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1.
J Cell Biochem ; 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597421

RESUMO

Emerging nosocomial strains of Acinetobacter baumannii are of recent concern as they are expressing extensive drug resistance (XDR). Using whole-genome sequencing and molecular characterisation analysis, the current study reveals the presence of carbapenemase genes in 92.86% of studied Indian isolates. These included blaOXA-51 , blaOXA-23 , blaOXA-58 , and blaNDM genes, with over a third expressing dual carbapenemase genes. As per the MLST scheme, IC2Oxf /CC2Pas was the predominant clone, with 57.14% isolates belonging to this lineage. The presence of these carbapenemase genes resulted in sulbactam (SUL) resistance (MIC: 16-256 µg/ml) in all of the studied isolates. The efficacy of durlobactam (DUR), a novel ß-lactamase inhibitor that also inhibits PBP2 was assessed through in silico intermolecular interaction analysis. Several nonsynonymous single nucleotide polymorphisms were identified in PBP2 (G264S, I108V, S259T) and PBP3 (A515V, T526S) sequences. Minimal variations were recorded in the protein backbone dynamics in active-site motifs of wild-type and mutants, which correlated with negligible binding energy fluctuations for the PBP3-SUL (-5.85 ± 0.04 kcal/mol) and PBP2-DUR (-5.16 ± 0.66 kcal/mol) complexes. Furthermore, higher binding affinities and low inhibition constants were noted in OXA23-DUR (-7.36 kcal/mol; 4.01 µM), OXA58-DUR (-6.44 kcal/mol; 19.07 µM), and NDM-DUR (-6.82 kcal/mol; 10.01 µM) complexes when compared with the conventional drugs avibactam and aztreonam. Stable interaction profiles of DUR with carbapenemases can possibly restore SUL activity against both PBP3WT and PBP3MTs . The study establishes the efficacy of the novel SUL-DUR combination as a successful treatment strategy in combating emerging XDR strains of A. baumannii.

2.
Front Cell Infect Microbiol ; 11: 709681, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589442

RESUMO

Background: The incidence of hypervirulent (hv) carbapenem-resistant (CR) Klebsiella pneumoniae (Kp) is increasing globally among various clones and is also responsible for nosocomial infections. The CR-hvKp is formed by the uptake of a virulence plasmid by endemic high-risk clones or by the uptake of plasmids carrying antimicrobial resistance genes by the virulent clones. Here, we describe CR-hvKp from India belonging to high-risk clones that have acquired a virulence plasmid and are phenotypically unidentified due to lack of hypermucoviscosity. Methods: Twenty-seven CRKp isolates were identified to possess rmpA2 by whole-genome sequencing; and resistance and virulence determinants were characterized. By in silico protein modeling (and validation), protein backbone stability analysis, and coarse dynamics study, the fitness of RmpA, RmpA2, and aerobactin-associated proteins-IucA and IutA, were determined to establish a reliable marker for clinical identification of CR-hvKp. Results: The CR-hvKp belonged to multidrug-resistant (MDR) high-risk clones such as CG11, CG43, ST15, and ST231 and carried OXA-232 as the predominant carbapenemase followed by NDM. The virulence plasmid belonged to IncHI1B replicon type and carried frameshifted and truncated rmpA and rmpA2. This resulted in a lack of hypermucoviscous phenotype. However, functional aerobactin was expressed in all high-risk clones. In silico analysis portrayed that IucA and IutA were more stable than classical RmpA. Furthermore, IucA and IutA had lower conformational fluctuations in the functional domains than the non-functional RmpA2, which increases the fitness cost of the latter for its maintenance and expression among CR-hvKp. Hence, RmpA and RmpA2 are likely to be lost among CR-hvKp owing to the increased fitness cost while coding for essential antimicrobial resistance and virulence factors. Conclusion: Increasing incidence of convergence of AMR and virulence is observed among K. pneumoniae globally, which warrants the need for reliable markers for identifying CR-hvKp. The presence of non-functional RmpA2 among high-risk clones highlights the significance of molecular identification of CR-hvKp. The negative string test due to non-functional RmpA2 among CR-hvKp isolates challenges phenotypic screening and faster identification of this pathotype. This can potentially be counteracted by projecting aerobactin as a stable, constitutively expressed, and functional marker for rapidly evolving CR-hvKp.

