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The Journal of Veterinary Medical... Nov 2022American foulbrood (AFB) is a honeybee disease caused by Paenibacillus larvae, and tylosin is used as the prophylactic in Japan. Honey contains macrolide-resistant...
American foulbrood (AFB) is a honeybee disease caused by Paenibacillus larvae, and tylosin is used as the prophylactic in Japan. Honey contains macrolide-resistant bacteria that are a potential source of genes that may confer tylosin resistance to P. larvae. To investigate the potential risk of such genes in Japanese honey, we developed real-time PCR assays for the detection of important macrolide resistance genes, ermC and ermB, and analyzed 116 Japanese honey samples with known contamination status of P. larvae. Consequently, 91.38% of samples contained ermC and/or ermB, and 71.55% of samples contained both ermC and P. larvae, suggesting the possible emergence of tylosin-resistant P. larvae in Japan. Therefore, judicious use of the prophylactic is essential in maintaining its effectiveness.
Topics: Bees; United States; Animals; Macrolides; Anti-Bacterial Agents; Tylosin; Honey; Japan; Real-Time Polymerase Chain Reaction; Drug Resistance, Bacterial; Larva
PubMed: 36123020
DOI: 10.1292/jvms.22-0307 -
Treponema pallidum Macrolide Resistance and Molecular Epidemiology in Southern Africa, 2008 to 2018.Journal of Clinical Microbiology Sep 2021Treponema pallidum macrolide resistance and clinical treatment failure have emerged rapidly within communities where macrolides have been used as convenient, oral...
Treponema pallidum macrolide resistance and clinical treatment failure have emerged rapidly within communities where macrolides have been used as convenient, oral therapeutic alternatives to benzathine penicillin G for syphilis or for other clinical indications. Macrolides are not included in the South African syndromic management guidelines for genital ulcer disease; however, in 2015, a 1-g dose of azithromycin was incorporated into treatment algorithms for genital discharge. We determined the prevalence of 23S rRNA macrolide resistance-associated point mutations in 135 T. pallidum-positive surveillance specimens from Botswana, Zimbabwe, and South Africa between 2008 and 2018. Additionally, we investigated the association between macrolide resistance, T. pallidum strain type, and HIV coinfection. A significant increase in the prevalence of the A2058G macrolide resistance-associated point mutation was observed in specimens collected after 2015. There was a high level of molecular heterogeneity among T. pallidum strains circulating in the study communities, with strain type 14d/f being the most predominant in South Africa. Fourteen novel strain types, derived from three new gene restriction fragment length polymorphism patterns and seven new gene sequence types, were identified. There was an association between A2058G-associated macrolide resistance and T. pallidum strain types 14d/f and 14d/g but no association between T. pallidum macrolide resistance and HIV coinfection. The majority of T. pallidum strains, as well as strains containing the A2058G mutation, belonged to the SS14-like clade. This is the first study to extensively detail the molecular epidemiology and emergence of macrolide resistance in T. pallidum in southern Africa.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Humans; Macrolides; Molecular Epidemiology; Treponema pallidum
PubMed: 34346717
DOI: 10.1128/JCM.02385-20 -
Microbiology Spectrum Oct 2022Due to the resistance of Streptococcus pneumoniae to β-lactams, macrolides, and tetracyclines, treatment alternatives have become increasingly limited worldwide. We aim...
