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N Dermatol Online. 2011; 2(3): 135-138
Date of submission: 06.03.2011 / acceptance: 22.03.2011
Conflicts of interest: None



Sierra-Téllez Daniela1, Ponce-Olivera Rosa María1, Tirado-Sánchez Andrés1, Hernández Marco Antonio2, Bonifaz Alexandro2

1Dermatology Department, General Hospital of Mexico
2Micology Section, Dermatology Department, General Hospital of Mexico

Corresponding author: Dr. Hernández Marco Antonio   e-mail: danaya_25@hotmail.com


Gram-negative folliculitis may be the result of prolonged antibacterial treatments in patients with acne and rosacea. It is caused by alteration of facial skin flora and the nasal mucous, a decrease of Gram-positive bacteria and a proliferation of Gram-negative bacteria (for example Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Klebsiella sp. and Proteus mirabilis). It should be considered in patients with acne who have not had a clinical improvement after 3-6 months of treatment with tetracyclines. The disease is underestimated, probably because bacteriological studies are rarely requested and the increased use of oral isotretinoin for acne management. One of the most effective treatments for Gram-negative folliculitis is oral isotretinoin (0.5-1 mg / kg / day for 4-5 months). We report the case of Gram negative folliculitis successfully treated with oral isotretinoin.
Gram-ujemne zapalenie mieszków włosowych mo?e być wynikiem długotrwałego leczenia przeciwbakteryjnego u pacjentów z trądzikiem i trądzikiem ró?owatym. Jest to spowodowane zmianą flory bakteryjnej skóry twarzy i błony śluzowej nosa, zmniejszeniem ilości bakterii Gram-dodatnich i wzrost liczby bakterii Gram-ujemnych (na przykład Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, sp Klebsiella. i Proteus mirabilis). Nale?y rozwa?yć u pacjentów z trądzikiem, którzy nie mieli poprawy klinicznej po 3-6 miesiącach leczenia tetracyklinami. Częstotliwość tej choroby jest zani?ona, prawdopodobnie dlatego, ?e badania bakteriologiczne rzadko są wykonywane i istnieje zwiększone u?ywanie doustnej izotretynoiny w leczeniu trądziku. Jednym z najbardziej skutecznych metod leczenia Gram-ujemnych zapaleń mieszków włosowych jest doustna izotretynoina (0,5-1 mg / kg mc. / dobę przez 4-5 miesięcy). Prezentujemy przypadek Gram-ujemnego zapalenia mieszków włosowych skutecznie leczonego doustną izotretynoiną.
Key words:  folliculitis; Gram-negative; acne; isotretinoin
Słowa klucze:  zapalenie mieszków włosowych; Gram-ujemne; trądzik; izotretynoina


