Microbiology of secondary infections in Buruli ulcer lesions; implications for therapeutic interventions

Abstract

Background Buruli ulcer (BU) is a skin disease caused by Mycobacterium ulcerans and is the second most common mycobacterial disease after tuberculosis in Ghana and Côte d’Ivoire. M. ulcerans produces mycolactone, an immunosuppressant macrolide toxin, responsible for the characteristic painless nature of the infection. Secondary infection of ulcers before, during and after treatment has been associated with delayed wound healing and resistance to streptomycin and rifampicin. However, not much is known of the bacteria causing these infections as well as antimicrobial drugs for treating the secondary microorganism. This study sought to identify secondary microbial infections in BU lesions and to determine their levels of antibiotic resistance due to the prolonged antibiotic therapy required for Buruli ulcer. Results Swabs from fifty-one suspected BU cases were sampled in the Amansie Central District from St. Peters Hospital (Jacobu) and through an active case surveillance. Forty of the samples were M. ulcerans (BU) positive. Secondary bacteria were identified in all sampled lesions (N = 51). The predominant bacteria identified in both BU and Non-BU groups were Staphylococci spp and Bacilli spp. The most diverse secondary bacteria were detected among BU patients who were not yet on antibiotic treatment. Fungal species identified were Candida spp, Penicillium spp and Trichodema spp. Selected secondary bacteria isolates were all susceptible to clarithromycin and amikacin among both BU and Non-BU patients. Majority, however, had high resistance to streptomycin. Conclusions Microorganisms other than M. ulcerans colonize and proliferate on BU lesions. Secondary microorganisms of BU wounds were mainly Staphylococcus spp, Bacillus spp and Pseudomonas spp. These secondary microorganisms were less predominant in BU patients under treatment compared to those without treatment. The delay in healing that are experienced by some BU patients could be as a result of these bacteria and fungi colonizing and proliferating in BU lesions. Clarithromycin and amikacin are likely suitable drugs for clearance of secondary infection of Buruli ulcer.

Variable Number Tandem Repeat Profiling of Mycobacterium ulcerans Reveals New Genotypes in Buruli Ulcer Endemic Communities in Ghana and Côte d’Ivoire

“…The clinical samples were processed according to Gyamfi et al (2021) . The swabs were processed for culture and DNA extraction.…”

“…The disease causes extensive necrosis of the skin and underlying tissues which can lead to severe ulceration if treatment is delayed ( Johnson et al, 2005 ). Even though BU is not fatal, the associated lengthy hospital stays during treatment, risk of secondary infections, permanent deformities and joint contractures, cost of surgery, and social stigma often result in a dire social and economic burden on the families of affected individuals ( Grietens et al, 2008 ; Adamba and Owusu, 2011 ; Gyamfi et al, 2021 ).…”

Recent Advances in the Management Strategies for Buruli Ulcers

“…The combination of rifampicin, levofloxacin, and clarithromycin is used in Japan [ 9 ]. Microbiological studies on patients with BU revealed that there is additional colonization with Staphylococcus spp., Bacillus spp., and Pseudomonas spp., which can delay recovery [ 49 ]. Since the lesions are painless, patients frequently seek medical attention in later stages, when antibiotic therapy is less effective.…”

Clinical and microbiological predictors of healing in Buruli ulcer disease

“…Time to complete wound closure is a crucial endpoint for clinicians managing BU wounds. Buruli lesions treated with antibiotics may heal rapidly or enlarge due to breakdown of necrotic tissue, experience a paradoxical reaction, or develop secondary bacterial infection; these can delay wound healing [3] , [7] , [8] , [9] , [10] , [11] . Establishing the time to healing or rate of healing at patient presentation can be a challenge highlighting the need for tools to guide critical care decisions.…”