Antibiotic-resistant Streptococcus Research Articles

Identification of Novel PBP2B Protein Inhibitors against Streptococcus pneumoniae in Marine Natural Products using an In-Silico Approach

Background: The aim of this research is to identify marine natural compounds derived from green, red, and brown algae that might possibly inhibit the Penicillin-Binding Proteins (PBPs) protein, which is responsible for the development of antibiotic resistance in Streptococcus pneumoniae (mutated resistant 5204-PBP2B strain). We obtained this by using virtual screening and molecular docking. In AutoDock Vina and the Schrodinger suite software, we screened a library of marine natural chemicals and discovered four intriguing candidates that had strong binding affinities to the active region of the PBPs protein. Based on our findings, four naturally occurring marine chemicals show great promise as new inhibitors of S. pneumoniae 5204-PBP2B protein. These discoveries reveal important new information on the potential application of marine natural products as a source of new drugs to combat antibiotic resistance in Streptococcus pneumoniae and other bacterial infections. Methods: The 3318 compounds in the Comprehensive Marine Natural Products Database (CMNPD) derived from green algae (293 compounds), brown algae (1212 compounds) and red algae (1813 compounds) were taken into consideration for this study. Through virtual screening and molecular docking investigations, we found the optimum compounds for the Penicillin-Binding Proteins (PBPs) protein in Streptococcus pneumoniae. Utilizing AutoDock Vina and Schrodinger Suite software, the 5204-PBP2B protein selected for this investigation was examined. The structure and binding interaction have been displayed using PyMOL software. Results: Through virtual screening and molecular docking investigations for the 5204-PBP2B protein in Streptococcus pneumoniae, we were able to identify four marine natural products that are present in brown algae from the Comprehensive Marine Natural Products Database. Conclusion: The study has indicated that the main cause of bacterial resistance to antibiotics is 5204-PBP2B in S. pneumoniae. This study's methodology has been shown to be effective in identifying four strong inhibitors of the CMNPD. In this work, potent molecules from CMNPD compounds were screened using the 3D structure of mutated resistant 5204 strain, named 5204- PBP2B (PDB ID: 2WAE) of S. pneumoniae. Out of 3318 compounds that showed strong interactions with PBP2B, docking studies revealed that four of the compounds were inhibitory for the protein and could be used to treat PBP2B. These four marine products were selected as a result of our earlier research on Klebsiella pneumonia’s New Delhi metallo-β-lactamase-1 (NDM-1) protein. This study thus reveals the importance of marine natural products for improving the drug development process, as well as the ability of four marine products generated from brown algae to inhibit both the NDM-1 protein of Klebsiella pneumoniae and the 5204-PBP2B protein in Streptococcus pneumoniae. It is also possible to expand this approach by investigating how different receptor inhibitors interact in a lab setting. Potential inhibitors can be discovered by evaluating the biological activity of the drugs and applying virtual screening and molecular docking techniques.

Decreased susceptibility to viscosin in Streptococcus pneumoniae.

Growing numbers of infections caused by antibiotic-resistant Streptococcus pneumoniae strains are a major concern for healthcare systems that will require new antibiotics for treatment as well as preventative measures that reduce the number of infections. Lipopeptides are antimicrobial molecules, of which some are used as antibiotics, including the last resort antibiotics daptomycin and polymyxins. Here we have studied the antimicrobial effect of the cyclic lipopeptide viscosin on S. pneumoniae growth and morphology. Most lipopeptides function as surfactants that create pores in membrane layers, which is regarded as their main antimicrobial activity. We show that viscosin can inhibit growth of S. pneumoniae without disintegration of the cytoplasmic membrane. Instead, the cells developed abnormal shapes and misplaced new division sites. The cell wall of these bacteria appeared less dense in electron microscopy images, suggesting that viscosin interfered with normal cell wall synthesis. Corroborating this observation, a luciferase reporter assay was used to show that the two-component systems LiaFSR and CiaRH, which are known to be activated upon cell wall stress, were strongly induced by viscosin. Furthermore, a mutant displaying 1.8-fold decreased susceptibility to viscosin was generated by sequential exposure to increasing concentrations of the lipopeptide. The mutant suffered from significant fitness loss and had mutations in genes involved in fatty acid synthesis, teichoic acid synthesis, and cell wall synthesis as well as transcription and translation. How these mutations might be linked to decreased viscosin susceptibility is discussed.IMPORTANCEStreptococcus pneumoniae is a leading cause of bacterial pneumonia, sepsis, and meningitis in children, and the incidence of infections caused by antibiotic-resistant strains is increasing. Development of new antibiotics is therefore necessary to treat these types of infections in the future. Here, we have studied the activity of the antimicrobial lipopeptide viscosin on S. pneumoniae and show that in addition to having the typical membrane destabilizing activity of lipopeptides, viscosin inhibits pneumococcal growth by obstructing normal cell wall synthesis. This suggests a more specific mode of action than just the surfactant activity. Furthermore, we show that S. pneumoniae does not easily acquire resistance to viscosin, which makes it a promising molecule to explore further, for example, by synthesizing less toxic derivates that can be tested for therapeutic potential.

