In vitro activity of fidaxomicin and combinations of fidaxomicin with other antibiotics against Clostridium perfringens strains isolated from dogs and cats.

BACKGROUND: Previous studies have demonstrated that fidaxomicin, a macrocyclic lactone antibiotic used to treat recurrent Clostridioides difficile-associated diarrhea, also displays potent in vitro bactericidal activity against Clostridium perfringens strains isolated from humans. However, to date, there is no data on the susceptibility to fidaxomicin of C. perfringens strains of animal origin. On the other hand, although combination therapy has become popular in human and veterinary medicine, limited data are available on the effects of antibiotic combinations on C. perfringens. We studied the in vitro response of 21 C. perfringens strains obtained from dogs and cats to fidaxomicin and combinations of fidaxomicin with six other antibiotics. RESULTS: When tested by an agar dilution method, fidaxomicin minimum inhibitory concentrations (MICs) ranged between 0.004 and 0.032 µg/ml. Moreover, the results of Etest-based combination assays revealed that the incorporation of fidaxomicin into the test medium at a concentration equivalent to half the MIC significantly increased the susceptibility of isolates to metronidazole and erythromycin in 71.4% and 61.9% of the strains, respectively, and the susceptibility to clindamycin, imipenem, levofloxacin, and vancomycin in 42.9-52.4% of the strains. In contrast, » × MIC concentrations of fidaxomicin did not have any effect on levofloxacin and vancomycin MICs and only enhanced the effects of clindamycin, erythromycin, imipenem, and metronidazole in ≤ 23.8% of the tested strains. CONCLUSIONS: The results of this study demonstrate that fidaxomicin is highly effective against C. perfringens strains of canine and feline origin. Although fidaxomicin is currently considered a critically important antimicrobial that has not yet been licensed for veterinary use, we consider that the results reported in this paper provide useful baseline data to track the possible emergence of fidaxomicin resistant strains of C. perfringens in the veterinary setting.

[Prevalence and Antimicrobial Resistance of Campylobacter jejuni/coli and Analysis of Macrolide Resistance Isolates from Retail Meat in Tokyo, Japan (2010-2019)].

This study aimed to investigate the prevalence and antimicrobial sensitivity of Campylobacter jejuni and Campylobacter coli in retail meat (chicken, beef, pork, venison, wild boar, horse, lamb and mutton) in Tokyo (Japan) from 2010 to 2019. Furthermore, the resistance mechanism of erythromycin (EM)-resistant strains was analysed. C. jejuni had a highly positive rate in domestic chicken meat (53.4%, 334/626 samples), domestic chicken offal (49.3%, 34/69 samples), and domestic beef offal (28.3%, 47/166 samples), while C. coli had a high positivity rate in domestic pork offal (31.7%, 44/139 samples). The positive rate of C. jejuni was significantly higher in offal than that in meat in domestic beef, while the positive rate of C. coli was significantly higher in offal than that in meat in domestic beef and domestic pork (p<0.05). In the isolates, 1.0% (6/631 strains) of C. jejuni and 36.2% (55/152 strains) of C. coli were EM resistant, with 41.5% (262/631 strains) of C. jejuni and 65.1% (99/152 strains) of C. coli being ciprofloxacin resistant. A2075G mutation of the 23S rRNA gene was confirmed in all EM-resistant strains.

[Evolution of the serotypes causing invasive pneumococcal disease along 2008-2022 in a Level 2 Public Hospital of the Madrid Region, in relation to their inclusion in different conjugate vaccines]. / Evolución de los serotipos causantes de enfermedad neumocócica invasiva aislados durante 2008-2022 en un Hospital Público Madrileño de nivel dos, en relación con su inclusión en diferentes vacunas conjugadas.

