Activity of KRM 1648 alone or in combination with ethambutol or clarithromycin against Mycobacterium avium in beige mouse model of disseminated infection.

Rifamycins are active against slowly growing mycobacteria, such as Mycobacterium tuberculosis and Mycobacterium kansasii, but the majority of rifamycins thus far investigated both in vitro and in vivo are inactive or have only modest activity against the Mycobacterium avium complex (MAC). We investigated the activity of three doses of the semisynthetic benzoxazinorifamycin KRM 1648, alone or in combination with ethambutol or clarithromycin, in beige mice challenged with the MAC strain 101. Our results show the following. (i) KRM 1648 was significantly effective against MAC infection as determined by the reduction of the number of bacteria in the blood, liver, and spleen when administered at doses of 20 and 40 mg/kg of body weight per day but not at 10 mg/kg/day, compared with untreated controls. (ii) KRM 1648 (40 mg/kg/day) administered in combination with ethambutol (100 mg/kg/day) resulted in significant reduction in bacteremia compared with values for untreated controls (P 0.001), KRM 1648 alone (P = 0.019), and ethambutol alone (P = 0.003). Furthermore, the combination of KRM 1648 and ethambutol was associated with a significant decrease of the number of bacteria in the spleen and the liver compared with values for both untreated controls and each drug alone (P < 0.001 for all comparisons). (iii) KRM 1648 (40 mg/kg/day) administered in combination with clarithromycin (200 mg/kg/day) resulted in a significant decrease of the number of bacteria in the blood and the spleen compared with the number for untreated controls (P < 0.001 for all comparisons). In our experience, using MAC 101 as the challenging organism, KRM 1648 is the first the number of bacteria in the blood and spleen compared with the number for untreated controls (P >0.001 for all comparions). In our experience, using MAC 101 as the challenging organism, KRM 1648 is the first rifamycin with significant activity in vivo against MAC infection in beige mice.     

How effective is KRM-1648 in treatment of disseminated Mycobacterium avium complex infections in beige mice?

Although the MICs of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin, or KRM-1648 (KRM), for Mycobacterium avium complex (MAC) were significantly lower than those of other drugs, its in vivo activity was very weak. Beginning 28 days after inoculation, beige mice that had been infected intravenously with 1.87 x 10(7) CFU of MAC 101 were administered KRM alone, clarithromycin (CLARI) alone, or CLARI plus KRM six times weekly for 16 weeks. In contrast to the mice treated with CLARI-containing regimens, the mortality and the mean spleen weights of mice treated with KRM alone (either 10 or 20 mg/kg of body weight per dose) did not differ significantly from those of untreated mice, their numbers of CFU were very much greater than pretreatment values, and multiplication of MAC was only slightly inhibited. Although monotherapy by KRM selected KRM-resistant mutants, the selection was very weak; the mean number of CFU and the frequency of KRM-resistant mutants increased by no more than 1 order of magnitude after 16 weeks of treatment with KRM at 20 mg/kg per dose. Selection of CLARI-resistant mutants was inhibited but not completely prevented by treatment of the mice with CLARI plus KRM. These results indicate that KRM displayed only a weak bacteriostatic effect against the isolate tested in the beige mouse model; its ability to enhance the antimicrobial effect of CLARI or to prevent emergence of CLARI-resistant mutants was very limited.     

Enhanced in vitro activity of WR99210 in combination with dapsone against Mycobacterium avium complex.

WR99210, a dihydrofolate reductase inhibitor, has promising in vitro activity against Mycobacterium avium complex (MAC). The in vitro activities of WR99210 alone and in combination with a fixed concentration of dapsone (0.5 microgram/ml) were evaluated against 35 clinical MAC isolates by a broth dilution method. The MIC at which 50% of isolates were inhibited (MIC50) and MIC90 of WR99210 alone were 2 and 8 micrograms/ml, respectively. The MIC50 and MIC90 of WR99210 in combination with dapsone were 0.25 and 4 micrograms/ml, respectively. Overall, 75% of the MAC isolates displayed enhanced susceptibility to the combination.     

