Background In spite of intensive efforts, understanding of the genetic aspects of familial prostate cancer remains largely incomplete. In a previous microsatellite-based linkage scan of 1233 prostate cancer (PC) families, we identified suggestive evidence for linkage (i.e. LOD≥1.86) at 5q12, 15q11, 17q21, 22q12, and two loci on 8p, with additional regions implicated in subsets of families defined by age at diagnosis, disease aggressiveness, or number of affected members. Methods In an attempt to replicate these findings and increase linkage resolution, we used the Illumina 6000 SNP linkage panel to perform a genome-wide linkage scan of an independent set of 762 multiplex PC families, collected by 11 ICPCG groups. Results Of the regions identified previously, modest evidence of replication was observed only on the short arm of chromosome 8, where HLOD scores of 1.63 and 3.60 were observed in the complete set of families and families with young average age at diagnosis, respectively. The most significant linkage signals found in the complete set of families were observed across a broad, 37 cM interval on 4q13-25, with LOD scores ranging from 2.02 to 2.62, increasing to 4.50 in families with older average age at diagnosis. In families with multiple cases presenting with more aggressive disease, LOD scores over 3.0 were observed at 8q24 in the vicinity of previously identified common PC risk variants, as well as MYC, an important gene in PC biology. Conclusions These results will be useful in prioritizing future susceptibility gene discovery efforts in this common cancer.

Introduction. Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major cause of clinical infection. However, K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae ST15 strains are occasionally identified and have seldom been reported to cause hospital outbreaks in PR China. Hypothesis/Gap Statement. In this study, we describe nosocomial outbreaks caused by KPC-producing K. pneumoniae ST15 strains in a Chinese tertiary hospital. Aim. To characterize the molecular relationship, resistance and virulence factors of the 32 KPC-producing K. pneumoniae ST15 strains isolated in a Chinese hospital. Methodology. A total of 102 non-repetitive carbapenem-resistant Enterobacteriaceae (CRE) strains were collected from a Chinese tertiary hospital in 2018. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to characterize the clonal relationship of the K. pneumoniae isolates, and the ST15 strains were selected for further study. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Fifteen carbapenem resistance genes, bla KPC genetic structures and 12 virulence factors were detected by PCR. Whole-genome sequencing (WGS) was performed using next-generation sequencing combined with single-molecule real-time sequencing. Results. Thirty-two K. pneumoniae ST15 strains were characterized, and 31 of them presented a PFGE similarity of >92 %, indicating clonal spread. In 81.3 % (26/32) of strains, the imipenem (IPM) and meropenem (MEM) MICs were ≤8 and≤16 µg ml−1, while only 1 isolate (KP18069) exhibited ≥64 µg ml−1 for both agents. The bla KPC-2 gene embedded in the Tn3-Tn4401 chimaera and synonymous mutations of the ompK35 gene were detected in all the strains. However, a nonsense mutation at amino acid position 248 (K248X) of OmpK36 was found in the highly carbapenem-resistant strain KP18069. No virulence gene was detected in any of the ST15 strains. WGS analyses further confirmed the genetic characteristics of the K. pneumoniae KP18069 strain. Conclusion. Nosocomial outbreaks caused by the clonal spread of K. pneumoniae ST15 strains were characterized in a Chinese tertiary hospital, and strict monitoring of highly resistant CRKP is required.

Introduction. Members of the genus Citrobacter are facultative anaerobic Gram-negative bacilli belonging to the Enterobacterales [Janda J Clin Microbiol 1994; 32(8):1850–1854; Arens Clin Microbiol Infect 1997;3(1):53–57]. Formerly, Citrobacter species were occasionally reported as nosocomial pathogens with low virulence [Pepperell Antimicrob Agents Chemother 2002;46(11):3555–60]. Now, they are consistently reported to cause nosocomial infections of the urinary tract, respiratory tract, bone, peritoneum, endocardium, meninges, intestines, bloodstream and central nervous system. Among Citrobacter species, the most common isolates are C. koseri and C. freundii , while C. amalonaticus has seldom been isolated [Janda J Clin Microbiol 1994; 32(8):1850–1854; Marak Infect Dis (Lond) 2017;49(7):532–9]. Further, Citrobacter spp. are usually susceptible to carbapenems, aminoglycosides, tetracyclines and colistin [Marak Infect Dis (Lond) 2017;49(7):532–9]. Hypothesis/Gap Statement. As C. amalonaticus is rare, only one clinical isolate, coharbouring carbapenem resistance gene bla IMP-4 and quinolone resistance gene qnrs1, has been reported. Aim. To characterize a carbapenem-resistant C. amalonaticus strain from PR China coharbouring bla IMP-4 and qnrs1. Methodology. Three hundred and forty nonrepetitive carbapenem-resistant Enterobacterales (CRE) strains were collected during 2011–2018. A carbapenem-resistant C. amalonaticus strain was detected and confirmed using a VITEK mass spectrometry-based microbial identification system and 16S rRNA sequencing. Minimum inhibitory concentrations (MICs) for clinical antimicrobials were obtained by the broth microdilution method. Whole-genome sequencing (WGS) was performed for antibiotic resistance gene analysis, and a phylogenetic tree of C. amalonaticus strains was constructed using the Bacterial Pan Genome Analysis (BPGA) tool. The transferability of the resistance plasmid was verified by conjugal transfer. Results. A rare carbapenem-resistant C. amalonaticus strain (CA71) was recovered from a patient with cerebral obstruction and the sequences of 16S rRNA gene shared more than 99 % similarity with C. amalonaticus CITRO86, FDAARGOS 165. CA71 is resistant to β-lactam, quinolone and aminoglycoside antibiotics, and even imipenem and meropenem (MICs of 2 and 4 mg l−1 respectively), and is only sensitive to polymyxin B and tigecycline. Six antibiotic resistance genes were detected via WGS, including the β-lactam genes bla IMP-4, bla CTX-M-18 and bla Sed1, the quinolone gene qnrs1, and the aminoglycoside genes AAC(3)-VIIIa, AadA24. Interestingly, bla IMP-4 and qnrs1 coexist on an IncN1-type plasmid (pCA71-IMP) and successfully transferred to Escherichia coli J53 via conjugal transfer. Phylogenetic analysis showed that CA71 is most similar to C. amalonaticus strain CJ25 and belongs to the same evolutionary cluster along with seven other strains. Conclusion. To the best of our knowledge, this is the first report of a carbapenem-resistant C. amalonaticus isolate coharbouring bla IMP-4 and qnrs1.

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