In older patients, urinary tract infection (UTI) often has an atypical clinical presentation, making its diagnosis difficult. We aimed to describe the clinical presentation in older inpatients with ...UTI-related bacteremia and to determine the prognostic impact of atypical presentation. This cohort study included all consecutive patients older than 75 years hospitalized in a university hospital in 2019 with a UTI-related gram-negative bacillus (GNB) bacteremia, defined by blood and urine cultures positive for the same GNB, and followed up for 90 days. Patients with typical symptoms of UTI were compared to patients with atypical forms. Among 3865 inpatients over 75 with GNB-positive urine culture over the inclusion period, 105 patients (2.7%) with bacteremic UTI were included (mean age 85.3 ± 5.9, 61.9% female). Among them, UTI symptoms were reported in only 38 patients (36.2%) and 44 patients (41.9%) had no fever on initial management. Initial diagnosis of UTI was made in only 58% of patient. Mortality at 90 days was 23.6%. After adjustment for confounders, hyperthermia (HR = 0.37; IC95 (0.14-0.97)) and early UTI diagnosis (HR = 0.35; IC95 (0.13-0.94)) were associated with lower mortality, while UTI symptoms were not associated with prognosis. In conclusion, only one third of older patients with UTI developing bacteremia had UTI symptoms. However, early UTI diagnosis was associated with better survival.
In the eighties, a multidrug resistant clone of Salmonella Typhimurium DT104 emerged in UK and disseminated worldwide. This clone harbored a Salmonella genomic island 1 (SGI1) that consists of a ...backbone and a multidrug resistant region encoding for penta-resistance (ampicillin, chloramphenicol/florfenicol, streptomycin/spectinomycin, sulphonamides and tetracycline (ACSSuT)). Several authors suggested that SGI1 might have a potential role in enhancement of virulence properties of Salmonella enterica. The aim of this study was to investigate whether nontyphoidal S. enterica isolates carrying SGI1 cause more severe illness than SGI1 free ones in humans.
From 2011 to 2016, all patients infected with nontyphoidal S. enterica in our hospital were retrospectively included. All nontyphoidal S. enterica isolates preserved in our University Hospital (Dijon, France) were screened for the presence of SGI1. Clinical and biological data of patients were retrospectively collected to evaluate illness severity. Statistical analysis of data was performed by Kruskal-Wallis test or Fisher's exact test for univariate analysis, and by logistic regression for multivariate analysis.
A total of 100 isolates of S. enterica (22 serovars) were collected. Twelve isolates (12%) belonging to 4 serovars harbored SGI1: S. Typhimurium, S. Infantis, S. Kentucky, S. St Paul. The severity of the disease was age-related (for invasive infection, sepsis and inflammatory response) and was associated with immunosuppression (for invasive infection, sepsis and bacteremia) but not with the presence of SGI1 or with antimicrobial resistance.
A rather high proportion (12%) of human clinical isolates belonging to various serovars (for the first time serovar St Paul) and harboring various antimicrobial resistance profile carried SGI1. Diseases due to SGI1-positive S. enterica or to antimicrobial resistant isolates were not more severe than the others. This first clinical observation should be confirmed by a multicenter and prospective study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•No antagonism of daptomycin regarding the activity of cefotaxime against Neisseria meningitidis.•Daptomycin improves β-lactam antimicrobial activity towards pneumococcus and Listeria.•Reassuring ...evidence of the clinical potential of daptomycin adjunction in the treatment of bacterial meningitis.
As daptomycin adjunction is currently under clinical evaluation in the multicentre phase II AddaMAP study to improve the prognosis of pneumococcal meningitis, the present work aimed at evaluating the in vitro antimicrobial activity of daptomycin-based combinations against some of the most frequent species responsible for bacterial meningitis.
Clinically relevant strains of Streptococcus pneumoniae, Listeria monocytogenes, Haemophilus influenzae and Neisseria meningitidis were obtained from National Reference Centers. The antimicrobial activity of amoxicillin, cefotaxime and rifampicin, either alone or in association with daptomycin, was explored through the determination of minimum inhibitory concentration (MIC) and fractional inhibitory concentration index (FICI) as well as time–kill assay (TKA) using the broth microdilution method.