L-Thyroxine and L-thyroxine-based antimicrobials against Streptococcus pneumoniae and other Gram-positive bacteria

ObjectivesThe rise of antibiotic-resistant Streptococcus pneumoniae (Sp) poses a significant global health threat, urging the quest for novel antimicrobial solutions. We have discovered that the human hormone l-thyroxine has antibacterial properties. In order to explore its drugability we perform here the characterization of a series of l-thyroxine analogues and describe the structural determinants influencing their antibacterial efficacy. MethodWe performed a high-throughput screening of a library of compounds approved for use in humans, complemented with ITC assays on purified Sp-flavodoxin, to pinpoint molecules binding to this protein. Antimicrobial in vitro susceptibility assays of the hit compound (l-thyroxine) as well as of 13 l-thyroxine analogues were done against a panel of Gram-positive and Gram-negative bacteria. Toxicity of compounds on HepG2 cells was also assessed. A combined structure-activity and computational docking analysis was carried out to uncover functional groups crucial for the antimicrobial potency of these compounds. ResultsHuman l-thyroxine binds to Sp-flavodoxin, forming a 1:1 complex of low micromolar Kd. While l-thyroxine specifically inhibited Sp growth, some derivatives displayed activity against other Gram-positive bacteria like Staphylococcus aureus and Enterococcus faecalis, while remaining inactive against Gram-negative pathogens. Neither l-thyroxine nor some selected derivatives exhibited toxicity to HepG2 cells. Conclusionsl-thyroxine derivatives targeting bacterial flavodoxins represent a new and promising class of antimicrobials.

Proteomics-based vaccine targets annotation and design of multi-epitope vaccine against antibiotic-resistant Streptococcus gallolyticus

Streptococcus gallolyticus is a non-motile, gram-positive bacterium that causes infective endocarditis. S. gallolyticus has developed resistance to existing antibiotics, and no vaccine is currently available. Therefore, it is essential to develop an effective S. gallolyticus vaccine. Core proteomics was used in this study together with subtractive proteomics and reverse vaccinology approach to find antigenic proteins that could be utilized for the design of the S. gallolyticus multi-epitope vaccine. The pipeline identified two antigenic proteins as potential vaccine targets: penicillin-binding protein and the ATP synthase subunit. T and B cell epitopes from the specific proteins were forecasted employing several immunoinformatics and bioinformatics resources. A vaccine (360 amino acids) was created using a combination of seven cytotoxic T cell lymphocyte (CTL), three helper T cell lymphocyte (HTL), and five linear B cell lymphocyte (LBL) epitopes. To increase immune responses, the vaccine was paired with a cholera enterotoxin subunit B (CTB) adjuvant. The developed vaccine was highly antigenic, non-allergenic, and stable for human use. The vaccine's binding affinity and molecular interactions with the human immunological receptor TLR4 were studied using molecular mechanics/generalized Born surface area (MMGBSA), molecular docking, and molecular dynamic (MD) simulation analyses. Escherichia coli (strain K12) plasmid vector pET-28a ( +) was used to examine the ability of the vaccine to be expressed. According to the outcomes of these computer experiments, the vaccine is quite promising in terms of developing a protective immunity against diseases. However, in vitro and animal research are required to validate our findings.