In vitro activities of trimethoprim and sulfamethoxazole against Listeria monocytogenes

The in vitro activities of trimethoprim and sulfamethoxyazole against clinical isolates of Listeria monocytogenes were examined separately and in combination with a microtiter broth dilution system. Sulfamethoxazole demonstrated variable activity and was generally bacteriostatic. Trimethoprim alone was bactericidal against 96% of isolates at less than 0.5 microgram/ml. The bactericidal action of trimethoprim against L. monocytogenes was generally potentiated by sulfamethoxyazole even when isolates were relatively resistant to sulfamethoxyazole alone.     

In vitro and in vivo activities of the benzoxazinorifamycin KRM-1648 against Mycobacterium tuberculosis.

The in vitro and in vivo activities of a new benzoxazinorifamycin, KRM-1648 (KRM), against Mycobacterium tuberculosis were studied. The MIC at which 50% of the isolates are inhibited (MIC50) and the MIC90 of KRM for 30 fresh isolates of M. tuberculosis measured by the BACTEC 460 TB System were 0.016 and 2 micrograms/ml, respectively. These values were much lower than those for rifampin (RMP), which were 4 and >128 micrograms/ml, respectively, and considerably lower than those for rifabutin (RBT), which were 0.125 and 8 micrograms/ml, respectively. A correlational analysis of the MICs of these drugs for the clinical isolates revealed the presence of cross-resistance of the organisms to KRM and either RMP or RBT although the MICs of KRM were distributed over a much lower range than were those of the other two drugs. KRM and RMP at concentrations of 1 to 10 micrograms/ml almost completely inhibited the bacterial growth of RMP-sensitive strains (H37Rv, Kurono, and Fujii) of M. tuberculosis phagocytosed in macrophage-derived J774.1 cells. KRM was more active than RMP in inhibiting the growth of the RMP-resistant (MIC = 8 micrograms/ml) Kurata strain but failed to show such an effect against the RMP-resistant (MIC >128 micrograms/ml) Watanabe stain. When KRM was given to M. tuberculosis-infected mice at dosages of 5 to 20 mg/kg of body weight by gavage, one daily six times per week from day 1 after infection, it was much more efficacious than RMP against infections induced in mice by the RMP-sensitive Kurono strain, as measured by a reduction of rates of mortality, a reduction of the frequency and extent of gross lung lesions, histopathological changes in lung tissues, and a decrease in the bacterial loads in the lungs and spleens of infected mice. KRM also displayed significant therapeutic efficacy against infection induced by the RMP-resistant Kurata strain, while neither KRM nor RMP was efficacious against infection by the RMP-resistant Watanabe strain. In the case of infection with the Kurono strain, the efficacy of the drugs in prolonging the time of survival was in the order KRM, RBT, RMP. KRM was much more efficacious than RMP, when given at 1- to 4-week intervals. These findings suggest that KRM may be useful for the clinical treatment of tuberculosis contracted through RMP-sensitive strains, even when it is administered at long intervals.     

In vitro activity of amoxicillin in combination with clavulanic acid against Mycobacterium tuberculosis.

The comparative in vitro activity of amoxicillin alone and in combination with clavulanic acid against 15 isolates of Mycobacterium tuberculosis was evaluated by broth dilution susceptibility testing. Amoxicillin inhibited 4 of 15 isolates at 8 micrograms/ml or less but was not bactericidal against any of the isolates at that concentration. Amoxicillin in combination with clavulanic acid was bactericidal for 14 of 15 isolates tested at an amoxicillin concentration of 4 micrograms/ml or less and a clavulanic acid concentration of 2 micrograms/ml or less.     

In vitro extracellular and intracellular activities of clavulanic acid and those of piperacillin and ceftriaxone alone and in combination with tazobactam against clinical isolates of Legionella species.

