Increase In Macrolide Resistance Research Articles

Prolonged mass azithromycin distributions and macrolide resistance determinants among preschool children in Niger: A sub-study of a cluster-randomized trial (MORDOR).

Randomized controlled trials found that twice-yearly mass azithromycin administration (MDA) reduces childhood mortality, presumably by reducing infection burden. World Health Organization (WHO) issued conditional guidelines for mass azithromycin administration in high-mortality settings in sub-Saharan Africa given concerns for antibiotic resistance. While prolonged twice-yearly MDA has been shown to increase antibiotic resistance in small randomized controlled trials, the objective of this study was to determine if macrolide and non-macrolide resistance in the gut increases with the duration of azithromycin MDA in a larger setting. The Macrolide Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) study was conducted in Niger from December 2014 to June 2020. It was a cluster-randomized trial of azithromycin (A) versus placebo (P) aimed at evaluating childhood mortality. This is a sub-study in the MORDOR trial to track changes in antibiotic resistance after prolonged azithromycin MDA. A total of 594 communities were eligible. Children 1 to 59 months in 163 randomly chosen communities were eligible to receive treatment and included in resistance monitoring. Participants, staff, and investigators were masked to treatment allocation. At the conclusion of MORDOR Phase I, by design, all communities received an additional year of twice-yearly azithromycin treatments (Phase II). Thus, at the conclusion of Phase II, the treatment history (1 letter per 6-month period) for the participating communities was either (PP-PP-AA) or (AA-AA-AA). In Phase III, participating communities were then re-randomized to receive either another 3 rounds of azithromycin or placebo, thus resulting in 4 treatment histories: Group 1 (AA-AA-AA-AA-A, N = 51), Group 2 (PP-PP-AA-AA-A, N = 40), Group 3 (AA-AA-AA-PP-P, N = 27), and Group 4 (PP-PP-AA-PP-P, N = 32). Rectal swabs from each child (N = 5,340) were obtained 6 months after the last treatment. Each child contributed 1 rectal swab and these were pooled at the community level, processed for DNA-seq, and analyzed for genetic resistance determinants. The primary prespecified outcome was macrolide resistance determinants in the gut. Secondary outcomes were resistance to beta-lactams and other antibiotic classes. Communities recently randomized to azithromycin (groups 1 and 2) had significantly more macrolide resistance determinants than those recently randomized to placebo (groups 3 and 4) (fold change 2.18, 95% CI 1.5 to 3.51, Punadj < 0.001). However, there was no significant increase in macrolide resistance in communities treated 4.5 years (group 1) compared to just the most recent 2.5 years (group 2) (fold change 0.80, 95% CI 0.50 to 1.00, Padj = 0.010), or between communities that had been treated for 3 years in the past (group 3) versus just 1 year in the past (group 4) (fold change 1.00, 95% CI 0.78 to 2.35, Padj = 0.52). We also found no significant differences for beta-lactams or other antibiotic classes. The main limitations of our study were the absence of phenotypic characterization of resistance, no complete placebo arm, and no monitoring outside of Niger limiting generalizability. In this study, we observed that mass azithromycin distribution for childhood mortality among preschool children in Niger increased macrolide resistance determinants in the gut but that resistance may plateau after 2 to 3 years of treatment. Co-selection to other classes needs to be monitored. NCT02047981 https://classic.clinicaltrials.gov/ct2/show/NCT02047981.

Multidrug-resistant conjugative plasmid carrying mphA confers increased antimicrobial resistance in Shigella

Shigellosis remains a common gastrointestinal disease mostly in children < 5 years of age in developing countries. Azithromycin (AZM), a macrolide, is currently the first-line treatment for shigellosis in Bangladesh; ciprofloxacin (CIP) and ceftriaxone (CRO) are also used frequently. We aimed to evaluate the current epidemiology of antimicrobial resistance (AMR) and mechanism(s) of increasing macrolide resistance in Shigella in Bangladesh. A total of 2407 clinical isolates of Shigella from 2009 to 2016 were studied. Over the study period, Shigella sonnei was gradually increasing and become predominant (55%) over Shigella flexneri (36%) by 2016. We used CLSI-guided epidemiological cut-off value (ECV) for AZM in Shigella to set resistance breakpoints (zone-diameter ≤ 15 mm for S. flexneri and ≤ 11 mm for S. sonnei). Between 2009 and 2016, AZM resistance increased from 22% to approximately 60%, CIP resistance increased by 40%, and CRO resistance increased from zero to 15%. The mphA gene was the key macrolide resistance factor in Shigella; a 63MDa conjugative middle-range plasmid was harboring AZM and CRO resistance factors. Our findings show that, especially after 2014, there has been a rapid increase in resistance to the three most effective antibiotics. The rapid spread of macrolide (AZM) resistance genes among Shigella are driven by horizontal gene transfer rather than direct lineage.

