A multicenter clinical epidemiology of pediatric pneumococcal meningitis in China: results from the Chinese Pediatric Bacterial Meningitis Surveillance (CPBMS) 2019-2020.

Objective: To analyze the clinical epidemiological characteristics including clinical features, disease prognosis of pneumococcal meningitis (PM), and drug sensitivity of S. pneumoniae isolates in Chinese children. Methods: A retrospective analysis was performed on the clinical, laboratory microbiological data of 160 hospitalized children less than 15 years of age with PM from January 2019 to December 2020 in 33 tertiary hospitals in China. Results: A total of 160 PM patients were diagnosed, including 103 males and 57 females The onset age was 15 days to 15 years old, and the median age was 1 year and 3 months. There were 137 cases (85.6%) in the 3 months to <5 years age group, especially in the 3 months to <3 years age group (109 cases, 68.2%); S. pneumoniae was isolated from cerebrospinal fluid (CSF) culture in 95(35.6%), and 57(35.6%) in blood culture. The positive rates of S. pneumoniae detection by CSF metagenomic next-generation sequencing (mNGS)and antigen detection method were 40.2% (35/87) and 26.9% (21/78). Fifty-five cases (34.4%) had one or more predisposing factors of bacterial meningitis; and 113 cases (70.6%) had one or more extracranial infection diseases Fever (147, 91.9%) was the most common clinical symptom, followed by vomiting (61, 38.1%) and altered mental status (47,29.4%). Among 160 children with PM, the main intracranial imaging complications were subdural effusion and (or) empyema in 43 cases (26.9%), hydrocephalus in 24 cases (15.0%), cerebral abscess in 23 cases (14.4%), intracranial hemorrhage in 8 cases (5.0%), and other cerebrovascular diseases in 13 cases (8.1%) including encephalomalacia, cerebral infarction, and encephalatrophy. Subdural effusion and (or) empyema and hydrocephalus mainly occurred in children < 1 years old (90.7% (39/43) and 83.3% (20/24), respectively). 17 cases with PM (39.5%) had more than one intracranial imaging abnormality. S. pneumoniae isolates were completely sensitive to vancomycin (100.0%, 75/75), linezolid (100.0%,56/56), ertapenem (6/6); highly sensitive to levofloxacin (81.5%, 22/27), moxifloxacin (14/17), rifampicin (96.2%, 25/26), and chloramphenicol (91.3%, 21/23); moderately sensitive to cefotaxime (56.1%, 23/41), meropenem (51.1%, 23/45) and ceftriaxone (63.5, 33/52); less sensitive to penicillin (19.6%, 27/138) and clindamycin (1/19); completely resistant to erythromycin (100.0%, 31/31). The cure and improvement rate were 22.5% (36/160)and 66.3% (106/160), respectively. 18 cases (11.3%) had an adverse outcome, including 6 cases withdrawing treatment therapy, 5 cases unhealed, 5 cases died, and 2 recurrences. S. pneumoniae was completely susceptible to vancomycin (100.0%, 75/75), linezolid (100.0%, 56/56), and ertapenem (6/6); susceptible to cefotaxime, meropenem, and ceftriaxone in the order of 56.1% (23/41), 51.1% (23/45), and 63.5 (33/52); completely resistant to erythromycin (100.0%, 31/31). Conclusion: Pediatric PM is more common in children aged 3 months to < 3 years old. Intracranial complications mostly occur in children < 1 year of age with fever being the most common clinical manifestations and subdural effusion and (or) empyema and hydrocephalus being the most common complications, respectively. CSF non-culture methods can facilitate improving the detection rate of pathogenic bacteria. More than 10% of PM children had adverse outcomes. S. pneumoniae strains are susceptible to vancomycin, linezolid, ertapenem, levofloxacin, moxifloxacin, rifampicin, and chloramphenicol.

Efficacy of delafloxacin alone and incombination with cefotaxime againstcefotaxime non-susceptible invasive isolatesof Streptococcus pneumoniae / Eficacia de delafloxacino solo y en combinación con cefotaxima frente a aislados invasivos de Streptococcus pneumoniae no sensible acefotaxima

