Isolation and characterisation of a new antimicrobial peptide from the skin of Xenopus laevis

A new antimicrobial peptide (AMP) named PGLa-H has been isolated from the skin of the African clawed frog (Xenopus laevis) using gel filtration and reverse-phase high-performance liquid chromatography (RP-HPLC). Its amino acid sequence was determined as KIAKVALKAL by Edman degradation, with a molecular weight of 1053.727 Da as analysed by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). No similar AMP was found by BLAST search. Purified PGLa-H demonstrated antimicrobial ability against the reference bacteria Escherichia coli ATCC 25922 [minimum inhibitory concentration (MIC) = 23.6 μg/mL], Staphylococcus aureus ATCC 25923 (MIC = 8.7 μg/mL) and Bacillus subtilis (MIC = 14.4 μg/mL) and was active against multidrug-resistant meticillin-resistant S. aureus (MRSA) (MIC = 67.8 μg/mL). The antimicrobial mechanism for this new peptide was further investigated by transmission electron microscopy. PGLa-H killed cells by destroying the cell membrane.     

Drug-resistant Streptococcus pneumoniae in the Lebanon: implications for presumptive therapy

A total of 50 consecutive clinical isolates of Streptococcus pneumoniae, collected between 1996 and 1998, were tested against six antimicrobial agents using the E-test. The percentages of fully resistant (R) and intermediately-R strains, respectively, were: benzyl penicillin 18 and 38%, amoxycillin-clavulanate 6 and 12%, cefuroxime 22 and 16%, ceftriaxone 2 and 16%, and clarithromycin 10%. Fully and or intermediately multidrug-resistance (two or more drugs) was seen in 44% of the isolates, 18% being fully resistant. The MIC breakpoint for cefaclor is not defined by the National Committee for Clinical Laboratory Standards (NCCLS) but MICs showed that: 76% of the isolates had an MIC of ≤8 mg/l, 4% had an MIC of 16 mg/l and 20% had an MIC of ≥32 mg/l. There was agreement between the E-test Pen MIC results and the 1 μg oxacillin (oxa) disk diffusion screen test for the 22 susceptible and the nine fully R strains but not for the 19 strains with Pen MICs between 0.1 and 1 mg/l; this shows the importance of MIC determination in such isolates. Penicillin and multiply antibiotic-resistant pneumococci are spreading in Lebanon, emphasizing the necessity to reconsider current treatment regimens in this country.     

Diospyrone, crassiflorone and plumbagin: three antimycobacterial and antigonorrhoeal naphthoquinones from two Diospyros spp.

The aim of this study was to evaluate the antimycobacterial and antigonorrhoeal activities of three naphthoquinones (diospyrone, crassiflorone and plumbagin) from Diospyros canaliculata and Diospyros crassiflora as well as the crude extracts from these plants. The agar disk diffusion assay, broth microdilution method, microplate Alamar blue assay (MABA) and radiometric respiratory technique using the BACTEC 460 TB system were used. Results of the antimycobacterial assays indicated that the minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations ranged from 1.22 μg/mL to 39.06 μg/mL for Mycobacterium smegmatis and all studied Mycobacterium tuberculosis strains for the crude extract from D. crassiflora, diospyrone and crassiflorone. Results of the killing rate experiment revealed that a total inhibition effect on M. tuberculosis H37Rv strain was observed at Day 18 for D. crassiflora and Day 21 for the crude extract from D. canaliculata and diospyrone at 4× MIC as determined by MABA. Results of the antigonorrhoeal assay indicated that diospyrone was able to prevent the growth of all studied strains of Neisseria gonorrhoeae. The overall results of this work provide evidence that the studied plant extracts (diospyrone, crassiflorone and plumbagin) might be potential sources of new antimicrobial drugs against tuberculosis and gonorrhoea.     