3.
J Infect Dis ; 224(Supplement_3): S161-S173, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469555

RESUMO

BACKGROUND: The World Health Organization (WHO) coordinates the Global Invasive Bacterial Vaccine-Preventable Diseases (IB-VPD) Surveillance Network to support vaccine introduction decisions and use. The network was established to strengthen surveillance and laboratory confirmation of meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. METHODS: Sentinel hospitals report cases of children <5 years of age hospitalized for suspected meningitis. Laboratories report confirmatory testing results and strain characterization tested by polymerase chain reaction. In 2019, the network included 123 laboratories that follow validated, standardized testing and reporting strategies. RESULTS: From 2014 through 2019, >137 000 suspected meningitis cases were reported by 58 participating countries, with 44.6% (n = 61 386) reported from countries in the WHO African Region. More than half (56.6%, n = 77 873) were among children <1 year of age, and 4.0% (n = 4010) died among those with reported disease outcome. Among suspected meningitis cases, 8.6% (n = 11 798) were classified as probable bacterial meningitis. One of 3 bacterial pathogens was identified in 30.3% (n = 3576) of these cases, namely S. pneumoniae (n = 2177 [60.9%]), H. influenzae (n = 633 [17.7%]), and N. meningitidis (n = 766 [21.4%]). Among confirmed bacterial meningitis cases with outcome reported, 11.0% died; case fatality ratio varied by pathogen (S. pneumoniae, 12.2%; H. influenzae, 6.1%; N. meningitidis, 11.0%). Among the 277 children who died with confirmed bacterial meningitis, 189 (68.2%) had confirmed S. pneumoniae. The proportion of pneumococcal cases with pneumococcal conjugate vaccine (PCV) serotypes decreased as the number of countries implementing PCV increased, from 77.8% (n = 273) to 47.5% (n = 248). Of 397 H. influenzae specimens serotyped, 49.1% (n = 195) were type b. Predominant N. meningitidis serogroups varied by region. CONCLUSIONS: This multitier, global surveillance network has supported countries in detecting and serotyping the 3 principal invasive bacterial pathogens that cause pediatric meningitis. Streptococcus pneumoniae was the most common bacterial pathogen detected globally despite the growing number of countries that have nationally introduced PCV. The large proportions of deaths due to S. pneumoniae reflect the high proportion of meningitis cases caused by this pathogen. This global network demonstrated a strong correlation between PCV introduction status and reduction in the proportion of pneumococcal meningitis infections caused by vaccine serotypes. Maintaining case-based, active surveillance with laboratory confirmation for prioritized vaccine-preventable diseases remains a critical component of the global agenda in public health.The World Health Organization (WHO)-coordinated Invasive Bacterial Vaccine-Preventable Disease (IB-VPD) Surveillance Network reported data from 2014 to 2019, contributing to the estimates of the disease burden and serotypes of pediatric meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

4.
Infect Dis Ther ; 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34357517

RESUMO

The treatment of urinary tract infections (UTIs) has been complicated by the emergence of multidrug-resistant, ß-lactamase-expressing pathogens. As a result of the limited treatment options, patients often require hospitalization and intravenous therapy. In essence, a strong unmet need for oral antibiotics, active against extended-spectrum ß-lactamase (ESBL) uropathogens has emerged. Oral carbapenems (tebipenem and sulopenem) and oral cephalosporin/ß-lactamase inhibitor combinations are in various stages of clinical development for the treatment of uncomplicated and complicated UTI. Tebipenem, if approved, will be the first oral treatment for complicated UTI while sulopenem will be for uncomplicated UTI. The ß-lactamase inhibitors ETX0282, VNRX7145, ARX1796, and QPX7728 are combined with cefpodoxime proxetil or ceftibuten that achieve favorable exposures in urine compared to other uropathogen-active oral cephalosporins. The combination ceftibuten-QPX7728 has potential broad-spectrum coverage against carbapenemase producers including metallo ß-lactamase producers. Other novel combinations, namely cefpodoxime/ETX0282, ceftibuten/VNRX-7145, and ceftibuten/ARX1796, have also demonstrated excellent activity against Klebsiella pneumoniae carbapanemase (KPC) and OXA-48-like producers. All these agents, upon their arrival for commercial use, would strengthen the outpatient therapy.

