ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Nov. 2008, p. 4184–4186 0066-4804/08/$08.00⫹0 doi:10.1128/AAC.00695-08 Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Vol. 52, No. 11
In Vitro Activities of Tigecycline and 10 Other Antimicrobials against Nonpigmented Rapidly Growing Mycobacteria䌤 R. Ferna´ndez-Roblas, N. Z. Martín-de-Hijas, A. I. Ferna´ndez-Martínez, D. García-Almeida, I. Gadea, and J. Esteban* Department of Clinical Microbiology, Fundacio ´n Jime´nez Díaz, Madrid, Spain Received 28 May 2008/Returned for modification 2 August 2008/Accepted 15 August 2008
We evaluated the in vitro activities of tigecycline and 10 other antibiotics against clinical isolates of nonpigmented rapidly growing mycobacteria. Fifteen collection strains and 165 clinical isolates were included in the study. Tigecycline showed the highest activity among all antibiotics studied: all the strains were inhibited by 1 mg/liter.
was performed. Prior to testing, strains were subcultured, checked for purity, and reidentified. The following antibiotics were used in the study: tigecycline (Wyeth, Madison, NJ), levofloxacin (GSK, Brentford, United Kingdom), cefoxitin, ciprofloxacin, amikacin, tobramycin, doxycycline, cotrimoxazole, erythromycin (Sigma, St. Louis, MO), azithromycin (Pfizer, New York, NY), and clarithromycin (Abbott, Abbott Park, IL). MICs were determined by the broth microdilution technique (8). Mycobacteria were grown on tryptic soy (5%) sheep blood ´ toile, France) and incubated at agar (bioMe´rieux, Marcy l’E 35°C for 4 days in room air. The inoculum was prepared directly from blood agar plates in cation-supplemented MuellerHinton broth (Difco, Detroit, MI) with 0.02% Tween 80 (Difco, Detroit, MI). Double dilutions of antibiotics were prepared and added to the wells at concentrations ranging from 64 to 0.03 g/ml. After inoculation, the plates were incubated at 30°C in room air and read at 3 days. Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, and Enterococcus faecalis ATCC 29212 were used as controls. Table 1 shows the results of the study. For the species with ⱖ10 strains tested, the MIC at which 50% of strains were inhibited (MIC50), MIC90, and range are shown. For the strains with ⬍10 strains tested, only the MIC range is given. In this study, tigecycline showed the best activity (by weight) of all the antibiotics for the species with a high number of strains tested (M. abscessus, M. fortuitum, M. chelonae, and M. peregrinum), with a MIC90 of ⱕ0.5 g/ml, and all the strains were inhibited by 1 g/ml. All of the less frequent species were also inhibited by 0.5 g/ml of tigecycline. Tigecycline is a new antimicrobial that has shown good activity against some grampositive and gram-negative organisms (1, 9), but only scarce data about its activity against NPRGM are available (11). Our data showed that this antibiotic has good activity against all species of this group of mycobacteria, so it could be a potentially useful antibiotic for treating infections caused by these organisms. Among all the other antimicrobials, ciprofloxacin was the most active quinolone (especially against M. fortuitum and M. peregrinum) and clarithromycin the most active macrolide (especially for M. chelonae), results reported previously for these mycobacteria (2–4, 6). Cefoxitin showed low activity against
Nonpigmented rapidly growing mycobacteria (NPRGM) constitute a group of species of the genus Mycobacterium that share some characteristics. They are among the most commonly isolated species in clinical mycobacteriology laboratories (7). NPRGM, especially the nonrespiratory isolates (5), cause human infections (3, 4). Due to differences between strains, these organisms require individualized treatment that needs to be selected on the basis of results obtained from in vitro susceptibility tests. New antibiotics have been added to those previously recognized as active against these species, such as linezolid (12) or telithromycin (6). Tigecycline is a new antibiotic that has good activity against some of these species (11). However, because regional differences can exist, moredetailed studies with NPRGM from different areas are required. Here we report a study of the susceptibilities of NPRGM to tigecycline and other antimicrobials used for the treatment of infections caused by these organisms. Fifteen collection strains (Mycobacterium fortuitum ATCC 6841 and ATCC 13756, Mycobacterium chelonae ATCC 19235 and ATCC 35752, Mycobacterium abscessus DSM 44196, Mycobacterium peregrinum ATCC 14467, Mycobacterium