All species taken together, the adjunction of daptomycin had no deleterious impact on the antimicrobial activity of amoxicillin, cefotaxime or rifampicin in vitro. Regarding Gram-positive bacteria, FICI and TKA analysis confirmed a global improvement of growth inhibition and bactericidal activity due to the adjunction of daptomycin. The synergistic effect prevailed for L. monocytogenes as demonstrated by FICI mainly <0.5 and a dynamic TKA-based synergy rate >50%. In addition, daptomycin-based associations did not modify the activity of β-lactam antibiotics or rifampicin against Gram-negative bacteria, notably N. meningitidis.
These results bring comforting evidence towards the clinical potential of daptomycin adjunction in the treatment of bacterial meningitis, which supports the ongoing AddaMAP clinical trial.
In 2015, a major increase in incident hospital-onset Clostridioides difficile infections (HO-CDI) in a geriatric university hospital led to the implementation of a diagnosis-centered antibiotic ...stewardship program (ASP). We aimed to evaluate the impact of the ASP on antibiotic consumption and on HO-CDI incidence. The intervention was the arrival of a full-time infectiologist in the acute geriatric unit in May 2015, followed by the implementation of new diagnostic procedures for infections associated with an antibiotic withdrawal policy. Between 2015 and 2018, the ASP was associated with a major reduction in diagnoses for inpatients (23% to 13% for pneumonia, 24% to 13% for urinary tract infection), while median hospital stays and mortality rates remained stable. The reduction in diagnosed bacterial infections was associated with a 45% decrease in antibiotic consumption in the acute geriatric unit. HO-CDI incidence also decreased dramatically from 1.4‰ bed-days to 0.8‰ bed-days in the geriatric rehabilitation unit. The ASP focused on reducing the overdiagnosis of bacterial infections in the acute geriatric unit was successfully associated with both a reduction in antibiotic use and a clear reduction in the incidence of HO-CDI in the geriatric rehabilitation unit.
Acquired antimicrobial resistance among Achromobacter isolates from cystic fibrosis (CF) patients is frequent. Data concerning the mechanisms involved are scarce. The role of the AxyXY-OprZ and ...AxyEF-OprN Resistance Nodulation Division (RND) efflux systems has been demonstrated, but not that of AxyABM.
To explore the role of efflux systems in the acquired multiresistance observed in a one-step mutant selected after ofloxacin exposure.
The in vitro resistant mutant NCF-39-Bo2 and its parental strain NCF-39 (MICs of meropenem of 8 and 0.19 mg/L, of ceftazidime of 12 and 3 mg/L, of cefiderocol of 0.094 and 0.032 mg/L and of ciprofloxacin of 8 and 1.5 mg/L, respectively) were investigated by RNA-seq and WGS. Gene inactivation and reverse transcription quantitative PCR (RT-qPCR) were used to explore the role of the efflux systems of interest.
RNA-seq showed that the AxyABM efflux system was overproduced (about 40-fold) in the in vitro mutant NCF-39-Bo2 versus its parental strain NCF-39. A substitution in AxyR, the putative regulator of AxyABM, was detected in NCF-39-Bo2. Gene inactivation of axyB (encoding the transporter component) in NCF-39-Bo2 led to a decrease in MICs of ciprofloxacin (5-fold), meropenem (64-fold), ceftazidime (12-fold) and cefiderocol (24-fold). Inactivation of axyB in the clinical isolate AXX-H2 harbouring a phenotype of resistance close to that of NCF-39-Bo2 enhanced the activity of the same molecules, especially meropenem.
AxyABM overproduction is involved in acquired resistance of Achromobacter to ciprofloxacin, meropenem and ceftazidime, antibiotics widely used in CF patients, and increases the MIC of the new promising antibiotic cefiderocol.
Achromobacter xylosoxidans (AX) is a non-fermentative aerobic gram-negative bacillus. It is an opportunistic pathogen and the causative agent of various infections. We report an original case of late ...posttraumatic meningitis due to AX denitrificans.
