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Molecular insights into 14-membered macrolides using the MM-PBSA method

Yam WK, Wahab HA

J Chem Inf Model, 2009 Jun;49(6):1558-67.
PMID: 19469526 DOI: 10.1021/ci8003495

Erythromycin A and roxithromycin are clinically important macrolide antibiotics that selectively act on the bacterial 50S large ribosomal subunit to inhibit bacteria's protein elongation process by blocking the exit tunnel for the nascent peptide away from ribosome. The detailed molecular mechanism of macrolide binding is yet to be elucidated as it is currently known to the most general idea only. In this study, molecular dynamics (MD) simulation was employed to study their interaction at the molecular level, and the binding free energies for both systems were calculated using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The calculated binding free energies for both systems were slightly overestimated compared to the experimental values, but individual energy terms enabled better understanding in the binding for both systems. Decomposition of results into residue basis was able to show the contribution of each residue at the binding pocket toward the binding affinity of macrolides and hence identified several key interacting residues that were in agreement with previous experimental and computational data. Results also indicated the contributions from van der Waals are more important and significant than electrostatic contribution in the binding of macrolides to the binding pocket. The findings from this study are expected to contribute to the understanding of a detailed mechanism of action in a quantitative matter and thus assisting in the development of a safer macrolide antibiotic.

Matched MeSH terms: Macrolides/metabolism*; Macrolides/chemistry*
Macrolide resistance and genotypic characterization of Streptococcus pneumoniae in Asian countries: a study of the Asian Network for Surveillance of Resistant Pathogens (ANSORP)

Song JH, Chang HH, Suh JY, Ko KS, Jung SI, Oh WS, et al.

J Antimicrob Chemother, 2004 Mar;53(3):457-63.
PMID: 14963068

To characterize mechanisms of macrolide resistance among Streptococcus pneumoniae from 10 Asian countries during 1998-2001.

Matched MeSH terms: Macrolides/pharmacology*
Multiple and multigeneric anthelmintic resistance on a sheep farm in Malaysia

Sivaraj S, Dorny P, Vercruysse J, Pandey VS

Vet Parasitol, 1994 Oct;55(1-2):159-65.
PMID: 7886917

The anthelmintic efficacy of benzimidazoles, levamisole, closantel, ivermectin and moxidectin was evaluated on an institutional farm in Malaysia using faecal egg count reduction tests, controlled slaughter trials and an in vitro egg hatch assay. The results of this study indicated simultaneous resistance of Haemonchus contortus against benzimidazoles and ivermectin and of Trichostrongylus colubriformis against benzimidazoles and levaminsole on the same farm. Moxidectin was effective against the ivermectin resistant H. contortus.

Matched MeSH terms: Macrolides
Hydroxychloroquine and Chloroquine in Prophylaxis and Treatment of COVID-19: What Is Known?

Shankar PR, Palaian S, Gulam SM

J Pharm Bioallied Sci, 2020 10 06;13(1):4-10.
PMID: 34084043 DOI: 10.4103/jpbs.JPBS_404_20

The corona virus disease-19 (COVID-19) pandemic has affected the entire world causing huge economic losses and considerable morbidity and mortality. Considering the explosive growth of the pandemic repurposing existing medicines may be cost-effective and may be approved for use in COVID-19 faster. Researchers and medical practitioners worldwide have explored the use of chloroquine and hydroxychloroquine, in few occasions combined with the macrolide antibiotic azithromycin, for COVID-19 treatment. These two drugs are economic and easily available, and hence gained attention as a potential option for COVID-19 management. As per the available evidence, the outcomes of treatments with these medications are conflicting from both the efficacy and safety (predominantly cardiac related) perspectives. Currently, multiple studies are underway to test the safety and efficacy of these medications and more results are expected in the near future. The retina, the endocrine system (with risk of hypoglycemia), the musculoskeletal system, the hematological system, and the neurological system may also be affected. The use of these drugs is contraindicated in patients with arrhythmias, known hypersensitivity, and in patients on amiodarone. In addition to the published literature, personal communication with doctors treating COVID-19 patients seems to suggest the drugs may be effective in reducing symptoms and hastening clinical recovery. The literature evidence is still equivocal and further results are awaited. There has been recent controversy including retraction of articles published in prestigious journals about these medicines. Their low cost, long history of use, and easy availability are positive factors with regard to use of these drugs in COVID-19.

