Recently, new combinations of β-lactams and β-lactamase inhibitors became available, including ceftazidime-avibactam, and increased the ability to treat infections caused by carbapenem-resistant Enterobacterales (CRE). Despite the reduced time of clinical use, isolates expressing resistance to ceftazidime-avibactam have been reported, even during treatment or in patients with no previous contact with this drug. Here, we detailed review data on global ceftazidime-avibactam susceptibility, the mechanisms involved in resistance, and the molecular epidemiology of resistant isolates. Ceftazidime-avibactam susceptibility remains high (≥ 98.4%) among Enterobacterales worldwide, being lower among extended-spectrum β-lactamase (ESBL) producers and CRE. Alterations in class A β-lactamases are the major mechanism involved in ceftazidime-avibactam resistance, and mutations are mainly, but not exclusively, located in the Ω loop of these enzymes. Modifications in Klebsiella pneumoniae carbapenemase (KPC) 3 and KPC-2 have been observed by many authors, generating variants with different mutations, insertions, and/or deletions. Among these, the most commonly described is Asp179Tyr, both in KPC-3 (KPC-31 variant) and in KPC-2 (KPC-33 variant). Changes in membrane permeability and overexpression of efflux systems may also be associated with ceftazidime-avibactam resistance. Although several clones have been reported, ST258 with Asp179Tyr deserves special attention. Surveillance studies and rationale use are essential to retaining the activity of this and other antimicrobials against class A CRE.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• azabicyklické sloučeniny MeSH
• bakteriální proteiny genetika   MeSH
• beta-laktamasy genetika   MeSH
• ceftazidim farmakologie   MeSH
• fixní kombinace léků MeSH
• infekce bakteriemi rodu Klebsiella * farmakoterapie   MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH
• avibactam, ceftazidime drug combination MeSH Prohlížeč
• azabicyklické sloučeniny MeSH
• bakteriální proteiny MeSH
• beta-laktamasy MeSH
• carbapenemase MeSH Prohlížeč
• ceftazidim MeSH
• fixní kombinace léků MeSH

The aim of the present study is to describe the ongoing spread of the KPC-producing strains, which is evolving to an epidemic in Czech hospitals. During the period of 2018-2019, a total of 108 KPC-producing Enterobacterales were recovered from 20 hospitals. Analysis of long-read sequencing data revealed the presence of several types of blaKPC-carrying plasmids; 19 out of 25 blaKPC-carrying plasmids could be assigned to R (n = 12), N (n = 5), C (n = 1) and P6 (n = 1) incompatibility (Inc) groups. Five of the remaining blaKPC-carrying plasmids were multireplicon, while one plasmid couldn't be typed. Additionally, phylogenetic analysis confirmed the spread of blaKPC-carrying plasmids among different clones of diverse Enterobacterales species. Our findings demonstrated that the increased prevalence of KPC-producing isolates was due to plasmids spreading among different species. In some districts, the local dissemination of IncR and IncN plasmids was observed. Additionally, the ongoing evolution of blaKPC-carrying plasmids, through genetic rearrangements, favours the preservation and further dissemination of these mobile genetic elements. Therefore, the situation should be monitored, and immediate infection control should be implemented in hospitals reporting KPC-producing strains.

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriální léková rezistence * MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• beta-laktamasy metabolismus   MeSH
• epidemie MeSH
• infekce bakteriemi rodu Klebsiella epidemiologie   mikrobiologie   MeSH
• Klebsiella pneumoniae izolace a purifikace   metabolismus   MeSH
• lidé MeSH
• nemocnice statistika a číselné údaje   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Názvy látek
• antibakteriální látky MeSH
• bakteriální proteiny MeSH
• beta-laktamasy MeSH
• carbapenemase MeSH Prohlížeč

