eMedicine Specialties > Dermatology > Bacterial Infections
Gram-Negative Folliculitis
Updated: Nov 13, 2009
Introduction
Background
Gram-negative folliculitis, first described by Fulton et al in 1968,1 is an infection caused by gram-negative organisms. The infection may occur as a complication in patients with acne vulgaris and rosacea and usually develops in patients who have received systemic antibiotics for prolonged periods.2 Gram-negative folliculitis should be considered in patients with acne who have a flare-up of pustular or cystic lesions and in patients whose acne is resistant to treatment. Gram-negative folliculitis may also occur in the setting of hot-tub immersion and in people infected with HIV.
Pathophysiology
The anterior nares serve as a reservoir of gram-negative organisms. Prolonged systemic antibiotic treatment can alter the relative prevalence of bacterial flora carried in the nasal passages. An inverse relationship has been demonstrated between the presence of gram-positive organisms and gram-negative organisms in the pharyngeal, axillary, and toe-web flora. In patients with acne who are treated with oral antibiotics, the number of Staphylococcus aureus organisms and diphtheroids decreases and the number of coagulase-negative staphylococcal and enterobacterial organisms increases in the nose. Usually, gram-negative bacteria constitute less than 1% of the total bacterial flora in the nose. In patients with gram-negative folliculitis, enterobacteria constitute approximately 4% of the total bacterial flora.
The antibiotic-induced increase in gram-negative organisms usually does not result in adverse effects, and once antibiotic treatment is discontinued, the nasal flora reverts to its previous state. However, in a small number of patients, the increased number of gram-negative organisms results in a transfer of organisms to neighboring areas of the face. The bacteria populate existing acne lesions and can also cause pustules to arise de novo.
In addition to the need for suppression of interspecies interference, gram-negative organisms require a sufficiently moist environment to survive and proliferate. The presence of excessive seborrhea may promote the survival of gram-negative bacteria by trapping moisture in the face. The effectiveness of isotretinoin in the treatment of gram-negative folliculitis has been attributed to its ability to make the skin and the mucous membranes dry as a result of the marked reduction in sebaceous gland secretion.
Another factor has been implicated in the pathogenesis of gram-negative folliculitis. An assessment of hypersensitivity reactions to various microbial recall antigens and granulocyte functions was performed. Lowered serum concentrations of immunoglobulin M (IgM) and alpha1-antitrypsin and elevated levels of immunoglobulin E (IgE) were found, suggesting that altered immunologic factors may play a critical role in the pathogenesis of gram-negative folliculitis.
Frequency
United States
Gram-negative folliculitis is a relatively uncommon complication of prolonged antibiotic therapy. In 2 studies, approximately 4% of patients with acne vulgaris who were under treatment with broad-spectrum antibiotics reported this infection. However, the frequency of this infection is probably generally underestimated because clinicians rarely perform correct sampling and bacteriology.
Mortality/Morbidity
Gram-negative folliculitis has no associated increase in mortality. Morbidity is related to local pain and to the unwanted cosmetic effect of the folliculitis.
Race
No racial predilection is documented for gram-negative folliculitis.
Sex
No sexual predilection is documented for gram-negative folliculitis.
Age
Although gram-negative folliculitis is largely a complication of acne vulgaris and thus is expected to follow the age distribution of that entity, a slightly increased age at onset has been observed. The tendency for gram-negative folliculitis to begin after the early teenage years is most likely because most patients who develop gram-negative folliculitis have undergone treatment of acne with a broad-spectrum antibacterial agent for a prolonged period.
Clinical
History
A history is helpful in suggesting the diagnosis of gram-negative folliculitis.
- Patients usually have been receiving a course of antibiotics for a prolonged period. Patients with gram-negative folliculitis may present with 1 of 2 histories as follows:
- A history of apparent acne, usually of the nodulocystic form, may be present. The acne has not been responding to antimicrobial therapy or other therapy.
- A history of acne that has responded well to therapy and suddenly flares may be present. This exacerbation may occur a few days following cessation of an effective antibiotic or a few days following institution of a new antibiotic.
Physical
Because gram-negative folliculitis usually occurs in patients with existing acne, the development of this new process is often mistaken as an exacerbation of acne.
- Morphology of the lesions
- Type 1 (approximately 80% of patients) - Superficial pustular lesions without comedones
- Type 2 (approximately 20% of patients) - Deep, nodular, and cystic lesions
- Distribution of the lesions - Extending from the infranasal area to the chin and the cheeks
Causes
Systemic antibiotics, such as tetracyclines, can alter the nasal flora. The resultant overgrowth of gram-negative bacteria can lead to folliculitis.
