Use of beta-lactam/beta-lactamase-inhibitor combinations as antimycobacterial agents.

Mycobacterium tuberculosis and Mycobacterium leprae develop resistance against the drugs used to treat tuberculosis and leprosy, respectively. Now multidrug-resistant tuberculosis is spreading in many countries, especially with the emergence of AIDS. Multidrug treatment is being promoted at present to eradicate leprosy. Since M. leprae may also become multidrug-resistant, new approaches have to be adopted for controlling mycobacterial diseases. Mycobacteria usually synthesize beta-lactamase and are insensitive to beta-lactam antibiotics. M. tuberculosis contains a constitutive beta-lactamase; de-repression of beta-lactamase has been reported in M. leprae. Three different beta-lactam/beta-lactamase-inhibitor combinations (ampicillin/sulbactam, amoxicillin/clavulanate and piperacillin/tazobactam) were used to suppress the growth of several strains of mycobacteria (including M. tuberculosis H37Rv) in vitro. Ampicillin/sulbactam is a potent bactericidal agent against M. leprae multiplying in mouse foot pads. In the present work, ampicillin/sulbactam showed higher activity than the other drug combinations. The beta-lactam/beta-lactamase inhibitors are likely to be effective as rational therapeutic agents against mycobacterial infections.

Unique metabolic properties of Mycobacterium leprae.

My first contact with Dr. Dharmendra was through correspondence. While working for Ph.D., I wrote to him that a section in his book "Notes on Leprosy" was ambiguous. Instead of ignoring the letter, he replied, agreeing to clarify it in the revised edition. I went to work at Carville at the invitation of Dr. Kirchheimer, who had seen my Ph.D. thesis. Dr. Dharmendra visited Carville to receive the Damien-Dutton award and stayed there for a few days. Carville is an isolated place with no public transportation. I used to take him for afternoon drives to the countryside around Carville. He published some of our papers in Leprosy in India and later in Indian Journal of Leprosy. He was very prompt in acknowledging receipt of manuscripts and suggesting any changes to be made. He also reprinted in the Journal several of our papers published elsewhere, and also a lecture I gave at a meeting of the Japanese Leprosy Association. During one of my visits to India, Dr. M. C. Vaidya had arranged a talk by me at the All India Institute of Medical Sciences, New Delhi. At the invitation of Dr. Dharmendra, I visited him in his home. We used to exchange new year cards and letters. He wrote to me about his eye infection and consequent loss of sight in one eye. He asked me to write an editorial for an issue of Indian Journal of Leprosy (January 1989). The last time I met him was during the International Leprosy Congress held in New Delhi.