The activities of ceftriaxone, piperacillin, tazobactam, clavulanic acid, and combinations of ceftriaxone or piperacillin with tazobactam against 22 clinical Legionella isolates were measured by broth microdilution and macrodilution methods and in macrophages. The broth microdilution MICs that inhibited 90% of strains tested were 2 and 1 microgram/ml for ceftriaxone and tazobactam, respectively. Broth macrodilution MICs were 8 and 1 microgram/ml, respectively, for the two Legionella pneumophila strains tested with piperacillin and were 0.25 and 0.5 microgram/ml, respectively, for clavulanate. No significant intracellular anti-L. pneumophila activity was observed for ceftriaxone (32 micrograms/ml), piperacillin (32 micrograms/ml), tazobactam alone (16 micrograms/ml), clavulanate alone (2 micrograms/ml), or tazobactam in combination with ceftriaxone (ceftriaxone/tazobactam at 32/4 and 16/16 micrograms/ml) or piperacillin (32/4 micrograms/ml). Erythromycin (1 microgram/ml) was active against intracellular L. pneumophila in the same macrophage model of infection. It is very unlikely that tazobactam or clavulanate, alone or in combination with beta-lactam antimicrobial agents, will be effective for the treatment of Legionnaires' disease in humans.     

Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice.

Newly synthesized benzoxazinorifamycin, KRM-1648, was studied for its in vivo anti-Mycobacterium avium complex (MAC) activities. When the MICs were determined by the agar dilution method with Middlebrook 7H11 agar medium, KRM-1648 exhibited similarly potent in vitro antimicrobial activities against the MAC isolated from AIDS and non-AIDS patients, indicating possible usefulness of KRM-1648 against AIDS-associated MAC infections. KRM-1648 exhibited potent therapeutic activity against experimental murine infections induced by M. intracellulare N-260 (virulent strain) and N-478, which has much weaker virulence. Similarly, KRM-1648 exhibited an excellent therapeutic efficacy against M. intracellulare infection induced in NK-cell-deficient beige mice (as a plausible model for AIDS-associated MAC infection), in which a much more progressed state of gross lesions and bacterial loads at the sites of infection were observed. When the infected beige mice were killed at weeks 4 and 8, obvious therapeutic efficacy was seen on the basis of reduction in the incidence and degree of lung lesions and bacterial loads in the lungs and spleen with infections due to M. intracellulare N-241, N-256, and N-260. In this case, the efficacy was the highest in N-260 infection, followed by strain N-241. When mice were observed until infection-induced death, survival time of the infected beige mice was found to be prolonged by KRM treatment. However, KRM-1648 was not efficacious in suppressing the progression of pulmonary lesions and the increase in bacterial loads at the sites of infection, including lungs and spleen, at the late phase of infection. This may imply some difficulty with chemotherapy for AIDS-associated MAC infection, even with KRM-1648 treatment, which has excellent in vitro and in vivo anti-MAC activities, as shown in present study.     

In vitro activities of rifamycin derivatives ABI-1648 (Rifalazil,KRM-1648), ABI-1657, and ABI-1131 against Chlamydia trachomatis and recent clinical isolates of Chlamydia pneumoniae

ABI-1648 (rifalazil) is a semisynthetic rifamycin with potent bactericidal activity against intracellular respiratory bacteria, including Mycobacterium tuberculosis, and a long half-life (approximately 60 h) and thus can be administered once weekly. We therefore tested the in vitro activities of ABI-1648, its derivatives ABI-1657 and ABI-1131, azithromycin, and levofloxacin against 10 strains of Chlamydia trachomatis and 10 recent clinical isolates of Chlamydia pneumoniae. The MICs at which 90% of the isolates were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed for ABI-1648, ABI-1657, and ABI-1131 were 0.0025 micro g/ml for C. trachomatis and 0.00125 to 0.0025 micro g/ml for C. pneumoniae. ABI-1648, ABI-1657, and ABI-1131 were 10- to 1,000-fold more active than azithromycin and levofloxacin.     

In vitro activity of the benzoxazinorifamycin KRM-1648 against drug-susceptible and multidrug-resistant tubercle bacilli.

