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Drosophila suzukii lay eggs in soft-skinned, ripening fruits, making this insect a serious threat to berry production. Since its 2008 introduction into North America, growers have used insecticides, such as pyrethroids and spinosads, as the primary approach for D. suzukii management, resulting in development of insecticide resistance in this pest. This study sought to identify the molecular mechanisms conferring insecticide resistance in these populations. We sequenced the transcriptomes of two pyrethroid- and two spinosad-resistant isofemale lines. In both pyrethroid-resistant lines and one spinosad-resistant line, we identified overexpression of metabolic genes that are implicated in resistance in other insect pests. In the other spinosad-resistant line, we observed an overexpression of cuticular genes that have been linked to resistance. Our findings enabled the development of molecular diagnostics that we used to confirm persistence of insecticide resistance in California, U.S.A. To validate these findings, we leveraged D. melanogaster mutants with reduced expression of metabolic or cuticular genes that were found to be upregulated in resistant D. suzukii to demonstrate that these genes are involved in promoting resistance. This study is the first to characterize the molecular mechanisms of insecticide resistance in D. suzukii and provides insights into how current management practices can be optimized.

BACKGROUND: Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting. METHODS AND FINDINGS: The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability. CONCLUSIONS: In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored. TRIAL REGISTRATION: NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981.

The synthesis of a novel disorazole C1 analogue is described, and its biological activity as a cytotoxic compound is reported. Based on our convergent and flexible route to the disorazole core, we wish to report a robust strategy to synthesize a non-symmetrical disorazole in which we couple one half of the molecule containing the naturally occurring oxazole heterocycle and the second half of the disorazole macrocycle containing a thiazole heterocycle. This resulted in a very unusual non-symmetrical disorazole C1 analogue containing two different heterocycles, and its biological activity was studied. This provided exciting information about SAR (structure-activity-relationship) for this highly potent class of antitumor compounds.

Mass antibiotic distribution to preschool children resulted in alterations of the gut microbiome months after distribution. This individually randomized, placebo-controlled trial evaluated changes in the gut microbiome and resistome in children aged 8 days to 59 months after one dose of oral azithromycin in Burkina Faso. A total of 450 children were randomized in a 1:1 ratio to either placebo or azithromycin. Rectal samples were collected at baseline, 2 weeks, and 6 months after randomization and subjected to DNA deep sequencing. Gut microbiome diversity and normalized antimicrobial resistance determinants for different antibiotic classes were evaluated. Azithromycin decreased gut bacterial diversity (Shannon P < 0.0001; inverse Simpson P < 0.001) 2 weeks after treatment relative to placebo. Concurrently, the normalized abundance of macrolide resistance genetic determinants was 243-fold higher (95% CI: 76-fold to 776-fold, P < 0.0001). These alterations did not persist at 6 months, suggesting that disruptions were transient. Furthermore, we were unable to detect resistance changes in other antibiotic classes, indicating that co-resistance with a single course of azithromycin when treated at the individual level was unlikely.

The Yamaguchi reagent, based on 2,4,6-trichlorobenzoyl chloride (TCBC) and 4-dimethylaminopyridine (DMAP), is an efficient tool for conducting the intermolecular (esterification) reaction between an acid and an alcohol in the presence of a suitable base (Et3N or iPr2NEt) and solvent (THF, DCM, or toluene). The Yamaguchi protocol is renowned for its ability to efficiently produce a diverse array of functionalized esters, promoting high yields, regioselectivity, and easy handling under mild conditions with short reaction times. Here, the recent utilization of the Yamaguchi reagent was reviewed in the synthesis of various natural products such as macrolides, terpenoids, polyketides, peptides, and metabolites. [ABSTRACT FROM AUTHOR]

Macrolides are a group of compounds used to treat bacterial infections in humans and animals. Their widespread use results in the contamination of the water environment, which, on the one hand, has a detrimental effect on aquatic organisms and, on the other hand, can lead to the emergence of resistant strains of microorganisms. All of the above determines the need for monitoring of these compounds in the environment, particularly, in water objects. Usually, the high‐performance liquid chromatography combined with tandem mass spectrometry method is used to solve this problem, however, this work shows the possibility of using the supercritical fluid chromatography‐tandem mass spectrometry method. An approach for the determination of four common macrolides, namely erythromycin, clarithromycin, midecamycin, and josamycin, was developed. The use of solid‐phase extraction allowed to achieve limits of quantification at 0.57–6.8 ng/L. The presented approach was validated and tested on a real object—a sample of municipal wastewater. [ABSTRACT FROM AUTHOR]

Background Macrolides are recommended for treating the emerging enteropathogen Arcobacter butzleri ; nonetheless, this bacterium often exhibits highly variable resistance rates, and the mechanisms behind this resistance phenotype remain largely unexplored. Objectives To understand the phenotypic and genotypic consequences associated with the acquisition of erythromycin resistance in A. butzleri , as well as the effects on the fitness of this species. Methods Resistant strains resulting from spontaneous mutations and adaptive laboratory evolution under increasing erythromycin concentrations were examined regarding their cross-resistance and collateral susceptibility profiles. Genetic causes of phenotypic antibiotic resistance were analysed by sequencing and bioinformatics, with functional correlation through ethidium bromide accumulation assays. Growth profiles in the presence and absence of erythromycin, motility and biofilm formation abilities were assessed to detect potential changes in fitness and virulence. Results Clones from spontaneous mutation rate evolution demonstrated decreased susceptibility to erythromycin and other classes of antibiotics, associated with mutations in the transcriptional repressor areR , causing overexpression of the AreABC efflux pump. In turn, WGS analysis of the evolved strain showed additional mutations in the ribosomal proteins L4 and L22 and in the areR gene. Furthermore, the acquisition of macrolide resistance altered A. butzleri virulence and entailed a high biological cost. Conclusions The findings of this study have proved that efflux activity contributes synergistically with mutations in the ribosomal proteins L4 and L22 to A. butzleri 's high-level macrolide resistance. The results further suggest an impact on the bacterial physiology and virulence, with the increased fitness cost justifying the low worldwide prevalence of high-level resistant circulating strains. [ABSTRACT FROM AUTHOR]