Recent Scientific Advancements towards a Vaccine against Group A Streptococcus.

Group A Streptococcus (GAS), or Streptococcus pyogenes, is a gram-positive bacterium that extensively colonises within the human host. GAS is responsible for causing a range of human infections, such as pharyngitis, impetigo, scarlet fever, septicemia, and necrotising fasciitis. GAS pathogens have the potential to elicit fatal autoimmune sequelae diseases (including rheumatic fever and rheumatic heart diseases) due to recurrent GAS infections, leading to high morbidity and mortality of young children and the elderly worldwide. Antibiotic drugs are the primary method of controlling and treating the early stages of GAS infection; however, the recent identification of clinical GAS isolates with reduced sensitivity to penicillin-adjunctive antibiotics and increasing macrolide resistance is an increasing threat. Vaccination is credited as the most successful medical intervention against infectious diseases since it was discovered by Edward Jenner in 1796. Immunisation with an inactive/live-attenuated whole pathogen or selective pathogen-derived antigens induces a potent adaptive immunity and protection against infectious diseases. Although no GAS vaccines have been approved for the market following more than 100 years of GAS vaccine development, the understanding of GAS pathogenesis and transmission has significantly increased, providing detailed insight into the primary pathogenic proteins, and enhancing GAS vaccine design. This review highlights recent advances in GAS vaccine development, providing detailed data from preclinical and clinical studies across the globe for potential GAS vaccine candidates. Furthermore, the challenges and future perspectives on the development of GAS vaccines are also described.

Molecular characterization of Streptococcus pneumoniae causing disease among children in Nigeria during the introduction of PCV10 (GSK).

Streptococcus pneumoniae (pneumococcus) is a leading vaccine-preventable cause of childhood invasive disease. Nigeria has the second highest pneumococcal disease burden globally, with an estimated ~49 000 child deaths caused by pneumococcal infections each year. Ten-valent pneumococcal conjugate vaccine (GSK; PCV10) was introduced in December 2014 in a phased approach. However, few studies have characterized the disease-causing pneumococci from Nigeria. This study assessed the prevalence of serotypes, antibiotic susceptibility and genomic lineages using whole genome sequencing and identified lineages that could potentially escape PCV10 (GSK). We also investigated the potential differences in pneumococcal lineage features between children with and without sickle cell disease. A collection of 192 disease-causing pneumococcal isolates was obtained from Kano (n=189) and Abuja (n=3) states, Nigeria, between 1 January 2014 and 31 May 2018. The majority (99 %, 190/192) of specimens were recovered from children aged 5 years or under. Among them, 37 children had confirmed or traits of sickle cell disease. Our findings identified 25 serotypes expressed by 43 Global Pneumococcal Sequence Clusters (GPSCs) and 85 sequence types (STs). The most common serotypes were 14 (18 %, n=35), 6B (16 %, n=31), 1 (9 %, n=17), 5 (9 %, n=17) and 6A (9 %, n=17); all except serotype 6A are included in PCV10 (GSK). PCV10 (SII; PNEUMOSIL) and PCV13 formulations include serotypes 6A and 19A which would increase the overall coverage from 67 % by PCV10 (GSK) to 78 and 82 %, respectively. The pneumococcal lineages were a mix of globally spreading and unique local lineages. Following the use of PCV10 (GSK), GPSC5 expressing serotype 6A, GPSC10 (19A), GPSC26 (12F and 46) and GPSC627 (9L) are non-vaccine type lineages that could persist and potentially expand under vaccine-selective pressure. Approximately half (52 %, 99/192) of the pneumococcal isolates were resistant to the first-line antibiotic penicillin and 44 % (85/192) were multidrug-resistant. Erythromycin resistance was very low (2 %, 3/192). There was no significant difference in clinical manifestation, serotype prevalence or antibiotic resistance between children with and without traits of or confirmed sickle cell disease. In summary, our findings show that a high percentage of the pneumococcal disease were caused by the serotypes that are covered by currently available vaccines. Given the low prevalence of resistance, macrolide antibiotics, such as erythromycin, should be considered as an option to treat pneumococcal disease in Nigeria. However, appropriate use of macrolide antibiotics should be vigilantly monitored to prevent the potential increase in macrolide resistance.