Transfer and accumulation of antibiotic resistance genes and bacterial pathogens in the mice gut due to consumption of organic foods

Over the last few decades, organic food demand has grown largely because of increasing personal health concerns. Organic farming introduces antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) into foods. However, potential effects of organic foods on the gut microbiome and ARGs have been overlooked. Using high-throughput quantitative PCR and 16S rRNA high-throughput sequencing technology, we examined 132 ARGs from major classes, eight transposase genes, universal class I integron-integrase gene (intI), clinical class I integron-integrase gene (cintI), and the bacterial community in mouse gut after 8 weeks with an either organic or inorganic lettuce and wheat diet. A total of 8 types of major ARGs and 10 mobile genetic elements (MGEs) were detected in mice gut, including tetracycline, multidrug, sulfonamide, aminoglycoside, beta-lactamase, chloramphenicol, MLSB and vancomycin resistance genes. We found that abundance and diversity of ARGs, mobile gene elements, and potential ARB in the gut increased with time after consumption of organic foods, whereas no significant changes were observed in inorganic treated groups. Moreover, MGEs, including IS613, Tp614 and tnpA_03 were found to play an important role in regulating ARG profiles in the gut microbiome following consumption of organic foods. Importantly, feeding organic food increased the relative abundance of the potentially antibiotic-resistant pathogens, Bacteroides and Streptococcus. Our results confirm that there is an increasing risk of ARGs and ARB in the gut microbiome, which highlights the importance of organic food industries taking into account the potential accumulation and transmission of ARGs as a risk factor.

Effect of Partially Purified Flavonoids from Albizia lebbeck (L) Benth Leaves Against Antibiotic-Resistant Streptococcus Isolates

Background:Plant flavonoids have strong biological activity, one of which is their antimicrobial activity. The design of this study, the content of flavonoids was determined in the leaves of the Albizia lebbeck plant, which is considered one of the medicinal plants.Materils and Methods: Extraction of flavonoids from the leaves of Albizia lebbeck ,Qualitative determination of flavonoids using thin-layer chromatography (TLC) of Albizia lebbeck leaf extract and quantitative analysis using high-performance liquid chromatography (HPLC) .Results: showed the appearance of spots of flavonoid groups. Kaempferol, while quantitative analysis using high-performance liquid chromatography (HPLC) showed the presence of Catechin, Gallic acid Epicatechin, Chlorogenic acid as two isomers a & b, Caffaic acid, Luetolin, Apigenin and Querecetin. Partially purified flavonoid extract from Albizia leaves showed a clear inhibition activity against 4 types of Streptococcus bacteria resistant to antibiotics: ampicillin, tetracycline, clarithromycine, clindamycin, and rifampin.Conclusion: These results encourage the possibility of using the active compounds of this plant as safe alternatives against pathogenic isolates of the genus Streptococcus. other bacterial genera.

Zinc Oxide Quantum Dots May Provide a Novel Potential Treatment for Antibiotic-Resistant Streptococcus agalactiae in Lama glama.

Streptococcus agalactiae is a significant pathogen that can affect both human beings and animals. The extensive current use of antibiotics has resulted in antibiotic resistance. In our previous research, we found that zinc oxide quantum dots (ZnO QDs) had inhibitory effects on antibiotic-resistant microorganisms. In this study, a strain of Streptococcus agalactiaeWJYT1 with a broad antibiotic-resistant spectrum was isolated and identified from Lama glama at Sichuan Agricultural University Teaching Animal Hospital. The genome for the resistance and virulence genes was analyzed. Additionally, the antibacterial effects and anti-virulence mechanism of ZnO QDs for S. agalactiaeWJYT1 were investigated. The results showed that the genome of S. agalactiaeWJYT1 is 1,943,955 bp, containing 22 resistance genes and 95 virulence genes. ZnO QDs have a good antibacterial effect against S. agalactiaeWJYT1 by reducing bacterial growth and decreasing the expression of virulence genes, including bibA, hylB, sip, and cip, which provides a novel potential treatment for S. agalactiae.

Ozone ultrafine bubble water exhibits bactericidal activity against pathogenic bacteria in the oral cavity and upper airway and disinfects contaminated healthcare equipment.