2020—2022年清镇市第一人民医院妊娠期妇女尿路感染病原菌构成特点及耐药性分析

目的 探讨清镇市第一人民医院妊娠期妇女尿路感染病原菌的构成特点及耐药性,为临床治疗提供参考。方法 收集2020年1月—2022年12月清镇市第一人民医院疑为尿路感染妊娠期妇女清洁中段尿标本,使用法国梅里埃VITEK-2Compact或VITEK MS质谱仪进行病原菌鉴定和抗生素最低抑菌浓度（MIC）检测,根据美国临床试验室标准化研究所（CLSI）的标准判断药敏结果,采用WHONET 5.6和SPSS 20.0软件进行数据统计。结果 共检出384株病原菌,其中革兰阴性菌占84.9%(326株);革兰阳性菌占13.3%(51株),念珠菌占1.8%(7株),病原菌以大肠埃希菌（297株,占77.3%）和无乳链球菌（30株,占7.8%）最为常见。大肠埃希菌对氨苄西林、氨苄西林/舒巴坦、复方磺胺甲噁唑、头孢唑啉、环丙沙星和左氧氟沙星的耐药率高于70.0%,对呋喃妥因、哌拉西林/他唑巴坦、阿米卡星和头孢替坦的耐药率低于10.0%,多重耐药菌株占42.1%;无乳链球菌对四环素和克林霉素的耐药率高于65.0%,对青霉素、氨苄西林、喹努普汀/达福普汀、替加环素、利奈唑胺和万古霉素的耐药率为0。结论 妊娠...     

2015-2020年新郑市人民医院妇科肿瘤术后患者医院感染的病原菌分布和耐药情况分析

目的 探讨新郑市人民医院妇科肿瘤术后发生医院感染的病原菌情况。方法 选取2015年9月-2020年9月在新郑市人民医院接受妇科肿瘤手术的120例患者的治疗资料进行分析。结果 妇科肿瘤术120例患者总计检出病原菌208株,革兰阴性菌134株（64.42%）,革兰阳性菌60株（28.85%）,真菌14株（6.73%）。大肠埃希菌耐药性较高的药物依次为头孢曲松（59.09%）、复方新诺明（56.82%）、环丙沙星（54.55%）,对替加环素为0。肺炎克雷伯菌耐药性较高的药物依次为阿莫西林（71.42%）、头孢曲松（42.86%）、头孢噻肟（39.29%）,最低为替加环素（3.57%）。铜绿假单胞菌耐药性较高的药物依次为头孢曲松（81.25%）、复方新诺明（81.25%）、阿莫西林（68.75%）。鲍氏不动杆菌耐药性较高的药物依次为亚胺培南（100%）、哌拉西林（92.86%）、头孢吡肟（85.71%）。从主要革兰阳性菌对抗菌药物的耐药性来看,金黄色葡萄球菌对氨苄西林（90.00%）、复方新诺明（90.00%）耐药率较高。表皮葡萄球菌对青霉素（81.82%）、四环素（81.82%）耐药率较高。结论 妇科肿瘤手术后感染的发生与多种病原菌有关,主要为革兰阴性菌,不同病原菌的耐药性存在差异,临床治疗方案需要全面评估感染情况,保证用药方案的科学合理,并注重监测,结合病原学证据及时调整治疗方案。     

Anti-staphylococcal activity of ent-kaurane-type diterpenoids from Croton tonkinensis

Ent-kaurane-type diterpenpoids 1–11, isolated from the dried leaves of the endemic Vietnamese medicinal plant Croton tonkinensis Gagnep. (Euphorbiaceae), were evaluated for inhibitory activity against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) strains. The most active diterpenoids, 2, 3, and 8, exhibited minimum inhibitory concentrations (MICs) of 32, 500, and 125 g/ml, respectively, against MRSA strains.     

Mechanisms of in-vitro-selected daptomycin-non-susceptibility in Staphylococcus aureus

Daptomycin is highly active against Staphylococcus aureus, including multidrug-resistant strains and those with reduced susceptibility to vancomycin. However, daptomycin-non-susceptible (Dap^NS) strains [minimum inhibitory concentration (MIC) >1 mg/L] have been derived clinically and in vitro. The mechanism(s) by which this occurs is incompletely understood, but existing data indicate that it is multifactorial. Dap^NS derivatives of one laboratory and three clinical strains of S. aureus produced using gradient plates were evaluated. The Dap^NS phenotype included increases in glycopeptide and nisin MICs and in some instances defective autolysis and reduced susceptibility to lysostaphin lysis. Amino acid substitutions in MprF, YycG (WalK), or both, were identified in all Dap^NS strains. Reduced cytochrome c binding and ability of daptomycin to depolarise whole cells correlated with the Dap^NS phenotype, consistent with an increase in cell surface positivity. Gene expression data revealed increased expression of vraS, one member of a two-component system involved in the regulation of cell wall biosynthesis, in three of five Dap^NS strains. The pathway to the Dap^NS phenotype is not linear, as variable genetic and phenotypic changes may result in identical increases in MICs.     

