients. 

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ARTICLE SOURCE: Br J Dermatol (England), Feb 1990, 122(2) p233-44 

AUTHOR(S): Eady EA; Cove JH; Holland KT; Cunliffe WJ 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: Twenty-five previously untreated acne patients were monitored

throughout a 6-month course of therapy with either tetracycline or

minocycline for changes in the numbers of staphylococci, propionibacteria

and yeasts of the genus Malessezia on the skin surface. Antibiotic

resistant staphylococci and propionibacteria were also counted. Minocycline

(50 mg b.d.) produced a 10-fold greater reduction in propionibacterial

numbers compared to tetracycline (500 mg b.d.) after 12 (P less than 0.02,

t-test) and 24 weeks (P less than 0.05) of therapy. As treatment

progressed, propionibacteria were replaced by yeasts, numbers of which were

significantly increased by week 12 (P less than 0.02) in

tetracycline-treated patients and by week 24 (P less than 0.01) in

minocycline-treated patients. This suggests that yeasts have no role in the

pathogenesis of acne but may compete with propionibacteria for the same

niche. Overgrowth of antibiotic resistant staphylococci prevented any

decrease in staphylococcal numbers in tetracycline-treated patients, but

minocycline produced a significant and sustained reduction in

staphylococcal numbers after 1 week of therapy (P less than 0.001). An

increase in the number of multiply resistant (greater than or equal to 3

resistances) staphylococci occurred in 67% of tetracycline-treated and 33%

of minocycline-treated patients by the end of the treatment period. There

was no evidence of propionibacterial resistance in either treatment group.

This study shows that minocycline has much greater antibacterial activity

in vivo against both staphylococci and propionibacteria and produces less

staphylococcal antibiotic resistance than tetracycline. 

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2.) Tetracycline-resistant propionibacteria from acne patients are

cross-resistant to doxycycline, but sensitive to minocycline. 

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ARTICLE SOURCE: Br J Dermatol (England), May 1993, 128(5) p556-60 

AUTHOR(S): Eady EA; Jones CE; Gardner KJ; Taylor JP; Cove JH; Cunliffe WJ 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: Antibiotic-resistant propionibacteria are being isolated with

increasing frequency from antibiotic-treated acne patients. Minimum

inhibitory concentrations (MICs) of three tetracyclines, extensively used

in acne therapy, were determined for 46 resistant and 19 sensitive

propionibacteria isolates. Sensitive strains were inhibited by or = 1

microgram/ml of all three tetracyclines. For every resistant strain tested,

the MIC of tetracycline exceeded that of doxycycline which, in turn,

exceeded that of minocycline. The mean MIC for resistant strains was 20.61

+/- 4.56 micrograms/ml of tetracycline, 9.70 +/- 2.03 micrograms/ml of

doxycycline and 1.95 +/- 0.35 micrograms/ml of minocycline. In order to

determine whether these strains could be inhibited by concentrations of

minocycline achievable in vivo, serum levels of minocycline were determined

in acne patients receiving either the recommended dose of 50 mg b.d. (20

males, 14 females), or twice this dose (21 males, 12 females). Serum levels

were significantly higher (P 0.001, Student's t-test) in patients receiving

100 mg b.d. Males on 50 mg b.d. had significantly lower serum levels than

females on the same dose (P 0.05. Student's t-test). For all patients, the

mean serum level on high-dose minocycline was 2.46 +/- 0.45 micrograms/ml,

compared with 1.38 +/- 0.30 micrograms/ml on the smaller dose. These

results indicate that tetracycline-resistant propionibacteria should be

considered clinically minocycline sensitive, if patients who harbour such

strains are prescribed 100 mg b.d. The recommended dose of minocycline for

treating acne, especially in male patients, should be re-assessed. 

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3.) Research letters : Minocycline in early diffuse scleroderma

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The Lancet 1998;352(9142):1755-6

Minocycline may effectively treatearly diffuse scleroderma. 11 patients in

the early stages of skin disease treated in open-label fashion for up to one

year with minocycline. Six patients completed the study, of whom four had

complete resolution of disease. 

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4.) Minocycline in lepromatous leprosy. 

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Author 

Fajardo TT Jr; Villahermosa LG; dela Cruz EC; Abalos RM; Franzblau SG;

Walsh GP 

Address 

Clinical Research Branch, Leonard Wood Memorial Center, Cebu City, The

Philippines. 

Source 

Int J Lepr Other Mycobact Dis, 63(1):8-17 1995 Mar 

Abstract 

Twelve patients were treated with three dose levels of minocycline for 30

days, primarily to detect the dose-related effects on Mycobacterium leprae

viability, followed by another 5 months of daily minocycline for overall

efficacy and persistence of clinical and antibacterial effects.

Subsequently, the patients were given standard WHO/MDT chemotherapy for

multibacillary leprosy. Clinical improvement was recognizable during the

first month, occurring much earlier among those on minocycline 200 mg daily

than those who received minocycline 100 mg daily. A similar change also was

observed in one patient 11 days after three daily doses of 100 mg of

minocycline. At the end of 6 months, all patients were clinically improved

with a slight reduction in the average bacterial index (BI) and logarithmic

index of bacilli in biopsy (LIB). The effects of minocycline on viability

by mouse foot pad inoculation and palmitic acid oxidation assays were noted

beginning at 10 to 14 days of daily dosing and becoming more definite after

30 days of treatment. Both tests correlated fairly well. Doses of 200 mg

daily did not appear to be more efficient than minocycline 100 daily.

Phenolic glycolipid-I (PGL-I) antigen determinations done on some patients

during the first month remained positive and did not correlate with changes

in viability results. At the end of 6 months, after 5 months of 100 mg of

minocycline monotherapy, no viable organisms could be demonstrated by mouse

foot pad inoculation and palmitic acid oxidation assays; assays for PGL-I

antigen were all negative.(ABSTRACT TRUNCATED AT 250 WORDS) 

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5.) Efficacy of minocycline in single dose and at 100 mg twice daily for

lepromatous leprosy. 

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Int J Lepr Other Mycobact Dis (United States), Dec 1994, 62(4) p568-73 

AUTHOR(S): Gelber RH; Murray LP; Siu P; Tsang M; Rea TH 

AUTHOR'S ADDRESS: San Francisco Regional Hansen's Disease Program, CA 94115. 

PUBLICATION TYPE: CLINICAL TRIAL; JOURNAL ARTICLE 

ABSTRACT: A clinical trial of minocycline in a total of 10 patients with

previously untreated lepromatous leprosy was conducted in order to evaluate

the efficacy of a single, initial, 200-mg dose and 100 mg twice daily of

minocycline for a total duration of up to 3 months. Patients improved

remarkably quickly. Although single-dose therapy did not result in a

significant killing of Mycobacterium leprae, viable M. leprae were cleared

from the dermis regularly by 3 months of twice-daily therapy, a rate

similar to that achieved by minocycline 100 mg once daily. Because more

side effects were noted herein than previously with 100 mg daily, we

recommend that minocycline, when applied, be administered at 100 mg daily

to leprosy patients. 

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6.) Field trial on efficacy of supervised monthly dose of 600 mg rifampin,

400 mg ofloxacin and 100 mg minocycline for the treatment of leprosy; first

results. 

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Author 

Mane I; Cartel JL; Grosset JH 

Address 

Institut de Leprologie Appliquee, Dakar CD Annexe, Senegal. 

