Abstract
Objectives
To study the in vitro activity of imipenem/relebactam and comparators and the imipenem/relebactam resistance mechanisms in a Pseudomonas aeruginosa collection from Portugal (STEP, ...2017–18) and Spain (SUPERIOR, 2016–17) surveillance studies.
Methods
P. aeruginosa isolates (n = 474) were prospectively recovered from complicated urinary tract (cUTI), complicated intra-abdominal (cIAI) and lower respiratory tract (LRTI) infections in 11 Portuguese and 8 Spanish ICUs. MICs were determined (ISO broth microdilution). All imipenem/relebactam-resistant P. aeruginosa isolates (n = 30) and a subset of imipenem/relebactam-susceptible strains (n = 32) were characterized by WGS.
Results
Imipenem/relebactam (93.7% susceptible), ceftazidime/avibactam (93.5% susceptible) and ceftolozane/tazobactam (93.2% susceptible) displayed comparable activity. The imipenem/relebactam resistance rate was 6.3% (Portugal 5.8%; Spain 8.9%). Relebactam restored imipenem susceptibility to 76.9% (103/134) of imipenem-resistant isolates, including MDR (82.1%; 32/39), XDR (68.8%; 53/77) and difficult-to-treat (DTR) isolates (67.2%; 45/67). Among sequenced strains, differences in population structure were detected depending on the country: clonal complex (CC)175 and CC309 in Spain and CC235, CC244, CC348 and CC253 in Portugal. Different carbapenemase gene distributions were also found: VIM-20 (n = 3), VIM-1 (n = 2), VIM-2 (n = 1) and VIM-36 (n = 1) in Spain and GES-13 (n = 13), VIM-2 (n = 3) and KPC-3 (n = 2) in Portugal. GES-13-CC235 (n = 13) and VIM type-CC175 (n = 5) associations were predominant in Portugal and Spain, respectively. Imipenem/relebactam showed activity against KPC-3 strains (2/2), but was inactive against all GES-13 producers and most of the VIM producers (8/10). Mutations in genes affecting porin inactivation, efflux pump overexpression and LPS modification might also be involved in imipenem/relebactam resistance.
Conclusions
Microbiological results reinforce imipenem/relebactam as a potential option to treat cUTI, cIAI and LRTI caused by MDR/XDR P. aeruginosa isolates, except for GES-13 and VIM producers.
Abstract
Objectives
To analyse the epidemiology, the resistome and the virulome of ceftolozane/tazobactam-susceptible or -resistant Pseudomonas aeruginosa clinical isolates recovered from ...surveillance studies in Portugal (STEP, 2017–18) and Spain (SUPERIOR, 2016–17).
Methods
P. aeruginosa isolates were recovered from intra-abdominal, urinary tract and lower respiratory tract infections in ICU patients admitted to 11 Portuguese and 8 Spanish hospitals. MICs were determined (ISO-standard broth microdilution, EUCAST 2020 breakpoints). A subset of 28 ceftolozane/tazobactam-resistant P. aeruginosa isolates were analysed and compared with 28 ceftolozane/tazobactam-susceptible P. aeruginosa strains by WGS.
Results
Clonal complex (CC) 235 (27%) and CC175 (18%) were the most frequent, followed by CC244 (13%), CC348 (9%), CC253 (5%) and CC309 (5%). Inter-hospital clonal dissemination was observed, limited to a geographical region (CC235, CC244, CC348 and CC253 in Portugal and CC175 and CC309 in Spain). Carbapenemases were detected in 25 isolates (45%): GES-13 (13/25); VIM type (10/25) VIM-2 (4/10), VIM-20 (3/10), VIM-1 (2/10) and VIM-36 (1/10); and KPC-3 (2/25). GES-13-CC235 (13/15) and VIM type-CC175 (5/10) associations were observed. Interestingly, KPC-3 and VIM-36 producers showed ceftolozane/tazobactam-susceptible phenotypes. However, ceftolozane/tazobactam resistance was significantly associated with GES-13 and VIM-type carbapenemase production. Six non-carbapenemase producers also displayed ceftolozane/tazobactam resistance, three of them showing known ceftolozane/tazobactam resistance-associated mutations in the PBP3 gene, ftsI (R504C and F533L). Overall, an extensive virulome was identified in all P. aeruginosa isolates, particularly in carbapenemase-producing strains.
Conclusions
GES-13-CC235 and VIM type-CC175 were the most frequent MDR/XDR P. aeruginosa clones causing infections in Portuguese and Spanish ICU patients, respectively. Ceftolozane/tazobactam resistance was mainly due to carbapenemase production, although mutations in PBP-encoding genes may additionally be involved.
Objectives
CARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing
K. pneumoniae
(CP-Kpn) and
E. coli
...(CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.
Methods
In total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.
Results
In total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were
bla
OXA–48
(263/377),
bla
KPC–3
(62/377),
bla
VIM–1
(28/377), and
bla
NDM–1
(12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).