Antitubercular triterpenes and phytosterols from <Emphasis Type="Italic">Pandanus tectorius </Emphasis>Soland. var. <Emphasis Type="Italic">laevis</Emphasis>

Bioassay-guided chromatographic purification of the antitubercular chloroform extract of Pandanus tectorius Soland. var. laevis leaves afforded a new tirucallane-type triterpene, 24,24-dimethyl-5β-tirucall-9(11),25-dien-3-one (1), squalene and a mixture of the phytosterols stigmasterol and β-sitosterol. Microplate Alamar Blue Assay (MABA) showed that 1 inhibited the growth of Mycobacterium tuberculosis H₃₇Rv with a MIC of 64 μg/mL, while squalene and the sterol mixture have MICs of 100 and 128 μg/mL, respectively.     

‘In vitro’ development of metronidazole, erythromycin, amoxicillin and gentamicin resistance in Helicobacter pylori

Serial passage of 37 Helicobacter pylori clinical isolates on increasing concentrations of metronidazole rapidly produced five strains with MICs up to 512 fold higher than those for the original strains. For these five metronidazole-resistant strains the MICs of erythromycin, gentamicin and amoxicillin were unchanged. When they were submitted to the same technique for these last antimicrobial agents, only one strain developed high level resistance to erythromycin and gentamicin having MIC values respectively up to 32 and 64-fold increased. Finally, no amoxicillin-resistant Helicobacter pylori could be obtained.     

Terbinafine susceptibility patterns for onychomycosis-causative dermatophytes and Scopulariopsis brevicaulis

The in vitro antifungal activity of terbinafine against 521 clinical isolates of seven species of dermatophytes, including four onychomycosis-causative species, as well as five Scopulariopsis brevicaulis isolates was determined by a modified Clinical and Laboratory Standards Institute microdilution method. Results showed a high antifungal activity of terbinafine against all dermatophyte isolates (geometric minimal inhibitory concentration (MIC)=0.026 microg/mL; concentration inhibiting 50% of mycological growth (MIC50)=0.03 microg/mL; and concentration inhibiting 90% of mycological growth (MIC90)=0.06 microg/mL). The geometric mean MICs against onychomycosis-causative dermatophyte species was lower (0.024 microg/mL) than the global MIC. However, the in vitro activity of terbinafine against S. brevicaulis was considerably lower (geometric mean MIC=1.38 microg/mL) in comparison with dermatophytes. The antifungal activity of itraconazole was lower than that of terbinafine against these fungi. These data confirm the high in vitro antifungal activity of terbinafine against dermatophytes, under standardised conditions.     

In vitro activity of BAL30072 against Burkholderia pseudomallei

Burkholderia pseudomallei is an intrinsically antibiotic-resistant Category B priority pathogen and the aetiological agent of melioidosis. Treatment of B. pseudomallei infection is biphasic and lengthy in order to combat the acute and chronic phases of the disease. Acute-phase treatment preferably involves an intravenous cephalosporin (ceftazidime) or a carbapenem (imipenem or meropenem). In this study, the anti-B. pseudomallei efficacy of a new monosulfactam, BAL30072, was tested against laboratory strains 1026b and 1710b and several isogenic mutant derivatives as well as a collection of clinical and environmental B. pseudomallei strains from Thailand. More than 93% of the isolates had minimal inhibitory concentrations (MICs) in the range 0.004-0.016 μg/mL. For the laboratory strain 1026b, the MIC of BAL30072 was 0.008 μg/mL, comparable with the MICs of 1.5 μg/mL for ceftazidime, 0.5 μg/mL for imipenem and 1 μg/mL for meropenem. Time-kill curves revealed that BAL30072 was rapidly bactericidal, killing >99% of bacteria in 2 h. BAL30072 activity was not significantly affected by efflux, it was only a marginal substrate of PenA β-lactamase, and activity was independent of malleobactin production and transport and the ability to transport pyochelin. In summary, BAL30072 has superior in vitro activity against B. pseudomallei compared with ceftazidime, meropenem or imipenem and it is rapidly bactericidal.     

