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Chemico-biological Interactions Sep 2022The sea is a vast ecosystem that has remained primarily unexploited and untapped, resulting in numerous organisms. Consequently, marine organisms have piqued the... (Review)
Review
The sea is a vast ecosystem that has remained primarily unexploited and untapped, resulting in numerous organisms. Consequently, marine organisms have piqued the interest of scientists as an abundant source of natural resources with unique structural features and fascinating biological activities. Marine macrolide is a top-class natural product with a heavily oxygenated polyene backbone containing macrocyclic lactone. In the last few decades, significant efforts have been made to isolate and characterize macrolides' chemical and biological properties. Numerous macrolides are extracted from different marine organisms such as marine microorganisms, sponges, zooplankton, molluscs, cnidarians, red algae, tunicates, and bryozoans. Notably, the prominent macrolide sources are fungi, dinoflagellates, and sponges. Marine macrolides have several bioactive characteristics such as antimicrobial (antibacterial, antifungal, antimalarial, antiviral), anti-inflammatory, antidiabetic, cytotoxic, and neuroprotective activities. In brief, marine organisms are plentiful in naturally occurring macrolides, which can become the source of efficient and effective therapeutics for many diseases. This current review summarizes these exciting and promising novel marine macrolides in biological activities and possible therapeutic applications.
Topics: Animals; Anti-Bacterial Agents; Aquatic Organisms; Biological Products; Cnidaria; Ecosystem; Macrolides; Porifera
PubMed: 35952775
DOI: 10.1016/j.cbi.2022.110072 -
Mediators of Inflammation 2012
Topics: Anti-Bacterial Agents; Bronchiectasis; Chronic Disease; Humans; Inflammation; Macrolides; Respiratory Tract Infections; Skin Diseases
PubMed: 23326017
DOI: 10.1155/2012/692352 -
Journal of Infection in Developing... Apr 2021The role of antibiotics in the treatment in COVID-19 cases has not yet been adequately defined, and no criteria have been established for antibiotic treatment, type and... (Observational Study)
Observational Study
INTRODUCTION
The role of antibiotics in the treatment in COVID-19 cases has not yet been adequately defined, and no criteria have been established for antibiotic treatment, type and duration.
METHODOLOGY
This paper reports the results of an observational study on the extent of antibiotic use in 52 randomly selected patients in the intensive care unit (ICU) at the University Hospital in Pristina, Kosovo with severe forms of COVID-19.
RESULTS
Antibiotics were prescribed in all the cases (52; 100%). Of the 52 patients, 1) 13 (25%) were given antibiotics before hospitalisation, 2) 49 (94.2%) during treatment in the ward and 3) 52 (100%) during treatment in the ICU. Most often, empirical antibiotics were administered in 32 cases (61.5%) to treat methicillin resistant Staphylococcus aureus (MRSA) infections, and in 23 patients (44.2%) to treat atypical pathogens. The most prescribed antibiotics were ceftriaxone/cefotaxime plus macrolide in (17 cases; 32.7%), ceftriaxone/cefotaxime in (15 cases; 28.8%), ampicillin/amoxicillin plus clavulanic acid or sulbactam (five cases; 9.6%), and quinolones (five cases; 9.6%). Imipenem was the most frequently used antibiotic in the ICU (30 cases; 57.7%), followed by ceftriaxone (28 cases; 53.8%), and piperacillin/tazobactam and fluoroquinolone (17 cases; 32.7%). In 18 cases (34.6%), three antibiotics were given simultaneously; two antibiotics in 29 cases (55.8%) and in five cases (9.6%) only one antibiotic was given. The mean duration of antibiotic treatment was 12.71 days (3-22 days; SD 4.026).
CONCLUSIONS
The study showed unrestricted use of broad-spectrum antibiotics in the treatment of severe cases with COVID-19.
Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; COVID-19; Comorbidity; Female; Humans; Intensive Care Units; Kosovo; Macrolides; Male; Middle Aged; Respiration, Artificial; Young Adult; COVID-19 Drug Treatment
PubMed: 33956649
DOI: 10.3855/jidc.14404 -
The Clinical Respiratory Journal Nov 2022Macrolide-resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and...
INTRODUCTION
Macrolide-resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and macrolide-sensitive M. pneumoniae (MSMP) and identified factors associated with prolonged hospital admission in children.