- Type 1 lesions are usually associated with a lactose-fermenting, gram-negative rod, including Klebsiella, Escherichia, and Serratia species. Cases associated with Citrobacter species, another organism of the Enterobacteriaceae family, have also been described.3,4
- Type 2 lesions are associated with Proteus species. These species are motile and, thus, have the ability to invade more deeply, producing the large suppurative abscesses that result in deeper cystic lesions.
- Folliculitis caused by Pseudomonas organisms is typically associated with immersion in hot tubs and swimming pools, resulting in a generalized folliculitis. Aeromonas hydrophila has also been associated with water sources, including an inflatable pool.5,6 Home spas have also been implicated in causing gram-negative folliculitis. In the reported patients who were swimmers, a sudden unmanageable flare-up of facial acne associated with chronic bilateral otitis externa was reported. A case of Acinetobacter baumannii folliculitis of the face, neck, arms, and upper part of the trunk has been reported in a patient with AIDS.7
Differential Diagnoses
Acne Vulgaris
Acneiform Eruptions
Perioral Dermatitis
Workup
Laboratory Studies
- The diagnosis of gram-negative folliculitis can often be made based on the history and the physical examination findings alone. However, confirmation with Gram stain and culture is recommended.
- In confirming the diagnosis with Gram stain and culture, use special care in culturing. Gram-negative organisms are sensitive to desiccation; samples must be taken quickly and cultured as soon as possible. The pustule that is sampled should also be fresh. A small pustule on an erythematous base is preferable for culturing purposes.
- Culture pustules in any patient with acne who is in their late teens or older and has been on antibiotics and develops a pustular form of the disease.
- Gram-negative organisms cannot be recovered from every pustule.
- Selective medium-containing dyes, such as methylene blue, allow selective growth of gram-negative organisms while inhibiting growth of gram-positive organisms.
- The organisms that produce colonies on eosin-methylene blue agar are classified as either lactose-fermenting gram-negative rods or Proteus species by their cultural characteristics and their ability to ferment lactose.
- Lactose-fermenting, gram-negative rods produce small, dark, discreet, metallic colonies.
- Proteus species produce rapidly spreading, translucent, and odorous colonies.
- In patients with facial folliculitis that presents a diagnostic challenge, a potassium hydroxide mount (10-20% potassium hydroxide is used to stain a sample on a slide and look for possible fungal elements) and a skin biopsy specimen may be of value.
Histologic Findings
In contrast to typical acne lesions, lesions of gram-negative folliculitis do not contain a comedonal core. A minimal amount of keratinous material is present in an intrafollicular sea of pus. Occasionally, segments of the follicular wall may be dissolved. Organisms are located in nests around clumps of keratinous material, around hairs, and in phagocytes. In contrast to the predominant gram-negative rod recovered on culture, Gram stain of the tissue section may show a mixed flora (ie, gram-positive rods and cocci, gram-negative rods, budding yeasts).
Treatment
Medical Care
Treatment of gram-negative folliculitis includes the use of isotretinoin and systemic antibiotics.
- Isotretinoin offers the most effective cure for gram-negative folliculitis.8,9,10
- It is a synthetic beta-carotene derivative that is highly effective when used in patients with severe nodulocystic acne unresponsive to conventional therapy. Studies in patients with gram-negative folliculitis have demonstrated effective eradication of facial lesions and nasal carriage with isotretinoin, with an average clearance time of approximately 2-3 months. A low incidence of recurrence has been reported with this therapy.
- Isotretinoin has no antibiotic effect against the organisms causing gram-negative folliculitis.
- Several mechanisms have been proposed for its action, including sebum suppression, because all patients with this disease have severe seborrhea prior to isotretinoin treatment, and drying out of the mucous membranes, including the nasal mucosa, which is the reservoir for the organisms.
- Systemic antibiotics were the mainstay of therapy for gram-negative folliculitis prior to the development of isotretinoin; the choice of antibiotic was dictated by antibiotic sensitivities. Topical therapy rarely works.
- The most effective antibiotics have come from the bacteriostatic group, which includes ampicillin and trimethoprim-sulfamethoxazole.
- Reports have conflicted concerning the degree to which these medications can eradicate the carriage of gram-negative organisms and induce remission. Most studies describe recurring infection after therapy is discontinued, making antibiotic use largely a suppressive modality.