Source 

Int J Lepr Other Mycobact Dis, 65(2):224-9 1997 Jun 

Abstract 

In 1995, a field trial was implemented in Senegal in order to evaluate the

efficacy of a regimen based on the monthly supervised intake of rifampin

600 mg, ofloxacin 400 mg and minocycline 100 mg to treat leprosy. During

the first year of the trial, 220 patients with active leprosy (newly

detected or relapsing after dapsone monotherapy) were recruited: 102

paucibacillary (PB) (60 males and 42 females) and 118 multibacillary (MB)

(71 males and 47 females). All of them accepted the new treatment (none

requested to be preferably put under standard WHO/MDT), no clinical sign

which could be considered as a toxic effect of the drug was noted, and none

of the patients refused to continue treatment because of any clinical

trouble. The compliance was excellent: the 113 patients (PB and MB)

detected during the first 6 months of the trial have taken six monthly

doses in 6 months, as planned. The rate of clearance and the progressive

decrease of cutaneous lesions was satisfactory. Although it is too soon to

give comprehensive results, it should be noted that no treatment failure

was observed in the 56 PB patients who have completed treatment and have

been followed up for 6 months. The long-term efficacy of the new regimen is

to be evaluated on the rate of relapse during the years following the

cessation of treatment. If that relapse rate is acceptable (similar to that

observed in patients after treatment with current standard WHO/ MDT), the

new regimen could be a solution to treat, for instance, patients very

irregular and/or living in remote or inaccessible areas since no selection

of rifampin-resistant Mycobacterium leprae should be possible (a monthly

dose of ofloxacin and minocycline being as effective as a dose of dapsone

and clofazimine taken daily for 1 month). Nevertheless, until longer term

results of this and other trials become available, there is no

justification for any change in the treatment strategy, and all leprosy

patients should be put under standard WHO/MDT. 

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7.) Bactericidal activity of a single-dose combination of ofloxacin plus

minocycline, with or without rifampin, against Mycobacterium leprae in mice

and in lepromatous patients. 

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Author 

Ji B; Sow S; Perani E; Lienhardt C; Diderot V; Grosset J 

Address 

Facult´e de M´edecine Piti´e-Salp^etri`ere, Paris, France.

bacterio@biomath.jussieu.fr 

Source 

Antimicrob Agents Chemother, 42(5):1115-20 1998 May 

Abstract 

To develop a fully supervisable, monthly administered regimen for treatment

of leprosy, the bactericidal effect of a single-dose combination of

ofloxacin (OFLO) and minocycline (MINO), with or without rifampin (RMP),

against Mycobacterium leprae was studied in the mouse footpad system and in

previously untreated lepromatous leprosy patients. Bactericidal activity

was measured by the proportional bactericidal method. In mouse experiments,

the activity of a single dose of the combination OFLO-MINO was dosage

related; the higher dosage of the combination displayed bactericidal

activity which was significantly inferior to that of a single dose of RMP,

whereas the lower dosage did not exhibit a bactericidal effect. In the

clinical trial, 20 patients with previously untreated lepromatous leprosy

were treated with a single dose consisting of either 600 mg of RMP plus 400

mg of OFLO and 100 mg of MINO or 400 mg of OFLO plus 100 mg of MINO. The

OFLO-MINO combination exhibited definite bactericidal activity in 7 of 10

patients but was less bactericidal than the RMP-OFLO-MINO combination. Both

combinations were well tolerated. Because of these promising results, a

test of the efficacy of multiple doses of ROM in a larger clinical trial

appears justified. 

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8.) Efficacy of single dose multidrug therapy for the treatment of

single-lesion paucibacillary leprosy. Single-lesion Multicentre Trial Group. 

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Source 

Indian J Lepr, 69(2):121-9 1997 Apr-Jun 

Abstract 

A multicentre double-blind controlled clinical trial was carried out to

compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin

400 mg plus minocycline 100 mg (ROM) administered as single dose with that

of the standard six-month WHO/MDT/PB regimen. The subjects included 1483

cases with one skin lesion who were previously untreated, were

smear-negative, and had no evidence of peripheral nerve trunk involvement,

and they were randomly divided into study and control groups. The total

duration of the study from the day of intake was 18 months, and 1381

patients completed study. Only 12 patients were categorized as treatment

failure and no difference was observed between the two regimens. Occurrence

of mild side-effects and leprosy reactions were minimal (less than 1%) in

both groups. This study showed that ROM is almost as effective as the

standard WHO/MDT/PB in the treatment of single lesion PB leprosy. 

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9.) Bactericidal activity of single dose of clarithromycin plus

minocycline, with or without ofloxacin, against Mycobacterium leprae in

patients. 

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Author 

Ji B; Jamet P; Perani EG; Sow S; Lienhardt C; Petinon C; Grosset JH 

Address 

Facult´e de M´edecine Piti´e-Salp^etri`ere, Paris, France. 

Source 

Antimicrob Agents Chemother, 40(9):2137-41 1996 Sep 

Abstract 

Fifty patients with newly diagnosed lepromatous leprosy were allocated

randomly to one of five groups and treated with either a month-long

standard regimen of multidrug therapy (MDT) for multibacillary leprosy, a

single dose of 600 mg of rifampin, a month-long regimen with the dapsone

(DDS) and clofazimine (CLO) components of the standard MDT, or a single

dose of 2,000 mg of clarithromycin (CLARI) plus 200 mg of minocycline

(MINO), with or without the addition of 800 mg of ofloxacin (OFLO). At the

end of 1 month, clinical improvement accompanied by significant decreases

of morphological indexes in skin smears was observed in about half of the

patients of each group. A significant bactericidal effect was demonstrated

in the great majority of patients in all five groups by inoculating the

footpads of mice with organisms recovered from biopsy samples obtained

before and after treatment. Rifampin proved to be a bactericidal drug

against Mycobacterium leprae more potent than any combination of the other

drugs. A single dose of CLARI-MINO, with or without OFLO, displayed a

degree of bactericidal activity similar to that of a regimen daily of doses

of DDS-CLO for 1 month, suggesting that it may be possible to replace the

DDS and CLO components of the MDT with a monthly dose of CLARI-MINO, with

or without OFLO. However, gastrointestinal adverse events were quite

frequent among patients treated with CLARI-MINO, with or without OFLO, and

may be attributed to the higher dosage of CLARI or MINO or to the

combination of CLARI-MINO plus OFLO. In future trials, therefore, we

propose to reduce the dosages of the drugs to 1,000 mg of CLARI, 100 mg of

MINO, and 400 mg of OFLO. 

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10.) WHO Expert Committee on Leprosy. 

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Source: World Health Organ Tech Rep Ser, 874():1-43 1998 

Abstract 

Considerable progress has been made in the fight against leprosy during the

past 10-15 years, following the introduction of multidrug therapy (MDT)

regimens and the establishment of the goal of eliminating leprosy as a

public health problem by the year 2000. Current estimates indicate that

there are about 1.15 million cases of leprosy in the world, compared with

10-12 million cases in the mid-1980s. This report presents the conclusions

of a WHO Expert Committee convened to review the global leprosy situation

and the technology available for eliminating the disease, to identify the

remaining obstacles to reaching the goal of eliminating leprosy as a public

health problem, and to make appropriate recommendations for the future on

technical and operational matters. The current status of leprosy

elimination is discussed, and the various antileprosy drugs are reviewed,

including the most recently available drugs. On the basis of field trials

and clinical studies, the Committee concludes that a single dose of a

combination of rifampicin, ofloxacin and minocycline is an acceptable and

cost-effective alternative regimen for the treatment of single-lesion

paucibacillary leprosy, and that the duration of the current MDT regimen

for multibacillary leprosy could possibly be shortened to 12 months. The

Committee points out the need for improved management of reactions and

neuritis and prevention of leprosy-related disabilities and impairments,

and recommends that antileprosy activities should become an integral part

of general health services and should involve communities to the fullest

extent possible. 

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11.) Experimental evaluation of possible new short-term drug regimens for

treatment of multibacillary leprosy. 

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Author 

Banerjee DK; McDermott-Lancaster RD; McKenzie S 

Address 

Department of Medical Microbiology, St George's Hospital Medical School,

London, United Kingdom. banerjee@sghms.ac.uk. 

Source 

Antimicrob Agents Chemother, 41(2):326-30 1997 Feb 

Abstract 

Groups of nude mice, with both hind footpads infected with 10(8)

Mycobacterium leprae organisms, were treated with 4-week courses of

different drug combinations. The effect treatment on each group was

evaluated by subinoculating footpad homogenates from the treated mice into

groups of normal and nude mice for subsequent regrowth, assessed 1 year

later. A combination of rifampin (RMP) with clarithromycin (CLARI),

minocycline (MINO), and ofloxacin (OFLO) resulted in the complete killing

of M. leprae after 3 weeks of treatment. A combination of sparfloxacin

(SPAR) and RMP also resulted in a similar bactericidal effect after 3 weeks

of treatment. Other drug combinations showed variable effects. Very little

or no effect was observed with any regimen if the treatment was given for

less than 2 weeks. World Health Organization (WHO) multidrug therapy (MDT)

given for 8 weeks was as effective as the two combinations described above.