Ozone is strong oxidizing agent that is applied in aqueous form for sanitation. However, ozonated water is unstable and has a short half-life. Ultrafine bubble technology is promising to overcome these issues. Ultrafine bubble is nanoscale bubble and can exist in water for a considerable duration of time. This study aims to investigate the application of ozone ultrafine bubble water (OUFBW) as a disinfectant. We produced an OUFBW generator which generates OUFBW containing 4-6 ppm of ozone. Thereafter, we examined the bactericidal activity of the OUFBW against various pathogenic bacteria in oral cavity and upper airway, including antibiotic-susceptible and antibiotic-resistant Streptococcus pneumoniae, Pseudomonas aeruginosa, Streptococcus mutans, Streptococcus sobrinus, Fusobacterium nucleatum, Prevotella intermedia, and Porphyromonas gingivalis. Exposure of planktonic culture of these bacterial species to OUFBW reduced viable bacteria by > 99% within 30s. Additionally, OUFBW exerted bactericidal activity against S. pneumoniae and P. aeruginosa adhered to toothbrush and gauze, respectively. We also observed disruption of bacterial cell wall of S. pneumoniae exposed to OUFBW by transmission electron microscope. Additionally, OUFB did not show any significant cytotoxicity toward the human gingival epithelial cell line Ca9-22. These results suggest that OUFBW exhibits bactericidal activity against broad spectrum of bacteria and has low toxicity towards human cells.

A novel proteinaceous molecule produced by Lysinibacillus sp. OF-1 depends on the Ami oligopeptide transporter to kill Streptococcus pneumoniae.

Infections caused by antibiotic-resistant Streptococcus pneumoniae are of growing concern for healthcare systems, which need new treatment options. Screening microorganisms in terrestrial environments has proved successful for discovering antibiotics, while production of antimicrobials by marine microorganisms remains underexplored. Here we have screened microorganisms sampled from the Oslo Fjord in Norway for production of molecules that prevent the human pathogen S. pneumoniae from growing. A bacterium belonging to the genus Lysinibacillus was identified. We show that this bacterium produces a molecule that kills a wide range of streptococcal species. Genome mining in BAGEL4 and AntiSmash suggested that it was a new antimicrobial compound, and we therefore named it lysinicin OF. The compound was resistant to heat (100 °C) and polymyxin acylase but susceptible to proteinase K, showing that it is of proteinaceous nature, but most probably not a lipopeptide. S. pneumoniae became resistant to lysinicin OF by obtaining suppressor mutations in the ami locus, which encodes the AmiACDEF oligo peptide transporter. We created ΔamiC and ΔamiEF mutants to show that pneumococci expressing a compromised Ami system were resistant to lysinicin OF. Furthermore, by creating mutants expressing an intact but inactive Ami system (AmiED184A and AmiFD175A) we could conclude that the lysinicin OF activity depended on the active form (ATP-hydrolysing) of the Ami system. Microscopic imaging and fluorescent labelling of DNA showed that S. pneumoniae treated with lysinicin OF had an average reduced cell size with condensed DNA nucleoid, while the integrity of the cell membrane remained intact. The characteristics and possible mode of action of lysinicin OF are discussed.

Cross-sectional Study of Multiple Antibiotic-resistant Streptococcus suis in Pigs and Environs

Streptococcus suis; a dominant specie found in pigs and environs, has been receiving drastically attention not only in causing human infections but also for its involvement in antibiotic resistance, of which 80% of these resistant genes are encoded in the plasmid. This study was undertaken to evaluate the plasmid curing potentials of some selected plant seed extracts against antibiotic-resistant Streptococcus suis isolated from pigs and environs. Samples were collected from different anatomical sites of the pigs and their environs and screened for the presence of Streptococcus suis using standard microbiological techniques. The resistant strains were detected by subjecting the isolates to an antibiotic susceptibility test using the disk diffusion method. The study revealed the presence of Streptococcus suis Q, Streptococcus suis R, Streptococcus suis S and Streptococcus suis Y, of which 24.14%, 100.00%, 41.67% and 39.23% of isolates Q, R, S and Y respectively that were resistant to antibiotics; 64.29%, 100.00% and 63.64% were multiple antibiotic resistant (MAR) strains, and 61.76% of the resistant strains had MAR index greater than 0.2. From the above study, different strains of multiple antibiotic-resistant Streptococcus suis were isolated from pigs and environs, of which isolate Q was most predominant, especially in nasal samples.

Genetic markers of antibiotic resistance of Streptococcus spp. and Staphylococcus spp. isolated from various biotopes of livestock production objects

Genetic markers of antibiotic resistance of Streptococcus spp. and Staphylococcus spp. isolated from various biotopes of livestock production objects

Aloe-Emodin-Mediated Photodynamic Therapy Attenuates Sepsis-Associated Toxins in Selected Gram-Positive Bacteria In Vitro.

