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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
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
Anthelmintic resistance in sheep and goat farms on Peninsular Malaysia

Chandrawathani P, Adnan M, Waller PJ

Vet Parasitol, 1999 May;82(4):305-10.
PMID: 10384906

The faecal egg count reduction test (FECRT) was conducted on 39 sheep farms and 9 goat farms located in Peninsular Malaysia. The anthelmintic groups used in these tests were the benzimidazoles, levamisole, the benzimidazole/levamisole combination, macrocyclic lactones and closantel. Results indicated that the prevalence of resistance to the benzimidazole group was high, with approximately 50% of the sheep farms and 75% of the goat farms having resistant nematode parasite populations present. Resistance to levamisole, closantel and ivermectin was also detected. Differentiation of the infective larvae derived from faecal cultures indicated that by far the most predominant parasite species was Haemonchus contortus.

Matched MeSH terms: Macrolides
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*
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 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 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
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 Biosafety of Campylobacter jejuni from raw vegetables consumed as ulam with reference to their resistance to antibiotics

Chai, L.C., Fatimah, A.B., Ghazali, F.M., Lee, H.Y., Tunung, R., Shamsinar, A.T., et al.

International Food Research Journal, 2008;15(2):125-134.
MyJurnal

Antibiotic resistance in campylobacter is an emerging global public health problem after MRSA and VRE. Fluoroquinolone and macrolide resistance have been found to be more common in this world leading foodborne pathogen. A total of fifty-six isolates of Campylobacter jejuni obtained from raw vegetables
which are consumed as ulam (salad) in Malaysia, were tested with 12 antibiotics used clinically and
agriculturally. The resistance was determined using the disk diffusion method. Results were determined
by hierarchic numerical methods to cluster strains and antibiotics according to similarity profiles. Fifty
five C. jejuni isolates from different isolation sites were all clustered together into ten groups. This indicates that the commodities (raw salad vegetables/ulam) where the isolates originated might share a similar source of cross-contamination along the production route. All antibiotics tested correlated and there were four groupings reflecting their mode of actions. Generally, C. jejuni isolates were found to be highly resistant to erythromycin (91.1%) and tetracycline (85.7%). Both agents are popular antibiotics used clinically to treat bacterial infections. On the other hand, the C. jejuni isolates showed high percentage (80.4%) of resistance towards enrofloxacin, an extensively used antimicrobial agent in agriculture practices. This study showed that C. jejuni isolates were highly multi-resistance to as many as 10 antibiotics. Therefore, in terms of biosafety, the presence of antibiotic resistance strains in the food chain has raised concerns that the treatment of human infections will be compromised.

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
Fulltext Antibiotic prescribing in public and private practice: a cross-sectional study in primary care clinics in Malaysia

Ab Rahman N, Teng CL, Sivasampu S

BMC Infect Dis, 2016 05 17;16:208.
PMID: 27188538 DOI: 10.1186/s12879-016-1530-2

BACKGROUND: Antibiotic overuse is driving the emergence of antibiotic resistance worldwide. Good data on prescribing behaviours of healthcare providers are needed to support antimicrobial stewardship initiatives. This study examined the differences in antibiotic prescribing rates of public and private primary care clinics in Malaysia.

METHODS: We used data from the National Medical Care Survey (NMCS), a nationwide cluster sample of Malaysian public and private primary care clinics in 2014. NMCS contained demographic, diagnoses and prescribing from 129 public clinics and 416 private clinics. We identified all encounters who were prescribed antibiotic and analyse the prescribing rate, types of antibiotics, and diagnoses that resulted in antibiotic.

RESULTS: Five thousand eight hundred ten encounters were prescribed antibiotics; antibiotic prescribing rate was 21.1 % (public clinics 6.8 %, private clinics 30.8 %). Antibiotic prescribing was higher in private clinics where they contributed almost 87 % of antibiotics prescribed in primary care. Upper respiratory tract infection (URTI) was the most frequent diagnosis in patients receiving antibiotic therapy and accounted for 49.2 % of prescriptions. Of the patients diagnosed with URTI, 46.2 % received antibiotic treatment (public 16.8 %, private 57.7 %). Penicillins, cephalosporins and macrolides were the most commonly prescribed antibiotics and accounted for 30.7, 23.6 and 16.0 % of all antibiotics, respectively. More recently available broad-spectrum antibiotics such as azithromycin and quinolones were more frequently prescribed in private clinics.

CONCLUSIONS: Antibiotic prescribing rates are high in both public and private primary care settings in Malaysia, especially in the latter. This study provides evidence of excessive and inappropriate antibiotic prescribing for self-limiting conditions. These data highlights the needs for more concerted interventions targeting both prescribers and public. Improvement strategies should focus on reducing inappropriate prescribing.

Matched MeSH terms: Macrolides/therapeutic use
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
Langkolide, a 32-membered macrolactone antibiotic produced by Streptomyces sp. Acta 3062

Helaly SE, Kulik A, Zinecker H, Ramachandaran K, Tan GY, Imhoff JF, et al.

