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  1. 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*
  2. Jeevajothi Nathan J, Mohd Taib N, Mohd Desa MN, Masri SN, Md Yasin R, Jamal F, et al.
    Med J Malaysia, 2013 Apr;68(2):119-24.
    PMID: 23629556 MyJurnal
    The in vitro activities of 6 antimicrobial agents against clinical isolates of Streptococcus pneumoniae (pneumococci) were investigated and the erythromycin minimum inhibitory concentrations (MICs) were correlated with the two major macrolide resistance determinants, mef(A) and erm(B). MICs of commonly used antibiotics as well as the presence of macrolide resistance determinant genes in all isolates were tested. Seventy one pneumococcal isolates collected at Institute for Medical Research (IMR) were included in this study. Phenotypic characterization, MIC determination using E-test strips and polymerase chain reactions for antibiotic resistance determination were included. Among the isolates, 25 (35.2%) isolates were erythromycin susceptible, 3 (4.2%) were intermediate and 42 (60.6%) were resistant. Fifty three isolates (74.7%) were found with mef(A) alone, 15 (21.1%) isolates with erm(B) + mef(A) combination and 3 (4.2%) isolates with none of the two genes. The in vitro activity of penicillin, amoxicillin clavulanic acid, ceftriaxone and cefotaxime is superior to trimethoprim-sulfamethoxazole and erythromycin. In conclusion, pneumococcal isolates in this study were highly susceptible to penicillin with very low MICs. However, a very high prevalence rate of erythromycin resistance was observed. Erythromycin resistant S. pneumoniae isolates with both mef(A) and erm(B) showed very high MICs ≥256 μg/mL.
    Matched MeSH terms: Macrolides*
  3. 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*
  4. 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*
  5. Ahmad I, Abdullah N, Koji I, Yuzir A, Ahmad MD, Rachmadona N, et al.
    Chemosphere, 2023 Jun;325:138236.
    PMID: 36868419 DOI: 10.1016/j.chemosphere.2023.138236
    The number of restaurants is increasing day by day in almost all the developing countries, causing the increase in the generation of restaurant wastewater. Various activities (i.e., cleaning, washing, and cooking) going on in the restaurant kitchen lead to restaurant wastewater (RWW). RWW has high concentrations of chemical oxygen demand (COD), biochemical oxygen demand (BOD), nutrients such as potassium, phosphorus, and nitrogen, and solids. RWW also contains fats, oil, and grease (FOG) in alarmingly high concentration, which after congealing can constrict the sewer lines, leading to blockages, backups, and sanitatry sewer overflows (SSOs). The paper provides an insight to the details of RWW containing FOG collected from a gravity grease interceptor at a specific site in Malaysia, and its expected consequences and the sustainable management plan as prevention, control, and mitigation (PCM) approach. The results showed that the concentrations of pollutants are very high as compared to the discharge standards given by Department of Environment, Malaysia. Maximum values for COD, BOD and FOG in the restaurant wastewater samples were found to be 9948, 3170, and 1640 mg/l, respectively. FAME and FESEM analysis are done on the RWW containing FOG. In the FOG, palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c) are the dominant lipid acids with a maximum of 41, 8.4, 43.2, and 11.5%, respectively. FESEM analysis showed formation of whitish layers fprmed due to the deposition of calcium salts. Furthermore, a novel design of indoor hydromechanical grease interceptor (HGI) was proposed in the study based on the Malaysian conditions of restaurant. The HGI was designed for a maximum flow rate of 132 L per minute and a maximum FOG capacity of 60 kg.
    Matched MeSH terms: Macrolides/analysis
  6. 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*
  7. 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
  8. 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*
  9. 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*
  10. Huang XQ, Deng L, Lu G, He CH, Wu PQ, Xie ZW, et al.
    Open Med (Wars), 2015;10(1):479-482.
    PMID: 28352740 DOI: 10.1515/med-2015-0082
    To observe a therapeutic effect of macrolide antibiotics in children with Pseudomonas aeruginosa pneumonia. Fifty-four cases of children with Pseudomonas aeruginosa pneumonia were randomly divided into an observation group (n=30) and a control group (n=24). The observation group was treated with macrolide antibiotics and cefoperazone/sulbactam. The control group was treated with cefoperazone/sulbactam during a course of 10-14 days. The total effective rate was 93.3% in the observation group, and 58.3% in the control group, and results in the observation group were superior to the control group notably (P>0.05). There were no significant differences in bacterial clearance rate, adverse reaction rate between two groups (P>0.05). The combined application of cefoperazone/sulbactam with macrolide antibiotics to treat Pseudomonas aeruginosa pneumonia in children would be a more effective clinical method.
    Matched MeSH terms: Macrolides
  11. 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
  12. 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
  13. Navindra Kumari Palanisamy, Parasakthi Navaratnam, Shamala Devi Sekaran
    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
  14. 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
  15. Navindra Kumari Palanisamy, Parasakthi Navaratnam, Shamala Devi Sekaran
    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
  16. 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*
  17. El Sayed I, Liu Q, Wee I, Hine P
    Cochrane Database Syst Rev, 2018 09 24;9:CD002150.
    PMID: 30246875 DOI: 10.1002/14651858.CD002150.pub2
    BACKGROUND: Scrub typhus, an important cause of acute fever in Asia, is caused by Orientia tsutsugamushi, an obligate intracellular bacterium. Antibiotics currently used to treat scrub typhus include tetracyclines, chloramphenicol, macrolides, and rifampicin.