OBJECTIVE: The use of conjugate vaccines against Streptococcus pneumoniae originates changes in the invasive pneumococcal disease (IPD). The aim of this study was to in vestigate the evolution of S. pneumoniae serotypes isolated in the Hospital Universitario de Getafe between 2008 and 2022. METHODS: 313 of S. pneumoniae strains were studied. Serotyping was carried out by latex agglutination (Pneumotest-latex) and the Quellung reaction. In addition, the minimal inhibitory concentration (MIC) was determined against penicillin, erythromycin and levofloxacin by the concentration gradient method (E-test) according the EUCAST breakpoints. RESULTS: The most frequent serotypes throughout the study period were 8, 3, 19A, 1, 11A and 22F corresponding to 46.6% of the isolates. Along 2008-2012 the serotypes 3, 1, 19A, 7F, 6C and 11A represented altogether 53.6% of the isolates. Between 2013 and 2017 the serotypes 3, 8, 12F, 19A, 22F and 19F grouped 51% of the isolates. During 2018-2022 the serotypes 8, 3, 11A, 15A, 4 and 6C included the 55.5% of the cases. In total 5 strains (1.6%) were penicillin resistant, 64 (20.4%) erythromycin resistant and 11 (3.5%) levofloxacin resistant. The MIC50 and MIC90 levels maintained stables along the time. CONCLUSIONS: The conjugate vaccines use with different serotype coverage conditioned a decrease of the vaccine-included and an increase of non-covered. Despite these changes, the global antimicrobial susceptibility patterns to erythromycin and levofloxacin maintained relatively stables. The resistance a penicillin was low, not finding this type of resistant strains in the last study period.

Modular Drug-Loaded Nanocapsules with Metal Dome Layers as a Platform for Obtaining Synergistic Therapeutic Biological Activities.

Multifunctional drug-loaded polymer-metal nanocapsules have attracted increasing attention in drug delivery due to their multifunctional potential endowed by drug activity and response to physicochemical stimuli. Current chemical synthesis methods of polymer/metal capsules require specific optimization of the different components to produce particles with precise properties, being particularly complex for Janus structures combining polymers and ferromagnetic and highly reactive metals. With the aim to generate tunable synergistic nanotherapeutic actuation with enhanced drug effects, here we demonstrate a versatile hybrid chemical/physical fabrication strategy to incorporate different functional metals with tailored magnetic, optical, or chemical properties on solid drug-loaded polymer nanoparticles. As archetypical examples, we present poly(lactic-co-glycolic acid) (PLGA) nanoparticles (diameters 100-150 nm) loaded with paclitaxel, indocyanine green, or erythromycin that are half-capped by either Fe, Au, or Cu layers, respectively, with application in three biomedical models. The Fe coating on paclitaxel-loaded nanocapsules permitted efficient magnetic enhancement of the cancer spheroid assembly, with 40% reduction of the cross-section area after 24 h, as well as a higher paclitaxel effect. In addition, the Fe-PLGA nanocapsules enabled external contactless manipulation of multicellular cancer spheroids with a speed of 150 µm/s. The Au-coated and indocyanine green-loaded nanocapsules demonstrated theranostic potential and enhanced anticancer activity in vitro and in vivo due to noninvasive fluorescence imaging with long penetration near-infrared (NIR) light and simultaneous photothermal-photodynamic actuation, showing a 3.5-fold reduction in the tumor volume growth with only 5 min of NIR illumination. Finally, the Cu-coated erythromycin-loaded nanocapsules exhibited enhanced antibacterial activity with a 2.5-fold reduction in the MIC50 concentration with respect to the free or encapsulated drug. Altogether, this technology can extend a nearly unlimited combination of metals, polymers, and drugs, thus enabling the integration of magnetic, optical, and electrochemical properties in drug-loaded nanoparticles to externally control and improve a wide range of biomedical applications.

Pathognomonic features of Pasteurella multocida isolates among various avian species in Sharkia Governorate, Egypt.

The present study aimed to isolate Pasteurella multocida (P. multocida) from pulmonary cases in several avian species and then investigate the histopathological features, antimicrobial resistance determinants, virulence characteristics, and risk factors analysis of the isolates in each species in correlation with epidemiological mapping of pasteurellosis in Sharkia Governorate, Egypt. The obtained data revealed a total occurrence of 9.4% (30/317) of P. multocida among the examined birds (chickens, ducks, quails, and turkeys). The incidence rate was influenced by avian species, climate, breed, age, clinical signs, and sample type. Antimicrobial susceptibility testing revealed that all isolates were sensitive to florfenicol and enrofloxacin, while 86.6 and 73.3% of the isolates displayed resistance to amoxicillin-clavulanic acid and erythromycin, respectively. All of the P. multocida isolates showed a multiple-drug resistant pattern with an average index of 0.43. Molecular characterization revealed that the oma87, sodA, and ptfA virulence genes were detected in the all examined P. multocida isolates. The ermX (erythromycin), blaROB-1 (ß-lactam), and mcr-1(colistin) resistance genes were present in 60, 46.6, and 40% of the isolates, respectively. Ducks and quails were the most virulent and harbored species of antimicrobial-resistant genes. These results were in parallel with postmortem and histopathological examinations which detected more severe interstitial pneumonia lesions in the trachea and lung, congestion, and cellular infiltration especially in ducks. Epidemiological mapping revealed that the Fakous district was the most susceptible to pasteurellosis infection. Thus, farmers are recommended to monitor their flocks for signs of respiratory disease, seek veterinary care promptly if any birds are sick, and avoid the random usage of antibiotics. In conclusion, this study presents a comprehensive picture of the risk factors in correlation to the pathognomonic characteristics of P. multocida infection in poultry sectors to help in developing more effective strategies for prevention and control.

