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1.
Virol J ; 21(1): 183, 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39129001

RESUMO

BACKGROUNDS: Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Throat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020-2022 and after COVID-19 pandemic (2023). RESULTS: M. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236). CONCLUSION: Outbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.


Assuntos
COVID-19 , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Humanos , China/epidemiologia , Pneumonia por Mycoplasma/epidemiologia , Pneumonia por Mycoplasma/microbiologia , COVID-19/epidemiologia , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Masculino , Feminino , Criança , Adulto , Adolescente , Pessoa de Meia-Idade , Pré-Escolar , Adulto Jovem , Surtos de Doenças , SARS-CoV-2/genética , Lactente , Idoso , Incidência , Prevalência , Pandemias
2.
J Infect Chemother ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39122182

RESUMO

The WHO recently proposed a new indicator for judging the appropriateness of antimicrobial selection according to the AWaRe classification. Although macrolides are often administered for long-term macrolide therapy, the impact of this therapy on the indicator remains unclear. This study examined the impact of this therapy on the indicator for outpatient oral antimicrobial use. Using the JMDC claims database, outpatients who were prescribed an oral antimicrobial at least once between January and December 2022 (n = 2.66 million) were included in the study. The ratio of patient numbers and antimicrobial usage (AMU) were calculated based on age group (<15, 15-64, and ≥65 years) and prescription days (1-15, 16-30, 31-60, 61-90, and ≥91 days), and AMU of each drug was corrected for defined daily doses and classified according to the AWaRe. Patients with chronic airway disease for whom macrolides were prescribed for 91 days and more were defined as long-term macrolide therapy. Macrolides accounted for more than 30 % of total oral AMU in all age groups. In the elderly, 11.2 % of patients were prescribed macrolides for 91 days or more, accounting for 66.4 % of macrolide use. With regard to diseases that were associated with macrolide prescriptions, the percentage of patients prescribed for chronic airway diseases increased as the number of days of prescription increased. These results suggest that the impact of long-term macrolide therapy should be considered when assessing the appropriateness of outpatient oral AMU according to the AWaRe classification.

3.
Environ Res ; 262(Pt 1): 119808, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153565

RESUMO

The widespread application of macrolide antibiotics has caused antibiotic resistance pollution, threatening the river ecological health. In this study, five macrolide antibiotics (azithromycin, clarithromycin, roxithromycin, erythromycin, and anhydro erythromycin A) were monitored in the Zao River across three hydrological periods (April, July, and December). Simultaneously, the changes in antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and planktonic bacterial communities were determined using metagenomic sequencing. A clear pollution gradient was observed for azithromycin and roxithromycin, with the concentrations in the dry season surpassing those in other seasons. The highest concentration was observed for azithromycin (1.36 µg/L). The abundance of MLS resistance genes increased along the Zao River during the dry season, whereas the opposite trend was obtained during the wet season. A significant correlation between the levels of MLS resistance genes and macrolide antibiotics was identified during the dry season. Notably, compared with the reference site, the abundance of transposase in the effluent from wastewater treatment plants (WWTPs) was significantly elevated in both dry and wet seasons, whereas the abundance of insertion sequences (IS) and plasmids declined during the dry season. The exposure to wastewater containing macrolide antibiotics altered the diversity of planktonic bacterial communities. The bacterial host for ARGs appeared to be Pseudomonas, primarily associated with multidrug subtypes. Moreover, the ARG subtypes were highly correlated with MGEs (transposase and istA). The partial least-squares path model (PLS-PM) demonstrated a positive correlation between the abundance of MGEs and ARGs, indicating the significance of horizontal gene transfer (HGT) in the dissemination of ARGs within the Zao River. Environmental variables, such as TN and NO3--N, were significantly correlated with the abundance of MGEs, ARGs, and bacteria. Collectively, our findings could provide insights into the shift patterns of the microbiome and ARGs across the contamination gradient of AZI and ROX in the river.

