Effects of Combined Treatment with Sansanmycin and Macrolides on Pseudomonas aeruginosa and Formation of Biofilm

Objective To observe the effects of combined treatment with sansanmycin and macrolides on Pseudomonas aeruginosa and formation of biofilm. Methods Micro-dilution method was used to determine the minimal inhibitory concentrations （MICs） of sansanmycin, gentamycin, carbenicillin, polymyxin B, roxithromycin, piperacillin, and tazobactam. PAl and PA27853 biofilms were observed under optical microscope after staining and under SEM after treatment with sansanmycin at different dosages and combined treatment with sansanmycin and roxithromycin. Viable bacteria in PAl and PA27853 biofilms were counted after treatment with sansanmycin at different dosages or combined treatment with sansanmycin and roxithromycin. Results The MIC of sansanmycin was lower than that of gentamycin and polymyxin B, but was higher than that of carbenicillin. Roxithromycin enhanced the penetration of sansanmycin to PAl and PA27853 strains through biofilms. PAl and PA27853 biofilms were gradually cleared with the increased dosages of sansanmycin or with the combined sansanmycin and roxithromycin. Conclusion Sub-MIC levels of roxithromycin and sansanmycin substantially inhibit the generation of biofilms and proliferation of bacteria. Therefore, combined antibiotics can be used in treatment of intractable bacterial infection.

Mycoplasma pneumoniae Macrolide Resistance and MLVA Typing in Children in Beijing,China,in 2016:Is It Relevant?

Objective The aim of this study is to investigate the macrolide resistance rate and molecular type with multiple-locus variable-number tandem-repeat analysis(MLVA)of Mycoplasma pneumoniae of Beijing in 2016 in pediatric patients.Methods Real-time quantitative polymerase chain reaction(PCR)was used to identify M.pneumoniae,and MLVA was performed.The domain V of the 23 S rRNA was sequenced to detect macrolide-resistant point mutations.We also investigated the activities of antibiotics against M.pneumoniae isolates in vitro.Results The PCR detection rate of M.pneumoniae in children in Beijing was 40%,and the macrolide resistance rate was 66%.The A2063 G mutation in the 23 S rRNA V region is the dominant mutation(137/146,93.84%),whereas the A2064 G mutation is rare(9/146,6.16%).Seventy-three samples were typed successfully by MLVA typing,including 86.3%(63/73)were MLVA type 4-5-7-2,and 13.7%(10/73)were MLVA type 3-5-6-2.No other types were found.No strains were resistant to levofloxacin or tetracycline.Conclusion In 2016,a specific decrease in the macrolide resistance rate occurred in Beijing.The detection rate and macrolide resistance rate of outpatients are lower than those of inpatients.The A2063 G mutants M.pneumoniae have high levels of resistance to erythromycin and azithromycin.The primary MLVA type is 4-5-7-2,followed by 3-5-6-2.No other MLVA types were detected.No strains resistant to tetracycline or levofloxacin were found in vitro.

Preliminary Study on Drug Susceptibility Profile and Resistance Mechanisms to Macrolides of Clinical Isolates of Non-tuberculous Mycobacteria from China