Matched MeSH terms: Macrolides
Genetics of spinosad resistance in a multi-resistant field-selected population of Plutella xylostella

Sayyed AH, Omar D, Wright DJ

Pest Manag Sci, 2004 Aug;60(8):827-32.
PMID: 15307676

Resistance to the bacteria-derived insecticides spinosad (Conserve), abamectin (Vertimec), Bacillus thuringiensis var kurstaki (Btk) (Dipel), B thuringiensis var aizawai (Bta) (Xentari), B thuringiensis crystal endotoxins Cry1Ac and Cry1Ca, and to the synthetic insecticide fipronil was estimated in a freshly-collected field population (CH1 strain) of Plutella xylostella (L) from the Cameron Highlands, Malaysia. Laboratory bioassays at G1 indicated significant levels of resistance to spinosad, abamectin, Cry1Ac, Btk, Cry1Ca, fipronil and Bta when compared with a laboratory insecticide-susceptible population. Logit regression analysis of F1 reciprocal crosses indicated that resistance to spinosad in the CH1 population was inherited as a co-dominant trait. At the highest dose of spinosad tested, resistance was close to completely recessive, while at the lowest dose it was incompletely dominant. A direct test of monogenic inheritance based on a back-cross of F1 progeny with CH1 suggested that resistance to spinosad was controlled by a single locus.

Matched MeSH terms: Macrolides/toxicity*
Fipronil resistance in the diamondback moth (Lepidoptera: Plutellidae): inheritance and number of genes involved

Sayyed AH, Wright DJ

J Econ Entomol, 2004 Dec;97(6):2043-50.
PMID: 15666763

Bioassays (at generation 1, G1) using fipronil, spinosad, indoxacarb, and Bacillus thuringiensis toxins Cry1Ac and Cry1Ca with a newly collected field population of Plutella xylostella (L.) from farmers fields in the Cameron Highlands, Malaysia, indicated a resistance ratio of approximately 400-, 1,170-, 330-, 2,840-, and 1,410-fold, respectively, compared with a laboratory-susceptible population of P. xylostella (ROTH). At G3, the field-derived population was divided into two subpopulations, one was selected (G3 to G7) with fipronil (fip-SEL), whereas the second was left unselected (UNSEL). Bioassays at G8 found that selection with fipronil gave a resistance ratio of approximately 490 compared with UNSEL and approximately 770 compared with ROTH. The resistance ratio for fipronil, spinosad, indoxacarb, Cry1Ac, and Cry1Ca in the UNSEL population declined significantly by G8. Logit regression analysis of F1 reciprocal crosses between fip-SEL (at G8) and UNSEL indicated that resistance to fipronil in the fip-SEL population was inherited as an autosomal, incompletely recessive (D(LC) = 0.37) trait. At the highest dose of fipronil tested, resistance was completely recessive, whereas at the lowest dose it was incompletely recessive. A direct test of monogenic inheritance based on a backcross of F1 progeny with fip-SEL suggested that resistance to fipronil was controlled by a single locus. The fip-SEL population at G8 showed little change in its response to spinosad and indoxacarb compared with G1, whereas its susceptibility to Cry1Ac and Cry1Ca increased markedly over the selection period. This suggests that there may be some low level of cross-resistance between fipronil, spinosad, and indoxacarb.

Matched MeSH terms: Macrolides
Fulltext Burkholderia pseudomallei isolates from Sarawak, Malaysian Borneo, are predominantly susceptible to aminoglycosides and macrolides

Podin Y, Sarovich DS, Price EP, Kaestli M, Mayo M, Hii K, et al.