Sepsis is an acute inflammatory response that leads to life-threatening complications if not quickly and adequately treated. Cytolysin, hemolysin, and pneumolysin are toxins produced by gram-positive bacteria and are responsible for resistance to antimicrobial drugs, cause virulence and lead to sepsis. This work assessed the effects of aloe-emodin (AE) and photodynamic therapy (PDT) on sepsis-associated gram-positive bacterial toxins. Standard and antibiotic-resistant Enterococcus faecalis, Staphylococcus aureus, and Streptococcus pneumonia bacterial strains were cultured in the dark with varying AE concentrations and later irradiated with 72 J/cm-2 light. Colony and biofilm formation was determined. CCK-8, Griess reagent reaction, and ELISA assays were done on bacteria-infected RAW264.7 cells to determine the cell viability, NO, and IL-1β and IL-6 pro-inflammatory cytokines responses, respectively. Hemolysis and western blot assays were done to determine the effect of treatment on hemolysis activity and sepsis-associated toxins expressions. AE-mediated PDT reduced bacterial survival in a dose-dependent manner with 32 μg/ml of AE almost eliminating their survival. Cell proliferation, NO, IL-1β, and IL-6 cytokines production were also significantly downregulated. Further, the hemolytic activities and expressions of cytolysin, hemolysin, and pneumolysin were significantly reduced following AE-mediated PDT. In conclusion, combined use of AE and light (435 ± 10 nm) inactivates MRSA, S. aureus (ATCC 29213), S. pneumoniae (ATCC 49619), MDR-S. pneumoniae, E. faecalis (ATCC 29212), and VRE (ATCC 51299) in an AE-dose dependent manner. AE and light are also effective in reducing biofilm formations, suppressing pro-inflammatory cytokines, hemolytic activities, and inhibiting the expressions of toxins that cause sepsis.

Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains.

Antibiotic resistance in Streptococcus pneumoniae has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Levofloxacin (12.5 to 50 mg/kg) or seconeolitsine (5 to 40 mg/kg) were administered every 12 h during two days in mice infected with a serotype 8-resistant strain. At 48 h, a 70% protection was obtained with seconeolitsine (40 mg/kg; p < 0.001). However, survival with levofloxacin was 20%, regardless of the dose. In addition, seconeolitsine decreased bacteremia efficiently. Levofloxacin had higher levels in serum than seconeolitsine (Cmax of 14.7 vs. 1.6; p < 0.01) and higher values of area under the serum concentration-time curve (AUC0-12h of 17.3 vs. 5; p < 0.01). However, seconeolitsine showed higher levels of time to peak concentration and elimination half-life. This is consistent with the higher binding of seconeolitsine to plasma proteins (40% and 80% when used at 1 µg/mL and 50 µg/mL, respectively) in comparison to levofloxacin (12% at 5 µg/mL and 33% at 50 µg/mL). Our results suggest that seconeolitsine would be a promising therapeutic alternative against pneumococcal isolates with high fluoroquinolone resistance levels.

Tackling Multidrug Resistance in Streptococci - From Novel Biotherapeutic Strategies to Nanomedicines.

The pyogenic streptococci group includes pathogenic species for humans and other animals and has been associated with enduring morbidity and high mortality. The main reason for the treatment failure of streptococcal infections is the increased resistance to antibiotics. In recent years, infectious diseases caused by pyogenic streptococci resistant to multiple antibiotics have been raising with a significant impact to public health and veterinary industry. The rise of antibiotic-resistant streptococci has been associated to diverse mechanisms, such as efflux pumps and modifications of the antimicrobial target. Among streptococci, antibiotic resistance emerges from previously sensitive populations as result of horizontal gene transfer or chromosomal point mutations due to excessive use of antimicrobials. Streptococci strains are also recognized as biofilm producers. The increased resistance of biofilms to antibiotics among streptococci promote persistent infection, which comprise circa 80% of microbial infections in humans. Therefore, to overcome drug resistance, new strategies, including new antibacterial and antibiofilm agents, have been studied. Interestingly, the use of systems based on nanoparticles have been applied to tackle infection and reduce the emergence of drug resistance. Herein, we present a synopsis of mechanisms associated to drug resistance in (pyogenic) streptococci and discuss some innovative strategies as alternative to conventional antibiotics, such as bacteriocins, bacteriophage, and phage lysins, and metal nanoparticles. We shall provide focused discussion on the advantages and limitations of agents considering application, efficacy and safety in the context of impact to the host and evolution of bacterial resistance.