Antimicrobial resistance monitoring in the Danish swine production by phenotypic methods and metagenomics from 1999 to 2018.

BackgroundIn Denmark, antimicrobial resistance (AMR) in pigs has been monitored since 1995 by phenotypic approaches using the same indicator bacteria. Emerging methodologies, such as metagenomics, may allow novel surveillance ways.AimThis study aimed to assess the relevance of indicator bacteria (Escherichia coli and Enterococcus faecalis) for AMR surveillance in pigs, and the utility of metagenomics.MethodsWe collated existing data on AMR and antimicrobial use (AMU) from the Danish surveillance programme and performed metagenomics sequencing on caecal samples that had been collected/stored through the programme during 1999-2004 and 2015-2018. We compared phenotypic and metagenomics results regarding AMR, and the correlation of both with AMU.ResultsVia the relative abundance of AMR genes, metagenomics allowed to rank these genes as well as the AMRs they contributed to, by their level of occurrence. Across the two study periods, resistance to aminoglycosides, macrolides, tetracycline, and beta-lactams appeared prominent, while resistance to fosfomycin and quinolones appeared low. In 2015-2018 sulfonamide resistance shifted from a low occurrence category to an intermediate one. Resistance to glycopeptides consistently decreased during the entire study period. Outcomes of both phenotypic and metagenomics approaches appeared to positively correlate with AMU. Metagenomics further allowed to identify multiple time-lagged correlations between AMU and AMR, the most evident being that increased macrolide use in sow/piglets or fatteners led to increased macrolide resistance with a lag of 3-6 months.ConclusionWe validated the long-term usefulness of indicator bacteria and showed that metagenomics is a promising approach for AMR surveillance.

Pathogenesis, epidemiology and control of Group A Streptococcus infection.

Streptococcus pyogenes (Group A Streptococcus; GAS) is exquisitely adapted to the human host, resulting in asymptomatic infection, pharyngitis, pyoderma, scarlet fever or invasive diseases, with potential for triggering post-infection immune sequelae. GAS deploys a range of virulence determinants to allow colonization, dissemination within the host and transmission, disrupting both innate and adaptive immune responses to infection. Fluctuating global GAS epidemiology is characterized by the emergence of new GAS clones, often associated with the acquisition of new virulence or antimicrobial determinants that are better adapted to the infection niche or averting host immunity. The recent identification of clinical GAS isolates with reduced penicillin sensitivity and increasing macrolide resistance threatens both frontline and penicillin-adjunctive antibiotic treatment. The World Health Organization (WHO) has developed a GAS research and technology road map and has outlined preferred vaccine characteristics, stimulating renewed interest in the development of safe and effective GAS vaccines.

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States.

BackgroundManagement of pneumococcal disease is complicated by high rates of antimicrobial resistance (AMR). This study assessed AMR trends for Streptococcus pneumoniae isolates from adults with pneumococcal disease.MethodsFrom January 2011 to February 2020, we evaluated 30-day nonduplicate S. pneumoniae isolates from 290 US hospitals (BD Insights Research Database) from adults (≥18 years) in inpatient and outpatient settings. Isolates were required to have ≥1 AMR result for invasive (blood, cerebrospinal fluid/neurologic) or noninvasive (respiratory or ear/nose/throat) pneumococcal disease samples. Determination of AMR was based on facility reports of intermediate or resistant. Descriptive statistics and generalized estimated equations were used to assess variations over time.ResultsOver the study period, 34 039 S. pneumoniae isolates were analyzed (20 749 [61%] from noninvasive sources and 13 290 [39%] from invasive sources). Almost half (46.6%) of the isolates were resistant to ≥1 drug, and noninvasive isolates had higher rates of AMR than invasive isolates. Total S. pneumoniae isolates had high rates of resistance to macrolides (37.7%), penicillin (22.1%), and tetracyclines (16.1%). Multivariate modeling identified a significant increasing trend in resistance to macrolides (+1.8%/year; P < .001). Significant decreasing trends were observed for penicillin (−1.6%/year; P < .001), extended-spectrum cephalosporins (ESCs; −0.35%/year; P < .001), and ≥3 drugs (−0.5%/year; P < .001).ConclusionsDespite decreasing trends for penicillin, ESCs, and resistance to ≥3 drugs, AMR rates are persistently high in S. pneumoniae isolates among US adults. Increasing macrolide resistance suggests that efforts to address AMR in S. pneumoniae may require antimicrobial stewardship efforts and higher-valent pneumococcal conjugate vaccines.