Objectives. We assessed the in vitro activity of delafloxacin and the synergy between cefotaxime and delafloxacin among cefotaxime non-susceptible invasive isolates of Streptococcus pneumoniae (CNSSP). Material and methods. A total of 30 CNSSP (cefotaxime MIC > 0.5 mg/L) were studied. Serotyping was performed by the Pneumotest-Latex and Quellung reaction. Minimum inhibitory concentrations (MICs) of delafloxacin, levofloxacin, penicillin, cefotaxime, erythromycin and vancomycin were determined by gradient diffusion strips (GDS). Synergistic activity of delafloxacin plus cefotaxime against clinical S. pneumoniae isolates was evaluated by the GDS cross method. Results. Delafloxacin showed a higher pneumococcal activity than its comparator levofloxacin (MIC50, 0.004 versus 0.75 mg/L and MIC90, 0.047 versus >32 mg/L). Resistance to delafloxacin was identified in 7/30 (23.3%) isolates, belonging to serotypes 14 and 9V. Synergy between delafloxacin and cefotaxime was detected in 2 strains (serotypes 19A and 9V). Antagonism was not observed. Addition of delafloxacin increased the activity of cefotaxime in all isolates. Delafloxacin susceptibility was restored in 5/7 (71.4%) strains. Conclusions. CNSSP showed a susceptibility to delafloxacin of 76.7%. Synergistic interactions between delafloxacin and cefotaxime were observed in vitro among CNSSP by GDS cross method. (AU)

Objetivos. Evaluamos la actividad in vitro de delafloxacino y la sinergia entre cefotaxima y delafloxacino entre aislados invasivos de Streptococcus pneumoniae no sensibles a cefotaxima (SPNSC). Material y métodos. Se estudiaron un total de 30 SPNSC (CIM de cefotaxima > 0,5 mg/L). El serotipado se realizó mediante la reacción Pneumotest-Latex y Quellung. Las concentraciones mínimas inhibitorias (CMI) de delafloxacino, levofloxacino, penicilina, cefotaxima, eritromicina y vancomicina se determinaron mediante tiras de difusión en gradiente (GDS). La actividad sinérgica de delafloxacino y cefotaxima frente aislados clínicos de S. pneumoniae se evaluó mediante el método cruzado GDS. Resultados. Delafloxacino mostró una mayor actividad neumocócica que su comparador levofloxacino (CIM50, 0,004 versus 0,75 mg/L y MIC90, 0,047 versus > 32 mg/L). Se identificó resistencia a delafloxacino en 7/30 (23,3%) aislados, pertenecientes a los serotipos 14 y 9V. Se detectó sinergia entre delafloxacino y cefotaxima en 2 cepas (serotipos 19A y 9V). No se observó antagonismo. La adición de delafloxacino aumentó la actividad de cefotaxima en todos los aislados. La sensibilidad a delafloxacino se restableció en 5/7 (71,4%) cepas. Conclusiones. SPNSC mostraron una susceptibilidad a delafloxacino del 76,7%. Se observaron interacciones sinérgicas in vitro entre delafloxacino y cefotaxima entre SPNSC mediante el método cruzado GDS. (AU)

Antimicrobial resistance and virulence profiling of Staphylococcus pseudintermedius isolated from cats, Bangladesh.

Staphylococcus pseudintermedius is a significant bacterial pathogen that frequently colonizes different body sites and mucous membranes of pets. The objectives of the cross-sectional study were to estimate the prevalence, antimicrobial resistance pattern, and detection of diverse resistance as well as virulence genes of S. pseudintermedius in cats. A standard bacteriological method, species-specific gene and different antimicrobial resistance as well as virulence genes were confirmed by PCR assay. A total of 233 swab samples were collected from different body sites of 102 cats, among them 146 swabs from 73 healthy cats, and 87 from 29 diseased cats. Overall, prevalence of S. pseudintermedius in cats was 12.01%, while dermatitis and otitis affected cats were 26.08% and 33.33%, respectively. The highest antimicrobial resistance was observed against penicillin (96.42%) followed by streptomycin (85.71%) and erythromycin (78.57%). Moreover, 89.28% of S. pseudintermedius isolates exhibit multi-drug resistance (MDR) (≥ 3 classes' antimicrobial resistant). In addition, 17.86% isolates harbored the mecA gene; thus, were classified as methicillin-resistant S. pseudintermedius (MRSP). Furthermore, the erythromycin resistance genes ermA and ermB were harbored by 25% and 10.71% of isolates, while 42.86% and 17.86% of isolates carried tetK and tetL (tetracycline resistance) genes, respectively. In virulence profiling, 32.14% (sea) and 10.71% (seb) of isolates were found positive for enterotoxin genes, whereas, the toxic shock syndrome toxin-1 (tst-1) gene and the Panton-Valentine leukocidin gene (pvl) were detected in 25% and 14.29% of isolates, respectively. To our knowledge, this is the first report of cats in Bangladesh for MDR S. pseudintermedius, MRSP, and their virulence profiling.

Removal efficiency of antibiotic residues, antibiotic resistant bacteria, and genes across parallel secondary settling tank and membrane bioreactor treatment trains in a water reclamation plant.

