The in vitro activities of TP-271, a novel fluorocycline antimicrobial, against 22 isolates of Mycobacterium abscessus, 22 isolates of Mycobacterium fortuitum, and 19 isolates of Nocardia spp. were studied by a microtiter broth dilution method. The MIC 90 s for M. abscessus, M. fortuitum, and Nocardia spp. were 0.5 g/ml, 0.03 g/ml, and 8 g/ml, respectively. TP-271 was significantly more active than the respective control drug in virtually all tests. Mycobacterium abscessus and Mycobacterium fortuitum are rapidly growing mycobacteria that are associated primarily with opportunistic infections in immunocompromised subjects (2). Patients with bronchiectasis, especially those with cystic fibrosis, are at increased risk of M. abscessus infection. Other manifestations of M. abscessus infection include localized skin infections, postoperative wound infections, and infection of implanted medical devices. M. fortuitum is a relatively rare pathogen, even in immunocompromised individuals, but has been associated with skin infections and hospital-acquired postoperative infections (2). The most common clinical form of Nocardia infection is pulmonary nocardiosis, with and without dissemination, followed by skin and soft tissue infection (5).Infections due to these microorganisms are occurring with increasing frequency and are often difficult to treat, especially the mycobacterial infections. Successful treatment is often hindered by the need for combination therapy, resistance to multiple drugs, necessity of long treatment duration, and lack of sufficiently active oral drugs (2, 3, 6).While Nocardia remains susceptible to trimethoprim-sulfamethoxazole in the majority of cases, effective alternative oral therapy is lacking. Mortality from pulmonary nocardiosis remains high, in the range of 15 to 40% (5, 11).TP-271 is a novel, fully synthetic fluorocycline antimicrobial related to tetracycline ( Fig. 1) (1, 10). It has been shown to have potent broad-spectrum in vitro and in vivo activity against multiple community-acquired organisms, including Staphylococcus spp., Streptococcus spp., Haemophilus influenzae, Moraxella catarrhalis, Legionella pneumophila, and Acinetobacter baumannii, as well as biothreat organisms (Bacillus anthracis, Francisella tularensis, Burkholderia pseudomallei, and Burkholderia mallei) (4). The activity of TP-271 was shown to be unaffected by the Gram-positive tetracycline-specific pump tet(K) and ribosomal protection mechanism tet(M) and minimally affected by the most common Gram-negative efflux mechanisms, tet(A) and tet(B) (7). Promising oral activity was demonstrated by TP-271 in neutropenic mouse models of pneumonia caused by methicillin-resistant Staphylococcus aureus and Streptococcus pneumoniae and in immunocompetent models of pneumonia caused by S. pneumoniae in mice and H. influenzae in rats (4).As a first step in its assessment as a novel therapy to treat infections caused by M. abscessus, M. fortuitum, and Nocardia spp., we evaluated the in vitro activity of TP-271 in comparison to those of se...
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