4.
Front Microbiol ; 15: 1449511, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39171272

RESUMO

We collected respiratory specimens from 128 pediatric patients diagnosed with pneumonia in Beijing in late 2023. Mycoplasma pneumoniae was detected in 77.3% (99/128) patients, with 36.4% (4/11), 82.9% (34/41), 80.3% (61/76) in children aged less than 3 years, 3-6 years, over 7 years, respectively. Mycoplasma pneumoniae (M. pneumoniae) was characterized using P1 gene typing, MLVA typing and sequencing of domain V of the 23S rRNA gene. P1 gene type 1 (P1-1; 76.1%, 54/71) and MLVA type 4-5-7-2 (73.7%, 73/99) were predominant. MLVA identified a new genotype: 3-4-6-2. Macrolide resistance-associated mutations were detected in 100% of samples, with A2063G accounting for 99% and A2064G for 1%. The positive rate of M. pneumoniae was higher compared to previous reports, especially in children less than 3 years, suggesting a M. pneumoniae epidemic showing a younger age trend occurred in late 2023 in Beijing, China. Higher proportions of macrolide-resistant M. pneumoniae, P1-1 and 4-5-7-2 genotype M. pneumoniae indicated increased macrolide resistance rate and genotyping shift phenomenon, which might be attributable to this epidemic. Additionally, complete clinical information from 73 M. pneumoniae pneumonia inpatients were analyzed. The incidence of severe M. pneumoniae pneumonia was 56.2% (41/73). Mycoplasma pneumoniae pneumonia patients exhibited longer duration of fever, with a median value of 10.0 days (IQR, 8.0-13.0), and higher incidence of complications (74.0%, 54/73). However, in this cohort, we found that the severity of M. pneumoniae pneumonia, co-infection, or complications were not associated with M. pneumoniae P1 gene or MLVA types. Clinicians should be aware that patients infected with macrolide-resistant M. pneumoniae exhibited more severe clinical presentations.

5.
Emerg Microbes Infect ; 13(1): 2389086, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39101270

RESUMO

Pertussis, an acute respiratory infection caused by Bordetella pertussis, has recently experienced a dramatic increase in incidence and associated deaths in China, drawing significant clinical attention. This article retrospectively analyzes national data on pertussis incidence and mortality from 2010 to 2024, exploring potential factors contributing to this trend. It also discusses strategies for enhancing vaccination programs, improving early diagnosis and treatment, and optimizing the clinical management of high-risk infants, with the aim of addressing the challenges posed by the current pertussis epidemic.


Assuntos
Bordetella pertussis , Coqueluche , Humanos , Coqueluche/epidemiologia , Coqueluche/mortalidade , Coqueluche/prevenção & controle , China/epidemiologia , Estudos Retrospectivos , Incidência , Lactente , Bordetella pertussis/genética , Pré-Escolar , Vacina contra Coqueluche/administração & dosagem , Vacina contra Coqueluche/imunologia , Vacinação , Recém-Nascido , Feminino , Criança , Programas de Imunização , Masculino
6.
Front Cell Infect Microbiol ; 14: 1391879, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104851

RESUMO

This study aimed to investigate the bacterial characteristics of pneumococcal isolates obtained from a tertiary care hospital in Japan. We analyzed the antimicrobial susceptibility, possession of macrolide resistance genes, pneumococcal serogroup/serotype, and sequence type (ST) of pneumococcal isolates from patients aged 15 years or older between 2011 and 2020 at Nagasaki University Hospital. Of the 73 isolates analyzed, 86.3% showed resistance to macrolides, and 28.8%, 46.6%, and 11.0% harbored mefA, ermB, and both, respectively. Of the isolates possessing ermB, 97.6% showed high levels of macrolide resistance [minimal inhibitory concentration (MIC) range, > 16 µg/mL]. Solithromycin (MIC range, 0.03-0.25 µg/mL), regardless of the presence of macrolide resistance genes, and lascufloxacin (MIC range, 0.06-0.5 µg/mL) showed potent in vitro activity against pneumococci. Serotype 19A was the most prevalent (six isolates), followed by serotypes 10A, 15A, and 15B/C (five isolates each). Four serotypes (11A, 19A, 22F, and 23B) and five STs (36, 99, 433, 558, and 3111) were significantly correlated with the presence of macrolide resistance genes. All four isolates with serotype 11A/ST99 and three isolates with serotype 19A/ST3111 harbored both mefA and ermB. No macrolide resistance genes were detected in either of the two isolates with serotype 22F/ST433, while all ten isolates with serogroup 15 (serotypes 15A and 15B/C, five isolates each) possessed ermB alone. Our study revealed the bacterial characteristics of the pneumococcal isolates obtained from our hospital. In vitro activity of solithromycin and lascufloxacin against these isolates was confirmed.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas , Sorogrupo , Streptococcus pneumoniae , Centros de Atenção Terciária , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/isolamento & purificação , Streptococcus pneumoniae/classificação , Humanos , Infecções Pneumocócicas/microbiologia , Japão , Antibacterianos/farmacologia , Macrolídeos/farmacologia , Farmacorresistência Bacteriana/genética , Adulto Jovem , Adolescente , Fenótipo , Idoso , Pessoa de Meia-Idade , Adulto , Proteínas de Bactérias/genética , Feminino , Masculino , Metiltransferases/genética , Idoso de 80 Anos ou mais , População do Leste Asiático , Proteínas de Membrana
7.
Artigo em Inglês | MEDLINE | ID: mdl-39179105