Background Over the years, reports have associated fluoroquinolones (FQ) with seizures. The incidence and whether FQ compared to non-epileptogenic antibiotic are associated with increased risk of seizures has yet to be examined. Methods A retrospective observational study of hospitalized patients treated with FQ (ofloxacin, ciprofloxacin, levofloxacin, moxifloxacin) or macrolides (MA: azithromycin or roxithromycin) between January 2009 and January 2021 in a large tertiary academic medical centre. The outcome was the occurrence of a seizure during treatment. The Naranjo scale was used to assess causality between FQ treatment and seizures. Comparative analysis was conducted using propensity score matching to correct for possible bias due to non-random selection, followed by inverse probability weighting (IPW) to estimate the difference in seizure risk between FQ and MA. Results Overall, 52 722 patients were treated with FQ during a total of 178 982 days. Mean age was 65 (±19) years and 47% were females. Thirty-three patients (0.06%) experienced a seizure, yielding an incidence of 1:5422 treatment days. Causality was deemed probable and possible among 9/33 and 24/33, respectively. The MA group composed of 8522 patients treated during 17 954 treatment days. Mean age was 65 (±21) years, 49% were females. Six (0.07%) patients experienced each a single seizure. IPW estimated OR for seizures among the FQ versus MA group was 1.44 (95%CI 0.59–3.5, P  = 0.42). Discussion The incidence of FQ associated seizures among hospitalized patients is low and the risk did not significantly exceed that under macrolides. Our results provide evidence for clinicians and decision-makers when balancing fluoroquinolones risks and benefits. [ABSTRACT FROM AUTHOR]

Previous studies evaluating the risk of spontaneous abortions following exposure to macrolides reported controversial results. The goal of the current study was to examine the risk for spontaneous abortions following exposure to macrolides during pregnancy. We conducted a population‐based retrospective cohort study by linking three computerized databases: Clalit Health Services drug dispensation database, Soroka Medical Center (SMC) birth database, and SMC hospitalizations database. Multivariate time‐varying Cox regressions were performed and adjusted for suspected confounders and known risk factors for spontaneous abortions. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. A secondary analysis was performed to assess the association between exposure to macrolides in terms of the defined daily dose dispensed and spontaneous abortions. The study cohort included 65,457 pregnancies that ended at Soroka Medical Center between 2004 and 2009, of which 6508 (9.9%) resulted in a spontaneous abortion. A total of 825 (1.26%) pregnancies were exposed to macrolides during the exposure period. Exposure to macrolides was not associated with spontaneous abortions as a group (adjusted HR 1.00 95% CI 0.77‐1.31) or as specific medications. There was no evidence of a dose‐response relationship between exposure to macrolides and spontaneous abortions. In conclusion, this population‐based retrospective cohort study did not detect an increased risk for spontaneous abortion following exposure to macrolides during the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

The emergence of inactivation enzyme-encoding genes tet(X), blaEBR, and estT challenges the effectiveness of tetracyclines, β-lactams, and macrolides. This study aims to explore the concurrence and polymorphism of their variants in Empedobacter sp. strains from food-producing animals and surrounding environments. A total of eight tet(X) variants, seven blaEBR variants, and seven estT variants were detected in tet(X)-positive Empedobacter sp. strains (6.7%) from chickens, sewage, and soil, including 31 Empedobacter stercoris and 6 novel species of Taxon 1. All of them were resistant to tigecycline, tetracycline, colistin, and ciprofloxacin, and 16.2% were resistant to meropenem, florfenicol, and cefotaxime. The MIC90 of tylosin, tilmicosin, and tildipirosin was 128 mg/L, 16 mg/L, and 8 mg/L, respectively. Cloning expression confirmed that tet(X6) and the novel variants tet(X23), tet(X24), tet(X25), tet(X26), and tet(X26.2) conferred high-level tigecycline resistance, while all of the others exhibited relatively low-level activities or were inactivated. The bacterial relationship was diverse, but the genetic environments of tet(X) and blaEBR were more conserved than estT. An ISCR2-mediated tet(X6) transposition structure, homologous to those of Acinetobacter sp., Proteus sp., and Providencia sp., was also identified in Taxon 1. Therefore, the tet(X)-positive Empedobacter sp. strains may be ignored and pose a serious threat to food safety and public health. [ABSTRACT FROM AUTHOR]

The strasseriolide macrolides show promising in vitro and in vivo activities against P. falciparum and T. cruzi, the parasites causing malaria and Chagas disease, respectively. However, the as yet poor understanding of structure/activity relationships and the fact that one family member proved systemically toxic for unknown reasons render a more detailed assessment of these potential lead compounds difficult. To help overcome these issues, a collective total synthesis was devised. The key steps consisted of a ring closing alkyne metathesis (RCAM) reaction to forge a common macrocyclic intermediate followed by a hydroxy‐directed ruthenium catalyzed trans‐hydrostannation of the propargyl alcohol site thus formed. The resulting alkenyltin derivative served as the central node of the synthesis blueprint, which could be elaborated into the natural products themselves as well as into a set of non‐natural analogues according to the concept of diverted total synthesis. The recorded biological data confirmed the potency of the compounds and showed the lack of any noticeable cytotoxicity. The "northern" allylic alcohol subunit was recognized as an integral part of the pharmacophore, yet it provides opportunities for chemical modification. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to explore the prevalence of macrolide resistance and the underlying resistance mechanisms in Haemophilus influenzae (n  = 2556) and Haemophilus parainfluenzae (n  = 510) collected between 2018 and 2021 from Bellvitge University Hospital, Spain. Methods Antimicrobial susceptibility was tested by microdilution. Whole-genome sequencing was performed using Illumina MiSeq and Oxford Nanopore technologies, and sequences were examined for macrolide resistance determinants and mobile genetic structures. Results Macrolide resistance was detected in 67 H. influenzae (2.6%) and 52 (10.2%) H. parainfluenzae strains and associated with resistance to other antimicrobials (co-trimoxazole, chloramphenicol, tetracycline). Differences in macrolide resistance existed between the two species. Acquired resistance genes were more prevalent in H. parainfluenzae (35/52; 67.3%) than in H. influenzae (12/67; 17.9%). Gene mutations and amino acid substitutions were more common in H. influenzae (57/67; 85%) than in H. parainfluenzae (16/52; 30.8%). Substitutions in L22 and in 23S rRNA were only detected in H. influenzae (34.3% and 29.0%, respectively), while substitutions in L4 and AcrAB/AcrR were observed in both species. The MEGA element was identified in 35 (67.3%) H. parainfluenzae strains, five located in an integrative and conjugative element (ICE); by contrast, 11 (16.4%) H. influenzae strains contained the MEGA element (all in an ICE). A new ICE HpaHUB8 was described in H. parainfluenzae. Conclusions Macrolide resistance was higher in H. parainfluenzae than in H. influenzae , with differences in the underlying mechanisms. H. parainfluenzae exhibits co-resistance to other antimicrobials, often leading to an extensively drug-resistant phenotype. This highlights the importance of conducting antimicrobial resistance surveillance. [ABSTRACT FROM AUTHOR]

