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Colistin-resistant KPC-2-producing Klebsiella pneumoniae ST423 harboring an IS5-like element in the mgrB gene isolated from cerebrospinal fluid. Expansion of KPC-producing Klebsiella pneumoniae with various mgrB mutations giving rise to colistin resistance: the role of ISL3 on plasmids. Colistin resistance due to insertional inactivation of the mgrB in Klebsiella pneumoniae of clinical origin: First report from India: Resistencia a colistina debido a inactivación insercional del gen mgrB en aislados clínicos de Klebsiella pneumoniae: Primera notificación en India. [Extracted from the article]

Background: Recently, in India, there has been a shift from NDM to OXA48-like carbapenemases. OXA-181 and OXA-232 are the frequently produced variants of OXA48-like carbapenemases. OXA48-like carbapenemases are also known to be carried on transposons such as Tn1999, Tn1999.2 and it is also associated with IS1R carried on Tn1999. In India, there are no previous reports studying the association of mobile genetic elements (MGEs) with OXA48-like carbapenemases. The present study was aimed at determining the genetic backbone of OXA48-like carbapenemases to determine the role of MGEs in its transfer and to investigate the Inc plasmid type carrying blaOXA48-like. Results: A total of 49 carbapenem resistant K. pneumoniae which included 25 isolates from South India and 24 isolates from North India, were included in the study. Whole genome sequencing using Ion Torrent PGM was performed to study the isolates. OXA-232 was present in 35 isolates (71%). In 19 isolates (39%), blaOXA48-like was associated with MGEs. Insertion sequences such as ISX4, IS1, IS3, ISKpn1, ISKpn26, ISKpn25, ISSpu2, ISKox1, IS4321R, ISEc36, and ISPa38; and transposons such as TnAs3 and Tn2, were present. Isolates from northern and southern India belonging to same sequence type (ST) had diverse genetic backbone for blaOXA48-like. ST14 isolates from north had IS5 and Tn3 families while from south they had IS1, IS5 and IS630 families. ST231 from north had IS5, IS6 and Tn3 families with blaOXA-232 while from south, IS1, IS3 and IS5 families were observed; with ISKpn26 being present among isolates from both the regions. blaOXA48-like was predominantly found on ColKP3 plasmid. ST231 was the predominant ST in 22 isolates (45%). Conclusion: OXA-232 is the predominant variant of OXA48-like carbapenemase with ST231 being the commonest ST of OXA48-like carbapenemase producing K. pneumoniae in India. Diverse MGEs have been associated with both blaOXA-232 and blaOXA-181 which contribute to their spread. The MGEs in the present study are different from those reported earlier. There is no clonal expansion of blaOXA48-like producing K. pneumoniae since diverse STs were observed. Monitoring the genetic backbone of OXA48-like carbapenemase is essential to better understand the transmission dynamics of XDR K. pneumoniae. [ABSTRACT FROM AUTHOR]

Background & objectives: Klebsiella pneumoniae (KP), a common cause of invasive infections, is often extensively drug resistant in India. At present, studies on resistance mechanism and clonal relationship of KP from India are limited. The present study was undertaken to determine the resistance mechanism and clonal relationship of colistin-resistant isolates obtained from various specimens. Carbapenemases were also determined since the isolates were carbapenem resistant. Methods: Sixty five isolates from blood, exudates and respiratory specimens collected between 2016 and 2017 were studied. Colistin minimum inhibitory concentration (MIC) was performed by broth-micro dilution method. Multiplex PCR was carried out to determine carbapenemases. Targeted sequencing was performed to determine mutations in mgrB, phoP, phoQ and multilocus sequence typing was performed to determine the prevalent clones. Results: Colistin MIC ranged from 4 to 256 μg/ml. SHV, TEM and CTX-M were co-produced in 60 per cent and OXA48-like in 71 per cent. Thirteen isolates had mutations in mgrB. Mutations included a premature stop codon at 21st amino acid, the presence of insertion sequences such as IS903, IS Kpn 14 and ISK pn 26; and elongation of mgrB. Novel mutations were also observed among phoP and phoQ genes. Colistin resistance due to mcr genes was absent. Fifteen clonal types were seen with ST231, ST14 and ST2096 being predominant. Interpretation & conclusions: This study revealed the changing trend of carbapenem resistance mechanism predominantly to OXA48-like from NDM. Known mgrB mutations and novel mutations in phoP and phoQ were detected. There was no plasmid-mediated colistin resistance. ST14 and ST231 were international clones associated with carbapenem resistance. Colistin-resistant KP was of diverse clones with predominantly ST231, ST14 and ST2096. [ABSTRACT FROM AUTHOR]