Antimicrobial resistance of Streptococcus uberis isolated from bovine mastitis: Systematic review and meta-analysis.

Streptococcus uberis is one of the most common pathogens associated with bovine mastitis, commonly treated with antimicrobials (AM), favoring the appearance of antimicrobial resistance (AMR). The objective of this work was to determine the proportion of phenotypic AMR among S. uberis isolated worldwide from bovine intramammary infections between the years 1983-2022, and to assess the variables associated by means of a systematic review and metanalysis. Sixty articles were eligible for quantitative review. Ninety-four independent studies were obtained. The antimicrobials evaluated in more S. uberis strains were penicillin (21,987 strains), oxacillin (21,727 strains), erythromycin (20,013 strains), and ampicillin (19,354 strains). Most of the studies included in this meta-analysis were from Europe (44), followed by America (25), Africa (10), Asia (10), and Oceania (5). Among the included articles, 22 were published from 1983 to 2006, 23 from 2007 to 2012, 25 from 2013 to 2015, and the remaining 24 after 2016. Penicillin, erythromycin, and tetracycline were the antimicrobials with >25 studies. Therefore, the following analyses were performed only for these antimicrobials, presenting a high heterogeneity index (I2). The variability observed for penicillin and tetracycline was only explained, partially, by continent of origin. The variability observed for erythromycin was not explained by any of the potential explanatory variables included in this study. The S. uberis proportion of resistance to antimicrobials is highly variable and probably influenced by many factors other than those studied in this meta-analysis, where it was not possible to inform a unique average proportion of resistance.

[Prevalence and Characteristics of Campylobacter and Salmonella in Meat Derived from Spent Hens].

Meat derived from spent hens as well as broilers is destined for human consumption. There are many reports on the prevalence and antimicrobial resistance of Campylobacter and Salmonella in broiler meat, but few in spent hen meat. Therefore, we investigated the prevalence and antimicrobial resistance of these genera in spent hen meat collected at chicken processing plants. Campylobacter and Salmonella were isolated from 47 (92.2%) and 18 (35.5%), respectively, of breast meat derived from 51 spent hen flocks. Campylobacter jejuni accounted for 87.5% of Campylobacter isolates. The highest resistant rate in C. jejuni isolates was found for ampicillin (45.3%), followed by tetracycline (14.3%) and ciprofloxacin (14.3%). There was no Campylobacter isolate resistant to erythromycin, which is recommended as a first-choice antimicrobial for humans when Campylobacter enteritis is strongly suspected. Of Salmonella isolates, the first and second most frequent serovars were Salmonella Corvallis (30.4%) and S. Braenderup (21.7%), respectively. Of Salmonella isolates, 30.4% were resistant to streptomycin. There was no Salmonella isolate resistant to ciprofloxacin, which is one of the recommended antimicrobials for humans against Salmonella enteritis. This study shows that one third of spent hen meat is contaminated with Campylobacter or Salmonella, and administration of erythromycin or cefotaxime is an effective option for patients with Campylobacter- or Salmonella- enteritis, respectively, caused by consumption of spent hen meat.

Prevalence of erythromycin-resistant emm92-type invasive group A streptococcal infections among injection drug users in West Virginia, United States, 2021-23.

