Molecular epidemiology of KPC-producing<i>Klebsiella pneumoniae</i>from invasive infections in Italy: increasing diversity with predominance of the ST512 clade II sublineage

Conte, Viola; Monaco, Monica; Giani, Tommaso; D’Ancona, Fortunato; Moro, Maria Luisa; Arena, Fabio; D’Andrea, Marco Maria; Rossolini, Gian María; Pantosti, Annalisa

doi:10.1093/jac/dkw337

Cited by 69 publications

(71 citation statements)

References 37 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The most important mechanism in carbapenem resistance in Enterobacteriaceae is the production of carbapenemases, primarily KPC VIM NDM and OXA-48 types, which display remarkable geographycal variability. KPC production is the most frequent mechanism of resistance to carbapenems in K. pneumoniae in Italy, as already reported in the 2011 Italian survey [4] and KPC-type carbapenemases-producing K. pneumoniae has become endemic, as very recently confirmed [5]. Underlying haematological disease, intensive chemotherapy, neutropenia, gastrointestinal mucositis and prolonged hospitalization are all conditions favouring the CRKP spread and infections, mainly bacteremias [6–11].…”

Section: Introductionmentioning

confidence: 84%

“…The diffusion of carbapenem-resistant Klebsiella pneumoniae (CRKP) [1–5] in the setting of patients with haematological malignancies undergoing intensive myelosuppressive chemotherapy is a very worrying challenge [6–11], especially in endemic areas. The most important mechanism in carbapenem resistance in Enterobacteriaceae is the production of carbapenemases, primarily KPC VIM NDM and OXA-48 types, which display remarkable geographycal variability.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Carbapenem-resistant Klebsiella pneumoniae in high-risk haematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias

et al. 2017

View full text Add to dashboard Cite

BackgroundCarbapenem-resistant Klebsiella pneumoniae (CRKP) spread and infections in patients with haematological malignancies are a serious concern especially in endemic areas. Treatment failures and delay in appropriate therapy for CRKP infections are frequent and the mortality rate associated with CRKP bacteremia in neutropenic haematological patients is reported about 60%.MethodsHaematological patients harboring CRKP hospitalized between February 2012 and May 2013 in an Italian Teaching hospital were examined. Conditions favouring CRKP spread in a haematological unit, risk factors for bacteremia in CRKP-carriers and for CRKP bacteremia-related death were evaluated in this observational retrospective study.ResultsCRKP was isolated in 22 patients, 14 (64%) had bacteremia. Control measures implementation, particularly the weekly rectal screening for CRKP performed in all hospitalized patients and contact precautions for CRKP-carriers and newly admitted patients until proved CRKP-negative, reduced significantly the CRKP spread (14 new carriers identified of 131 screened patients vs 5 of 242 after the intervention, p = 0.001). Fifty-eight percent of carriers developed CRKP bacteremia, and acute myeloid leukemia (AML) resulted independently associated with the bacteremia occurrence (p = 0.02). CRKP bacteremias developed mainly during neutropenia (86%) and in CRKP-carriers (79%). CRKP bacteremias were breakthrough in 10 cases (71%). Ten of 14 patient with CRKP bacteremias died (71%) and all had AML. The 70% of fatal bacteremias occurred in patients not yet recognized as CRKP-carriers and 80% were breakthrough. Initial adequate antibiotic therapy resulted the only independent factor able to protect against death (p = 0.02).ConclusionsThe identification of CRKP-carriers is confirmed critical to prevent CRKP spread. AML patients colonized by CRKP resulted at high risk of CRKP-bacteremia and poor outcome and the adequacy of the initial antibiotic therapy may be effective to improve survival. To limit the increase of resistance, the extensive use of antibiotics active against CRKP should be avoided, but in the setting of high CRKP pressure and high-risk CRKP-colonized haematological patients, timely empiric antibiotic combinations active against CRKP could be suggested as treatment of febrile neutropenia.

show abstract

Section: Introductionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Carbapenem-resistant Klebsiella pneumoniae in high-risk haematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Remarkably, very similar pulsotypes were recently observed for K . pneumoniae isolates included in a recent surveillance study conducted in Italian hospitals, suggesting the persistence of the two clonal lineages in our country [20]. …”