The results suggest that multidrug combinations consisting of RMP-OFLO (or

SPAR)-CLARI (and/or MINO) are as effective as the WHO MDT for the treatment

of experimental leprosy. Moreover, they imply that these combinations,

which were found to be active in a 4-week experimental treatment protocol,

could be administered as treatment to patients for a period of time shorter

than the present 2-year regimen without a loss of effectiveness. 

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12.) Powerful bactericidal activities of clarithromycin and minocycline

against Mycobacterium leprae in lepromatous leprosy. 

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ARTICLE SOURCE: J Infect Dis (United States), Jul 1993, 168(1) p188-90 

AUTHOR(S): Ji B; Jamet P; Perani EG; Bobin P; Grosset JH 

AUTHOR'S ADDRESS: Faculte de Medecine Pitie-Salpetriere, Paris, France. 

PUBLICATION TYPE: CLINICAL TRIAL; JOURNAL ARTICLE; RANDOMIZED CONTROLLED

TRIAL 

ABSTRACT: Thirty-six patients with newly diagnosed lepromatous leprosy

were allocated randomly to three groups and treated for 56 days with

minocycline (100 mg daily), clarithromycin (500 mg daily), or

clarithromycin (500 mg) plus minocycline (100 mg daily). All groups had

rapid and remarkable clinical improvement and significant decline of the

bacterial and morphologic indices in skin smears during treatment. More

than 99% and 99.9% of the viable Mycobacterium leprae had been killed by 28

and 56 days of treatment, respectively, as measured by inoculation of

organisms recovered from skin samples, taken before and during treatment,

into the footpads of immunocompetent and nude mice. Clinical improvement

and bactericidal activity did not differ significantly among the three

groups. Adverse reactions were rare and mild, and no laboratory abnormality

was detected during the trial. Both clarithromycin and minocycline

displayed powerful bactericidal activities against M. leprae in leprosy

patients and may be considered important components of new multidrug

regimens for the treatment of multibacillary leprosy. 

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13.) Minocycline is a useful adjuvant therapy for pemphigus. 

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Author 

Gaspar ZS; Walkden V; Wojnarowska F 

Address 

Department of Dermatology, Churchill, Oxford Radcliffe Hospital,

Headington, UK. 

Source 

Australas J Dermatol, 37(2):93-5 1996 May 

Abstract 

Pemphigus is an autoimmune blistering disease with high mortality if

untreated. The cases of 10 patients who had minocycline 100 mg daily added

as adjuvant therapy are reported. Prior to the use of minocycline, all

patients had active disease, nine were on prednisolone (10-40 mg) and five

were on azathioprine (100-200 mg). The response was assessed on clinical

improvement and reduction of immunosuppressive (IS) drugs. It was graded

into four categories: major, minor, equivocal and no significant response.

A major response was seen in four patients, minor in two, equivocal in one

and no improvement in three patients. The prednisolone dose in the six

responders was reduced to 0-6 mg (0 mg in three patients), with an average

decrease of 21 mg. The average time to respond was 8 months. Of the six

responders, three were on azathioprine, which was ceased in two patients

and reduced by two-thirds in the other patient. No patient ceased

minocycline because of side effects. In conclusion, minocycline 100 mg

daily is a simple, safe and well tolerated treatment that should be tried

in patients with pemphigus to reduce disease activity and/or the dose of

potent IS agents. 

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14.) Confluent and reticulated papillomatosis: response to minocycline. 

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Author 

Montemarano AD; Hengge M; Sau P; Welch M 

Address 

Department of Dermatology, Walter Reed Army Medical Center, Washington, DC

20307, USA. 

Source 

J Am Acad Dermatol, 34(2 Pt 1):253-6 1996 Feb 

Abstract 

BACKGROUND: Confluent and reticulated papillomatosis (CRP) of Gougerot and

Carteaud is an uncommon disorder of unknown cause for which a variety of

treatments have been proposed. OBJECTIVE: We attempted to evaluate the

effectiveness of oral minocycline. METHODS: Nine patients with CRP were

treated with oral minocycline, 50 mg twice a day, for 6 weeks. The average

follow-up period was 11 months. Recurrence rate, side effects, and

effectiveness of therapy were assessed. RESULTS: All patients except two

had a 90% to 100% response to therapy. Recurrences were noted in three

patients, all of whom responded to re-treatment with minocycline. None of

the nine patients had an adverse reaction. CONCLUSION: Minocycline, 50 mg

twice a day, is safe and effective for CRP. 

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15.) Minocycline treatment for confluent and reticulated papillomatosis. 

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Author 

Chang SN; Kim SC; Lee SH; Lee WS 

Address 

Department of Dermatology, Yonsei University College of Medicine, Seoul,

Korea. 

Source 

Cutis, 57(6):454-7 1996 Jun 

Abstract 

We report six cases of confluent and reticulated papillomatosis in which

the skin lesions cleared almost completely after treatment with

minocycline. Patients with confluent and reticulated papillomatosis often

do not respond well to a variety of therapeutic agents. The response of

confluent and reticulated papillomatosis to minocycline was first described

in 1965. Although the pharmacologic mechanisms of minocycline in confluent

and reticulated papillomatosis are unknown, we suggest that it should be

considered as a first-choice therapeutic agent because of its marked

effectiveness. 

=========================================================================

16.) No detection of Borrelia burgdorferi-specific DNA in erythema migrans

lesions after minocycline treatment. 

=========================================================================

ARTICLE SOURCE: Arch Dermatol (United States), Jun 1995, 131(6) p678-82 

AUTHOR(S): Muellegger RR; Zoechling N; Soyer HP; Hoedl S; Wienecke R;

Volkenandt M; Kerl H 

AUTHOR'S ADDRESS: Department of Dermatology, Karl-Franzens University,

Graz, Austria. 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: BACKGROUND AND DESIGN: Early treatment of erythema migrans is

important to prevent late complications. Minocycline possesses several

attributes, making it potentially useful in the treatment of borrelial

infections. In our study, minocycline was administered to 14 patients with

erythema migrans. Punch biopsy specimens were obtained from the (affected)

skin of all patients before and after therapy. The formalin-fixed,

paraffin-embedded specimens were analyzed by polymerase chain reaction for

the presence of Borrelia burgdorferi-specific DNA. RESULTS: Polymerase

chain reaction assay succeeded in amplifying B burgdorferi-specific DNA

from the first biopsy specimen, obtained from the border of erythema

migrans before initiating treatment, in eight (57%) of 14 patients. At the

end of minocycline therapy, however, polymerase chain reaction analysis

disclosed no B burgdorferi-specific DNA in any of the 14 patients. The good

clinical response of our patients with erythema migrans substantiates our

molecular findings. CONCLUSIONS: The presented polymerase chain reaction

data, together with the clinical outcome, indicate that minocycline may be

useful for treatment of early Lyme borreliosis. 

=========================================================================

17.) Minimizing cicatricial pemphigoid orodynia with minocycline. 

=========================================================================

ARTICLE SOURCE: Br J Dermatol (England), May 1995, 132(5) p784-9 

AUTHOR(S): Poskitt L; Wojnarowska F 

AUTHOR'S ADDRESS: Dermatology Department, Amersham General Hospital,

Bucks, U.K. 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: Cicatricial pemphigoid is a rare autoimmune blistering disease

of the elderly. It predominantly affects the mucosae, causing pain and

scarring. the target antigen is within the lamina lucida of the basement

membrane zone. Potential complications of systemic steroid and other

immunosuppressive therapy have prompted trials of other means of treatment.

We describe a series of seven patients treated with minocycline, six of

whom derived sustained alleviation of orodynia. Four patients developed

hyperpigmentation, and two complained of gastrointestinal discomfort which

necessitated cessation of minocycline. Complete steroid withdrawal was

achieved in two cases. Neither the disease progression nor the response to

treatment was influenced by the immunoglobulin isotype or titre. The role

of minocycline as a useful adjunct to therapy is discussed. 

=========================================================================

18.) Response of atypical bullous pyoderma gangrenosum to oral minocycline

hydrochloride and topical steroids. 

