Outbreak of ST395 KPC-Producing <i>Klebsiella pneumoniae</i> in a Neonatal Intensive Care Unit in Palermo, Italy

Maida, Carmelo Massimo; Bonura, Celestino; Geraci, Daniela Maria; Graziano, Giorgio; Carattoli, Alessandra; Rizzo, Angelo; Torregrossa, Maria Valeria; Vecchio, Davide; Giuffrè, Mario

doi:10.1017/ice.2017.267

Cited by 22 publications

(16 citation statements)

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“…ST307, ST395, ST392, ST348, ST405 and ST101) have been detected in our area. These results are consistent with the surveillance data from other authors [20–24, 28]. Moreover, our findings on β-lactamase characterisation showed that the bla SHV gene was the most commonly found in our sample, followed by bla TEM and bla KPC, deviating from other studies [11, 29, 30], while respect to the KPC-type enzyme our results are in line with those of other studies - as the most commonly encountered is bla KPC-3 [21, 23, 31–33].…”

Section: Discussionsupporting

confidence: 94%

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Co-existence of virulence factors and antibiotic resistance in new Klebsiella pneumoniae clones emerging in south of Italy

Fasciana

Gentile²,

Aquilina

et al. 2019

BMC Infect Dis

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BackgroundEndemic presence of Klebsiella pneumoniae resistant to carbapenem in Italy has been due principally to the clonal expansion of CC258 isolates; however, recent studies suggest an ongoing epidemiological change in this geographical area.Methods50 K. pneumoniae strains, 25 carbapenem-resistant (CR-Kp) and 25 susceptible (CS-Kp), collected from march 2014 to march 2016 at the Laboratory of Bacteriology of the Paolo Giaccone Polyclinic University hospital of Palermo, Italy, were characterized for antibiotic susceptibility and fully sequenced by next generation sequencing (NGS) for the in silico analysis of resistome, virulome, multi-locus sequence typing (MLST) and core single nucleotide polymorphism (SNP) genotypesResultsMLST in silico analysis of CR-Kp showed that 52% of isolates belonged to CC258, followed by ST395 (12%), ST307 (12%), ST392 (8%), ST348 (8%), ST405 (4%) and ST101 (4%). In the CS-Kp group, the most represented isolate was ST405 (20%), followed by ST392 and ST15 (12%), ST395, ST307 and ST1727 (8%). The in silico β-lactamase analysis of the CR-Kp group showed that the most detected gene was blaSHV (100%), followed by blaTEM (92%), blaKPC (88%), blaOXA (88%) and blaCTX-M (32%). The virulome analysis detected mrk operon in all studied isolates, and wzi-2 was found in three CR-Kp isolates (12%). Furthermore, the distribution of virulence genes encoding for the yersiniabactin system, its receptor fyuA and the aerobactin system did not show significant distribution differences between CR-Kp and CS-Kp, whereas the Klebsiella ferrous iron uptake system (kfuA, kfuB and kfuC genes), the two-component system kvgAS and the microcin E495 were significantly (p < 0.05) prevalent in the CS-Kp group compared to the CR-Kp group.Core SNP genotyping, correlating with the MLST data, allowed greater strain tracking and discrimination than MLST analysis.ConclusionsOur data support the idea that an epidemiological change is ongoing in the Palermo area (Sicily, Italy). In addition, our analysis revealed the co-existence of antibiotic resistance and virulence factors in CR-Kp isolates; this characteristic should be considered for future genomic surveillance studies.

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Section: Discussionsupporting

confidence: 94%

“…However, several reports have suggested an ongoing epidemiological change in the last years. In fact, whereas CC258 (ST258 and ST512) is still prevalent, several other STs are emerging and circulating [23, 24, 28].…”

Section: Discussionmentioning

confidence: 99%

Co-existence of virulence factors and antibiotic resistance in new Klebsiella pneumoniae clones emerging in south of Italy

Fasciana

Gentile²,

Aquilina

et al. 2019

BMC Infect Dis

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“…The bla KPC-41 -positive K. pneumoniae UM belonged to ST395, although the previously reported KPC producers exhibiting CZA resistance belonged to ST258 (6), ST307 (3), and ST1519 (11). It is noteworthy that an outbreak caused by a KPC-3-producing K. pneumoniae ST395 isolate (susceptibility to CZA not reported) has been reported in a neonatal intensive care unit in Palermo, Italy, and in our study the patient carrying K. pneumoniae UM also originated from Sicily (12).…”

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confidence: 42%

Phenotypic, Biochemical, and Genetic Analysis of KPC-41, a KPC-3 Variant Conferring Resistance to Ceftazidime-Avibactam and Exhibiting Reduced Carbapenemase Activity

Mueller

Masseron

Prod’hom

et al. 2019

Antimicrob Agents Chemother

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A novel KPC variant, KPC-41, was identified in a Klebsiella pneumoniae clinical isolate from Switzerland. This β-lactamase possessed a 3-amino-acid insertion (Pro-Asn-Lys) located between amino acids 269 and 270 compared to the KPC-3 amino acid sequence. Cloning and expression of the blaKPC-41 gene in Escherichia coli, followed by determination of MIC values and kinetic parameters, showed that KPC-41, compared to those of KPC-3, has an increased affinity to ceftazidime and a decreased sensitivity to avibactam, leading to resistance to ceftazidime-avibactam once produced in K. pneumoniae. Furthermore, KPC-41 exhibited a drastic decrease of its carbapenemase activity. This report highlights that a diversity of KPC variants conferring resistance to ceftazidime-avibactam already circulate in Europe.