Conclusion
This study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3.
•Overall prevalence of carbapenemase-producing Enterobacteriaceae (CPE) in urine specimens in Spain was 1.6%.•Klebsiella pneumoniae was the most common isolate (87.8%).•Distribution of CPE was as ...follows: OXA-48 (86.8%), KPC (6.9%), VIM (4.8%), NDM (1.1%) and IMP (0.6%).•Ceftazidime-avibactam showed 100% susceptibility in KPC and OXA-48 producers.
The increasing rates of carbapenemase-producing Enterobacteriaceae (CPE) represent an important threat to health care systems and treatment of CPE infections is a challenge. The aim of the infection-carbapenem resistance evaluation surveillance trial (iCREST) was to determinate the prevalence of CPE in urine specimens in Spain and to evaluate the in vitro activity of ceftazidime-avibactam. Urine specimens (n = 11 826) were included and activity of ceftazidime-avibactam and comparators were investigated by broth microdilution in CPE. Carbapenemases were characterised by polymerase chain reaction (PCR) and sequencing as well as by whole genome sequencing (WGS). Overall prevalence of CPE was 1.6%. OXA-48 was the most prevalent (86.8%), followed by KPC (6.9%), VIM (4.8%), NDM (1.1%) and IMP (0.6%) carbapenemases. Klebsiella pneumoniae was the most common carbapenemase producer (87.8%). An uncommon carbapenemase type (IMP-8) in Spain was identify by WGS in an Enterobacter cloacae isolate, reinforcing the utility of surveillance programmes as effectives tools to detect unexpected genes that encode antimicrobial resistance. Ceftazidime-avibactam showed 100% susceptibility in KPC and OXA-48 producers and the rates of susceptibility in CPE non-susceptible to ceftazidime or meropenem were 92.1% and 96.9%, respectively. Ceftazidime-avibactam could be considered an adequate treatment option for urinary tract infections caused by KPC and OXA-48 producers.
Background
We described the real‐life epidemiology and causes of infections on the different therapy phases in patients undergoing chimeric antigen receptor (CAR) T‐cells directed towards CD19+ or ...BCMA+ cells.
Methods
All consecutive patients receiving CAR T‐cell therapy at our institution were prospectively followed‐up. We performed various comparative analyses of all patients and subgroups with and without infections.
Results
Ninety‐one adults mainly received CAR T‐cell therapy for acute leukaemia (53%) and lymphoma (33%). We documented a total of 77 infections in 47 (52%) patients, 37 (48%) during the initial neutropenic phase and 40 (52%) during the non‐neutropenic phase. Infections during the neutropenic phase were mainly due to bacterial (29, 78%): catheter infections (11 38% cases), endogenous source (5 17%), and Clostridioides difficile (5 17%). Patients receiving corticosteroids after CAR T‐cell therapy had a higher risk of endogenous infection (100% vs. 16%; p = .006). During the non‐neutropenic phase, bacterial infections remained very frequent (24, 60%), mainly with catheter source (8, 33%). Respiratory tract infections were common (17, 43%).
Conclusions
Infections after CAR T‐cell therapy were frequent. During the neutropenic phase, it is essential to prevent nosocomial infections and balance the use of antibiotics to lower endogenous bacteraemia and Clostridial infection rates.
Abstract
Objectives
To characterize the clonal spread of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates between different healthcare institutions in Catalonia, Spain.
...Methods
Antimicrobial susceptibility was tested by disc diffusion. MICs were determined by gradient diffusion or broth microdilution. Carbapenemase production was confirmed by lateral flow. PCR and Sanger sequencing were used to identify the allelic variants of resistance genes. Clonality studies were performed by PFGE and MLST. Plasmid typing, conjugation assays, S1-PFGE plus Southern blotting and MinION Oxford Nanopore sequencing were used to characterize resistance plasmids.
Results
Twenty-nine carbapenem-resistant isolates recovered from three healthcare institutions between January and November 2016 were included: 14 K. pneumoniae isolates from a tertiary hospital in the south of Catalonia (hospital A); 2 K. pneumoniae isolates from a nearby healthcare centre; and 12 K. pneumoniae isolates and 1 E. coli isolate from a tertiary hospital in Barcelona (hospital B). The majority of isolates were resistant to all antimicrobial agents, except colistin, and all were NDM producers. PFGE identified a major K. pneumoniae clone (n = 27) belonging to ST147 and co-producing NDM-1 and CTX-M-15, with a few isolates also harbouring blaOXA-48. Two sporadic isolates of K. pneumoniae ST307 and E. coli ST167 producing NDM-7 were also identified. blaNDM-1 was carried in two related IncR plasmid populations and blaNDM-7 in a conjugative 50 kb IncX3 plasmid.
Conclusions
We report the inter-hospital dissemination of XDR high-risk clones of K. pneumoniae and E. coli associated with the carriage of small, transferable plasmids harbouring blaNDM genes.
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