The antimicrobial resistance is a significant public health threat, particularly for healthcare-associated infections caused by carbapenem-resistant Gram-negative pathogens which are increasingly ...reported worldwide. The aim of this study was to provide data on the in vitro antimicrobial activity of cefiderocol and that of commercially available comparator antibiotics against a defined collection of recent clinical multi-drug resistant (MDR) microorganisms, including carbapenem resistant Gram-negative bacteria collected from different regions in Spain and Portugal.
A total of 477 clinical isolates of Enterobacterales, Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia were prospectively (n=265) and retrospectively (n=212) included (2016-2019). Susceptibility testing was performed using standard broad microdilution and results were interpreted using CLSI-2021 and EUCAST-2021 criteria.
Overall, cefiderocol showed a good activity against Enterobacterales isolates, being 99.5% susceptible by CLSI and 94.5% by EUCAST criteria. It also demonstrated excellent activity against P. aeruginosa and S. maltophilia isolates, all being susceptible to this compound considering CLSI breakpoints. Regarding A. baumannii (n=64), only one isolate was resistant to cefiderocol.
Our results are in agreement with other studies performed outside Spain and Portugal highlighting its excellent activity against MDR gram-negative bacteria. Cefiderocol is a therapeutic alternative to those available for the treatment of infections caused by these MDR bacteria.
Antimicrobial resistance data for
Neisseria gonorrhoeae
is globally sparse and resistant strains are emerging in Catalonia. We aim to describe epidemiological and antimicrobial resistance in all ...patients infected with
N. gonorrhoeae
during the period from 2016 to 2019, using available antimicrobial susceptibility data. We retrospectively analysed confirmed
N. gonorrhoeae
cases notified to Catalonia’s microbiological reporting system. Antibiotic susceptibility testing (azithromycin, cefixime, ceftriaxone, ciprofloxacin, penicillin, spectinomycin, and tetracycline) was assessed using clinical breakpoints published by the European Committee on Antimicrobial Susceptibility Testing. Incidence rates were calculated and proportions were compared using the χ
2
test or Fisher’s exact test, and analysed using the Statistical Package for Social Sciences (SPSS 18.0). A total of 14,251 confirmed cases of
N. gonorrhoeae
were notified. Incidence increased from 30.7 cases/100,000 person-years (
p
< 0.001) in 2016 to 64.7 in 2019. Culture was available in 6,292 isolates (44.2%), of which 5,377 (85.5%) were resistant to at least one of the antibiotics tested. Azithromycin resistance rose from 6.1% in 2016 to 16% in 2019 (
p
< 0.001). Only 1.0% (45 cases) were resistant to ceftriaxone. Multidrug-resistant
N. gonorrhoeae
increased from 0.25% in 2016 to 0.42% in 2019 (
p
= 0.521). One case presented extensively drug-resistant
N. gonorrhoeae
. In Catalonia, 10% of the
N. gonorrhoeae
isolates were resistant to azithromycin in the 2016–2019 period. According to World Health Organization guidelines, resistance above 5% indicates an alert to review treatment guidelines. Antimicrobial susceptibility testing in clinical practice followed by surveillance and interventions are essential to monitor trends and prevent the spread of antimicrobial resistance.
Abstract We evaluated the OXA-48 K-Set, a rapid immunochromatographic test for the detection of Oxacillinase-48 (OXA-48) carbapenemases, among 37 strains expressing OXA-48 and OXA-48-like ...carbapenemases and 20 additional strains harboring other β-lactamases. The test showed 100% sensitivity and specificity and the results were obtained in 15 minutes.
Abstract Objectives We performed a multicentre study (2020–2022) to compare the in vitro activity of ozenoxacin and comparator agents against Staphylococcus aureus and Streptococcus pyogenes clinical ...isolates from skin and soft-tissue infections (SSTI). Methods A total of 1725 isolates (1454 S. aureus and 271 S. pyogenes) were collected in 10 centres from eight countries between January 2020 and December 2022. Antimicrobial susceptibility testing was determined (microdilution-SENSITITRE). Results were interpreted following European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2023 (clinical breakpoints, ECOFF) and CLSI criteria. Results Ozenoxacin exhibited high in vitro activity against S. aureus (MIC50/90 = 0.002/0.12 mg/L) and S. pyogenes (MIC50/90 = 0.015/0.03 mg/L), inhibiting 99% of the isolates at MIC ≤ 0.5 mg/L and at MIC ≤ 0.06, respectively. The most active comparators against S. aureus were retapamulin (MIC90 = 0.12 mg/L), fusidic acid (MIC90 = 0.25 mg/L) and mupirocin (MIC90 = 0.5 mg/L); and against S. pyogenes were retapamulin (MIC90 = 0.03 mg/L), clindamycin (MIC90 = 0.12 mg/L) and mupirocin (MIC90 = 0.25 mg/L). Ciprofloxacin and methicillin resistant rates for S. aureus were 31.3% (455/1454) and 41% (598/1454), respectively. Additionally, 62% (373/598) of the MRSA were also ciprofloxacin non-susceptible, whereas only 10% (23/271) of the MSSA were ciprofloxacin resistant. Ozenoxacin was more active against ciprofloxacin-susceptible S. aureus than against ciprofloxacin-resistant isolates, and showed a slightly higher MIC in MRSA isolates than in MSSA. However, ozenoxacin activity was comparable in both ciprofloxacin-resistant MSSA and MRSA subsets. On the other hand, ozenoxacin had similar activity in ciprofloxacin-susceptible and resistant S. pyogenes isolates. Conclusions Ozenoxacin is a potent antimicrobial agent of topic use against Gram-positive bacteria causing SSTI, including MRSA isolates non-susceptible to ciprofloxacin.