We investigated the activity of benzoxazinorifamycin (KRM-1648) against several drug-susceptible and multidrug-resistant strains of tubercle bacilli. Since KRM-1648 is a rifamycin derivative, we included some strains of Mycobacterium tuberculosis resistant to rifampin (RIF) among the multidrug-resistant strains. For RIF-susceptible strains, the MIC of KRM-1648 was much lower than that of RIF (MICs of KRM-1648 and RIF at which 90% of strains are inhibited, < or = 0.015 and < or = 0.25 micrograms/ml, respectively). The MBC of KRM-1648 (range, 0.007 to 0.03 microgram/ml) was also much lower than that of RIF (range, 0.5 to 1.0 microgram/ml). Postantibiotic effect studies with KRM-1648 showed a rapid reduction in the CFU counts with an exposure of 24 h or more, and its sterilizing effect was maintained even up to 21 days thereafter. Parallel postantibiotic effect studies with RIF showed a less significant effect with a faster recovery of growth, and RIF failed to sterilize the organisms even after 72 h of exposure. KRM-1648 at 0.125 and 0.25 microgram/ml caused complete inhibition of intracellular growth of M. tuberculosis in J774 A.1 macrophages after 48 h of exposure. After a similar exposure time RIF at a concentration of 0.25 microgram/ml caused complete inhibition of growth, but a concentration of 0.125 microgram/ml caused only a 50% reduction in growth compared with that of controls at day 7. With 24 h of pulsed exposure of the intracellular organisms to 0.25 micrograms of the drugs per ml, KRM-1648 caused complete inhibition of intracellular growth, while RIF caused only moderate inhibition of intracellular growth. These findings suggest that KRM-1648 is a potentially useful drug for the treatment of tuberculosis.     

Mefloquine is active in vitro and in vivo against Mycobacterium avium complex.

Despite the development of several agents, new classes of antimicrobials with activity against the Mycobacterium avium complex (MAC) are needed. Based on a broad screening of compounds, we found that mefloquine has MICs of 8 to 16 microg/ml by the BACTEC system and 16 microg/ml by broth microdilution for five MAC strains tested. An expansion of the screening with broth microdilution to 24 macrolide-susceptible strains and 6 macrolide-resistant strains determined that the MIC for all strains was 16 microg/ml. To determine the intracellular activity of mefloquine, U937 macrophage monolayers infected with MAC strain 101, 100, or 109 (serovars 1, 8, and 4) were treated with mefloquine daily, and the number of intracellular bacteria was quantitated after 4 days. Significant growth inhibition against the three MAC strains at concentrations greater than or equal to 10 microg/ml (P < 0.05) was obtained. Due to the encouraging anti-MAC activity, in vivo efficacy in beige mice infected with MAC 101 was evaluated. Animals were treated with 5, 10, 20, or 40 mg/kg of body weight daily, three times a week, twice a week, or once a week for 4 weeks, and bacteria were quantitated in blood, liver, and spleen. No toxicity was observed with any of the treatment regimens. Mefloquine had borderline bactericidal activity at a dosage of 40 mg/kg daily (100% inhibition compared with a 1-week control), and significant inhibition was obtained at dosages of 40 mg/kg three times a week, as well as 20 mg/kg daily. Mefloquine had no significant effect on bacteremia. A combination of mefloquine and ethambutol showed significantly more activity than did either drug alone in liver, spleen, and blood; the combination was also bactericidal against M. avium. Although safety is a potential concern, mefloquine and related compounds deserve further investigation as anti-MAC therapies.     

Activities and postantibiotic effects of gemifloxacin compared to those of 11 other agents against Haemophilus influenzae and Moraxella catarrhalis

The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents. All quinolones were very active (MICs, 相似文献   

Activity of LY146032 compared with that of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin against staphylococci as determined by kill-kinetic studies.

Kill-kinetic methods were used to provide data on the bactericidal activity of subinhibitory (0.5x MIC), inhibitory (1x MIC), and suprainhibitory (4x MIC) concentrations of LY146032 against methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis. These bactericidal activities were compared with those of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin. LY146032 was among the most active of the antistaphylococcal agents tested, as determined by broth microdilution methods, with all strains being inhibited at concentrations of less than or equal to 1 microgram/ml. Time kill-kinetic studies demonstrated that at 4x MIC, LY146032 was rapidly bactericidal against all strains of staphylococci. Our data show that LY146032 has significant bactericidal activity against staphylococci in comparison with other antistaphylococcal agents. Further evaluation of LY146032 against serious staphylococcal infections is warranted.     