Objective Macrolide susceptibility and drug resistance mechanisms of clinical non-tuberculous mycobacteria（NTM） isolates were preliminarily investigated for more accurate diagnosis and treatment of the infection in China. Methods Four macrolides, including clarithromycin（CLAR）, azithromycin（AZM）, roxithromycin（ROX）, and erythromycin（ERY）, were used to test the drug susceptibility of 310 clinical NTM isolates from six provinces of China with the broth microdilution method. Two resistance mechanisms, 23 S r RNA and erm, were analyzed with nucleotide sequence analysis. Results Varied effectiveness of macrolides and species-specific resistance patterns were observed. Most Mycobacterium abscessus subsp. massiliense were susceptible and all M. fortuitum were highly resistant to macrolides. All the drugs, except for erythromycin, exhibited excellent activities against slow-growing mycobacteria, and drug resistance rates were below 22.2%. Only four highly resistant strains harbored 2,058/2,059 substitutions on rrl and none of other mutations were related to macrolide resistance. G2191 A and T2221 C on rrl were specific for the M. abscessus complex（MABC）. Seven sites, G2140 A, G2210 C, C2217 G, T2238 C, T2322 C, T2404 C, and A2406 G, were specifically carried by M. avium and M. intracellulare. Three sites, A2192 G, T2358 G, and A2636 G, were observed only in M. fortuitum and one site G2152 A was specific for M. gordonae. The genes erm（39） and erm（41） were detected in M. fortuitum and M. abscessus and inducible resistance was observed in relevant sequevar. Conclusion The susceptibility profile of macrolides against NTM was demonstrated. The well-known macrolide resistance mechanisms, 23 S r RNA and erm, failed to account for all resistant NTM isolates, and further studies are warranted to investigate macrolide resistance mechanisms in various NTM species.

Selective Association between Cephalosporin, Quinolone, Macrolide, and Penicillin Antibiotic Consumption and Childhood Obesity in Europe

The accelerated weight gain in productive animals as a result of feeding antibiotic enriched fodder has been well known for decades. The better energy harvest is the result of modified gut microbiota as a consequence of applied antibiotics. Similar mechanisms might result obesity in humans as well. Objectives: Finding associations between global antibiotic consumption of different classes in EU countries and obesity data in adults and children prove that antibiotics might play a significant role in the development of obesity “epidemics” and related illnesses. Methods: Antibiotic consumption data were compared with obesity figures in adults and children in European countries and statistically analyzed for significance. Results: Significant correlation was found between the average yearly consumption of cephalosporins (p = 0.007), quinolones (p = 0.031), macrolides (p = 0.000083) and childhood obesity data, but no significant association was observed with the average penicillin consumption. No association was observed between adult obesity and any of the antibiotic classes studied. Conclusions: Our results support the hypothesis that different types of antibiotics might influence the development of obesity among children, and this finding can serve as a unified explanation for the development of obesity “epidemics”, similarly to the obesity and gut flora alteration-related diseases (type 2 diabetes mellitus, autism, etc.).

Antifungalmycin,an antifungal macrolide from Streptomyces padanus 702

Two polyene macrolide antibiotics:antifungalmycin(1)and fungichromin(2)were isolated from the culture mycelia of Streptomyces padanus 702 via bioactivity-guided fractionation using various chromatographic procedures.Their structures were elucidated on the basis of spectral analysis,and 1 is a new polyene macrolide.Compounds 1 and 2 showed significant inhibition against Gibberella zeae with EC_(50)values of 26.71 and 2.21μg/mL,Fusicoccum sp.(plantain head blight)with EC_(50)values of 23.4 and 3.17μg/mL,Mucor ssp.8894 with EC_(50)values of 28.80 and 2.11μg/mL,Ustilaginoidea virens with EC_(50)values of 26.72 and 0.21μg/mL,respectively.This shows that the microbial secondary metabolites 1 and 2 have the potential to be developed as agricultural fungicides for use against G.zeae,Fusicoccum sp.,Mucor ssp.8894,and U.virens.

Synthesis of novel 15-membered macrolide derivatives

以便开发对抵抗细菌有效的新抗菌素，一系列新奇 15 成员 macrolide 衍生物被羟基的修正在 C-11 设计并且综合， C-12 和 C-4 ″位置。他们的结构被 MS，红外， 1H NMR 或 13C NMR 证实。