METHODS
A prospective multicenter study was conducted in 1063 children <18 years old in July 2018-June 2020. The 454 had a positive M. pneumoniae polymerase chain reaction assay.
RESULTS
Most subjects had MRMP (78.4%), and all mutated strains had the A2063G transition. We defined MRMP* (n = 285) as MRMP pneumonia requiring admission and MSMP* (n = 72) as MSMP pneumonia requiring admission. Patients with MRMP pneumonia were older, more likely to have segmental/lobar pneumonia, and had more febrile days than those with MSMP pneumonia. C-reactive protein (CRP), lactate dehydrogenase (LDH), and percentage neutrophils were more strongly associated with MRMP* than MSMP* groups. Percentage neutrophils, CRP, and alanine aminotransferase significantly changed between admission and follow-up measurements in patients with MRMP* (P < 0.05). The duration of admission positively correlated with the number of febrile days after initiation of antibiotic medication and laboratory variables (white blood cell count, CRP, and aspartate aminotransferase [AST]) (P < 0.05). Random forest analysis indicated that the number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission was over five.
CONCLUSIONS
This study indicated that children with M. pneumoniae pneumonia with a higher number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission were more likely to have prolonged admission duration.
Topics: Child; Humans; Adolescent; Mycoplasma pneumoniae; Prospective Studies; Drug Resistance, Bacterial; Pneumonia, Mycoplasma; Macrolides; Anti-Bacterial Agents; C-Reactive Protein
PubMed: 36205104
DOI: 10.1111/crj.13549 -
Treponema pallidum Macrolide Resistance and Molecular Epidemiology in Southern Africa, 2008 to 2018.Journal of Clinical Microbiology Sep 2021Treponema pallidum macrolide resistance and clinical treatment failure have emerged rapidly within communities where macrolides have been used as convenient, oral...
Treponema pallidum macrolide resistance and clinical treatment failure have emerged rapidly within communities where macrolides have been used as convenient, oral therapeutic alternatives to benzathine penicillin G for syphilis or for other clinical indications. Macrolides are not included in the South African syndromic management guidelines for genital ulcer disease; however, in 2015, a 1-g dose of azithromycin was incorporated into treatment algorithms for genital discharge. We determined the prevalence of 23S rRNA macrolide resistance-associated point mutations in 135 T. pallidum-positive surveillance specimens from Botswana, Zimbabwe, and South Africa between 2008 and 2018. Additionally, we investigated the association between macrolide resistance, T. pallidum strain type, and HIV coinfection. A significant increase in the prevalence of the A2058G macrolide resistance-associated point mutation was observed in specimens collected after 2015. There was a high level of molecular heterogeneity among T. pallidum strains circulating in the study communities, with strain type 14d/f being the most predominant in South Africa. Fourteen novel strain types, derived from three new gene restriction fragment length polymorphism patterns and seven new gene sequence types, were identified. There was an association between A2058G-associated macrolide resistance and T. pallidum strain types 14d/f and 14d/g but no association between T. pallidum macrolide resistance and HIV coinfection. The majority of T. pallidum strains, as well as strains containing the A2058G mutation, belonged to the SS14-like clade. This is the first study to extensively detail the molecular epidemiology and emergence of macrolide resistance in T. pallidum in southern Africa.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Macrolides; Molecular Epidemiology; Treponema pallidum
PubMed: 34346717
DOI: 10.1128/JCM.02385-20 -
The New Microbiologica Oct 2019Macrolides are widely used for the treatment of Ureaplasma spp. infection. The aim of this study was to investigate possible genetic resistance determinants in...
Macrolides are widely used for the treatment of Ureaplasma spp. infection. The aim of this study was to investigate possible genetic resistance determinants in Ureaplasma spp. isolates. A total of eleven macrolide- resistant Ureaplasma spp. isolates, recovered from urogenital specimens, were investigated for genetic mechanisms of macrolide resistance. The 23S rRNA operons, as well as L4 and L22 ribosomal protein genes, were amplified and sequenced. Our study identified that the mutation A2066G in the 23S rRNA and four mutations (G361T, A406G, C422T and G196A) in the L22 ribosomal protein, may be responsible for the resistance of Ureaplasma spp. to macrolides, in China.