Lefamulin: a New Hope in the Field of Community-Acquired Bacterial Pneumonia

Purpose of ReviewCommunity-acquired bacterial pneumonia (CABP) continues to be a worldwide health concern since it is the major cause of mortality and hospitalisation worldwide. Increased macrolide resistance among Streptococcus pneumoniae and other infections has resulted in a significantly larger illness burden, which has been exacerbated by evolving demography and a higher prevalence of comorbid disorders. Owing to such circumstances, the creation of new antibiotic classes is critical.Recent FindingsLefamulin, also referred to as BC-3781, is the primary pleuromutilin antibiotic which has been permitted for both intravenous and oral use in humans for the remedy of bacterial infections. It has shown activity against gram-positive bacteria including methicillin-resistant strains as well as atypical organisms which as often implicated in CABP. It has a completely unique mechanism of action that inhibits protein synthesis via way of means of stopping the binding of tRNA for peptide transfer. The C(14) side chain is responsible for its pharmacodynamic and antimicrobial properties, together with supporting in overcoming bacterial ribosomal resistance and mutations improvement amplifying the number of hydrogen bonds to the target site.SummaryThis review aims to highlight the pre-existing treatment options and specific purposes to shed some light upon the development of a new drug lefamulin and its specifications and explore this novel drug’s superior efficacy to already existing treatment strategies.

Increase of Macrolide-Resistance in Streptococcus pneumoniae Strains After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Lima, Peru.

Streptococcus pneumoniae upper respiratory infections and pneumonia are often treated with macrolides, but recently macrolide resistance is becoming an increasingly important problem. The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the National Immunization Program of Peru in 2015. This study aimed to evaluate the temporal evolution of macrolide resistance in S. pneumoniae isolates collected in five cross-sectional studies conducted before and after this vaccine introduction, from 2006 to 2019 in Lima, Peru. A total of 521 and 242 S. pneumoniae isolates recovered from nasopharyngeal swabs from healthy carrier children < 2 years old (2 carriage studies) and samples from normally sterile body areas from pediatric patients with invasive pneumococcal disease (IPD) (3 IPD studies), respectively, were included in this study. Phenotypic macrolide resistance was detected using the Kirby-Bauer method and/or MIC test. We found a significant increase in macrolide resistance over time, from 33.5% to 50.0% in carriage studies, and from 24.8% to 37.5% and 70.8% in IPD studies. Macrolide resistance genes [erm(B) and mef(A/E)] were screened using PCR. In carriage studies, we detected a significant decrease in the frequency of mef(A/E) genes among macrolide-resistant S. pneumoniae strains (from 66.7% to 50.0%) after introduction of PCV13. The most common mechanism of macrolide-resistant among IPD strains was the presence of erm(B) (96.0%, 95.2% and 85.1% in the 3 IPD studies respectively). Macrolide resistance was more common in serotype 19A strains (80% and 90% among carriage and IPD strains, respectively) vs. non-serotype 19A (35.5% and 34.4% among carriage and IPD strains, respectively). In conclusion, S. pneumoniae macrolide resistance rates are very high among Peruvian children. Future studies are needed in order to evaluate macrolide resistance trends among pneumococcal strains, especially now after the COVID-19 pandemic, since azithromycin was vastly used as empiric treatment of COVID-19 in Peru.

Population Genomics Reveals Distinct Temporal Association with the Emergence of ST1 Serotype V Group B Streptococcus and Macrolide Resistance in North America.