J Nat Prod, 2012 Jun 22;75(6):1018-24.
PMID: 22642587 DOI: 10.1021/np200580g

A new 32-membered macrolactone antibiotic, named langkolide, was isolated from the mycelium of Streptomyces sp. Acta 3062. The langkolide structure was determined by HR-MS and 1D and 2D NMR as a 32-membered macrolactone connected from an overhanging polyketide tail to a naphthoquinone unit mediated by two carbohydrate moieties. The producing strain was isolated from a rhizosphere soil of Clitorea sp. collected at Burau Bay, Langkawi, Malaysia, and was characterized by its morphological and chemotaxonomic features in addition to its 16S rRNA gene sequence. It was identified as a member of the Streptomyces galbus clade. Langkolide exhibited various bioactivities including antimicrobial and antiproliferative activities. Furthermore, langkolide inhibited human recombinant phosphodiesterase 4 with an IC(50) value of 0.48 μM.

Matched MeSH terms: Macrolides/isolation & purification*; Macrolides/pharmacology*; Macrolides/chemistry
Fulltext Macrolactin A as a Novel Inhibitory Agent for SARS-CoV-2 Mpro: Bioinformatics Approach

Bharadwaj KK, Sarkar T, Ghosh A, Baishya D, Rabha B, Panda MK, et al.

Appl Biochem Biotechnol, 2021 Oct;193(10):3371-3394.
PMID: 34212286 DOI: 10.1007/s12010-021-03608-7

COVID-19 is a disease that puts most of the world on lockdown and the search for therapeutic drugs is still ongoing. Therefore, this study used in silico screening to identify natural bioactive compounds from fruits, herbaceous plants, and marine invertebrates that are able to inhibit protease activity in SARS-CoV-2 (PDB: 6LU7). We have used extensive screening strategies such as drug likeliness, antiviral activity value prediction, molecular docking, ADME, molecular dynamics (MD) simulation, and MM/GBSA. A total of 17 compounds were shortlisted using Lipinski's rule in which 5 compounds showed significant predicted antiviral activity values. Among these 5, only 2 compounds, Macrolactin A and Stachyflin, showed good binding energy of -9.22 and -8.00 kcal/mol, respectively, within the binding pocket of the Mpro catalytic residues (HIS 41 and CYS 145). These two compounds were further analyzed to determine their ADME properties. The ADME evaluation of these 2 compounds suggested that they could be effective in developing therapeutic drugs to be used in clinical trials. MD simulations showed that protein-ligand complexes of Macrolactin A and Stachyflin with the target receptor (6LU7) were stable for 100 nanoseconds. The MM/GBSA calculations of Mpro-Macrolactin A complex indicated higher binding free energy (-42.58 ± 6.35 kcal/mol). Dynamic cross-correlation matrix (DCCM) and principal component analysis (PCA) on the residual movement in the MD trajectories further confirmed the stability of Macrolactin A bound state with 6LU7. In conclusion, this study showed that marine natural compound Macrolactin A could be an effective therapeutic inhibitor against SARS-CoV-2 protease (6LU7). Additional in vitro and in vivo validations are strongly needed to determine the efficacy and therapeutic dose of Macrolactin A in biological systems.

Matched MeSH terms: Macrolides/chemistry*
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
Chrysomya bezziana (Diptera: Calliphoridae) infestation: case report of three dogs in Malaysia treated with spinosad/milbemycin

Han HS, Sharma R, Jeffery J, Noli C

Vet Dermatol, 2017 Apr;28(2):239-e62.
PMID: 27918123 DOI: 10.1111/vde.12403

BACKGROUND: Infestation of wounds with the larvae of Callophorid flies is relatively common in countries where these parasites are found. The most common species associated with infections in Southeast Asia is Chrysomya bezziana (Ch. bezziana), the Old World screw worm. Treatment consists of either subcutaneous injection of ivermectin or oral administration of nitenpyram combined with aggressive tissue debridement under general anaesthesia.
OBJECTIVES: To describe the treatment of cutaneous myiasis in three dogs caused by the larvae of Ch. bezziana in Malaysia and their treatment with spinosad plus milbemycin.
RESULTS: In all dogs, a single oral dose of spinosad plus milbemycin at the recommended dosage of 31-62 mg/kg and 0.5-1.0 mg/kg, respectively, was able to kill all larvae within 8 h. Most dead larvae fell off the host and those remaining on the host were dead and easily removed with simple saline flushing and gentle debridement. Neither general anaesthesia nor aggressive mechanical debridement were needed in any patient.
CONCLUSIONS AND CLINICAL IMPORTANCE: Oral spinosad plus milbemycin is a safe, licensed and effective treatment at the recommended dose for the rapid elimination of Ch. bezziana myiasis, with no need for sedation or anaesthesia.

Matched MeSH terms: Macrolides/administration & dosage; Macrolides/therapeutic use*
Inhibition of lysosomal vacuolar proton pump down-regulates cellular acidification and enhances E. coli bactofection efficiency

Akinsola RO, Lee CW, Sim EUH, Narayanan K

Anal Biochem, 2021 03 01;616:114088.
PMID: 33358938 DOI: 10.1016/j.ab.2020.114088

Endosomal escape is considered a crucial barrier that needs to be overcome by integrin-mediated E. coli for gene delivery into mammalian cells. Bafilomycin, a potent inhibitor of the H+ proton pump commonly employed to lower endosomal pH, was evaluated as part of the E. coli protocol during delivery. We found an increase in green fluorescent protein expression up 6.9, 3.2, 5.0, 2.8, and 4.5 fold in HeLa, HEK-293, A549, HT1080, and MCF-7 respectively, compared to untreated cells. Our result showed for the first time that Inhibition of lysosomal V-ATPase enhances E. coli efficiency.

Matched MeSH terms: Macrolides/pharmacology
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*

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