5.
Bull World Health Organ ; 99(8): 562-571, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34354311

RESUMO

Objective: To assess the preparedness of veterinary laboratories in India to participate in an integrated antimicrobial resistance surveillance network and to address gaps in provision identified. Methods: The Indian Council of Medical Research and the Indian Council of Agricultural Research collaborated: (i) to select eight nationally representative veterinary microbiology laboratories whose capacity for participating in an integrated antimicrobial resistance surveillance network would be assessed using a standardized tool; (ii) to identify gaps in provision from the assessment findings; and (iii) to develop a plan, and take the necessary steps to address these gaps in consultation with participating organizations. Findings: The main gaps in provision identified were: (i) a lack of dedicated funding for antimicrobial resistance surveillance; (ii) the absence of standard guidelines for antimicrobial susceptibility testing; (iii) a shortage of reference strains for testing and quality assurance; and (iv) the absence of mechanisms for sharing data. We addressed these gaps by creating a veterinary standard operating procedure for antimicrobial susceptibility testing, by carrying out a validation exercise to identify problems with implementing the procedure and by conducting capacity-building workshops for veterinary laboratories. Conclusion: Antimicrobial resistance surveillance networks depend on the availability of accurate, quality-controlled testing. The challenges identified in creating an integrated surveillance network for India can be overcome by developing a comprehensive plan for improving laboratory capacity in human, veterinary and environmental sectors that is supported by the necessary funds. The study's findings may provide guidance for other low- and middle-income countries planning to develop a similar network.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana/efeitos dos fármacos , Antibacterianos/farmacologia , Fortalecimento Institucional , Estudos Transversais , Humanos , Índia , Laboratórios , Testes de Sensibilidade Microbiana , Vigilância de Evento Sentinela
6.
Artigo em Inglês | MEDLINE | ID: mdl-34454775

RESUMO

BACKGROUND: Following a relatively mild first wave of coronavirus disease 2019 (COVID-19) in India, a deadly second wave of the pandemic overwhelmed the healthcare system due to the emergence of fast-transmitting SARS-CoV-2 genetic variants. The emergence and spread of the B.1.617.2/Delta variant considered to be driving the devastating second wave of COVID-19 in India. Currently, the Delta variant has rapidly overtaken the previously circulating variants to become the dominant strain. Critical mutations in the spike/RBD region of these variants have raised serious concerns about the virus's increased transmissibility and decreased vaccine effectiveness. As a result, significant scientific and public concern has been expressed about the impact of virus variants on COVID-19 vaccines. OBJECTIVES: The purpose of this article is to provide an additional explanation in the context of the evolutionary trajectory of SARS-CoV-2 variants in India, the vaccine-induced immune response to the variants of concern (VOC), and various vaccine deployment strategies to rapidly increase population immunity. CONTENT: Phylogenetic analysis of SARS-CoV-2 isolates circulating in India suggests the emergence and spread of B.1.617 variant. The immunogenicity of currently approved vaccines indicates that the majority of vaccines elicit an antibody response and some level of protection. According to current data, vaccines in the pre-fusion configuration (2p substitution) have an advantage in terms of nAb titer, but the duration of vaccine-induced immunity, as well as the role of T cells and memory B cells in protection, remain unknown. Since vaccine efficacy on virus variants is one of the major factors to be considered for achieving herd immunity, existing vaccines need to be improved or effective next-generation vaccines should be developed to cover the new variants of the virus.

7.
mBio ; 12(4): e0118821, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34281387

