Granuloma Inguinale (Donovanosis) Treatment & Management

Although various antimicrobial regimens have been used in the past and have been shown to be effective, there have only been a limited number of published controlled trials demonstrating the effectiveness of a particular therapeutic agent.

The current first-line drug according to the US Centers for Disease Control and Prevention (CDC) is azithromycin. ^[13] Alternative regimens include doxycycline, ciprofloxacin, erythromycin base, and trimethoprim-sulfamethoxazole. All antibiotics should be given for at least a 3-week course and continued until reepithelialization of the ulcer occurs and all signs of the disease have resolved. If the granuloma inguinale ulcers do not respond within the first days of therapy, add an aminoglycoside (eg, gentamicin 1 mg/kg IV q8h). Relapse of granuloma inguinale may occur 6-18 months after apparently effective therapy and treatment should be reinitiated at that time.

Since there have been past documented reports of tetracycline resistance, it is no longer recommended. ^[14]

Special considerations

The drugs of choice in pregnant and lactating women are macrolides (erythromycin or azithromycin). However, since erythromycin estolate has been associated with hepatotoxicity in as many as 10% of pregnancies, erythromycin base or erythromycin ethylsuccinate should be prescribed. ^{[15, 16]}

Doxycycline is classified as FDA category D and should be avoided in pregnancy, especially after 15 weeks’ gestation because of the risk of maternal hepatitis and brown discoloration of the infant’s deciduous teeth and inhibition of bone growth. It should also avoided in patients who are breastfeeding, since prolonged exposure beyond 3 weeks may also cause decreased bone growth. ^[17]

Ciprofloxacin is classified as FDA category C since animal studies indicate that it can be associated with damage to fetal cartilage. When given to breastfeeding women, observe for diarrhea in the infant since it can cause pseudomembranous colitis. ^[17]

Trimethoprim-sulfamethoxazole is also classified as FDA category C since there is a risk of cardiovascular defects when given in the first trimester, and it is associated with preterm delivery, low birth rate, and miscarriage. Sulfonamides are also associated with serious kernicterus in patients with G-6-P deficiency, and, when given in the third trimester of pregnancy, there is a higher risk of neonatal hyperbilirubinemia. Lastly, since trimethoprim is associated with depression of folate levels, supplementation of folate should be given if the medication must be used, especially during the first trimester. ^[17]

HIV-associated granuloma inguinale may take longer to heal, and the addition of a parenteral aminoglycoside to the regimen is highly recommended. ^[18] Note that malignant transformation and autoamputation have both been reported in HIV-positive patients with granuloma inguinale. ^{[10, 19]}

Sexual contacts within 60 days prior to onset of symptoms should be examined and offered therapy if clinical signs and symptoms are established; however, the value of empiric therapy in asymptomatic patients is uncertain.

Just as with immunocompetent patients with granuloma inguinale, patients with concomitant HIV infection or who are pregnant, the addition of a parenteral aminoglycoside (eg, gentamicin) should be considered if no improvement is seen within the first few days of standard antibiotic therapies.

Recommended dosing is as follows:

• Azithromycin 1 g PO once a week or 500 mg/day for at least 3 weeks or until all lesions have completely healed

• Doxycycline 100 mg PO twice a day for at least 3 weeks or until all lesions have completely healed

• Erythromycin base 500 mg PO 4 times a day for at least 3 weeks or until all lesions have completely healed

• Ciprofloxacin 750 mg PO twice a day for at least 3 weeks or until all lesions have completely healed

• Trimethoprim-sulfamethoxazole 1 double strength (160 mg/800 mg) tablet PO twice a day for at least 3 weeks or until all lesions have completely healed

A clinical guideline summary is available from the US Centers for Disease Control and Prevention: 2015 Sexually Transmitted Diseases Treatment Guidelines-Granuloma Inguinale (Donovanosis). ^{[20, 21]}

Once granuloma inguinale is healed, disfiguring genital swellings may need to be surgically corrected.

Positive strides have been made in reducing the incidence of granuloma inguinale in endemic regions.

Australia and its surrounding indigenous areas have witnessed a decrease in the incidence of granuloma inguinale through the establishment of a National Donovanosis Eradication Advisory Committee. The committee consists of project officers representing different geographic areas who work closely with primary care healthcare providers.

The goal is to develop educational materials, conduct in-service teaching for staff in rural and remote areas, implement common protocols for treatment and diagnosis, and undertake active surveillance. Since the development of the committee in 2001, the number of new cases of granuloma inguinale has fallen to the lowest levels since the commencement of accurate epidemiological data collection.

This committee represents a proven model of public health intervention, using centralized officers with expertise in sexually transmitted infection who liaise with primary healthcare providers. A similar model may help reduce the incidence of disease in other endemic areas. ^[22]