Background: Hypervirulent K. pneumoniae (hvKp) causes severe community acquired infections, predominantly in Asia. Though initially isolated from liver abscesses, they are now prevalent among invasive infections such as bacteraemia. There have been no studies reported till date on the prevalence and characterisation of hvKp in India. The objective of this study is to characterise the hypervirulent strains isolated from bacteraemic patients for determination of various virulence genes and resistance genes and also to investigate the difference between healthcare associated and community acquired hvKp with respect to clinical profile, antibiogram, clinical outcome and molecular epidemiology. Results: Seven isolates that were susceptible to all of the first and second line antimicrobials and phenotypically identified by positive string test were included in the study. They were then confirmed genotypically by presence of rmpA and rmpA2 by PCR. Among the study isolates, four were from patients with healthcare associated infections; none were fatal. All patients with community acquired infection possessed chronic liver disease with fatal outcome. Genes encoding for siderophores such as aerobactin, enterobactin, yersiniabactin, allantoin metabolism and iron uptake were identified by whole genome sequencing. Five isolates belonged to K1 capsular type including one K. quasipneumoniae. None belonged to K2 capsular type. Four isolates belonged to the international clone ST23 among which three were health-care associated and possessed increased virulence genes. Two novel sequence types were identified in the study; K. pneumoniae belonging to ST2319 and K. quasipneumoniae belonging to ST2320. Seventh isolate belonged to ST420. Conclusion: This is the first report on whole genome analysis of hypervirulent K. pneumoniae from India. The novel sequence types described in this study indicate that these strains are evolving and hvKp is now spread across various clonal types. Studies to monitor the prevalence of hvKp is needed since there is a potential for the community acquired isolates to develop multidrug resistance in hospital environment and may pose a major challenge for clinical management. [ABSTRACT FROM AUTHOR]

Background: Infections caused by carbapenem resistant K. pneumoniae are increasing and associated with high mortality rates. There are increasing reports of hypermucoviscous/ hypervirulent K. pneumoniae isolated from various sources. However, there is limited data on the prevalence of hypermucoviscous strains among carbapenem-resistant K. pneumoniae from invasive infections in India and its association with mortality. rmpA, rmpA2 and magA genes are associated with these hypervirulent strains. In this study, we investigate the prevalence of hypermucoviscous strains amongst carbapenem resistant K. pneumoniae isolated from blood culture. Association of mortality rate with meropenem minimum inhibitory concentration and hypermucoviscous strains are determined., Methods: 86 non-repetitive carbapenem resistant K. pneumoniae isolated from bacteremia underwent E-test for meropenem minimum inhibitory concentration (MIC) determination and PCR for detection of carbapenamase genes. String test, PCR for rmpA, rmpA2 and magA were performed for characterisation of hypervirulent strains. Results: 31.3% of the 86 isolates displayed hypermucoviscous phenotype as indicated by a positive string test. Among the two genotypic markers, 7% were positive for rmpA2 and all were negative for rmpA and magA. 74.1% and 67.9% mortality were seen among string test positives and isolates meropenem MIC of ≥16µg/ml respectively (p 0.036 and 0.008 respectively). Isolates with both string positivity and meropenem MIC of ≥16µg/ml had a very high mortality rate of 84.2%., Conclusion: String test, aids prediction of disease severity, and is independently associated with increased mortality in invasive carbapenem resistant K.pneumoniae health care-acquired infections. High meropenem MIC is a significant risk factor for mortality. Combination of string positive carbapenem resistant hypermucoviscous K. pneumoniae resulted in mortality rate of 84.2%. It is important to monitor prevalence of carbapenem resistant hypermucoviscous/hypervirulent K. pneumoniae among invasive isolates especially in a setting with high resistance rates as combination of increased virulence and decreased susceptibility to antimicrobials results in worse outcomes., (© Journal of the Association of Physicians of India 2011.)