Metagenomics reveals the resistance patterns of electrochemically treated erythromycin fermentation residue.

Erythromycin fermentation residue (EFR) represents a typical hazardous waste produced by the microbial pharmaceutical industry. Although electrolysis is promising for EFR disposal, its microbial threats remain unclear. Herein, metagenomics was coupled with the random forest technique to decipher the antibiotic resistance patterns of electrochemically treated EFR. Results showed that 95.75% of erythromycin could be removed in 2 hr. Electrolysis temporarily influenced EFR microbiota, where the relative abundances of Proteobacteria and Actinobacteria increased, while those of Fusobacteria, Firmicutes, and Bacteroidetes decreased. A total of 505 antibiotic resistance gene (ARG) subtypes encoding resistance to 21 antibiotic types and 150 mobile genetic elements (MGEs), mainly including plasmid (72) and transposase (52) were assembled in EFR. Significant linear regression models were identified among microbial richness, ARG subtypes, and MGE numbers (r2=0.50-0.81, p< 0.001). Physicochemical factors of EFR (Total nitrogen, total organic carbon, protein, and humus) regulated ARG and MGE assembly (%IncMSE value = 5.14-14.85). The core ARG, MGE, and microbe sets (93.08%-99.85%) successfully explained 89.71%-92.92% of total ARG and MGE abundances. Specifically, gene aph(3')-I, transposase tnpA, and Mycolicibacterium were the primary drivers of the resistance dissemination system. This study also proposes efficient resistance mitigation measures, and provides recommendations for future management of antibiotic fermentation residue.

Assessing and harnessing updated polyketide synthase modules through combinatorial engineering.

The modular nature of polyketide assembly lines and the significance of their products make them prime targets for combinatorial engineering. The recently updated module boundary has been successful for engineering short synthases, yet larger synthases constructed using the updated boundary have not been investigated. Here we describe our design and implementation of a BioBricks-like platform to rapidly construct 5 triketide, 25 tetraketide, and 125 pentaketide synthases to test every module combination of the pikromycin synthase. Anticipated products are detected from 60% of the triketide synthases, 32% of the tetraketide synthases, and 6.4% of the pentaketide synthases. We determine ketosynthase gatekeeping and module-skipping are the principal impediments to obtaining functional synthases. The platform is also employed to construct active hybrid synthases by incorporating modules from the erythromycin, spinosyn, and rapamycin assembly lines. The relaxed gatekeeping of a ketosynthase in the rapamycin synthase is especially encouraging in the quest to produce designer polyketides.

[Occurrence and environmental risks of antibiotics in surface water of China].

Antibiotics as emerging pollutants are frequently detected in surface water, raising concerns about the associated risk of antibiotic resistance genes (ARGs). Despite the widespread apprehension, there are still research gaps in the occurrence of antibiotic pollution in surface water and the associated ecological risks to aquatic organisms in China. Here, we established a dataset of antibiotic pollution in surface water in China during 2018-2022, which encompassed 3 368 concentration values of 128 antibiotics reported in 124 articles. Our analysis showed that antibiotic concentrations were predominantly in the ng/L-µg/L range, reaching up to 26 µg/L. Notably, sulfonamides (e.g., sulfamethoxazole) and quinolones (e.g., ciprofloxacin) were frequently reported at high concentrations. The pollution degree of antibiotics represented by sulfamethoxazole, ciprofloxacin, roxithromycin, and tetracycline exhibited no significant variation across different years but was lower in summer than that in spring and autumn. Additionally, distinct spatial distribution characteristics of the pollution were observed. According to calculation results of the aquatic ecological risk assessment model and the weighted frequency, we proposed a list of priority antibiotics including clarithromycin, erythromycin, sulfamethoxazole, ofloxacin, and oxytetracycline in surface water. Last but not least, this study points out the deficiencies in current research on the occurrence and ecological risks of antibiotics in surface water of China and provides viable screening strategies and monitoring recommendations in this context.

Tracking trends in the Top End: clindamycin and erythromycin resistance in Group A Streptococcus in the Northern Territory, 2012-2023.

Abstract: This retrospective study reviewed the macrolide resistance rates of Group A Streptococcus (GAS) isolates in the Northern Territory from 2012 to 2023. Clindamycin and erythromycin resistance rates peaked in 2021, at 6.0% and 12.2% respectively, and then returned to near baseline at 1-2% in 2023. Increased resistance rates were identified in the Top End of Australia from mid-2020, followed 15 months later by high rates in central Australia in 2022. Factors associated with resistant isolates were living in a rural region and of age 18 years and older. Possible explanations include a transient clonal introduction of a resistant GAS strain to the Northern Territory from 2020 to 2022. Ongoing surveillance is required to monitor regional trends and identify temporal variations in resistant isolates.