Antimicrobial resistance is recognized as a potent threat to human health. Wastewater treatment facilities are viewed as hotspots for the spread of antimicrobial resistance. This study provides comprehensive data on the occurrences of 3 different antibiotic resistant opportunistic pathogens (with resistance to up to 5 antibiotics), 13 antibiotic resistant genes and intI1, and 22 different antimicrobial residues in a large water reclamation plant (176 million gallons per day) that runs a conventional Modified Ludzack-Ettinger (MLE) reactor followed by a secondary settling tank (SST) and membrane bioreactor (MBR) in parallel. All the antibiotic resistant bacteria and most of the antibiotic resistance genes were present in the raw influent, ranging from 2.5 × 102-3.7 × 106 CFU/mL and 1.2× 10-1-6.5 × 1010 GCN/mL, respectively. MBR outperformed the SST system in terms of ARB removal as the ARB targets were largely undetected in MBR effluent, with log removals ranging from 2.7 to 6.8, while SST only had log removals ranging from 0.27 to 4.6. Most of the ARG concentrations were found to have significantly higher in SST effluent than MBR permeate, and MBR had significantly higher removal efficiency for most targets (p < 0.05) except for sul1, sul2, blaOXA48, intI1 and 16S rRNA genes (p > 0.05). As for the antibiotic residues (AR), there was no significant removal from the start to the end of the treatment process, although MBR had higher removal efficiencies for azithromycin, chloramphenicol, erythromycin, erythromycin-H2O, lincomycin, sulfamethoxazole and triclosan, compared to the SST system. In conclusion, MBR outperformed SST in terms of ARB and ARGs removal. However low removal efficiencies of most AR targets were apparent.

Generic role of zeolite in enhancing anaerobic digestion and mitigating diverse inhibitions: Insights from degradation performance and microbial characteristics.

Zeolite was shown to mitigate anaerobic digestion (AD) inhibition caused by several inhibitors such as long-chain fatty acids, ammonia, and phenolic compounds. In this paper, we verified the genericity of zeolite's mitigating effect against other types of inhibitors found in AD such as salts, antibiotics, and pesticides. The impacts of inhibitors and zeolite were assessed on AD performance and microbial dynamics. While sodium chloride and erythromycin reduced methane production rates by 34% and 32%, zeolite mitigated the inhibition and increased methane production rates by 72% and 75%, respectively, compared to conditions without zeolite in the presence of these two inhibitors. Noticeably, zeolite also enhanced methane production rate by 51% in the uninhibited control condition. Microbial community structure was analyzed at two representative dates corresponding to the hydrolysis/fermentation and methanogenesis stages through 16S rRNA gene sequencing. The microbial characteristics were further evidenced with common components analysis. Results revealed that sodium chloride and erythromycin inhibited AD by targeting distinct microbial populations, with more pronounced inhibitory effects during hydrolysis and VFAs degradation phases, respectively. Zeolite exhibited a generic effect on microbial populations in different degradation stages across all experimental conditions, ultimately contributing to the enhanced AD performance and mitigation of different inhibitions. Typically, hydrolytic and fermentative bacteria such as Cellulosilyticum, Sedimentibacter, and Clostridium sensu stricto 17, VFAs degraders such as Mesotoga, Syntrophomonas, and Syntrophobacter, and methanogens including Methanobacterium, Methanoculleus, and Methanosarcina were strongly favored by the presence of zeolite. These findings highlighted the promising use of zeolite in AD processes for inhibition mitigation in general.

Heat stress enhances the occurrence of erythromycin resistance of Enterococcus isolates in mice feces.

Heat stress is a common environmental factor in livestock breeding that has been shown to impact the development of antibiotic resistance within the gut microbiota of both human and animals. However, studies investigating the effect of temperature on antibiotic resistance in Enterococcus isolates remain limited. In this study, specific pathogen free (SPF) mice were divided into a control group maintained at normal temperature and an experimental group subjected to daily 1-h heat stress at 38 °C, respectively. Gene expression analysis was conducted to evaluate the activation of heat shock responsive genes in the liver of mice. Additionally, the antibiotic-resistant profile and antibiotic resistant genes (ARGs) in fecal samples from mice were analyzed. The results showed an upregulation of heat-inducible proteins HSP27, HSP70 and HSP90 following heat stress exposure, indicating successful induction of cellular stress within the mice. Furthermore, heat stress resulted in an increase in the proportion of erythromycin-resistant Enterococcus isolates, escalating from 0 % to 0.23 % over a 30-day duration of heat stress. The resistance of Enterococcus isolates to erythromycin also had a 128-fold increase in minimum inhibitory concentration (MIC) within the heated-stressed group compared to the control group. Additionally, a 2∼8-fold rise in chloramphenicol MIC was observed among these erythromycin-resistant Enterococcus isolates. The acquisition of ermB genes was predominantly responsible for mediating the erythromycin resistance in these Enterococcus isolates. Moreover, the abundance of macrolide, lincosamide and streptogramin (MLS) resistant-related genes in the fecal samples from the heat-stressed group exhibited a significant elevation compared to the control group, primarily driven by changes in bacterial community composition, especially Enterococcaceae and Planococcaceae, and the transfer of mobile genetic elements (MGEs), particularly insertion elements. Collectively, these results highlight the role of environmental heat stress in promoting antibiotic resistance in Enterococcus isolates and partly explain the increasing prevalence of erythromycin-resistant Enterococcus isolates observed among animals in recent years.