2018—2021年武汉大学人民医院儿童血流感染的病原菌分布特征及耐药性分析

目的 分析武汉大学人民医院儿童血流感染病原菌特征及耐药性分析。方法 选取2018年1月—2021年12月武汉大学人民医院患儿血培养标本分离的病原菌及其药物敏感性数据进行统计分析。结果 共收集到21 571份住院儿童的血培养标本,共分离出病原菌1 646株,检测阳性率为7.63%。其中革兰阳性菌910株,占比为55.29%,革兰阴性菌715株,占比43.44%,真菌21株,占比1.28%。儿童血流感染前5位的病原菌依次为肺炎克雷伯菌、表皮葡萄球菌、肺炎链球菌、人葡萄球菌和大肠埃希菌,占比分别为20.60%、15.25%、14.52%、10.69%、10.57%。耐甲氧西林的凝固酶阴性葡萄球菌（MRCNS）检出率为20.47%,未发现有万古霉素耐药的凝固酶阴性葡萄球菌。肺炎克雷伯菌产超广谱β-内酰胺酶（ESBL）阳性占比为74.93%,大肠埃希菌ESBL阳性占比为6.90%;耐碳青霉烯酶的肠杆菌目（CRE）大肠埃希菌占比为56.32%,CRE肺炎克雷伯菌占比为0%。肺炎链球菌对红霉素、克林霉素、四环素耐药率较高,分别为100.0%、92.9%、85.2%,未发现对莫西沙星、利奈唑胺以及万古霉素耐药菌株。结论 武汉大学人民医院儿童血流感染主要菌株为肺炎克雷伯菌、肺炎链球菌和凝固酶阴性葡萄球菌（CNS）,且CNS耐药性较高,肺炎克雷伯菌对第3代头孢有了较高耐药性。应加强医院儿童耐药菌株监测,合理使用抗菌药物。     

Identification of Bacteria Isolated from an Oligotrophic Lake with Pesticide Removal Capacities

We studied the growth and capacities for pesticides removal of bacterial strains isolated from the Laguna Grande, an oligotrophic lake at the South of Spain (Archidona, Málaga). Strains were isolated from water samples amended with 10 and 50 g/ml of nine pesticides: organochlorinated insecticides (aldrin and lindane), organophosphorous insecticides (dimetoate, methyl-parathion and methidation), s-triazine herbicides (simazine and atrazine), fungicide (captan) and diflubenzuron (1-(-4-chlorophenyl)-3-(2,6-difluorobenzoyl urea), a chitinase inhibitor. The majority of the strains belonged to the genera Pseudomonas and Aeromonas and only 9% of the total of strains were Gram positive. From all the strains isolated, only 22 showed a wide growth range in all the pesticides tested and 4 of them were chosen for pesticide removal studies. The genetic identification of these strains showed their affiliation to Pseudomonas pseudoalcaligenes, Micrococcus luteus, Bacillus sp. and Exiguobacterium aurantiacum. These last two strains were those that showed the highest pesticide removal capacities and a high bacterial growth.     

Detection of lfrA and tap efflux pump genes among clinical isolates of non-pigmented rapidly growing mycobacteria

This study was performed to detect LfrA and Tap efflux pumps among clinical isolates of non-pigmented rapidly growing mycobacteria (NPRGM). Gene detection was performed using polymerase chain reaction (PCR) with specific primers designed for each gene. Susceptibility of the strains to doxycycline, tigecycline and ciprofloxacin was analysed using the broth microdilution reference technique. In total, 166 clinical isolates were included in the study. The lfrA gene was detected in four strains (2.4%), comprising two strains of Mycobacterium chelonae (6.7% of this species), one Mycobacterium fortuitum (1.1%) and one Mycobacterium mucogenicum (14.3%). The tap gene was detected in 109 strains (65.7%), comprising 3 Mycobacterium abscessus (33.3%), 12 M. chelonae (40%), 75 M. fortuitum (84.3%), 2 Mycobacterium mageritense (40%), 15 Mycobacterium peregrinum (68.2%), 1 Mycobacterium alvei and 1 Mycobacterium porcinum; no strains of M. mucogenicum were tap-positive. No differences between tap-positive and -negative strains were observed for resistance to doxycycline (Fisher's exact test, P = 0.055). lfrA is rare among clinical isolates of NPRGM, whilst tap is found more commonly. No correlation was detected between the presence of the efflux pumps and resistance to quinolones or tetracyclines.     