A resurgence of Mycoplasma pneumoniae (MP)—the leading cause of community-acquired bacterial pneumonia, particularly in children—occurred following the COVID-19 pandemic. We aimed to investigate the clinical manifestations, macrolide resistance patterns, and therapeutic approaches related to the MP pneumonia epidemic. Children and adolescents diagnosed with MP pneumonia in September–December 2023 were screened. Clinical data were retrospectively collected from 13 major hospitals using concordant microbiological criteria, including either a positive PCR result or four-fold increase in serological markers. Demographic characteristics, treatment modalities, and clinical outcomes were analyzed. Of the 474 screened patients, 374 (median age: 7.7 [IQR, 5.4–9.6] years; hospitalization rate: 88.6%) met the microbiological confirmation criteria. Most patients experienced fever (98.9%), and lobular/lobar consolidation (59.1%) was the dominant radiological finding. The macrolide resistance rate remained high at 87.0%; corticosteroids were widely used (55.6%) alongside macrolides, despite resistance. Patients with consolidation had prolonged fever (median 8 vs. 7 days, p = 0.020) and higher hospitalization rates (92.3% vs. 83.0%, p = 0.008). Macrolide resistance did not significantly influence radiological outcomes. This study highlights the ongoing challenge of macrolide resistance in MP pneumonia and need for tailored therapeutic approaches. Despite high resistance, macrolides remain commonly prescribed, often concurrently with corticosteroids. [ABSTRACT FROM AUTHOR]

Low-dose azithromycin prophylaxis is associated with improved outcomes in people suffering frequent exacerbations of chronic obstructive pulmonary disease (COPD), but the use of macrolides in patients with cardiovascular disease has been debated. To investigate the risk of adverse events after COPD exacerbations in patients with atrial fibrillation (AF) treated with azithromycin prophylaxis. Retrospective cohort study within the TriNetX Platform, including AF patients with COPD exacerbations. Risks of primary and secondary outcomes were recorded up to 30 days post-COPD exacerbations and compared between azithromycin users and azithromycin non-users. The primary outcomes were the risks for a composite of (1) cardiovascular (all-cause death, heart failure, ventricular arrhythmias, ischemic stroke, myocardial infarction, and cardiac arrest), and (2) hemorrhagic events (intracranial hemorrhage (ICH), and gastro-intestinal bleeding). Cox-regression analyses compared outcomes between groups after propensity score matching (PSM). After PSM, azithromycin users (n = 2434, 71 ± 10 years, 49% females) were associated with a lower 30-day risk of post-exacerbation cardiovascular (HR 0.67, 95% CI 0.61–0.73) and hemorrhagic composite outcome (HR 0.45, 95% CI 0.32–0.64) compared to azithromycin non-users (n = 2434, 72 ± 11 years, 51% females). The beneficial effect was consistent for each secondary outcomes, except ICH. On sensitivity analyses, the reduced risk of adverse events in azithromycin users was irrespective of smoking status, exacerbation severity, and type of oral anticoagulation. Azithromycin prophylaxis is associated with a lower risk of all-cause death, thrombotic and hemorrhagic events in AF patients with COPD. The possible role of azithromycin prophylaxis as part of the integrated care management of AF patients with COPD needs further study. [ABSTRACT FROM AUTHOR]

In this Account, we summarize the development of a new strategy for streamlined synthesis of tetrahydropyran-embedded macrolactones and its successful implementation to a 13-step synthesis of (–)-exiguolide and an 11-step synthesis of (+)-neopeltolide. 1 Introduction 2 Development of Macrocyclization/Transannular Pyran Cyclization Strategy 3 Total Synthesis of (–)-Exiguolide 4 Total Synthesis of (+)-Neopeltolide 5 Conclusions [ABSTRACT FROM AUTHOR]

Published data on the molecular mechanisms underlying antimicrobial resistance in Group B Streptococcus (GBS) isolates from Saudi Arabia are lacking. Here, we aimed to determine the genetic basis of resistance to relevant antibiotics in a collection of GBS clinical isolates (n = 204) recovered from colonized adults or infected patients and expressing serotypes Ia, Ib, II, III, V, and VI. Initial susceptibility testing revealed resistance to tetracycline (76.47%, n = 156/204), erythromycin (36.76%, n = 75/204), clindamycin (25.49%, n = 52/204), levofloxacin (6.37%, n = 13/204), and gentamicin (2.45%, n = 5/204). Primers designed for the detection of known resistance determinants in GBS identified the presence of erm(A), erm(B), mef(A), and/or lsa(C) genes at the origin of resistance to macrolides and/or clindamycin. Of these, erm(B) and erm(A) were associated with the cMLSB (n = 46) and iMLSB (n = 28) phenotypes, respectively, while mef(A) was linked to the M phenotype (n = 1) and lsa(C) was present in isolates with the L phenotype (n = 8). Resistance to tetracycline was mainly mediated by tet(M) alone (n = 112) or in combination with tet(O) (n = 10); the remaining isolates carried tet(O) (n = 29), tet(L) (n = 2), or both (n = 3). Isolates resistant to gentamicin (n = 5) carried aac(6′)-Ie-aph(2′)-Ia, and those exhibiting resistance to levofloxacin (n = 13) had alterations in GyrA and/or ParC. Most isolates with the erm gene (93.24%, n = 69/74) also had the tet gene and were therefore resistant to erythromycin, clindamycin, and tetracycline. Overall, there were no clear associations between serotypes and resistance genotypes except for the presence of erm(B) in serotype Ib isolates. Dissemination of antibiotic resistance genes across different serotypes represents a public health concern that requires further surveillance and appropriate antibiotic use in clinical practice. [ABSTRACT FROM AUTHOR]