Due to the resistance of Streptococcus pneumoniae to β-lactams, macrolides, and tetracyclines, treatment alternatives have become increasingly limited worldwide. We aim to describe the characterization of erythromycin-resistant S. pneumoniae (ERSP) strains in northeastern China over a period of 20 years. A total of 1,240 ERSP strains were collected and classified into five groups based on the ages of the patients. Etest strips and Kirby-Bauer disk diffusion were performed for drug susceptibility testing. The capsule swelling test was used for capsule typing. The phenotype of drug resistance was detected by the erythromycin and clindamycin double-disk method. The , , , and genes were detected by PCR. Among the 1,240 ERSP strains, 510 were invasive isolates, and 730 were noninvasive isolates. The results of drug susceptibility testing showed that the rates of resistance to penicillin, amoxicillin, cefotaxime, ceftriaxone, meropenem, tetracycline, trimethoprim-sulfamethoxazole, and chloramphenicol varied among the different age groups. 19F, 19A, 23F, 14, and 6B were the serotypes that were commonly found among ERSP strains. Among all strains, 99.03% (1,228/1,240) exhibited an MLSB (macrolide-lincosamide-streptogramin B) resistance phenotype, of which 1,221 strains displayed a constitutive MLSB (cMLSB) phenotype and 7 strains showed an inducible MLSB (iMLSB) phenotype. All of these strains carried the gene. In contrast, only 0.97% of strains of M phenotypes were found to carry the gene. Both the and genes were detected in 704 strains that exhibited multidrug resistance, whereas the gene was not detected. Furthermore, 1,185 tetracycline-resistant strains were found to carry the gene. Macrolide antimicrobial drugs should be used cautiously for the empirical treatment of S. pneumoniae infections. This study presents a retrospective analysis using 1,240 clinical erythromycin-resistant Streptococcus pneumoniae (ERSP) isolates collected in northeastern China between January 2000 and December 2019. The serotype distribution, corresponding vaccine coverage, as well as resistance phenotypes, genes, and mechanisms to macrolide and tetracycline of these isolates were systematically described, analyzed, and discussed. We hope that this study will inform clinicians in their respective regions when selecting antimicrobial agents. We also hope that this study is useful for researchers in related fields. Finally, we emphasize in this study that vaccination is the best preventive measure for S. pneumoniae infection considering its resistance to commonly used antibiotics. The determination of the S. pneumoniae serotype distribution also provides valuable empirical evidence for local health authorities when introducing appropriate vaccines in a specific area.
Topics: Amoxicillin; Anti-Bacterial Agents; Ceftriaxone; Chloramphenicol; Clindamycin; Drug Resistance, Multiple, Bacterial; Erythromycin; Macrolides; Meropenem; Microbial Sensitivity Tests; Penicillins; Retrospective Studies; Streptococcus pneumoniae; Streptogramin B; Tetracycline; Trimethoprim, Sulfamethoxazole Drug Combination; China
PubMed: 35938873
DOI: 10.1128/spectrum.00546-22 -
PloS One 2020The surveillance of emm types and macrolide susceptibility of group A streptococcus (GAS) in various areas and time periods enhances the understanding of the...
BACKGROUND
The surveillance of emm types and macrolide susceptibility of group A streptococcus (GAS) in various areas and time periods enhances the understanding of the epidemiology of GAS infections and may guide treatment strategies and the formulation of type-specific vaccines. Greece has emerged as a country with high macrolide use. However, studies suggest a gradual reduction in macrolide consumption after 2007.
METHODS
During a 7-year period (2011-2017), 604 GAS isolates were recovered from consecutive children presenting with pharyngeal or nonpharyngeal infections in Central Greece; 517 viable isolates underwent molecular analysis, including emm typing.
RESULTS
Isolates belonged to 20 different emm types (in decreasing order of prevalence: 1, 89, 4, 12, 28, 3, 75 and 6, accounting for 88.2% of total isolates). The emm types comprised 10 emm clusters (five most common clusters: E4, A-C3, E1, A-C4 and A-C5). The emm89 isolates were acapsular ('new clade'). Overall macrolide resistance rate was 15.4%, and cMLSB emerged as the predominant resistance phenotype (56.4%). The lowest annual resistance rates occurred in 2014 (13.1%), 2016 (5.5%) and 2017(8.0%) (P for trend = 0.002). Consumption of macrolide/lincosamide/streptogramin B declined by 22.6% during 2011-2017. Macrolide resistance and emm28 and emm77 types were associated (both P<0.001). The most frequently identified genetic lineages of macrolide-resistant GAS included emm28/ST52, emm77/ST63, emm12/ST36, emm89/ST101 and emm4/ST39. We estimated that 98.8% of the isolates belonged to emm types incorporated into a novel 30-valent M protein vaccine.
CONCLUSIONS
In Central Greece during 2011-2017, the acapsular emm89 isolates comprised the second most prevalent type. Susceptibility testing and molecular analyses revealed decreasing GAS macrolide resistance rates, which may be attributed to the reduction in the consumption of macrolides and/or the reduced circulation of macrolide-resistant clones in recent years. Such data may provide valuable baseline information in targeting therapeutic intervention and the formulation of type-specific GAS vaccines.