- Gram-negative folliculitis caused by Pseudomonas organisms in whirlpools usually subsides spontaneously within 10 days without recurrence. In patients with facial folliculitis caused by Pseudomonas organisms associated with acne vulgaris, the infection clears when the source of the organism, external otitis, is cured. Acinetobacter baumannii folliculitis in the setting of AIDS has responded to intravenous treatment with ticarcillin-clavulanic acid.
- Most patients have ordinary acne in addition to gram-negative folliculitis. Once the folliculitis has responded, residual acne must be treated by other methods, including retinoic acid, benzoyl peroxide, cryotherapy, and other therapies.
- Gram-negative folliculitis is relatively uncommon, and the general benefit from antibiotics far outweighs the occasional complication of folliculitis.
Medication
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Retinoids
These agents modulate keratinocyte differentiation and decrease sebum production.
Isotretinoin (Accutane)
Oral agent that treats serious dermatologic conditions, isotretinoin is synthetic 13-cis isomer of naturally occurring tretinoin (trans -retinoic acid). Both agents are structurally related to beta-carotene. Decreases sebaceous gland size and sebum production. May inhibit sebaceous gland differentiation and abnormal keratinization.
A US Food and Drug Administration–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin. For more information on this registry, see iPLEDGE. This registry aims to further decrease the risk of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Female patients must sign an informed consent that they will use contraceptives during treatment course and for 30 d after discontinuing therapy.
Dosing
Adult
0.5-1 mg/kg PO qd
Pediatric
Not established
Interactions
Toxicity may occur with beta-carotene coadministration; pseudotumor cerebri or papilledema may occur when coadministered with tetracyclines; may reduce plasma levels of carbamazepine
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
May decrease night vision; inflammatory bowel disease may occur; may be associated with development of hepatitis; occasional exaggerated healing response of folliculitis and acne (excessive granulation with crusting) may occur; patients with diabetes may experience problems controlling blood sugar levels; advise patients to avoid exposure to UV light or sunlight until tolerance is achieved; discontinue if rectal bleeding, abdominal pain, or severe diarrhea occur
Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.
Ampicillin (Principen, Omnipen, Marcillin)
Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.
Dosing
Adult
250-500 mg PO q6h
500-1500 mg IM q4-6h
500-3000 mg IV q4-6h; not to exceed 12 g/d
Pediatric
50-100 mg/kg/d PO divided q4-6h
100-400 mg/kg/d IM/IV divided q4-6h
Interactions
Probenecid and disulfiram elevate levels; allopurinol decreases effects and worsens ampicillin rash; may decrease effects of oral contraceptives
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction
Trimethoprim and sulfamethoxazole (Bactrim, Septra)
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid.
Dosing
Adult
160 mg TMP/800 mg SMZ PO q12h
Pediatric
<2 months: Do not administer
>2 months: 15-20 mg TMP/kg/d PO tid/qid
Interactions
May increase PT levels when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenic purpura in elderly patients; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Contraindications
Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue at first appearance of skin rash or signs of adverse reaction; monitor CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, administer leucovorin 5-15 mg/d); caution in folate deficiency (eg, patients who drink excessive amounts of alcohol, elderly patients, patients receiving anticonvulsant therapy, or patients with malabsorption syndrome); hemolysis may occur in individuals with G-6-PD deficiency; patients with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation
Follow-up
Prognosis
- Complete remission of the gram-negative folliculitis results with isotretinoin use. If antibiotic therapy is used, long-term suppression is required.
Patient Education
- Teach patients that the lesions of gram-negative folliculitis are a different disease entity and that the treatment of the primary disease (acne or rosacea) is causing the gram-negative folliculitis. If antibiotic therapy is used, make patients aware that treatment is usually only suppressive.
Miscellaneous
Medicolegal Pitfalls
- Failure to recognize the development of a new process that is exacerbated by continued use of antibiotic therapy is a pitfall.
References
Fulton JE Jr, McGinley K, Leyden J, Marples R. Gram-negative folliculitis in acne vulgaris. Arch Dermatol. Oct 1968;98(4):349-53. [Medline].
Leyden JJ, Marples RR, Mills OH Jr, Kligman AM. Gram-negative folliculitis--a complication of antibiotic therapy in acne vulgaris. Br J Dermatol. Jun 1973;88(6):533-8. [Medline].
Chastain MA. A cycle: recurrent gram-negative folliculitis with Citrobacter diversus (koseri) following eradication of recurrent staphylococcal pyoderma. Arch Dermatol. Jun 2000;136(6):803. [Medline].
