In vitro susceptibilities of clinical and environmental isolates of Cryptococcus neoformans to five antifungal drugs.

A total of 53 Cryptococcus neoformans strains, including clinical and environmental Brazilian isolates, were tested for their susceptibilities to amphotericin B, 5-flucytosine, ketoconazole, fluconazole, and itraconazole. The tests were performed according to the National Committee of Clinical Laboratory Standards recommendations (document M27-P). In general, there was a remarkable homogeneity of results for all strains, and comparable MICs were found for environmental and clinical isolates. This paper represents the first contribution in which susceptibility data for Brazilian C. neoformans isolates are provided.     

In vitro activities of six fluoroquinolones against 250 clinical isolates of Mycobacterium tuberculosis susceptible or resistant to first-line antituberculosis drugs

Two hundred fifty isolates of Mycobacterium tuberculosis were evaluated for susceptibility to ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, trovafloxacin, and gemifloxacin (SB-265805). Levofloxacin, ciprofloxacin, and grepafloxacin showed the greatest activity (MIC for 90% of strains tested [MIC(90)] 1 microg/ml), although ofloxacin also showed good activity, with an MIC(90) of 2 microg/ml. Trovafloxacin and gemifloxacin showed lower in vitro activity, with MIC(90)s of 64 and 8 microg/ml, respectively.     

Synergistic effect of antituberculosis drugs and azoles in vitro against Histoplasma capsulatum var. capsulatum

This study evaluated in vitro interactions of antituberculosis drugs and triazoles against Histoplasma capsulatum. Nine drug combinations, each including an antituberculosis drug (isoniazid, pyrazinamide, or ethambutol) plus a triazole (itraconazole, fluconazole, or voriconazole), were tested against both growth forms of H. capsulatum. Stronger synergistic interactions were seen in isoniazid or pyrazinamide plus triazoles for the mold form and ethambutol plus voriconazole for the yeast-like form. Further studies should evaluate these combinations in vivo.     

In vitro activities of 10 antifungal drugs against 508 dermatophyte strains

We have tested 508 strains belonging to 24 species of dermatophytes against 10 antifungal drugs following mainly the NCCLS (M38-P) standard for filamentous fungi. However, several important factors, such as the temperature (28 versus 35 degrees C) and time of incubation (4 to 10 days versus 21 to 74 h), have been modified. The antifungals used were itraconazole, ketoconazole, miconazole, clotrimazole, voriconazole, terbinafine, amphotericin B, fluconazole, UR-9825, and G-1. In general, with the exception of fluconazole and G-1, all antifungals were shown to be highly effective.     

In vitro and in vivo activities of posaconazole against Coccidioides immitis

Posaconazole (SCH 56592) was tested against 25 strains of Coccidioides immitis to determine their in vitro susceptibilities. The geometric mean 48-h MIC of posaconazole (POSA) was 0.5 microg/ml, the MIC range was 0.25 to 1 microg/ml, and the MIC at which 50% of the isolates tested are inhibited (MIC50) and the MIC90 were 0.5 and 1 microg/ml, respectively. The geometric mean 48-h MIC of itraconazole (ITRA) was 0.23 microg/ml, the MIC range was 0.125 to 0.5 microg/ml, and the MIC50 and MIC90 were both 0.25 microg/ml. Two strains of C. immitis were selected for in vivo studies on the basis of the POSA 48-h MICs for the isolates. POSA orally administered at 0.01, 0.1, 0.5, 1, 5, and 10 mg/kg of body weight/day was compared with ITRA administered at 10 and 30 mg/kg three times a day. The spleens and livers of mice that died or survived to day 50 were removed to measure the fungal burdens. Mice had >or=90% survival when they were treated with >or=0.5 mg of POSA per kg or 30 mg of ITRA per kg. Cultures of whole spleens and livers from mice treated with 10 mg of POSA per kg showed >or=70% sterilization. No sterilization of whole spleens and livers from mice treated with ITRA was seen. POSA displayed potent in vivo activity against the two strains of C. immitis tested.     