Gram-negative folliculitis (GNF) is a hair follicle infection by Gram-negative organisms that can occur as a complication in patients receiving prolonged treatment with broad spectrum antibiotics for the treatment of acne vulgaris and rosacea. It must be suspected in a sudden exacerbation of acne treatment or in patients non-responding to conventional acne treatments [1]. There are two clinical variants of GNF; type I, is the most common, about 80% of cases, with the presence of multiple papules and pustules in the middle of the face; the type II occurs in 20% of cases and is characterized by inflammatory nodules or cysts [1-4]. Oral isotretinoin is the treatment of choice at doses of 0.5 to 1mg/kg/day for 4-5 months [4]. Its mechanism of action is to control the proliferation of Gram-negative bacteria through microenvironmental changes produced in the skin and nasal mucous [5,6].
Case Report
A 24-year old female came to our service with a skin disease that affects the perioral zone, characterized by multiple papules and pustules (Fig. 1A). Patient started one week before their assessment and with a history of having received tetracycline hydrochloride for 2 months for mild to moderate acne, as well as topical clindamycin intermittently for six months. The patient underwent clinical examination and laboratory test such as Gram stain (Fig. 1C) and culturing on McConkey agar (Fig. 1D). A treatment with oral isotretinoin was proposed with resolution of the skin disease within a 3 month treatment period (Fig. 1B).
Figure 1. A. Perioral pustules. B. Post-treatment control. C. Gram-negative bacilli (x100). D. Lactose +, red-pink colonies (McConkey agar). Escherichia Coli
Gram-negative folliculitis was first reported in 1968 by Fulton et al [1], in a group of patients with acne vulgaris resistant to conventional treatments [1-4]. It is a hair follicle infection that occurs mainly in patients with inflammatory acne or rosacea that have long treatments with broad spectrum antibiotics, mainly tetracycline [3- 5]. It should be suspected when there is an increase in pustules with resistance to systemic treatment [4,6]. It is reported a prevalence of 4%. Prolonged treatment alters the normal bacterial flora of the nasal mucous and adjacent skin with reduced Gram-positive bacteria and coagulase positive aerobic diphtheroids, with an increase in Gram-negative bacilli mainly enteric bacteria [2-4]. Its characteristic features include: predominance in male gender, severe seborrhea, papules, pustules and perinasal and/or perioral involvement, recurrent folliculitis of the scalp, and prolonged antibacterial pretreatment, asymptomatic intervals tend to be shortened, acne and rosacea resistant to conventional treatment and isolation repeatedly of Gram-negative bacteria in cultures of pustules and facial nasal mucous [2-3]. Gram-negative folliculitis has been reported after eradication of recurrent staphylococcal pyodermas and prolonged treatment with topical antibacterials. Bartholow & Maibach [7], described a patient with acne who had been treated with topical clindamycin, followed by benzoyl peroxide and topical erythromycin and developed GNF due to E. coli. Fulton et al [1], described patients using antibacterial soaps, which selectively inhibit Gram-positive bacteria [8]. Leyden et al [9], clinically differentiated two types of GNF. The type I, superficial or pustular, is the most common (80-90%), with presence of multiple papules and pustules in the middle of the face, 3 to 6 mm in diameter with an erythematous halo, mainly caused by E. coli, Klebsiella sp., Enterobacter sp. and P. aeruginosa. The type II, deep or nodular (10-20%), is characterized by deep and painfully inflammatory nodules or cysts, on the face, neck and/or chest, caused by Proteus mirabilis. Sebaceous follicles are colonized with these bacteria, mainly in the perioral and perinasal zone, with subsequent follicular and perifollicular inflammation with formation of papules and pustules [3,4,10,11]. Marples et al [12], confirmed an inverse ratio between nasal carriers of S. aureus and enterobacteria. The proportion of Gram-negative bacteria results in a 1% of the total flora under normal conditions. In the case of nasal carriers this ratio increases 3-4%, being nasal cavity the reservoir for facial cases of GNF [2,3]. The role of immune mechanisms of defense as a factor in the development of the GNF in patients with acne is not clear yet. Neubert et al [3], report that in addition to seborrhea and microflora changes induced by antibiotics, there are various mechanisms in the host immune defense, which appear to be an important factor in the GNF, induced by a depressed cell-mediated immunity, as evidenced by weak or absent response of hypersensitivity, which results in increased susceptibility to infections, showing a decrease of serum IgM, with a weak or absent response to enterobacterial antigens, similar events occur in patients with type V dysgammaglobulinemia (selective deficiency of IgM), which are liable to septicemia episodes by Gramnegative bacteria, and a deficiency in the complement system causing alterations in opsonization, chemotaxis and bacterial lysis. There is also evidence that chemotaxis of neutrophils may be inhibited by IgEmediated histamine release, which is elevated in these patients. It is well known that tetracyclines, the most commonly used systemic antibiotic in acne and rosacea, impair protein synthesis and function of lymphocytes and neutrophil chemotaxis, increasing the risk of bacterial infection [3,4]. The diagnosis should be confirmed with a smear of the pustules. The lesions (pustules) and the anterior nasal mucosa should be sampled for bacteriological studies. Treatment antibiotics must be withdrawn [4,10]. Oral isotretinoin is the treatment of choice [4-5,11,13]. Oral doses ranged from 0.5 to 1mg/kg/day for a period of 4-5 months, remission of the symptoms of facial and nasal colonization is achieved since the first three months of treatment [5]. The therapeutic success of isotretinoin in the GNF is due to decreased secretion of the sebaceous glands (thereby reducing the amount of sebum in more than 90%) and reduction of the follicular space size and anti-inflammatory effect, returning the environment uninhabitable for Gram-negative bacteria [5,8]. The most effective dose with a lower recurrence rate is 1mg/kg/day [4,11,13]. Systemic antibiotics such as cephalosporins combined with oral isotretinoin for 2 weeks are often useful on patients with frequent relapses [4]. Ampicillin and trimethoprim-sulfamethoxazole are reported with good results with remission of lesions in two weeks, with subsequent gradual reduction in dose. The clinical course determines the time of withdrawal, with remission rates ranged from 4 to 48 months [3] (Tab. I). Finally, we concluded the gram-negative folliculitis is an underdiagnosed disease, probably because the increased use of oral isotretinoin for acne management. We must suspected it when there is an exacerbation of centrofacial papules, pustules and/or nodules and cyst in patients with inflammatory acne or rosacea that have long treatments with broad spectrum antibiotics, nonresponding to conventional treatments. We must request the bacteriological studies before initiating the oral isotretinoin. 
Patients Clinical Status Agent Treatment
Neubert et al [10]
n= 46
Centrofacial folliculitis combined
with open and/or closed comedon.
Klebsiella spp.,
Escherichia coli,
Enterobacter spp.,
and Proteus spp.
Isotretinoin, mean duration
18.6 weeks, mean total
dosage 109 mg/kg.