RESUMO

The currently ongoing COVID-19 pandemic caused by SARS-CoV-2 has accounted for millions of infections and deaths across the globe. Genome sequences of SARS-CoV-2 are being published daily in public databases and the availability of these genome data sets has allowed unprecedented access to the mutational patterns of SARS-CoV-2 evolution. We made use of the same genomic information for conducting phylogenetic analysis and identifying lineage-specific mutations. The catalogued lineage-defining mutations were analyzed for their stabilizing or destabilizing impact on viral proteins. We recorded persistence of D614G, S477N, A222V, and V1176F variants and a global expansion of the PANGOLIN variant B.1. In addition, a retention of Q57H (B.1.X), R203K/G204R (B.1.1.X), T85I (B.1.2-B.1.3), G15S+T428I (C.X), and I120F (D.X) variations was observed. Overall, we recorded a striking balance between stabilizing and destabilizing mutations, therefore leading to well-maintained protein structures. With selection pressures in the form of newly developed vaccines and therapeutics to mount in the coming months, the task of mapping viral mutations and recording their impact on key viral proteins should be crucial to preemptively catch any escape mechanism for which SARS-CoV-2 may evolve. IMPORTANCE Since its initial isolation in Wuhan, China, large numbers of SARS-CoV-2 genome sequences have been shared in publicly accessible repositories, thus enabling scientists to do detailed evolutionary analysis. We investigated the evolutionarily associated mutational diversity overlaid on the major phylogenetic lineages circulating globally, using 513 representative genomes. We detailed the phylogenetic persistence of key variants facilitating global expansion of the PANGOLIN variant B.1, including the recent, fast-expanding, B.1.1.7 lineage. The stabilizing or destabilizing impact of the catalogued lineage-defining mutations on viral proteins indicates their possible involvement in balancing the protein function and structure. A clear understanding of this mutational profile is of high clinical significance to catch any vaccine escape mechanism, as the same proteins make crucial components of vaccines that have recently been approved or are in development. In this vein, our study provides an imperative framework and baseline data upon which further analysis could be built as newer variants of SARS-CoV-2 continue to appear.


Assuntos
COVID-19/epidemiologia , Genoma Viral/genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Substituição de Aminoácidos/genética , COVID-19/transmissão , Evolução Molecular , Humanos , Mutação/genética , Filogenia , SARS-CoV-2/isolamento & purificação , Sequenciamento Completo do Genoma
8.
Curr Microbiol ; 78(8): 3239-3245, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34223923

RESUMO

Streptococcus pneumoniae is the major cause of childhood pneumonia and related deaths in India. Widespread use of erythromycin for the treatment of pneumonia has led to the emergence of erythromycin resistance. Despite this increase in erythromycin resistance, there are very little data on resistance determinants from India. Hence, we aimed to perform the molecular characterization of erythromycin-resistant invasive pneumococcal isolates in India. In this study, 250 erythromycin-resistant invasive isolates obtained from four Indian hospitals between 2014 and 2019 were included. The isolates were reconfirmed by standard CDC protocols, followed by detection of erm(B), mef(A/E) genes, and screening for mutations in 23S rRNA, ribosomal proteins L4 and L22. Among the 250 erythromycin-resistant isolates, 46% (n = 114) and 35% (n = 87) carried the mef(A/E) gene and erm(B) gene, respectively; both genes were present in 8% (n = 20) of the isolates and 12% (n = 29) of the studied strains did not bear any of them. The major mutations associated with erythromycin resistance in 23S rRNA, such as A2060C, A2061G, and C2613G, were absent. The predominant serotypes were 19F, 14, 23F, 6A, 6B, 19A, and 9V. The major clonal complexes were CC320, followed by CC230 and CC63. The predominant gene was mef(A/E), and most of the serotypes were PCV13 (54%). This study contributes to the baseline understanding of the erythromycin resistance determinants associated with the serotypes and sequence types (ST) of Indian invasive S. pneumoniae.


Assuntos
Infecções Pneumocócicas , Streptococcus pneumoniae , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Eritromicina/farmacologia , Humanos , Índia , Testes de Sensibilidade Microbiana , Sorogrupo , Sorotipagem , Streptococcus pneumoniae/genética
9.
Vaccine ; 39(28): 3737-3744, 2021 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-34074545

RESUMO

INTRODUCTION: A hospital-based sentinel surveillance network for bacterial meningitis was established in India to estimate the burden of bacterial meningitis, and the proportion of major vaccine-preventable causative organisms. This report summarises the findings of the surveillance conducted between March 2012, and September 2016 in eleven hospitals. METHODS: We enrolled eligible children with bacterial meningitis in the age group of one to 59 months. CSF samples were collected and processed for biochemistry, culture, latex agglutination, and real-time PCR. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. RESULTS: Among 12 941 enrolled suspected meningitis cases, 586 (4.5%) were laboratory confirmed. S. pneumoniae (74.2%) was the most commonly detected pathogen, followed by H. influenzae (22.2%), and N. meningitidis (3.6%). Overall 58.1% of confirmed bacterial meningitis cases were children aged between one, and 11 months. H. influenzae meningitis cases had a high (12.3%) case fatality rate. The serotypes covered in PCV13 caused 72% pneumococcal infections, and the most common serotypes were 14 (18.3%), 6B (12.7%) and 19F (9.9%). Non-susceptibility to penicillin was 57%. Forty-five (43.7%) isolates exhibited multidrug resistance, of which 37 were PCV13 serotype isolates. CONCLUSIONS: The results are representative of the burden of bacterial meningitis among under-five children in India. The findings were useful in rolling out PCV in the National Immunization Program. The non-susceptibility to penicillin and multidrug resistance was an important observation. Timely expansion of PCV across India will significantly reduce the burden of antimicrobial resistance. Continued surveillance is needed to understand the trend after PCV expansion in India.


