AUTHOR AND EDITOR INFORMATION

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
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INTRODUCTION

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• Differentials
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• Follow-up
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Background

Gram-negative interweb foot impetigo is a relatively common and troubling disorder.¹ The infection is commonly associated with the use of closed-toe or tight-fitting shoes and in individuals in whom strong physical exertion plays an important role in athletic, occupational, or recreational activities.

Gram-negative mixed bacterial infection with organisms, such as Moraxella, Alcaligenes, Acinetobacter, Pseudomonas, Proteus, and Erwinia species, may represent a mild secondary infection of tinea pedis, and it may progress to advanced stages of gram-negative infection with sepsis.

Pathophysiology

Typically, the interweb space is colonized by polymicrobial flora. Initially, a dermatophyte infection at this site may damage the stratum corneum and produce natural substances with antibiotic properties that alter the composition of the resident bacterial flora, encouraging the proliferation of antibiotic-resistant strains.²

Gram-negative bacteria may resist the antibacterial agents and many of the commonly used therapeutic agents. In other cases, marked hyperhidrosis with cutaneous maceration, often seen in people who enjoy vigorous athletic endeavors, may predispose individuals to gram-negative bacterial toe web infection. Pseudomonas aeruginosa, often together with other gram-negative bacteria, is the most common etiologic agent.¹

The toe web space provides a hospitable niche for gram-negative microorganisms; infection can quickly progress from mild overgrowth of resident bacteria to an advanced, severe, gram-negative infection. Lesions that affect the interdigital spaces can occasionally extend to the planta and the backs of the toes. The most frequent complaint of patients is burning and pain, and, in severe infection, problems with walking are noted.

Gram-negative bacteria gain access to the bloodstream from foci of tissue infection or possibly from heavy colonization. Trauma, tinea pedis, or depressed host resistance, as in diabetes mellitus or HIV disease, may also predispose individuals to the infection.

Frequency

United States

Few data are available on the frequency of gram-negative toe web infections.

International

A limited number of cases have been reported.

Mortality/Morbidity

This disorder can rarely progress to a life-threatening situation. Occasionally, in advanced severe cases, certain microorganisms (eg, P aeruginosa) can cause therapeutic problems in relation to antibiotic resistance and a risk of potential lethal complications. If septicemia occurs, especially in a patient who is immunocompromised, the condition may produce shock and death.

Acute bacterial cellulitis is a potentially serious, often recurrent infection. Risk factors for acute bacterial cellulitis in hospitalized patients were found to include the presence of sites of pathogen entry on toe webs. Improved awareness and management of toe web intertrigo, which may harbor bacterial pathogens, may reduce the prevalence of cellulitis.³

Race

Gram-negative toe web infection can affect any race.

Sex

Men appear to be more frequently affected, with a male-to-female ratio of 4:1 reported in one study.¹

Age

Gram-negative toe web infection affects young and elderly persons. In one series, patients were reported to be aged 1-74 years. The disorder rarely involves infants or children.

CLINICAL

Section 3 of 11  

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• Clinical
• Differentials
• Workup
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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

The patient usually complains of a burning sensation between the toes, often with maceration. A malodorous exudate may be evident.

• Gram-negative infections may cause an inability to walk, accompanied by a profuse or purulent discharge. Edematous toes and tight interdigital spaces may be evident in the early stages of the disease. In severe occurrences, individuals may have a purulent discharge with edema and intense erythema of the surrounding tissues outside the infected area. In some patients, a green discoloration may be seen with advanced gram-negative infections.
• The erythematous-desquamatous type of infection may be more chronic than the acute form, with exudative, macerating, painful inflammation that causes functional disability of the feet.
• Redness and swelling, which suggests concurrent cellulitis, are occasionally present and extend up the ankles and the legs.
• Although malodor may be evident, it tends to be more closely associated with dermatophytic infection than with gram-negative infections. This finding may be due to suppression of malodor-producing Brevibacterium by the gram-negative organisms.
• Risk factors for erysipelas (cellulitis) of the leg were evaluated.⁴ In multivariate analysis, disruption of the cutaneous barrier (ie, traumatic wound, toe-web intertrigo, excoriated leg dermatosis, plantar squamous lesions) and leg edema were found to be independently associated with erysipelas of the leg, yet no association was observed with diabetes mellitus, alcoholism, or smoking. Detecting and treating toe-web intertrigo is important in the prevention of erysipelas of the leg.

Physical

Clinical manifestations are similar for most patients.

• Clinical features can include erythema, vesicopustules, erosions, and marked maceration caused by abundant malodorous exudate.
• Marked hyperhidrosis is often noted. Hyperhidrosis creates an optimum situation for overgrowth of bacteria and gram-negative organisms.
• An examination should be performed to determine if the patient has a tinea pedis foot infection; contact dermatitis; foot trauma; or other predisposing local factors, such as wearing tight-fitting shoes.

