scholarly journals Genomic Surveillance of Pseudomonas aeruginosa in the Philippines from 2013-2014

2020 ◽  
Author(s):  
Jeremiah Chilam ◽  
Silvia Argimón ◽  
Marilyn T. Limas ◽  
Melissa L. Masim ◽  
June M. Gayeta ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Sequence Data ◽  
Acquired Resistance ◽  
Carbapenem Resistance ◽  
The Philippines ◽  
Surveillance Program ◽  
Drug Resistant ◽  
Loss Of Function ◽  
Genotypic Resistance

AbstractPseudomonas aeruginosa is an opportunistic pathogen often causing nosocomial infections that are resilient to treatment due to an extensive repertoire of intrinsic and acquired resistance mechanisms. In recent years, increasing resistance rates to antibiotics such as carbapenems and extended-spectrum cephalosporins have been reported, as well as multi-drug resistant and possible extremely drug-resistant rates of approximately 21% and 15%, respectively. However, the molecular epidemiology and AMR mechanisms of this pathogen remains largely uncharacterized.We sequenced the whole genomes of 176 P. aeruginosa isolates collected in 2013-2014 by the Antimicrobial Resistance Surveillance Program. The multi-locus sequence type, presence of antimicrobial resistance (AMR) determinants, and relatedness between the isolates were derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.Carbapenem resistance was associated namely with loss-of function of the OprD porin, and acquisition of the metallo-β-lactamase VIM. The concordance between phenotypic and genotypic resistance was 93.27% overall for 6 antibiotics in 3 classes, but varied widely between aminoglycosides. The population of P. aeruginosa in the Philippines was diverse, with clonal expansions of XDR genomes belonging to multi-locus sequence types ST235, ST244, ST309, and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, as well as transfer between hospitals. Most of the ST235 genomes formed a distinct Philippine lineage when contextualized with international genomes, thus raising the possibility that this is a lineage unique to the Philippines. This was further supported by long-read sequencing of one representative XDR isolate, which revealed the presence of an integron carrying multiple resistance genes, including blaVIM-2, with differences in gene composition and synteny to other P. aeruginosa class 1 integrons described before.We produced the first comprehensive genomic survey of P. aeruginosa in the Philippines, which bridges the gap in genomic data from the Western Pacific region and will constitute the genetic background to contextualize ongoing prospective surveillance. Our results also highlight the importance of infection control interventions aimed to curtail the spread of international epidemic clone ST235 within the country.

scholarly journals Genomic Surveillance of Methicillin-Resistant Staphylococcus aureus in the Philippines from 2013-2014

2020 ◽  
Author(s):  
Melissa L. Masim ◽  
Silvia Argimón ◽  
Holly O. Espiritu ◽  
Mariane A. Magbanua ◽  
Marietta L. Lagrada ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Sequence Data ◽  
The Philippines ◽  
Surveillance Program ◽  
Genotypic Resistance ◽  
Methicillin Resistant ◽  
Whole Genomes ◽  
Invasive Infections ◽  
The Western Pacific

AbstractMethicillin Resistant Staphylococcus aureus (MRSA) remains one of the leading causes of both nosocomial and community infections worldwide. In the Philippines, MRSA rates have remained above 50% since 2010, but resistance to other antibiotics, including vancomycin, is low. The MRSA burden can be partially attributed to pathogen-specific characteristics of the circulating clones, but little was known about the S. aureus circulating clones in the Philippines.We sequenced the whole genomes of 116 S. aureus isolates collected in 2013-2014 by the Antimicrobial Resistance Surveillance Program. The multi-locus sequence type, spa type, SCC-mec type, presence of antimicrobial resistance (AMR) determinants and virulence genes, and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.The MRSA population in the Philippines was composed of a limited number of genetic clones, including several international epidemic clones, such as CC30-spa-t019-SCCmec-IV-PVL+, CC5-SCCmec-typeIV, and ST239-spa-t030-SCCmec-typeIII. The CC30 genomes were related to the South West Pacific clone, but formed a distinct and diverse lineage, with evidence of global dissemination. We showed the independent acquisition of resistance to sulfamethoxazole/trimethoprim across different locations and genetic clones, but mostly in pediatric patients with invasive infections. The concordance between phenotypic and genotypic resistance was 99.68% overall for 8 antibiotics in 7 classes.We produced the first comprehensive genomic survey of S. aureus in the Philippines, which bridges the gap in genomic data from the Western Pacific region and will constitute the genetic background to contextualize ongoing prospective surveillance.

scholarly journals Genomic surveillance of Neisseria gonorrhoeae in the Philippines, 2013–2014