Nitrate input inhibited the biodegradation of erythromycin through affecting bacterial network modules and keystone species in lake sediments.

Antibiotic contamination and excessive nitrate loads are generally concurrent in aquatic ecosystems. However, little is known about the effects of nitrate input on the biodegradation of antibiotics. In this study, the effects of nitrate input on microbial degradation of erythromycin, a typical macrolide antibiotic widely detected in lake sediments, were investigated. The results showed that the nitrate input significantly inhibited the erythromycin removal and such an inhibitory effect was strengthened with the increased input dosages. Nitrate input significantly increased sediment nitrite concentration, indicating enhanced denitrification under high nitrate pressure. Bacterial network module and keystone species analysis showed that nitrate input enriched the keystone species involved in denitrification (e.g., Simplicispira and Denitratisoma). In contrast, some potential erythromycin-degrading bacteria (e.g., Desulfatiglandales, Pseudomonadales, Nitrospira) were inhibited by nitrate input. The variations in dominant bacterial groups implied competition between denitrification and erythromycin degradation in response to nitrate input. Based on the partial least squares path modeling analysis, keystone species (total effect: 0.419) and bacterial module (total effect: 0.403) showed strong association with erythromycin removal percentage. This indicated that the inhibitory effect of nitrate input on erythromycin degradation was mainly explained by bacterial network modules and keystone species. These findings will help us to assess the bioremediation potential of antibiotic-contaminated sediments suffering from excessive nitrogen discharge concurrently.

Discovery of novel dihydronaphthalene-imidazole ligands as potential inhibitors of Staphylococcus aureus multidrug resistant NorA efflux pump: A combination of experimental and in silico molecular docking studies.

Overexpression of the efflux pump is a predominant mechanism by which bacteria show antimicrobial resistance (AMR) and leads to the global emergence of multidrug resistance (MDR). In this work, the inhibitory potential of library of dihydronapthyl scaffold-based imidazole derivatives having structural resemblances with some known efflux pump inhibitors (EPI) were designed, synthesized and evaluated against efflux pump inhibitor against overexpressing bacterial strains to study the synergistic effect of compounds and antibiotics. Out of 15 compounds, four compounds (Dz-1, Dz-3, Dz-7, and Dz-8) were found to be highly active. DZ-3 modulated the MIC of ciprofloxacin, erythromycin, and tetracycline by 128-fold each against 1199B, XU212 and RN4220 strains of S. aureus respectively. DZ-3 also potentiated tetracycline by 64-fold in E. coli AG100 strain. DZ-7 modulated the MIC of both tetracycline and erythromycin 128-fold each in S. aureus XU212 and S. aureus RN4220 strains. DZ-1 and DZ-8 showed the moderate reduction in MIC of tetracycline in E. coli AG100 only by 16-fold and 8-fold, respectively. DZ-3 was found to be the potential inhibitor of NorA as determined by ethidium bromide efflux inhibition and accumulation studies employing NorA overexpressing strain SA-1199B. DZ-3 displayed EPI activity at non-cytotoxic concentration to human cells and did not possess any antibacterial activity. Furthermore, molecular docking studies of DZ-3 was carried out in order to understand the possible binding sites of DZ-3 with the active site of the protein. These studies indicate that dihydronaphthalene scaffolds could serve as valuable cores for the development of promising EPIs.

Prevalence and antimicrobial resistance of bacterial agents isolated from the cases of dental caries.