BACKGROUND: Increasing incidence of invasive group A Streptococcus (iGAS) disease has been reported in Europe and the USA over the past several years. Coupled with this are observations of higher rates of resistance to erythromycin and clindamycin. OBJECTIVES: To characterize iGAS and pharyngitis isolates from West Virginia (WV), a US state outside of the national Active Bacteria Core surveillance purview, where risk factors associated with iGAS infections are prevalent. METHODS: Seventy-seven invasive group A Streptococcus isolates were collected from 67 unique patients at the J.W. Ruby Memorial Hospital Clinical Microbiology Laboratory in WV from 2021 to 2023. Invasive isolates and 20 unique pharyngitis isolates were tested for clindamycin and erythromycin susceptibility in the clinical laboratory. Patient demographic and clinical information was retrieved from patient electronic health records. Isolates were further characterized based on emm subtype and detection of MLSB resistance determinants. RESULTS: Twenty-six (39%) isolates were of a single emm92 type. All emm92 isolates were uniformly erythromycin/clindamycin resistant with inducible or constitutive MLSB resistance imparted by the plasmid-borne erm(T) gene. The majority of emm92 infections were associated with adult patients who reported IV drug use, whereas no pharyngitis infections were caused by an emm92 strain. Overall, 51 (76%) of the 67 iGAS isolates were determined to carry MLSB resistance. CONCLUSIONS: Isolates of emm92 type (clonal subtype emm92.0) were associated with iGAS infections in adult IV drug users, but not with paediatric pharyngitis, and were uniformly resistant to erythromycin and clindamycin.

Effect of veterinary feed directive rule changes on tetracycline-resistant and erythromycin-resistant bacteria (Salmonella, Escherichia, and Campylobacter) in retail meats in the United States.

BACKGROUND: Antimicrobial-resistant bacteria are a growing public health threat. In 2017 the U.S. Food and Drug Administration implemented Veterinary Feed Directive (VFD) rules changes to limit medically important antimicrobial use in food-producing animals, combating antimicrobial-resistant bacteria. The effect of the VFD rule changes on the occurrence of bacteria resistant to medically-important antimicrobials in retail meats is yet to be investigated in the U.S. This study investigates whether the VFD rule changes affected the occurrence of tetracycline-resistant and erythromycin-resistant bacteria (Salmonella, Escherichia, and Campylobacter) in retail meats in the U.S. METHODS: Multivariable mixed effect logistic regression models were used to analyze 2002-2019 retail meats surveillance data from the National Antimicrobial Resistance Monitoring System (NARMS) in the U.S. Variables included VFD rule changes, meat type, quarter of year, and raising claims. A potential association between these variables and the occurrence of tetracycline-resistant and erythromycin-resistant bacteria (Salmonella, Escherichia, and Campylobacter) in retail meats was estimated. RESULTS: Analysis included data regarding tetracycline-resistant Salmonella (n = 8,501), Escherichia (n = 20, 283), Campylobacter (n = 9,682), and erythromycin-resistant Campylobacter (n = 10,446) in retail meats. The odds of detecting tetracycline-resistant Escherichia (OR = 0.60), Campylobacter (OR = 0.89), and erythromycin-resistant Campylobacter (OR = 0.43) in chicken breast significantly decreased after the VFD rule changes, compared to the pre-VFD rule change period. The odds of detecting tetracycline-resistant Salmonella (0.66), Escherichia (OR = 0.56), and Campylobacter (OR = 0.33) in ground turkey also significantly decreased. However, the odds of detecting tetracycline-resistant Salmonella (OR = 1.49) in chicken breast and erythromycin-resistant Campylobacter (OR = 4.63) in ground turkey significantly increased. There was no significant change in the odds of detecting tetracycline-resistant Salmonella and Escherichia in ground beef or pork chops. CONCLUSIONS: The implementation of VFD rule changes had a beneficial effect by reducing the occurrence of tetracycline-resistant and erythromycin-resistant bacteria in chicken and ground turkey. Ongoing surveillance of antimicrobial resistance and antimicrobial use could complement the implementation of stewardship such as VFD rule in food-producing animals in the U.S.

Indole-3-Acetamido-Polyamines as Antimicrobial Agents and Antibiotic Adjuvants.

