Ureaplasma species (Ureaplasma spp.) are commonly found as commensals in the human urogenital tracts , but their overgrowth can lead to infection in the urogenital tract and at distal sites. Treatment of Ureaplasma spp. infections is difficult. The lack of a cell wall confers resistance to all β-lactam and glycopeptide antibiotics whereas the lack of de novo synthesis of folic acid makes them resistant to sulfonamides and diaminopyrimidines. Thus, there is a need to search for new drugs effective against these bacteria. In the presented studies, the effect of N,N-diethyldithiocarbamate (DDC) at a concentration of 2 µg/ml, 20 µg/ml and 200 µg/ml on the growth and survival of Ureaplasma urealyticum and Ureaplasma parvum was tested. Our results indicated that all DDC concentrations used showed both bacteriostatic and bactericidal activity against both tested strains In brief, for the first time we showed the bacteriostatic and bactericidal activity of DDC against Ureplasma urealyticum and Ureaplasma parvum. Based on literature data, we conclude that this DDC activity is related to the inhibition of urease activity, which is an indispensable enzyme for these bacteria. Further research is needed and the results obtained in the present study should be verified in in vivo models of infection.

Lyme disease and associated co-infections are increasing worldwide and approximately 20% of individuals develop chronic Lyme disease (CLD)/Post-Treatment Lyme Disease Syndrome (PTLDS) despite early antibiotics. A 7–8-week protocol of double dose dapsone combination therapy (DDDCT) for CLD/PTLDS results in symptom remission in approximately 50% of patients for one year or longer, with published culture studies indicating higher doses of dapsone demonstrate efficacy against resistant biofilm forms of Borrelia burgdorferi. The purpose of this study was therefore to evaluate higher doses of dapsone in the treatment of resistant CLD/PTLDS and associated co-infections. Twenty-five patients with a history of Lyme and associated co-infections, most of whom had ongoing symptoms despite several courses of DDDCT, took one or more courses of high dose pulsed dapsone combination therapy (200 mg dapsone X 3-4 days and/or 200 mg BID x 4 days), depending on persistent symptoms. The majority of patients noticed sustained improvement in 8 major Lyme symptoms, including fatigue, pain, headaches, neuropathy, insomnia, cognition, and sweating, where dapsone dosage, not just treatment length, positively affected outcomes. High dose pulsed dapsone combination therapy may represent a novel therapeutic approach for the treatment of resistant CLD/PTLDS, and should be confirmed in randomized, controlled clinical trials.

Disulfiram (DSF), an anti-alcoholism medicine, exerts treatment effects in patients suffering from persistent Borreliosis and also exhibits anti-cancer effects by its copper chelating derivatives. Since chronic/persistent borreliosis is characterized by increased amounts of proinflammatory macrophages, this study investigated opsonin-independent phagocytosis, migration and surface marker expression of in vivo activated human monocyte-derived macrophages and dendritic cells with and without DSF treatment. Phagocytosis of non-opsonized Dynabeads® M-450 and migration of macrophages and dendritic cells were monitored using live cell analyzer Juli™ Br for 24h by imaging every 3.5 min. Results were analyzed by a newly developed software based on the differential phase contrast images of cells before and after ingestion of Dynabeads bearing an electron dense iron core. As a control, phagocytosis was also monitored by visual counting of ingested beads. DSF decreased the phagocytic capacities exhibited by global macrophages and dendritic cells. DSF also impaired the migration of human monocyte-derived macrophages and dendritic cells (hMDMD) and significantly reduced the expression densities of surface antigens CD45 and CD14. In cells consisting of anti-inflammatory M2 macrophages, DSF led to a remarkable cell death and also increased oxidative stress as determined by MitoSox staining. Mitochondrial oxidative stress was a prominent feature in M2 macrophages which were more sensitive to DSF-induced cytotoxicity.