Spectrum and resistance determinants of oral streptococci clinical isolates.

The profiles of oral streptococci sensitivity to antibacterial drugs may reflect information about the presence of macroorganism resistance determinants. The aim of the work was to isolate the spectrum of oral streptococci from the microbiota of the oral cavity of patients and to determine their sensitivity to a wide range of antibiotics. A total of 342 microbial streptococcal isolates were isolated from saliva samples and a periodontal pocket and tested for antibiotic sensitivity. Species identification of streptococci was carried out using biochemical API test systems. Evaluation of antibiotic resistance was performed using E-tests. Real-time PCR was used to identify the presence of tetracycline and macrolide resistance genes. The study identified six types of oral streptococci: S. oralis, S. salivarius, S. mitis, S. sanguinis, S. anginosus and S. mutans. All streptococci were sensitive to linezolid and meropenem. The proportion of penicillin-resistant streptococci in the subgroup S. oralis / mitis / mutans was 47,8% versus 23,5% in the subgroup S. salivarius / sanguinis / anginosus (p = 0.020). Significant levels of resistance were revealed to macrolides (erythromycin) - 47,9%, tetracyclines (tetracycline) - 44,4% and quinolones (ofloxacin) - 41%. Multiple drug resistance (MDR) was detected in 31,9% of oral streptococcal isolates, a combination of erythromycin, tetracycline and ofloxacin resistance was prevalent in 79 isolates (23,1%). The most common genotypes of macrolides and tetracycline resistant oral streptococci (in 127 streptococcal isolates with combined resistance) were ermB-mefE + and tetM + tetQ-, respectively. Thus, S. oralis / mitis / mutans group streptococci predominated in the structure of antibiotic-resistant oral streptococci, including MDR. So, being in one of the most densely populated biotopes of a macroorganism, oral streptococci can mediate the transfer of resistance determinants to more pathogenic and clinically significant microorganisms, which requires careful monitoring of their level of susceptibility to antimicrobial agents.

Antibiotic resistance of Streptococcus pneumoniae isolated from children in Moscow before&#x0D; and after the introduction of 13-valent pneumococcal conjugate vaccination

Introduction. The formation and spread of antibiotic-resistant Streptococcus pneumoniae isolates is a concern. After the thirteen-valent pneumococcal conjugate vaccine (PCV13) was added to the children’s immunization program in Russia in 2014, an important task is to monitor the resistance level to antimicrobials and the spectrum of circulating antibiotic-resistant pneumococcal serotypes. Materials and methods. The study included 708 nasopharyngeal pneumococcal isolates from children patients under 5 years who recovered from 2010 to 2018, received inpatient and outpatient care at the National Medical Research Center for Children’s Health (Moscow). The determination of sensitivity to antimicrobials was performed by the disk diffusion method. The MICs of penicillin, amoxicillin, and erythromycin were determined using the E-test method. Evaluation of the results was carried out according to the EUCAST-2019 criteria. Results. In total, 33 different serotypes were identified in the S. pneumoniae collection. Six predominant serotypes accounted for 68.6% of the total distribution and included serotypes: 19F, 6B, 23F, 14, 15B/C, 6A. In general, antimicrobial resistance ranged from 3.5% to chloramphenicol to 54.8% to tetracycline. The level of resistance to oxacillin, erythromycin, and clindamycin increased by 15-20% between 2010 and 2018. However, since 2016, there has established a prevalence level of 40-46%, this process is offset by an increase in the proportion of non-vaccine pneumococcal serotypes. Conclusion. A high level of resistance to penicillin and erythromycin remains. Monitoring the resistance level to antibiotics and the epidemiology of serotypes, clarifying the laws of formation of resistance, and its spread in a dynamically changing pneumococcal population is an important area of microbiology.

Pneumococcal Carriage and Antibiotic Resistance in Children Younger than 5 Years in Nouna District, Burkina Faso.