Dental caries are mainly occur owing to the presence and activity of bacterial agents. The present study was done to assess the prevalence and antibiotic resistance of bacterial strains isolated from the cases of dental caries. Fifty patients with approved dental carries were included in the study. Sampling from the site of dental caries was done using the sterile swab. Swabs were transferred to laboratory and subjected to microbial culture. Species identification of bacteria was done using biochemical test. Bacterial isolates were subjected to disk diffusion to assess their antimicrobial resistance. S. aureus (40%) harboured the highest rate of contamination, while S. oralis (16%) and E. aerogenes (10%) harbored the lowest. S. aureus and S. mutans (6%) harbored the highest distribution amongst the cases of mix infections, while S. aureus and S. oralis (2%) harbnored the lowest. S. aureus strains harbored the highest rate of resistance toward tetracycline (90%), penicillin (75%), ampicillin (75%), amoxicillin (60%), and erythromycin (60%). E. coli strains harbored the highest rate of resistance toward tetracycline (90%), gentamicin (80%), ampicillin (70%), and erythromycin (70%). S. mutans strains harbored the highest rate of resistance toward tetracycline (93.33%), ampicillin (86.66%), penicillin (80%), amoxicillin (80%), and erythromycin (80%). S. oralis strains harbored the highest rate of resistance toward tetracycline (100%), ampicillin (75%), penicillin (62.50%), and amoxicillin (62.50%). E. aerogenes strains harbored the highest rate of resistance toward tetracycline (80%), gentamicin (80%), and ampicillin (80%). S. aureus bacteria isolated from dental caries harbored the highest rate of MDR. Distribution of resistance against more than 3 antimicrobial agents amongst the S. aureus, E. coli, S. mutans, S. oralis, and E. aerogenes bacteria isolated from the cases of dental caries was 90%, 60%, 80%, 62.50%, and 80%, respectively. Application of disk diffuin can help practitioners to reduce the rate of resistance in bacteria responsible for dental caries.

Antimicrobial resistance markers distribution in Staphylococcus aureus from Nsukka, Nigeria.

BACKGROUND: Multidrug resistance in Staphylococcus aureus continues to influence treatment complications in clinical settings globally. Multidrug-resistant-S. aureus (MDR-SA) is often genetically driven by resistance markers transferable in pathogenic strains. This study aimed to determine the distribution of resistance markers in clinical isolates of S. aureus in Nsukka, Nigeria. METHODS: A total of 154 clinical samples were cultured on mannitol salt agar. Isolates were characterized using conventional cultural techniques and confirmed by PCR detection of S. aureus-specific nuc gene. Antibiotic resistance profiles of the isolates were determined against selected antibiotics using the disk-diffusion method, while screening for antibiotic resistance genes (Mec A, Erm A, Erm B, Erm C, Van A, and Van B) was by PCR. RESULTS: A total of 98 isolates were identified as S. aureus by conventional methods. Of these, 70 (71.43%) were confirmed by PCR. Phenotypically, the isolates exhibited high degrees of resistance to oxacillin (95.72%), erythromycin (81.63%), and ertapenem (78.57%) and 75.51% and 47.30% against methicillin and vancomycin, respectively. Multiple antibiotic resistance indexes of the isolates ranged from 0.3 to 1, and the most prevalent pattern of resistance was oxacillin-ertapenem-vancomycin-erythromycin-azithromycin-clarithromycin-ciprofloxacin- cefoxitin-amoxicillin-clavulanic acid. PCR screening confirmed the existence of various antibiotic resistance makers among the strains, with the most common resistance genes found in the isolates being Mec A (32.14%), Van A (21.43%), Van B (10.71%), Erm B (10.71%), and Erm C (17.86%). None possessed the Erm A gene. CONCLUSION: The study supports the need for necessary action, including rational drug use, continuous surveillance, and deployment of adequate preventive and curative policies and actions.

Antimicrobial Resistance and the Prevalence of the Panton-Valentine Leukocidin Gene among Clinical Isolates of Staphylococcus aureus in Lithuania.

This study aimed to determine resistance to antimicrobials of Staphylococcus aureus strains isolated from clinical specimens in Lithuanian hospitals and to identify the genes conferring resistance and virulence. The study was carried out from June 2019 to September 2021. S. aureus strains were isolated from skin, soft tissues, blood, lower respiratory tract, urine and other specimens. Antibiotic susceptibility testing was performed using the disc diffusion method according to EUCAST guidelines. All isolates were analyzed for detection of the ermA, ermC, mecA, mecC, tetK, tetM, and lukF-PV genes by multiplex real-time PCR. The 16S rRNA coding sequence was applied as an internal PCR control. Altogether, 745 S. aureus strains were analyzed. Antimicrobial susceptibility testing revealed that all isolates were susceptible to rifampin and vancomycin. Of the 745 strains, 94.8% were susceptible to tetracycline, 94.5% to clindamycin, and 88.3% to erythromycin. The lowest susceptibility rate was found for penicillin (25.8%). Six percent of the tested strains were methicillin-resistant S. aureus (MRSA). The majority of methicillin-resistant strains were isolated from skin and soft tissues (73.3%), with a smaller portion isolated from blood (17.8%) and respiratory tract (8.9%). The ermC gene was detected in 41.1% of erythromycin-resistant S. aureus strains, whereas ermA was detected in 32.2% of erythromycin-resistant S. aureus strains. 69.2% of tetracycline-resistant S. aureus strains had tetK gene, and 28.2% had tetM gene. 7.3% of S. aureus isolates harbored lukF-PV gene. The frequency of the pvl gene detection was significantly higher in MRSA isolates than in methicillin-susceptible S. aureus isolates (p < 0.0001).