Neutral Complex Extraction and Synergistic Extraction of Macrolide Antibiotics

Based on the theory of reactive extraction, new solvent systems were developed to replace butylacetate for extraction of macrolide antibiotics (erythromycin, kitasamycin, spiramycin meleumycin etc.). A new neutral complex solvent extraction system, fatty alcohol-kerosene (marked by El), was used for extraction of erythromycin,one of the macrolide antibiotics. The extraction equilibrium equation is obtained, and the extraction distribution is as follows D=exp(-36.33×10^3/RT+18.77(B)1.2/(o)/(1+10^8.07-pH)The effects of several parameters on extraction equilibrium were investigated. Furthermore, a new synergistic extraction system (marked by E2) was developed, in which another solvent was used as synergistic agent to replace the diluent kerosene in the neutral complex extraction system. Based on these new extraction systems, an improved process for extraction of erythromycin was developed, showing remarkable advantages in technology and economics owing to its low solvent consumption of 3 kg per billion unit compared with 9-10 for butylacetate. The recovery process of solvent from raffinate may be eliminated.

Synthesis of derivatives of imidazo[4,5-b]pyridine:Novel sulfur contained side chains for macrolide antibiotics

imidazo 的新奇衍生物的二个系列[4,5-b ] 烯丙基吡啶被综合。这些混合物能被用作半 synthesised ketolide 抗菌素的侧链。侧链有罐头属于 ketolide 的免费的胺组核心。有这种侧链的 Macrolides 将对抗生素的一种抵抗的紧张显示出明显的活动。侧链的结构被 1H 证实， 13C NMR， MS， HMBC 系列。

Whole Genome Analysis Reveals New Insights into Macrolide Resistance in Mycoplasma pneumoniae

Objective Mutations in 23 S rRNA gene are known to be associated with macrolide resistance in Mycoplasma pneumoniae（M. pneumoniae）. However, these mutations alone do not fully explain the high resistance rates in Asia. The aim of this study was to investigate other possible mutations involved in macrolide resistance in M. pneumoniae. Methods The whole genomes of 10 clinical isolates of M. pneumoniae with macrolide resistance were sequenced by Illumina Hi Seq2000 platform. The role of the macrolide-specific efflux transporter was assessed by efflux-pump inhibition assays with reserpine and carbonyl cyanide m-chlorophenyl-hydrazone（CCCP）. Results A total of 56 single nucleotide polymorphisms（SNPs） were identified in 10 clinical isolates in comparison to the reference strains M129 and FH. Strikingly, 4 of 30 SNPs causing non-synonymous mutations were clustered in macrolide-specific efflux system gene mac B encoding macrolide-specific efflux pump protein of the ATP-binding cassette transporter family. In assays of the minimal inhibitory concentrations（MIC） of macrolide antibiotics in the presence of the efflux pump inhibitors caused a significant decrease of MICs, even under detectable levels in some strains. Conclusion Our study suggests that macrolide efflux pump may contribute to macrolide resistance in M. pneumoniae in addition to the common point mutations in 23 S r RNA gene.

Macrolide-Clarithromycin Task-Force for the Treatment and Prophylaxis of Covid-19 as a Single Agent

SARS-CoV-2 is a novel RNA coronavirus responsible of a deadly pandemic: the clinical illness COVID-19. With only one authorized drug for emergency use in critically ill patients: Remdesivir, there is not any other approved drug or vaccine yet with proven potential to overcome this infection. We exposed here many scientific evidences to support our novel idea that a macrolide, basically Clarithromycin, could be effective as a single agent for treatment and prophylaxis of COVID-19. Clarithromycin could change the history of this pandemic. It could reduce the costs of treatment and the potential adverse effects when combining more than one drug such as with Hydroxychloroquine. Clarithromycin treatment and prophylaxis as a single agent could be much more simple, safe and cheaper as giving Chloroquine or Hydroxychloroquine alone or in combination with Azithromycin as well as other therapeutic options.

