Emerging carbapenemases: a global perspective.

The emergence of Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria has become a significant global public health challenge while the optimal treatment remains undefined. We performed a systematic review of published studies and reports of treatment outcomes of KPC infections using MEDLINE (2001–2011). Articles or cases were excluded if one of the following was fulfilled: no individual patient data provided, no treatment regimen specified, no treatment outcome specified, report of colonization, or greater than three antibiotics were used to treat the KPC infection. Data extracted included patient demographics, site of infection, organism, KPC subtype, antimicrobial therapy directed at KPC-infection, and treatment outcome. Statistical analysis was performed in an exploratory manner. A total of 38 articles comprising 105 cases were included in the analysis. The majority of infections were due to K. pneumoniae (89%). The most common site of infection was blood (52%), followed by respiratory (30%), and urine (10%). Forty-nine (47%) cases received monotherapy and 56 (53%) cases received combination therapy directed at the KPC-infection. Significantly more treatment failures were seen in cases that received monotherapy compared to cases who received combination therapy (49% vs 25%; p= 0.01). Respiratory infections were associated with higher rates of treatment failure with monotherapy compared to combination therapy (67% vs 29% p= 0.03). Polymyxin monotherapy was associated with higher treatment failure rates compared to polymyxin-based combination therapy (73% vs 29%; p= 0.02); similarly, higher treatment failure rates were seen with carbapenem monotherapy compared to carbapenem-based combination therapy (60% vs 26%; p= 0.03). Overall treatment failure rates were not significantly different in the three most common antibiotic-class combinations: polymyxin plus carbapenem, polymyxin plus tigecycline, polymyxin plus aminoglycoside (30%, 29%, and 25% respectively; p=0.6). In conclusion, combination therapy is recommended for the treatment of KPC infections; however, which combination of antimicrobial agents needs to be established in future prospective clinical trials.

/pdf/treatment-of-klebsiella-pneumoniae-carbapenemase-kpc-3g7b5r348b.pdf

Treatment of Klebsiella Pneumoniae Carbapenemase (KPC) infections: a review of published case series and case reports

Plasmids have a key role in the horizontal transfer of genes among bacteria. Although plasmids are catalysts for bacterial evolution, it is challenging to understand how they can persist in bacterial populations over the long term because of the burden they impose on their hosts (the ‘plasmid paradox’). This paradox is especially perplexing in the case of ‘small’ plasmids, which are unable to self-transfer by conjugation. Here, for the first time, we investigate how interactions between co-infecting plasmids influence plasmid persistence. Using an experimental model system based on interactions between a diverse assemblage of ‘large’ plasmids and a single small plasmid, pNI105, in the pathogenic bacterium Pseudomonas aeruginosa, we demonstrate that positive epistasis minimizes the cost associated with carrying multiple plasmids over the short term and increases the stability of the small plasmid over a longer time scale. In support of these experimental data, bioinformatic analysis showed that associations between small and large plasmids are more common than would be expected owing to chance alone across a range of families of bacteria; more generally, we find that co-infection with multiple plasmids is more common than would be expected owing to chance across a wide range of bacterial phyla. Collectively, these results suggest that positive epistasis promotes plasmid stability in bacterial populations. These findings pave the way for future mechanistic studies aimed at elucidating the molecular mechanisms of plasmid–plasmid interaction, and evolutionary studies aimed at understanding how the coevolution of plasmids drives the spread of plasmid-encoded traits.

/pdf/positive-epistasis-between-co-infecting-plasmids-promotes-59wcnerc7z.pdf

Positive epistasis between co-infecting plasmids promotes plasmid survival in bacterial populations

https://onlinelibrary.wiley.com/doi/pdf/10.1111/1469-0691.12275

A nosocomial outbreak of KPC-2-producing Klebsiella pneumoniae in a Chinese hospital: dissemination of ST11 and emergence of ST37, ST392 and ST395

KPC-2-producing Klebsiella pneumoniae isolates mainly correspond to clonal complex 258 (CC258); however, we describe KPC-2-producing K. pneumoniae isolates belonging to invasive sequence type 23 (ST23). KPC-2 has scarcely been reported to occur in ST23, and this report describes the first isolation of this pathogen in the Americas. Acquisition of resistant markers in virulent clones could mark an evolutionary step toward the establishment of these clones as major nosocomial pathogens.

First Isolate of KPC-2-Producing Klebsiella pneumonaie Sequence Type 23 from the Americas

/pdf/coexistence-of-plasmid-mediated-kpc-2-and-imp-4-14t24r0a1j.pdf

Coexistence of plasmid-mediated KPC-2 and IMP-4 carbapenemases in isolates of Klebsiella pneumoniae from China

Four isolates of Klebsiella pneumoniae and one isolate of Enterobacter cloacae exhibiting resistance to most β-lactam antibiotics, including oxyimino-cephalosporins and carbapenems, were obtained from different patients among four hospitals in China. Pulsed-field gel electrophoresis demonstrated that all the K. pneumoniae isolates belonged to two clone patterns. Multilocus sequence typing showed that the four isolates of K. pneumoniae belonged to two sequence types: ST 23 and ST 351. Conjugation studies with Escherichia coli (EC600) resulted in the transfer of reduced carbapenem susceptibility compared with that of the original isolates. Plasmid restriction analysis and hybridization experiment showed that the five isolates of Enterobacteriaceae carried a common 50 kb blaKPC-2-encoding plasmid.

Detection of a Common Plasmid Carrying blaKPC-2 in Enterobacteriaceae Isolates from Distinct Cities in China

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Coexistence of plasmid-mediated KPC-2 and IMP-4 carbapenemases in isolates of Klebsiella pneumoniae from China

Detection of a Common Plasmid Carrying blaKPC-2 in Enterobacteriaceae Isolates from Distinct Cities in China