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Azithromycin mass drug administration decreases child mortality but also selects for antibiotic resistance. Herein, we evaluate macrolide resistance of nasopharyngeal Streptococcus pneumoniae after azithromycin MDA. In a cluster-randomized trial, children 1-59 months received azithromycin or placebo biannually. Fifteen villages from each arm were randomly selected for antimicrobial resistance testing, and 10-15 randomly selected swabs from enrolled children at each village were processed for S. pneumoniae isolation and resistance testing. The primary prespecified outcome was macrolide resistance fraction for azithromycin versus placebo villages at 36 months. Secondary non-prespecified outcomes were comparisons of azithromycin and placebo for: 1) macrolide resistance at 12, 24, and 36 months; 2) nonmacrolide resistance at 36 months; and 3) suspected-erm mutation. At 36 months, 423 swabs were obtained and 322 grew S. pneumoniae, (azithromycin: 146/202, placebo: 176/221). Mean resistance prevalence was non-significantly higher in treatment than placebo (mixed-effects model: 14.6% vs. 8.9%; OR = 2.0, 95% CI: 0.99-3.97). However, when all time points were evaluated, macrolide resistance prevalence was significantly higher in the azithromycin group (β = 0.102, 95% CI: 0.04-0.167). For all nonmacrolides, resistance prevalence at 36 months was not different between the two groups. Azithromycin and placebo were not different for suspected-erm mutation prevalence. Macrolide resistance was higher in the azithromycin group over all time points, but not at 36 months. Although this suggests resistance may not continue to increase after biannual MDA, more studies are needed to clarify when MDA can safely decrease mortality and morbidity in lower- and middle-income countries.

Abstract Background The characteristics of bronchiectasis (BE) in Asia, including Japan, remain largely unknown. We aimed to provide insights into the clinical characteristics and treatment outcomes of BE, especially regarding nontuberculous mycobacteria (NTM) infection and its poorly understood impact on prognosis. We also aimed to clarify the effect of long-term macrolide antibiotic use in patients with BE, who had no history of exacerbations. Methods In this single-center, retrospective study, the medical records of patients who satisfied the BE criteria between January 1, 2012, and August 31, 2023, were reviewed. Severe exacerbations and mortality during the observation period were recorded. Baseline characteristics and overall survival of patients with and without NTM infection, and factors influencing the time to the first exacerbation and death were analyzed. Additionally, the effects of long-term macrolide antibiotic use in patients without a history of severe exacerbations were estimated. Results In a cohort of 1044 patients with BE, the rate of severe exacerbation was 22.3%, with mortality rates of 3.2% over 3 years. Notably, the high prevalence of NTM infection (n = 410, 39.3%) in this cohort was distinctive. NTM infection was not associated with either the time to first severe exacerbation (p = 0.5676, adjusted hazard ratio = 1.11) or mortality (p = 0.4139, adjusted hazard ratio = 0.78). Compared with the NTM group, the non-NTM group had a higher proportion of elevated inflammatory markers, with significant differences in C-reactive protein levels (p = 0.0301) and blood neutrophil counts (p = 0.0273). Pseudomonas aeruginosa colonization was more frequent in the non-NTM group (p = 0.0003). Among patients with non-NTM infection and without a history of exacerbation in the past 2 years, 38.2% received long-term macrolide antibiotics that did not invariably prolong the time to first severe exacerbation (p = 0.4517, IPW p = 0.3555). Conclusions This study highlights BE epidemiology in Japan, noting that the presence of NTM infection may not necessarily worsen the prognostic outcomes and advising caution in the casual use of macrolides for milder cases without a history of exacerbations. Clinical trial registration UMIN Clinical Trials Registry Number: UMIN000054726 (Registered on 21 June 2024).

Background: Macrolides inhibit the growth of bacterial cells by preventing the elongation of polypeptides during protein biosynthesis and include natural, synthetic, and semi-synthetic products. Elongation prevention occurs by blocking the passage of the polypeptide chain as the macrolides bind at the nascent peptide exit tunnel. Objective: Recent data of ribosome profiling via ribo-seq further proves that, other than blocking the polypeptide chain, macrolides are also able to affect the synthesis of individual proteins. Thus, this shows that the mode of action of macrolides is more complex than we initially thought. Since the discovery of macrolides in the 1950s, they have been widely used in veterinary practice, agriculture, and medicine. Due to misuse and overuse of antibiotics, bacteria have acquired resistance against them. Hence, it is of utmost importance for us to fully understand the mode of action of macrolides as well as the mechanisms of resistance against macrolides in order to mitigate antibiotic-resistance issues. Results: Chemical modifications can be performed to improve macrolide potency if we have a better understanding of their mode of action. Furthermore, a complete and detailed understanding of the mode of action of macrolides has remained vague, as new findings have challenged theories that are already in existence—due to this obscurity, research into macrolide modes of action continues to this day. Conclusion: In this review, we present an overview of macrolide antibiotics, with an emphasis on the latest knowledge regarding the mode of action of macrolides as well as the mechanisms of resistance employed by bacteria against macrolides.