RESUMO

OBJECTIVE: This study aimed to assess the overall antibiotic susceptibility of Cutibacterium acnes (C. acnes), a bacterium implicated in acne vulgaris, with a particular focus on clindamycin and fluoroquinolones, which are commonly used in inflammatory acne treatment. METHODS: A systematic search of Scopus, PubMed, Web of Science, and EMBASE databases was conducted to identify relevant studies. Pooled prevalence estimates were calculated using a random-effects model, and additional analyses included quality assessment, evaluation of publication bias, meta-regression, and subgroup analyses based on antimicrobial susceptibility methods and year of publication. RESULTS: The analysis incorporated a total of 39 studies. The random-effects model revealed that the proportion of clindamycin-resistant isolates was 0.031 (95% CI: 0.014-0.071). Additionally, macrolides, including erythromycin (0.366; 95% CI, 0.302-0.434) and azithromycin (0.149; 95% CI, 0.061-0.322), exhibited distinct prevalence rates. Tetracyclines, including doxycycline (0.079; 95% CI, 0.014-0.071), tetracycline (0.062; 95% CI, 0.036-0.107), and minocycline (0.025; 95% CI, 0.012-0.051), displayed varying prevalence estimates. Fluoroquinolones, including ciprofloxacin (0.050; 95% CI, 0.017-0.140) and levofloxacin (0.061; 95% CI, 0.015-0.217), demonstrated unique prevalence rates. Additionally, the prevalence of the combination antibiotic trimethoprim/sulfamethoxazole (SXT) was estimated to be 0.087 (95% CI: 0.033-0.208). CONCLUSION: The study findings highlight a concerning increase in antimicrobial-resistant C. acnes with the use of antibiotics in acne treatment. The strategic utilization of appropriate antimicrobials has emerged as a crucial measure to mitigate the emergence of antimicrobial-resistant skin bacteria in acne management.

8.
Euro Surveill ; 29(31)2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39092529

RESUMO

As other European countries, France is experiencing a resurgence of pertussis in 2024. Between 1 January and 31 May 2024, 5,616 (24.9%) positive Bordetella pertussis qPCR tests were identified, following a 3-year period of almost null incidence. Of 67 cultured and whole genome sequenced B. pertussis isolates, 66 produced pertactin and 56 produced FIM2, in contrast to pre-COVID-19 years. One isolate of genotype Bp-AgST4 was resistant to macrolides. Pertussis resurgence may favour isolates that produce FIM2 and pertactin.


Assuntos
Antibacterianos , Bordetella pertussis , Macrolídeos , Coqueluche , Bordetella pertussis/genética , Bordetella pertussis/isolamento & purificação , Bordetella pertussis/efeitos dos fármacos , Humanos , França/epidemiologia , Macrolídeos/farmacologia , Coqueluche/epidemiologia , Coqueluche/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Proteínas da Membrana Bacteriana Externa/genética , Sequenciamento Completo do Genoma , Fatores de Virulência de Bordetella/genética , Genótipo , Adulto , Criança , Incidência , Pré-Escolar
9.
Front Microbiol ; 15: 1427702, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206369