Assuntos
Meningites Bacterianas , Infecções Pneumocócicas , Criança , Pré-Escolar , Hospitais , Humanos , Índia/epidemiologia , Lactente , Meningites Bacterianas/epidemiologia , Vacinas Pneumocócicas , Vigilância de Evento Sentinela , Sorogrupo , Sorotipagem
10.
Indian J Med Microbiol ; 39(2): 192-195, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33966861

RESUMO

BACKGROUND: Recently, a novel species contaminans belonging to the family Burkholderia cepacia complex (Bcc) is rising as a hospital pathogen. Detection of Burkholderia contaminans, a member of Bcc can be done only by MALDI TOF and sequencing techniques. We report the diagnostic challenges faced in an outbreak of bacteremia due to B. contaminans grown in diltiazem vials. METHOD: The department of microbiology notified the infection control team about a cluster of eleven patients with B. contaminans isolated from blood culture. An outbreak investigation was initiated by performing environmental surveillance and sterility testing of solutions given for the patients. Routine phenotypical methods for identification of species followed by MALDI-TOF and sequencing was performed to identify the pathogen. RESULTS: All the patients detected with B. contaminans were having cardiac disease and received diltiazem. Sterility testing of diltiazem vials given for the patient and an unopened vial of same batch has grown B. contaminans. Clonal typing has confirmed the sequence similarities between patient and solution isolates. CONCLUSION: Due to diagnostic challenge in identifying the species of Bcc, MALDI TOF and clonal typing remains the key diagnostic tools available to detect Bcc species at an earliest especially in an outbreak.

11.
J Cell Biochem ; 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33998043

RESUMO

BAG3, a co-chaperone protein with a Bcl-2-associated athanogene (BAG) domain, has diverse functionalities in protein-folding, apoptosis, inflammation, and cell cycle regulatory cross-talks. It has been well characterised in cardiac diseases, cancers, and viral pathogenesis. The multiple roles of BAG3 are attributed to its functional regions like BAG, Tryptophan-rich (WW), isoleucine-proline-valine-rich (IPV), and proline-rich (PXXP) domains. However, to study its structural impact on various functions, the experimental 3D structure of BAG3 protein was not available. Hence, the structure was predicted through in silico modelling and validated through computational tools and molecular dynamics simulation studies. To the best of our knowledge, the role of BAG3 in bacterial infections is not explicitly reported. We attempted to study them through an in-silico protein-protein interaction network and host-pathogen interaction analysis. From structure-function relationships, it was identified that the WW and PXXP domains were associated with cellular cytoskeleton rearrangement and adhesion-mediated response, which might be involved in BAG3-related intracellular bacterial proliferation. From functional enrichment analysis, Gene Ontology terms and topological matrices, 18 host proteins and 29 pathogen proteins were identified in the BAG3 interactome pertaining to Legionellosis, Tuberculosis, Salmonellosis, Shigellosis, and Pertussis through differential phosphorylation events associated with serine metabolism. Furthermore, it was evident that direct (MAPK8, MAPK14) and associated (MAPK1, HSPD1, NFKBIA, TLR2, RHOA) interactors of BAG3 could be considered as therapeutic markers to curb down intracellular bacterial propagation in humans.

