Although infections due to the six ESKAPE pathogens have recently been identified as a serious emerging problem, information regarding bacteremia caused by these organisms in solid-organ transplant ...(SOT) recipients is lacking. We sought to determine the frequency, risk factors, and outcomes of bacteremia due to drug-resistant ESKAPE (rESKAPE) organisms in liver, kidney, and heart adult transplant recipients.
All episodes of bacteremia prospectively documented in hospitalized SOT recipients from 2007 to 2012 were analyzed.
Of 276 episodes of bacteremia, 54 (19.6%) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium 0, methicillin-resistant Staphylococcus aureus 5, extended-spectrum β-lactamase-producing Klebsiella pneumoniae 10, carbapenem-resistant Acinetobacter baumannii 8, carbapenem- and quinolone-resistant Pseudomonas aeruginosa 26, and derepressed chromosomal β-lactam and extended-spectrum β-lactamase-producing Enterobacter species 5). Factors independently associated with rESKAPE bacteremia were prior transplantation, septic shock, and prior antibiotic therapy. Patients with rESKAPE bacteremia more often received inappropriate empirical antibiotic therapy than the others (41% vs. 21.6%; P=0.01). Overall case-fatality rate (30 days) was higher in patients with rESKAPE bacteremia (35.2% vs. 14.4%; P=0.001).
Bacteremia due to rESKAPE pathogens is frequent in SOT recipients and causes significant morbidity and mortality. rESKAPE organisms should be considered when selecting empirical antibiotic therapy for hospitalized SOT recipients presenting with septic shock, particularly those with prior transplantation and antibiotic use.
Background. Empirical combination therapy is recommended for patients with known or suspected Pseudomonas aeruginosa (PA) infection as a means to decrease the likelihood of administering inadequate ...antimicrobial treatment, to prevent the emergence of resistance, and to achieve a possible additive or even synergistic effect. Methods. We performed a post hoc analysis of patients with PA bloodstream infections from a published prospective cohort. Mortality was compared in patients treated with adequate empirical and definitive combination therapy (AECT, ADCT), and adequate empirical and definitive single-drug therapy (AESD, ADSD). Confounding was controlled by Cox regression analysis, and a propensity score for receiving AECT or ADCT was also used. Results. The final cohort comprised 593 patients with a single episode of PA bacteremia. The 30-day mortality was 30% (176 patients); 76 patients (13%) died during the first 48 hours. The unadjusted probabilities of survival until day 30 were 69.4% (95% confidence interval CI, 59.1–81.6) for the patients receiving AECT, 73.5% (95% CI, 68.4%–79.0%) for the AESD group, and 66.7% (95% CI, 61.2%–72.7%) for patients who received inadequate empirical therapy (P = .17, log-rank test). After adjustment for confounders, the AESD group (adjusted hazard ratio AHR, 1.17; 95% CI, .70–1.96; P = .54) and patients who received ADSD (AHR, 1.34; 95% CI, .73–2.47; P = .35) showed no association with 30-day mortality compared with the AECT and ADCT groups, respectively. Conclusions. These results suggests that treatment with combination antimicrobial therapy did not reduce the mortality risk compared with single-drug therapy in PA bloodstream infections.
Abstract
Objectives
To phenotypically and genetically characterize the antibiotic resistance determinants and associated mobile genetic elements (MGEs) among macrolide-resistant (MR) Streptococcus ...pyogenes Group A streptococci (GAS) clinical isolates collected in Barcelona, Spain.
Methods
Antibiotic susceptibility testing was performed by microdilution. Isolates were emm and MLST typed and 55 were whole-genome sequenced to determine the nature of the macrolide resistance (MR) determinants and their larger MGE and chromosomal context.
Results
Between 1998 and 2018, 142 of 1028 GAS (13.8%) were MR. Among 108 isolates available for molecular characterization, 41.7% had cMLSB, 30.5% iMLSB and 27.8% M phenotype. Eight erm(B)-containing strains were notable in having an MDR phenotype conferred by an MGE encoding several antibiotic resistance genes. MR isolates were comprised of several distinct genetic lineages as defined by the combination of emm and ST. Although most lineages were only transiently present, the emm11/ST403 clone persisted throughout the period. Two lineages, emm9/ST75 with erm(B) and emm77/ST63 with erm(TR), emerged in 2016–18. The erm(B) was predominantly encoded on the Tn916 family of transposons (21/31) with different genetic contexts, and in other MGEs (Tn6263, ICESpHKU372 and one harbouring an MDR cluster called ICESp1070HUB). The erm(TR) was found in ICESp2905 (8/17), ICESp1108-like (4/17), ICESpHKU165 (3/17) and two structures described in this study (IMESp316HUB and ICESp3729HUB). The M phenotype mef(A)-msr(D) was linked to phage φ1207.3. Eight integrative conjugative element/integrative mobilizable element (ICE/IME) cluster groups were classified on the basis of gene content within conjugation modules. These groups were found among MGEs, which corresponded with the MR-containing element or the site of integration.