2021 ◽  
Vol 12 (1) ◽  
pp. 17-25
Author(s):  
Alfred Villamin ◽  
Silvia Argimon ◽  
Karis Bohme ◽  
Melissa Masim ◽  
June Gayeta ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Sequence Data ◽  
The Philippines ◽  
Sequence Type ◽  
Surveillance Program ◽  
Gyra Gene ◽  
Genotypic Resistance ◽  
Genomic Epidemiology ◽  
Epidemiology Studies

Antimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health and is of particular concern in the Western Pacific Region, where the incidence of gonorrhoea is high. The Antimicrobial Resistance Surveillance Program (ARSP) has been capturing information on resistant gonorrhoea since 1996, but genomic epidemiology studies on this pathogen are lacking in the Philippines. We sequenced the whole genomes of 21 N. gonorrhoeae isolates collected in 2013–2014 by ARSP. The multilocus sequence type, multiantigen sequence type, presence of determinants of antimicrobial resistance and relatedness among the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. Ten of 21 isolates were resistant to penicillin, ciprofloxacin and tetracycline, due mainly to the presence of the blaTEM gene, the S91F mutation in the gyrA gene and the tetM gene, respectively. None of the isolates was resistant to ceftriaxone or cefixime. The concordance between phenotypic and genotypic resistance was 92.38% overall for five antibiotics in four classes. Despite the small number of isolates studied, they were genetically diverse, as shown by the sequence types, the N. gonorrhoeae multiantigen sequence typing types and the tree. Comparison with global genomes placed the Philippine genomes within global lineage A and led to the identification of an international transmission route.

scholarly journals Genomic Surveillance of Neisseria gonorrhoeae in the Philippines from 2013-2014

2020 ◽  
Author(s):  
Alfred S. Villamin ◽  
Silvia Argimón ◽  
Manuel C. Jamoralin ◽  
Karis D. Boehme ◽  
Melissa L. Masim ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Neisseria Gonorrhoeae ◽  
Sequence Data ◽  
The Philippines ◽  
Sequence Type ◽  
Western Pacific ◽  
Surveillance Program ◽  
Genotypic Resistance ◽  
Genomic Epidemiology ◽  
The Western Pacific

AbstractAntimicrobial-resistant Neisseria gonorrhoeae is a major threat to public health, and of particular concern in the Western Pacific Region, where the incidence of gonorrhoea is high. The Antimicrobial Resistance Surveillance Program (ARSP) has been capturing information on resistant gonorrhoea since 1996, but studies of the genomic epidemiology of gonorrhoea in the Philippines are lacking.We sequenced the whole genomes of 21 N. gonorrhoeae isolates collected in 2013-2014 by the ARSP. The multi-locus sequence type, multi-antigen sequence type, presence of antimicrobial resistance (AMR) determinants, and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined.Ten out of 21 isolates were resistant to penicillin, ciprofloxacin and tetracycline, mostly linked to the presence of blaTEM gene, the S91F mutation in the gyrA gene, and the tetM gene, respectively. None of the isolates were resistant to azithromycin, ceftriaxone or cefixime, although we identified the A24-deletion in the mtrR promoter in one isolate. The concordance between phenotypic and genotypic resistance was 92.38% overall for 5 antibiotics in 4 classes. Despite the small number of isolates studied, they were genetically diverse, as shown by the sequence types, the NG-MAST types and the tree. Comparison with global genomes placed the Philippine genomes within global Lineage A and led to the identification of an international transmission route.This first genomic survey of N. gonorrhoeae isolates collected by ARSP will be used to contextualize ongoing prospective surveillance, and it highlights the importance of genomic surveillance in the Western Pacific and other endemic regions to understand the spread of drug-resistant gonorrhoea worldwide.

scholarly journals Genomic surveillance of methicillin-resistant Staphylococcus aureus in the Philippines, 2013–2014

2021 ◽  
Vol 12 (1) ◽  
pp. 6-16
Author(s):  
Melissa Masim ◽  
Silvia Argimon ◽  
Holly Espiritu ◽  
Mariane Magbanua ◽  
Agnettah Olorosa ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Resistance ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Sequence Data ◽  
Sccmec Type ◽  
The Philippines ◽  
Surveillance Program ◽  
Genotypic Resistance ◽  
Methicillin Resistant ◽  
Invasive Infections

Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the leading causes of both nosocomial and community infections worldwide. In the Philippines, MRSA rates have remained above 50% since 2010, but resistance to other antibiotics, including vancomycin, is low. The MRSA burden can be partially attributed to pathogen-specific characteristics of the circulating clones, but little was known about the S. aureus clones circulating in the Philippines. We sequenced the whole genomes of 116 S. aureus isolates collected in 2013–2014 within the Antimicrobial Resistance Surveillance Program. The multilocus sequence type, spa type, SCCmec type, presence of antimicrobial resistance (AMR) determinants and virulence genes and relatedness between the isolates were all derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. The MRSA population in the Philippines comprised a limited number of genetic clones, including several international epidemic clones, such as CC30-spa-t019-SCCmec-IV-PVL+, CC5-SCCmec-typeIV and ST239-spa-t030-SCCmec-typeIII. The CC30 genomes were related to the South-West Pacific clone but formed a distinct, diverse lineage, with evidence of global dissemination. We showed independent acquisition of resistance to sulfamethoxazole/trimethoprim in various locations and genetic clones but mostly in paediatric patients with invasive infections. The concordance between phenotypic and genotypic resistance was 99.68% overall for eight antibiotics in seven classes. We have made the first comprehensive genomic survey of S. aureus in the Philippines, which bridges the gap in genomic data from the Western Pacific Region and will constitute the genetic background for contextualizing prospective surveillance.

scholarly journals Genomic surveillance of Pseudomonas aeruginosa in the Philippines, 2013–2014

2021 ◽  
Vol 12 (2) ◽  
pp. 4-18
Author(s):  
Jeremiah Chilam ◽  
Silvia Argimon ◽  
Marilyn Limas ◽  
Melissa Masim ◽  
June Gayeta ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Carbapenem Resistance ◽  
Opportunistic Pathogen ◽  
Multidrug Resistant ◽  
The Philippines ◽  
Loss Of Function ◽  
Genotypic Resistance ◽  
Class 1 ◽  
Long Read ◽  
Ongoing Surveillance

Pseudomonas aeruginosa is an opportunistic pathogen that often causes nosocomial infections resistant to treatment. Rates of antimicrobial resistance (AMR) are increasing, as are rates of multidrug-resistant (MDR) and possible extensively drug-resistant (XDR) infections. Our objective was to characterize the molecular epidemiology and AMR mechanisms of this pathogen. We sequenced the whole genome for each of 176 P. aeruginosa isolates collected in the Philippines in 2013–2014; derived the multilocus sequence type (MLST), presence of AMR determinants and relatedness between isolates; and determined concordance between phenotypic and genotypic resistance. Carbapenem resistance was associated with loss of function of the OprD porin and acquisition of the metallo-β-lactamase (MBL) gene blaVIM. Concordance between phenotypic and genotypic resistance was 93.27% overall for six antibiotics in three classes, but varied among minoglycosides. The population of P. aeruginosa was diverse, with clonal expansions of XDR genomes belonging to MLSTs ST235, ST244, ST309 and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, and of transfer between hospitals. Most of the ST235 genomes formed a distinct lineage from global genomes, thus raising the possibility that they may be unique to the Philippines. In addition, long-read sequencing of one representative XDR ST235 isolate identified an integron carrying multiple resistance genes (including blaVIM-2), with differences in gene composition and synteny from the P. aeruginosa class 1 integrons described previously. The survey bridges the gap in genomic data from the Western Pacific Region and will be useful for ongoing surveillance; it also highlights the importance of curtailing the spread of ST235 within the Philippines.

scholarly journals See and Sequence: Integrating Whole-Genome Sequencing Within the National Antimicrobial Resistance Surveillance Program in the Philippines

2019 ◽  
Author(s):  
Silvia Argimón ◽  
Melissa A. L. Masim ◽  
June M. Gayeta ◽  
Marietta L. Lagrada ◽  
Polle K. V. Macaranas ◽  
...  
Keyword(s):  
Public Health ◽  
Antimicrobial Resistance ◽  
Genome Sequencing ◽  
Genomic Data ◽  
Carbapenem Resistance ◽  
The Philippines ◽  
Surveillance Program ◽  
Whole Genome ◽  
Genomic Epidemiology ◽  
Carbapenem Resistant