Study of Serotypes, Susceptibility to Macrolide and Virulence and Resistance Molecular Profiles in Invasive Strains of <i>Streptococcus agalactiae</i>in Two Argentine Provinces

A study of invasive strains of Streptococcus agalactiae (GBS) from Cordoba and Misiones, Argentina;was conducted to determine serotypes, the susceptibility to macrolides and molecular profiles of virulence and resistance. We studied 17 strains, recovered from cerebrospinal fluid, blood and cellulite and, a strain of trophoblastic remnants from Misiones. The serotypes were determined by agglutination with sera and phenotypes of resistance to macrolide-lincosamide-streptogramin B (MLSB), were determined with the double-disk test (D-test). The confirmation was performed by E-test by ERI and CLI respectively that determined the minimum inhibitory concentration (MIC). Results were interpreted as recommended by the Clinical and Laboratory Standards Institute (CLSI) 2013. Resistance genes: ermB, ermTR and mefA and the virulence genes: bac, bca, rib, lmb, hylB, scpB, fbsA, fbsB and cylB were investigated by conventional PCR. Serotype III (50%) and Ia (50%) were detected in Cordoba. One strain showed cMLSB phenotype, confirmed by MIC. The same strains showed a resistance gene ermB. All studied virulence genes were detected in 100% of these strains. In Misiones, serotypes were III (72.7%), Ia (18.2%) and Ib (9.1%). All strains were susceptible to CLI and ERI by D-test, confirmed by MIC. None of the strains showed resistance genes. Virulence genes bca, rib, hylB, lmb, fbsA, fbsB and cylB were detected in 100% of the strains, bac in 81.8% and scpB in 90.9%. Our results are in accordance with international data, associating higher frequency of serotype III of invasive neonatal disease followed by Ia. The presence of serotype Ib could indicate a regional difference for Misiones. We highlight the macrolides susceptibility in strains of Misiones and consistency in the results for D-test, MIC and PCR for the single strain resistant phenotype cMLSB from Cordoba. The virulence genes studied were presented with high frequency as expected for invasive strains.

Antibiotic Treatment for Chronic Rhinosinusitis after Endoscopic Surgery: How Long Should Macrolide Antibiotics Be Given?

Background: The purpose of this study was to determine an appropriate period for macrolide antibiotic therapy, and to investigate whether this period could be shorter, for patients with chronicrhino sinusitis (CRS) after functional endoscopic sinus surgery (FESS). Methods: A retrospective analysis of 41 patients undergoing FESS for CRS was performed. All patients underwent pre-operative computed tomography (CT). Patients with fungal sinusitis, allergic fungal sinusitis, and eosinophilic sinusitis were excluded. After FESS, normalized sinus mucosa was confirmed by CT and endoscopy in all patients. Postoperative antibiotic therapy consisted of first-line and second-line regimens. Garenoxacin (GRNX), or clarithromycin (CAM, 400 mg/day) was used as the first-line regimens and low-dose macrolide therapy (CAM, 200 mg/day) was used as the second-line regimen and was prescribed at outpatient visits based on our clinical criteria. Results: Second-line antibiotic therapy (low-dose CAM) was not necessary in 12 of 41 (29%) patients, while it was prescribed in 29 of 41 (71%). The mean duration of low-dose CAM therapy after FESS was 36 days (range 7 to 122 days;median, 25 days). Patients who received second-line therapy (n = 29) were divided into two groups based on the choice of first-line therapy, a GRNX group (n = 13) and a non-GRNX group (n = 16). Those in the non-GRNX had longer periods of postoperative CAM therapy than those in the GRNX group. Conclusion: GRNX was associated with a shorter duration of low-dose macrolide therapy after FESS, and 29% of patients did not need any low-dose macrolide therapy postoperatively. Therefore, macrolide antibiotics should not be routinely prescribed after FESS.

Synthesis of novel 15-membered macrolide dimers

15 成员 macrolides 的一系列新奇暗淡 ers 被综合并且评估。暗淡 ers 对抗生素的一种易受影响的 S 展出了优秀活动。肺病，但是没对抗生素的一种抵抗的 S 显示出任何改进活动。pneumoniae 由 erm 基因编码了。

The non-antibacterial effects and possible clinical applications of macrolide antibiotics

As one group of the most widely used oral antibacterial drugs, macrolides have been clinically applied for more than 50 years because of their safety and efficacy. Recently, the non-antibacterial applications of macrolides are frequently reported, such as the therapy of malignant tumor, exudative pleurisy, pulmonary fibrosis, rheumatoid arthritis, bronchiectasis, asthma, gastrointestinal peristalsis disorders, and so on with new pharmacological effects, including reverse of tumor resistance, anti-chemical adherence, anti-fibrosis, and modulations of gastrointestinal motility as well as immune activity. The in-depth research of marcolides’ non-antibiotic actions can not only extend the application fields of macrolides, but provide a new way to treat some refractory diseases.