The widespread incidence of antimicrobial resistance necessitates the discovery of new classes of antimicrobials as well as adjuvant molecules that can restore the action of ineffective antibiotics. Herein, we report the synthesis of a new class of indole-3-acetamido-polyamine conjugates that were evaluated for antimicrobial activities against a panel of bacteria and two fungi, and for the ability to enhance the action of doxycycline against Pseudomonas aeruginosa and erythromycin against Escherichia coli. Compounds 14b, 15b, 17c, 18a, 18b, 18d, 19b, 19e, 20c and 20d exhibited strong growth inhibition of methicillin-resistant Staphylococcus aureus (MRSA) and Cryptococcus neoformans, with minimum inhibitory concentrations (MIC) typically less than 0.2 µM. Four analogues, including a 5-bromo 15c and three 5-methoxyls 16d-f, also exhibited intrinsic activity towards E. coli. Antibiotic kill curve analysis of 15c identified it to be a bactericide. While only one derivative was found to (weakly) enhance the action of erythromycin against E. coli, three examples, including 15c, were found to be strong enhancers of the antibiotic action of doxycycline against P. aeruginosa. Collectively, these results highlight the promising potential of α,ω-disubstituted indole-3-acetamido polyamine conjugates as antimicrobials and antibiotic adjuvants.

Occurrence of antimicrobial-resistant Staphylococcus aureus in a Brazilian veterinary hospital environment.

Antimicrobial resistance is a threat to public health. The emergence of antibiotic-resistant Staphylococcus aureus represents a priority for the implementation of preventive measures. The objective was to isolate S. aureus in humans, animals, and animal health care environment, and to characterize the genotypic and phenotypic profile of antimicrobial resistance in these isolates. We isolated S. aureus from staff, animals, and environment of a veterinary hospital, and identified their antimicrobial resistance profiles. Samples were collected from 20 humans, 13 animals, 14 surfaces, 8 mobile phones, and 7 veterinarians' stethoscopes by using sterile swabs. S. aureus was isolated by culturing on mannitol salt agar and preliminary identification was done by Gram staining and catalase test. Subsequently, a polymerase chain reaction was performed for species confirmation and investigating their antimicrobial-resistant genotypic profiles. Phenotypic profiles of resistant isolates were determined using the disk-diffusion technique. Ten S. aureus isolates were recovered from 5/20 humans (25%), it was also recovered from 2/13 animals (15.38%), including 1 dog and 1 cat, and from 1/14 of surfaces (7.14%). The oxacillin-susceptible mecA-positive Staphylococcus aureus phenotype was identified in a feline. Most of the isolates carried at least two resistance genes of different antimicrobial classes, with 90% (9/10) presenting the gene blaZ, with 10% (1/10) presenting the gene mecA, 20% (2/10) presenting tet38, 10% (1/10) presenting tetM, 90% (9/10) presenting norA, 50% (5/10) presenting norC, 10% (1/10) presenting ermA, and 60% (6/10) presenting ermB. In antibiograms, resistance to penicillin was identified in all the isolates, resistance to erythromycin was identified in 80% (8/10), and all the isolate's resistance to erythromycin presented erythromycin-induced resistance to clindamycin. Antimicrobial resistance in the veterinary hospital requires attention due to the risk of interspecies transmission, gene transfer between bacteria that colonize companion animals and humans and, can make antimicrobial therapy difficult.

Mechanistic insights into Fe3O4-modified biochar relieving inhibition from erythromycin on anaerobic digestion.

Anaerobic digestion (AD) of antibiotic manufacturing wastewater to degrade residual antibiotics and produce mixture of combustible gases has been investigated actively in the past decades. However, detrimental effect of residual antibiotic to microbial activities is commonly faced in AD process, leading to the reduction of treatment efficiency and energy recovery. Herein, the present study systematically evaluated the detoxification effect and mechanism of Fe3O4-modified biochar in AD of erythromycin manufacturing wastewater. Results showed that Fe3O4-modified biochar had stimulatory effect on AD at 0.5 g/L erythromycin existence. A maximum methane yield of 327.7 ± 8.0 mL/g COD was achieved at 3.0 g/L Fe3O4-modified biochar, leading to the increase of 55.7% compared to control group. Mechanistic investigation demonstrated that different levels of Fe3O4-modified biochar could improve methane yield via different metabolic pathways involved in specific bacteria and archaea. Low levels of Fe3O4-modified biochar (i.e., 0.5-1.0 g/L) led to the enrichment of Methanothermobacter sp., strengthening the hydrogenotrophic pathway. On the contrary, high levels of Fe3O4-modified biochar (2.0-3.0 g/L) favored the proliferation of acetogens (e.g., Lentimicrobium sp.) and methanogen (Methanosarcina sp.) and their syntrophic relations played vital role on the simulated AD performance at erythromycin stress. Additionally, the addition of Fe3O4-modified biochar significantly decreased the abundance of representative antibiotic resistant genes (ARGs), benefiting the reduction of environmental risk. The results of this study verified that the application of Fe3O4-modified biochar could be an efficient approach to detoxify erythromycin on AD system, which brings high impacts and positive implications for biological antibiotic wastewater treatment.