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“…In one of our previous studies, 30 day fatality of infections with ST101 K.pneumoniae was found to be 72% (30). The ST395 clone is known as a potentially high-risk clone (32), and recent studies pointed out the emergence of carbapenem-resistant ST395 in France and Italy (33, 34). KPC-2 producing ST101 K. pneumoniae was shown to have the highest number of virulence genes associated with capsule type, attachment and iron uptake than the other epidemic clones of K.pneumonia (10).…”

Section: Discussionmentioning

confidence: 99%

The role of iron uptake systems in the pathogenesis of colistin-resistant hypervirulent K.pneumoniae infections

Doğan

Vatansever

Ataç

et al. 2019

Preprint

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16Here we proposed the hypothesis that hypervirulent colistin resistant K.pneumoniae (ColR-Kp) exhibit 17 high number of virulence factors and have enhanced survival capacity against neutrophil activity. 18We studied virulence genes of ColR-Kp isolates and neutrophil response in 142 patients with invasive 19 infections. 20The patients infected with hypervirulent ST101 and ST395 ColR-Kp had higher 30-day mortality (58%, 21 p=0.005 and 75%, p=0.003, respectively. The yersiniabactin biosynthesis gene (ybtS) and ferric uptake 22 operon associated gene (kfu) were significantly higher in ST101 (99%, p=<0.001) and in ST395 23 (94%,p<0.012). Being in ICU (OR: 7.9; CI: 1.43-55.98; p=0.024), kfu (OR:27.0; CI:5.67-179.65; p<0.001) 24 and ST101 (OR: 17.2; CI: 2.45-350.40; p=0.01) were found to be predictors of 30-day mortality. The 25 uptake of kfu + -ybtS + ColR-Kp by neutrophils was significantly higher than kfu --ybtS -ColR-Kp (78% vs 26 65%, p<0.001). However, kfu + -ybtS + ColR-Kp were more resistant to the killing activity of neutrophils 27 than negative ones (7.90 vs 4.22; p=0.001). The kfu + -ybtS + ColR-Kp stimulated excessive NET formation 28 while the NET's against kfu --ybtS -ColR-Kp were weak and rare. 29Iron uptake systems enhance successful survival of K.pneumoniae against neutrophil phagocytic 30 defense, and stimulate excessive NET formation. The drugs targeted to iron uptake systems would be 31 a promising approach for treatment of hypervirulent K.pneumoniae infections. 32 33 34 35 39 40 41 65 diseases, type of infection, isolation site, blood biochemical parameters, predisposing factors such as 66 having operation within last one month, intensive care unit admission (ICU), type of antimicrobial 67 agents used for empirical and agent-specific therapy, duration of colistin therapy before isolation of 68 colistin-resistant isolates, and carbapenem resistance was used. The patients were followed up for 157 13.13) vs 4.22 (range:0.36-5.64), respectively (p=0.001). The survival index of S.epidermidis and 158 K.pneumoniae controls were 0.64 and 1.89, respectively (Figure2). The survival index of two ybtSkfu + 159isolates were 12.04 and 12.13, and it was 5.13 in one ybtS + kfuisolate. 161Among 21 isolates, four was in ST101 clone. The median phagocytosis rate 80% was found to be and 162 the survival index was 8.51. 164After NETosis, the mean colony count of two kfu + -ybtS + isolates was 5.50X10 6 and it was 4.05x10 6 for 165 kfu --ybtSstrains. The colony count of ATCC K.pneumoniae was 4.3x10 6 . Confocal microscopy study 166 showed that the kfu + -ybtS + isolate stimulated abundant NET formation with excessive release of 167 chromatin granular content to the extracellular area. However, the NET's against kfu --ybtSnegative 168 ColR-Kp were weak and seen only in few areas (Figure 3). 169 170 Discussion 171 ColR-HvKP infections are usually fatal because of limited therapeutic options due to extensive drug 172 resistance and successful immune escape mechanisms of these pathogens. Alternative approaches are

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Outbreak of ST395 KPC-Producing Klebsiella pneumoniae in a Neonatal Intensive Care Unit in Palermo, Italy

Cited by 22 publications

References 9 publications

Co-existence of virulence factors and antibiotic resistance in new Klebsiella pneumoniae clones emerging in south of Italy

Co-existence of virulence factors and antibiotic resistance in new Klebsiella pneumoniae clones emerging in south of Italy

Phenotypic, Biochemical, and Genetic Analysis of KPC-41, a KPC-3 Variant Conferring Resistance to Ceftazidime-Avibactam and Exhibiting Reduced Carbapenemase Activity

The role of iron uptake systems in the pathogenesis of colistin-resistant hypervirulent K.pneumoniae infections

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