With the excessive genome plasticity,
Acinetobacter baumannii
can acquire and disseminate antimicrobial resistance (AMR) genes often associated with mobile genetic elements (MGEs). Analyzing the ...genetic environment of resistance genes often provides valuable information on the origin, emergence, evolution, and spread of resistance. Thus, we characterized the genomic features of some clinical isolates of carbapenem-resistant
A. baumannii
(CRAb) to understand the role of diverse MGEs and their genetic context responsible for disseminating carbapenem resistance genes. For this, 17 clinical isolates of
A. baumannii
obtained from multiple hospitals in India between 2018 and 2019 were analyzed. AMR determinants, the genetic context of resistance genes, and molecular epidemiology were studied using whole-genome sequencing. This study observed an increased prevalence of
bla
OXA–23
followed by dual carbapenemases,
bla
OXA–23
, and
bla
NDM
. This study identified three novel Oxford MLST sequence types. The majority of the isolates belonged to the dominant clone, IC2, followed by less prevalent clones such as IC7 and IC8. This study identified variations of AbaR4 and AbGRI belonging to the IC2 lineage. To the best of our knowledge, this is the first study that provides comprehensive profiling of resistance islands, their related MGEs, acquired AMR genes, and the distribution of clonal lineages of CRAb from India.
To investigate the epidemiology of invasive pneumococcal disease (IPD), prevalent serotypes, and pattern of antimicrobial resistance (AMR) in Indian adults.
Prospective laboratory based surveillance ...of IPD was carried out in >18 years age group between January 2007 and July 2017, from a tertiary care hospital in South India. All Streptococcus pneumoniae culture positives from blood, CSF and sterile body fluids were characterized to identify the serotypes and AMR.
A total of 408 IPD cases were characterized in this study. The overall case fatality rate in this study was 17.8% (95% confidence interval (CI): 14.1, 22.4). Pneumonia (39%), meningitis (24.3%), and septicaemia (18.4%) were the most common clinical conditions associated with IPD. Serotypes 1, 3, 5, 19F, 8, 14, 23F, 4, 19A and 6B were the predominant serotypes in this study. Penicillin non-susceptibility was low with 6.4%
Serotype data from this study helped in accurate estimation of pneumococcal conjugate vaccine-13 and pneumococcal polysaccharide vaccine-23 protective coverage against serotypes causing IPD in India as 58.7% (95% CI: 53.8, 63.4) and 67.4% (95% CI: 62.7, 71.8) respectively. Penicillin non-susceptibility in meningeal IPD cases is 27.4%. Empirical therapy for meningeal IPD must be cephalosporin in combination with vancomycin since cefotaxime non-susceptibility in meningeal IPD is 9.9%
Hypervirulent variants of
(HvKp) were typically associated with a broadly antimicrobial susceptible clone of sequence type (ST) 23 at the time of its emergence. Concerningly, HvKp is now also ...emerging within multidrug-resistant (MDR) clones, including ST11, ST15, and ST147. MDR-HvKp either carry both the virulence and resistance plasmids or carry a large hybrid plasmid coding for both virulence and resistance determinants. Here, we aimed to genetically characterize a collection of MDR-HvKp ST2096 isolates haboring hybrid plasmids carrying both antimicrobial resistance (AMR) and virulence genes.
Nine
ST2096 isolated over 1 year from the blood sample of hospitalized patients in southern India that were MDR and suspected to be HvKp were selected. All nine isolates were subjected to short-read whole-genome sequencing; a subset (n = 4) was additionally subjected to long-read sequencing to obtain complete genomes for characterization. Mucoviscosity assay was also performed for phenotypic assessment.
Among the nine isolates, seven were carbapenem-resistant, two of which carried
on an IncFII plasmid and five carried
on a ColKP3 plasmid. The organisms were confirmed as HvKp, with characteristic virulence genes (
,
, and
) carried on a large (~320 kbp) IncFIB-IncHI1B co-integrate. This hybrid plasmid also carried the
,
,
,
,
,
, and
AMR genes in addition to the heavy-metal resistance genes. The hybrid plasmid showed about 60% similarity to the IncHI1B virulence plasmid of
SGH10 and ~70% sequence identity with the first identified IncHI1B pNDM-MAR plasmid. Notably, the hybrid plasmid carried its type IV-A3 CRISPR-Cas system which harbored spacer regions against
of IncF plasmids, thereby preventing their acquisition.
The convergence of virulence and AMR is clinically concerning in
. Our data highlight the role of hybrid plasmids carrying both AMR and virulence genes in
ST2096, suggesting that MDR-HvKp is not confined to selected clones; we highlight the continued emergence of such genotypes across the species. The convergence is occurring globally amidst several clones and is of great concern to public health.
Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and other serious infections among children in India. India introduced the 13-valent pneumococcal conjugate vaccine (PCV) in ...several states in 2017, and is expected to expand to nationwide coverage in the near future. To establish a baseline for measuring the impact of PCV in India, we assessed overall and serotype-specific nasopharyngeal carriage in two pediatric populations.