A phase II, multicenter, nonblinded, randomized controlled trial for evaluating protective effects of ABPC/SBT plus, azithromycin versus erythromycin, in pregnant women with pPROM occurring at <28 weeks of gestation on the development of BPD in neonates: Study protocol.

This is a protocol for PPROM-AZM Study, phase II, nonblinded, randomized controlled trial. Bronchopulmonary dysplasia (BPD) at a postmenstrual age of 36 weeks (BPD36) is often observed in infants with preterm premature rupture of the membranes (pPROM). A regimen of ampicillin (ABPC) intravenous infusion for 2 days and subsequent amoxicillin (AMPC) oral administration for 5 days plus erythromycin (EM) intravenous infusion for 2 days followed by EM oral administration for 5 days is standard treatment for pPROM. However, the effect on the prevention of moderate/severe BPD36 using the standard treatment has not been confirmed. Recently, it is reported that ampicillin/sulbactam (ABPC/SBT) plus azithromycin (AZM) was effective for the prevention of moderate/severe BPD36 in pPROM patients with amniotic infection of Ureaplasma species. Therefore, our aim is to evaluate the occurrence rate of the composite outcome of "incidence rate of either moderate/severe BPD36 or intrauterine fetal death, and infantile death at or less than 36 weeks 0 days" comparing subjects to receive ABPC/SBT for 14 days plus AZM for 14 days (intervention group) and those to receive ABPC/SBT for 14 days plus EM for 14 days (control group), in a total of 100 subjects (women with pPROM occurring at 22-27 weeks of gestation) in Japan. The recruit of subjects was started on April 2022, and collection in on-going. We also investigate the association between the detection of Ureaplasma species and occurrence of BPD36. In addition, information on any adverse events for the mother and fetus and serious adverse events for infants are collected during the observation period. We allocate patients at a rate of 1:1 considering two stratification factors: onset of pPROM (22-23 or 24-27 weeks) and presence/absence of a hospital policy for early neonatal administration of caffeine. Trial registration: The trial number in the Japan Registry of Clinical Trials is jRCTs031210631.

Machine learning-based classification reveals distinct clusters of non-coding genomic allelic variations associated with Erm-mediated antibiotic resistance.

The erythromycin resistance RNA methyltransferase (erm) confers cross-resistance to all therapeutically important macrolides, lincosamides, and streptogramins (MLS phenotype). The expression of erm is often induced by the macrolide-mediated ribosome stalling in the upstream co-transcribed leader sequence, thereby triggering a conformational switch of the intergenic RNA hairpins to allow the translational initiation of erm. We investigated the evolutionary emergence of the upstream erm regulatory elements and the impact of allelic variation on erm expression and the MLS phenotype. Through systematic profiling of the upstream regulatory sequences across all known erm operons, we observed that specific erm subfamilies, such as ermB and ermC, have independently evolved distinct configurations of small upstream ORFs and palindromic repeats. A population-wide genomic analysis of the upstream ermB regions revealed substantial non-random allelic variation at numerous positions. Utilizing machine learning-based classification coupled with RNA structure modeling, we found that many alleles cooperatively influence the stability of alternative RNA hairpin structures formed by the palindromic repeats, which, in turn, affects the inducibility of ermB expression and MLS phenotypes. Subsequent experimental validation of 11 randomly selected variants demonstrated an impressive 91% accuracy in predicting MLS phenotypes. Furthermore, we uncovered a mixed distribution of MLS-sensitive and MLS-resistant ermB loci within the evolutionary tree, indicating repeated and independent evolution of MLS resistance. Taken together, this study not only elucidates the evolutionary processes driving the emergence and development of MLS resistance but also highlights the potential of using non-coding genomic allele data to predict antibiotic resistance phenotypes. IMPORTANCE: Antibiotic resistance (AR) poses a global health threat as the efficacy of available antibiotics has rapidly eroded due to the widespread transmission of AR genes. Using Erm-dependent MLS resistance as a model, this study highlights the significance of non-coding genomic allelic variations. Through a comprehensive analysis of upstream regulatory elements within the erm family, we elucidated the evolutionary emergence and development of AR mechanisms. Leveraging population-wide machine learning (ML)-based genomic analysis, we transformed substantial non-random allelic variations into discernible clusters of elements, enabling precise prediction of MLS phenotypes from non-coding regions. These findings offer deeper insight into AR evolution and demonstrate the potential of harnessing non-coding genomic allele data for accurately predicting AR phenotypes.