=========================================================================

ARTICLE SOURCE: Acta Derm Venereol (Sweden), 1990, 70(6) p538-9 

AUTHOR(S): Reynolds NJ; Peachey RD 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: An 80-year-old Caucasian female with rheumatoid arthritis and

recurrent atypical bullous pyoderma gangrenosum is described. There was no

evidence of any underlying myeloproliferative disorder. Rapid healing

occurred in response to oral minocycline hydrochloride and topical

clobetasol propionate. 

=========================================================================

19.) Blastomycosis-like pyoderma--report of a case responsive to

combination therapy utilizing minocycline and carbon dioxide laser

debridement. 

=========================================================================

ARTICLE SOURCE: J Dermatol Surg Oncol (United States), Oct 1986, 12(10)

p1041-4 

AUTHOR(S): Sawchuk WS; Heald PW 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: Blastomycosis-like pyoderma is an uncommon reaction pattern to a

superficial bacterial infection in persons with a variety of predisposing

conditions such as chronic ethanol use and poor nutrition. We are reporting

a case that initially responded poorly to previously described treatment

regimens but responded well to combination treatment with carbon dioxide

laser debridement and long-term minocycline. 

=========================================================================

20.) A sporotrichoid-like Mycobacterium kansasii infection of the skin

treated with minocycline hydrochloride. 

=========================================================================

ARTICLE SOURCE: Br J Dermatol (England), Jul 1979, 101(1) p75-9 

AUTHOR(S): Dore N; Collins JP; Mankiewicz E 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: A sporotrichoid-like Mycobacterium kansasii infection of the

skin is reported. This is the fifth reported case in the English literature

of dermatological manifestations of a M. kansasii infection and the first

reported case of a response to minocycline hydrochloride therapy. 

=========================================================================

21.) Primary lymphocutaneous nocardiosis due to Nocardia otitidiscaviarum:

the first case report from Japan. 

=========================================================================

ARTICLE SOURCE: J Dermatol (Japan), May 1995, 22(5) p344-7 

AUTHOR(S): Suzuki Y; Toyama K; Utsugi K; Yazawa K; Mikami Y; Fujita M;

Shinkai H 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: We report a case of lymphocutaneous syndrome caused by Nocardia

otitidiscaviarum (formerly known as N. caviae) in a 78-year-old woman who

underwent long-term therapy with prednisolone for bronchial asthma.

Histological examination showed granulomatous reaction with multiple

polymorphonuclear leukocytes and revealed a Gram positive filament in the

dermis. Gram-positive, slightly acid-fast branched filaments were also

found in the smear of the purulent material. The cell wall constituents of

the isolate were meso-diaminopimelic acid, arabinose, and galactose; the

mycolic acid pattern of the isolate was Nocardia type. The organism

decomposed xanthine and hypoxanthine, but not tyrosine or casein, which

distinguished it from N. asteroides and N. brasiliensis. The skin lesions

responded to minocycline and later to a combination of doxycycline and

ofloxacin. This primary lymphocutaneous nocardiosis due to N.

otitidiseaviarum is the first in Japan. 

=========================================================================

22.) Minocycline treatment of pulmonary nocardiosis. 

=========================================================================

ARTICLE SOURCE: JAMA (United States), Aug 19 1983, 250(7) p930-2 

AUTHOR(S): Petersen EA; Nash ML; Mammana RB; Copeland JG 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: Minocycline hydrochloride was used to treat pulmonary infections

with Nocardia asteroides in five cardiac allograft recipients. In three

patients, minocycline was successfully used as the only antinocardial

agent. Two other patients were found to have leukopenia after initial

therapy with sulfisoxazole. These two patients were subsequently treated

with minocycline. The clinical success with minocycline in these highly

immunosuppressed patients suggests that minocycline is an effective

antinocardial agent. These data did not allow any conclusion regarding

which drug, minocycline or sulfisoxazole, is superior in the treatment of

this disease. 

=========================================================================

23.) Minocycline in rheumatoid arthritis. A 48-week, double-blind,

placebo-controlled trial. MIRA Trial Group [see comments] 

=========================================================================

Author 

Tilley BC; Alarc´on GS; Heyse SP; Trentham DE; Neuner R; Kaplan DA; Clegg

DO; Leisen JC; Buckley L; Cooper SM; et al 

Address 

Henry Ford Health Sciences Center, Detroit, Michigan. 

Source 

Ann Intern Med, 122(2):81-9 1995 Jan 15 

Abstract 

OBJECTIVE: To assess the safety and efficacy of minocycline in the

treatment of rheumatoid arthritis. DESIGN: A double-blind, randomized,

multicenter, 48-week trial of oral minocycline (200 mg/d) or placebo.

SETTING: 6 clinical centers in the United States. PATIENTS: 219 adults with

active rheumatoid arthritis who had previous limited treatment with

disease-modifying drugs. MEASUREMENTS: As the primary outcomes, 60

diarthrodial joints were examined for tenderness, and 58 joints were

examined for swelling (hips excluded). Grip strength, evaluator's global

assessment, morning stiffness, Modified Health Assessment Questionnaire,

patient's global assessment, hematocrit, erythrocyte sedimentation rate,

platelet count, and IgM rheumatoid factor levels were also assessed;

radiographs of both hands and wrists were taken. RESULTS: 109 and 110

patients were randomly assigned to receive minocycline and placebo,

respectively. At entry, demographic, clinical, and laboratory measurements

were similar in both groups. Most patients had mild to moderate disease

activity and some evidence of destructive disease. At the week 48 visit,

79% of the minocycline group and 78% of the placebo group continued to

receive the study medication. At 48 weeks, more patients in the minocycline

group than in the placebo group showed improvement in joint swelling (54%

and 39%) and joint tenderness (56% and 41%) (P < 0.023 for both

comparisons). The minocycline group also showed greater improvement in

hematocrit, erythrocyte sedimentation rate, platelet count, and IgM

rheumatoid factor levels (all P values < 0.001), and more patients

receiving minocycline had laboratory values within normal ranges at 48

weeks. For the remaining outcomes, P values ranged from 0.04 to 0.76, all

greater than the critical value of 0.005 (Bonferroni adjustment for

multiple comparisons). The frequency of reported side effects was similar

in both groups, and no serious toxicity occurred. CONCLUSIONS: Minocycline

was safe and effective for patients with mild to moderate rheumatoid

arthritis. Its mechanisms of action remain to be determined. 

=========================================================================

24.) Minocycline prevents the decrease in bone mineral density and

trabecular bone in ovariectomized aged rats. 

=========================================================================

Author 

Williams S; Wakisaka A; Zeng QQ; Barnes J; Martin G; Wechter WJ; Liang CT 

Address 

Gerontology Research Center, National Institute of Aging, National

Institutes of Health, Baltimore, MD 21224, USA. 

Source 

Bone, 19(6):637-44 1996 Dec 

Abstract 

In the current study, we examined the effects of minocycline, on the

osteopenia of ovariectomized aged rats. Old female rats were randomly

divided into five groups: sham, ovariectomized control and ovariectomized

treated with minocycline, 17beta-estradiol, or both agents. Bone samples

were collected 8 wk after the treatment. Ovariectomy reduced bone mineral

density of the whole femur and at the condylar, distal metaphyseal and

head-neck-trochanter regions 10%-19% and the loss of bone density was

prevented by treatment with minocycline or 17beta-estradiol.

Histomorphometric analysis of distal femur showed ovariectomy reduced the

trabecular bone area, the trabecular bone number, trabecular bone thickness

and increased the trabecular bone separation. The microanatomic structure

of trabecular bone also showed that the number of nodes, node to node,

cortical to node, node to free end was reduced by ovariectomy. Treatment

with minocycline attenuated the effect of ovariectomy on trabecular bone in

aged animals. In contrast, cortical bone was not affected by ovariectomy or

minocycline treatment. The effect of minocycline on bone turnover was also

examined. Minocycline increased osteoid surface, mineralizing surface,

mineral apposition rate, bone formation rate and reduced eroded surface. We

have therefore concluded that the modest increase in bone mineral density

and the improvement in the trabecular bone status noted in minocycline

treated ovariectomized aged rats is likely due to an increase in bone

formation coupled with a decrease in bone resorption. 