Clinical utility of daptomycin in infective endocarditis caused by Gram-positive cocci

Gram-positive bacteria account for >80% of all cases of endocarditis. Currently, staphylococci are the leading cause of endocarditis worldwide. Daptomycin is the drug of choice for empirical antibiotic therapy of staphylococcal endocarditis due to its optimal activity both against meticillin-susceptible Staphylococcus aureus and meticillin-resistant S. aureus (MRSA) strains. Daptomycin has not been proven to be superior to vancomycin in the treatment of MRSA endocarditis. However, daptomycin should be considered the drug of choice for the treatment of MRSA endocarditis caused by strains with a vancomycin minimum inhibitory concentration (MIC) of 2 μg/mL, for heterogeneous vancomycin-intermediate S. aureus (hVISA) phenotypes and for glycopeptide-intermediate S. aureus (GISA) strains. Daptomycin is the drug of choice for rescue therapy in cases of MRSA endocarditis in which vancomycin has failed. The appropriate dose of daptomycin has not yet been established; however, for treatment of left-sided endocarditis the dose of daptomycin should be higher than the recommended dose of 6 mg/kg/day. Combination antibiotic therapy with daptomycin (e.g. combined with fosfomycin) is a promising treatment for MRSA endocarditis and warrants further investigation. In vivo studies show that daptomycin is superior to vancomycin in the treatment of meticillin-resistant coagulase-negative staphylococci experimental endocarditis, although clinical data are required. Daptomycin could represent an efficacious treatment for vancomycin-resistant Enterococcus faecium endocarditis. Finally, the pharmacokinetic profile of daptomycin makes it an excellent drug for outpatient parenteral antimicrobial therapy.     

Antimicrobial activity of confertifolin from Polygonum hydropiper

Confertifolin (6,6,9a-trimethyl-4,5,5a,6,7,8,9,9a-octahydronaphtho[1,2-c] furan-3 (1H)-one) was isolated from the essential oil of Polygonum hydropiper L. (Polygonaceae) leaves using column chromatography. Confertifolin showed activity both in bacteria and fungi. The lowest MIC for bacteria was observed against Enterococcus faecalis (31.25 μg/mL). Significant MIC for fungi was observed against Scopulariopsis sp (7.81 μg/mL), Curvularia lunata (7.81 μg/mL), Epidermophyton floccosum (7.81 μg/mL), Trichophyton mentagrophytes (16.62 μg/mL), Trichophyton rubrum (MTCC 296) (16.62 μg/mL), Aspergillus niger (31.25 μg/mL), Botrytis cinerea (31.25 μg/mL) Magnaporthe grisea (62.5 μg/mL), Trichophyton simii (125 μg/mL) and Trichophyton rubrum (clinical isolate) (125 μg/mL).     

2018—2019年西安交通大学第二附属医院鲍曼不动杆菌的分布及耐药性分析

目的 分析西安交通大学第二附属医院鲍曼不动杆菌的临床分布及耐药性,为临床医师选择合理的抗感染治疗方案提供参考依据。方法 以2018年1月-2019年12月西安交通大学第二附属医院住院的患者为研究对象,按照美国临床实验室标准化委员会（CLSI）推荐的方法进行鲍曼不动杆菌的初步筛选,用梅里埃VITEK 2 Compact全自动细菌鉴定及药敏分析系统进行细菌鉴定和药敏实验,用Excel进行数据统计分析。结果 2018-2019年本院住院患者中共分离出935株鲍曼不动杆菌,主要分布于急诊科,共181株;主要来源于痰液标本,共676株。感染人群主要为14岁以上的中青年及老年患者。药敏结果显示鲍曼不动杆菌对替卡西林/克拉维酸、多西环素、哌拉西林/他唑巴坦具有较高的耐药性,耐药率依次为87.43%、75.96%、64.98%;鲍曼不动杆菌对黏菌素、阿米卡星和替加环素具有良好的敏感性,敏感率依次为99.61%、85.02%、73.56%。结论 本院临床上鲍曼不动杆菌感染的高发人群为14岁以上的中青年及老年患者,鲍曼不动杆菌对多种抗生素都有很强的耐药性,应加强病原菌培养及耐药性监测,指导临床医师合理使用抗生素。     

