Chambers HF, Turner J, Wagner C, Schecter G, Hopewell P; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 1996 Sep 15-18; 285 (abstract no. LM27).

San Francisco General Hospital, San Francisco, CA.

Biochemical and susceptibility data indicate that Imi is the most active of all beta-lactam antibiotics against Mycobacterium tuberculosis [Mtb]. Imi and Ak were shown to be synergistic against Mtb in time-kill studies. 3 consecutive patients with MDR TB who were failing therapy [Rx] with second line agents were treated with Imi, 15 mg/kg, iv bid + Ak, 15 mg/kg/d, iv. Patient 1, a 30 year old [y/o] female, had positive smears and cultures [cult.] for 11 years despite multiple courses of directly observed therapy [DOT]. The isolate was resistant to isoniazid [INH], rifampin [RIF], pyrazinamide [PZA], ethionamide [ETH], ofloxacin [OFX], and ethambutol [EMB] (5 micrograms/ml). DOT with cycloserine [CS], para-aminosalicylic acid [PAS], streptomycin [STM], and clofazamine [CFZ] was instituted. Sputum remained smear positive and secondary [2(degrees)] resistance to STM developed. Imi, Ami and EMB 50 mg/kg twice weekly were added to the regimen of CS, PAS, and CFZ. Sputum became cult.-negative after 60 d of Rx and remains so at 12 mo follow-up [f/u]. Patient 2, a 27 y/o female, developed acute respiratory failure while receiving INH, RIF, PZA, and EMB for sputum smear-positive TB. The isolate was resistant to INH, RIF, PZA, and to INH, RIF, PZA, and STM and 2(degrees) resistance developed to EMB. Rx with Imi, Ak, and OFX, 60 mg/d orally, was instituted. Sputum became cult.-negative at 2 mo and remains negative after 6 mo f/u. Patient 3, a 61 y/o female with TB resistant to INH, RIF, PZA, and EMB was cult.-positive for 2 years despite DOT with CFZ, CS, ciprofloxacin, and Ak. Imi + Ak (10 mg/kg thrice weekly), ETH, OFX, and CFZ was instituted. Cult. became negative after 7d and remains so at 3 mo f/u. Use of multiple drugs complicates analysis of efficacy of individual agents, nevertheless the temporal association of microbiological response with institution of Imi-Ak combination therapy argues strongly that these agents were responsible. These results suggest that beta-lactam antibiotics have a role in Rx of TB.

Publication Types:

• Meeting Abstracts

Keywords:

• Amikacin
• Directly Observed Therapy
• Drug Therapy, Combination
• Ethambutol
• Ethionamide
• Female
• Humans
• Imipenem
• Isoniazid
• Monobactams
• Mycobacterium tuberculosis
• Ofloxacin
• Pyrazinamide
• Rifampin
• Sputum
• Streptomycin
• Tuberculosis, Multidrug-Resistant
• p-Aminosalicylic Acid

Other ID:

• 98927999

UI: 102235173

From Meeting Abstracts