Identified in the 1970s as the leading cause of invasive bacterial disease in neonates and young infants, group B Streptococcus (GBS) is now also recognized as a significant cause of morbidity and mortality among adults with underlying medical conditions and the elderly. Concomitant with the increasing incidence of GBS invasive disease in adults is the rise of resistance among GBS isolates to second line antibiotics. Previous research shows that among serotype V GBS, one of the most common capsular types causing adult invasive disease, sequence type 1 (ST1), accounts for an overwhelming majority of adult invasive disease isolates and frequently harbors macrolide resistance. In this study, using whole-genome sequencing data from strains isolated in the United States and Canada over a 45-year period, we examined the association of antimicrobial resistance with the emergence of invasive serotype V ST1 GBS. Our findings show a strong temporal association between increased macrolide resistance and the emergence of serotype V ST1 GBS subpopulations that currently co-circulate to cause invasive disease in adults and young infants. ST1 GBS subpopulations are defined, in part, by the presence of macrolide resistance genes in mobile genetic elements. Increased frequency of macrolide resistance-encoding mobile genetic elements among invasive GBS ST1 strains suggests the presence of such elements contributes to GBS virulence. Our work provides a foundation for the investigation of genetic features contributing to the increasing prevalence and pathogenesis of serotype V GBS in adult invasive disease.

Increased Macrolide Resistance Rate of M3562 Mycoplasma pneumoniae Correlated With Macrolide Usage and Genotype Shifting.

To characterize Mycoplasma pneumoniae (MP) strains and to clarify the continuous high rates of macrolide resistance, 1,524 oropharyngeal swabs collected from children in Beijing Children’s Hospital infected with MP during 2016-2019 were analyzed. Among the 1,524 samples, 1,386 harbored mutations associated with macrolide resistance; 1,049 samples were successfully classified into 11 genotypes using multiple locus variable-number tandem-repeat analysis (MLVA). The proportion of the predominant type, M4572, decreased from 84.49 to 70.77% over the time period examined, while that of M3562 increased from 11.63 to 24.67%. Notably, we also found that the frequency of macrolide resistance in M3562 drastically increased, from 60% in 2016 to 93.48% in 2019. Clinical data suggested that the frequency of resistant M3562 was higher in the macrolide usage group than in the nondrug usage group (90.73 vs 53.57%, P<0.0001), while the resistance rate of M4572 was not substantially affected by previous macrolide exposure. These findings validated that antimicrobial application and clonal expansion of resistant MP strains play important roles in the high rates of macrolide resistance.

Risk factors for the development of post-infectious bronchiolitis obliterans after Mycoplasma pneumoniae pneumonia in the era of increasing macrolide resistance

BackgroundThe prevalence of macrolide-resistant Mycoplasma pneumoniae (MP) pneumonia has been rapidly increased. MP pneumonia is a risk factor for the development of post-infectious bronchiolitis obliterans (PIBO). The aim of the present study was to identify the risk factors for the development of PIBO after MP pneumonia in the era of increasing macrolide resistance of MP. Materials and methodsThis retrospective study enrolled 150 children with a mean age of 6.0 years admitted to the hospital due to MP pneumonia between May 2019 and February 2020 at a tertiary hospital. The clinical, radiologic, and laboratory data were obtained using retrospective chart review. ResultsEighteen children (12%) were diagnosed with PIBO after MP pneumonia. PIBO was diagnosed after a mean duration of 100.0 days (range, 6–268 days) from symptom onset. The respiratory virus co-infection (adjusted odds ratio [aOR], 4.069; 95% confidence interval [95% CI], 1.224–13.523), adenovirus co-infection (aOR, 5.607; 95% CI, 1.801–17.454), longer duration between symptom onset and admission (aOR, 1.150; 95% CI, 1.020–1.298), higher levels of serum lactate dehydrogenase (LDH) at the time of admission (aOR, 1.001; 95% CI, 1.000–1.003), and poor response to stepwise treatment increased the risk for development of PIBO after MP pneumonia. However, macrolide resistance of MP was not associated with development of PIBO after MP pneumonia. ConclusionThe present study suggests that respiratory virus co-infection, including adenovirus, poor response to the treatment of MP pneumonia, and higher levels of serum LDH, but not macrolide resistance of MP, are risk factors of PIBO after MP pneumonia.