Antimicrob Agents Chemother, 2014;58(1):162-6.
PMID: 24145517 DOI: 10.1128/AAC.01842-13

Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei. Resistance to gentamicin is generally a hallmark of B. pseudomallei, and gentamicin is a selective agent in media used for diagnosis of melioidosis. In this study, we determined the prevalence and mechanism of gentamicin susceptibility found in B. pseudomallei isolates from Sarawak, Malaysian Borneo. We performed multilocus sequence typing and antibiotic susceptibility testing on 44 B. pseudomallei clinical isolates from melioidosis patients in Sarawak district hospitals. Whole-genome sequencing was used to identify the mechanism of gentamicin susceptibility. A novel allelic-specific PCR was designed to differentiate gentamicin-sensitive isolates from wild-type B. pseudomallei. A reversion assay was performed to confirm the involvement of this mechanism in gentamicin susceptibility. A substantial proportion (86%) of B. pseudomallei clinical isolates in Sarawak, Malaysian Borneo, were found to be susceptible to the aminoglycoside gentamicin, a rare occurrence in other regions where B. pseudomallei is endemic. Gentamicin sensitivity was restricted to genetically related strains belonging to sequence type 881 or its single-locus variant, sequence type 997. Whole-genome sequencing identified a novel nonsynonymous mutation within amrB, encoding an essential component of the AmrAB-OprA multidrug efflux pump. We confirmed the role of this mutation in conferring aminoglycoside and macrolide sensitivity by reversion of this mutation to the wild-type sequence. Our study demonstrates that alternative B. pseudomallei selective media without gentamicin are needed for accurate melioidosis laboratory diagnosis in Sarawak. This finding may also have implications for environmental sampling of other locations to test for B. pseudomallei endemicity.

Matched MeSH terms: Macrolides/pharmacology*
Fulltext Effect of Macrolide Prophylactic Therapy on AIDS-Defining Conditions and HIV-Associated Mortality

Pasayan MKU, S Mationg ML, Boettiger D, Lam W, Zhang F, Ku SW, et al.

J Acquir Immune Defic Syndr, 2019 04 01;80(4):436-443.
PMID: 30550488 DOI: 10.1097/QAI.0000000000001933

BACKGROUND: Mycobacterium avium complex prophylaxis is recommended for patients with advanced HIV infection. With the decrease in incidence of disseminated Mycobacterium avium complex infection and the availability of antiretroviral therapy (ART), the benefits of macrolide prophylaxis were investigated. This study examined the impact of macrolide prophylaxis on AIDS-defining conditions and HIV-associated mortality in a cohort of HIV-infected patients on ART.
METHODS: Patients from TREAT Asia HIV Observational Database (September 2015 data transfer) aged 18 years and older with a CD4 count <50 cells/mm at ART initiation were included. The effect of macrolide prophylaxis on HIV-associated mortality or AIDS-defining conditions (as a combined outcome) and HIV-associated mortality alone were evaluated using competing risk regression. Sensitivity analysis was conducted in patients with a CD4 <100 cells/mm at ART initiation.
RESULTS: Of 1345 eligible patients, 10.6% received macrolide prophylaxis. The rate of the combined outcome was 7.35 [95% confidence interval (CI): 6.04 to 8.95] per 100 patient-years, whereas the rate of HIV-associated mortality was 3.14 (95% CI: 2.35 to 4.19) per 100 patient-years. Macrolide use was associated with a significantly decreased risk of HIV-associated mortality (hazard ratio 0.10, 95% CI: 0.01 to 0.80, P = 0.031) but not with the combined outcome (hazard ratio 0.86, 95% CI: 0.32 to 2.229, P = 0.764). Sensitivity analyses showed consistent results among patients with a CD4 <100 cells/mm at ART initiation.
CONCLUSIONS: Macrolide prophylaxis is associated with improved survival among Asian HIV-infected patients with low CD4 cell counts and on ART. This study suggests the increased usage and coverage of macrolide prophylaxis among people living with HIV in Asia.

Matched MeSH terms: Macrolides/therapeutic use*
Mycoplasma hominis, Ureaplasma urealyticum and Chlamydia trachomatis Respiratory Colonization in Malaysian Preterm Infants

Ng KF, Kee Tan K, Chok MC, Zamil Mohd Muzzamil N, Choo P, Paramasivam U, et al.

