Emergence of Mycobacterium avium populations resistant to macrolides during experimental chemotherapy

被引:22
作者
Bermudez, LE [1 ]
Petrofsky, M [1 ]
Kolonoski, P [1 ]
Young, LS [1 ]
机构
[1] Calif Pacific Med Ctr, Res Inst, Kuzell Inst Arthritis & Infect Dis, San Francisco, CA 94115 USA
关键词
D O I
10.1128/AAC.42.1.180
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Macrolide resistance is an emerging problem in AIDS patients who receive these agents for treatment or prophylaxis against Mycobacterium avium (MAC) infection, We compared the emergence of resistant MAC strains during therapy with clarithromycin (clarithromycin resistance was defined as MIC greater than or equal to 32 mu g/ml) and azithromycin (azithromycin resistance was defined as MIC greater than or equal to 128 mu g/ml) in C57BL/6 beige mice. Treatment with clarithromycin and azithromycin resulted in a decrease of 98.5% in the number of viable bacteria in spleens at week 8 and 99% at week 12 compared with the number of bacteria present in spleen before the initiation of therapy (P < 0.001). Splenic homogenates were also plated onto 7H11 agar plus clarithromycin at 32 mu g/ml or azithromycin at 128 mu g/ml. Resistance emerged significantly more often in mice treated with clarithromycin (100% of treated mice at both 8 and 12 weeks) than in those receiving azithromycin (0% at week 8 and 14% at week 12). The frequencies of resistance of the MAC population in the spleen to clarithromycin were 2.1 x 10(-3) at week 8 and 1.1 x 10(-2) at week 12, whereas resistance to azithromycin was absent at week 8 (all mice) and was similar to 3.5 x 10(-5) (mean for the three positive animals) at week 12. Clarithromycin was more effective in initial reduction of MAC burden in tissue after 8 and 12 week of treatment, but resistant strains emerged significantly more frequently after treatment with clarithromycin than after treatment with azithromycin.
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收藏
页码:180 / 183
页数:4
相关论文
共 23 条
[11]   CURRENT CONCEPTS - MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN THE ACQUIRED-IMMUNODEFICIENCY-SYNDROME [J].
HORSBURGH, CR .
NEW ENGLAND JOURNAL OF MEDICINE, 1991, 324 (19) :1332-1338
[12]   INVITRO AND INVIVO ACTIVITY OF AZITHROMYCIN (CP-62,993) AGAINST THE MYCOBACTERIUM-AVIUM COMPLEX [J].
INDERLIED, CB ;
KOLONOSKI, PT ;
WU, M ;
YOUNG, LS .
JOURNAL OF INFECTIOUS DISEASES, 1989, 159 (05) :994-997
[13]   THE MYCOBACTERIUM-AVIUM COMPLEX [J].
INDERLIED, CB ;
KEMPER, CA ;
BERMUDEZ, LEM .
CLINICAL MICROBIOLOGY REVIEWS, 1993, 6 (03) :266-310
[14]   SELECTION OF RESISTANT MUTANTS OF MYCOBACTERIUM-AVIUM IN BEIGE MICE BY CLARITHROMYCIN MONOTHERAPY [J].
JI, BH ;
LOUNIS, N ;
TRUFFOTPERNOT, C ;
GROSSET, J .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1992, 36 (12) :2839-2840
[15]   ACTIVITY OF CLARITHROMYCIN AGAINST MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN BEIGE MICE [J].
KLEMENS, SP ;
DESTEFANO, MS ;
CYNAMON, MH .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1992, 36 (11) :2413-2417
[16]   IDENTIFICATION OF MUTATIONS IN 23S RIBOSOMAL-RNA GENE OF CLARITHROMYCIN-RESISTANT MYCOBACTERIUM-INTRACELLULARE [J].
MEIER, A ;
KIRSCHNER, P ;
SPRINGER, B ;
STEINGRUBE, VA ;
BROWN, BA ;
WALLACE, RJ ;
BOTTGER, EC .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (02) :381-384
[17]   GENETIC-BASIS OF MACROLIDE RESISTANCE IN MYCOBACTERIUM-AVIUM ISOLATED FROM PATIENTS WITH DISSEMINATED DISEASE [J].
NASH, KA ;
INDERLIED, CB .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1995, 39 (12) :2625-2630
[18]   2 CONTROLLED TRIALS OF RIFABUTIN PROPHYLAXIS AGAINST MYCOBACTERIUM-AVIUM COMPLEX INFECTION IN AIDS [J].
NIGHTINGALE, SD ;
CAMERON, DW ;
GORDIN, FM ;
SULLAM, PM ;
COHN, DL ;
CHAISSON, RE ;
ERON, LJ ;
SPARTI, PD ;
BIHARI, B ;
KAUFMAN, DL ;
STERN, JJ ;
PEARCE, DD ;
WEINBERG, WG ;
LAMARCA, A ;
SIEGAL, FP .
NEW ENGLAND JOURNAL OF MEDICINE, 1993, 329 (12) :828-833
[19]   INCIDENCE OF MYCOBACTERIUM-AVIUM-INTRACELLULARE COMPLEX BACTEREMIA IN HUMAN-IMMUNODEFICIENCY-VIRUS POSITIVE PATIENTS [J].
NIGHTINGALE, SD ;
BYRD, LT ;
SOUTHERN, PM ;
JOCKUSCH, JD ;
CAL, SX ;
WYNNE, BA .
JOURNAL OF INFECTIOUS DISEASES, 1992, 165 (06) :1082-1085
[20]   A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome [J].
Pierce, M ;
Crampton, S ;
Henry, D ;
Heifets, L ;
LaMarca, A ;
Montecalvo, M ;
Wormser, GP ;
Jablonowski, H ;
Jemsek, J ;
Cynamon, M ;
Yangco, BG ;
Notario, G ;
Craft, JC .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (06) :384-391