Activity of moxalactam and cefotaxime alone and in combination with ampicillin or penicillin against group B streptococci

The activities of moxalactam and cefotaxime, alone and combined with ampicillin or penicillin, against 40 isolates of group B streptococci were assessed by using the microtiter broth dilution, checkerboard, and time-kill techniques. Penicillin and cefotaxime were bactericidal for all isolates at concentrations of 0.06 micrograms/ml or less. Ampicillin was slightly less active. Moxalactam was bactericidal for all strains at concentrations of 4 to 8 micrograms/ml. The ampicillin- moxalactam combination was partially synergistic for 60% of the isolates tested; the ampicillin-cefotaxime combination was partially synergistic for 35% of these isolates. No instances of antagonism were observed. In time-kill evaluations, ampicillin (3.0 micrograms/ml) and penicillin (0.75 micrograms/ml) effected 2.5 to 3.5 log10 reductions in numbers of colony-forming units. The addition of 4 micrograms of cefotaxime per ml or 8 to 16 micrograms of moxalactam per ml to penicillin or ampicillin did not alter killing kinetics. Moxalactam and cefotaxime neither enhanced nor decreased the activity of ampicillin or penicillin against group B streptococci.     

Comparison of in vitro activity of moxalactam (LY127935) with cefazolin, amikacin, tobramycin, carbenicillin, piperacillin, and ticarcillin against 420 blood culture isolates.

To compare the in vitro activity of moxalactam (LY127935), a new broad-spectrum antimicrobial agent, with cefazolin, amikacin, tobramycin, carbenicillin, piperacillin, and ticarcillin, each drug was tested against 420 bacterial isolates from the blood of septic patients. Standard broth dilution methods were used to determine minimum inhibitory and bactericidal concentrations. LY127935 was as active as the aminoglycosides against aerobic gram-negative organisms, including Pseudomonas aeruginosa, and was at least 10-fold more active than the other beta-lactam agents against these bacteria. LY127935 was the most active agent tested against Bacteroides fragilis; its activity against all other anaerobic bacteria and Staphylococcus aureus was similar to those of the other agents tested. All streptococci, however, grew at higher concentrations of LY127935 than any other drug, and Streptococcus faecalis and Listeria monocytogenes were not inhibited at the highest concentration tested (minimum inhibitory concentration, > 64 microgram/ml). Although a greater proportion of blood culture isolates were susceptible to LY127935 than to any other drug tested, LY127935 does not have a sufficiently broad spectrum of in vitro activity to be recommended safely alone for empirical treatment of sepsis of unknown etiology.     

Effect of human serum on the bactericidal activity of daptomycin and vancomycin against staphylococcal and enterococcal isolates as determined by time-kill kinetic studies

The bactericidal activity of daptomycin and vancomycin alone in cation-supplemented Mueller-Hinton broth and in human serum against clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis was evaluated by exposing replicating microorganisms to concentrations ranging from 2 to 128 micrograms/ml for 24 hr. In addition, the possibility of emergence of resistance, the stability of each agent in the respective medium, and the percent of protein binding by human serum for each agent was evaluated. We found that a concentration of less than or equal to 8 micrograms/ml of daptomycin was sufficient to achieve bactericidal activity (greater than or equal to 99.9% killing of the inoculum) in cation-supplemented Mueller-Hinton broth for all staphylococcal isolates tested; a concentration of less than or equal to 16 micrograms/ml of daptomycin was required for bactericidal activity in cation-supplemented Mueller-Hinton broth for enterococcal isolates. In human serum, comparable bactericidal activity with daptomycin was achieved only with concentrations 8-16 times higher. A similar but less pronounced effect in human serum was seen for vancomycin. Neither daptomycin nor vancomycin was appreciably degraded in human serum over a 24-hr period. It is likely that the clinical efficacy of daptomycin in humans would be enhanced by higher dosing than has been studied to date.     