Therapeutic Efficacy of an Erythromycin-Loaded Coaxial Nanofiber Coating in a Rat Model of S. aureus-Induced Periprosthetic Joint Infection.

Implant surface nanofiber (NF) coatings represent an alternative way to prevent/treat periprosthetic joint infection (PJI) via local drug release. We developed and characterized a coaxial erythromycin (EM)-doped PLGA/PCL-PVA NF coating. The purpose of this study was to determine the efficacy of EM-NF coatings (EM0, no EM, EM100 (100 mg/mL), and EM1000 (1000 mg/mL) wt/wt) in a rat PJI model. A strong bond of the EM-NF coating to the surface of titanium (Ti) pins was confirmed by in vitro mechanical testing. Micro-computed tomography (mCT) analysis showed that both EM100 and EM1000 NF effectively reduced periprosthetic osteolysis compared to EM0 at 8 and 16 weeks after implantation. Histology showed that EM100 and EM1000 coatings effectively controlled infection and enhanced periprosthetic new bone formation. The bone implant contact (BIC) of EM100 (35.08%) was higher than negative controls and EM0 (3.43% and 0%, respectively). The bone area fraction occupancy (BAFO) of EM100 (0.63 mm2) was greater than controls and EM0 (0.390 mm2 and 0.0 mm2, respectively). The BAFO of EM100 was higher than that of EM1000 (0.3 mm2). These findings may provide a basis for a new implant surface fabrication strategy aimed at reducing the risks of defective osseointegration and PJI.

Activated carbon adsorption for mitigating the harmful effects of antibiotics on the biological activated sludge: Effect on heterotrophic kinetics through respirometry.

Conventional wastewater treatment plants (WWTPs) are not designed for the abatement of antibiotics, and their effluents are one of the main entry ways of these emerging contaminants to the aquatic environment, causing major concern due to their toxicity, persistence, and bioaccumulation. When wastewater containing antibiotics enters the bioreactor, they can impact microbial communities of the activated sludge, affecting biodegradation processes of organic matter and nutrients. There is scarce information about the effect of activated carbon on the activated sludge within the bioreactor in presence of antibiotics. In light of this, the effect of representative antibiotics, ciprofloxacin (CIP), nalidixic acid (NAL), and erythromycin (ERY), on the performance of a conventional activated sludge of a WWTP was analyzed by respirometry with and without activated carbon. NAL and ERY negatively affected the net heterotrophic biomass growth rate (r'x,H), with reduction percentages of 26%-90% and 31%-81%, respectively. The addition of activated carbon mitigated this effect, especially for ERY, with increments of even 8% in the r'x,H for the hybrid process when working with 5 ppm of ERY and 80 ppm of activated carbon compared with the value in the absence of antibiotic and activated carbon. This effect was attributed to the enhanced retention of ERY, in comparison to NAL, on the surface of the activated carbon, probably due to its higher molecular size and affinity towards the activated carbon (log Kow = 3.06). This effect was more marked at low sludge retention times (below 8 days). PRACTITIONER POINTS: Ciprofloxacin (CIP), nalidixic acid (NAL), and erythromycin (ERY) were studied. NAL and ERY exerted negative impact on heterotrophic growth rate. Effect of antibiotics on microorganisms in the presence of activated carbon was studied. Activated carbon was mainly relevant for ERY due to its adsorption retention. Enhancement by activated carbon was more significant at low sludge retention times.

CRISPR/Cas9-Mediated Promoter Engineering in Saccharopolyspora erythraea.

In situ promoter engineering is an effective way to alter target gene expression without introducing excess DNA sequences. Recently, the CRISPR/Cas9 technologies have been proved to be efficient tools for genome editing in actinomycetes, making it easier and more efficient to perform gene insertion and substitution in actinomycetes in a scarless manner. In this chapter, we describe a routine protocol for CRISPR/Cas9-mediated promoter engineering in Saccharopolyspora erythraea NRRL 23338, which is the wild-type producer of erythromycin. This protocol can be adapted to CRISPR/Cas9-mediated gene editing, not limited to promoter engineering, in other actinomycetes, with modifications.