Community-acquired (CA) and healthcare-associated (HCA) infections caused by carbapenemase-producing Enterobacterales (CPE) are not well characterized. The objective was to provide detailed ...information about the clinical and molecular epidemiological features of nosocomial, HCA and CA infections caused by carbapenemase-producing Klebsiella pneumoniae (CP-Kp) and Escherichia coli (CP-Ec).
A prospective cohort study was performed in 59 Spanish hospitals from February to March 2019, including the first 10 consecutive patients from whom CP-Kp or CP-Ec were isolated. Patients were stratified according to acquisition type. A multivariate analysis was performed to identify the impact of acquisition type in 30-day mortality.
Overall, 386 patients were included (363 94% with CP-Kp and 23 6% CP-Ec); in 296 patients (76.3%), the CPE was causing an infection. Acquisition was CA in 31 (8.0%) patients, HCA in 183 (47.4%) and nosocomial in 172 (48.3%). Among patients with a HCA acquisition, 100 (54.6%) had been previously admitted to hospital and 71 (38.8%) were nursing home residents. Urinary tract infections accounted for 19/23 (82.6%), 89/130 (68.5%) and 42/143 (29.4%) of CA, HCA and nosocomial infections, respectively. Overall, 68 infections (23%) were bacteremia (8.7%, 17.7% and 30.1% of CA, HCA and nosocomial, respectively). Mortality in infections was 28% (13%, 14.6% and 42.7% of CA, HCA and nosocomial, respectively). Nosocomial bloodstream infections were associated with increased odds for mortality (adjusted OR, 4.00; 95%CI 1.21-13.19).
HCA and CA infections caused by CPE are frequent and clinically significant. This information may be useful for a better understanding of the epidemiology of CPE.
ABSTRACT
A carbapenem-resistant
Escherichia coli
isolate (sequence type 448 ST448) was recovered from a urine culture of a female patient with no recent record of traveling. PCR screening identified ...the presence of
bla
NDM-5
,
bla
TEM-1
,
bla
OXA-1
,
bla
CMY-42
, and
rmtB. bla
NDM-5
was carried in a conjugative IncFII-type plasmid (90 kb) together with
bla
TEM-1
and
rmtB
. The genetic environment of
bla
NDM-5
showed a structure similar to those of pMC-NDM and pGUE-NDM, identified in Poland and France in
E. coli
of African and Indian origin, respectively.
Objectives Enteroaggregative Escherichia coli (EAEC) and enterotoxigenic E. coli (ETEC) are among the most frequent microorganisms causing traveller's diarrhoea. The aim of this study was to ...investigate the evolution of antimicrobial resistance in EAEC and ETEC causing diarrhoea in patients who had travelled to different developing countries, comparing two periods of time, 1994–97 and 2001–04. Methods Overall, 134 EAEC and 190 ETEC clinical isolates were studied. The MICs of ampicillin, chloramphenicol, nalidixic acid, tetracycline, trimethoprim/sulfamethoxazole, ciprofloxacin and amoxicillin/clavulanic acid were determined by the Etest method. Detection of mutations in the quinolone-resistance determining region of the gyrA and parC genes was performed by PCR and DNA sequencing. Results When antimicrobial resistance in EAEC and ETEC isolates was compared between the two periods of time, a statistically significant increase in resistance (P < 0.01) was observed in EAEC for chloramphenicol and amoxicillin/clavulanic acid, whereas in ETEC it was for trimethoprim/sulfamethoxazole, nalidixic acid, ciprofloxacin and amoxicillin/clavulanic acid. Mutations in the gyrA gene were found in all nalidixic acid-resistant isolates, whereas mutation(s) in both gyrA and parC genes were found in the ciprofloxacin-resistant isolates. Conclusions The high percentage of resistance to quinolones in ETEC and EAEC isolated from travellers to North Africa and India is a matter for concern. These agents should therefore be used with caution in patients with traveller's diarrhoea returning from these geographical areas.
CARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing
(CP-Kpn) and
(CP-Eco) to determine their ...incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.
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.
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
(263/377),
(62/377),
(28/377), and
(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).
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.
Introduction
Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant
Pseudomonas aeruginosa
, including isolates producing acquired carbapenemases, constitute a ...prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically
Escherichia coli
,
Klebsiella pneumoniae
,
Enterobacter cloacae
complex, and
Klebsiella aerogenes
) and carbapenemase-producing
P. aeruginosa
(CPPA) in Spain from January 2014 to December 2018.
Methods
A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0.
Results
A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and
P. aeruginosa
were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing
K. pneumoniae
was reported in 1821 cases (79.9%), followed by
E. cloacae
complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding
P. aeruginosa
, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017–2018 compared to 2014–2016.
Discussion
Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.