Multidrug-resistant Enterococcus faecium strains enter the Norwegian marine environment through treated sewage.

This study aimed to understand the antibiotic resistance prevalence among Enterococcus spp. from raw and treated sewage in Bergen city, Norway. In total, 517 Enterococcus spp. isolates were obtained from raw and treated sewage from five sewage treatment plants (STPs) over three sampling occasions, with Enterococcus faecium as the most prevalent (n = 492) species. E. faecium strains (n = 307) obtained from the influent samples, showed the highest resistance against quinupristin/dalfopristin (67.8%). We observed reduced susceptibility to erythromycin (30.6%) and tetracycline (6.2%) in these strains. E. faecium strains (n = 185) obtained from the effluent samples showed highest resistance against quinupristin/dalfopristin (68.1%) and reduced susceptibility to erythromycin (24.9%) and tetracycline (8.6%). We did not detect resistance against last-resort antibiotics, such as linezolid, vancomycin, and tigecycline in any of the strains. Multidrug-resistant (MDR) E. faecium strains were detected in both influent (2.3%) and effluent (2.2%) samples. Whole genome sequencing of the Enterococcus spp. strains (n = 25) showed the presence of several antibiotic resistance genes, conferring resistance against aminoglycosides, tetracyclines, and macrolides, as well as several virulence genes and plasmid replicons. Two sequenced MDR strains from the effluents belonged to the hospital-associated clonal complex 17 and carried multiple virulence genes. Our study demonstrates that clinically relevant MDR Enterococcus spp. strains are entering the marine environment through treated sewage.

Clinical isolate characteristics and demographics of patients with C.jejuni and C.coli infections in Northern Israel, 2015-2021.

C.coli is a significant cause of foodborne gastroenteritis worldwide, with the majority of cases attributed to C.jejuni. Although most clinical laboratories do not typically conduct antimicrobial susceptibility testing for C.coli, the rise in resistant strains has underscored the necessity for such testing and epidemiological surveillance. The current study presents clinical isolate characteristics and demographics of 221 patients with C.coli (coli and jejuni) infections in Northern Israel, between 2015 and 2021. Clinical and demographic data were collected from patient medical records. Susceptibility to erythromycin, tetracycline, ciprofloxacin, and gentamicin was assessed using the standard E-test. No significant correlations were found between bacterial species and patient ethnicity, patient gender, or duration of hospitalization. In contrast, significant differences were found between infecting species and patient age and age subgroup (P < 0.001). Furthermore, erythromycin resistance was observed in only 0.5% of the study population, while resistance to ciprofloxacin, tetracycline, and gentamicin was observed in 95%, 93%, and 2.3% of the population, respectively. The presented study underscores the need for routine surveillance of C.coli antibiotic resistance.

Doxycycline post-exposure prophylaxis could theoretically select for resistance to various antimicrobials in 19 pathobionts: an in silico analysis.

OBJECTIVES: Doxycycline post exposure prophylaxis (PEP) has been shown to reduce the incidence of bacterial STIs. However, if there is genetic linkage between resistance to tetracycline and other antimicrobials, then it could also select for resistance to these other antimicrobials. We therefore undertook to evaluate if there is an association between the minimum inhibitory concentrations (MICs) of tetracycline and other antimicrobials in 19 clinically important bacterial species. METHODS: Mixed-effects linear regression was used to assess if minocycline MICs were associated with the MICs of eight other antimicrobials (ceftriaxone, ampicillin, oxacillin, vancomycin, erythromycin, levofloxacin, amikacin, and trimethoprim-sulfamethoxazole) in 19 bacterial species in the Antimicrobial Testing Leadership and Surveillance (ATLAS) database. RESULTS: With the notable exception of vancomycin, where no association was found, strong positive associations were typically found between the MICs of minocycline and each of the eight antimicrobials in each of the species assessed. For example, the minocycline MICs of all the Gram-positive species were positively associated with ampicillin, ceftriaxone, oxacillin and erythromycin MICs (all P-values < 0.001). The only exceptions were ampicillin for Streptococcus pyogenes and ceftriaxone for S. dysgalactiae, where no significant associations were found. Similarly in the Gram-negative species, the minocycline MICs of all the species except Haemophilus influenzae and Stenotrophomonas maltophilia were positively associated with the MICs of ceftriaxone, ampicillin, levofloxacin and amikacin (all P-values < 0.001). CONCLUSIONS: There is a theoretical risk that doxycycline PEP could select for resistance not only to tetracyclines but to a range of other antimicrobials in each of the 19 pathobionts assessed.