Mass drug administration with azithromycin for trachoma elimination and the population structure of Streptococcus pneumoniae in the nasopharynx

ObjectiveMass drug administration (MDA) with azithromycin for trachoma elimination reduces nasopharyngeal carriage of Streptococcus pneumoniae in the short term. We evaluated S. pneumoniae carried in the nasopharynx before and after a round of azithromycin MDA to determine whether MDA was associated with changes in pneumococcal population structure and resistance. MethodsWe analysed 514 pneumococcal whole genomes randomly selected from nasopharyngeal samples collected in two Gambian villages that received three annual rounds of MDA for trachoma elimination. The 514 samples represented 293 participants, of which 75% were children aged 0–9 years, isolated during three cross-sectional surveys (CSSs) conducted before the third round of MDA (CSS-1) and at 1 (CSS-2) and 6 (CSS-3) months after MDA. Bayesian Analysis of Population Structure (BAPS) was used to cluster related isolates by capturing variation in the core genome. Serotype and multilocus sequence type were inferred from the genotype. Antimicrobial resistance determinants were identified from assemblies, including known macrolide resistance genes. ResultsTwenty-seven BAPS clusters were assigned. These consisted of 81 sequence types (STs). Two BAPS clusters not observed in CSS-1 (n = 109) or CSS-2 (n = 69), increased in frequency in CSS-3 (n = 126); BAPS20 (8.73%, p 0.016) and BAPS22 (7.14%, p 0.032) but were not associated with antimicrobial resistance. Macrolide resistance within BAPS17 increased after treatment (CSS-1 n = 0/6, CSS-2/3 n = 5/5, p 0.002) and was carried on a mobile transposable element that also conferred resistance to tetracycline. DiscussionLimited changes in pneumococcal population structure were observed after the third round of MDA, suggesting treatment had little effect on the circulating lineages. An increase in macrolide resistance within one BAPS highlights the need for antimicrobial resistance surveillance in treated villages.

First Detection and Characterization of Macrolide-Resistant Mycoplasma pneumoniae from People with Community-Acquired Pneumonia in Iran.

Objectives: Increasing macrolide resistance of Mycoplasma pneumoniae strains is becoming a public health concern worldwide. Nevertheless, no comprehensive genomic background of circulating isolates is available in our region. We aimed to study the genetic diversity of this microorganism using the multiple-locus variable-number tandem-repeat analysis method and to investigate the relationships between MLVA types and macrolide susceptibility profiles of the isolates. Materials and Methods: A total of 270 patients attending Tehran general university hospitals were included in this study. One throat swab was taken from each patient. M. pneumoniae was identified using culture and PCR assay. Macrolide resistance was determined using the broth microdilution method. The MLVA was performed by amplification of four variable-number tandem-repeat loci. Results: Of 270 specimens, M. pneumoniae was detected in 25.2% (n = 68) and 21.8% (n = 59) samples using PCR and culture, respectively. Approximately 56.9% of isolates were resistant to macrolides. Fifty-one of 59 M. pneumoniae isolates were divided into 6 distinct MLVA types. Conclusion: The macrolide-resistant M. pneumoniae (MRMP) rate in this study was relatively high and most of the MRMP isolates were assigned into the type 4/5/7/2. Since a significant association between MLVA type 4/5/7/2 and macrolide resistance of M. pneumoniae isolates was observed, further monitoring of genetic diversity of MRMP isolates might facilitate better understanding of epidemiology of this microorganism. Besides surveillance of the antibiotic susceptibility might be helpful to make necessary reconsiderations on guidelines for treatment of M. pneumoniae infection.

Macrolide resistance pattern of staphylococci collected from hospitalized patients in Egypt