To evaluate the water compartment antibiotic-resistance contamination rates, 11 wells, five streams, and four treatment plants located in the Oltrepò Pavese area were screened for the presence of third generation cephalosporins resistant Gram-negative bacteria. Enterobacteriaceae were also characterized for the Extended-Spectrum-β-Lactamases (ESBLs), carbapenemases, and mcr-1 genes presence. From December 2014 to November 2015, 246 water samples were filtered, plated on Plate Count Agar, MacConkey Agar, and MacConkey Agar with cefotaxime. Isolates were species identified using AutoSCAN-4-System and ESBLs, carbapenemases, and colistin resistance determinants were characterized by PCR, sequencing, and microarray. Plasmid conjugative transfer experiments, PCR-based Replicon typing, Pulsed-Field Gel Electrophoresis, Multi-Locus-Sequence-Typing, and in-silico plasmid characterization were performed. A total of 132 enterobacteria isolates grew on MacConkey agar with cefotaxime: 82 (62.1%) were obtained from streams, 41 (31.1%) from treatment plants, and 9 (6.8%) from wells. Thirty out of 132 (22.7%) isolates, mainly belonging to Escherichia coli (n = 15) species, showed a synergic effect with piperacillin-tazobactam. A single ESBL gene of blaCTX-M-type was identified in 19/30 isolates. In further two E. coli strains, a blaCTX-M-1 gene co-existed with a blaSHV-type ESBL determinant. A blaSHV-12 gene was detected in two isolates of E. coli (n = 1) and Klebsiella oxytoca (n = 1), while any ESBL determinant was ascertained in seven Yersinia enterocolitica strains. A blaDHA-type gene was detected in a cefoxitin resistant Y. enterocolitica from a stream. Interestingly, two Klebsiella pneumoniae strains of ST307 and ST258, collected from a well and a wastewater treatment plant, resulted KPC-2, and KPC-3 producers, respectively. Moreover, we report the first detection of mcr-1.2 ST10 E. coli on a conjugative IncX4 plasmid (33.303 bp in size) from a stream of Oltrepò Pavese (Northern Italy). Both ESBLs E. coli and ESBLs/carbapenemase-producing K. pneumoniae strains showed clonal heterogeneity by Pulsed-Field Gel Electrophoresis and Multi-Locus-Sequence-Typing. During one-year study and taking in account the whole Gram-negative bacterial population, an average percentage of cefotaxime resistance of 69, 32, and 10.3% has been obtained for the wastewater treatment plants, streams, and wells, respectively. These results, of concern for public health, highlight the need to improve hygienic measures to reduce the load of discharged bacteria with emerging resistance mechanisms.

• Klíčová slova
• Gram-negative bacteria, carbapenemases, colistin resistance, molecular characterization, water ecosystems,
• Publikační typ
• časopisecké články MeSH

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

• MeSH
• antibiotická rezistence MeSH
• antiinfekční látky farmakologie   MeSH
• lidé MeSH
• mezinárodní spolupráce * MeSH
• mikrobiální testy citlivosti MeSH
• nitrobřišní infekce * diagnóza   farmakoterapie   mikrobiologie   MeSH
• prognóza MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antiinfekční látky MeSH

KPC-3-producing bacteria are endemic in many countries but only recently became apparent their wide distribution in different Portuguese hospitals. The aim of this study is to characterize genetic backgrounds associated with bla KPC-3 among Klebsiella pneumoniae isolates recently identified on non-hospitalized patients in Portugal. Twenty KPC-producing K. pneumoniae identified between October 2014 and November 2015 in three different community laboratories were characterized. Isolates were mainly from patients from long-term care facilities (n = 11) or nursing homes (n = 6), most of them (75%) previously hospitalized in different Portuguese hospitals. Standard methods were used for bacterial identification and antibiotic susceptibility testing. Carbapenemase production was assessed by the Blue-Carba test, and identification of bla genes was performed by PCR and sequencing. Epidemiological features of KPC-producing K. pneumoniae included population structure (XbaI-PFGE, MLST and wzi sequencing), genetic context (mapping of Tn4401), and plasmid (replicon typing, S1-PFGE, and hybridization) analysis. All K. pneumoniae isolates produced KPC-3, with two MDR K. pneumoniae epidemic clones representing 75% of the isolates, namely ST147 (wzi64/K14.64, February-November 2015) and ST15 (two lineages exhibiting capsular types wzi19/K19 or wzi93/K60, July-November 2015). Other sporadic clones were detected: ST231 (n = 3; wzi104), ST348 (n = 1; wzi94) and ST109 (n = 1, wzi22/K22.37). bla KPC-3 was identified within Tn4401d in all isolates, located in most cases (80%) on cointegrated plasmids (repA FIA+repA FII+ori ColE1;105-250 kb) or in 50 kb IncN plasmids. In conclusion, this study highlights a polyclonal structure of KPC-3-producing K. pneumoniae and the predominance of the ST147 clone among non-hospitalized patients in Portugal, linked to platforms still unnoticed in Europe (bla KPC-3-Tn4401d-IncFIA) or firstly reported (bla KPC-3-Tn4401d-IncN). This scenario underlines the recent penetration of successful mobile genetic elements in previously circulating MDR K. pneumoniae lineages (mainly ST147 and ST15) in Portugal, rather than the importation of the global lineages from clonal group 258.

• Klíčová slova
• ColE, ST147, ST15, carbapenemases, cointegrated plasmids, international clones, multidrug resistance,
• Publikační typ
• časopisecké články MeSH