Causes

The cause of gram-negative toe web infections may be related to several factors.

• Overgrowth of gram-negative organisms between the toes may cause the infection.
• Marked hyperhidrosis may predispose to the infection.
• Constant wearing of closed-toe shoes so that air does not circulate around the feet increases the likelihood of overgrowth of the microorganisms that create infections.
• Sporting activities, especially water-related sports, increase the likelihood of growth of the bacterial organisms.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

Group A beta-hemolytic streptococci may produce a variety of common childhood cutaneous infections.⁵ It is typically seen as intense, fiery red erythema and maceration in the intertriginous folds of the neck, axillae, or inguinal spaces, and has a distinctive foul odor. It should also be considered in the differential diagnosis of interweb toe infections.

Fusarium solani infection may also be considered. Bilateral intertrigo of the third and fourth interdigital spaces of the feet due to a Fusarium solani infection in an immunocompetent Senegalese man has been described.⁶ Infection with this mold is potentially dangerous for the immunodepressed.

WORKUP

Section 5 of 11  

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• Clinical
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• Medication
• Follow-up
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Lab Studies

• To determine the etiologic agents, bacterial culturing and sensitivity testing, potassium hydroxide preparation, and fungal culturing should be performed.
• • Some of the gram-negative organisms isolated and identified on Gram staining and/or culturing include P aeruginosa, Proteus mirabilis, and Enterococcus species. Usually, patients are infected by more than one organism. Some other organisms found on gram-negative cultures include Serratia marcescens, Escherichia coli, alpha streptococci, Proteus vulgaris, and Enterobacter species.
  • Fungal culturing can be used to isolate a fungus associated with the infection, whether it is a dermatophyte or a yeast.

• A patient's immune status may need to be evaluated, especially if response to therapy is slow, because serious potentially lethal systemic complications may occur. In addition, complete blood cell counts with differential and fasting blood glucose levels may be used to screen the patient's immune status and to exclude diabetes mellitus.
• A Wood light examination and culture should be performed to establish the diagnosis of Pseudomonas toe web infection.

Histologic Findings

Histologically, an eroded epidermis is anticipated, sometimes with a serous or serosanguineous exudate at its base, with numerous neutrophils and scattered bacteria.

The infection can begin primarily as a typical tinea pedis infection, but it can escalate and become severe, manifesting erythema and erosions and extending beyond the toes.

TREATMENT

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Medical Care

In a 1972 study describing gram-negative toe infection, the authors found no single or simple therapeutic agent to be regularly effective as a quick cure. Patients with positive fungal culture results were treated with bedrest and supportive measures to prevent maceration. In severe infection, hospitalization is often required.

Treatment options that may be helpful are listed below.

• Drying of the interdigital web spaces eliminates the causative organisms that require high humidity for growth. Pledgets placed between the toes and a fan to circulate air are easy, inexpensive modalities.
• Topical econazole nitrate therapy may be beneficial. Randomized treatment with either econazole nitrate or its vehicle was administered to 24 patients with severe interdigital toe web infections and no evidence of dermatophyte colonization. Of the patients treated with econazole nitrate, 88% had a good-to-excellent response, while no patients treated with the vehicle showed improvement. Total aerobic flora decreased 93% in the econazole group, with a decrease in the number of large-colony diphtheroids, lipophilic diphtheroids, and gram-negative bacteria. The results of this study demonstrate that the antibacterial activity of econazole nitrate makes it an effective agent for the treatment of severe interdigital bacterial infections uncomplicated by dermatophyte colonization.⁷
• Another option is treatment with oral ciprofloxacin and local application of Castellani paint.
• Proper identification of the gram-negative organisms is critical so that effective antibiotic therapy can be initiated. Early diagnosis, patient education and awareness of the infection, and a timely therapy all help lead to recovery in most patients.
• In severe cases where systemic symptoms suggest septicemia, therapy should be initiated while awaiting blood culture results.

Surgical Care

Occasionally, if the infection is advanced, superficial debridement may allow creams, ointments, or other antibiotic agents to reach infected areas faster, promoting healing and stopping the spread of the infection into surrounding areas.

Consultations

• If a diagnosis of sepsis is considered, an internist with advanced knowledge in infectious diseases should be consulted.
• Possible deep tissue infection should prompt surgical evaluation.

Activity

Patients should be educated on the importance of keeping the toe webs dry. After a shower, the feet and the areas between the toes should be thoroughly dried. Wearing an open-toed sandal or shoe can be beneficial. The risk is higher in individuals who participate in water-related activities.