=========================================================================

25.) Minocycline and cefotaxime in the treatment of experimental murine

Vibrio vulnificus infection. 

=========================================================================

Author 

Chuang YC; Ko WC; Wang ST; Liu JW; Kuo CF; Wu JJ; Huang KY 

Address 

Department of Internal Medicine, National Cheng Kung University Hospital,

Tainan, Taiwan. 

Source 

Antimicrob Agents Chemother, 42(6):1319-22 1998 Jun 

Abstract 

We conducted an in vivo study with the mouse model of Vibrio vulnificus

infection to evaluate the efficacies of therapy with minocycline or

cefotaxime alone and in combination. V. vulnificus was introduced

subcutaneously into the area over the right thigh. The inoculum size ranged

from 1.0 x 10(3) to 1.2 x 10(8) CFU from experiment to experiment but was

constant for all animals in the same experiment. Antibiotics were given

intraperitoneally 2 h after the bacteria were inoculated. In experiments 1

to 4, the standard dose for humans was used to treat the infection, while

in experiment 5, five times the standard dose for humans was used to treat

the infection. In experiment 1, with a small inoculum of 5 x 10(3) CFU, all

mice in the saline-treated control group and the cefotaxime-, minocycline-,

and combined antibiotic-treated groups survived. In experiment 2, with a

moderate inoculum of 1.2 x 10(5) CFU, all the mice in the three

antibiotic-treated groups survived, while only two of nine mice in the

control group survived. In experiment 3, with a large inoculum of 8.0 x

10(7) CFU, six of nine mice in the combined antibiotic-treated group

survived, while only one of nine mice in the cefotaxime-treated group and

none of the mice in the control and minocycline-treated groups survived. In

experiment 4, with a large inoculum of 1.2 x 10(8) CFU, 8 of 20 mice in the

combined antibiotic-treated group survived, while none of the 20 mice in

the control group, the group treated with cefotaxime alone, and the group

treated with minocycline alone survived. In experiment 5, in which mice

were infected with a large inoculum of 6.6 x 10(7) CFU and treated with

five times the standard human dose of antibiotics, 10 of 12 mice in the

combined antibiotic-treated group survived, while only 4 of 12 mice in the

minocycline-treated group, 1 of 12 mice in the cefotaxime-treated group,

and none of the mice in the control group survived. In experiments 3 to 5,

the difference in the survival rates between the combined

antibiotic-treated and minocycline-treated groups was statistically

significant (P < 0.05). These results indicate that combination therapy

with cefotaxime and minocycline is distinctly more advantageous than

therapy with the single antibiotic regimen for the treatment of severe

experimental V. vulnificus infections. 

=========================================================================

26.) The role of minocycline in the treatment of intracranial 9L glioma. 

=========================================================================

Author 

Weingart JD; Sipos EP; Brem H 

Address 

Department of Neurological Surgery, Johns Hopkins University School of

Medicine, Baltimore, Maryland. 

Source 

J Neurosurg, 82(4):635-40 1995 Apr 

Abstract 

This study was designed to explore the question of whether minocycline, a

semisynthetic tetracycline shown to inhibit tumor-induced angiogenesis,

could control the growth of the rat intracranial 9L gliosarcoma.

Minocycline was tested alone and in combination with

1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in vivo. Treatment was started

at the time of intracranial implantation of 9L gliosarcoma into male

Fischer 344 rats, 5 days later, or after tumor resection. Minocycline was

delivered locally with a controlled-release polymer or systemically by

intraperitoneal injection. Systemic minocycline did not extend survival

time. Local treatment with minocycline by a controlled-release polymer

implanted at the time of tumor implantation extended median survival time

by 530% (p < 0.001) compared to treatment with empty polymer. When

treatment was begun 5 days after tumor implantation, minocycline delivered

locally or systemically had no effect on survival. However, after tumor

resection, treatment with locally delivered minocycline resulted in a 43%

increase in median survival time (p < 0.002) compared to treatment with

empty polymer. Treatment with a combination of minocycline delivered

locally in a controlled-release polymer and systemic BCNU 5 days after

tumor implantation resulted in a 93% extension of median survival time

compared to BCNU alone (p < 0.002). In contrast, treatment with a

combination of systemic minocycline and BCNU did not increase survival time

compared to systemic BCNU alone. These results demonstrate that minocycline

affects tumor growth when delivered locally and suggest that minocycline

may be a clinically effective modulator of intracranial tumor growth when

used in combination with a chemotherapeutic agent and surgical resection. 

=========================================================================

27.) Evaluation of the long-term efficacy and safety of locally-applied

minocycline in adult periodontitis patients. 

=========================================================================

Author 

Timmerman MF; van der Weijden GA; van Steenbergen TJ; Mantel MS; de Graaff

J; van der Velden U 

Address 

Department of Periodontology, Academic Centre for Dentistry, Amsterdam, The

Netherlands. 

Source 

J Clin Periodontol, 23(8):707-16 1996 Aug 

Abstract 

The objectives of the present study were to establish in a long-term

investigation the safety as well as the clinical and microbiological

efficacy of scaling and rootplaning combined with local application of 2%

minocycline hydrochloride-gel versus placebo-gel in patients with moderate

to severe chronic adult periodontitis. This was an 18 months, randomized,

double-blind, parallel, comparative study, in which 20 healthy patients

with moderate to severe chronic periodontitis participated. At baseline,

all patients received professional oral hygiene-instruction and supra- and

subgingival scaling and root planing. The minocycline-gel was applied

subgingivally baseline, 2 weeks, 1, 3, 6, 9 and 12 months. Microbiological

evaluation was carried out using DMDx to identify the following bacteria:

Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus

actinomycetemcomitans, Campylobacter rectus, Fusobacterium nucleatum and

Treponema denticola. In addition standard microbiological techniques were

used for the detection of P. gingivalis, P. intermedia, P. micros, A.

actinomycetemcomitans, C. rectus, F. nucleatum, C. albicans and

Enterobacteriaceae. Results showed a statistically significant improvement

for all clinical parameters irrespective of the treatment modality. No

differences were observed between test and control with regard to probing

depth and attachment level. The DMDx data showed a significant reduction in

both the numbers and the prevalence over the 15 months period, but no

significant difference between groups. Culture data showed that at baseline

two-third were positive for P. gingivalis and P. intermedia. Analysis over

the 18 month period showed no significant difference between the two

treatment modalities. C. albicans and Enterobacteriaceae were detected only

in small proportions at each time interval in a limited number of patients.

No adverse reactions were observed during the trial period. The present

patient group responded favourably to scaling and rootplaning, but did not

benefit from an effect of local of minocycline. Subgingival debridement in

combination with oral hygiene instruction by itself has been shown to be

effective. It remains to be studied whether local application of

minocycline can be effective as an adjunct to mechanical therapy in sites

that respond poorly to conventional treatment. 

=========================================================================

28.) Clinical and microbiological effects of minocycline-loaded

microcapsules in adult periodontitis. 

=========================================================================

Author 

Yeom HR; Park YJ; Lee SJ; Rhyu IC; Chung CP; Nisengard RJ 

Address 

Department of Periodontology, College of Dentistry, Seoul National

University, Korea. 

Source 

J Periodontol, 68(11):1102-9 1997 Nov 

Abstract 

Clinical and microbiological effects of subgingival delivery of 10%

minocycline-loaded (MC), bioabsorbable microcapsules were examined in 15

adult periodontitis patients. Patients received oral hygiene instruction 2

weeks prior to the study. At baseline (day 0) all teeth received

supragingival scaling (SC); 2 quadrants received no further treatment and 1

quadrant received subgingival scaling and root planning (SRP). In the

fourth quadrant, the tooth with the deepest probing sites (at least 1 site

> or = 5 mm) was treated with minocycline microcapsules. The sites were

evaluated at baseline and weeks 1, 2, 4, and 6. Clinical indices included

bleeding on probing (BOP), probing depths (PD), and attachment loss (AL).

