Secondary bacterial infections of buruli ulcer lesions before and after chemotherapy with streptomycin and rifampicin

Buruli ulcer (BU), caused by Mycobacterium ulcerans is a chronic necrotizing skin disease. It usually starts with a subcutaneous nodule or plaque containing large clusters of extracellular acid-fast bacilli. Surrounding tissue is destroyed by the cytotoxic macrolide toxin mycolactone produced by microcolonies of M. ulcerans. Skin covering the destroyed subcutaneous fat and soft tissue may eventually break down leading to the formation of large ulcers that progress, if untreated, over months and years. Here we have analyzed the bacterial flora of BU lesions of three different groups of patients before, during and after daily treatment with streptomycin and rifampicin for eight weeks (SR8) and determined drug resistance of the bacteria isolated from the lesions. Before SR8 treatment, more than 60% of the examined BU lesions were infected with other bacteria, with Staphylococcus aureus and Pseudomonas aeruginosa being the most prominent ones. During treatment, 65% of all lesions were still infected, mainly with P. aeruginosa. After completion of SR8 treatment, still more than 75% of lesions clinically suspected to be infected were microbiologically confirmed as infected, mainly with P. aeruginosa or Proteus miriabilis. Drug susceptibility tests revealed especially for S. aureus a high frequency of resistance to the first line drugs used in Ghana. Our results show that secondary infection of BU lesions is common. This could lead to delayed healing and should therefore be further investigated

Challenges associated with management of Buruli ulcer/human immunodeficiency virus coinfection in a treatment center in Ghana : a case series study

The synergy between Mycobacterium tuberculosis infection and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome is well established but not so in Buruli ulcer (BU). We screened confirmed BU cases for HIV infection and followed seven BU/HIV-coinfected patients. Management of BU/HIV was based on the World Health Organization guidelines and patient condition. The HIV positivity among BU patients (8.2%; 11/134) was higher compared with that of general patients attending the facility (4.8%; 718/14,863; P = 0.07) and that of pregnant women alone (2.5%; 279/11,125; P = 0.001). All seven BU/HIV-coinfected cases enrolled in the study presented with very large (category III) lesions with four having multiple lesions compared with 54.5% of category III lesions among HIV-negative BU patients. During the recommended BU treatment with streptomycin and rifampicin (SR) all patients developed immune infiltrates including CD4 T cells in their lesions. However, one patient who received antiretroviral therapy (ART) 1 week after beginning SR treatment developed four additional lesions during antibiotic treatment, while two out of the four who did not receive ART died. Further evidence is required to ascertain the most appropriate time to commence ART in relation to SR treatment to minimize paradoxical reactions

An extensive category III oedematous lesion involving the anterior and posterior chest and neck regions, with two ulcers: one at the anterior triangle of the neck, measuring 6 cm x 8 cm, and another over the midsternal region of the chest, measuring 3 cm x 4 cm.

<p>An extensive category III oedematous lesion involving the anterior and posterior chest and neck regions, with two ulcers: one at the anterior triangle of the neck, measuring 6 cm x 8 cm, and another over the midsternal region of the chest, measuring 3 cm x 4 cm.</p

Chest radiographs of patient before and during antibiotic chemotherapy for <i>M. ulcerans</i> disease.

<p>(A) Chest X-ray taken before antibiotic therapy was started. (B) Chest X-ray taken 2 weeks after initiation of antibiotic therapy, showing bilateral pleural effusions. (C) Week 3 after drainage of pleural effusion. (D) Recurrence of pleural effusion on the right hemithorax at week 4.</p

Histopathological analysis of tissue from two patients excised weeks after SR8 treatment respectively.

<p>Histological sections were stained with Ziehl-Neelsen (acid fast bacteria) and methylene blue (DNA, secondary infection). A: clinical presentation of patient 9 presenting with a large lesion on the right foot. B: overview over excised tissue specimen (open ulcer surface) revealing the presence of an infection (blue band, box). C/D: higher magnification confirming the presence of densely packed rods. E: clinical presentation of patient 16 presenting with a large lesion covering the left leg. F: overview over excised tissue specimen revealing an epidermal hyperplasia as well as a strong edema. G/H: secondary infection with rods of the dermal and subcutaneous tissue.</p

Antibiotic susceptibility pattern of different bacterial species isolated from BU wounds.

<p>Antibiotic susceptibility pattern of different bacterial species isolated from BU wounds.</p

Presentation of wounds that were clinically infected after SR8 compared to microbiology and histology findings.

<p>We compared the clinical presentation to microbiological categorization based on quantification and histological findings. Lesions with a bacterial load less than 10⁶ CFU/ml (or CFU/g) were categorized as contaminated, while lesions with bacterial loads above were considered as infected.</p>1<p>WHD = Wound healing delay.</p>2<p>SGF = Skin grafting failure.</p><p>n/d = not done.</p

Histopathological analysis of tissue excised before start of SR8 treatment.

<p>Histological sections were stained with Ziehl-Neelsen (acid fast bacteria) and methylene blue (DNA, secondary infection). A: Overview over excised tissue specimen revealing infection at the lower end of the specimen (box), as well as BU characteristic histopathological features, including fat cell ghosts, necrosis and epidermal hyperplasia. B/C: higher magnification revealing the presence of cocci. D: clinical presentation of the lesion on the belly.</p