MEDICATION

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The best treatment for a gram-negative toe infection is often a combined approach by using both antibacterial agents and antifungal agents; sometimes, astringents are used. Debridement may be of value. Drying of the interdigital spaces is paramount.

Drug Category: Antifungal agents (topical)

The mechanism of action may involve increasing the permeability of the cell membrane, which, in turn, causes intracellular components to leak.

Drug Category: Antibiotic agents

Therapy must cover all likely pathogens in the context of the clinical setting.

Drug Name	Cefotaxime sodium (Claforan)
Description	Third-generation semisynthetic broad-based antibiotic with gram-negative spectrum. Lower efficacy against gram-positive organisms. Specimens for bacteriologic culture should be obtained prior to therapy to test for susceptibilities to cefotaxime sodium.
Adult Dose	500 mg or 1 g IM; not to exceed 12 g/d
Pediatric Dose	<50 kg: 50-180 mg/kg IV/IM divided into 4-6 equal doses >50 kg: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Probenecid may increase levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy; has been associated with severe colitis; caution in history of gastrointestinal tract disease, particularly colitis

Drug Name	Ciprofloxacin (Cipro)
Description	Synthetic broad-spectrum antimicrobial agent that inhibits bacterial DNA synthesis and, consequently, growth. Film-coated tab is available in 100 mg, 250 mg, 500 mg, and 750 mg. Oral susp is white to slightly yellow with a strawberry flavor and may contain yellow-orange droplets. Tablets are well absorbed in gastrointestinal tract after oral administration. Has a wide range of activity against gram-negative organisms.
Adult Dose	500 mg PO q12h
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy

Drug Name	Gentamicin sulfate (G-Myticin, Jenamicin, Garamycin)
Description	Wide-spectrum antibiotic that provides highly effective topical treatment in primary and secondary bacterial infections of the skin. Gentamicin sulfate may clear infections that have not responded to other topical antibiotic agents. Treats superinfections caused by fungi or viruses. Treats skin and skin structure infections. Usual duration of treatment is 7-10 d. In more serious infections, longer course of therapy is needed. Patients should be well hydrated during treatment. May also be used parenterally as a water-soluble injection against a wide variety of pathogenic bacteria. May be considered as initial therapy in suggested or confirmed gram-negative infections, and therapy may be instituted before obtaining results of susceptibility testing.
Adult Dose	Topical: Apply sparingly to lesions tid/qid; area may be covered with gauze dressing Parenteral: 3 mg/kg/d IV divided tid/qid; reduce dose to 1.25 mg/kg/d for maintenance as soon as clinically indicated; can eventually be reduced to 1.15 mg/kg/d IV q8h
Pediatric Dose	Topical Apply as in adults Parenteral <5 years: 2.5 mg/kg/dose IV/IM q8h >5 years: 1.5-2.5 mg/kg/dose IV/IM q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults
Contraindications	Documented hypersensitivity; non–dialysis-dependent renal insufficiency if administered parenterally
Interactions	None reported for topical formulation; coadministration of parenteral formulation with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; because aminoglycosides enhance effects of neuromuscular-blocking agents, prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)
Pregnancy	D - Unsafe in pregnancy
Precautions	Pregnancy category D if administered parenterally; topical antibiotics occasionally allow overgrowth of nonsusceptible organisms, including fungi (discontinue treatment if overgrowth occurs or if irritation or sensitization develops); adverse reactions include irritation, erythema, and pruritus; parenteral formulation has narrow therapeutic index (not intended for long-term therapy); caution in renal failure (patients not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Drug Name	Castellani paint
Description	Castellani paint acquired its name from an Italian physician, Sir Aldo Castellani (1877-1971); it is also called carbolfuchsin paint. Is a fungicidal and bactericidal liquid with an anesthetic effect on the skin and an antiseptic and drying agent. Is a magenta liquid that stains the skin red. The paint mixture is composed of resorcinol (8 g), acetone (4 mL), magenta (0.4 g), phenol (4.0 g), boric acid (0.8 g), industrial methylated spirit 90% (8.5 mL), and water (100 mL). Can be prepared in colorless form.
Adult Dose	Apply daily for 2 wk usually qhs
Pediatric Dose	<10 years: Do not administer >10 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Phenols may cross react with resorcin, cresols, and hydroquinone
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Guard against spilling; can stain clothing and skin; may be toxic in children because of phenol content; may cause irritation, especially in diaper or other intertriginous regions; may be toxic in dilute solutions if used over large areas

FOLLOW-UP

Section 8 of 11  

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• Follow-up
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Further Outpatient Care

• Patients should have a follow-up visit after completing the course of therapy. Culturing may be performed to ensure that the infection has cleared.
• Occasionally, when the bacterial infection is resolving, a sudden recurrence and reactivation of an underlying fungal infection may occur because the bacteria can no longer suppress the fungal proliferation.