Chromosomal mutations that accompany qnr in clinical isolates of Escherichia coli

We examined 13 qnr-positive and 14 qnr-negative clinical isolates of Escherichia coli for mutations previously seen in a qnr-containing laboratory strain exposed to supra minimum inhibitory concentrations (MICs) of ciprofloxacin. Among the qnr-positive strains, those with ciprofloxacin MICs of?≥?2?µg/mL had at least one mutation in gyrA. Mutations in parC were present in strains with a ciprofloxacin MIC of?≥?128?µg/mL. The 6 most ciprofloxacin-resistant strains contained additional plasmid-mediated quinolone resistance determinants. aac(6')-Ib-cr was found in 5 of the 6 strains. Eleven of the 13 strains had alterations in MarR, 9 in SoxR, and 5 had mutations in AcrR. All had elevated expression of at least one efflux pump gene, predominantly acrA (92% of the strains), followed by mdtE (54%) and ydhE (46%). Nine had functionally silent alterations in rfa, two had mutations in gmhB, and one of these also had a mutation in surA. An E. coli with ciprofloxacin MIC of 1024?µg/mL contained 4 different plasmid-mediated quinolone resistance determinants as well as gyrA, parC, parE and pump overexpression mutations. Nine of the 14 qnr-negative strains had mutations in topoisomerase genes with a ciprofloxacin MIC of 0.25 to 256?µg/mL. The three most resistant strains also had mutations in parE. Twelve had alterations in MarR, 10 in SoxR and 5 in AcrR. Ten of the 14 strains had elevated expression of efflux pumps with acrA (71.4%), followed by ydhE (50%) and mdtE (14.3%). A diversity of resistance mechanisms occurs in clinical isolates with and without qnr genes.     

Comparative in vitro susceptibility of Burkholderia pseudomallei to doripenem, ertapenem, tigecycline and moxifloxacin

Burkholderia pseudomallei, the causative agent of melioidosis, continues to present therapeutic challenges in endemic areas. A number of clinical issues have prompted consideration of alternative antimicrobial therapies. These include stability in 24-h infusion pumps, broad-spectrum coverage in the empirical treatment of community-acquired pneumonia, cost, the need for effective oral agents and rare reports of emerging resistance. This study aimed to examine the in vitro susceptibility of B. pseudomallei to four new antimicrobial agents, namely moxifloxacin, tigecycline, ertapenem and doripenem. A total of 100 clinical isolates were tested by Etest and disk diffusion. As there are no interpretative standards for these antimicrobials, MIC(90) values (minimum inhibitory concentrations for 90% of the isolates) were compared with those for meropenem. MIC values for each agent were correlated with zone of inhibition diameters. MICs for doripenem were broadly similar to those for meropenem, with a MIC(90) of 1.5 μg/mL (range 0.38-4 μg/mL). There was good correlation (r=-0.71; P<0.001) between the MIC and disk diffusion for doripenem. Ertapenem, tigecycline and moxifloxacin had limited in vitro activity in this study, although no interpretative criteria exist for these agents. Further in vitro, animal and clinical studies are suggested to validate the efficacy of doripenem in the management of melioidosis.     

Patent Evaluation: Hydrogenated Rapamycin Derivatives as Antifungal Agents

Summary

Novelty: Hydrogenated derivatives of rapamycin are disclosed as antifungal agents.

Biology: Data are presented which show that both claimed compounds are less active against five strains of Candida albicans than the parent rapamycin. 1,2-Dihydrorapamycin is significantly less active, whereas the 1,2,3,4-tetrahydro derivative was generally only half as effective (MIC = 0.006 μg/ml, compared with 0.003 μg/ml). However, Candida albicans 3669 was more sensitive to the tetrahydroderivative (MIC = 0.0125 μg/ml) than rapamycin (MIC = 0.025 μg/ml). Both new derivatives were relatively inactive in in vitro LAF and in vivo PLN tests and hence lack the immunosuppresive activity associated with rapamycin.

Chemistry: 1,2-Dihydro and 1,2,3,4-tetrahydro rapamycin were prepared by high pressure hydrogenation of rapamycin, which employs tris(triphenylphosphine)rhodium(I)chloride as a catalyst.