James et al [5]
Patients with
nodulocystic acne with several facial pustules resistant to
all therapies.
Isotretinoin 0.48-0.74
mg/kg/day for 20 weeks.

James et al [5] n=11
Patients with nodulocystic
acne with several facial pustules
resistant to all therapies.
aerogenes, Proteus
mirabilis, Klebsiella
pneumoniae, E. coli
and S. marcescens.
Isotretinoin 1mg/kg/day for
5 months.

Leyden et al [9]
Folicular pustules grouped around the nose.

Lactose fermenting
Gram-negative rods
often Klebsiella,

Ampicillin 1gr/day for 7-14
days, lowered to a
maintenance level 250mg
twice daily.

Leyden et al [9]
Deep, nodular and cystic lesions.

Ampicillin 1gr/day for 7-14
days, lowered to a
maintenance level 250mg
twice daily.

Eady et al [13]
n= 8
Non-responding acne patients.
Gram-negative rods.
Trimethoprim or cotrimoxazole.
Presented Case
n= 1
Perioral pustules with acne resistant to
all therapies.
Escherichia coli.
Isotretinoin, 0.3mg/kg/day
for 10 months.

Table I. Summary of Gram-negative Folliculitis. Case reports

1. Fulton JE Jr, McGinley K, Leyden J: Gram-negative folliculitis in acne vulgaris. Arch Dermatol 1968; 98: 349- 53. 2. Blankenship ML: Gram-negative folliculitis. Follow-up observations in 20 patients. Arch Dermatol 1984; 120: 1301-1303. 3. Neubert U, Jansen T, Plewig G: Bacteriologic and immunologic aspects of gram-negative folliculitis: a study of 46 patients. Int J Dermatol 1999; 38: 270-274. 4. Böni R, Nehrhoff B: Treatment of gram-negative folliculitis in patients with acne. Am J Clin Dermatol 2003; 4: 273-276. 5. James WD, Leyden JJ: Treatment of gram-negative folliculitis with isotretinoin: positive clinical and microbiologic response. J Am Acad Dermatol 1985; 12: 319-324. 6. Ruocco E, Donnarumma G, Baroni A, Tufato M: Bacterial and viral skin diseases. Dermatol Clin 2007; 25: 663-676. 7. Bartholow P, Maibach HI: Gram-negative folliculitis without systemic antibiotics?. Arch Dermatol 1979; 115: 676. 8. Harkaway KS, McGinley KJ, Foglia AN, Lee WL, Fried F, Shalita AR, et al. Antibiotic resistance patterns in coagulase-negative staphylococci after treatment with topical erythromycin, benzoyl peroxide and combination therapy. Br J Dermatol 1992; 126: 586-590. 9. Leyden JJ, Marples RR, Mills OH Jr, Kligman AM: Gram-negative folliculitis-a complication of antibiotic therapy in acne vulgaris. Br J Dermatol 1973; 88: 533-538. 10. Neubert U, Plewing G, Ruhfus A: Treatment of gramnegative folliculitis with isotrenoin. Arch Dermatol Res 1986; 278: 307-313. 11. Chivot M. Residual acne lesions after treatment. Ann Dermatol Venereol 1996: 123: 594-600. 12. Marples RR, Fulton JE, Leyden J, McGinley KJ: Effect of antibiotics on the nasal flora in acne patients. Arch Dermatol 1969; 99: 647-651. 13. Eady EA, Cove JH, Blake J, Holland KT, Cunliffe WJ: Recalcitrant acne vulgaris. Clinical, biochemical and microbiological investigation of patients not responding to antibiotic treatment. Br J Dermatol 1988 Mar; 118: 415- 423.



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