Section: Methodsmentioning

confidence: 99%

Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases

et al. 2017

Self Cite

View full text Add to dashboard Cite

ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital-acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines. Significant differences between the strains were found in their ability to induce the production of IL-1β: KK207-1/clade I was much less effective than KKBO-1/clade II in inducing IL-1β production by monocytes and dendritic cells. The activation of NLRP3 inflammasome pathway by live cells and/or purified capsular polysaccharides was studied in monocytes and dendritic cells. We found that glibenclamide, a NLRP3 inhibitor, inhibits more than 90% of the production of mature IL-1β induced by KKBO1 and KK207-1. KK207-1 was always less efficient compared to KKBO-1 in: a) inducing NLRP3 and pro-IL-1β gene and protein expression; b) in inducing caspase-1 activation and pro-IL-1β cleavage. Capsular composition may play a role in the differential inflammatory response induced by the ST258-KP strains since capsular polysaccharides purified from bacterial cells affect NLRP3 and pro-IL-1β gene expression through p38MAPK- and NF-κB-mediated pathways. In each of these functions, capsular polysaccharides from KK207-1 were significantly less efficient compared to those purified from KKBO-1. On the whole, our data suggest that the change in capsular phenotype may help bacterial cells of clade I to partially escape innate immune recognition and IL-1β-mediated inflammation.

show abstract

“…Recent studies demonstrated that strains of ST258 are hybrid clones originated by a number of large genomic recombination events that gave rise to two major clades (clade I and clade II), characterized mainly by different capsule polysaccharide (CPS) gene clusters 13–15 . Clade II strains contribute to the majority of ST258 and of other STs of CG258 causing outbreaks reported in several regions including USA, Italy, South America, Israel and Greece 14, 16–20 .…”

Section: Introductionmentioning

confidence: 99%

φBO1E, a newly discovered lytic bacteriophage targeting carbapenemase-producing Klebsiella pneumoniae of the pandemic Clonal Group 258 clade II lineage

D’Andrea

Marmo

Angelis

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

The pandemic dissemination of KPC carbapenemase-producing Klebsiella pneumoniae (KPC-KP) represents a major public health problem, given their extensive multidrug resistance profiles and primary role in causing healthcare-associated infections. This phenomenon has largely been contributed by strains of Clonal Group (CG) 258, mostly of clade II, which in some areas represent the majority of KPC-KP isolates. Here we have characterized a newly discovered lytic Podoviridae, named φBO1E, targeting KPC-KP strains of clade II lineage of CG258. Genomic sequencing revealed that φBO1E belongs to the Kp34virus genus (87% nucleotide identity to vB_KpnP_SU552A). ΦBO1E was stable over a broad pH and temperature range, exhibited strict specificity for K. pneumoniae strains of clade II of CG258, and was unable to establish lysogeny. In a Galleria mellonella infection model, φBO1E was able to protect larvae from death following infection with KPC-KP strains of clade II of CG258, including one colistin resistant strain characterized by a hypermucoviscous phenotype. To our best knowledge φBO1E is the first characterized lytic phage targeting K. pneumoniae strains of this pandemic clonal lineage. As such, it could be of potential interest to develop new agents for treatment of KPC-KP infections and for decolonization of subjects chronically colonized by these resistant superbugs.

show abstract

Molecular epidemiology of KPC-producingKlebsiella pneumoniaefrom invasive infections in Italy: increasing diversity with predominance of the ST512 clade II sublineage

Abstract: Although a trend to a polyclonal evolution of the Italian KPC-KP was noted, this study showed that the KPC-KP population remained largely oligoclonal with the wide diffusion of an ST512 lineage carrying cps-2 capsular type and producing the KPC-3 enzyme.

Cited by 69 publications

References 37 publications

Carbapenem-resistant Klebsiella pneumoniae in high-risk haematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias

Carbapenem-resistant Klebsiella pneumoniae in high-risk haematological patients: factors favouring spread, risk factors and outcome of carbapenem-resistant Klebsiella pneumoniae bacteremias

Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases

φBO1E, a newly discovered lytic bacteriophage targeting carbapenemase-producing Klebsiella pneumoniae of the pandemic Clonal Group 258 clade II lineage

Contact Info

Product

Resources

About