J Trop Pediatr, 2017 Dec 01;63(6):447-453.
PMID: 28334949 DOI: 10.1093/tropej/fmx011

This prospective observational study aims to determine the incidence, predictors and clinical features of Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Chlamydia trachomatis (CT) respiratory colonization in infants <37 weeks of gestation. A total of 200 preterm newborns admitted to a tertiary center in Malaysia between 2013 and 2015 for increased breathing effort had their respiratory secretions tested for these bacteria by polymerase chain reaction. Fifteen of the 200 (7.5%) infants were detected to have these organisms in their respiratory tracts. Preterm prelabor rupture of membrane was associated with positive detection (odds ratio: 3.7; 95% confidence interval: 1.2-11.3). Seventy-three of the 200 (36.5%) infants were given macrolide for presumed infection but only 4.1% (3 of 73) were positive for these organisms. The incidence of UU respiratory colonization among preterm infants in our center is lower than other published reports, while the frequency of MH and CT isolation is comparable with many studies. There should be judicious use of empirical antibiotics for presumed UU, MH and CT infection in preterm infants.

Matched MeSH terms: Macrolides
Fulltext Quintuplex PCR to detect antibiotic resistance genes in Streptococcus pneumoniae

Navindra Kumari Palanisamy, Parasakthi Navaratnam, Shamala Devi Sekaran

Journal of Clinical and Health Sciences, 2016;1:22-28.

Introduction: Streptococcus pneumoniae is an important bacterial pathogen, causing respiratory infection. Penicillin resistance in S. pneumoniae is associated with alterations in the penicillin binding proteins, while resistance to macrolides is conferred either by the modification of the ribosomal target site or efflux mechanism. This study aimed to characterize S. pneumoniae and its antibiotic resistance genes using 2 sets of multiplex PCRs. Methods: A quintuplex and triplex PCR was used to characterize the pbp1A, ermB, gyrA, ply, and the mefE genes. Fifty-eight penicillin sensitive strains (PSSP), 36 penicillin intermediate strains (PISP) and 26 penicillin resistance strains (PRSP) were used. Results: Alteration in pbp1A was only observed in PISP and PRSP strains, while PCR amplification of the ermB or mefE was observed only in strains with reduced susceptibility to erythromycin. The assay was found to be sensitive as simulated blood cultures showed the lowest level of detection to be 10cfu. Conclusions: As predicted, the assay was able to differentiate penicillin susceptible from the non-susceptible strains based on the detection of the pbp1A gene, which correlated with the MIC value of the strains.

Matched MeSH terms: Macrolides
Fulltext Quintuplex PCR to detect antibiotic resistance genes in Streptococcus pneumoniae

Navindra Kumari Palanisamy, Parasakthi Navaratnam, Shamala Devi Sekaran

Journal of Clinical and Health Sciences, 2016;1(2):22-28.
MyJurnal

Introduction: Streptococcus pneumoniae is an important bacterial pathogen, causing respiratory infection. Penicillin resistance in S. pneumoniae is associated with alterations in the penicillin binding proteins, while resistance to macrolides is conferred either by the modification of the ribosomal target site or efflux mechanism. This study aimed to characterize S. pneumoniae and its antibiotic resistance genes using 2 sets of multiplex PCRs. Methods: A quintuplex and triplex PCR was used to characterize the pbp1A, ermB, gyrA, ply, and the mefE genes. Fifty-eight penicillin sensitive strains (PSSP), 36 penicillin intermediate strains (PISP) and 26 penicillin resistance strains (PRSP) were used. Results: Alteration in pbp1A was only observed in PISP and PRSP strains, while PCR amplification of the ermB or mefE was observed only in strains with reduced susceptibility to erythromycin. The assay was found to be sensitive as simulated blood cultures showed the lowest level of detection to be 10cfu. Conclusions: As predicted, the assay was able to differentiate penicillin susceptible from the non-susceptible strains based on the detection of the pbp1A gene, which correlated with the MIC value of the strains.