抗结核药物不良反应的观察护理

结核病是临床上常见病、多发病，严重危害着人们的身体健康。抗结核病治疗必须遵循早期、联合、规律、适量、全程的十字方针。为了确保抑菌效果，防止结核杆菌产生耐药性，常需联合应用抗结核药，但若超过4种以上，较易引发不良反应，而不良反应导致的药源性疾病已是现代人类死亡的重要原因之一，因此药物的不良反应成为临床一个不容忽视的问题。多年来我们在临床工作中仔细观察，及时正确处理药物不良反应，提高病人服药顺从性，帮助病人完成全程化疗达到了治愈目的。经验证明，抗结核药物治疗的不良反应发生率高，但只要及时发现，防治得当，仍是一个安全系数较高完全能治愈的疾病。具体做法如下。     

抗结核药物不良反应的观察护理

结核病是临床上常见病、多发病,严重危害着人们的身体健康。抗结核病治疗必须遵循早期、联合、规律、适量、全程的十字方针。为了确保抑菌效果,防止结核杆菌产生耐药性,常需联合应用抗结核药,但若超过4种以上,较易引发不良反应,而不良反应导致的药源性疾病已是现代人类死亡的重要原因之一[1],因此药物的不良反应成为临床一个不容忽视的问题。多年来我们在临床工作中仔细观察,及时正确处理药物不良反应,提高病人服药顺从性,帮助病人完成全程化疗达到了治愈目的。经验证明,抗结核药物治疗的不良反应发生率高,但只要及时发现,防治得当,仍是一个…     

Disease modifying antirheumatic drugs with inhibitory effect on osteoclastogenesis

Suppression of bone destruction is a requirement for effective therapeutic strategies for autoimmune arthritis. Although numerous antirheumatic drugs are in clinical use, little is known about whether they ameliorate bone destruction by acting on activated T cells or other cell types, such as bone-resorbing osteoclasts. Leflunomide has a direct inhibitory effect on RANKL-mediated osteoclast differentiation by inhibiting the induction of NFATc1, the master switch regulator for osteoclast differentiation. We show that the direct inhibitory action of leflunomide on osteoclast differentiation constitutes an important aspect to ameliorate bone destruction, and that RANKL dependent NFATc1 induction pathway is an auspicious target for pharmacological intervention into arthritic bone destruction.     

MIC as a quantitative measurement of the susceptibility of Mycobacterium avium strains to seven antituberculosis drugs

MICs of isoniazid, rifampin, ethionamide, streptomycin, amikacin, kanamycin, and capreomycin were determined for Mycobacterium avium complex strains by two methods: broth dilution in 7H12 medium radiometrically and agar dilution on 7H10 agar plates. The broth-determined MICs of all drugs with the exception of isoniazid were two to eight times lower than the agar-determined MICs for most of the tested M. avium strains, which is probably due to the higher absorption and degradation of the drugs in solid media. The MICs, especially those determined in broth, are suggested as quantitative measurements of the degree of susceptibility of M. avium complex strains. For a certain percentage of the M. avium strains the broth-determined MICs were within the limits of MICs found for wild susceptible Mycobacterium tuberculosis strains. These M. avium strains were classified as presumably susceptible. In contrast to M. tuberculosis, the MICs for M. avium strains had a wide range. When the MICs for M. avium strains were only one dilution higher than those for M. tuberculosis, they were tentatively classified as moderately susceptible. The designation moderately resistant or resistant, respectively, is suggested for those M. avium strains for which the MICs were at or above the concentrations achievable in blood. The quantitation of the degree of susceptibility by the MICs and the tentative interpretation of the MICs are suggested for future use in clinical trials as a means of evaluating the patients' responses to chemotherapy compared with the degree of susceptibility of the initial strain isolated before treatment.     

In vitro activity of Proveblue (methylene blue) on Plasmodium falciparum strains resistant to standard antimalarial drugs

The geometric mean 50% inhibitory concentration (IC50) for Proveblue, a methylene blue complying with the European Pharmacopoeia, was more active on 23 P. falciparum strains than chloroquine, quinine, mefloquine, monodesethylamodiaquine, and lumefantrine. We did not find significant associations between the Proveblue IC50 and polymorphisms in the pfcrt, pfmdr1, pfmdr2, pfmrp, and pfnhe-1 genes or the copy numbers of the pfmdr1 and pfmdr2 genes, all of which are involved in antimalarial resistance.     

In vitro activities of PD 117,596 and reference antibiotics against 448 clinical bacterial strains.