RESUMO

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the infection of Mycoplasma pneumoniae (MP) decreased significantly. At the beginning of the summer of 2023, there was an increasing trend of MP infection in China and the MP pneumonia (MPP) is surging when it comes to the school season and lasts for several months which has attracted widespread attention. Objective: This study aims to investigate the prevalent characteristics of the MP and the difference between the COVID-19 pandemic and the post in Shanghai, China. Methods: The demographic information and the results of laboratory pathogen detection from July 2021 to May 2024 were collected and analyzed to find out the prevalent characteristics of MP. Two periods, during the COVID-19 pandemic and the post-pandemic, were divided and compared. The P1 genotyping and macrolide resistance-associated gene of 23 s rRNA were detected using the remaining MP-positive samples. Results: During the COVID-19 pandemic, the prevalence of the MP has significantly decreased. Female children are more susceptible to MP infection than the male. The school-aged group (>6 years) had the highest infection rate. The rate of MP P1 genotype during post panel is higher than that during COVID-19 pandemic, which is dominant from July 2021 to May 2024, while the macrolide-resistant associated mutations (A2063G) keep high percentage during or post pandemic. Conclusion: After the COVID-19 pandemic, an outbreak of MP infection occurred from summer onwards in 2023 with children in Shanghai, China. Immunity debt and high rate of macrolide-resistance may take effects in this MP epidemic. Continuous surveillance of MP is necessary to help to alert the prevalence of MPP.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39209267

RESUMO

OBJECTIVES: China has experienced a notable upsurge in pertussis cases post-COVID-19, alongside an age shift to older children, increased vaccine escape, and a notable rise in the prevalence of macrolide-resistant Bordetella pertussis (MRBP). Here, we present a genomic epidemiological investigation of these events. METHODS: We performed a retrospective observational study using culture-positive B. pertussis isolated in Shanghai, China between 2016 and 2024. We analysed strain and pertussis epidemiology dynamics by integrating whole-genome sequencing of 723 strains with antimicrobial susceptibility, transcriptomic profile, and clinical data. We compared the genome sequences of Shanghai strains with 6450 Chinese and global strains. RESULTS: From pre-COVID-19 (before December 2019) to post-COVID-19, patients shifted from predominantly infants (90%, 397/442) to a higher proportion of infections in older children (infant: 16%, 132/844), with the share of vaccinated individuals surging from 31% (107/340) to 88% (664/756). The MRBP prevalence increased from 60% (267/447) to 98% (830/845). The emergence and expansion of a ptxP3-lineage macrolide-resistant clone, MR-MT28, which is uniquely capable of causing substantial infections among older children and vaccinated individuals, was temporally strongly associated with the pertussis upsurge and epidemiological transition. While MR-MT28 showed increased expression of genes encoding pertussis toxin, it was associated with significantly milder clinical symtoms and a lower hospitalization rate. MR-MT28 likely originated in China around 2016, after acquiring several key mutations including a novel prn150 allele, and has been detected across multiple regions in China. Additionally, 26% (50/195) of MR-MT28 has evolved into predicted PRN-deficient strains, with an IS481 insertion being the predominant mechanism. CONCLUSIONS: We report that the post-COVID-19 upsurge of pertussis in China is associated with ptxP3-MR-MT28, and provide evidence that pathogen evolution is likely the primary factor driving pertussis upsurge, age shift and vaccine escape. MR-MT28 poses a high risk of global spread and warrants global surveillance.

11.
Bioorg Chem ; 151: 107712, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39146761

RESUMO

Ketolides (3-keto) such as TE-802 and acylides (3-O-acyl) like TEA0929 are ineffective against constitutively resistant pathogens harboring erythromycin ribosomal methylation (erm) genes. Following our previous work on alkylides (3-O-alkyl), we explored the structure-activity relationships of hybrids combining (R/S) 3-descladinosyl erythromycin with 6/7-quinolone motifs, featuring extended ether-linked spacers, with a focus on their efficacy against pathogens bearing constitutive erm gene resistance. Optimized compounds 17a and 31f not only reinstated efficacy against inducibly resistant pathogens but also demonstrated significantly augmented activities against constitutively resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes, which are typically refractory to existing C-3 modified macrolides. Notably, hybrid 31f (coded ZN-51) represented a pioneering class of agents distinguished by its dual modes of action, with ribosomes as the primary target and topoisomerases as the secondary target. As a novel chemotype of macrolide-quinolone hybrids, alkylide 31f is a valuable addition to our armamentarium against macrolide-resistant bacteria.