Topics: Adolescent; Anti-Bacterial Agents; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Child; Child, Preschool; Drug Resistance, Bacterial; Female; Greece; Humans; Infant; Macrolides; Male; Multilocus Sequence Typing; Pharyngeal Diseases; Streptococcal Infections; Streptococcus pyogenes
PubMed: 32379802
DOI: 10.1371/journal.pone.0232777 -
Microbiology Spectrum Feb 2023Patients with chronic obstructive pulmonary disease (COPD) benefit from the immunomodulatory effect of azithromycin, but long-term administration may alter colonizing...
Genetic Adaptation and Acquisition of Macrolide Resistance in Haemophilus spp. during Persistent Respiratory Tract Colonization in Chronic Obstructive Pulmonary Disease (COPD) Patients Receiving Long-Term Azithromycin Treatment.
Patients with chronic obstructive pulmonary disease (COPD) benefit from the immunomodulatory effect of azithromycin, but long-term administration may alter colonizing bacteria. Our goal was to identify changes in Haemophilus influenzae and Haemophilus parainfluenzae during azithromycin treatment. Fifteen patients were followed while receiving prolonged azithromycin treatment (Hospital Universitari de Bellvitge, Spain). Four patients (P02, P08, P11, and P13) were persistently colonized by H. influenzae for at least 3 months and two (P04 and P11) by . Isolates from these patients (53 H. influenzae and 18 ) were included to identify, by whole-genome sequencing, antimicrobial resistance changes and genetic variation accumulated during persistent colonization. All persistent lineages isolated before treatment were azithromycin-susceptible but developed resistance within the first months, apart from those belonging to P02, who discontinued the treatment. H. influenzae isolates from P08-ST107 acquired mutations in 23S rRNA, and those from P11-ST2480 and P13-ST165 had changes in L4 and L22. In , P04 persistent isolates acquired changes in , and P11 carried genes encoding MefE/MsrD efflux pumps in an integrative conjugative element, which was also identified in H. influenzae P11-ST147. Other genetic variation occurred in genes associated with cell wall and inorganic ion metabolism. Persistent H. influenzae strains all showed changes in and genes. Other genes (, , , and ) had variation in multiple lineages. Furthermore, persistent strains showed loss, acquisition, or genetic changes in prophage-associated regions. Long-term azithromycin therapy results in macrolide resistance, as well as genetic changes that likely favor bacterial adaptation during persistent respiratory colonization. The immunomodulatory properties of azithromycin reduce the frequency of exacerbations and improve the quality of life of COPD patients. However, long-term administration may alter the respiratory microbiota, such as Haemophilus influenzae, an opportunistic respiratory colonizing bacteria that play an important role in exacerbations. This study contributes to a better understanding of COPD progression by characterizing the clinical evolution of H. influenzae in a cohort of patients with prolonged azithromycin treatment. The emergence of macrolide resistance during the first months, combined with the role of Haemophilus parainfluenzae as a reservoir and source of resistance dissemination, is a cause for concern that may lead to therapeutic failure. Furthermore, genetic variations in cell wall and inorganic ion metabolism coding genes likely favor bacterial adaptation to host selective pressures. Therefore, the bacterial pathoadaptive evolution in these severe COPD patients raise our awareness of the possible spread of macrolide resistance and selection of host-adapted clones.
Topics: Humans; Azithromycin; Haemophilus; Anti-Bacterial Agents; Quality of Life; Haemophilus Infections; Macrolides; Drug Resistance, Bacterial; Pulmonary Disease, Chronic Obstructive; Respiratory System; Haemophilus influenzae
PubMed: 36475849
DOI: 10.1128/spectrum.03860-22 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Sep 2021Macrolide antibiotics are a class of broad-spectrum antibiotics with the macrolide as core nucleus. Recently, antibiotic pollution has become an important environmental... (Review)
Review
Macrolide antibiotics are a class of broad-spectrum antibiotics with the macrolide as core nucleus. Recently, antibiotic pollution has become an important environmental problem due to the irregular production and abuse of macrolide antibiotics. Microbial degradation is one of the most effective methods to deal with antibiotic pollution. This review summarizes the current status of environmental pollution caused by macrolide antibiotics, the degradation strains, the degradation enzymes, the degradation pathways and the microbial processes for degrading macrolide antibiotics. Moreover, the critical challenges on the biodegradation of macrolide antibiotics were also discussed.
Topics: Anti-Bacterial Agents; Biodegradation, Environmental; Macrolides
PubMed: 34622622
DOI: 10.13345/j.cjb.200714 -
The Clinical Respiratory Journal Nov 2022Macrolide-resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and...