Matched MeSH terms: Macrolides
Heterogeneity of mycolactones produced by clinical isolates of Mycobacterium ulcerans: implications for virulence

Mve-Obiang A, Lee RE, Portaels F, Small PL

Infect Immun, 2003 Feb;71(2):774-83.
PMID: 12540557

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a severe necrotizing skin disease endemic in tropical countries. Clinical evidence suggests that M. ulcerans isolates from Asia, Mexico, and Australia may be less virulent than isolates from Africa. In vivo studies suggest that mycolactone, a polyketide-derived macrolide toxin, plays a major role in the tissue destruction and immune suppression which occur in cases of Buruli ulcer. Mycolactones were extracted from 34 isolates of M. ulcerans representing strains from Africa, Malaysia, Asia, Australia, and Mexico. Thin-layer chromatography, mass spectroscopic analysis, and cytopathic assays of partially purified mycolactones from these isolates revealed that M. ulcerans produces a heterogeneous mixture of mycolactone variants. Mycolactone A/B, the most biologically active mycolactone species, was identified by mass spectroscopy as [M(+)Na](+) at m/z 765.5 in all cytotoxic isolates except for those from Mexico. Mycolactone C [M+Na](+) at m/z 726.3 was the dominant mycolactone species in eight Australian isolates, and mycolactone D [M+Na](+) m/z 781.2 was characteristic of two Asian strains. Mycolactone species are conserved within specific geographic areas, suggesting that there may be a correlation between mycolactone profile and virulence. In addition, the core lactone, [M+Na](+) m/z 447.4, was identified as a minor species, supporting the hypothesis that mycolactones are synthesized by two polyketide synthases. A cytopathic assay of the core lactone showed that this molecule is sufficient for cytotoxicity, although it is much less potent than the complete mycolactone.

Matched MeSH terms: Macrolides
Impact of mycolactone produced by Mycobacterium ulcerans on life-history traits of Aedes aegypti (L.) and resulting habitat selection for oviposition

Mashlawi AM, Jordan HR, Crippen LT, Tomberlin JK

Trop Biomed, 2020 Dec 01;37(4):973-985.
PMID: 33612750 DOI: 10.47665/tb.37.4.973

Buruli ulcer (BU) is a globally recognized, yet largely neglected tropical disease whose etiologic agent is Mycobacterium ulcerans. Although the exact mode of transmission is unclear, epidemiological evidence links BU incidence with slow-moving or stagnant, aquatic habitats, and laboratory-based experiments have shown disease manifestation in animals with dermal punctures. Therefore, hypotheses for transmission include contact with slowmoving aquatic habitats and associated biting aquatic insects, such as mosquitoes. Recent research demonstrated the toxin produced by M. ulcerans, mycolactone, is an attractant for adult mosquitoes seeking a blood-meal as well as oviposition sites. In the study presented here, we examined the impact of mycolactone at different concentrations on immature lifehistory traits of Aedes aegypti, which commonly occurs in the same environment as M. ulcerans. We determined percent egg hatch was not significantly different across treatments. However, concentration impacted the survivorship of larval mosquitoes to the adult stage (p < 0.001). Resulting adults also showed a slight preference, but not significant (p > 0.05), for oviposition in habitats contaminated with mycolactone suggesting a legacy effect.

Matched MeSH terms: Macrolides/metabolism*
Fulltext Community-acquired pneumonia in Malaysian patients: addition of macrolide and the use of BTS "curb" index to assess severity

Loh LC

Med J Malaysia, 2006 Mar;61(1):128-30.
PMID: 16708753

Sir, I read with interest the elegantly written CME article by Liam C K recently!. The choice of empiric antibiotic(s) in treating hospitalized adult patients with communityacquired pneumonia (CAP) is important as it can influence clinical outcomes 2. As correctly pointed out by the author, patients with CAP requiring hospitalization should, in addition to a ~-lactam stable antibiotic, be covered with a macrolide, to combat atypical pathogens such as Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydia pneumoniae. Such is the recommendation from most foreign guidelines 3. 4. Here I wish to add our own observation based on a prospective study conducted between 2002 and 2004 of 141 adult patients with CAP hospitalized in Seremban Hospital in which we studied the clinical outcomes of patients treated empirically with and without a macrolide added to their ~-lactam stable antibiotic, recently published in Respirology 5.

Matched MeSH terms: Macrolides/therapeutic use*
Addition of macrolide in treating adult hospitalized community-acquired pneumonia

Loh LC, Quah SY, Khoo SK, Vijayasingham P, Thayaparan T

Respirology, 2005 Jun;10(3):371-7.
PMID: 15955152

Current clinical practice guidelines, including those in south Asia, recommend the addition of a macrolide to a broad-spectrum antibiotic for the treatment of severe hospitalized community-acquired pneumonia (CAP). The aim of this study was to observe the influence of macrolide addition on clinical outcomes of hospitalized adult patients with CAP.