AbstractDrug-resistant bacterial infections constitute a growing threat to public health globally 1. National networks of laboratory-based surveillance of antimicrobial resistance (AMR) monitor the emergence and spread of resistance and are central to the dissemination of these data to AMR stakeholders 2. Whole-genome sequencing (WGS) can support these efforts by pinpointing resistance mechanisms and uncovering transmission patterns 3, 4. However, genomic surveillance is rare in low- and middle-income countries (LMICs), which are predicted to be the most affected by AMR 5. We implemented WGS within the established Antimicrobial Resistance Surveillance Program (ARSP) of the Philippines via ongoing technology transfer, capacity building in and binational collaboration. In parallel, we conducted an initial large-scale retrospective sequencing survey to characterize bacterial populations and dissect resistance phenotypes of key bug-drug combinations, which is the focus of this article. Starting in 2010, the ARSP phenotypic data indicated increasing carbapenem resistance rates for Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli. We first identified that this coincided with a marked expansion of specific resistance phenotypes. By then linking the resistance phenotypes to genomic data, we revealed the diversity of genetic lineages (strains), AMR mechanisms, and AMR vehicles underlying this expansion. We discovered a previously unreported plasmid-driven hospital outbreak of carbapenem-resistant K. pneumoniae, uncovered the interplay of carbapenem resistance genes and plasmids in the geographic circulation of epidemic K. pneumoniae ST147, and found that carbapenem-resistant E. coli ST410 consisted of diverse lineages of global circulation that carried both international and local plasmids, resulting in a combination of carbapenemase genes variants previously unreported for this organism. Thus, the WGS data provided an enhanced understanding of the interplay between strains, genes and vehicles driving the dissemination of carbapenem resistance in the Philippines. In addition, our retrospective survey served both as the genetic background to contextualize local prospective surveillance, and as a comprehensive dataset for training in bioinformatics and genomic epidemiology. Continued prospective sequencing, capacity building and collaboration will strengthen genomic surveillance of AMR in the Philippines and the translation of genomic data into public-health action. We generated a blueprint for the integration of WGS and genomic epidemiology into an established national system of laboratory-based surveillance of AMR through international collaboration that can be adapted and utilized within other locations to tackle the global challenge of AMR.

scholarly journals Integrating whole-genome sequencing within the National Antimicrobial Resistance Surveillance Program in the Philippines

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Silvia Argimón ◽  
Melissa A. L. Masim ◽  
June M. Gayeta ◽  
Marietta L. Lagrada ◽  
Polle K. V. Macaranas ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
The Philippines ◽  
Surveillance Program ◽  
Whole Genome ◽  
Antimicrobial Resistance Surveillance

Stress responses as determinants of antimicrobial resistance in Pseudomonas aeruginosa: multidrug efflux and more

2014 ◽  
Vol 60 (12) ◽  
pp. 783-791 ◽  
Author(s):  
Keith Poole
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Environmental Stress ◽  
Stress Responses ◽  
Acquired Resistance ◽  
Resistance Mechanisms ◽  
Resistant Organism ◽  
Multidrug Efflux ◽  
Resistance Development ◽  
Endogenous Genes

Pseudomonas aeruginosa is a notoriously antimicrobial-resistant organism that is increasingly refractory to antimicrobial chemotherapy. While the usual array of acquired resistance mechanisms contribute to resistance development in this organism a multitude of endogenous genes also play a role. These include a variety of multidrug efflux loci that contribute to both intrinsic and acquired antimicrobial resistance. Despite their roles in resistance, however, it is clear that these efflux systems function in more than just antimicrobial efflux. Indeed, recent data indicate that they are recruited in response to environmental stress and, therefore, function as components of the organism’s stress responses. In fact, a number of endogenous resistance-promoting genes are linked to environmental stress, functioning as part of known stress responses or recruited in response to a variety of environmental stress stimuli. Stress responses are, thus, important determinants of antimicrobial resistance in P. aeruginosa. As such, they represent possible therapeutic targets in countering antimicrobial resistance in this organism.

scholarly journals Reversing resistance to counter antimicrobial resistance in the World Health Organisation’s critical priority of most dangerous pathogens

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Henrietta Venter
Keyword(s):  
Antimicrobial Resistance ◽  
Acquired Resistance ◽  
Carbapenem Resistance ◽  
World Health Organisation ◽  
Resistance Mechanisms ◽  
World Health ◽  
Permeability Barrier ◽  
Intrinsic Resistance ◽  
The World ◽  
Antibiotic Discovery

AbstractThe speed at which bacteria develop antimicrobial resistance far outpace drug discovery and development efforts resulting in untreatable infections. The World Health Organisation recently released a list of pathogens in urgent need for the development of new antimicrobials. The organisms that are listed as the most critical priority are all Gram-negative bacteria resistant to the carbapenem class of antibiotics. Carbapenem resistance in these organisms is typified by intrinsic resistance due to the expression of antibiotic efflux pumps and the permeability barrier presented by the outer membrane, as well as by acquired resistance due to the acquisition of enzymes able to degrade β-lactam antibiotics. In this perspective article we argue the case for reversing resistance by targeting these resistance mechanisms – to increase our arsenal of available antibiotics and drastically reduce antibiotic discovery times – as the most effective way to combat antimicrobial resistance in these high priority pathogens.

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