Activity of Sulfa Drugs and Their Combinations against Stationary Phase B. burgdorferi In Vitro

Abstract

Lyme disease is a most common vector-borne disease in the US. Although the majority of Lyme patients can be cured with the standard two- to four-week antibiotic treatment, at least 10%–20% of patients continue to suffer from prolonged post-treatment Lyme disease syndrome (PTLDS). While the cause for this is unclear, one possibility is that persisting organisms are not killed by current Lyme antibiotics. In our previous studies, we screened an FDA drug library and an NCI compound library on B. burgdorferi and found some drug hits including sulfa drugs as having good activity against B. burgdorferi stationary phase cells. In this study, we evaluated the relative activity of three commonly used sulfa drugs, sulfamethoxazole (Smx), dapsone (Dps), sulfachlorpyridazine (Scp), and also trimethoprim (Tmp), and assessed their combinations with the commonly prescribed Lyme antibiotics for activities against B. burgdorferi stationary phase cells. Using the same molarity concentration, dapsone, sulfachlorpyridazine and trimethoprim showed very similar activity against stationary phase B. burgdorferi enriched in persisters; however, sulfamethoxazole was the least active drug among the three sulfa drugs tested. Interestingly, contrary to other bacterial systems, Tmp did not show synergy in drug combinations with the three sulfa drugs at their clinically relevant serum concentrations against B. burgdorferi. We found that sulfa drugs combined with other antibiotics were more active than their respective single drugs and that four-drug combinations were more active than three-drug combinations. Four-drug combinations dapsone + minocycline + cefuroxime + azithromycin and dapsone + minocycline + cefuroxime + rifampin showed the best activity against stationary phase B. burgdorferi in these sulfa drug combinations. However, these four-sulfa-drug–containing combinations still had considerably less activity against B. burgdorferi stationary phase cells than the Daptomycin + cefuroxime + doxycycline used as a positive control which completely eradicated B. burgdorferi stationary phase cells. Future studies are needed to evaluate and optimize the sulfa drug combinations in vitro and also in animal models.

Effect of Dapsone Alone and in Combination With Intracellular Antibiotics Against the Biofilm Form of B. Burgdorferi

“…In this study, we compared and evaluated the antimicrobial effect of dapsone along with the other clinically tested antibiotics (doxycycline, rifampin, azithromycin, cefuroxime) on the growth and viability of attached B. burgdorferi bio lms using standard crystal violet bio lm mass and dimethylmethylene blue glycosaminoglycan assays combined with BacLight Live/Dead microscopic analysis. As in the previous studies from our group and others [30,35], we tested two different antibiotic concentrations (10 µM and 50 µM) against attached B. burgdorferi bio lm structures. The 10 µM in vitro concentration corresponds well to the achievable serum level after administration of the antibiotics tested in this study [37,38,39,40,41].…”

“…An in vitro study [35] evaluated DDS for activity against persisters and found it was not only the most active sulfa drug, but clinically superior to other antibiotics including rifampin, azithromycin, and minocycline. Unfortunately, these researchers did not evaluate DDS combinations against attached B.…”

Synthesis and Antimicrobial Activity of Arylazopyrazole Pyrimidone Clubbed Heterocyclic Compounds

“…Where, X: Area of colony in control plate Y: Area of colony in test plate The fungicidal activity all compounds (5a-e) and (4a-e) are shown in Table- The structures of (3a-e) were confirmed by elemental analysis and IR spectra showing an absorption bands at 3500(N-H),3030-3080 cm -1 (C-H of Ar), 1680 cm -1 (CONH), 2950, 1370 cm -1 (-CH 3 , CH 2 ), 1080(-Cl),1555, 1375(-NO 2 ),1695-1750 cm -1 (C=O). 1 Table -2.…”

“…), 2960, 1370 cm -1 (-CH 3 ), 1710-1760(C=O),1380, 1160(SO 2 ), 1080(-Cl),1555, 1375(-NO 2 ), 3330 and 3155 cm -1 (NH) and 1585, 1548, and 1530 cm -1 (C=C). 1 Table -3.…”

“…The sulphonamides are synthetic antimicrobial agents with a wide spectrum encompassing most Gram-positive and many Gram-negative organisms. [1][2][3] The heterocyclic compound, pyrimidinones shows various antimicrobial, hypnotic, antiviral, sedative, antineoplastic, anticonvulsant, analgesic and anti-inflammatory. [4][5][6][7][8][9] The nitrogen containing pyrazole and its derivatives is show application in medicinal chemistry like antibactiral,antifungal,analgesic, anti-inflammatory, antipyretic, antiparasitic and antimalarial.…”