Macrolide resistance of staphylococci has risen dramatically in recent years generating a real challenge for their treatment as therapeutic options have become very limited. In this study, an antibiogram analysis of one hundred and fifty Staphylococcus sp. isolates collected from various clinical specimens, against erythromycin, azithromycin, spiramycin, and clindamycin was carried out. Out of the 150 collected Staphylococcus sp. isolates, 54 isolates (36%) showed resistance to two or more of the tested macrolides. Inducible macrolide, lincosamides and streptogramin type B resistance phenotype (iMLS) using D-test was identified in 15 of the resistant isolates (27.8%). Molecular detection of major genes coding for macrolide resistance, including erythromycin ribosomal methylase (ermA and ermC), and macrolide-streptogramin resistance gene (msrA) was carried out using PCR. It was found that 51.8, 37.1 and 11.1% of the resistant isolates carried one, two and three types of the resistance genes, respectively. However, ermC was the most frequently occurring gene (81.5%), followed by the msrA gene (42.6%), then the ermA gene (35.2%). In conclusion, the genotypic analysis revealed that the majority of the tested isolates harbored two or more macrolide resistance-coding genes where 36% displayed resistance to at least two of the most common macrolide antibiotics used in the treatment of such important pathogens particularly in patients exhibiting hypersensitivity to penicillins according to several international guidelines. Therefore, it is crucial to carry out more epidemiologic studies to clearly understand the problem of increasing macrolide resistance among Staphylococci and to implement new guidelines for the treatment of such important pathogens, particularly in Egypt.

Comparative efficacy of Chinese herbal injections combined with azithromycin for mycoplasma pneumonia in children: A Bayesian network meta-analysis of randomized controlled trials.

What is known and objectiveAn increasing macrolide resistance leads to complex clinical treatment schemes in mycoplasma pneumonia in children. Chinese herbal injection (CHI) is widely used to treat it and may provide a new treatment regimen. This study was conducted to systematically evaluate the efficacy of CHIs combined with azithromycin for treating mycoplasma pneumonia in children by Bayesian network meta‐analysis.MethodsRandomized controlled trials (RCTs) of CHIs combined with azithromycin for mycoplasma pneumonia in children were searched in electronic databases and related references from initiation to 30 October 2018. Two researchers conducted data extraction and risk of bias assessment. WinBUGS software and STATA software were adopted to analyse the data.ResultsA total of 167 RCTs were included with 5 CHIs involving 16 144 patients. All CHIs combined with azithromycin had superior effects than azithromycin only among overall outcomes. Yanhuning injection combined with azithromycin ranked highest in four different outcomes and second in two based on surface under the cumulative ranking probabilities (SUCRA). Meanwhile, the results of MD and 95% CIs of concerned outcomes indicated that only Yanhuning injection combined with azithromycin had better response than other CHIs combined with azithromycin. Moreover, cluster analysis results revealed Reduning injection combined with azithromycin was associated with a positive effect on the three group outcomes. Similarly, it was found to be the top three ranking in all outcomes based on SUCRA.What is new and conclusionYanhuning injection combined with azithromycin and Reduning injection combined with azithromycin were found to be preferable treatments based on the data of this study.

Lack of correlation between reduced outpatient consumption of macrolides and macrolide resistance of invasive Streptococcus pneumoniae isolates in Slovenia during 1997-2017.

The objective of this study was to investigate the correlation between decreased national consumption of macrolides and resistance of invasive Streptococcus pneumoniae isolates in Slovenia during 1997-2017. A total of 4241 invasive S. pneumoniae isolates were collected in Slovenia from 1997 to 2017. The presence of erm(B), mef(E), mef(A) and erm(TR) genes was determined by PCR in 612 erythromycin-resistant isolates. Selected isolates carrying the mef(A) gene were further examined by pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing (MLST) was performed for 161 erythromycin-resistant isolates from 2004 to 2009. Consumption of macrolides decreased by 42.5% between 1997 and 2017, and by 57.0% from the highest consumption during 1999 to 2017. Resistance of S. pneumoniae increased by 120.7% in the same period, from 5.8% in 1997 to 12.8% in 2017. The most prevalent serotypes among macrolide-resistant isolates were 14 (54.9%), 19A (9.0%), 19F (8.3%), 6B (7.2%), 6A (5.2%) and 9V (19; 3.0%). The most prevalent determinant of macrolide resistance in the observed period was erm(B) (43.0%; 263/612), followed by mef(A) (36.3%; 222/612) and mef(E) (14.9%; 91/612). During the study period, an increasing trend in serotype 14, mef(A)-carrying isolates was observed, with a peak in 2011 (P<0.001); 63/71 isolates (88.7%) with the mef(A) gene were clonally related and were related to the international England14-9 clonal cluster. The reason for the observed increase in macrolide resistance among invasive S. pneumoniae in Slovenia despite decreased macrolide consumption was spread of the England14-9 clonal cluster.