Implementation of temporal moments to elucidate the reactive transport of metformin and erythromycin in the saturated porous media.

This study investigates the fate and transport dynamics of metformin (MTN) and erythromycin (ETM), both classified as pharmaceutical and personal care products (PPCPs), in a saturated sandy soil column using temporal moment analysis (TMA). The key flow and transport parameters, including Darcy velocity, longitudinal dispersivity, adsorption, and degradation coefficients, were analyzed. The results reveal that MTN, a highly mobile contaminant, is eliminated from the column in approximately 40 days, while ETM shows significant adsorption due to its hydrophobic and adsorptive nature. Darcy velocity significantly affects PPCP transport; a one-order magnitude change alters contaminant mass recovery at the column outlet by 88% for MTN and 39-fold for ETM. Longitudinal dispersivity has minimal impact on the transport of PPCPs. However adsorption primarily governs the fate of PPCPs with high adsorption coefficients (Kd), and degradation rates control the fate of low-sorbing PPCPs. A one-order magnitude change in Kd results in a 55% change in the zeroth temporal moment (ZTM) of MTN and a 30-fold change in the case of ETM. Additionally, a one-order magnitude change in the degradation coefficient leads to a 60% variation in MTN's ZTM and a 5% variation in ETM's ZTM. Thus, TMA is a valuable tool for understanding PPCP dynamics in subsurface environments, providing critical insights for managing their increasing concentrations.

Effect of erythromycin residuals in food on the development of resistance in Streptococcus pneumoniae: an in vivo study in Galleria mellonella.

Background: The use of antimicrobials to treat food animals may result in antimicrobial residues in foodstuffs of animal origin. The European Medicines Association (EMA) and World Health Organization (WHO) define safe antimicrobial concentrations in food based on acceptable daily intakes (ADIs). It is unknown if ADI doses of antimicrobials in food could influence the antimicrobial susceptibility of human-associated bacteria. Objectives: This aim of this study was to evaluate if the consumption of ADI doses of erythromycin could select for erythromycin resistance in a Galleria mellonella model of Streptococcus pneumoniae infection. Methods: A chronic model of S. pneumoniae infection in G. mellonella larvae was used for the experiment. Inoculation of larvae with S. pneumoniae was followed by injections of erythromycin ADI doses (0.0875 and 0.012 µg/ml according to EMA and WHO, respectively). Isolation of S. pneumoniae colonies was then performed on selective agar plates. Minimum inhibitory concentrations (MICs) of resistant colonies were measured, and whole genome sequencing (WGS) was performed followed by variant calling to determine the genetic modifications. Results: Exposure to single doses of both EMA and WHO ADI doses of erythromycin resulted in the emergence of erythromycin resistance in S. pneumoniae. Emergent resistance to erythromycin was associated with a mutation in rplA, which codes for the L1 ribosomal protein and has been linked to macrolide resistance in previous studies. Conclusion: In our in vivo model, even single doses of erythromycin that are classified as acceptable by the WHO and EMA induced significant increases in erythromycin MICs in S. pneumoniae. These results suggest the need to include the induction of antimicrobial resistance (AMR) as a significant criterion for determining ADIs.

Effects of quorum sensing-interfering agents, including macrolides and furanone C-30, and an efflux pump inhibitor on nitrosative stress sensitivity in Pseudomonas aeruginosa.

Long-term administration of certain macrolides is efficacious in patients with persistent pulmonary Pseudomonas aeruginosa infection, despite how limited the clinically achievable concentrations are, being far below their MICs. An increase in the sub-MIC of macrolide exposure-dependent sensitivity to nitrosative stress is a typical characteristic of P. aeruginosa. However, a few P. aeruginosa clinical isolates do not respond to sub-MIC of macrolide treatment. Therefore, we examined the effects of sub-MIC of erythromycin (EM) on the sensitivity to nitrosative stress together with an efflux pump inhibitor (EPI) phenylalanine arginyl ß-naphthylamide (PAßN). The sensitivity to nitrosative stress increased, suggesting that the efflux pump was involved in inhibiting the sub-MIC of macrolide effect. Analysis using efflux pump-mutant P. aeruginosa revealed that MexAB-OprM, MexXY-OprM, and MexCD-OprJ are factors in reducing the sub-MIC of macrolide effect. Since macrolides interfere with quorum sensing (QS), we demonstrated that the QS-interfering agent furanone C-30 (C-30) producing greater sensitivity to nitric oxide (NO) stress than EM. The effect of C-30 was decreased by overproduction of MexAB-OprM. To investigate whether the increase in the QS-interfering agent exposure-dependent sensitivity to nitrosative stress is characteristic of P. aeruginosa clinical isolates, we examined the viability of P. aeruginosa treated with NO. Although treatment with EM could reduce cell viability, a high variability in EM effects was observed. Conversely, C-30 was highly effective at reducing cell viability. Treatment with both C-30 and PAßN was sufficiently effective against the remaining isolates. Therefore, the combination of a QS-interfering agent and an EPI could be effective in treating P. aeruginosa infections.