Assuntos
Antibacterianos , Macrolídeos , Testes de Sensibilidade Microbiana , Quinolonas , Streptococcus pneumoniae , Relação Estrutura-Atividade , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Quinolonas/química , Quinolonas/farmacologia , Quinolonas/síntese química , Macrolídeos/química , Macrolídeos/farmacologia , Streptococcus pneumoniae/efeitos dos fármacos , Estrutura Molecular , Desenho de Fármacos , Streptococcus pyogenes/efeitos dos fármacos , Streptococcus pyogenes/enzimologia , Relação Dose-Resposta a Droga , Éteres/química , Éteres/farmacologia , Éteres/síntese química
12.
World J Pediatr ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143259

RESUMO

BACKGROUND: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. METHODS: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world's first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for "macrolide-resistant", "Mycoplasma pneumoniae", "MP", "M. pneumoniae", "pneumonia", "MRMP", "lower respiratory tract infection", "Mycoplasma pneumoniae infection", "children", and "pediatric". RESULTS: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. CONCLUSIONS: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

13.
Heliyon ; 10(13): e33697, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39040303

RESUMO

Objective: Mycoplasma pneumoniae (Mp) is one of the major pathogens that causes respiratory tract infections, and macrolide resistance has increased rapidly in recent years due to the inappropriate use of macrolides in northeastern Asia. In the present study, we aimed to investigate Mp infection and macrolide resistance during a period of high incidence of Mp infection in Henan, China. Methods: A total of 29473 suspected children with Mp infection were enrolled in the study from July to December 2023. Throat swab specimens were collected from all the study subjects, and real-time PCR was performed to detect the Mp-DNA and macrolide resistance-associated A2063G or A2064G mutations. Results: The overall percentage of Mp-DNA-positive patients was 51.1 %, and the percentage of macrolide-resistant strains was 91 %. The rate of macrolide resistance remained stable from July to December. The Mp-DNA positivity rates among the different age groups from low to high were 0-1, 1-3, 3-6, 10-18 and 6-10 years. The macrolide resistance rate was the lowest in the 0-1 age group and highest in the 6-10 age group. No difference in the rate of macrolide resistance was observed between male and female children. Conclusions: The macrolide resistance rate of Mp did not change during the investigated period of high incidence of infection, and no sex difference existed. The macrolide resistance rate of Mp was the lowest in children under 1 year old.

15.
Access Microbiol ; 6(7)2024.
Artigo em Inglês | MEDLINE | ID: mdl-39081780

RESUMO

Asthma is a significant public health concern, particularly in children with severe symptoms. Exacerbation of asthma (EOA) is life-threatening, and respiratory infections (RIs) play a crucial role. Though viruses play a significant role in EOA, patients are empirically treated with antibiotics, contributing to antibiotic resistance development. Although there are widely reported associations of EOA with viral or Mycoplasma pneumoniae infections, there are no published data for Sri Lanka. The present study aimed to identify the association of common respiratory viruses, typical respiratory bacterial pathogens and M. pneumoniae in children with EOA and relate them with the compatibility of antimicrobial use. A case-control study was conducted in the paediatric unit of North Colombo Teaching Hospital, Sri Lanka, involving two groups of children between 5 and 15 years of age. Group 1 is children with EOA and Group 2 is children with stable asthma (SA). Each group consisted of 100 children. Sputum/throat swabs were tested for common respiratory viruses using virus-specific fluorescein isothiocyanate-labelled monoclonal antibodies (MAbs), bacteria by routine culture, and M. pneumoniae by real-time polymerase chain reaction. Macrolide resistance in M. pneumoniae was detected using conventional PCR and sequencing specific genetic mutations in the 23S rRNA gene. M. pneumoniae was genotyped using nested multilocus sequence typing, which targeted eight housekeeping genes (ppa, pgm, gyrB, gmk, glyA, atpA, arcC and adk). There was no significant difference in age, gender, demographic or geographical location between the two groups. In children with EOA, antibiotics were used in 66 % (66/100) and macrolides in 42 % (42/100). Samples comprised 78 % (78/100) sputum and 22 % (22/100) throat swabs. Adenovirus was the most common virus identified, and it was significantly higher in children with EOA compared to those with SA. Still, the two groups had no significant difference in typical bacteria findings. M. pneumoniae was detected in one patient with EOA, but none was detected in the SA group. The M. pneumoniae was macrolide-sensitive and ST14 by multilocus sequence typing. This study showed that the empiric use of antibiotics in children with asthma might be better targeted with prior pathogen screening to inform appropriate treatment to minimize antibiotic resistance.

18.
Eur J Med Chem ; 276: 116630, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38972081

RESUMO

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia.