Background: Mycoplasma genitalium is an emerging etiology of sexually transmitted infections (STIs) with increasing resistance to antimicrobials. Surveillance on the epidemiology of M. genitalium infection and antimicrobial resistance is warranted. Methods: Between September 2021 and August 2023, people with HIV (PWH) and people without HIV (PWoH) at risk of STIs were screened for M. genitalium infection using a multiplex polymerase-chain-reaction assay of specimens collected from the rectum, urethra, oral cavity, and vagina. The prevalences of resistance-associated mutations (RAMs) of M. genitalium to fluoroquinolones, macrolides, and tetracycline were investigated. Results: During the 2-year study period, 1021 participants were enrolled, including 531 PWH and 490 PWoH. Overall, 83 (8.1%) and 34 (7.6%) participants had M. genitalium infection at baseline and during follow-up, respectively, with the rectum being the most common site of detection (61.5%). With the first course of antimicrobial treatment, 27 of 63 (42.9%) participants with M. genitalium infection were cured during follow-up, including 24 of 58 (41.4%) who received doxycycline monotherapy. The prevalence of RAMs to macrolides, fluoroquinolones, and tetracyclines at baseline were 24.3%, 22.4%, and 7.9%, respectively. Though PWH had more M. genitalium infection (10.2% vs 5.9%, p = 0.01), a higher rate of RAMs to macrolides (41.0% vs 14.7%, p

Objective. To study epidemiology of resistance to macrolides and fluoroquinolones in Mycoplasmagenitalium isolated from pregnant women in Russia and Belarus. Materials and Methods. A total of 107 M. genitalium DNA samples isolated from pregnant women in Russia (n = 58) and Belarus (n = 49) was included in the study. In order to detect markers of macrolide or fluoroquinolone resistance, polymerase chain reaction in real time with the effect of quenching fluorescence of the probe by a primer was used. Confirmation of mutation type was performed using Sanger sequencing. Results. The prevalence of M. genitalium resistance mutations to macrolides in Russia (Tula, Smolensk) and Belarus (Vitebsk, Brest, Minsk) was 3.4% (2/58) and 6.1% (3/49), respectively. Markers of M. genitalium resistance to fluoroquinolones were detected in 5.2% (3/58) of samples from Russia and 8.2% (4/49) of samples from Belarus. The most common mutations associated with macrolide resistance were A2059G (n = 4), fluoroquinolone resistance – D84N (n = 3) and S80I (n = 3) (numbering according to E. coli). Conclusions. The prevalence of M. genitalium resistance markers isolated in pregnant women highlights a need for regular macrolide and fluoroquinolone resistance surveillance.

Objective: To determine the patterns of resistance among different macrolides and to detect macrolide resistance genes in Staphylococcus aureus collected from different clinical samples. Study Design: Cross-sectional observational study. Place and Duration of Study: The clinical samples sourced from the Pathology Labs of Railway Hospital, Tehsil Head Quarter (THQ) Hospital Taxila and Wah General Hospital Wah Cantt, Pakistan was collected from 01August 2017 to 01 February 2018. Materials and Methods: One hundred non-repetitive clinical isolates were obtained from different clinical samples (pus, urine, sputum and blood). Each Staphylococcus aureus isolate was obtained from only one sample, to avoid repetition of strain. They were selected on the criteria of their growth with bright yellow color colony formation on mannitol salt agar (MSA) media along with the color change of media from red to yellow and coagulase positive results. Kirbey-Baur disk diffusion test was followed for the detection of antimicrobial sensitivity, whereas genotypic resistance drift was determined using PCR. Results: Highest frequency of Staphylococcus aureus was observed in pus samples i.e. 45 (40.2%). Out of 100, 34 isolates of Staphylococcus aureus were resistant to macrolides group. Among 34 resistant isolates the frequency of ermC gene was 25 and msrAwas 14 respectively, whereas all isolates were negative for ermAgene. Maximum resistance was observed against erythromycin, n=33 (29.5%) and minimum against clarithromycin, n=26 (23.3%). The highest susceptibility trend was seen against Azithromycin, n=62 (55%). Conclusion: Resistance of Staphylococcus aureus may vary with different antibiotics within the same group. A high frequency of erythromycin resistance was seen in this study. The most predominant resistance was for ermC, among the resistance genes in isolates.

Background The WHO recommendation against the use of macrolides reflects the little low-quality evidence about the effect of azithromycin (AZ) on influenza A infection. Considering recent reports about AZ use despite the WHO’s unfavorable recommendations, we aimed to test the evidence for the usage of AZ in the treatment of influenza A infection. Methods Various online databases were searched till August 2023 and thorough text and evidence evaluation resulted in selecting 7 studies. Results The selected reports included randomized control trials (two), cohort (three), case/control (one) studies, and one case report. Pooling of the results was unattainable due to the variability among studies in patient criteria, study outcomes, and study designs. Based on the limited reports with insufficient evidence, a recommendation for the use of AZ in the treatment regimen was not possible despite the associated reduction in inflammatory cytokines by AZ administration and the absence of significant adverse effects or mortality in hospital-admitted or ICU patients. While these findings support the current guidelines for the treatment of influenza A infection, the evidence behind these guidelines and treatment characteristics were illustrated. Conclusion AZ shows a potential symptom improvement and pro-inflammatory laboratory indices in influenza A patients. Another positive aspect is the absence of complications associated with AZ administration to critically ill patients and acceptable prognosis. However, it is crucial to have more quality research on this matter that focuses on the indication of the use of AZ, and the timing of initiation, dosage, and duration of treatment while monitoring adverse events.

Mannheimia haemolytica is a major contributor to bovine respiratory disease (BRD), which causes substantial economic losses to the beef industry, and there is an urgent need for rapid and accurate diagnostic tests to provide evidence for treatment decisions and support antimicrobial stewardship. Diagnostic sequencing can provide information about antimicrobial resistance genes in M. haemolytica more rapidly than conventional diagnostics. Realizing the full potential of diagnostic sequencing requires a comprehensive understanding of the genetic markers of antimicrobial resistance. We identified genetic markers of resistance in M. haemolytica to macrolide class antibiotics commonly used for control of BRD. Genome sequences were determined for 99 M. haemolytica isolates with six different susceptibility phenotypes collected over 2 years from a feedlot in Saskatchewan, Canada. Known macrolide resistance genes estT, msr(E), and mph(E) were identified in most resistant isolates within predicted integrative and conjugative elements (ICEs). ICE sequences lacking antibiotic resistance genes were detected in 10 of 47 susceptible isolates. No resistance-associated polymorphisms were detected in ribosomal RNA genes, although previously unreported mutations in the L22 and L23 ribosomal proteins were identified in 12 and 27 resistant isolates, respectively. Pangenome analysis led to the identification of 79 genes associated with resistance to gamithromycin, of which 95% (75 of 79) had no functional annotation. Most of the observed phenotypic resistance was explained by previously identified antibiotic resistance genes, although resistance to the macrolides gamithromycin and tulathromycin was not explained in 39 of 47 isolates, demonstrating the need for continued surveillance for novel determinants of macrolide resistance. [ABSTRACT FROM AUTHOR]