Ammonium sulfate supplementation enhances erythromycin biosynthesis by augmenting intracellular metabolism and precursor supply in Saccharopolyspora erythraea.

In this study, the cellular metabolic mechanisms regarding ammonium sulfate supplementation on erythromycin production were investigated by employing targeted metabolomics and metabolic flux analysis. The results suggested that the addition of ammonium sulfate stimulates erythromycin biosynthesis. Targeted metabolomics analysis uncovered that the addition of ammonium sulfate during the late stage of fermentation resulted in an augmented intracellular amino acid metabolism pool, guaranteeing an ample supply of precursors for organic acids and coenzyme A-related compounds. Therefore, adequate precursors facilitated cellular maintenance and erythromycin biosynthesis. Subsequently, an optimal supplementation rate of 0.02 g/L/h was determined. The results exhibited that erythromycin titer (1311.1 µg/mL) and specific production rate (0.008 mmol/gDCW/h) were 101.3% and 41.0% higher than those of the process without ammonium sulfate supplementation, respectively. Moreover, the erythromycin A component proportion increased from 83.2% to 99.5%. Metabolic flux analysis revealed increased metabolic fluxes with the supplementation of three ammonium sulfate rates.

The Strength of hERG Inhibition by Erythromycin at Different Temperatures Might Be Due to Its Interacting Features with the Channels.

Erythromycin is one of the few compounds that remarkably increase ether-a-go-go-related gene (hERG) inhibition from room temperature (RT) to physiological temperature (PT). Understanding how erythromycin inhibits the hERG could help us to decide which compounds are needed for further studies. The whole-cell patch clamp technique was used to investigate the effects of erythromycin on hERG channels at different temperatures. While erythromycin caused a concentration-dependent inhibition of cardiac hERG channels, it also shifted the steady-state activation and steady-state inactivation of the channel to the left and significantly accelerated the onset of inactivation at both temperatures, although temperature itself caused a profound change in the dynamics of hERG channels. Our data also suggest that the binding pattern to S6 of the channels changes at PT. In contrast, cisapride, a well-known hERG blocker whose inhibition is not affected by temperature, does not change its critical binding sites after the temperature is raised to PT. Our data suggest that erythromycin is unique and that the shift in hERG inhibition may not apply to other compounds.

Erythromycin Attenuates Hyperoxia Induced Lung Injury by Enhancing GSH Expression and Inhibiting Expression of Inflammatory Cytokines.

Introduction: Oxidative stress and inflammation have proven to be key factors contributing to the occurrence of BPD. Erythromycin has been shown to be effective in treating the redox imbalance seen in many non-bacterial infectious chronic inflammatory diseases. Methods: Ninety-six premature rats were randomly divided into air + saline chloride group, air + erythromycin group, hyperoxia + saline chloride group and hyperoxia + erythromycin group. Lung tissue specimens were collected from 8 premature rats in each group on days 1, 7 and 14, respectively. Results: Pulmonary pathological changes in premature rats after hyperoxia exposure were similar to those of BPD. Hyperoxia exposure induced high expression of GSH, TNF-α, and IL-1ß. Erythromycin intervention caused a further increase in GSH expression and a decrease in TNF-α and IL-1ß expression. Conclusion: GSH, TNF-α and IL-1ß are all involved in the development of BPD. Erythromycin may alleviate BPD by enhancing the expression of GSH and inhibiting the release of inflammatory mediators.

The Impact of Long-Term Macrolide Exposure on the Gut Microbiome and Its Implications for Metabolic Control.