Assuntos
Antibacterianos , Claritromicina , Desenho de Fármacos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Claritromicina/farmacologia , Claritromicina/química , Claritromicina/síntese química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Estrutura Molecular , Diaminas/química , Diaminas/farmacologia , Diaminas/síntese química , Haemophilus influenzae/efeitos dos fármacos , Oximas/química , Oximas/farmacologia , Oximas/síntese química , Relação Dose-Resposta a Droga , Humanos , Animais , Streptococcus pyogenes/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos
19.
Talanta ; 279: 126547, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39018951

RESUMO

As we all know, SERS (Surface-enhanced Raman spectroscopy) is widely used in sensing, analysis and detection. The covalent organic frameworks (COFs) have performed well as a material for supporting metal nanoparticles and facilitating analyte adsorption in SERS, which may greatly enhance the detection sensitivity and reproducibility. The synthesis of traditional metal/COFs composites involved chemical reduction methods, however, the resulting metallic NPs exhibited reduced capacity to enhance SERS due to their small particle sizes (usually <20 nm). This paper presented a novel photoreduction method for the facile growth of AuNPs (diameters: 75 nm) on COFs matrix under light control, which represents the first report of such synthesis on COF. Subsequently, the photoreduction deposition induced AuNPs/COFs composites, which served as highly sensitive and reproducible SERS-active substrates for capturing the spectral information of four types of macrolide antibiotics. The detection limits for the four macrolide antibiotics were determined to be 3.30 × 10-11, 3.43 × 10-10, 1.10 × 10-10 and 5.78 × 10-11 M, respectively, exhibiting excellent linear relationships within the concentration range of 10-10 to 10-3 M. Therefore, our proposed SERS method opens up a new idea for the development of SERS substrates and environmental safety monitoring, and it has great potential for ensuring food safety in the future.


Assuntos
Antibacterianos , Ouro , Macrolídeos , Nanopartículas Metálicas , Estruturas Metalorgânicas , Análise Espectral Raman , Análise Espectral Raman/métodos , Ouro/química , Nanopartículas Metálicas/química , Antibacterianos/análise , Antibacterianos/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/efeitos da radiação , Macrolídeos/análise , Macrolídeos/química , Processos Fotoquímicos , Oxirredução , Limite de Detecção
20.
Eur J Clin Microbiol Infect Dis ; 43(9): 1825-1835, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39017999

RESUMO

PURPOSE: To investigate macrolide-resistant Mycobacterium pneumoniae (MRMP) pneumonia in children and construct a logistic regression model for mutations in the Mycoplasma pneumoniae drug-resistant gene. METHODS: Clinical data of 281 children were analyzed. Sequencing confirmed a mutation at the A2063G locus of the 23 S rRNA gene in 227 children (A2063G group); 54 children showed no mutations (non-MRMP [NMRMP] group). We compared clinical features, laboratory tests, imaging, and bronchoscopy results and constructed a multifactorial logistic regression model to analyze risk and protective factors. RESULTS: The A2063G group had longer durations of fever and hospitalization before admission, a higher proportion of treatment with sodium methylprednisolone succinate (MPS)/dexamethasone, longer time to discontinue hormones, and higher probability of combined infections. Monocyte percentage was significantly higher in the A2063G group. Imaging suggested a higher incidence of infections in the right lung compared to both lungs. Univariate analysis revealed fever duration before admission, hormone dose and duration, monocyte percentage, and mixed infections as risk factors for Mycoplasma pneumoniae infection with the A2063G mutation. The logistic regression model showed that mixed infections were an independent risk factor for the A2063G locus mutation, whereas hormone dose was a protective factor. CONCLUSION: A prevalence of macrolide resistance of 80.8% among children was observed in the region. Logistic regression analysis revealed that co-infection with other respiratory pathogens is an independent risk factor for the development of resistance genes, while the use of hormone dosage acts as a protective factor.


Assuntos
Antibacterianos , Farmacorresistência Bacteriana , Macrolídeos , Mycoplasma pneumoniae , Pneumonia por Mycoplasma , RNA Ribossômico 23S , Humanos , Pneumonia por Mycoplasma/microbiologia , Pneumonia por Mycoplasma/tratamento farmacológico , Pneumonia por Mycoplasma/epidemiologia , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/efeitos dos fármacos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Feminino , Masculino , Farmacorresistência Bacteriana/genética , Pré-Escolar , Criança , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , RNA Ribossômico 23S/genética , Modelos Logísticos , Lactente , Mutação , Fatores de Risco , Estudos Retrospectivos
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