Copyright of Biomédica: Revista del Instituto Nacional de Salud is the property of Instituto Nacional de Salud of Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Antibiotics are routinely added to ornamental fish tanks for treating bacterial infection or as a prophylactic measure. However, the overuse or subtherapeutical application of antibiotics could potentially facilitate the selection of antibiotic resistance in bacteria, yet no studies have investigated antibiotic use in the retail ornamental fish sector and its impact on microbial communities. The present study analyzed the concentrations of twenty antibiotics in the carriage water (which also originates from fish tanks in retail shops) collected monthly from ten local ornamental fish shops over a duration of three months. The antibiotic concentrations were correlated with the sequenced microbial community composition, and the risk of resistance selection in bacteria was assessed. Results revealed that the detected concentrations of tetracyclines were the highest among samples, followed by fluoroquinolones and macrolides. The concentrations of oxytetracycline (44.3 to 2,262,064.2 ng L−1) detected across three months demonstrated a high risk for resistance selection at most of the sampled shops. Zoonotic pathogens (species of Rhodococcus, Legionella, and Citrobacter) were positively correlated with the concentrations of oxytetracycline, tetracycline, chlortetracycline, and enrofloxacin. This suggests that antibiotic use in retail shops may increase the likelihood of selecting for zoonotic pathogens. These findings shed light on the potential for ornamental fish retail shops to create a favorable environment for the selection of pathogens with antibiotics, thereby highlighting the urgent need for enhanced antibiotic stewardship within the industry. [ABSTRACT FROM AUTHOR]

Neonatal ocular prophylaxis with 0.5% erythromycin ophthalmic ointment is mandated by law in many U.S. states despite its lack of efficacy in preventing chlamydial ophthalmia and the low incidence of gonococcal ophthalmia today. The current shortage of 0.5% erythromycin ophthalmic ointment is bringing into question what alternatives exist for neonatal ocular prophylaxis for the prevention of gonococcal ophthalmia. Providers in states with mandates are concerned with the implications of administering intramuscular ceftriaxone to every newborn. Azithromycin eye drops are being considered as an alternative. This article discusses 1% azithromycin eye drops as an alternative to 0.5% erythromycin ophthalmic ointment. Clinical experience, side effects, resistance, logistics, pharmacokinetics, and pharmacodynamics are considered. Azithromycin eye drops are not an appropriate alternative to 0.5% erythromycin ophthalmic ointment for ocular prophylaxis. Prenatal screening and treatment of pregnant women is the most effective way to prevent neonatal ophthalmia. Mandates for universal prophylaxis should be withdrawn to avoid unnecessary medication administration, healthcare costs, and potential harm. [ABSTRACT FROM AUTHOR]

Treatment of tularemia during pregnancy is challenging due to toxicity of standard treatment regimens. Here, we report a 31-year-old woman with glandular tularemia who was successfully treated with intravenous azithromycin. Follow-up examinations over a 6-month period showed a sustained response to treatment. She later gave birth to a healthy child. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Legionella pneumophila ( Lp) is aerobic, non-spore forming Gram-negative bacteria, which is ubiquitous in freshwater habitats, such as rivers and hot springs, as well as colonizing artificial aquatic environments. The ability of Lp to grow intracellularly within pulmonary macrophages is a prerequisite for the development of infection. Therefore, macrolides can achieve appropriate therapeutic concentrations in eukaryotic cells, such as azithromycin. This study aimed to investigate the macrolides susceptibility of Lp. METHODS: Pre-flash water samples (n=143) were collected from the public buildings (hospitals and hotels) water system in Istanbul. Colonies were confirmed as Lp ST1, ST2-14, and non-pneumophila Lp using latex agglutination kit. RESULTS: 30 Lp were detected in hospital (n=23) and hotel (n=7) water systems using latex agglutination. Regardless of serotype and excluding strains without zone formation (≥256 mg/L), the main MIC values of azithromycin, erythromycin and clarithromycin were 0.61 mg/L (range 0.047--1 mg/L), 0.47 mg/L (range 0.047--1 mg/L) and 0.44 mg/L (range 0.047--1 mg/L), respectively. The MIC50 and MIC90 values for macrolides were 0.5 and 3 mg/L for azithromycin, respectively; 0.38 and 1 mg/L for erythromycin, respectively; and 0.5 and 1 mg/L for clarithromycin, respectively. We compared the MIC values of the strains for all antimicrobial agents tested without serotype discrimination. We did not find a significant difference between the MIC values of the antibiotics (p=0.16). CONCLUSION: Although the data obtained from our study do not fully reflect the breakpoints, further epidemiological studies are needed to standardize MIC values. [ABSTRACT FROM AUTHOR]

Copyright of China Tropical Medicine is the property of China Tropical Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Microplastics (MPs) and antibiotics are emerging pollutants widely found in aquatic environments, potentially causing environmental harm. MPs may act as carriers for antibiotics, affecting their environmental distribution. This study investigates the adsorption of four macrolide antibiotics and a metabolite onto two types of MPs: polyethylene terephthalate (PET) and polyethylene (PE). Results revealed a linear isotherm adsorption model, with higher adsorption to PET than to PE (R2 > 0.936 for PE and R2 > 0.910 for PET). Hydrophobic interactions and hydrogen bonding could be the main adsorption mechanisms, with pore filling potentially involved. Reduced particle size enhances adsorption due to the increase of active adsorption sites. This increasement is more pronounced in PE than in PET, leading to an 11.6% increase in the average adsorption of all macrolides to PE, compared to only 5.1% to PET. Dissolved organic matter inhibits adsorption (azithromycin adsorption to PE was reduced from 12% to 5.1%), while salinity enhances it just until 1% salinity. pH slightly influences adsorption, with maximal adsorption at neutral pH. Results in real samples showed that complexity of the matrix decreased adsorption. Overall, these findings indicate that PE and PET MPs can be a vector of macrolides in aquatic environments. [ABSTRACT FROM AUTHOR]