INTRODUCTION
Macrolide-resistant Mycoplasma pneumoniae (MRMP) has become prevalent in children. This study investigated the clinical and laboratory variables of MRMP and macrolide-sensitive M. pneumoniae (MSMP) and identified factors associated with prolonged hospital admission in children.
METHODS
A prospective multicenter study was conducted in 1063 children <18 years old in July 2018-June 2020. The 454 had a positive M. pneumoniae polymerase chain reaction assay.
RESULTS
Most subjects had MRMP (78.4%), and all mutated strains had the A2063G transition. We defined MRMP* (n = 285) as MRMP pneumonia requiring admission and MSMP* (n = 72) as MSMP pneumonia requiring admission. Patients with MRMP pneumonia were older, more likely to have segmental/lobar pneumonia, and had more febrile days than those with MSMP pneumonia. C-reactive protein (CRP), lactate dehydrogenase (LDH), and percentage neutrophils were more strongly associated with MRMP* than MSMP* groups. Percentage neutrophils, CRP, and alanine aminotransferase significantly changed between admission and follow-up measurements in patients with MRMP* (P < 0.05). The duration of admission positively correlated with the number of febrile days after initiation of antibiotic medication and laboratory variables (white blood cell count, CRP, and aspartate aminotransferase [AST]) (P < 0.05). Random forest analysis indicated that the number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission was over five.
CONCLUSIONS
This study indicated that children with M. pneumoniae pneumonia with a higher number of febrile days after initiation of antibiotic medication, AST, and percentage neutrophils at admission were more likely to have prolonged admission duration.
Topics: Child; Humans; Adolescent; Mycoplasma pneumoniae; Prospective Studies; Drug Resistance, Bacterial; Pneumonia, Mycoplasma; Macrolides; Anti-Bacterial Agents; C-Reactive Protein
PubMed: 36205104
DOI: 10.1111/crj.13549 -
Journal of Global Antimicrobial... Jun 2022Macrolides have a long history of use in animals and humans. Dynamics of macrolide-antibiotic resistance genes (ARGs) in waterways from the origin to the sea has not...
OBJECTIVES
Macrolides have a long history of use in animals and humans. Dynamics of macrolide-antibiotic resistance genes (ARGs) in waterways from the origin to the sea has not been reported.
METHODS
Resistant bacterial rate was measured by culture method, and copy numbers of macrolide-ARGs, mef(A), erm(B), mph(B), mef(C)-mph(G), and mobile genetic elements (MGEs) traI and IntI1 were quantitated in environmental DNA. Community composition in each site was investigated by 16S rRNA gene metagenomic sequencing. In Yilan area, antibiotics were quantitated.
RESULTS
Surface water samples from pig farms to the sea in southern and northern areas in Taiwan were monitored. Macrolide-resistant bacteria accounted for 3%-28% of total colony-forming bacteria in aquaculture ponds and rivers, whereas in pig farm wastewater it was 26%-100%. Three common macrolide-ARGs mef(A), erm(B), and mph(B) and the relatively new mef(C)-mph(G) were frequently detected in pig farms, but not in aquaculture ponds and the sea. Rivers receiving pig wastewater showed ARG contamination similar to the pig farms. Among the MGEs, IntI1 was frequently distributed in all sites and was positively related to mef(A), erm(B), and mph(B) but not to mef(C)-mph(G).
CONCLUSION
Pig farms are the origin of macrolide-ARGs, although macrolide contamination is low. Since lincomycin was detected in pig farms in the northern area, the increase of macrolide-ARGs is a future concern due to cross-resistance to lincomycin. ARGs abundance in aquaculture ponds was low, though MGEs were detected. Relation of IntI1 to ARG suggests convergence of ARGs to specific MGEs might be time/history dependent.
Topics: Animals; Anti-Bacterial Agents; Bacteria; Drug Resistance, Bacterial; Genes, Bacterial; Interspersed Repetitive Sequences; Lincomycin; Macrolides; RNA, Ribosomal, 16S; Swine; Taiwan; Wastewater
PubMed: 35533984
DOI: 10.1016/j.jgar.2022.04.024 -
Microbiology Spectrum Aug 2023Mycoplasma pneumoniae (MP) is an important respiratory pathogen, the prevalence of macrolide-resistant MP (mainly containing A2063G mutation in 23S rRNA) increased in...