A cross-sectional study was conducted in Palwal District, Haryana, from December 2016 to July 2017, prior to vaccine introduction. Children 2-59 months of age with clinical pneumonia seeking healthcare and those in the community with no clear illness were targeted for enrollment. A nasopharyngeal swab was collected and tested for pneumococcus using conventional culture and sequential multiplex PCR. Isolates were tested for antimicrobial resistance using an E test. Children were considered colonized if pneumococcus was isolated by culture or PCR. The prevalence of pneumococcal and serotype-specific colonization was compared between groups of children using log-binomial regression.
Among 601 children enrolled, 91 had clinical pneumonia and 510 were community children. The proportion colonized with S. pneumoniae was 74.7 and 54.5% among children with clinical pneumonia and community children, respectively (adjusted prevalence ratio: 1.38; 95% confidence interval: 1.19, 1.60). The prevalence of PCV13 vaccine-type colonization was similar between children with clinical pneumonia (31.9%) and community children (28.0%; p = 0.46). The most common colonizing serotypes were 6A, 6B, 14, 19A, 19F, and 23F, all of which are included in the PCV13 vaccine product. Antimicrobial resistance to at least one drug was similar between isolates from children with clinical pneumonia (66.1%) and community children (61.5%; p = 0.49); while resistance to at least two drugs was more common among isolates from children with clinical pneumonia (25.8% vs. 16.4%; p = 0.08). Resistance for all drugs was consistently higher for PCV13 vaccine-type serotypes compared to non-vaccine serotypes in both groups.
This study provides baseline information on the prevalence of serotype-specific pneumococcal colonization among children prior to the introduction of PCV in India. Our results suggest a role for pneumococcal vaccines in reducing pneumococcal colonization and antimicrobial resistant isolates circulating in India.
Diphtheria is caused by a toxigenic bacterium Corynebacterium diphtheria which is being an emerging pathogen in India. Since diphtheria morbidity and mortality continues to be high in the country, ...the present study aimed to study the molecular epidemiology of C. diphtheriae strains from India. A total of 441 diphtheria suspected specimens collected as part of the surveillance programme between 2015 and 2020 were studied. All the isolates were confirmed as C. diphtheriae with standard biochemical tests, ELEK's test, and real-time PCR. Antimicrobial susceptibility testing for the subset of isolates showed intermediate susceptibility to penicillin and complete susceptible to erythromycin and cefotaxime. Isolates were characterized using multi locus sequence typing method. MLST analysis for the 216 C. diphtheriae isolates revealed major diversity among the sequence types. A total of 34 STs were assigned with majority of the isolates belonged to ST466 (30%). The second most common ST identified was ST405 that was present in 14% of the isolates. The international clone ST50 was also seen. The identified STs were grouped into 8 different clonal complexes (CC). The majority belongs to CC5 followed by CC466, CC574 and CC209, however a single non-toxigenic strain belongs to CC42. This epidemiological analysis revealed the emergence of novel STs and the clones with better dissemination properties. This study has also provided information on the circulating strains of C. diphtheriae among the different regions of India. The molecular data generated through surveillance system can be utilized for further actions in concern.
Bacteria acquire β-lactam resistance through a multitude of mechanisms among which production of β-lactamases (enzymes that hydrolyze β-lactams) is the most common, especially in Gram-negatives. ...Structural changes in the high-molecular-weight, essential penicillin-binding proteins (PBPs) are widespread in Gram-positives and increasingly reported in Gram-negatives. PBP-mediated resistance is largely achieved by accumulation of mutation(s) resulting in reduced binding affinities of β-lactams. Herein, we discuss PBP-mediated resistance among ESKAPE pathogens that cause diverse hospital- and community-acquired infections globally.
The steady increase in the proportion of Non-typhoidal
(NTS) infections in humans represents a major health problem worldwide. The current study investigated the serovar distribution and ...antimicrobial susceptibility trends of NTS isolated from faecal samples during the period 2000-2018.
Faecal specimens of patients were cultured according to standard lab protocol. The isolates were serotyped and antimicrobial susceptibility testing (AST) were performed according to CLSI guidelines.
A total of 1436 NTS isolates were obtained from faeces samples mostly comprising of
Typhimurium (27.3%),
Weltevreden (13%),
Bareilly (11%),
Newport (4.2%),
. Cholerasuis (4%),
Infantis (3.4%), and
. Enteritidis (2.4%). Resistance to nalidixic acid (26%) was most common among the tested NTS, followed by ampicillin (18.5%), cotrimoxazole (13.5%), ciprofloxacin (12%), ceftriaxone (6.3%) and chloramphenicol (3.6%). Multidrug resistance was observed in 5% of NTS isolates with the highest rate (10.52%) in 2014. The incidence of NTS infection was maximum in children < 5 years of age with an average 19.3% of the total affected patients during the time period.