Long-term low-dose macrolide therapy is now widely used in the treatment of chronic respiratory diseases for its immune-modulating effects, although the antimicrobial properties of macrolides can also have collateral impacts on the gut microbiome. We investigated whether such treatment altered intestinal commensal microbiology and whether any such changes affected systemic immune and metabolic regulation. In healthy adults exposed to 4 weeks of low-dose erythromycin or azithromycin, as used clinically, we observed consistent shifts in gut microbiome composition, with a reduction in microbial capacity related to carbohydrate metabolism and short-chain fatty acid biosynthesis. These changes were accompanied by alterations in systemic biomarkers relating to immune (interleukin 5 [IL-5], IL-10, monocyte chemoattractant protein 1 [MCP-1]) and metabolic (serotonin [5-HT], C-peptide) homeostasis. Transplantation of erythromycin-exposed murine microbiota into germ-free mice demonstrated that changes in metabolic homeostasis and gastrointestinal motility, but not systemic immune regulation, resulted from changes in intestinal microbiology caused by macrolide treatment. Our findings highlight the potential for long-term low-dose macrolide therapy to influence host physiology via alteration of the gut microbiome. IMPORTANCE Long-term macrolide therapy is widely used in chronic respiratory diseases although its antibacterial activity can also affect the gut microbiota, a key regulator of host physiology. Macrolide-associated studies on the gut microbiota have been limited to short antibiotic courses and have not examined its consequences for host immune and metabolic regulation. This study revealed that long-term macrolides depleted keystone bacteria and impacted host regulation, mediated directly by macrolide activity or indirectly by alterations to the gut microbiota. Understanding these macrolide-associated mechanisms will contribute to identifying the risk of long-term exposure and highlights the importance of targeted therapy for maintenance of the gut microbiota.

The Molecular Epidemiology of Pneumococcal Strains Isolated from the Nasopharynx of Preschool Children 3 Years after the Introduction of the PCV Vaccination Program in Poland.

The genetic mechanisms of resistance, clonal composition, and the occurrence of pili were analyzed in 39 pneumococcal strains isolated from healthy children in the southeastern region of Poland. Strains with resistance to combinations of erythromycin, clindamycin, and tetracycline were found in clonal groups (CGs) related to Tennessee 23F-4 and Taiwan 19F-14 clones. Capsular switching possibly occurred in the Spain 9V-3 clone and its variants to serotypes 35B and 6A, as well as DLVs of Tennessee 23F-4 to serotype 23A. The double-locus variants of Colombia 23F-26 presented serotype 23B. The major transposons carrying the erythromycin and tetracycline resistance genes were Tn6002 (66.6%), followed by Tn916 (22.2%) and Tn2009 (11.1%). The macrolide efflux genetic assembly (MEGA) element was found in 41.7% of all erythromycin-resistant isolates. The majority of the isolates carrying the PI-1 gene belonged to the CGs related to the Spain 9V-3 clone expressing serotypes 35B and 6A, and the presence of both PI-1 and PI-2 was identified in CG4 consisting of the isolates related to the Taiwan 19F-14 clone expressing serotypes 19F and 19A. Importantly, in the nearest future, the piliated strains of serogroups 23B, 23A, and 35B may be of concern, being a possible origin of the emerging clones of piliated non-vaccine pneumococcal serotypes in Poland. This study reveals that nasopharyngeal carriage in children is an important reservoir for the selection and spreading of new drug-resistant pneumococcal clones in the community after the elimination of vaccine serotypes.

Domination of an emerging erythromycin-resistant ptxP3 Bordetella pertussis clone in Shanghai, China.

The number of cases of pertussis has been increasing since 2014 in China, with high prevalence of macrolide resistance in ptxP1 isolates and low prevalence in ptxP3 isolates. This study aimed to investigate the dynamic changes in the B. pertussis population from paediatric patients and household contacts in Shanghai between 2018 and 2022. Clinical data of laboratory-confirmed cases of pertussis were analysed, while isolates recovered from hospitalized children and household contacts were characterized by antimicrobial susceptibility testing, whole-genome sequencing, vaccine antigen gene typing and phylogenetical analysis. Among 640 laboratory-confirmed cases, 340 (53.1%) were fully vaccinated with DTaP and 114 (17.8%) were hospitalized for treatment. The frequency of erythromycin resistance in the 103 B. pertussis isolates from inpatients (n=73) and household contacts (n=30) was 78.6% (81/103), increasing from 65% (13/20) in 2018 to 100% (26/26) in 2022. The proportion of ptxP3 isolates increased from 35% (7/20) in 2018 to 100% (26/26) in 2022. Based on genomic analysis, a novel ptxP3 clone (MT28-Shanghai) belonging to sublineage IVd was discovered and dominated in 2021-2022, which was characterized with ptxP3, erythromycin resistance and prn150. Twelve (11.7%) predicted pertactin-deficient isolates were found; of these, nine were ptxP3 isolates and three were ptxP1 isolates. A complete shift from ptxP1 to ptxP3 in Shanghai, China, which may have been accelerated by the domination of a novel erythromycin-resistant MT28 clone, challenges the pertussis vaccines used at present in China.