Increasing antibiotic consumption has been shown to lead to increased antibiotic resistance selection. We evaluated the prevalence of antibiotic resistance in Streptococcus pneumoniae to commonly used antibiotic classes as well as correlations between resistance and antibiotic consumption at the individual and community levels in children aged 0-59 months in Nouna district, Burkina Faso. A population-based sample of 300 children aged 0-59 months was randomly selected from the most recent census in 18 communities in the Nouna Health and Demographic Surveillance Site. Caregivers were interviewed about children's recent antibiotic use, and a nasopharyngeal swab was collected from each child. Nasopharyngeal swabs were processed using standard microbiological methods to determine pneumococcal carriage and resistance. Community-level antibiotic consumption was determined by record review from primary healthcare facilities, which routinely collect prescription data for children aged 0-59 months. Streptococcus pneumoniae was isolated from 101 (35.7%) nasopharyngeal samples. Among positive isolates, co-trimoxazole (75.6%) and tetracycline (69.3%) resistance was the most common, followed by oxacillin (26.7%) and azithromycin (9.9%). Recent antibiotic use was associated with decreased pneumococcal carriage (odds ratio 0.56, 95% CI: 0.33-0.93) at the individual level. There was no statistically significant relationship between antibiotic use and antibiotic resistance at the individual or community levels, although CIs were generally wide. The prevalence of antibiotic resistance to commonly used antibiotics was high in the study area. Expanding antimicrobial resistance surveillance in areas with little population-based data will be important for informing policy related to antibiotic use.

Horizontal gene transfer rate is not the primary determinant of observed antibiotic resistance frequencies in Streptococcus pneumoniae.

The extent to which evolution is constrained by the rate at which horizontal gene transfer (HGT) allows DNA to move between genetic lineages is an open question, which we address in the context of antibiotic resistance in Streptococcus pneumoniae. We analyze microbiological, genomic, and epidemiological data from the largest-to-date sequenced pneumococcal carriage study in 955 infants from a refugee camp on the Thailand-Myanmar border. Using a unified framework, we simultaneously test prior hypotheses on rates of HGT and a key evolutionary covariate (duration of carriage) as determinants of resistance frequencies. We conclude that in this setting, there is little evidence of HGT playing a major role in determining resistance frequencies. Instead, observed resistance frequencies are best explained as the outcome of selection acting on a pool of variants, irrespective of the rate at which resistance determinants move between genetic lineages.

Rising Pneumococcal Antibiotic Resistance in the Post-13-Valent Pneumococcal Conjugate Vaccine Era in Pediatric Isolates From a Primary Care Setting.

Antibiotic-resistant Streptococcus pneumoniae strains may cause infections that fail to respond to antimicrobial therapy. Results reported from hospitalized patients with invasive, bacteremic infections may not be the same as those observed in a primary care setting where young children receive care for noninvasive infections. Young children experience the highest burden of pneumococcal disease. The aim of this study was to determine the antibiotic susceptibility of S. pneumoniae strains isolated from children in a primary care setting in the post-13-valent pneumococcal conjugate vaccine (PCV13) era. This was a prospective collection of 1201 isolates of S. pneumoniae from 2006 through 2016 in a primary care setting. Antibiotic susceptibility testing to 16 different antibiotics of 10 classes was performed. Participants were children aged 6-36 months. Nasopharyngeal swabs were obtained from patients during acute otitis media (AOM) visits and routine healthy visits. Middle ear fluid was obtained by tympanocentesis. After introduction of PCV13, antibiotic susceptibility of pneumococci, especially to penicillin, initially improved largely due to disappearance of serotype 19A, included in PCV13. However, beginning in 2013, antibiotic susceptibility among pneumococcal strains began decreasing due to new serotypes not included in PCV13. In addition to reduced susceptibility to penicillin, the most recent isolates show reduced susceptibility to third-generation cephalosporins, fluoroquinolones, and carbapenems, antibiotics commonly used to treat life-threatening, invasive pneumococcal diseases. In recent years, pneumococcal nasopharyngeal and AOM isolates from children exhibit reduced susceptibility to penicillin, third-generation cephalosporin, fluoroquinolone, and carbapenem antibiotics. The new strains have a different profile of resistance compared to the pre-PCV13 era.

Azithromycin combination therapy increased emergence of antibiotic resistant Streptococcus pneumoniae in elderly patients hospitalized with pneumonia

Azithromycin combination therapy increased emergence of antibiotic resistant Streptococcus pneumoniae in elderly patients hospitalized with pneumonia