Conclusions
We detected several different MGEs harbouring erm(B) or erm(TR). This is the first known description of Tn6263 in GAS and three MGEs IMESp316HUB, ICESp3729HUB and ICESp1070HUB associated with MR. Periods of high MR rates in our area were mainly associated with the expansion of certain predominant lineages, while in low MR periods different sporadic and low prevalence lineages were more frequent.
Haemophilus parainfluenzae
(HPAR) is a Gram-negative bacterium that can become an opportunistic urogenital pathogen. Recently, multidrug resistant (MDR) strains have emerged. We aim to analyse the ...epidemiology of HPAR at Hospital Universitari de Bellvitge between 2013 and 2017 to determine its putative role in sexually transmitted infections (STI). Strains were classified by sample origin, and antimicrobial susceptibility was performed by disk-diffusion tested on Mueller-Hinton Fastidious. MDR was defined as the resistance of the antimicrobial to three or more antibiotic class. Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) after restriction with
Sma
I and
Cfr9
I. We classified 944 HPAR isolates as being of urogenital (
n
= 175; 18.5%), respiratory (
n
= 719; 76.2%), or other (
n
= 50; 5.3%) origins. Among the urogenital isolates, 50 (28.6%) were MDR, which was significantly higher than that found in respiratory samples (40/719; 5.6%;
p
< 0.01). The frequency of MDR increased progressively among urogenital samples from 13.3% (2013) to 33.3% (2017) (
r
= 0.8;
p
= 0.035). The resistance rates for all 944 episodes were significantly higher for cotrimoxazole (51.4%), tetracycline (46.3%), chloramphenicol (28.0%), ciprofloxacin (21.1%), and ampicillin (20.6%). After PFGE, no clonal relationship was found. Clinical charts were available for 40 symptomatic patients with MDR HPAR infections presenting mostly urethritis (
n
= 26; 65.0%). In all cases, symptoms were treated effectively with combination therapy. Furthermore, in 10 of those patients with urethritis, MDR HPAR was the only potential pathogen to be identified. The emergence of MDR HPAR is a matter of concern, and the detection as a single pathogen highlights its putative role as cause of STI.
The potential role of Pseudomonas aeruginosa (PA) intestinal colonization in the subsequent development of infections has not been thoroughly investigated. The aims of this study were to assess the ...role of PA intestinal colonization as a predictor of subsequent infections and to investigate the risk factors associated with the development of PA infection in patients in the intensive care unit (ICU). For this purpose, a prospective study was conducted that included (i) active surveillance of PA rectal colonization at ICU admission and weekly until ICU discharge, (ii) detection of PA clinical infections, and (iii) genotypic analysis by pulsed-field gel electrophoresis (PFGE). A total of 414 patients were included, of whom 179 (43%) were colonized with PA. Among the 77 patients who developed PA infection, 69 (90%) had prior PA colonization, and 60 (87%) of these showed genotyping concordance between rectal and clinical isolates. The probability of PA infection 14 days after ICU admission was 26% for carriers versus 5% for noncarriers (P < 0.001). Cox regression analysis identified prior PA rectal colonization as the main predictor of PA infection (hazard ratio HR, 15.23; 95% confidence interval CI, 6.9 to 33.7; P < 0.001). Prior use of nonantipseudomonal penicillins was also identified as an independent variable associated with PA infection (HR, 2.15; 95% CI, 1.3 to 3.55; P < 0.003). Our study demonstrated that prior PA rectal colonization is a key factor for developing PA infection.
Abstract
Objectives
To analyse the clonal dynamics and clinical characteristics of adult invasive pneumococcal disease (IPD) caused by MDR and penicillin-non-susceptible (PNS) pneumococci in Spain.
...Methods
All adult IPD episodes were prospectively collected (1994–2018). Streptococcus pneumoniae isolates were serotyped, genotyped and tested for antimicrobial susceptibility. Changes in the incidence of IPD were analysed and risk factors contributing to MDR were assessed by logistic regression.
Results
Of 2095 IPD episodes, 635 (30.3%) were caused by MDR/PNS isolates. Over the study period, the incidence of MDR/PNS-IPD decreased (IRR 0.70; 95% CI 0.53–0.93) whereas that of susceptible isolates remained stable (IRR 0.96; 95% CI 0.80–1.16). A reduction of resistance rates to penicillin (–19.5%; 95% CI –37% to 2%) and cefotaxime (–44.5%; 95% CI –64% to –15%) was observed. Two clones, Spain9V-ST156 and Denmark14-ST230, accounted for 50% of current resistant disease. Among current MDR/PNS isolates, 45.8% expressed serotypes not covered by the upcoming PCV15/PCV20 vaccines. MDR/PNS episodes were associated with older patients with comorbidities, nosocomial acquisition and higher 30 day mortality. MDR/PNS pneumococci were not independently associated with 30 day mortality in multivariate analysis OR 0.826 (0.648–1.054).
Conclusions
Our study shows an overall reduction of MDR/PNS isolates in adults after the introduction of pneumococcal conjugate vaccines. However, a significant proportion of current resistant isolates are not covered by any of the upcoming PCV15/PCV20 vaccines. The burden of resistant disease is related to older patients with underlying conditions and caused by two major clones. Our data show that MDR is not a statistically significant factor related to increased mortality.
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