Mostafa WZ. Citrobacter freundii in gram-negative folliculitis. J Am Acad Dermatol. Mar 1989;20(3):504-5. [Medline].
Julia Manresa M, Vicente Villa A, Gene Giralt A, Gonzalez-Ensenat MA. Aeromonas hydrophila folliculitis associated with an inflatable swimming pool: mimicking Pseudomonas aeruginosa infection. Pediatr Dermatol. Sep-Oct 2009;26(5):601-3. [Medline].
Mulholland A, Yong-Gee S. A possible new cause of spa bath folliculitis: Aeromonas hydrophila. Australas J Dermatol. Feb 2008;49(1):39-41. [Medline].
Bachmeyer C, Landgraf N, Cordier F, Lemaitre P, Blum L. Acinetobacter baumanii folliculitis in a patient with AIDS. Clin Exp Dermatol. May 2005;30(3):256-8. [Medline].
Böni R, Nehrhoff B. Treatment of gram-negative folliculitis in patients with acne. Am J Clin Dermatol. 2003;4(4):273-6. [Medline].
James WD, Leyden JJ. Treatment of gram-negative folliculitis with isotretinoin: positive clinical and microbiologic response. J Am Acad Dermatol. Feb 1985;12(2 Pt 1):319-24. [Medline].
Plewig G, Nikolowski J, Wolff HH. Action of isotretinoin in acne rosacea and gram-negative folliculitis. J Am Acad Dermatol. Apr 1982;6(4 Pt 2 Suppl):766-85. [Medline].
Blankenship ML. Gram-negative folliculitis. Follow-up observations in 20 patients. Arch Dermatol. Oct 1984;120(10):1301-3. [Medline].
Leyden JJ, McGinley KJ, Mills OH. Pseudomonas aeruginosa gram-negative folliculitis. Arch Dermatol. Oct 1979;115(10):1203-4. [Medline].
Marples RR, Fulton JE, Leyden J, McGinley KJ. Effect of antibiotics on the nasal flora in acne patients. Arch Dermatol. Jun 1969;99(6):647-51. [Medline].
Neubert U, Jansen T, Plewig G. Bacteriologic and immunologic aspects of gram-negative folliculitis: a study of 46 patients. Int J Dermatol. Apr 1999;38(4):270-4. [Medline].
Noble WC. Gram-negative bacterial skin infections. Semin Dermatol. Dec 1993;12(4):336-41. [Medline].
Simjee S, Sahm DF, Soltani K, Morello JA. Organisms associated with gram-negative folliculitis: in vitro growth in the presence of isotretinoin. Arch Dermatol Res. 1986;278(4):314-6. [Medline].
Tan HH. Antibacterial therapy for acne: a guide to selection and use of systemic agents. Am J Clin Dermatol. 2003;4(5):307-14. [Medline].
Tarlow MM, Piela Z, Schwartz RA. Gram-negative folliculitis - a diagnostic challenge. Dermatologia Kliniczna. 2002;4:7-9.
Keywords
gram-negative folliculitis, acne, acne vulgaris, rosacea, prolonged antibiotic therapy, acne treatment complications species, species, species, Citrobacter species, species,
Contributor Information and Disclosures
Author
Mordechai M Tarlow, MD, Clinical Associate, Department of Dermatology, University of Pennsylvania School of Medicine
Mordechai M Tarlow, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for MOHS Surgery, American Society of Cosmetic Dermatology and Aesthetic Surgery, and Sigma Xi
Disclosure: Nothing to disclose.
Coauthor(s)
Sofia Piela, MD, Head, Department of Dermatology, Rzeszow Regional Health Center, Poland
Disclosure: Nothing to disclose.
Michael Wiederkehr, MD, Consulting Staff, Livingston Dermatology Associates; Consulting Staff, Comprehensive Dermatology and Laser Center
Michael Wiederkehr, MD is a member of the following medical societies: Alpha Omega Alpha and American Medical Association
Disclosure: Nothing to disclose.
Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.
Medical Editor
Terry L Barrett, MD, Clinical Professor of Dermatology and Pathology, University of Texas Southwestern School of Medicine; Director, ProPath Dermatopathology, Dallas, Texas
Terry L Barrett, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, American Medical Association, American Society of Dermatopathology, College of American Pathologists, and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.
Pharmacy Editor
David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.
Managing Editor
Rosalie Elenitsas, MD, Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System
Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology
Disclosure: Nothing to disclose.
CME Editor
Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.
Chief Editor
Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.