Gram-Negative Toe Web Infection

Updated: Apr 07, 2023
Author: Robert A Schwartz, MD, MPH; Chief Editor: William D James, MD 


Practice Essentials

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. Over time, in the setting of moisture and maceration, multiple fungal and bacterial organisms may proliferate.[2] The process may progress to advanced stages of gram-negative infection with sepsis. Similarly, staphylococcal extranasal carriage in toe webs may also be a risk factor for sepsis in patients who receive hemodialysis.[3] Note the image below.

A 33-year-old man with interweb exudative patches. A 33-year-old man with interweb exudative patches. Courtesy of Rajendra Kapila, MD, Professor of Infectious Diseases, New Jersey Medical School.

Signs and symptoms

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.


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.

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.


Also see Treatment and Medication.

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.

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.[4]

Another approach is to combine acetic acid with a topical antifungal, a combination producing a complete response in 8 of 10 patients with a P aeruginosa toe web infection.[5]

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.

Recognizing concerns regarding antimicrobial resistance, other strategies have been suggested, such as antimicrobial photodynamic therapy and antimicrobial peptides.[6]

In severe cases where systemic symptoms suggest septicemia, therapy should be initiated while awaiting blood culture results.

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.[7]


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.[8]

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, 9]  Green nail syndrome, toe web infection, hot tub folliculitis, hot hand-foot infection, and external otitis are the most common infections originating from the skin itself.[10, 11, 12]

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.

A US military survey for gram-negative bacteria colonization in healthy, asymptomatic military personnel (101 in the United States and 100 in Afghanistan) showed toe web spaces colonized in 35% with non–multidrug-resistant bacteria.[13]


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. Predisposing factors may include eczema and psoriasis, tinea pedis, exposure to humidity or hyperhidrosis, and vascular disorders and diabetes mellitus. There may be an association between foot gram-negative bacteria and diabetic foot ulceration. A long duration of type 2 diabetes may produce an increased risk of gram-negative bacterial infection.[14]

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.



United States

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


A limited number of cases have been reported.

Gram-negative toe web infection can affect any race. Men appear to be more frequently affected, with a male-to-female ratio of 4:1 reported in 1 study.[1]

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


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.




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.[15] 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.


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.[16] Improved awareness and management of toe web intertrigo, which may harbor bacterial pathogens, may reduce the prevalence of cellulitis. This bacterial, nonnecrotizing cellulitis tends to remain localized and often is recurrent.[17]

A Pseudomonas toe web infection may be complicated by an autosensitization dermatitis.[18]



Diagnostic Considerations

Group A beta-hemolytic streptococci may produce a variety of common childhood cutaneous infections.[19] 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 contemplated in the differential diagnosis of interweb toe infections.

Fungal interdigital tinea pedis should also be considered.[20] Fusarium solani infection may be the nondermatophytic filamentous fungi responsible. 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.[21] Infection with this mold is potentially dangerous for the immunosuppressed.

Diabetic patients with ischemic foot ulcers differ with neuropathic foot ulcer patients in having a higher frequency of S epidermidis skin colonization and ulcer infection. S epidermidis may be a nosocomial pathogen.[22] The relationship of each other type to interweb infections remains to be determined.

Trichophyton tonsurans tinea gladiatorum is an emerging epidemic among combat-sport athletes, which may involve scalp, trunk, groin, and toe web spaces.[23]

Itchy maceration of the toe webs is a common disorder often confused with tinea. Bacterial cultures often grow mixed pathogens (93%). Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus were the most common pathogens in one study.[24]

In addition, dermatophytids, which result from sensitization to a dermatophyte infection, may be associated with toe web intertrigo.[25]

Interdigital intertrigo and onychomycosis may result in severe bacterial infection with complications including pain, mobility problems, abscess, erysipelas, cellulitis, fasciitis, and osteomyelitis.[26, 27] Dermatophytic infections in interdigital spaces damage the stratum corneum, leading to bacterial proliferation and secondary infection. Although toe web intertrigo temporarily disrupts the skin barrier and is a risk factor for erysipelas, it may not predispose to repeated episodes of erysipelas.[28] Another study found a significant association between interdigital tinea pedis and the recurrence rate of erysipelas, but not with erysipelas itself.[29]

The interdigital bacterial infection erythrasma, caused by Corynebacterium minutissimum, should also be considered.[30, 31] Wood-lamp examination is a good idea, but it may not identify all of those infected with this gram-positive rod.

Differential Diagnoses




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.


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.


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.

Long-Term Monitoring

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.



Medication Summary

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.[32] Debridement may be of value. Drying of the interdigital spaces is paramount. Sertaconazole nitrate cream 2% or any comparable azole or allylamine is beneficial the treatment of tinea pedis interdigitalis.[33]

Antifungal agents (topical)

Class Summary

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

Econazole topical (Ecoza)

Econazole nitrate cream is an antifungal agent that is a water-miscible base consisting of pegoxol 7 stearate, peglicol 5 oleate, mineral oil, benzoic acid, butylated hydroxyanisole, and purified water. The color of the soft cream is white to off white, and it is for topical use only. It exhibits broad-spectrum activity against many gram-negative organisms. Econazole nitrate cream 1% is supplied in tubes of 15 g, 30 g, and 85 g.

Antibiotic agents

Class Summary

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

Cefotaxime (Claforan)

This is a third-generation semisynthetic broad-based antibiotic with a gram-negative spectrum. It has lower efficacy against gram-positive organisms. Specimens for bacteriologic culture should be obtained prior to therapy to test for susceptibilities to cefotaxime.

Ciprofloxacin (Cipro)

Ciprofloxacin is a synthetic broad-spectrum antimicrobial agent that inhibits bacterial DNA synthesis and, consequently, growth. The film-coated tablet is available in 100 mg, 250 mg, 500 mg, and 750 mg. The oral suspension is white to slightly yellow with a strawberry flavor and may contain yellow-orange droplets. Tablets are well absorbed in the gastrointestinal tract after oral administration. Ciprofloxacin has a wide range of activity against gram-negative organisms.

Gentamicin sulfate (G-Myticin, Jenamicin, Garamycin)

Gentamicin sulfate is a 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. It treats superinfections caused by fungi or viruses. It treats skin and skin structure infections. The usual duration of treatment is 7-10 days. In more serious infections, a longer course of therapy is needed. Patients should be well hydrated during treatment. Gentamicin sulfate may also be used parenterally as a water-soluble injection against a wide variety of pathogenic bacteria. It may be considered as initial therapy in suggested or confirmed gram-negative infections, and therapy may be instituted before obtaining results of susceptibility testing.