Based on this study, the faecal NTS isolates have high resistance rates against first line antimicrobial agents except chloramphenicol. The gradual but consistent increase in resistance to fluoroquinolones, third generation cephalosporins and macrolide may restrict future treatment options. Hence periodic monitoring of NTS infections, serotype distribution and antimicrobial resistance trend is recommended.
In recent years, the emergence of multidrug resistant hypervirulent
(MDR hvKp) isolates poses severe therapeutic challenge to global public health. The present study used the complete genome sequence ...of two MDR hvKp isolates belonging to ST23 to characterize the phylogenetic background and plasmid diversity.
Two hvKp isolates from patients with bacteremia were sequenced using Ion Torrent PGM and Oxford Nanopore MinION platforms and assembled by hybrid genome assembly approach. Comparative genomics approaches were used to investigate the population structure, evolution, virulence, and antimicrobial resistance of MDR hvKp strains.
The study isolates exhibited typical features of hvKp phenotypes associated with ST23. The convergence of multidrug resistance and hypervirulence were attributed by the presence of multiple plasmids including a 216 kb virulence plasmid and MDR plasmids belonging to IncA/C
, IncFIB, IncX3, and ColKP3 groups. The insertion of
into virulence plasmid was observed along with genetic factors such as aerobactin, salmochelin, and
that confer hvKp's hypervirulent phenotype. The core genome single nucleotide polymorphism (SNP) phylogenetic analyses of the isolates showed the evolution of ST23 hvKp was predominantly driven by ICE
acquisitions.
To the best of our knowledge, this is the first report of MDR hvKp isolates of ST23 with insertion of
gene into the virulence plasmid which presents the possibility of hotspot integration sites on the plasmids to aid acquisition of AMR genes. ST23 is no longer confined to susceptible strains of hvKp. Our findings emphasize the need for more studies on recombinant events, plasmid transmission dynamics and evolutionary process involving hvKp.
Infections in critically-ill patients caused by extensively-drug-resistant (XDR)-Pseudomonas aeruginosa are challenging to manage due to paucity of effective treatment options. Cefepime/zidebactam, ...which is currently in global Phase 3 clinical development (Clinical Trials Identifier: NCT04979806, registered on July 28, 2021) is a novel mechanism of action based β-lactam/ β-lactam-enhancer combination with a promising activity against a broad-range of Gram-negative pathogens including XDR P. aeruginosa. We present a case report of an intra-abdominal infection-induced sepsis patient infected with XDR P. aeruginosa and successfully treated with cefepime/zidebactam under compassionate use. The 50 year old female patient with past-history of bariatric surgery and recent elective abdominoplasty and liposuction developed secondary pneumonia and failed a prolonged course of polymyxins. The organism repeatedly isolated from the patient was a New-Delhi metallo β-lactamase-producing XDR P. aeruginosa resistant to ceftazidime/avibactam, imipenem/relebactam and ceftolozane/tazobactam, susceptible only to cefepime/zidebactam. As polymyxins failed to rescue the patient, cefepime/zidebactam was administered under compassionate grounds leading to discharge of patient in stable condition. The present case highlights the prevailing precarious scenario of antimicrobial resistance and the need for novel antibiotics to tackle infections caused by XDR phenotype pathogens.
Typhoid fever causes nearly 110,000 deaths among 9.24 million cases globally and disproportionately affects developing countries. As a control measure in such regions, typhoid conjugate vaccines ...(TCVs) are recommended by the World Health Organization (WHO). We present here the protocol of a cluster randomised vaccine trial to assess the impact of introducing TyphiBEV® vaccine to those between 1 and 30 years of age in a high-burden setting.
The primary objective is to determine the relative and absolute rate reduction of symptomatic, blood-culture-confirmed S. Typhi infection among participants vaccinated with TyphiBEV® in vaccine clusters compared with the unvaccinated participants in non-vaccine clusters. The study population is residents of 30 wards of Vellore (a South Indian city) with participants between the ages of 1 and 30 years who provide informed consent. The wards will be divided into 60 contiguous clusters and 30 will be randomly selected for its participants to receive TyphiBEV® at the start of the study. No placebo/control is planned for the non-intervention clusters, which will receive the vaccine at the end of the trial. Participants will not be blinded to their intervention. Episodes of typhoid fever among participants will be captured via stimulated, passive fever surveillance in the area for 2 years after vaccination, which will include the most utilised healthcare facilities. Observers blinded to the participants' intervention statuses will record illness details. Relative and absolute rate reductions will be calculated at the end of this surveillance and used to estimate vaccine effectiveness.
The results from our trial will allow countries to make better-informed decisions regarding the TCV that they will roll-out and may improve the global supplies and affordability of the vaccines.
Clinical Trials Registry of India (CTRI) CTRI/2022/03/041314. Prospectively registered on 23 March 2022 ( https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62548&EncHid=&userName=vellore%20typhoid ). CTRI collects the full WHO Trial Registration Data Set.
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