mucogenicum DSM 44124, Mycobacterium septicum ATCC 700731, Mycobacterium mageritense ATCC 700351, Mycobacterium porcinum ATCC 33776, Mycobacterium smegmatis ATCC 607, ATCC 19420, and ATCC 14468, Mycobacterium alvei ATCC 51304, and Mycobacterium wolinskyi 700010) and 165 clinical isolates (M. abscessus [n ⫽ 9], M. alvei [n ⫽ 2], M. chelonae [n ⫽ 30], M. fortuitum [n ⫽ 89], M. mageritense [n ⫽ 5], M. mucogenicum [n ⫽ 6], M. peregrinum [n ⫽ 22], M. porcinum [n ⫽ 1], and M. septicum [n ⫽ 1]) of NPRGM were included in the study. The clinical isolates were from the area of Madrid, Spain, and were collected from 1990 to 2006. They were identified using a combination of standard biochemical tests and PCR with restriction fragment length polymorphism analysis (10). Strains were maintained frozen at ⫺20°C until the study
* Corresponding author. Mailing address: Department of Clinical Microbiology, Fundacio ´n Jime´nez Díaz, Av. Reyes Cato ´licos 2, 28040Madrid, Spain. Phone: 34 915504900. Fax: 34 915494764. E-mail:
[email protected]. 䌤 Published ahead of print on 25 August 2008. 4184
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TABLE 1. In vitro activities of tigecycline and 10 other antimicrobial agents against NPRGM MIC (g/ml)a against: Antimicrobial agent
M. abscessus (n ⫽ 10) MIC50
Tigecycline Erythromycin Clarithromycin Azithromycin Ciprofloxacin Levofloxacin Amikacin Tobramycin Cefoxitin Doxycycline Cotrimoxazole a
0.06 1 ⱕ0.03 0.5 2 16 2 8 ⬎64 2
MIC90
0.5 16 1 2 8 32 8 16 ⬎64 ⬎64
M. chelonae (n ⫽ 32)
M. peregrinum (n ⫽ 23)
M. fortuitum (n ⫽ 91)
Range
MIC50
MIC90
Range
MIC50
MIC90
Range
MIC50
MIC90
Range
ⱕ0.03–1 0.06–⬎64 ⱕ0.03–32 ⱕ0.03–16 ⱕ0.03–8 0.12–32 0.25–16 1–32
0.12 0.5 0.06 0.5 0.12 0.5 1 4
0.5 32 4 16 2 8 16 16
ⱕ0.03–0.5 ⱕ0.03–⬎64 ⱕ0.03–32 ⱕ0.03–⬎64 ⱕ0.03–4 ⱕ0.03–64 0.06–⬎64 1–⬎64
0.06 1 0.06 0.5 ⱕ0.03 0.06 0.5 4
0.06 16 2 64 0.06 0.25 1 8
ⱕ0.03–0.12 ⱕ0.03–⬎64 ⱕ0.03–16 ⱕ0.03–⬎64 ⱕ0.03–0.25 ⱕ0.03–0.25 ⱕ0.03–1 0.25–16
ⱕ0.03 64 2 8 ⱕ0.03 0.06 1 16
0.25 ⬎64 16 ⬎64 0.12 0.25 2 32
ⱕ0.03–0.5 0.06–⬎64 ⱕ0.03–64 ⱕ0.03–⬎64 ⱕ0.03–4 ⱕ0.03–8 0.06–32 0.12–64
8 0.5
64 32
ⱕ0.03–⬎64 0.12–64
8 0.25
32 1
ⱕ0.03–64 0.12–1
64 1
ⱕ0.03–⬎64 0.12–⬎64
4–⬎64 0.12–⬎64
4 0.12
Except where otherwise indicated, the MIC range is given.
TABLE 1—Continued MIC (g/ml)a against: Antimicrobial agent
Tigecycline Erythromycin Clarithromycin Azithromycin Ciprofloxacin Levofloxacin Amikacin Tobramycin Cefoxitin Doxycycline Cotrimoxazole
M. mucogenicum (n ⫽ 7)
M. mageritense (n ⫽ 6)
M. alvei (n ⫽ 3)
M. smegmatis (n ⫽ 3)
M. porcinum (n ⫽ 2)
M. septicum (n ⫽ 2)
M. wolinskyi (n ⫽ 1)
ⱕ0.03–0.5 ⱕ0.03–32 ⱕ0.03–16 ⱕ0.03–⬎64 ⱕ0.03–4 0.06–8 0.25–16 1–8 0.5–32 ⱕ0.03–64 0.12–64
ⱕ0.03–0.25 32–⬎64 2–16 2–16 ⱕ0.03–0.25 ⱕ0.03–1 0.5–⬎64 8–⬎64 1–32 ⱕ0.03–16 0.12–8
ⱕ0.03–0.12 ⱕ0.03–⬎64 ⱕ0.03–16 ⱕ0.03–⬎64 ⱕ0.03 ⱕ0.03–0.12 ⱕ0.5–4 4–32 2–32 ⱕ0.03–32 0.25–0.5
ⱕ0.03–0.06 0.12–16 ⱕ0.03–2 0.06–32 0.12–0.25 ⱕ0.03–0.25 ⱕ0.03–0.12 ⱕ0.03–0.06 1–32 ⱕ0.03 0.12–1
0.06 8–⬎64 0.5–8 32 ⱕ0.03–0.25 0.06–0.12 0.25–1 1–32 2–32 8–64 0.12
ⱕ0.03–0.25 2–32 ⱕ0.03–2 0.5–16 0.12–0.25 0.12–16 1–16 0.5–4 32–⬎64 32–64 0.12–32
0.12 128 32 128 0.25 0.06 1 8 1 0.25 0.12
these strains, and the activities of doxycycline and cotrimoxazole were variable. Of interest, three strains (two M. mageritense strains and one M. chelonae strain) appeared to be resistant to amikacin, and two other isolates (one M. fortuitum and one M. chelonae isolate) showed intermediate susceptibility, according to the CLSI criteria (8), a finding very uncommon in the literature (3, 13). Analysis of the different species with high numbers of strains showed that M. peregrinum was the most susceptible while M. chelonae and M. abscessus were the most resistant, findings also reported previously (3, 4, 6). However, our results (as well as those of others) showed that the susceptibilities of strains within these species differ widely, so the strains must be tested individually for proper selection of the antimicrobial treatment for each patient. In conclusion, our in vitro data show that tigecycline may be a good alternative for the treatment of infections caused by NPRGM. Likewise, the results shown here agree with those previously published about the activities of other antibiotics. However, these results should be assessed in the context of in vivo experience of treatment of these infections. This work was financed by a grant from Wyeth. N. Z. Martín-deHijas was funded by a grant from the Fundacio ´n Conchita Ra´bago de Jime´nez Díaz.
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