In vitro activities of two ketolides, HMR 3647 and HMR 3004, against gram-positive bacteria

The in vitro activities of two new ketolides, HMR 3647 and HMR 3004, were tested by the agar dilution method against 280 strains of gram-positive bacteria with different antibiotic susceptibility profiles, including Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Streptococcus spp. (group A streptococci, group B streptococci, Streptococcus pneumoniae, and alpha-hemolytic streptococci). Seventeen erythromycin-susceptible (EMs), methicillin-susceptible S. aureus strains were found to have HMR 3647 and HMR 3004 MICs 4- to 16-fold lower than those of erythromycin (MIC at which 50% of isolates were inhibited [MIC50] [HMR 3647 and HMR 3004], 0.03 microgram/ml; range, 0.03 to 0.06 microgram/ml; MIC50 [erythromycin], 0.25 microgram/ml; range, 0.25 to 0.5 microgram/ml). All methicillin-resistant S. aureus strains tested were resistant to erythromycin and had HMR 3647 and HMR 3004 MICs of > 64 micrograms/ml. The ketolides were slightly more active against E. faecalis than against E. faecium, and MICs for individual strains varied with erythromycin susceptibility. The MIC50s of HMR 3647 and HMR 3004 against Ems enterococci (MIC < or = 0.5 microgram/ml) and those enterococcal isolates with erythromycin MICs of 1 to 16 micrograms/ml were 0.015 microgram/ml. E. faecalis strains that had erythromycin MICs of 128 to > 512 micrograms/ml showed HMR 3647 MICs in the range of 0.03 to 16 micrograms/ml and HMR 3004 MICs in the range of 0.03 to 64 micrograms/ml. In the group of E. faecium strains for which MICs of erythromycin were > or = 512 micrograms/ml, MICs of both ketolides were in the range of 1 to 64 micrograms/ml, with almost all isolates showing ketolide MICs of < or = 16 micrograms/ml. The ketolides were also more active than erythromycin against group A streptococci, group B streptococci, S. pneumoniae, rhodococci, leuconostocs, pediococci, lactobacilli, and diphtheroids. Time-kill studies showed bactericidal activity against one strain of S. aureus among the four strains tested. The increased activity of ketolides against gram-positive bacteria suggests that further study of these agents for possible efficacy against infections caused by these bacteria is warranted.     

CP-45,899 in combination with penicillin or ampicillin against penicillin-resistant Staphylococcus, Haemophilus influenzae, and Bacteroides.

CP-45,899 is a new, semisynthetic beta-lactamase inhibitor. When tested alone, CP-45,899 displayed only weak antibacterial activity, with the notable exception of its potent action against penicillin-susceptible and -resistant Neisseria gonorrhoeae. A combination of 3.12 microgram of CP-45,899 per ml with 3.12 microgram of ampicillin per ml, tested in broth cultures, inhibited ca. 90% of resistant Staphylococcus and Haemophilus influenzae strains; similar data were obtained in a variety of media. The same combination of CP-45,899 with ampicillin or penicillin G inhibited 90% of Bacteroides fragilis as interpreted from agar dilution minimal inhibitory concentrations. Inhibitory concentrations of CP-45,899-ampicillin were bactericidal against H. influenzae strains and were as bactericidal as nafcillin or cephalothin against S. aureus. Ampicillin-resistant S. aureus, H. influenzae, and B. fragilis strains did not develop resistance to CP-45,899-ampicillin when transferred as many as six passages in the presence of a sublethal concentration of the combination.     

Telithromycin Is Active against Mycobacterium avium in Mice despite Lacking Significant Activity in Standard In Vitro and Macrophage Assays and Is Associated with Low Frequency of Resistance during Treatment

The activity of telithromycin, a new ketolide, was evaluated in vitro and in vivo against Mycobacterium avium complex (MAC) strains. The MIC of telithromycin for several M. avium isolates obtained from the blood of AIDS patients ranged from 16 to >128 microg/ml (MIC at which 90% of isolates are inhibited, >128 microg/ml), and the compound did show activity in the macrophage system at concentrations greater than 8 or 16 microg/ml, but this was dependent on the MAC strain used. Telithromycin was then administered to mice infected with MAC strain 101 for 4 weeks at doses of 100, 200, or 400 mg/kg of body weight/day. Treatment with 100 and 200 mg/kg/day was bacteriostatic, but at 400 mg/kg/day telithromycin was bactericidal for MAC strains. The frequency of the emergence of resistance to telithromycin was low despite prolonged usage (12 weeks). This study demonstrates that telithromycin is active in vivo against MAC and warrants further evaluation.