An 83-year-old man was hospitalized for acute headache, nausea and vomiting. The emergency brain computer tomography (CT) scan did not reveal any anomaly. In his medical history, there was an auditory injury due to a cranial trauma incurred in a skiing accident 60 years earlier. Cytobiochemical analysis of the cerebrospinal fluid (CSF) revealed increased levels of neutrophils and proteins. The CSF bacterial culture was positive: the Gram stain showed a gram-negative bacillus, oxidase + and catalase +, and the biochemical pattern using the API 20 NE strip revealed AX dentrificans. Late posttraumatic meningitis on a possible osteomeningeal breach was diagnosed even though the breach was not confirmed because the patient declined a second brain CT scan. The patient was successfully treated with meropenem.
This report demonstrates the importance of searching for unusual or atypical organisms when the clinician encounters meningitis in a particular context, as well as the importance of adequate follow-up of craniofacial traumas.
Purpose
Apyrexia is increasingly recognized as an indicator of inadequate inflammatory response in older patients with suspected infection. We aimed to evaluate whether temperature at admission could ...improve the prognostic value of the Quick Sequential Organ Failure Assessment (qSOFA) for predicting in-hospital mortality after acute infection.
Methods
We created a new score, named qSOFAGE (qSOFA in GEriatrics), by adding apyrexia as an item to the existing qSOFA (+ 1 point if temperature at admission ≤ 38 °C). We compared the prognostic value of the qSOFA, the qSOFAGE and temperature at admission for predicting in-hospital mortality after acute infection in two cohorts including older patients with acute pneumonia (AP) or bacteremic urinary tract infection (UTI).
Results
217 consecutive patients aged ≥ 75 hospitalized for AP (first cohort) and 105 for bacteremic UTI (second cohort) were recorded. Temperature at admission was strongly inversely correlated with in-hospital mortality in both cohorts (Odds Ratios per °C (95% Confidence Interval): 0.60 (0.45–0.80) and 0.46 (0.27–0.79) for AP and UTI. respectively). Adding the temperature ≤ 38 °C item to the qSOFA markedly improved its predictive value for in-hospital mortality in the two groups: C-statistics for qSOFAGE vs. qSOFA: 0.63 (0.53–0.73) vs. 0.56 (0.46–0.67) in AP cohort; 0.74 (0.58–0.89) vs. 0.69 (0.53–0.85) in UTI cohort. For patients with qSOFAGE ≥ 3, in-hospital mortality reached 37% after AP and 55% after bacteremic UTI.
Conclusion
Temperature at admission was strongly correlated with mortality in these two cohorts of older patients hospitalized for acute infection. The next step will be to validate this score in cohorts of older patients with suspected infection.
Abstract
Background
Achromobacter are emerging pathogens in cystic fibrosis patients. Mechanisms of resistance to fluoroquinolones are unknown in clinical isolates. Among non-fermenting Gram-negative ...bacilli, fluoroquinolone resistance is mostly due to amino acid substitutions in localized regions of the targets (GyrA, GyrB, ParC and ParE) named QRDRs, but also to efflux.
Objectives
To explore quinolone resistance mechanisms in Achromobacter.
Methods
The putative QRDRs of GyrA, GyrB, ParC and ParE were sequenced in 62 clinical isolates, and in vitro one-step mutants obtained after exposure to fluoroquinolones. An in vitro mutant and its parental isolate were investigated by RNASeq and WGS. RT–qPCR and gene inactivation were used to explore the role of efflux systems overexpression.
Results
We detected seven substitutions in QRDRs (Q83L/S84P/D87N/D87G for GyrA, Q480P for GyrB, T395A/K525Q for ParE), all in nine of the 27 clinical isolates with ciprofloxacin MIC ≥16 mg/L, whereas none among the in vitro mutants. The RND efflux system AxyEF-OprN was overproduced (about 150-fold) in the in vitro mutant NCF-39-Bl6 versus its parental strain NCF-39 (ciprofloxacin MICs 64 and 1.5 mg/L, respectively). A substitution in AxyT (putative regulator of AxyEF-OprN) was detected in NCF-39-Bl6. Ciprofloxacin MIC in NCF-39-Bl6 dropped from 64 to 1.5 mg/L following gene inactivation of either axyT or axyF. Substitutions in AxyT associated with overexpression of AxyEF-OprN were also detected in seven clinical strains with ciprofloxacin MIC ≥16 mg/L.
