No abstract

The in vitro activities of several 14-, 15-and 16-membered macrolides were compared with that of erythromycin. In general, 14-membered macrolides such as erythromycln, clarithromycin, and flurithromycin were more active against streptococci and Bordetelk pertussis than was the 15-membered mnacroZlde azithromycin, which was more active than 16-membered macrolides such as niocamycin and rokitamycin. Clarithromycin was the most active compound against Streptococcus pyogenes, pneumococti, Listeria monocytogenes, and Corynebactenium species. LegioneUla pneumophila was most susceptible to m pycin, clarithromycin, and rokitamycin. BranhameUa catarrhais, Neisseria gonorrhoeae, and Haemophillus iqluenzae were most susceptible to azithromycin. Azithromycin and dirithromycin were the most active compounds against Campylobacterjejuni. MICs of 16-membered macrolides for strais expressing inducible-type resisace to erythromycin were cl >&/ml, whereas none of the compounds had activity apinst strins expressing constitutive-type resistance. The MICs of roxlthromycin, miocamycin, rokitamycin, and josamycin increased in the presence of human serum, whereas MICs of the other compounds either were unchanged or decreased.

Tiacumicins B and C are members of a novel group of 18-membered macrolide antibiotics with in vitro activity against Clostridium difficile. The MICs against 15 strains of C. difficile were 0.12 to 0.25 ,ug/mI for tiacumicin B, 0.25 to 1 ,ug/ml for tiacumicin C, and 0.5 to 1 ,ug/ml for vancomycin. The The tiacumicins are a group of 18-membered macrolide antibiotics originally isolated from the fermentation broth of Dactylosporangium aurantiacum subsp. hamdenensis (7,16). Tiacumicin B, the major antibiotic component produced by this culture, contains an unsaturated 18-membered macrolide ring with a seven-carbon sugar at carbon 11 and a 6-deoxy sugar at carbon 20 (Fig. la). This compound is apparently identical to one of the lipiarmycins, a previously described group of antibiotics produced by Actinoplanes deccanensis (1, 10, 12), and to clostomicin Bi, an antibiotic from Micromonospora echinospora (9). Tiacumicin C differs in the position of butyrate esterification on the seven-carbon sugar (Fig. lb). Tiacumicin C appears to be identical to clostomicin B2, a member of the clostomicin complex isolated from M. echinospora (9).A preliminary report on the biological properties of the tiacumicins indicated that tiacumicin B has moderate activity against pathogenic strains of Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus faecium and demonstrated that it has limited, but potent, activity against several anaerobic bacteria (16). In the same study, tiacumicin C was found to have a similar spectrum of activity but to be less potent than tiacumicin B.The present study was designed to examine the in vitro activities of the tiacumicins against Clostridium difficile and to evaluate the efficacies of these compounds in treating antibiotic-associated pseudomembranous colitis caused by * Corresponding author. In vitro potency. MICs in Wilkins-Chalgren agar were determined by a standard twofold agar dilution procedure (13).Effect of serum and pH on in vitro activity. The effects of 50% hamster serum and at pHs 6.5, 7.3, and 8.0 on the in vitro potencies of the tiacumicins in Wilkins-Chalgren broth were determined by a microdilution method (13). To separate the effect of pH from the effect of serum, the pHs of the serum samples were adjusted to 7.3 prior to testing.Effect of hamster cecal contents on in vitro activity. The bioavailabilities of the tiacumicins in the presence of normal hamster cecal contents were determined by a previously described methodology (13). Briefly, MICs and MBCs of