Microbiological evaluations included percent morphotypes by phase-contrast

microscopy; cultivable anaerobic, aerobic, and black-pigmented Bacteroides

(BPB); and percent Porphyromonas gingivalis, Prevotella intermedia,

Eikenella corrodens, and Actinomyces viscosus by indirect

immunofluorescence. In the SC + MC group, BOP, PD, and AL were

significantly reduced from baseline for weeks 1 to 6. BOP in the SC + MC

group was significantly reduced compared to the SRP group from weeks 2 to

6. In the SC + MC group the percent of spirochetes and motile rods

decreased and the percent of cocci increased after 1 week. The increased

cocci and decreased motile rods were statistically greater at weeks 4 and 6

in the SC + MC group compared to the SRP group. This study demonstrates

that local subgingival delivery of 10% minocycline-loaded microcapsules as

an adjunct to scaling results in reduction in the percent sites bleeding on

probing greater than scaling and root planning alone and induces a

microbial response more favorable for periodontal health than scaling and

root planing. 

=========================================================================

29.) The broad-spectrum activity and efficacy of catheters coated with

minocycline and rifampin. 

=========================================================================

Author 

Raad I; Darouiche R; Hachem R; Mansouri M; Bodey GP 

Address 

Section of Infectious Diseases, University of Texas M. D. Anderson Cancer

Center, Houston 77030, USA. 

Source 

J Infect Dis, 173(2):418-24 1996 Feb 

Abstract 

The in vitro and in vivo activities of catheters coated with minocycline

and rifampin and with chlorhexidine gluconate and silver sulfadiazine were

evaluated. When incubated in serum at 37 degrees C, the half-life of the

inhibitory activity of catheters coated with minocycline and rifampin was

25 days compared with 3 days for catheters coated with chlorhexidine

gluconate and silver sulfadiazine. In a rabbit model, catheters coated with

minocycline and rifampin were significantly more efficacious than catheters

coated with chlorhexidine and silver sulfadiazine in preventing

colonization and infection with Staphylococcus aureus (P < .05). Catheters

coated with minocycline and rifampin demonstrated broad-spectrum in vitro

inhibitory activity against gram-positive bacteria, gram-negative bacteria,

and Candida albicans that was significantly superior to the inhibitory

activity of catheters coated with chlorhexidine gluconate and silver

sulfadiazine (P < .01). Minocycline and rifampin were also highly

efficacious in preventing colonization and infection in vivo. 

=========================================================================

30.) Symptomatic hepatic cysts: treatment with single-shot injection of

minocycline hydrochloride. 

=========================================================================

Author 

Cellier C; Cuenod CA; Deslandes P; Auroux J; Landi B; Siauve N; Barbier JP;

Frija G 

Address 

Department of Gastroenterology, Universit´e Ren´e Descartes, H^opital

Laennec, Paris, France. 

Source 

Radiology, 206(1):205-9 1998 Jan 

Abstract 

PURPOSE: To assess the efficacy of percutaneous minocycline hydrochloride

sclerotherapy in symptomatic hepatic cysts. MATERIALS AND METHODS: From

November 1992 to June 1994, seven of eight consecutive adults with large

symptomatic hepatic cysts (diameter, 55-130 mm) were treated with a single

intracystic injection of minocycline hydrochloride in an ambulatory

procedure. Five patients had a solitary cyst, and two had polycystic liver

disease. The target cyst was punctured under ultrasound guidance and local

anesthesia with a 22-gauge Chiba needle. Half of the cyst content was

aspirated before injection of 100-500 mg of minocycline hydrochloride

diluted in 5-25 mL of saline. The minocycline hydrochloride was left in the

cyst at the end of the procedure. RESULTS: After a mean follow-up of 28

months (range, 24-42 months), all five patients with solitary cysts were

asymptomatic and four had documented complete cyst regression; the two

patients with multiple hepatic cysts showed only transient clinical

improvement. CONCLUSION: Single-shot injection of minocycline hydrochloride

is an effective treatment for symptomatic solitary hepatic cysts but is

less effective in polycystic liver disease. 

=========================================================================

()()()()()()()()()()( LO MALO () THE BAD ()()()()()()()()()()()()()()()()

=========================================================================

31.) Minocycline induced autoimmune hepatitis and systemic lupus

erythematosus-like syndrome [see comments] 

=========================================================================

Author 

Gough A; Chapman S; Wagstaff K; Emery P; Elias E 

Address 

Department of Rheumatology, Harrogate District Hospital. 

Source 

BMJ, 312(7024):169-72 1996 Jan 20 

Abstract 

Monocycline is the most widely prescribed systemic antibiotic for acne

largely because it needs to be given only once or twice a day and seems not

to induce resistance. Up to April 1994 11 cases of minocycline induced

systemic lupus erythematosus and 16 cases of hepatitis had been reported to

the Committee on Safety of Medicines. An analysis of these cases together

with seven other cases shows the severity of some of these reactions. Two

patients died while taking the drug for acne and a further patient needed a

liver transplant. Acne itself can induce arthritis and is often seen in

association with autoimmine liver disease, but the clinical and biochemical

resolution seen after withdrawal of the drug, despite deterioration of the

acne, suggests a drug reaction. In five cases re-exposure led to

recurrence. Because reactions may be severe early recognition is important

to aid recovery and also to avoid invasive investigations and treatments

such as corticosteroids and immunosuppresants. Safer alternatives should be

considered for treating acne. 

=========================================================================

32.) Minocycline and Lupuslike Syndrome in Acne Patients 

=========================================================================

Miriam C. J. M. Sturkenboom, PhD, PharmD, MSc; Christoph R. Meier, PhD,

MSc; Hershel Jick, MD; Bruno H. C. Stricker, PhD, MB 

Arch Intern Med. 1999;159:493-497

Background: Recently several case reports described the association between

minocycline and lupuslike syndrome. Minocycline, one of

the tetracyclines, is widely used to treat acne. We aimed to examine the

association of exposure to minocycline and other tetracyclines with the

development

of lupuslike syndrome. 

Methods: We conducted a nested case-control study in a cohort of 27,688 acne

patients aged 15 to 29 years, using data automatically recorded on general

practitioners' office computers in the United Kingdom. Controls were matched

to cases on age, sex, and practice. The main outcome was lupuslike syndrome

defined as the occurrence of polyarthritis or polyarthralgia of unknown

origin,

with negative rheumatoid factor or latex agglutination test, positive or

unmeasured antinuclear factor, elevated or unmeasured erythrocyte

sedimentation rate, and absence of or unmeasured antinative DNA antibody

levels. 

Results: We identified 29 cases and selected 152 controls. Current single

use of

minocycline was associated with an 8.5-fold (95% confidence interval [CI],

2.1-35) increased risk of developing lupuslike syndrome compared with

nonusers and past users of tetracyclines combined. The risk of past

exposure to

any of the tetracyclines was closely similar to nonuse (relative risk, 1.3;

95%

CI, 0.5-3.3). Current use of doxycycline, oxytetracycline, or tetracycline

combined was associated with a 1.7-fold (95% CI, 0.4-8.1) increase of risk.

The

risk increased with longer use. 

Conclusion: Current use of minocycline increased the risk of developing

lupuslike syndrome 8.5-fold in the cohort of young acne patients. The

effect was

stronger in longer-term users. However, the absolute risk of developing

lupuslike syndrome seems to be relatively low. 

=========================================================================

33.) Minocycline-induced lupus. 

=========================================================================

Author 

Farver DK 

Address 

College of Pharmacy, South Dakota State University, Brookings, USA.

dfarver@sunflowr.usd.edu 

Source 

Ann Pharmacother, 31(10):1160-3 1997 Oct 

Abstract 

OBJECTIVE: To report a case of drug-induced lupus occurring 5 months after

the initiation of minocycline therapy for acne. DATA SOURCE: Case report

information was obtained from the physician, patient's family, and the

medical record. MEDLINE and Index Medicus were searched to obtain relevant

published literature from 1966 to 1996. CASE SUMMARY: A 14-year-old white

girl developed symptoms of myalgias, arthralgias, polyarthritis, and

flushed face. The antinuclear antibody test was positive. Minocycline was

discontinued and the patient's condition dramatically improved within 7

days. CONCLUSIONS: Healthcare providers should recognize early common and

unusual symptoms of minocycline-induced lupus in adolescents being treated

for acne. 

=========================================================================

34.) Minocycline related lupus. 