12.
J Glob Antimicrob Resist ; 25: 331-336, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957286

RESUMO

OBJECTIVES: Linezolid resistance in Enterococcus faecium is emerging worldwide. In this study, we aimed to characterise two linezolid-resistant E. faecium isolates using whole-genome sequencing. METHODS: Antimicrobial susceptibility testing was performed by the broth microdilution method. A hybrid assembly approach of IonTorrent and MinION sequencing reads was used to generate the complete genome of linezolid-resistant E. faecium isolates VB3025 and VB3240. RESULTS: VB3025 and VB3240 had minimum inhibitory concentration (MICs) for linezolid of 1024 µg/mL and 512 µg/mL, respectively. In addition, VB3025 was found to be resistant to both vancomycin and teicoplanin, while VB3240 was susceptible to these antibiotics. A hybrid assembly approach was used to generate the complete genome of VB3025 and VB3240 isolates harbouring the optrA gene. Notably, VB3025 carried two copies of optrA (chromosomal and plasmid), while in VB3240 optrA was identified on the chromosome. Interestingly, the plasmid pVB3025_2 co-carried the resistance gene clusters aph(3)-IIIa-sat4-ant(6)-Ia-ermB, the vanHAX operon and a copy of the optrA gene. Moreover, the optrA gene inserted into a Tn554 transposon carrying the ermA gene was identified in both VB3025 and VB3240 isolates. Furthermore, mutation analysis revealed the presence of a G2592T mutation in the 23S rRNA of both isolates. CONCLUSION: This is the first study reporting optrA-positive linezolid-resistant E. faecium from India. A novel plasmid co-carrying vancomycin and linezolid resistance determinants highlights the threat for potential dissemination.


Assuntos
Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Farmacorresistência Bacteriana/genética , Enterococcus faecium/genética , Genômica , Humanos , Índia , Linezolida/farmacologia
13.
Genomics ; 113(4): 2171-2176, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33965548

RESUMO

BACKGROUND: Recent reports have established the emergence and dissemination of extensively drug resistant (XDR) H58 Salmonella Typhi clone in Pakistan. In India where typhoid fever is endemic, only sporadic cases of ceftriaxone resistant S. Typhi are reported. This study aimed at elucidating the phylogenetic evolutionary framework of ceftriaxone resistant S. Typhi isolates from India to predict their potential dissemination. METHODS: Five ceftriaxone resistant S. Typhi isolates from three tertiary care hospitals in India were sequenced on an Ion Torrent Personal Genome Machine (PGM). A core genome single-nucleotide-polymorphism (SNP) based phylogeny of the isolates in comparison to the global collection of MDR and XDR S. Typhi isolates was built. Two of five isolates were additionally sequenced using Oxford Nanopore MinION to completely characterize the plasmid and understand its transmission dynamics within Enterobacteriaceae. RESULTS: Comparative genomic analysis and detailed plasmid characterization indicate that while in Pakistan (4.3.1 lineage I) the XDR trait is associated with blaCTX-M-15 gene on IncY plasmid, in India (4.3.1 lineage II), the ceftriaxone resistance is due to short term persistence of resistance plasmids such as IncX3 (blaSHV-12) or IncN (blaTEM-1B + blaDHA-1). CONCLUSION: Considering the selection pressure exerted by the extensive use of ceftriaxone in India, there are potential risks for the occurrence of plasmid transmission events in the predominant H58 lineages. Therefore, continuous monitoring of S. Typhi lineages carrying plasmid-mediated cephalosporin resistant genes is vital not just for India but also globally.

14.
Mol Biol Rep ; 48(4): 3265-3276, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33876375

RESUMO

The emergence of multi drug resistant clone CC320 serotype19F/19A and their capsular (cps) antigenic variants due to selective pressures such as vaccine had been reported worldwide. Hence, it is important to identify the prevalent clones, sequence types and cps variants of serotype 19F/19A in India, where PCV13 has been recently introduced. Multi-locus sequence typing (MLST) was performed for all (n = 21) invasive S. pneumoniae isolates of serotype 19A (n = 5) and 19F (n = 16) collected between the years 2012 and 2018 from children less than 5 years. The genome characterization by whole genome sequencing for the Sequence types (STs) 320 and 271(n = 7) were performed and compared with another six Indian WGSs of similar STs available from the GPS platform. The predominant STs in the serotype 19F/19A study isolates were of CC320: ST 320, 236 and 271, associated with PMEN clone Taiwan19F-14. The WGSs of CC320 study isolates showed high genomic similarity to the Taiwan19F-14 clone, and the penicillin binding protein (PBP) amino acid sequence similarity was 100% for PBP1A, 93% for PBP 2B and 2X. Whilst PBP comparison with other global MDR ST320 strains revealed that the ST320 clones in India are of low-level penicillin resistance. The presence of a few ST320/19A/19F invasive isolates with high similarity to the Taiwan clone suggests slow and gradual expansion of Taiwan19F-14 associated CC320 clones in India. Since serotype 19F/19A is covered by PCV13 vaccine, the expansion of 19F/19A cones with non-PCV13 vaccine serotype in India should be monitored.


