In vitro synergistic activity between ofloxacin and ansamycins against Mycobacterium leprae.

The antimicrobial effects of ofloxacin, alone and in combination with either rifampicin or rifabutin, were evaluated against M. leprae, using in vitro cell-free culture system. The minimum inhibitory concentration (MIC) of ofloxacin against M. leprae was 1.5 micrograms/ml, while MICs of rifampicin and rifabutin were 0.4 and 0.2 microgram/ml, respectively. Combination of 0.375 microgram/ml ofloxacin and 0.05 microgram/ml of rifabutin exhibited synergistic bactericidal activity while the effect of combination of 0.75 microgram/ml ofloxacin and 0.2 microgram/ml rifampicin was additive bactericidal. Thus, combination of ofloxacin and rifabutin deserves further attention in multi-drug therapy of leprosy.

In vitro and in vivo interactions of drugs used in multidrug therapy in leprosy.

Interactions of different drugs commonly used in multiple drug therapy were evaluated using both in vitro culture (cell-free as well as macrophage) system and mouse footpad. No additive effects were obtained in the in vitro system when dapsone was combined with either rifampicin or clofazimine, while a strong antagonism was observed when clofazimine was combined with rifampicin but not with rifabutin. In the mouse footpad system, a strong synergism was obtained when clofazimine was combined with either rifampicin or rifabutin, but significant antagonism was observed with the combination of clofazimine and dapsone.

In vitro and in vivo effects of N-methyl-3,5-dichloro-benzylamine hydrochloride on Mycobacterium leprae.

The antimicrobial effects of a new benzylamine, ME-93 (N-methyl-3,5-dichloro-benzylamine hydrochloride), alone and in combination with dapsone and rifampicin, have been evaluated in vitro in cell-free culture system and in vivo in mouse foot pad system. Even at 50 micrograms/ml, ME-93 did not completely inhibit the in vitro growth of M. leprae, and the effects were bacteriostatic. However, there was a synergism when ME-93 was combined with rifampicin, and the effects were bactericidal. Similar findings were also obtained in the mouse foot pad system. Thus, there is a new drug that needs further attention in the chemotherapy of leprosy.

Effect of brodimoprim on Mycobacterium leprae in vitro and in mouse foot-pads.

The new in vitro screening system reported earlier was adopted to determine anti-M. leprae activity of a dihydrofolate reductase inhibitor, brodimoprim, and the results were compared with those obtained using mouse foot-pad technique. Even though the MIC of brodimoprim against M. leprae was very high compared to other commonly used anti-leprosy drugs, in combination with dapsone it showed a remarkable synergistic activity in inhibiting the growth of M. leprae at concentrations much lower than the MICs of each of the drugs used singly. Similar effects were also demonstrated in mouse foot-pad experiments.

Surgical treatment in familial visceral myopathy.

In a kindred with a familial visceral myopathy, seven patients had operations seeking relief of chronic abdominal pain and other symptoms of intestinal obstruction; one patient had an 80% cystectomy and a Y-V-plasty of the bladder neck for urinary retention. Five patients with megaduodenum had bypass operations; a side-to-side duodenojejunostomy was done in four and a retrocolic gastrojejunostomy in one. Two of these died of postoperative complications, and one developed symptomatic adhesions. Two other patients who had duodenojejunostomy have done well for 6 years and 1 1/2 years respectively. One patient with dilation of the distal jejunum and proximal ileum had relief of intestinal obstructive symptoms from jejunostomy to decompress the destal jejunum. One patient who had a resection of the descending and sigmoid colon for sigmoid volvulus has done well for four years. Three of these seven patients developed peritonitis postoperatively, and two had symptomatic adhesions after operations. Duodenal aspiration from a patient who developed postoperative peritonitis grew E. coli, 10(13) colonies per ml. After review of the results of operations in other families and in our kindred, we favor side-to-side duodenojejunostomy in megaduodenum. Duodenal aspirate must be cultured before operation. Evidence of bacterial overgrowth in the aspirate should prompt appropriate antibiotic treatment to reduce the likelihood of sepsis.

A familial visceral myopathy.

A kindred contained at least 18 members with visceral myopathy. Sixteen had symptoms of chronic obstruction of the gastrointestinal or urinary tracts. Of six patients with megaduodenum on contrast roentgenograms, two were asymptomatic. Four patients had redundant colon on barium enema, and four had megacystis. Specimens from duodenum, jejunum, ileum, colon, or urinary bladder from five patients showed thinning and extensive collagen replacement of the longitudinal muscle layer; ganglion cells were normal by light and electron microscopy. Esophageal manometry in three patients showed decreased gastroesophageal sphincter pressures and no contractions in the smooth muscle segment of the esophagus; duodenal manometry showed a low frequency and amplitude of contractions. Three patients developed fever and signs of peritonitis after operations to bypass dilated segments. This seems to be a generalized smooth muscle disease with variable clinical manifestations and with an autosomal dominant or sex-linked dominant mode of inheritance.