Matched MeSH terms: Macrolides/therapeutic use*
Fulltext Comparative genomics analyses revealed two virulent Listeria monocytogenes strains isolated from ready-to-eat food

Lim SY, Yap KP, Thong KL

Gut Pathog, 2016;8:65.
PMID: 27999619 DOI: 10.1186/s13099-016-0147-8

BACKGROUND: Listeria monocytogenes is an important foodborne pathogen that causes considerable morbidity in humans with high mortality rates. In this study, we have sequenced the genomes and performed comparative genomics analyses on two strains, LM115 and LM41, isolated from ready-to-eat food in Malaysia.
RESULTS: The genome size of LM115 and LM41 was 2,959,041 and 2,963,111 bp, respectively. These two strains shared approximately 90% homologous genes. Comparative genomics and phylogenomic analyses revealed that LM115 and LM41 were more closely related to the reference strains F2365 and EGD-e, respectively. Our virulence profiling indicated a total of 31 virulence genes shared by both analysed strains. These shared genes included those that encode for internalins and L. monocytogenes pathogenicity island 1 (LIPI-1). Both the Malaysian L. monocytogenes strains also harboured several genes associated with stress tolerance to counter the adverse conditions. Seven antibiotic and efflux pump related genes which may confer resistance against lincomycin, erythromycin, fosfomycin, quinolone, tetracycline, and penicillin, and macrolides were identified in the genomes of both strains.
CONCLUSIONS: Whole genome sequencing and comparative genomics analyses revealed two virulent L. monocytogenes strains isolated from ready-to-eat foods in Malaysia. The identification of strains with pathogenic, persistent, and antibiotic resistant potentials from minimally processed food warrant close attention from both healthcare and food industry.

Matched MeSH terms: Macrolides
Fulltext Comparative Genomics of Two ST 195 Carbapenem-Resistant Acinetobacter baumannii with Different Susceptibility to Polymyxin Revealed Underlying Resistance Mechanism

Lean SS, Yeo CC, Suhaili Z, Thong KL

Front Microbiol, 2015;6:1445.
PMID: 26779129 DOI: 10.3389/fmicb.2015.01445

Acinetobacter baumannii is a Gram-negative nosocomial pathogen of importance due to its uncanny ability to acquire resistance to most antimicrobials. These include carbapenems, which are the drugs of choice for treating A. baumannii infections, and polymyxins, the drugs of last resort. Whole genome sequencing was performed on two clinical carbapenem-resistant A. baumannii AC29 and AC30 strains which had an indistinguishable ApaI pulsotype but different susceptibilities to polymyxin. Both genomes consisted of an approximately 3.8 Mbp circular chromosome each and several plasmids. AC29 (susceptible to polymyxin) and AC30 (resistant to polymyxin) belonged to the ST195 lineage and are phylogenetically clustered under the International Clone II (IC-II) group. An AbaR4-type resistance island (RI) interrupted the comM gene in the chromosomes of both strains and contained the bla OXA-23 carbapenemase gene and determinants for tetracycline and streptomycin resistance. AC29 harbored another copy of bla OXA-23 in a large (~74 kb) conjugative plasmid, pAC29b, but this gene was absent in a similar plasmid (pAC30c) found in AC30. A 7 kb Tn1548::armA RI which encodes determinants for aminoglycoside and macrolide resistance, is chromosomally-located in AC29 but found in a 16 kb plasmid in AC30, pAC30b. Analysis of known determinants for polymyxin resistance in AC30 showed mutations in the pmrA gene encoding the response regulator of the two-component pmrAB signal transduction system as well as in the lpxD, lpxC, and lpsB genes that encode enzymes involved in the biosynthesis of lipopolysaccharide (LPS). Experimental evidence indicated that impairment of LPS along with overexpression of pmrAB may have contributed to the development of polymyxin resistance in AC30. Cloning of a novel variant of the bla AmpC gene from AC29 and AC30, and its subsequent expression in E. coli also indicated its likely function as an extended-spectrum cephalosporinase.