Partial Synthesis of Macrolide Alkaloid Euonine

The macrolide alkaloid euonine 1 with pharmacologic activity was prepared from the alkaloid wilforgine 2. Their structures were confirmed by IR, NMR, MS and optical rotation.

百日咳病原新认识及其抗感染策略

百日咳是由百日咳鲍特菌感染引起的急性呼吸道传染病,本病历史悠久,任何年龄段的人群均可感染发病。百日咳再现已成为引起高度关注的全球性问题,包括我国在内。2022年起至今,我国报告百日咳病例数上升迅猛。当前百日咳鲍特菌流行株的主要抗原(百日咳毒素)的基因型已发生改变,相应抗原与疫苗株不同而产生免疫逃逸,是当前百日咳再现的重要原因之一。百日咳鲍特菌目前普遍对大环内酯类抗生素耐药是临床治疗失败的重要原因,因此不再推荐其作为百日咳抗感染治疗的首选用药。2月龄以上无磺胺禁忌症的患儿,百日咳卡他期和痉咳期推荐复方磺胺甲噁唑口服作为首选抗感染方案;对2月龄以下或症状危重的患儿,推荐哌拉西林或头孢哌酮-舒巴坦静滴治疗。改良或研发与流行株抗原一致的新一代百日咳疫苗将是提升易感人群免疫保护力、控制本病流行的长远策略。

儿童大环内酯类耐药肺炎支原体肺炎诊疗理念与实践

2023年7月以来我国乃至全球迎来了肺炎支原体肺炎的流行高峰,给儿童健康、家庭及社会均带来了沉重的负担。尽管大环内酯类抗菌药物为指南推荐的首选用药,本次流行的肺炎支原体肺炎住院患儿中,以大环内酯类耐药为主。这对传统的诊疗模式带来了巨大的挑战,特别是肺动脉栓塞病例的增多,需要临床医师思考并实践新的诊疗理念。

UHPLC-MS/MS法测定耕地周围地表水中5种除草剂含量

实验研究建立了超高压液相色谱-三重四级杆串联质谱法测定耕地周围地表水中2,4-二氯苯氧乙酸、灭草松、草铵膦、α-萘乙酸、马来酰肼除草剂含量的分析方法。随机采集耕地周围地表水样品,预处理后,取上述水样500 mL,调节酸度为中性,取HLB固相萃取柱,活化完毕后,设定程序,将上述水样以12 mL·min^(-1)的流量过柱,最后用16 mL甲醇洗脱,收集洗脱液;洗脱液于氮吹至近干,加甲醇1 mL定容,涡旋混匀,质谱分析采用多反应监测模式,定性、定量检测。2,4-二氯苯氧乙酸、灭草松、草铵膦、α-萘乙酸、马来酰肼质量浓度在0.004~4.0μg·mL^(-1)范围内呈良好的线性关系,检测限分别为0.21μg·L^(-1)、0.23μg·L^(-1)、0.14μg·L^(-1)、0.25μg·L^(-1)、0.15μg·L^(-1);三水平回收率范围在85.4%~96.6%;2,4-二氯苯氧乙酸、灭草松、草铵膦、α-萘乙酸、马来酰肼重复性RSD分别为3.4%,4.0%,3.2%,2.9%,3.6%,方法重复性良好。实验结果表明,此方法具有快速、准确等特点,方法可以用于耕地周围地表水中2,4-二氯苯氧乙酸、灭草松、草铵膦、α-萘乙酸、马来酰肼等除草剂的监测。