Conclusions
Target alteration is not the primary mechanism involved in fluoroquinolone resistance in Achromobacter. The role of AxyEF-OprN overproduction was demonstrated in one in vitro mutant.
spp. are increasingly reported among cystic fibrosis patients. Genotyping requires time-consuming methods such as multilocus sequence typing or pulsed-field gel electrophoresis. Therefore, data on ...the prevalence of multiresistant epidemic clones, especially A. xylosoxidans ST137 (AxST137) and the Danish epidemic strain
(DES), are lacking. We recently developed and published a database for
species identification by matrix-assisted laser desorption-ionization-time of flight mass spectrometry (MALDI-TOF MS; Bruker Daltonics). The aim of this study was to evaluate the ability of the MALDI-TOF MS to distinguish these multiresistant epidemic clones within
species. All the spectra of A. xylosoxidans (
= 1,571) and
(
= 174) used to build the local database were analyzed by ClinProTools, MALDI Biotyper PCA, MALDI Biotyper dendrogram, and flexAnalysis software for biomarker peak detection. Two hundred two isolates (including 48 isolates of AxST137 and 7 of DES) were tested. Specific biomarker peaks were identified: absent peak at
6,651 for AxST137 isolates and present peak at
9,438 for DES isolates. All tested isolates were well typed by our local database and clustered within distinct groups (ST137 or non-ST137 and DES or non-DES) no matter the MALDI-TOF software or only by simple visual inspection of the spectra by any user. The use of MALDI-TOF MS allowed us to identify isolates of A. xylosoxidans belonging to the AxST137 clone that spread in France and Belgium (the Belgian epidemic clone) and of
belonging to the DES clone. This tool will help the implementation of segregation measures to avoid interpatient transmission of these resistant clones.
OBJECTIVES:Ventilator-associated pneumonia is frequent in ICUs. Extended-spectrum β-lactamase–producing Enterobacteriaceae are difficult-to-treat pathogens likely to cause ventilator-associated ...pneumonia. We sought to assess the interest of screening for extended-spectrum β-lactamase–producing Enterobacteriaceae rectal carriage as a way to predict their involvement in ventilator-associated pneumonia.
DESIGN:A retrospective cohort study of patients with suspected ventilator-associated pneumonia in a medical ICU was conducted.
PATIENTS:Every patient admitted between January 2006 and August 2013 was eligible if subjected to mechanical ventilation for more than 48 hours. Each patient with suspected ventilator-associated pneumonia was included in the cohort. Active surveillance culture for extended-spectrum β-lactamase–producing Enterobacteriaceae detection was routinely performed in all patients at admission and then weekly throughout the study period. Extended-spectrum β-lactamase colonization was defined by the isolation of at least one extended-spectrum β-lactamase–producing Enterobacteriaceae from rectal swab culture.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:Among 587 patients with suspected ventilator-associated pneumonia, 40 (6.8%) were colonized with extended-spectrum β-lactamase–producing Enterobacteriaceae prior to the development of pneumonia. Over the study period, 20 patients (3.4%) had ventilator-associated pneumonia caused by extended-spectrum β-lactamase–producing Enterobacteriaceae; of whom, 17 were previously detected as being colonized with extended-spectrum β-lactamase–producing Enterobacteriaceae. Sensitivity and specificity of prior extended-spectrum β-lactamase–producing Enterobacteriaceae colonization as a predictor of extended-spectrum β-lactamase–producing Enterobacteriaceae involvement in ventilator-associated pneumonia were 85.0% and 95.7%, respectively. The positive and negative predictive values were 41.5% and 99.4%, respectively. The positive likelihood ratio was 19.8.
CONCLUSIONS:Screening for extended-spectrum β-lactamase–producing Enterobacteriaceae digestive colonization by weekly active surveillance cultures could reliably exclude the risk of the involvement of such pathogens in patients with ventilator-associated pneumonia in low-prevalence area.
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