=========================================================================

Author 

Masson C; Chevailler A; Pascaretti C; Legrand E; Br´egeon C; Audran M 

Address 

Service de Rhumatologie, CHU d'Angers, France. 

Source 

J Rheumatol, 23(12):2160-1 1996 Dec 

Abstract 

The determination of a factor triggering lupus-like symptoms could yield

new insights into the management of rheumatic disease. We describe a case

of minocycline related lupus in a young patient positive for HLA-DR2 who

was prescribed minocycline 4 times for mild acne and developed rheumatic

symptoms each time. We review 8 other cases. 

=========================================================================

35.) Acute hepatitis and drug-related lupus induced by minocycline treatment. 

=========================================================================

Author 

Golstein PE; Deviere J; Cremer M 

Address 

Department of Gastroenterology, Erasmus Hospital, Universit´e Libre de

Bruxelles, Belgium. 

Source 

Am J Gastroenterol, 92(1):143-6 1997 Jan 

Abstract 

Minocycline is widely prescribed for long-term treatment in acne. Major

side effects are rare and include hepatitis and drug-related lupus.

Hepatitis can be early and acute or late and chronic, whereas lupus

presents as a tardive and insidious disease. We report a case of

minocycline-induced lupus initially presenting as acute hepatitis, evolving

to chronic cytolysis, in a young man treated for facial acne. 

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36.) Minocycline-induced pneumonitis with bilateral hilar lymphadenopathy

and pleural effusion. 

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ARTICLE SOURCE: Intern Med (Japan), Mar 1994, 33(3) p177-9 

AUTHOR(S): Bando T; Fujimura M; Noda Y; Hirose J; Ohta G; Matsuda T 

PUBLICATION TYPE: JOURNAL ARTICLE; REVIEW (12 references); REVIEW, 

ABSTRACT: A 65-year-old man developed respiratory failure with diffuse

interstitial shadow, bilateral pleural effusion, and bilateral hilar

lymphadenopathy on chest X-ray and CT, after intravenous administration of

minocycline. Corticosteroid therapy was effective. The findings from

bronchoalveolar lavage (BAL) and transbronchial lung biopsy were compatible

with eosinophilic pneumonia. Provocation test supported this diagnosis, but

the lymphocyte stimulation test was negative. A review of the literature

and the diagnoses of drug-induced pulmonary diseases are discussed. 

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37.) Comparative safety of tetracycline, minocycline, and doxycycline. 

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Author 

Shapiro LE; Knowles SR; Shear NH 

Address 

Department of Medicine, Sunnybrook Hospital, University of Toronto Medical

School, Ontario, Canada. 

Source 

Arch Dermatol, 133(10):1224-30 1997 Oct 

Abstract 

BACKGROUND: Because minocycline can cause serious adverse events including

hypersensitivity syndrome reaction (HSR), serum sicknesslike reaction

(SSLR), and drug-induced lupus, a follow-up study based on a retrospective

review of our Drug Safety Clinic and the Health Protection Branch databases

and a literature review was conducted to determine if similar rare events

are associated with tetracycline and doxycycline. Cases of isolated single

organ dysfunction (SOD) attributable to the use of these antibiotics also

were identified. OBSERVATIONS: Nineteen cases of HSR due to minocycline, 2

due to tetracycline, and 1 due to doxycycline were identified. Eleven cases

of SSLR due to minocycline, 3 due to tetracycline, and 2 due to doxycycline

were identified. All 33 cases of drug-induced lupus were attributable to

minocycline. Forty cases of SOD from minocycline, 37 cases from

tetracycline, and 6 from doxycycline were detected. Hypersensitivity

syndrome reaction, SSLR, and SOD occur on average within 4 weeks of

therapy, whereas minocycline-induced lupus occurs on average 2 years after

the initiation of therapy. CONCLUSIONS: Early serious events occurring

during the course of tetracycline antibiotic treatment include HSR, SSLR,

and SOD. Drug-induced lupus, which occurs late in the course of therapy, is

reported only with minocycline. We theorize that minocycline metabolism may

account for the increased frequency of serious adverse events with this drug. 

=========================================================================

38.) Serious adverse reactions induced by minocycline. Report of 13

patients and review of the literature. 

=========================================================================

Author 

Knowles SR; Shapiro L; Shear NH 

Address 

Division of Clinical Pharmacology, Sunnybrook Health Science Centre,

Toronto, Ontario. 

Source 

Arch Dermatol, 132(8):934-9 1996 Aug 

Abstract 

BACKGROUND: Minocycline has been reported to cause serious, albeit rare,

adverse events, including serum sickness-like reaction, hypersensitivity

syndrome reaction, and drug-induced lupus. A retrospective review of

patients seen in our Adverse Drug Reaction Clinic as well as information

obtained from the Health Protection Branch was done to identify patients

with minocycline-induced reactions. In addition, the literature concerning

serious reactions to minocycline was reviewed. OBSERVATIONS: Six patients

with a hypersensitivity syndrome reaction, 6 patients with a serum

sickness-like reaction, and 1 patient who had symptoms consistent with

drug-induced lupus were identified. A review of the literature identified

11 cases of hypersensitivity syndrome reaction, 1 case of serum

sickness-like reaction, and 24 cases of drug-induced lupus. Serum

sickness-like reactions occur sooner than hypersensitivity syndrome

reactions (15.6 vs 23.7 days, P = .04). Drug-induced lupus occurs on

average 2 years after the start of minocycline therapy. CONCLUSIONS:

Dermatologists need to be aware of the serious adverse reactions that can

develop after minocycline use. In patients who may require long-term

therapy with minocycline ( > 1 year), we suggest that antinuclear antibody

and hepatic transaminase levels be determined at baseline. Rechallenge with

minocycline or other tetracyclines is currently not recommended for

patients who develop these serious reactions. 

Language 

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39.) [Side effects of minocycline in the treatment of acne vulgaris] 

=========================================================================

Author 

Hoefnagel JJ; van Leeuwen RL; Mattie H; Bastiaens MT 

Address 

Afd. Dermatologie, Leids Universitair Medisch Centrum, Leiden. 

Source 

Ned Tijdschr Geneeskd, 141(29):1424-7 1997 Jul 19 

Abstract 

Minocycline is the most commonly used systemic antibiotic in the long-term

treatment (weeks to months) of severe acne vulgaris. Currently much

attention is being paid in the Dutch and international literature to the

safety of minocycline, after several reports on serious adverse events. The

clinical efficacy of minocycline in the treatment of acne vulgaris is

better than that of tetracycline and equal to that of doxycycline. The

serious adverse events of minocycline therapy described consist of

hyperpigmentation of various tissues, autoimmune disorders (systemic lupus

erythematosus, autoimmune hepatitis) and serious hypersensitivity reactions

(hypersensitivity syndrome reaction, pneumonitis and eosinophilia, and

serum sickness-like syndrome). In relation to the number of prescriptions,

the number of serious adverse events of minocycline described is small.

However, it is very important that prescribing doctors should be aware of

the possibility of these adverse events occurring during long-term

minocycline therapy and able to recognize the characteristic symptoms at an

early stage. 

=========================================================================

40.) Serious dermatologic reactions in children. 

=========================================================================

Author 

Knowles S; Shapiro L; Shear NH 

Address 

Department of Clinical Pharmacology, Sunnybrook Health Science Centre,

Toronto, Ontario, Canada. 

Source 

Curr Opin Pediatr, 9(4):388-95 1997 Aug 

Abstract 

Although serious reactions comprise only a small percentage of total

adverse drug reactions, they are important in terms of morbidity and

potential mortality. An update on serious dermatologic reactions in

children is presented including serum sickness-like reactions due to

cefaclor, hypersensitivity syndrome reactions (HSRs), and drug-induced

pseudoporphyria. More detailed information on minocycline-induced reactions

including drug-induced lupus and HSRs and lamotrigine-induced toxic

epidermal necrolysis and Stevens-Johnson syndrome will be discussed. 

=========================================================================

41.) Serum sickness-like syndrome associated with minocycline therapy. 