Assuntos
Resistência às Penicilinas , Infecções Pneumocócicas/microbiologia , Vacinas Pneumocócicas/uso terapêutico , Sorogrupo , Streptococcus pneumoniae/genética , Pré-Escolar , Genômica , Humanos , Índia , Tipagem de Sequências Multilocus , Infecções Pneumocócicas/imunologia , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/fisiologia , Sequenciamento Completo do Genoma
15.
Indian J Med Microbiol ; 39(3): 286-288, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33892973

RESUMO

Serious infections caused by MBLs with or without OXA-48-like expressing Enterobacterales remain challenging to treat. Since aztreonam is stable to MBLs, it can be combined with ceftazidime/avibactam to protect against concurrently expressed ESBLs and class C ß-lactamases in MBL pathogens. However, in the light of dose-limiting hepatotoxicity of aztreonam, short half life of avibactam, significant protein binding of aztreonam, appropriate dosing and method of administration to optimize PK/PD and toxicodynamics for this combination is being debated. Based on in-vitro PK/PD studies, simultaneous administration of 6/1.5 g of ceftazidime/avibactam and 8 g of aztreonam per day has been recently suggested.

16.
Microb Drug Resist ; 27(8): 1096-1104, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33720791

RESUMO

Background: Klebsiella pneumoniae (Kp), a common multidrug-resistant pathogen, causes a wide spectrum of nosocomial infections with high rates of morbidity and mortality. The emergence of pan drug-resistant international high-risk clones such as ST258, ST14, ST15, ST147, and ST101 is a global concern. This study was performed to investigate the carbapenemases, the plasmid profile, and the clonal relationship among Indian K. pneumoniae. Materials and Methods: A total of 290 K. pneumoniae isolates from seven centers in India were characterized to determine sequence types (STs) and carbapenemases. A subset of isolates was subjected to whole genome sequencing and hybrid genome assembly to obtain the complete genome. Plasmids carrying carbapenemases were characterized to determine the dissemination of carbapenem-resistant (CR) K. pneumoniae. Results: From this study, 75 different STs were observed with ST231 being predominant. About 79% of the analyzed isolates were CR with 59% (n = 136) producing OXA48-like carbapenemases. While ST231 was the predominant clone among the OXA48-like producers; NDM producers and NDM+OXA48-like producers were mostly associated with ST14. Interestingly, 61% (n = 138) of the total CR K. pneumoniae were colistin resistant, belonging to 22 different STs. Plasmid profiling shows that blaOXA48-like was exclusively carried by ColKP3, whereas blaNDM was associated with IncFII-like plasmids. Conclusion: The highly mosaic genome of K. pneumoniae coupled with the diverse ecological niches in India makes it a hotspot for antimicrobial resistance, leading to increased morbidity and mortality. Extensive molecular surveillance of the clonal spread of K. pneumoniae could help in understanding AMR dynamics and thus rework therapeutic management.

17.
Nat Commun ; 12(1): 1500, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686077

RESUMO

Diphtheria is a respiratory disease caused by the bacterium Corynebacterium diphtheriae. Although the development of a toxin-based vaccine in the 1930s has allowed a high level of control over the disease, cases have increased in recent years. Here, we describe the genomic variation of 502 C. diphtheriae isolates across 16 countries and territories over 122 years. We generate a core gene phylogeny and determine the presence of antimicrobial resistance genes and variation within the tox gene of 291 tox+ isolates. Numerous, highly diverse clusters of C. diphtheriae are observed across the phylogeny, each containing isolates from multiple countries, regions and time of isolation. The number of antimicrobial resistance genes, as well as the breadth of antibiotic resistance, is substantially greater in the last decade than ever before. We identified and analysed 18 tox gene variants, with mutations estimated to be of medium to high structural impact.