The spliceosome is a staggeringly complex machine, comprising, in humans, 5 snRNAs and >150 proteins. We scaled haploid CRISPR-Cas9 base editing to target the entire human spliceosome and investigated the mutants using the U2 snRNP/SF3b inhibitor, pladienolide B. Hypersensitive substitutions define functional sites in the U1/U2-containing A complex but also in components that act as late as the second chemical step after SF3b is dissociated. Viable resistance substitutions map not only to the pladienolide B-binding site but also to the G-patch domain of SUGP1, which lacks orthologs in yeast. We used these mutants and biochemical approaches to identify the spliceosomal disassemblase DHX15/hPrp43 as the ATPase ligand for SUGP1. These and other data support a model in which SUGP1 promotes splicing fidelity by triggering early spliceosome disassembly in response to kinetic blocks. Our approach provides a template for the analysis of essential cellular machines in humans.

Marinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have been one of the most difficult undertakings in natural products chemistry, and in most cases, the use of X-ray diffraction methods and total synthesis have been the major methods of assigning their absolute configurations. More recently, however, it has become apparent that the integration of bioinformatic data is growing in utility to assign absolute configurations. Genome mining and bioinformatic analysis identified the 97 kb mld biosynthetic cluster harboring seven type I polyketide synthases. A detailed bioinformatic investigation of the ketoreductase and enoylreductase domains within the multimodular polyketide synthases, coupled with NMR and X-ray diffraction data, allowed for the absolute configurations of marinolides A and B to be determined. While using bioinformatics to assign the relative and absolute configurations of natural products has high potential, this method must be coupled with full NMR-based analysis to both confirm bioinformatic assignments as well as any additional modifications that occur during biosynthesis.

Highly functionalized skeletons of macrolide natural products gain access to rare spatial arrangements of atoms, where changes in stereochemistry can have a profound impact on the structure and function. Spliceosome modulators present a unique consensus motif, with the majority targeting a key interface within the SF3B spliceosome complex. Our recent preparative-scale synthetic campaign of 17S-FD-895 provided unique access to stereochemical analogues of this complex macrolide. Here, we report on the preparation and systematic activity evaluation of multiple FD-895 analogues. These studies examine the effects of modifications at specific stereocenters within the molecule and highlight future directions for medicinal chemical optimization of spliceosome modulators.

BackgroundHelicobacter pylori infection is a primary global health concern. However, the widespread use of antibiotics, particularly macrolides such as clarithromycin, has increased resistance among H. pylori strains. This study aimed to investigate the prevalence of macrolide resistance in H. pylori in different world regions.MethodsThis systematic literature search was performed using the appropriate search syntax after searching PubMed, Embase, Web of Science, and Scopus databases between May 2015 and December 2023. Statistical analysis was performed using Pooled and random effects model in R and the metafor package.ResultsA total of 7,768 articles were retrieved. After a thorough evaluation, 155 studies (by 178 reports) were finally eligible for inclusion in this systematic review and meta-analysis. According to the results, the majority of studies (178 reports from 43 countries) assessed clarithromycin susceptibility, with a pooled prevalence of 33.3% and high heterogeneity between studies (I2 = 98.57%, p

The Yamaguchi reagent, based on 2,4,6-trichlorobenzoyl chloride (TCBC) and 4-dimethylaminopyridine (DMAP), is an efficient tool for conducting the intermolecular (esterification) reaction between an acid and an alcohol in the presence of a suitable base (Et3N or iPr2NEt) and solvent (THF, DCM, or toluene). The Yamaguchi protocol is renowned for its ability to efficiently produce a diverse array of functionalized esters, promoting high yields, regioselectivity, and easy handling under mild conditions with short reaction times. Here, the recent utilization of the Yamaguchi reagent was reviewed in the synthesis of various natural products such as macrolides, terpenoids, polyketides, peptides, and metabolites.

Introduction: Mycoplasma genitalium is a bacterium associated with sexually transmitted infections that can cause urethritis in men and complications in women, including preterm birth. Increasing macrolide resistance in M. genitalium poses challenges to treatment efficacy. Objective: To present a case of treatment failure of urethritis caused by macrolide-resistant M. genitalium. Case report: This case report describes a 20-year-old man with persistent urethral symptoms despite azithromycin treatment, wherein M. genitalium harbored the A2058G mutation in the 23S rRNA. Subsequent treatment with moxifloxacin resolved symptoms and cleared M. genitalium. Conclusion: The study highlights the importance of resistance testing to guide antimicrobial therapy and emphasizes the need for updated treatment guidelines in Brazil.

Abstract Background Legionnaires’ disease (LD) is a common but under-diagnosed cause of community-acquired pneumonia (CAP), although rapid detection of urine antigen testing (UAT) and advances in molecular testing have improved the diagnosis. LD entails intensive care unit (ICU) admission in almost one-third of cases, and the mortality rate ranges from 4% to 40%. This review aims to discuss recent advances in the study of this condition and to provide an update on the diagnosis, pathogenesis and management of severe LD. Results The overall incidence of LD has increased worldwide in recent years due to the higher number of patients with risk factors, especially immunosuppression, and to improvements in diagnostic methods. Although LD is responsible for only around 5% of all-cause CAP, it is one of the three most common causes of CAP requiring ICU admission. Mortality in ICU patients, immunocompromised patients or patients with a nosocomial source of LD can reach 40% despite appropriate antimicrobial therapy. Regarding pathogenesis, no Legionella-specific virulence factors have been associated with severity; however, recent reports have found high pulmonary Legionella DNA loads, and impairments in immune response and lung microbiome in the most severe cases. The clinical picture includes severe lung injury requiring respiratory and/or hemodynamic support, extrapulmonary symptoms and non-specific laboratory findings. LD diagnostic methods have improved due to the broad use of UAT and the development of molecular methods allowing the detection of all Lp serogroups. Therapy is currently based on macrolides, quinolones, or a combination of the two, with prolonged treatment in severe cases. Conclusions Numerous factors influence the mortality rate of LD, such as ICU admission, the underlying immune status, and the nosocomial source of the infection. The host immune response (hyperinflammation and/or immunoparalysis) may also be associated with increased severity. Given that the incidence of LD is rising, studies on specific biomarkers of severity may be of great interest. Further assessments comparing different regimens and/or evaluating host-directed therapies are nowadays needed. Graphical Abstract