Clonal Expansion of Macrolide-Resistant Sequence Type 3 Mycoplasma pneumoniae, South Korea.

To investigate the genetic background for the emergence of macrolide resistance, we characterized the genetic features of Mycoplasma pneumoniae using multilocus sequence typing. Of the 146 M. pneumoniae strains collected during the 5 consecutive outbreaks of M. pneumoniae pneumonia during 2000–2016 in South Korea, macrolide resistance increased from 0% in the first outbreak to 84.4% in the fifth. Among the 8 sequence types (STs) identified, ST3 (74.7%) was the most prevalent, followed by ST14 (15.1%). Macrolide-susceptible strains comprised 8 different STs, and all macrolide-resistant strains were ST3 (98.3%) except 1 with ST14. The proportion of macrolide-resistant strains in ST3 remained 2.2% (1/46) until the 2006–2007 outbreak and then markedly increased to 82.6% (19/23) during the 2010–2012 outbreak and 95.0% (38/40) during the 2014–2016 outbreak. The findings demonstrated that clonal expansion of ST3 M. pneumoniae was associated with the increase in macrolide resistance in South Korea.

Increasing macrolide resistance among Streptococcus agalactiae causing invasive disease in non-pregnant adults was driven by a single capsular-transformed lineage, Portugal, 2009 to 2015.

We characterised Lancefield group B streptococcal (GBS) isolates causing invasive disease among non-pregnant adults in Portugal between 2009 and 2015. All isolates (n = 555) were serotyped, assigned to clonal complexes (CCs) by multilocus sequence typing and characterised by surface protein and pilus island gene profiling. Antimicrobial susceptibility was tested by disk diffusion and resistance genotypes identified by PCR. Overall, serotype Ia was most frequent in the population (31%), followed by serotypes Ib (24%) and V (18%). Serotype Ib increased significantly throughout the study period (p < 0.001) to become the most frequent serotype after 2013. More than 40% of isolates clustered in the CC1/alp3/PI-1+PI-2a genetic lineage, including most isolates of serotypes Ib (n = 110) and V (n = 65). Erythromycin and clindamycin resistance rates were 35% and 34%, respectively, both increasing from 2009 to 2015 (p < 0.010) and associated with CC1 and serotype Ib (p < 0.001). The Ib/CC1 lineage probably resulted from acquisition of the type Ib capsular operon in a single recombination event by a representative of the V/CC1 macrolide-resistant lineage. Expansion of the new serotype Ib/CC1 lineage resulted in increased macrolide resistance in GBS, causing invasive disease among adults in Portugal. The presence of this clone elsewhere may predict more widespread increase in resistance.

Molecular Typing and Macrolide Resistance of Syphilis Cases in Manitoba, Canada, From 2012 to 2016.

The province of Manitoba, Canada, with a population of approximately 1.3 million, has been experiencing increased incidence of syphilis cases since 2015. In this study, we examined the detection of Treponema pallidum DNA in 354 clinical samples from 2012 to 2016, and determined molecular types and mutations conferring resistance to azithromycin in the polymerase chain reaction (PCR)-positive samples. T. pallidum DNA detection was done by PCR amplification of tpp47, bmp, and polA genes. Syphilis serology results were reviewed for the PCR-positive cases. Molecular typing of syphilis strains was done by analysis of the T, pallidum arp, tpr, and tp0548 gene targets as well as partial sequencing of the 23S rRNA gene for azithromycin resistance. Of the 354 samples tested, 74 individual cases were PCR positive. A result from the treponemal antibody chemiluminescent microparticle immunoassay test was positive in 72 of these cases and that from the Venereal Disease Research Laboratory testing was positive in 66. Mutations conferring resistance to azithromycin were found in all 74 PCR-positive samples. Molecular typing was completed on 57 PCR-positive samples, and 12 molecular types were identified with 14d/g found in 63.2%. Increased strain diversity was observed with 8 molecular types detected in 2016, whereas only 2 to 3 types were found in 2012 to 2014. A patient with 2 episodes of infection 9 months apart caused by different molecular strain types was also identified. The finding of an increase in genetic diversity in the strains in this study and an increase in macrolide resistance compared with previous Canadian reports highlighted the need for continued surveillance including strain characterization.