Influence of dietary status on the obesogenic effects of erythromycin antibiotic on Caenorhabditis elegans.

As emerging pollutants, antibiotics were widely detected in water bodies and dietary sources. Recently, their obesogenic effects raised serious concerns. So far, it remained unclear whether their obesogenic effects would be influenced by water- and diet-borne exposure routes. In present study, Caenorhabditis elegans, nematodes free-living in air-water interface and feeding on bacteria, were exposed to water- and diet-borne erythromycin antibiotic (ERY). The statuses of the bacterial food, inactivated or alive, were also considered to explore their influences on the effects. Results showed that both water- and diet-borne ERY significantly stimulated body width and triglyceride contents. Moreover, diet-borne ERY's stimulation on the triglyceride levels was greater with alive bacteria than with inactivated bacteria. Biochemical analysis showed that water-borne ERY inhibited the activities of enzymes like adipose triglyceride lipase (ATGL) in fatty acid ß-oxidation. Meanwhile, diet-borne ERY inhibited the activities of acyl-CoA synthetase (ACS) and carnitine palmitoyl transferase (CPT) in lipolysis, while it stimulated the activities of fatty acid synthase (FAS) in lipogenesis. Gene expression analysis demonstrated that water-borne ERY with alive bacteria significantly upregulated the expressions of daf-2, daf-16 and nhr-49, without significant influences in other settings. Further investigation demonstrated that ERY interfered with bacterial colonization in the intestine and the permeability of the intestinal barrier. Moreover, ERY decreased total long-chained fatty acids (LCFAs) in bacteria and nematodes, while it decreased total short-chained fatty acids (SCFAs) in bacteria but increased them in nematodes. Collectively, the present study demonstrated the differences between water- and diet-borne ERY's obesogenic effects, and highlighted the involvement of insulin and nhr-49 signaling pathways, SCFAs metabolism and also the interaction between intestinal bacteria and the host.

Effects of Erythromycin on Nereis succinea and the Intestinal Microbiome across Different Salinity Levels.

The exposure of aquatic organisms to pollutants often occurs concomitantly with salinity fluctuations. Here, we reported the effects of erythromycin (0.250, 7.21, and 1030 µg/L) on marine invertebrate N. succinea and its intestinal microbiome under varying salinity levels (5‰, 15‰, and 30‰). The salinity elicited significant effects on the growth and intestinal microbiome of N. succinea. The susceptibility of the intestinal microbiome to erythromycin increased by 8.7- and 6.2-fold at salinities of 15‰ and 30‰, respectively, compared with that at 5‰ salinity. Erythromycin caused oxidative stress and histological changes in N. succinea intestines, and inhibited N. succinea growth in a concentration-dependent manner under 30‰ salinity with a maximum inhibition of 25%. At the intestinal microbial level, erythromycin enhanced the total cell counts at 5‰ salinity but reduced them at 15‰ salinity. Under all tested salinities, erythromycin diminished the antibiotic susceptibility of the intestinal microbiome. Two-way ANOVA revealed significant interactive effects (p < 0.05) between salinity and erythromycin on various parameters, including antibiotic susceptibility and intestinal microbial diversity. The present findings demonstrated the significant role of salinity in modulating the impacts of erythromycin, emphasizing the necessity to incorporate salinity fluctuations into environmental risk assessments.

Whole-Cell Configuration of the Patch-Clamp Technique in the hERG Channel Assay.

In vitro electrophysiological safety studies have become an integral part of the drug development process because, in many instances, compound-induced QT prolongation has been associated with a direct block of human ether-a-go-go-related gene (hERG) potassium channels or their native current, the rapidly activating delayed rectifier potassium current (IKr ). Therefore, according to the ICH S7B guideline, the in vitro hERG channel patch-clamp assay is commonly used as an early screen to predict the ability of a compound to prolong the QT interval prior to first-in-human testing. The protocols described in this article are designed to assess the effects of acute or long-term exposure to new chemical entities on the amplitude of IKr in HEK293 cells stably transfected with the hERG channel (whole-cell configuration of the patch-clamp technique). Examples of results obtained with moxifloxacin, terfenadine, arsenic, pentamidine, erythromycin, and sotalol are provided for illustrative purposes. © 2024 Wiley Periodicals LLC. Basic Protocol: Measurement of the acute effects of test items in the hERG channel test Alternate Protocol: Measurement of the long-term effects of test items in the hERG channel test.

Antimicrobial susceptibilities of Campylobacter fetus: report from a reference laboratory.