The Formation and Drug Resistance Mechanism of Biofilm for Streptococcus pneumoniae Infection in Severe Respiratory Patients.

This study was to explore whether Streptococcus pneumoniae would form biofilms and the formative factors of biofilms, as well as the drug resistance mechanism of S. pneumoniae. In this study, a total of 150 strains of S. pneumoniae were collected from 5 local hospitals in the past two years, and the minimum inhibitory concentrations (MIC) of levofloxacin, moxifloxacin and penicillin were determined by agar double dilution method to select the drug-resistant strains. The polymerase chain reaction (PCR) amplification and sequencing were performed on specific genes of drug-resistant strains. In addition, 5 strains of S. pneumoniae with penicillin MIC ≤ 0.065 µg/mL, 0.5 µg/mL, 2 µg/mL, ≥ 4µg/mL were randomly selected, and the biofilms were cultured on two kinds of well plates for 24 hours. Finally, whether the biofilms were formed was observed. Experimental results revealed that the resistance rate of S. pneumoniae to erythromycin in this area was as high as 90.3%, and the strains that were resistant to penicillin account for only 1.5%. The amplification and sequencing experiment revealed that one (strain 1) of the strains, which was resistant to both drugs, had a GyrA mutation and ParE mutation, and strain 2 had a parC mutation. All strains generated biofilms, and the optical density (OD) value of penicillin MIC ≤ 0.065 µg/mL group (0.235 ± 0.053) was higher than that of 0.5 µg/mL group (0.192 ± 0.073) (P< 0.05) and higher than the OD value of the 4 µg/mL group (0.200 ± 0.041) (P< 0.05), showing statistically great differences. It was confirmed that the resistance rate of S. pneumoniae to erythromycin remained high, the rate of sensitivity to penicillin was relatively high, and the moxifloxacin and levofloxacin-resistant strains had appeared; S. pneumoniae mainly showed QRDR mutations in gyrA, parE, and parC; and it was confirmed that S. pneumoniae can generate biofilms in vitro.

Antibiotic Sensitivity of Group B Streptococcus from Pregnant Mothers and Its Association with Resistance Genes.

OBJECTIVE: This study assessed the antibiotic susceptibility and characterized antibiotic resistance genes of group B Streptococcus (GBS) isolates from selected tertiary care hospitals in Western Province, Sri Lanka. METHODS: A descriptive cross-sectional study was carried out to determine antibiotic sensitivity of GBS among 175 pregnant women of >35 weeks of gestation attending antenatal clinics in four teaching hospitals. Low vaginal and rectal swabs were collected separately, and GBS was identified by standard microbiological methods. Antibiotic sensitivity and minimum inhibitory concentration (MIC) were performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. DNA was extracted from culture isolates, and antibiotic-resistant genes were identified by polymerase chain reaction using ermB, ermTR, mefA, and linB genes. RESULTS: GBS colonization in the study sample was 25.7% (45/175) with detection rate of 22.9% (40/175) and 2.9% (5/175) in vaginal and rectal samples, respectively. All isolates were susceptible to penicillin with an MIC range of 0.03-0.12 µg/mL. Six isolates (13.3%) were intermediate, and 11 isolates (24.4%) were resistant to erythromycin. There were 5 intermediately resistant isolates (11.1%) and 10 resistant isolates (22.2%) for clindamycin. Of them, seven had inducible clindamycin resistance (iMLSB). MIC range of erythromycin was 0.03-0.32 µg/mL and that of clindamycin was 0.06-0.32 µg/mL. ermB gene was detected in 7 (15.5%). ermTR gene was found in 16 (35.6%) and was significantly associated with iMLSB phenotype (p = 0.005). mefA gene was detected in two (4.4%) isolates, while linB gene was not detected in tested isolates. CONCLUSION: All isolates were sensitive to penicillin, and the most prevalent resistance genotype was ermTR in the study population.