The in vitro activity of PD 117,596, a new fluoroquinolone antibiotic, was tested against 448 bacterial isolates (15 genera) by agar dilution (inoculum, 10(4) CFU per spot). The activity of PD 117,596 was compared with that of 15 antibiotics against 327 gram-negative strains and with that of 8 other antibiotics against 121 gram-positive strains. PD 117,596 demonstrated the best activity against Klebsiella spp., Enterobacter spp., Acinetobacter spp., Serratia marcescens, and Branhamella catarrhalis (MICs for 90% of the isolates [MIC90S], 0.008 to 0.25 microgram/ml). PD 117,596 (MIC90, 0.25 microgram/ml) was at least twofold more active than ciprofloxacin against Pseudomonas aeruginosa and Pseudomonas spp. PD 117,596 and ciprofloxacin were similar in activity against Escherichia coli, Proteus mirabilis, Haemophilus influenzae, H. parainfluenzae, Neisseria gonorrhoeae, Legionella pneumophila, and Campylobacter jejuni (MIC90, 0.002 to 0.125 microgram/ml). PD 117,596 was more active than ciprofloxacin against streptococcal groups A, B, C, and G, S. pneumoniae, and enterococci (MIC90S, 0.06 to 0.125 microgram/ml). Against Staphylococcus aureus, including methicillin-resistant isolates, PD 117,596 (MIC90S, 0.03 to 0.06 microgram/ml) was 4- to 16-fold more active than ciprofloxacin and was most active against Corynebacterium spp. PD 117,596 appears to be the most active fluoroquinolone to date, with excellent activity against gram-positive bacteria and enhanced activity against gram-negative aerobic-facultative bacteria.     

In vitro effect of minocycline and colistin combinations on imipenem-resistant Acinetobacter baumannii clinical isolates

OBJECTIVES: The study investigated the effect of colistin and minocycline when tested singly and in combination against Acinetobacter baumannii. METHODS: Thirteen unrelated imipenem-resistant A. baumannii clinical isolates were included in the study. MICs of colistin sulphate and minocycline were determined by broth macrodilution and Etest. Organisms were also tested against the two antibiotics singly and in combination using time-kill methods and an Etest-based method. RESULTS: Neither colistin nor minocycline when tested alone demonstrated bactericidal activity. However, the combination of colistin and minocycline demonstrated bactericidal activity against most of the isolates tested. At 24 h, the combination of antibiotics demonstrated synergy in 12 of the 13 isolates by time-kill methods. None of the isolates demonstrated synergy by Etest methods. CONCLUSIONS: The combination of colistin and minocycline was found to be bactericidal and synergistic against A. baumannii by time-kill methods. There was no agreement between time-kill and Etest methods for synergy testing.     

足三里封闭对抗结核治疗所致胃肠不良反应的效果观察

[目的]探讨维生素B1和维生素B12注射液足三里封闭对预防抗结核药物引起的胃肠道不良反应的作用。[方法]将180例抗结核治疗的结核病人随机分为两组：观察组在抗结核治疗前采用维生素B1和维生素 B12隔日双侧足三里封闭1次,15 d 为1个疗程;对照组仅给予抗结核药物治疗,未采取预防胃肠道反应的其他措施。[结果]观察组胃肠道反应发生率为14.77%,对照组胃肠道反应发生率为28.26%,且观察组胃肠道反应轻于对照组。[结论]维生素 B1和维生素 B12足三里封闭可有效预防和控制抗结核药物引起的胃肠道反应,保证抗结核治疗的顺利进行。     

In vitro activities of free and lipid formulations of amphotericin B and nystatin against clinical isolates of Coccidioides immitis at various saprobic stages

We investigated the susceptibilities of hyphal, mixed hyphal, ungerminated arthroconidial, and germinated arthroconidial populations of Coccidioides immitis to lipid formulations of amphotericin B and nystatin and their conventional preparations, utilizing the National Committee for Clinical Laboratory Standards M38-P broth macrodilution method. The differences in effects of the three different growth stages of the saprobic phase of C. immitis on the MIC/minimum lethal concentration (MLC) ratio were not statistically significant for any of the antifungal agents tested. These results suggest that either inocula could be used for in vitro susceptibility studies with C. immitis.     

In vitro inhibitory effects of hinokitiol on proliferation of Chlamydia trachomatis

The inhibitory effects of hinokitiol (beta-thujaplicin) on Chlamydia trachomatis D/UW-3/Cx were shown by MIC, minimum lethal concentration (MLC), and preinoculation minimal microbicidal concentration assays using HeLa 229 cells. The MIC and the MLC were both 32 microg/ml. Further evaluation of hinokitiol as a topical agent against C. trachomatis is warranted.