There is no effective therapy to treat Mycobacterium avium complex infection in patients with acquired immune deficiency syndrome. Clarithromycin (A-56268; TE-031) is a new macrolide which is twofold more active than erythromycin against most aerobic bacteria. In addition, higher levels in serum and tissue are achieved with clarithromycin than with erythromycin. In this study, clarithromycin, erythromycin, difloxacin, temafloxacin, ciprofioxacin, rifampin, amikacin, and ethambutol were tested in vitro and in vivo against the M. avium complex. The MICs for 90% of strains tested were 4 ,ug/mI for clarithromycin, 64 ,tg/ml for erythromycin, 32 tig/ml for difloxacin, 8 ,ug/ml for temafloxacin, 4 ,ug/ml for ciprofloxacin, 4 ,ug/ml for rifampin, 32 ,tg/ml for amikacin, and 32 ug/ml for ethambutol. Beige mice were infected intravenously with 1 CFU of M. avium ATCC 25291. Treatment was started on day 6 after infection and was administered twice a day at 8-h intervals for 9 days. Clarithromycin was the most effective compound in these tests and was effective in reducing the viable bacterial counts in the spleen when it was administered subcutaneously or orally at a dose of 25 mg/kg. Amikacin was the only other compound which showed activity in vivo. The peak concentration in serum at which clarithromycin was active was approximately 1.0 ,ug/mil.The treatment of Mycobacterium avium complex infections in immunocompromised patients is a problem since no agent is clearly effective against these bacteria (8, 9). We tested the activity of a new macrolide, clarithromycin (A-56268; TE-031) (2), against the M. avium complex in vitro and also in the beige mouse model (1, 4) to determine whether it could be useful in treating these infections. 35°C. The plates were reincubated after they were read for up to 14 days, and the results were recorded again. The MIC was the lowest concentration of the antibacterial agent which allowed no growth. MATERIALSResistance frequency. The frequency of resistance to clarithromycin was determined by inoculating M. avium ATCC 25291 into Middlebrook 7H9 broth supplemented with 0.2% glycerol-0.2% glucose-10% OADC and incubating the culture for 24 days at 35°C. Serial 10-fold dilutions of this culture containing 6 x 109 CFU/ml were then prepared and

Invasive fungal infections (IFIs) are associated with a high mortality rate for liver transplantation (LT) recipients. To study the incidence of and risk factors for IFIs in LT recipients and the associated mortality rates, we retrospectively reviewed the records of first-time deceased donor LT recipients (January 2003 to December 2007). The incidence of IFIs was 12%. Nonalbicans Candida species accounted for 55% of IFIs; 50% of these IFIs were Candida parapsilosis. Only 43% of Candida isolates were fluconazole-susceptible (minimum inhibitory concentration 8 l/mL). All C. parapsilosis isolates were fluconazole-resistant, and this coincided with a surge of these isolates during a peak period of LT. Factors associated with IFIs included a creatinine level > 2 mg/mL [hazard ratio (OR) ¼ 2.4, 95% confidence interval (CI) ¼ 1.2-5.0, P ¼ 0.01], a Model for End-Stage Liver Disease score > 25 (OR ¼ 2.4, 95% CI ¼ 1.2-4.9, P ¼ 0.02), pretransplant fungal colonization (OR ¼ 7.0, 95% CI ¼ 3.2-15.3, P < 0.001), and a daily prophylactic fluconazole dosage < 200 mg (OR ¼ 2.8, 95% CI ¼ 1.1-7.4, P ¼ 0.03). According to a multivariate analysis, only pretransplant fungal colonization was associated with IFIs (OR ¼ 7.8, 95% CI ¼ 3.9-16.2, P < 0.001). The 1-year patient survival rates with and without IFIs were 41% and 80%, respectively, and the survival rates with C. parapsilosis, other non-albicans Candida, and Candida albicans IFIs were 28%, 50%, and 75%, respectively. In conclusion, IFIs after LT (especially non-albicans Candida species and fluconazole-resistant C. parapsilosis) were associated with reduced survival. The risk factors highlight the importance of pretransplant risk assessments. The identification of pretransplant fungal colonization may allow for risk modifications before or at the time of LT. Additionally, the number of LT procedures and prophylactic strategies may affect institutional outbreaks of resistant Candida strains.