Enhancing erythromycin production in Saccharopolyspora erythraea through rational engineering and fermentation refinement: A Design-Build-Test-Learn approach.

Industrial production of bioactive compounds from actinobacteria, such as erythromycin and its derivatives, faces challenges in achieving optimal yields. To this end, the Design-Build-Test-Learn (DBTL) framework, a systematic metabolic engineering approach, was employed to enhance erythromycin production in Saccharopolyspora erythraea (S. erythraea) E3 strain. A genetically modified strain, S. erythraea E3-CymRP21-dcas9-sucC (S. erythraea CS), was developed by suppressing the sucC gene using an inducible promoter and dcas9 protein. The strain exhibited improved erythromycin synthesis, attributed to enhanced precursor synthesis and increased NADPH availability. Transcriptomic and metabolomic analyses revealed altered central carbon metabolism, amino acid metabolism, energy metabolism, and co-factor/vitamin metabolism in CS. Augmented amino acid metabolism led to nitrogen depletion, potentially causing cellular autolysis during later fermentation stages. By refining the fermentation process through ammonium sulfate supplementation, erythromycin yield reached 1125.66 mg L-1, a 43.5% increase. The results demonstrate the power of the DBTL methodology in optimizing erythromycin production, shedding light on its potential for revolutionizing antibiotic manufacturing in response to the global challenge of antibiotic resistance.

Acute exposure and biomarkers assessment in rainbow trout exposed to selected pharmaceuticals.

Pharmaceuticals released from municipal effluents discharges pose a risk to aquatic organisms. The toxicity of 5 pharmaceuticals with distinct therapeutic actions were assessed in rainbow trout: olanzapine (antipsychotic), erythromycin (antibiotic), mycophenoate (immunosuppression), pinaverium (anti-inflammatory) and trazodone (sedative). Juveniles were exposed to these drugs for 96 h at concentrations between 64 µg/L up to 40 mg/L to reach lethality. Survival was determined and a suite of biomarkers was analyzed for drug biotransformation, oxidative stress/damage and metabolic activity at sublethal concentrations. The data revealed the following toxicity: olanzapine >trazodone>mycophenolate>pinaverium∼erythromycin based on mortality. The data also revealed that toxicity was associated to mass, pKa and hydrophobicity and the following sublethal effects: GST, LPO and DNA strand breaks. Pharmaceuticals with lower molecular weight, physiological pKa, moderate hydrophobicity, low biotransformation and DNA strand breaks were generally more toxic to fish. However, this should be considered as a general guide in identifying toxic pharmaceuticals in non-target organisms.

A novel 12-membered ring non-antibiotic macrolide EM982 attenuates cytokine production by inhibiting IKKß and IκBα phosphorylation.

Antimicrobial resistance poses a serious threat to human health worldwide and its incidence continues to increase owing to the overuse of antibiotics and other factors. Macrolide antibiotics such as erythromycin (EM) have immunomodulatory effects in addition to their antibacterial activity. Long-term, low-dose administration of macrolides has shown clinical benefits in treating non-infectious inflammatory respiratory diseases. However, this practice may also increase the emergence of drug-resistant bacteria. In this study, we synthesized a series of EM derivatives, and screened them for two criteria: (i) lack of antibacterial activity and (ii) ability to suppress tumor necrosis factor-α (TNF-α) production in THP-1 cells stimulated with lipopolysaccharide. Among the 37 synthesized derivatives, we identified a novel 12-membered ring macrolide EM982 that lacked antibacterial activity against Staphylococcus aureus and suppressed the production of TNF-α and other cytokines. The effects of EM982 on Toll-like receptor 4 (TLR4) signaling were analyzed using a reporter assay and Western blotting. The reporter assay showed that EM982 suppressed the activation of transcription factors, NF-κB and/or activator protein 1 (AP-1), in HEK293 cells expressing human TLR4. Western blotting showed that EM982 inhibited the phosphorylation of both IκB kinase (IKK) ß and IκBα, which function upstream of NF-κB, whereas it did not affect the phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and c-Jun N-terminal kinase, which act upstream of AP-1. These results suggest that EM982 suppresses cytokine production by inhibiting phosphorylation of IKKß and IκBα, resulting in the inactivation of NF-κB.