=========================================================================

ARTICLE SOURCE: Allergy (Denmark), May 1990, 45(4) p313-5 

AUTHOR(S): Puyana J; Urena V; Quirce S; Fernandez-Rivas M; Cuevas M; Fraj J 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: A 19 year-old youth was taking oral minocycline and after 8 days

he presented all four cardinal symptoms of serum sickness (urticaria,

fever, lymphadenopathy and joint symptoms). C3, C4 and CH50 evolution

imitate experimental serum sickness complement evolution. We exclude other

causes of this syndrome. Although other hypersensitivity reactions have

occurred with minocycline usage, to our knowledge serum sickness-like

syndrome has not been previously reported with this drug. 

=========================================================================

42.) Minocycline-induced loss of potassium from erythrocytes:

identification of a family with an augmented response. 

=========================================================================

ARTICLE SOURCE: J Infect Dis (United States), Oct 1978, 138(4) p455-62 

AUTHOR(S): Kornguth ML; Kunin CM 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: The effect of several tetracycline antibiotics of human

erythrocytes was examined because of previous findings that these drugs

bind to erythrocyte membranes. Minocycline and cetocycline, two highly

lipid-soluble analogues, but not tetracycline, induced loss of K+ from red

blood cells. Loss of K+ increased linearly with time of incubation,

concentration of minocycline, and temperature. The effect of minocycline

was inhibited by plasma and calcium. The cells from one volunteer

consistently showed an augmented response to minocycline; similar findings

for family members of the volunteer suggested a dominant autosomal mode of

inheritance. The only abnormality noted in the subject was mild

reticulocytosis and a slightly reduced K+ content in his red blood cells.

Preliminary studies did not demonstrate alterations in protein composition

of his red blood cell membranes, enhanced osmotic fragility, or defects in

Ca++-dependent or ouabain-sensitive (Na+-K+)-dependent adenosine

triphosphatase activity. The exact site of the minocycline effect remains

to be determined. 

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()()()()()()()()()()()()()() LO FEO () THE UGLY ()()()()()()()()()()()()

=========================================================================

43.) Minocycline-induced hyperpigmentation in leprosy. 

=========================================================================

Author 

Fleming CJ; Hunt MJ; Salisbury EL; McCarthy SW; Barnetson RS 

Address 

Department of Dermatology, Royal Prince Alfred Hospital, New South Wales,

Australia. 

Source 

Br J Dermatol, 134(4):784-7 1996 Apr 

Abstract 

A 36-year-old man was treated with dapsone, rifampicin and clofazimine for

borderline lepromatous leprosy. After 9 months, his leprosy plaques became

progressively more red and after 23 months, the clofazimine was stopped and

he was given minocycline instead. Six weeks later, he developed blue-black

pigmentation in his leprosy lesions. The histology was consistent with

minocycline-induced hyperpigmentation. This is the first report of

minocycline-induced pigmentation in leprosy. We suggest it is important to

consider this side-effect before the administration of minocycline in

leprosy, particularly if it is prescribed in place of clofazimine. 

=========================================================================

44.) Psoriatic arthritis and minocycline induced autoantibodies.

=========================================================================

Leitch DN; Haslock DI

Department of Rheumatology, South Cleveland Hospital, Middlesbrough,

Cleveland.

Clin Rheumatol (BELGIUM) May 1997 16 (3) p317-8 ISSN: 0770-3198

Language: ENGLISH

Document Type: JOURNAL ARTICLE 

Journal Announcement: 9710

Subfile: INDEX MEDICUS

A case of psoriatic arthritis where diagnosis was originally complicated

by the 

presence of minocycline-induced auto-antibodies and hepatic dysfunction.

The range 

of auto-antibodies associated with minocycline includes ds DNA and SCL 70.

=========================================================================

45.) Minocycline hydrochloride hyperpigmentation complicating treatment of

pyoderma gangrenosum. 

=========================================================================

ARTICLE SOURCE: J Dermatol (Japan), Dec 1994, 21(12) p965-7 

AUTHOR(S): Miralles ES; Nunez M; Perez B; Ledo A 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: Minocycline-associated hyperpigmentation is an uncommon side

effect. We report the case of a patient with pyoderma gangrenosum

successfully treated with oral minocycline but complicated by marked

hyperpigmentation in his pyoderma gangrenosum and acne scars. One of the

clinical forms of minocycline hyperpigmentation includes dark-blue or black

macules in depressed acne scars or other sites of skin inflammation; this

pattern seems to be independent of the total cumulative dose and the skin

process. 

=========================================================================

46.) Minocycline-induced oral pigmentation. 

=========================================================================

ARTICLE SOURCE: J Am Acad Dermatol (United States), Feb 1994, 30(2 Pt 2)

p350-4 

AUTHOR(S): Siller GM; Tod MA; Savage NW 

PUBLICATION TYPE: JOURNAL ARTICLE 

ABSTRACT: Oral mucosal pigmentation is an infrequently reported side

effect of minocycline. Two patients with minocycline deposition within

teeth and bone, demonstrated by fluorescence microscopy, are described.

Minocycline is the only tetracycline reported to cause discoloration of the

oral mucosa. This may be the result of deposition of an insoluble

degradation product of minocycline in the underlying bone. Pigmentation is

not necessarily dose-dependent and may take months or years to resolve. 

=========================================================================

47.) Nodular hyperplasia, black thyroid, and chronic minocycline ingestion

in a teenager. 

=========================================================================

ARTICLE SOURCE: Arch Surg (United States), Dec 1992, 127(12) p1476-7 

AUTHOR(S): Folsom DL; Gauderer MW; Dahms WT 

PUBLICATION TYPE: JOURNAL ARTICLE; REVIEW (7 references); REVIEW OF

REPORTED CASES 

ABSTRACT: An 18-year-old man with left-lobe thyroid hemiagenesis underwent

isthmectomy for management of a nodule that failed to take up radioactive

iodine during a nuclear scan. The resected tissue, which demonstrated

nodular hyperplasia, and the remaining right lobe, were black. The

association between deep staining and chronic minocycline ingestion was

subsequently recognized. Twelve years later, the patient remained

asymptomatic, suggesting that complete resection of tetracycline-stained

thyroid tissue is unnecessary. 

=========================================================================

48.) Black bones following long-term minocycline treatment. 

=========================================================================

ARTICLE SOURCE: Arch Pathol Lab Med (United States), Sep 1991, 115(9)

p939-41 

AUTHOR(S): Rumbak MJ; Pitcock JA; Palmieri GM; Robertson JT 

PUBLICATION TYPE: JOURNAL ARTICLE; REVIEW (16 references); REVIEW OF

REPORTED CASES 

ABSTRACT: During a surgical procedure, black vertebrae were observed in a

42-year-old white woman. An undecalcified iliac crest bone biopsy specimen

revealed intense fluorescence compatible with tetracycline labeling and

osteoporosis. A urinary screening test was negative for amino acids. The

patient had been treated with minocycline hydrochloride (100 to 300 mg/d)

for at least 6 years. Since minocycline is known to discolor many body

tissues, it is likely that the black discoloration of bone in our patient

was caused by the long-term intake of the antibiotic. 

=========================================================================

49.) Pigmented postacne osteoma cutis in a patient treated with

minocycline: report and review of the literature. 

=========================================================================

ARTICLE SOURCE: J Am Acad Dermatol (United States), May 1991, 24(5 Pt 2)

p851-3 

AUTHOR(S): Moritz DL; Elewski B 

PUBLICATION TYPE: JOURNAL ARTICLE; REVIEW (19 references); REVIEW, TUTORIAL 

ABSTRACT: Postacne osteoma cutis is a rare complication of acne vulgaris.

If it occurs during a course of tetracycline or minocycline therapy,

pigmented osteomas can occur as a result of tetracycline or minocycline

bone complexes. We report a case of pigmented postacne osteoma cutis that

developed after extensive acne surgery and a 2- to 3-month course of

minocycline. Previously reported cases have been treated surgically, but

our patient responded to 0.05% tretinoin cream, with transepidermal

elimination of some osteomas. 

=====================================================================

DATA-MÉDICOS/DERMAGIC-EXPRESS No (45) 17/03/99 DR. JOSE LAPENTA R. 

====================================================================== 

Produced by Dr. José Lapenta R. Dermatologist

Venezuela 1.998-2.024

Producido por Dr. José Lapenta R. Dermatólogo
Venezuela 1.998-2.024

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