Proteomic and Phenotypic Studies of Mycoplasma pneumoniae Revealed Macrolide-Resistant Mutation (A2063G) Associated Changes in Protein Composition and Pathogenicity of Type I Strains.
Mycoplasma pneumoniae (MP) is an important respiratory pathogen, the prevalence of macrolide-resistant MP (mainly containing A2063G mutation in 23S rRNA) increased in recent years. Epidemiological studies suggest a higher prevalence of type I resistant (IR) strains than corresponding sensitive (IS/IIS) strains, but not type II resistant (IIR) strains. Here, we aimed to analyze the factors underlying the altered prevalence of IR strains. First, proteomic analyses exhibit the protein compositions were type specific, while more differential proteins were detected between IS and IR (227) than IIS and IIR strains (81). mRNA level detection suggested posttranscriptional regulation of these differential proteins. Differential protein-related phenotypic changes were also detected: (i) P1 abundance was different between genotypes (I < II, IR < IS), the adhesion of MPs showed accordance to P1 abundance within IS and IIS strains; (ii) type I, especially IR, strains had a higher proliferation rate, which is potentially associated with differential proteins participating in glycolysis and one carbon pool metabolisms; (iii) A549 cells infected with IR strains had lower activity of caspase-3 and higher levels IL-8, but the differences were not significant between groups ( > 0.05). Correlations of P1 abundance to caspase-3 activity and proliferation rate to the level of IL-8 were obtained. These results suggest changes in protein composition influenced the pathogenicity of MP, especially in IR strains, which may impact the prevalence of MP strains of different genotypes. The prevalence of macrolide-resistant MPs increased the difficulty in treatment of MP infections and posed potential threats to children's health. Epidemiological studies showed a high prevalence of IR-resistant strains (mainly A2063G in 23S rRNA) in these years. However, the trigger mechanisms for this phenomenon are not clear. In this paper, proteomic and phenotypic studies suggest that IR strains have reduced levels of multiple adhesion proteins and increased proliferation rate, which may lead to higher transmission rate of IR strains in the population. This suggests that we should pay attention to the prevalence of IR strains.
Topics: Child; Humans; Mycoplasma pneumoniae; Macrolides; Caspase 3; RNA, Ribosomal, 23S; Virulence; Interleukin-8; Proteomics; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Anti-Bacterial Agents; Mutation
PubMed: 37378520
DOI: 10.1128/spectrum.04613-22 -
BMC Pulmonary Medicine Apr 2023Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and...
BACKGROUND
Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and immunomodulatory effect. The exact mechanism of inflammatory response is unknown. Here, we investigated the effect of maintenance macrolide treatment on the inflammatory response in BE. In addition, we assessed the inflammatory profile in BE in relation to disease severity.
METHODS
During the BAT randomized controlled trial (investigating the effect of 1 year of azithromycin (AZM) in 83 BE patients), data on BE severity, lung function and sputum microbiology was collected. For the current study, a wide range of inflammatory markers were analysed in 3- monthly sputum samples in all participants.
RESULTS
At baseline, marked neutrophilic but also eosinophilic inflammation was present in both groups, which remained stable throughout the study and was not affected by AZM treatment. Significant upregulation of pro-inflammatory markers correlated with FEV < 50% (TNFα, ECP, IL-21, IL-1, p = 0.01- 0.05), H. influenzae (HI) colonization (MPO, ECP, MIP-1, TNFα, IL-21, Il-8, IL-1, IL-1α, p < 0.001 - 0.04) and number of exacerbations (MPO, ECP, VEGF, MMP-9, p = 0.003 - 0.01). Surprisingly, colonization with P. aeruginosa (PA) was found to correlate with an attenuated inflammatory response compared to non-PA colonized. In placebo-treated patients, presence of an infectious exacerbation was reflected by a significant excessive increase in inflammation as compared to a non-significant upregulation in the AZM-treated patients.
CONCLUSION
One year of AZM treatment did not result in attenuation of the inflammatory response in BE. Increasing disease severity and the presence of an exacerbation were reflected by upregulation of pro-inflammatory markers.
Topics: Humans; Azithromycin; Tumor Necrosis Factor-alpha; Sputum; Bronchiectasis; Anti-Bacterial Agents; Macrolides; Bronchi; Inflammation; Interleukin-1
PubMed: 37118704
DOI: 10.1186/s12890-023-02444-1