The in vitro activities of tigecycline and other antimicrobials against 51 isolates of Nocardia spp. were evaluated. MIC 90 s and MIC ranges were as follows: tigecycline, 4 and <0.06 to 8 mg/liter, respectively; minocycline, 2 and <0.06 to 2 mg/liter, respectively; linezolid, 1 and <0.06 to 2 mg/liter, respectively; moxifloxacin, 2 and <0.06 to >64 mg/liter, respectively; ertapenem, 32 and <0.06->64 mg/liter, respectively; imipenem, 2 and <0.06 to >64 mg/liter, respectively; meropenem, 8 and <0.06 to >64 mg/liter, respectively; amikacin, 1 and <0.06 to 32 mg/liter, respectively; and trimethoprim-sulfamethoxazole, 1/19 and <0.5/9.5 to >2/38 mg/liter, respectively.Nocardia species cause serious infections, especially in immunocompromised patients (4, 6, 16). Trimethoprim-sulfamethoxazole has traditionally been the agent of choice for the treatment of nocardiosis, with alternative drugs including minocycline, amikacin, and imipenem (4, 16). Resistance to the previous drugs, toxicity, intolerance, and therapeutic failures justify the search for alternative antimicrobial agents. The activity of tigecycline (15) against Nocardia spp. has never been evaluated; and there is very little information regarding the activities of linezolid, moxifloxacin, and ertapenem (1, 2, 5, 10, 20). In the study described here, we compared the in vitro activities of tigecycline, linezolid, ertapenem, and moxifloxacin with those of minocycline, imipenem, meropenem, amikacin, and trimethoprim-sulfamethoxazole against 51 nonduplicate clinical isolates of different Nocardia species.(This study was presented in part at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2004 [E. Cercenado, M. Marín, J. Martínez-Alarcón, and E. Bouza, Abstr. 44th Intersci. Conf. Antimicrob. Agents Chemother., abstr. E-2062, 2006].).The isolates were obtained from 1995 to 2006 in our laboratory from respiratory samples (n ϭ 41), cutaneous abscesses (n ϭ 5), brain abscesses (n ϭ 2), blood (n ϭ 2), and cerebrospinal fluid (n ϭ 1). Molecular identification was performed by PCR-restriction fragment length polymorphism (RFLP) analysis of the hsp65 gene (hsp65 PCR-RFLP) with PCR primers TB11 and TB12 and restriction analysis with BstEII, MspI, HinfI, and BsaHI, as described previously (17, 18). Identification was confirmed by sequencing the first 500 bp of the 16S rRNA gene (7,12,14). A 5Ј-end 16S rRNA gene-specific PCR was performed with universal primers E8F and E533F. The amplicons obtained were sequenced by the BigDye Terminator method and were detected with an ABI Prism 3100 automatic DNA sequencer (Applied Byosystems, Inc.). The sequences of well-characterized Nocardia isolates (14) deposited in GenBank were used as references for phylogenetic tree construction with ClustalX 1.8 software. Only identifications with 100% similarity were considered. The strains were stored at Ϫ70°C in skim milk until they were tested for their susceptibilities.The solutions of the antimicrobials and the cation-adjusted Mueller-Hinton broth us...