Assuntos
Corynebacterium diphtheriae/genética , Toxina Diftérica/genética , Difteria/microbiologia , Difteria/prevenção & controle , Anti-Infecciosos/farmacologia , Corynebacterium diphtheriae/efeitos dos fármacos , Toxoide Diftérico , Farmacorresistência Bacteriana/genética , Variação Genética , Genoma Bacteriano , Genômica , Humanos , Índia , Testes de Sensibilidade Microbiana , Filogenia , Polimorfismo de Nucleotídeo Único
18.
Curr Treat Options Infect Dis ; : 1-18, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33519303

RESUMO

Purpose of review: There is a need for enhanced adoption of infection prevention and control (IPC) practices in both healthcare settings and the entire community, more so during pandemics. The exponential increase in the use of social media (SM) has made it a powerful tool for creating awareness, education, training and community engagement on IPC. Here, we review how social media can be used effectively to implement strategies to combat public health issues especially vis-à-vis infection prevention and control. Recent findings: According to the World Health Organization, 10% of patients get an infection whilst receiving care in healthcare institutions. Effective infection prevention and control measures can reduce healthcare-associated infections by at least 30%. Education and awareness play a vital role in implementation of infection prevention and control (IPC) strategies. Various studies show how social media has been used successfully in education and training activities, for awareness campaigns, community engagement, risk communications during outbreaks, disease surveillance and pharmacovigilance. Summary: Infection prevention and control (IPC) is the need of the hour to mitigate transmission of disease in healthcare settings as well as in the community. SM is the fastest and most efficient way of communicating with the general population as well as health professionals. SM can help people take the right decisions and enable change in their behaviour patterns to introduce infection control practices.

19.
Infect Dis Ther ; 10(1): 541-558, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33586088

RESUMO

INTRODUCTION: Available evidence from observational studies and meta-analyses has highlighted an increased mortality in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infections (BSI) compared with their carbapenem-susceptible (CSKP) counterparts, but the exact reasons for this outcome difference are still to be determined. METHODS: We updated the search of a previous meta-analysis through four databases up to April 2018. A two-stage individual-patient data (IPD) meta-analysis was conducted, building an adjusting model to account for age, comorbidities and activity of empirical and targeted antimicrobial therapy. The protocol was registered on PROSPERO (identifier: CRD42018104256). RESULTS: IPD data were obtained from 14 out of 28 eligible observational studies. A total of 1952 patients were investigated: 1093 in the CRKP group and 859 in the CSKP group. Patients with CRKP-BSI had a twofold risk of death compared with CSKP-infected patients [adjusted odds ratio (aOR) 2.17; 95% confidence interval (CI) 1.56-3.04; I2 = 44.1%]. Mortality was higher in patients with CRKP BSI, in both the subgroup of absent/inactive (aOR 1.75; 95% CI 1.24-2.47; I2 = 0) and of active initial therapy (aOR 2.66; 95% CI 1.70-4.16; I2 = 16%) as well as in case of active targeted therapy (aOR 2.21; 95% CI 1.36-3.59; I2 = 58%). CONCLUSION: Resistance to carbapenem is associated with worse outcome in patients with BSI by Klebsiella pneumoniae even adjusting for comorbidities and treatment appropriateness according to in vitro activity of empirical and targeted therapy. This applies to a scenario dominated by colistin-based therapies for CRKP. Further studies are needed to compare the mortality difference between CRKP and CSKP cases in the light of new anti-CRKP antimicrobials.

20.
Microb Drug Resist ; 27(3): 311-319, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32716253

RESUMO

Penicillin-binding proteins are the primary targets for beta lactam drugs, which are main stay of treatment for Streptococcus pneumoniae. The emergence of increased penicillin resistance in meningeal isolates of S. pneumoniae in India is alarming. With this background, we aimed to analyze the pbp gene mutations of penicillin nonsusceptible pneumococcal (PNSP) isolates from within India and their association with international clones. A total of 32 PNSP invasive isolates with a penicillin minimal inhibitory concentrations (MIC) of ≥0.12 µg/mL were subjected to PCR and sequencing for multilocus sequence typing and the pbp genes (pbp2b, pbp2x, and pbp1a). The S. pneumoniae R6 susceptible strain was used as the reference for the comparison analyses. In the majority of the present study isolates, amino acid substitutions were only seen in one of the three active sites of one of the three pbp genes. Thus, pbp genes in the absence of the major substitutions usually associated with penicillin resistance combined with mosaicism in pbp1a resulted in a slight increase in the penicillin MIC to between 0.06 and 2.0 µg/mL, which according to meningeal break point denote resistance. Clonal analyses revealed that the emergence of PNSP in India is due to the gradual expansion of the resistant clones CC320, CC230, and CC63.

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