    OBJECTIVES: To assess and compare the effects of different antibiotic regimens for treatment of scrub typhus.

    SEARCH METHODS: We searched the following databases up to 8 January 2018: the Cochrane Infectious Diseases Group specialized trials register; CENTRAL, in the Cochrane Library (2018, Issue 1); MEDLINE; Embase; LILACS; and the metaRegister of Controlled Trials (mRCT). We checked references and contacted study authors for additional data. We applied no language or date restrictions.

    SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs comparing antibiotic regimens in people with the diagnosis of scrub typhus based on clinical symptoms and compatible laboratory tests (excluding the Weil-Felix test).

    DATA COLLECTION AND ANALYSIS: For this update, two review authors re-extracted all data and assessed the certainty of evidence. We meta-analysed data to calculate risk ratios (RRs) for dichotomous outcomes when appropriate, and elsewhere tabulated data to facilitate narrative analysis.

    MAIN RESULTS: We included six RCTs and one quasi-RCT with 548 participants; they took place in the Asia-Pacific region: Korea (three trials), Malaysia (one trial), and Thailand (three trials). Only one trial included children younger than 15 years (N = 57). We judged five trials to be at high risk of performance and detection bias owing to inadequate blinding. Trials were heterogenous in terms of dosing of interventions and outcome measures. Across trials, treatment failure rates were low.Two trials compared doxycycline to tetracycline. For treatment failure, the difference between doxycycline and tetracycline is uncertain (very low-certainty evidence). Doxycycline compared to tetracycline may make little or no difference in resolution of fever within 48 hours (risk ratio (RR) 1.14, 95% confidence interval (CI) 0.90 to 1.44, 55 participants; one trial; low-certainty evidence) and in time to defervescence (116 participants; one trial; low-certainty evidence). We were unable to extract data for other outcomes.Three trials compared doxycycline versus macrolides. For most outcomes, including treatment failure, resolution of fever within 48 hours, time to defervescence, and serious adverse events, we are uncertain whether study results show a difference between doxycycline and macrolides (very low-certainty evidence). Macrolides compared to doxycycline may make little or no difference in the proportion of patients with resolution of fever within five days (RR 1.05, 95% CI 0.99 to 1.10; 185 participants; two trials; low-certainty evidence). Another trial compared azithromycin versus doxycycline or chloramphenicol in children, but we were not able to disaggregate date for the doxycycline/chloramphenicol group.One trial compared doxycycline versus rifampicin. For all outcomes, we are uncertain whether study results show a difference between doxycycline and rifampicin (very low-certainty evidence). Of note, this trial deviated from the protocol after three out of eight patients who had received doxycycline and rifampicin combination therapy experienced treatment failure.Across trials, mild gastrointestinal side effects appeared to be more common with doxycycline than with comparator drugs.