Can we use azithromycin eye drops for gonococcal ophthalmia prophylaxis in the United States?

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

A non-antibiotic erythromycin derivative improves muscle endurance by regulating endogenous anti-fatigue protein orosomucoid in mice.

At present, there are no official approved drugs for improving muscle endurance. Our previous research found acute phase protein orosomucoid (ORM) is an endogenous anti-fatigue protein, and macrolides antibiotics erythromycin can elevate ORM level to increase muscle bioenergetics and endurance parameters. Here, we further designed, synthesized and screened a new erythromycin derivative named HMS-01, which lost its antibacterial activity in vitro and in vivo. Data showed that HMS-01 could time- and dose-dependently prolong mice forced-swimming time and running time, and improve fatigue index in isolated soleus muscle. Moreover, HMS-01 treatment could increase the glycogen content, mitochondria number and function in liver and skeletal muscle, as well as ORM level in these tissues and sera. In Orm-deficient mice, the anti-fatigue and glycogen-elevation activity of HMS-01 disappeared. Therefore, HMS-01 might act as a promising small molecule drug targeting ORM to enhance muscle endurance.

Macrolide resistance among Streptococcus agalactiae during COVID-19 public health emergency in Brazil.

During COVID-19 public health emergence, azithromycin was excessively used in Brazil, as part of a controversial "early treatment", recommended by former national health authorities. Excessive usage of macrolides may increase resistance rates among beta-hemolytic streptococci. Therefore, this study aimed to investigate the occurrence of resistance to erythromycin and clindamycin among Streptococcus agalactiae recovered from February 2020 to May 2023. Bacterial isolates (n = 116) were obtained from pregnant women and submitted to antimicrobial susceptibility testing, investigation of macrolide resistance phenotypes and genotypes, and identification of capsular type. The overall rate of erythromycin not susceptible (NS) isolates was 25.9%, while resistance to clindamycin was 5.2%. Drug efflux, associated with the M phenotype and mef(A) gene, was the prevalent mechanism of resistance (80%). Capsular type Ia was predominant (39.8%), followed by II, III, and V (17.7% each). A higher diversity of types was observed in the last years of the study. Type IV has had an increasing trend over time, being the fourth most common in 2023. The majority of the isolates that expressed the M phenotype presented capsular type Ia, while those with iMLS phenotype presented capsular type V. Despite no causal relationship can be established, azithromycin excessive usage may be a possible factor associated with this higher rate of erythromycin NS isolates, compared with most previous national studies. On the other hand, resistance to clindamycin has not changed significantly. Therefore, in the studied clinical setting, clindamycin remains a useful alternative to intrapartum prophylaxis among penicillin-allergic pregnant women.

Chronic toxic effects of erythromycin and its photodegradation products on microalgae Chlorella pyrenoidosa.

The photodegradation products (PDPs) of antibiotics in the aquatic environment received increasing concern, but their chronic effects on microalgae remain unclear. This study initially focused on examining the acute effects of erythromycin (ERY), then explored the chronic impacts of ERY PDPs on Chlorella pyrenoidosa. ERY of 4.0 - 32 mg/L ERY notably inhibited the cell growth and chlorophyll synthesis. The determined 96 h median effective concentration of ERY to C. pyrenoidosa was 11.78 mg/L. Higher concentrations of ERY induced more serious oxidative damage, antioxidant enzymes alleviated the oxidative stress. 6 PDPs (PDP749, PDP747, PDP719, PDP715, PDP701 and PDP557) were identified in the photodegradation process of ERY. The predicted combined toxicity of PDPs increased in the first 3 h, then decreased. Chronic exposure showed a gradual decreasing inhibition on microalgae growth and chlorophyll content. The acute effect of ERY PDPs manifested as growth stimulation, but the chronic effect manifested as growth inhibition. The malonaldehyde contents decreased with the degradation time of ERY at 7, 14 and 21 d. However, the malonaldehyde contents of ERY PDPs treatments were elevated compared to those in the control group after 21 d. Risk assessment still need to consider the potential toxicity of degradation products under long-term exposure.