Topics: Anti-Bacterial Agents; China; Drug Resistance, Bacterial; Genetic Variation; Macrolides; Microbial Sensitivity Tests; Mutation; RNA, Ribosomal, 23S; Ribosomal Proteins; Ureaplasma
PubMed: 31305936
DOI: No ID Found -
Clinical Microbiology and Infection :... Apr 2013The relative efficacy, safety and ecological implications of macrolides vs. quinolones in the treatment of community-acquired pneumonia (CAP) are debatable. We performed... (Comparative Study)
Comparative Study Meta-Analysis Review
The relative efficacy, safety and ecological implications of macrolides vs. quinolones in the treatment of community-acquired pneumonia (CAP) are debatable. We performed a systematic review and meta-analysis of randomized controlled trials comparing any macrolide vs. any quinolone for the treatment of CAP among adult inpatients or outpatients, as monotherapy or both in combination with a beta-lactam. We did not limit inclusion by pneumonia severity, publication status, language or date of publication. The primary outcomes assessed were 30-day all-cause mortality and treatment failure. Two authors independently extracted the data. Fixed effect meta-analysis of risk ratios (RRs) with 95% confidence intervals was performed. Sixteen trials (4989 patients) fulfilling inclusion criteria were identified, mostly assessing outpatients with mild to moderate CAP. All-cause mortality was not significantly different for macrolides vs. quinolones, RR 1.03 (0.63-1.68, seven trials), with a low event rate (2%). Treatment failure was significantly lower with quinolones, RR 0.78 (0.67-0.91, 16 trials). The definition of failure used in the primary studies was not clearly representative of patients' benefit. Microbiological failure was lower with quinolones, RR 0.63 (0.49-0.81, 13 trials). All adverse events, adverse events requiring discontinuation and any premature antibiotic discontinuation were significantly more frequent with macrolides, mainly on account of gastrointestinal adverse events. Resistance development was not assessed in the trials. Randomized controlled trials show an advantage of quinolones in the treatment of CAP with regard to clinical cure without need for antibiotic modification at end of treatment and gastrointestinal adverse events. The clinical significance of this advantage is unclear.
Topics: Adult; Anti-Bacterial Agents; Community-Acquired Infections; Drug-Related Side Effects and Adverse Reactions; Humans; Macrolides; Pneumonia, Bacterial; Quinolones; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Failure
PubMed: 22489673
DOI: 10.1111/j.1469-0691.2012.03838.x -
Journal of Global Antimicrobial... Jun 2022Macrolides have a long history of use in animals and humans. Dynamics of macrolide-antibiotic resistance genes (ARGs) in waterways from the origin to the sea has not...
OBJECTIVES
Macrolides have a long history of use in animals and humans. Dynamics of macrolide-antibiotic resistance genes (ARGs) in waterways from the origin to the sea has not been reported.
METHODS
Resistant bacterial rate was measured by culture method, and copy numbers of macrolide-ARGs, mef(A), erm(B), mph(B), mef(C)-mph(G), and mobile genetic elements (MGEs) traI and IntI1 were quantitated in environmental DNA. Community composition in each site was investigated by 16S rRNA gene metagenomic sequencing. In Yilan area, antibiotics were quantitated.
RESULTS
Surface water samples from pig farms to the sea in southern and northern areas in Taiwan were monitored. Macrolide-resistant bacteria accounted for 3%-28% of total colony-forming bacteria in aquaculture ponds and rivers, whereas in pig farm wastewater it was 26%-100%. Three common macrolide-ARGs mef(A), erm(B), and mph(B) and the relatively new mef(C)-mph(G) were frequently detected in pig farms, but not in aquaculture ponds and the sea. Rivers receiving pig wastewater showed ARG contamination similar to the pig farms. Among the MGEs, IntI1 was frequently distributed in all sites and was positively related to mef(A), erm(B), and mph(B) but not to mef(C)-mph(G).