In/Out Patient Meds

• Medication to control hyperhidrosis may be beneficial in some patients.

Deterrence/Prevention

• The patient's lifestyle should be modified to help prevent recurrence of the infection.
• • Patients who engage in water-related sports should shower afterwards and ensure that interdigital spaces are thoroughly dried to prevent creating an environment for bacterial growth.
  • Open-toed shoes or sandals are encouraged in warm weather to allow air to circulate, which prevents perspiration between the toes that can lead to overgrowth of bacteria and can cause infection.
  • The use of gauze pledgets between the toes helps prevent occlusion, and the use of astringent soaps reduces the number of gram-negative bacteria.

• The use of rubber boots should be avoided.
• The feet should be kept dry if possible. Feet that actually become wet at the workplace rather than simply perspire heavily may be at increased risk of this infection.

Complications

• Cellulitis, as well as sepsis, may complicate this disorder.

Prognosis

• In most patients, the prognosis is excellent. With appropriate therapy, complete recovery is usually attained.

Patient Education

• Patients should be instructed about proper hygiene, which is a primary preventive measure.
• For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center and Skin, Hair, and Nails Center. Also, see eMedicine's patient education articles Impetigo and Antibiotics.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Ensure that the clinical evaluation is correct for gram-negative infection and that the infection is not misdiagnosed. Failure to diagnosis and to properly treat patients runs a small risk of a potentially fatal septicemia.

Special Concerns

• When gram-negative bacteria are treated, the eruption may appear to become worse either from the development of antibiotic resistance or from a proliferation of dermatophytes whose growth was suppressed by the bacillary proliferation.

MULTIMEDIA

Section 10 of 11  

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• Introduction
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• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  A 33-year-old man with interweb exudative patches. Courtesy of Rajendra Kapila, MD, Professor of Infectious Diseases, New Jersey Medical School.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

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2. Leyden JJ. Progression of interdigital infections from simplex to complex. J Am Acad Dermatol. May 1993;28(5 Pt 1):S7-S11. [Medline].
3. Bjornsdottir S, Gottfredsson M, Thorisdottir AS, Gunnarsson GB, Rķkardsdottir H, Kristjansson M, et al. Risk factors for acute cellulitis of the lower limb: a prospective case-control study. Clin Infect Dis. Nov 15 2005;41(10):1416-22. [Medline].
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5. Honig PJ, Frieden IJ, Kim HJ, Yan AC. Streptococcal intertrigo: an underrecognized condition in children. Pediatrics. Dec 2003;112(6 Pt 1):1427-9. [Medline].
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11. Elewski BE, Berlin SJ, Nyirady J. Treatment of tinea pedis when bacterial presence is suspected: a review of the literature. Today Therap Trends. 1999;17:159-65.
12. Fangman W, Burton C. Hyperkeratotic rim of gram-negative toe web infections. Arch Dermatol. May 2005;141(5):658. [Medline].
13. Goldman L, Krevans J. Cecil Textbook of Medicine. ed. Philadelphia, Pa: WB Saunders; 1999:1598.
14. Grunder K, Kroker A, Heppner M, Marre R. [Etiology of pathogen-induced changes between the toes in patients working under moist conditions]. Z Hautkr. Nov 15 1988;63(11):958-65. [Medline].
15. Hope YM, Clayton YM, Hay RJ, Noble WC, Elder-Smith JG. Foot infection in coal miners: a reassessment. Br J Dermatol. Apr; 1985;112(4):405-13. [Medline].
16. Iborra C, Petit A. [Pseudomonas aeruginosa toe web infections: successful treatment by ointment polymyxine B - oxytetracycline (Primyxine)]. Ann Dermatol Venereol. Oct 2000;127(10):844-5. [Medline].
17. Janniger CK, Schwartz RA, Szepietowski JC, Reich A. Intertrigo and common secondary skin infections. Am Fam Physician. Sep 1 2005;72(5):833-8. [Medline].
18. King DF, King LA. Importance of debridement in the treatment of gram-negative bacterial toe web infection. J Am Acad Dermatol. Feb 1986;14(2 Pt 1):278-9. [Medline].
19. Mlinaric-Missoni E, Kalenic S, Vazic-Babic V. Species distribution and frequency of isolation of yeasts and dermatophytes from toe webs of diabetic patients. Acta Dermatovenerol Croat. 2005;13(2):85-92. [Medline].
20. Shenoi SD, Davis SV, Rao S, Rao G, Nair S. Dermatoses among paddy field workers--a descriptive, cross-sectional pilot study. Indian J Dermatol Venereol Leprol. Jul-Aug 2005;71(4):254-8. [Medline].
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Article Last Updated: Jun 21, 2007