Campylobacter fetus is known to cause human disease, particularly in elderly and immunocompromised hosts. There are limited published data for antimicrobial susceptibility patterns with this organism, and no interpretive criteria are available. We reviewed antimicrobial susceptibilities of C. fetus isolates tested at a tertiary care center and reference laboratory over an 11-year period. C. fetus isolates from patients treated at Mayo Clinic and those sent as referrals for identification and susceptibility were included. Antimicrobial susceptibility testing was performed using agar dilution for ciprofloxacin, doxycycline, erythromycin, gentamicin, meropenem, and tetracycline. Geographic distribution, culture source, organism minimal inhibitory concentration (MIC) distributions, and MIC50 and MIC90 were examined. Excluding duplicates, 105 unique isolates were identified from 110 positive cultures. Blood cultures represented the most common source, followed by body fluids, skin and soft tissue, and central nervous system. Gentamicin and meropenem had favorable MIC50 and MIC90 of 1 µg/mL. Ciprofloxacin demonstrated an MIC50 of 1 µg/mL; however, the MIC90 was >2 µg/mL. Erythromycin demonstrated MIC50 and MIC90 of 2 µg/mL. Tetracycline and doxycycline were tested on a limited number of isolates and showed a wide range of MICs. Gentamicin and meropenem demonstrated favorable MICs in C. fetus isolates. These may represent therapeutic options for consideration in serious C. fetus infections, pending susceptibility results. Ciprofloxacin, which showed variable results, may be more appropriate for use only after susceptibility testing. C. fetus interpretive criteria are needed to aid clinicians in selection of both empiric and definitive therapies. IMPORTANCE: Our findings contribute to the scant literature on Campylobacter fetus antimicrobial susceptibility test results. We used a reference test method of agar dilution and provide MICs for a large number of organisms and antimicrobial agents.

Immunologic effect and clinical impact of erythromycin in septic patients: A randomized clinical trial.

To investigate the potential regulatory effect of erythromycin added to standard care in septic patients on sepsis biomarkers and clinical outcome. It was a single-blind randomized trial including critical septic patients. The primary endpoint was the change in the TNF/IL-10 ratio between days 0 and 6. Changes in other biomarkers, vasopressor use, and 28-day mortality were secondary endpoints. One hundred and ten patients were examined (erythromycin group, n = 55 versus placebo group, n = 55). Clinical features of the groups were well matched. Erythromycin addition had no beneficial effects on the TNF/IL-10 ratio or mortality (51% vs. 47%, p = 0.62). Both groups' serum TNF/IL-10 ratios did not significantly rise (from 0.48 [0.34-1.18] to 0.59 [0.21-1.10] vs. 0.65 [0.25-1.14] to 0.93 [0.24-1.88] in the erythromycin and placebo groups, respectively; p values = 0.86 and 0.12). Serum Procalcitonin (PCT) and CRP dropped considerably in the Erythromycin group, whereas only PCT showed a drop in the placebo group. On day 6, the non-survivors' serum TNF/IL-10 ratio was lower than that of the survivors (0.55 [0.17-1.04] vs 1.08 [0.4-2.28], p = 0.029). Neither the pro/anti-inflammatory imbalance nor the mortality were impacted by the addition of erythromycin to standard care in septic patients (ClinicalTrials.gov ID: NCT04665089 (11/12/2020)).

Macrolide and lincosamide resistance of Streptococcus agalactiae in pregnant women in Poland.

Knowing about the antibiotic resistance, serotypes, and virulence-associated genes of Group B Streptococcus for epidemiological and vaccine development is very important. We have determined antimicrobial susceptibility patterns, serotype, and virulence profiles. The antibiotic susceptibility was assessed for a total of 421 Streptococcus agalactiae strains, isolated from pregnant women and neonates. Then, 89 erythromycin and/or clindamycin-resistant strains (82 isolates obtained from pregnant women and seven isolates derived from neonates) were assessed in detail. PCR techniques were used to identify the studied strains, perform serotyping, and assess genes encoding selected virulence factors. Phenotypic and genotypic methods determined the mechanisms of resistance. All tested strains were sensitive to penicillin and levofloxacin. The constitutive MLSB mechanism (78.2%), inducible MLSB mechanism (14.9%), and M phenotype (6.9%) were identified in the macrolide-resistant strains. It was found that macrolide resistance is strongly associated with the presence of the ermB gene and serotype V. FbsA, fbsB, fbsC, scpB, and lmb formed the most recurring pattern of genes among the nine surface proteins whose genes were analysed. A minority (7.9%) of the GBS isolates exhibited resistance to lincosamides and macrolides, or either, including those that comprised the hypervirulent clone ST-17. The representative antibiotic resistance pattern consisted of erythromycin, clindamycin, and tetracycline resistance (71.9%). An increase in the fraction of strains resistant to macrolides and lincosamides indicates the need for monitoring both the susceptibility of these strains and the presence of the ST-17 clone.