CONCLUSION
Pig farms are the origin of macrolide-ARGs, although macrolide contamination is low. Since lincomycin was detected in pig farms in the northern area, the increase of macrolide-ARGs is a future concern due to cross-resistance to lincomycin. ARGs abundance in aquaculture ponds was low, though MGEs were detected. Relation of IntI1 to ARG suggests convergence of ARGs to specific MGEs might be time/history dependent.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Genes, Bacterial; Interspersed Repetitive Sequences; Lincomycin; Macrolides; RNA, Ribosomal, 16S; Swine; Taiwan; Wastewater
PubMed: 35533984
DOI: 10.1016/j.jgar.2022.04.024 -
Antimicrobial Agents and Chemotherapy Apr 2022While the use of long-term macrolide therapy to prevent exacerbations in chronic respiratory diseases is widespread, its impact on the oropharyngeal microbiota and... (Randomized Controlled Trial)
Randomized Controlled Trial
Assessment of Long-Term Macrolide Exposure on the Oropharyngeal Microbiome and Macrolide Resistance in Healthy Adults and Consequences for Onward Transmission of Resistance.
While the use of long-term macrolide therapy to prevent exacerbations in chronic respiratory diseases is widespread, its impact on the oropharyngeal microbiota and macrolide resistance, and the potential for onward transmission of resistance to close contacts are poorly understood. We determined the effects of long-term exposure to azithromycin or erythromycin on phenotypic and genotypic macrolide resistance within the oropharyngeal microbiome of healthy adults and their close contacts in a randomized, single-blinded, parallel-group trial of 4 weeks of twice-daily oral 400 mg erythromycin ethylsuccinate or twice-daily oral 125 mg azithromycin. Using oropharyngeal swabs collected from 20 index healthy adults and 20 paired close contacts, the oropharyngeal microbial composition and macrolide resistance in streptococci were assessed by 16S rRNA sequencing and antibiotic susceptibility testing of oropharyngeal cultures, respectively, at baseline and weeks 4 and 8 (washout). Targeted quantitative PCR of antibiotic resistance genes was performed to evaluate paired changes in resistance gene levels in index patients and close contacts and to relate the potential transmission of antibiotic resistance. Neither azithromycin nor erythromycin altered oropharyngeal microbiota characteristics significantly. Proportional macrolide resistance in oropharyngeal streptococci increased with both erythromycin and azithromycin, remaining above baseline levels for the azithromycin group at washout. Levels of resistance genes increased significantly with azithromycin[(B) and ] and erythromycin (), returning to baseline levels at washout only for the erythromycin group. We found no evidence of onward transmission of resistance to close contacts, as indicated by the lack of concomitant changes in resistance gene levels detected in close contacts. (This study has been registered with the Australian and New Zealand Clinical Trials Registry under identifier ACTRN12617000278336.).
Topics: Adult; Anti-Bacterial Agents; Australia; Azithromycin; Drug Resistance, Bacterial; Erythromycin; Humans; Macrolides; Microbiota; RNA, Ribosomal, 16S; Streptococcus
PubMed: 35293783
DOI: 10.1128/aac.02246-21 -
PLoS Biology Mar 2022Understanding how antibiotic use drives resistance is crucial for guiding effective strategies to limit the spread of resistance, but the use-resistance relationship...
Understanding how antibiotic use drives resistance is crucial for guiding effective strategies to limit the spread of resistance, but the use-resistance relationship across pathogens and antibiotics remains unclear. We applied sinusoidal models to evaluate the seasonal use-resistance relationship across 3 species (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) and 5 antibiotic classes (penicillins, macrolides, quinolones, tetracyclines, and nitrofurans) in Boston, Massachusetts. Outpatient use of all 5 classes and resistance in inpatient and outpatient isolates in 9 of 15 species-antibiotic combinations showed statistically significant amplitudes of seasonality (false discovery rate (FDR) < 0.05). While seasonal peaks in use varied by class, resistance in all 9 species-antibiotic combinations peaked in the winter and spring. The correlations between seasonal use and resistance thus varied widely, with resistance to all antibiotic classes being most positively correlated with use of the winter peaking classes (penicillins and macrolides). These findings challenge the simple model of antibiotic use independently selecting for resistance and suggest that stewardship strategies will not be equally effective across all species and antibiotics. Rather, seasonal selection for resistance across multiple antibiotic classes may be dominated by use of the most highly prescribed antibiotic classes, penicillins and macrolides.
Topics: Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Escherichia coli; Macrolides; Penicillins; Seasons
PubMed: 35263322
DOI: 10.1371/journal.pbio.3001579