Matched MeSH terms: Macrolides
Fulltext Macrolides for patients with COVID-19 and concurrent pertussis infection

Kow CS, Hasan SS

Diagn Microbiol Infect Dis, 2021 Feb;99(2):115245.
PMID: 33130501 DOI: 10.1016/j.diagmicrobio.2020.115245
Matched MeSH terms: Macrolides/adverse effects; Macrolides/therapeutic use*
Changes in serotype distribution and antimicrobial resistance of Streptococcus pneumoniae isolates from adult patients in Asia: Emergence of drug-resistant non-vaccine serotypes

Kim SH, Chung DR, Song JH, Baek JY, Thamlikitkul V, Wang H, et al.

Vaccine, 2020 08 27;38(38):6065-6073.
PMID: 31590932 DOI: 10.1016/j.vaccine.2019.09.065

This study was performed to investigate the serotype distribution and antimicrobial susceptibility of Streptococcus pneumoniae in Asian countries. A prospective surveillance study on S. pneumoniae collected from adult patients (≥50 years old) with invasive pneumococcal disease or community-acquired pneumonia was performed at 66 hospitals in Asian countries (Korea, China, Malaysia, Singapore, the Philippines, and Thailand) in 2012-2017. Serotyping and antimicrobial susceptibility tests of 850 pneumococcal isolates were performed. The proportions of isolates with serotypes covered by 13-valent pneumococcal conjugate vaccine (PCV13) were 37.0% in Korea, 53.4% in China, 77.2% in Malaysia, 35.9% in the Philippines, 68.7% in Singapore, and 60.2% in Thailand. Major serotypes were 19F (10.4%), 19A (10.1%), and 3 (8.5%) in 2012-2017, with different serotype distributions in each country. Macrolide resistance in pneumococci was high (66.8%) and prevalence of multidrug resistance (MDR) also remained high (50.8%). MDR non-PCV13 serotypes such as 11A, 15A, 35B, and 23A have emerged in Asian countries. This study showed the persistent prevalence of 19F and 19A with a noteworthy increase of certain non-PCV13 serotypes in Asian countries. High prevalence of macrolide resistance and MDR was also found in pneumococcal isolates. These data emphasize the need for continued surveillance of pneumococcal epidemiology in Asia in the post-pneumococcal vaccine era.

Matched MeSH terms: Macrolides
Antibacterial polyene-polyol macrolides and cyclic peptides from the marine-derived Streptomyces sp. MS110128

Jiang L, Huang P, Ren B, Song Z, Zhu G, He W, et al.

Appl Microbiol Biotechnol, 2021 Jun;105(12):4975-4986.
PMID: 34146138 DOI: 10.1007/s00253-021-11226-w

Marine microbes provide an important resource to discover new chemical compounds with biological activities beneficial to drug discovery. In our study, two new polyene macrolides, pyranpolyenolides A (1) and B (2), and one new natural cyclic peptide (9), together with two known polyenes (7 and 8) and three known cyclic peptides (10-12), were isolated from a culture of the marine Streptomyces sp. MS110128. In addition, four new polyene macrolides, pyranpolyenolides C-F (3-6), were identified as olefin geometric isomers that were most likely produced by photochemical conversion during the cultivation or isolation procedures. The pyranpolyenolides are 32-membered macrolides endowed with a conjugated tetraene and several pairs of 1,3-dihydroxyl groups. Pyranpolyenolides that contain a hydropyran group have not been previously reported. Four cyclic peptides (9-12) showed significant activities against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant S. aureus with supporting MIC values ranging from 0.025 to 1.25 μg/mL. These cyclic peptides containing piperazic moieties showed moderate activities with MIC values of 12.5 μg/mL against Bacille Calmette Guerin (BCG), an attenuated form of the bovine. Additionally, cyclic peptide 12 showed moderate antifungal activity against Candida albicans with an MIC value of 12.5 μg/mL. KEY POINTS: • Discovery of new polyenes and cyclic peptides from a marine-derived Actinomycete. • Cyclic peptides containing piperazic moieties exhibited good antibacterial activity.

Matched MeSH terms: Macrolides

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