    AUTHORS' CONCLUSIONS: Tetracycline, doxycycline, azithromycin, and rifampicin are effective treatment options for scrub typhus and have resulted in few treatment failures. Chloramphenicol also remains a treatment option, but we could not include this among direct comparisons in this review.Most available evidence is of low or very low certainty. For specific outcomes, some low-certainty evidence suggests there may be little or no difference between tetracycline, doxycycline, and azithromycin as treatment options. Given very low-certainty evidence for rifampicin and the risk of inducing resistance in undiagnosed tuberculosis, clinicians should not regard this as a first-line treatment option. Clinicians could consider rifampicin as a second-line treatment option after exclusion of active tuberculosis.Further research should consist of additional adequately powered trials of doxycycline versus azithromycin or other macrolides, trials of other candidate antibiotics including rifampicin, and trials of treatments for severe scrub typhus. Researchers should standardize diagnostic techniques and reporting of clinical outcomes to allow robust comparisons.

    Matched MeSH terms: Macrolides/therapeutic use
  18. D'Aeth JC, van der Linden MP, McGee L, de Lencastre H, Turner P, Song JH, et al.
    Elife, 2021 Jul 14;10.
    PMID: 34259624 DOI: 10.7554/eLife.67113
    Multidrug-resistant Streptococcus pneumoniae emerge through the modification of core genome loci by interspecies homologous recombinations, and acquisition of gene cassettes. Both occurred in the otherwise contrasting histories of the antibiotic-resistant S. pneumoniae lineages PMEN3 and PMEN9. A single PMEN3 clade spread globally, evading vaccine-induced immunity through frequent serotype switching, whereas locally circulating PMEN9 clades independently gained resistance. Both lineages repeatedly integrated Tn916-type and Tn1207.1-type elements, conferring tetracycline and macrolide resistance, respectively, through homologous recombination importing sequences originating in other species. A species-wide dataset found over 100 instances of such interspecific acquisitions of resistance cassettes and flanking homologous arms. Phylodynamic analysis of the most commonly sampled Tn1207.1-type insertion in PMEN9, originating from a commensal and disrupting a competence gene, suggested its expansion across Germany was driven by a high ratio of macrolide-to-β-lactam consumption. Hence, selection from antibiotic consumption was sufficient for these atypically large recombinations to overcome species boundaries across the pneumococcal chromosome.
    Matched MeSH terms: Macrolides/pharmacology
  19. Hart T, Tang WY, Mansoor SAB, Chio MTW, Barkham T
    BMC Infect Dis, 2020 Apr 28;20(1):314.
    PMID: 32345231 DOI: 10.1186/s12879-020-05019-1
    BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted infection, with increasing rates of resistance to fluroquinolones and macrolides, the recommended treatments. Despite this, M. genitalium is not part of routine screening for Sexually Transmitted Infections (STIs) in many countries and the prevalence of infection and patterns of disease remain to be determined in many populations. Such data is of particular importance in light of the reported rise in antibiotic resistance in M. genitalium isolates.

    METHODS: Urine and urethral swab samples were collected from the primary public sexual health clinic in Singapore and tested for C. trachomatis (CT) or N. gonorrhoeae (NG) infection and for the presence of M. genitalium. Antibiotic resistance in M. genitalium strains detected was determined by screening for genomic mutations associated with macrolide and fluroquinolone resistance.

    RESULTS: We report the results of a study into M. genitalium prevalence at the national sexual health clinic in Singapore. M. genitalium was heavily associated with CT infection (8.1% of cases), but present in only of 2.4% in CT negative cases and not independently linked to NG infection. Furthermore, we found high rates of resistance mutations to both macrolides (25%) and fluoroquinolones (37.5%) with a majority of resistant strains being dual-resistant. Resistance mutations were only found in strains from patients with CT co-infection.

    CONCLUSIONS: Our results support targeted screening of CT positive patients for M. genitalium as a cost-effective strategy to reduce the incidence of M. genitalium in the absence of comprehensive routine screening. The high rate of dual resistance also highlights the need to ensure the availability of alternative antibiotics for the treatment of multi-drug resistant M. genitalium isolates.

    Matched MeSH terms: Macrolides/pharmacology; Macrolides/therapeutic use
  20. 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*
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