AbstractTransdermal drug delivery systems (TDDS) for antibiotics have seen significant advances in recent years that aimed to improve the efficacy and safety of these drugs. TDDS offer many advantages over other conventional delivery systems such as non-invasiveness, controlled-release pattern, avoidance of first-pass metabolism. The objective of this review is to provide an overview on the recent advances in the TDDS of different groups of antibiotics including β-lactams, tetracyclines, macrolides, and lincosamides, utilized for their effective delivery through the skin and to explore the challenges associated with this field. The majority of antibiotics do not have favorable properties for passive transdermal delivery. Thus, novel strategies have been employed to improve the delivery of antibiotics through the skin, such as the use of nanotechnology (nanoparticles, solid-lipid nanoparticles, nanoemulsions, vesicular carriers, and liposomes) or the physical enhancement techniques like microneedles and ultrasound. In conclusion, the transdermal delivery systems could be a promising method for delivering antibiotics that have the potential to improve patient outcomes and enhance the efficacy of drugs. Further research and development are still needed to explore the potential of delivering more antibiotic drugs by using various transdermal drug delivery approaches.

BackgroundThe microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as antibiotics. Several studies have demonstrated that commonly used antibiotics can have sustained impacts on the diversity and the composition of the gut microbiome. The impact of the two most overused antibiotics, azithromycin, and amoxicillin, in the human microbiome has not been thoroughly described. In this study, we recruited a group of individuals and unrelated controls to decipher the effects of the commonly used antibiotics amoxicillin and azithromycin on their gut microbiomes.ResultsWe characterized the gut microbiomes by metagenomic sequencing followed by characterization of the resulting microbial communities. We found that there were clear and sustained effects of the antibiotics on the gut microbial community with significant alterations in the representations of Bifidobacterium species in response to azithromycin (macrolide antibiotic). These results were supported by significant increases identified in putative antibiotic resistance genes associated with macrolide resistance. Importantly, we did not identify these trends in the unrelated control individuals. There were no significant changes observed in other members of the microbial community.ConclusionsAs we continue to focus on the role that the gut microbiome plays and how disturbances induced by antibiotics might affect our overall health, elucidating members of the community most affected by their use is of critical importance to understanding the impacts of common antibiotics on those who take them. Clinical Trial Registration Number NCT05169255. This trial was retrospectively registered on 23-12-2021.

Simple Summary: Antibiotics are emerging contaminants found in several matrices of environmental, animal, and human origin. This high occurrence constitutes a major global threat, which is also responsible for the development of antimicrobial resistance. Therefore, it is vitally important to develop new, simple, and reliable methods by which to quantify them in several matrices. In this work, the mussel matrix was chosen as the sentinel organism; a new analytical method for the determination of two commonly used macrolides in mussels harvested along the Sardinian coasts was developed. None of the tested macrolides were found in the sampling sites at concentrations quantifiable by the developed method. These results can be useful for competent authorities evaluating the food safety of mussels (as concerns the studied antibiotics) and pollution derived from these drugs in the marine environment. Contaminants of emerging concern (CECs) are compounds found in several environmental compartments whose ubiquitous presence can cause toxicity for the entire ecosystem. Several personal care products, including antibiotics, have entered this group of compounds, constituting a major global threat. It is essential to develop simple and reliable methods by which to quantify these contaminants in several matrices. In this work, mussels were chosen as sentinel organisms to assess environmental pollution and the safety of bivalve mollusk consumption according to the "One Health perspective". A liquid chromatographic tandem mass spectrometry method (LC-MS/MS) was developed for the quantification of two macrolides, erythromycin (ERY) and azithromycin (AZI), in mussels. This new method was validated according to international guidelines, showing high selectivity, good recoveries (>60% for both of them), sensitivity, and precision. The method was successfully applied for ERY and AZI research in mussels farmed along the Sardinian coasts (Italy), demonstrating itself to be useful for routine analysis by competent authorities. The tested macrolides were not determined in the analyzed sites at concentrations above the limits of detection (LODs). These results demonstrate the food safety of mussels (as concerns the studied antibiotics) and a negligible amount of pollution derived from these drugs in the studied area. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Hypersensitivity reactions (HSR) are reported for the macrolides, lincosamides, and streptogramins (MLS) antibiotic family. Data about cross‐reactivity among and between MLS remain scarce or controversial.The aim of this study was to provide an overview of hypersensitivity cross‐reactions among MLSs based on data extracted from the French National Pharmacovigilance Database (FPVD).Cases of HSR to MLSs reported between January 1985 and December 2019 were extracted from the FPVD using standardized MedDRA queries (SMQ). Cases including an allergological test involving multiple MLSs and giving at least one positive result were included.Of the 8394 cases reviewed, 149 were included. HSR mainly involved pristinamycin (n = 83; 53.2%) and spiramycin (n = 31; 19.9%). HSR to MLS was immediate in 54 cases and delayed in 94 cases. Skin tests represented the majority of the allergological tests performed (n = 728; 84.7%), followed by reintroduction tests (n = 79; 9.2%). Eighty‐six cross‐reactivities among MLS were identified in 62 cases (41.6%). All the 25 explorations performed for streptogramins showed cross‐reactivities, but only 30/253 among macrolides (11.9%). Cross‐reactivities between the three MLS were observed in 31/322 (9.6%) of the allergological explorations.This study highlights the possibility of cross‐reactivity among and between MLSs. Dermatologists and allergologists managing patients with HSR to MLSs should be aware of a risk of cross‐reactivity among the macrolides and between the different classes of MLS and to perform MLSs allergological testing before recommending an alternative antibiotic, especially in severe drug hypersensitivity from the MLS family. [ABSTRACT FROM AUTHOR]