Infections are the major cause of morbidity and mortality in immunocompromised patients. Improving microbiological diagnosis in these patients is of paramount clinical importance.
We performed this ...multicentre, blinded, prospective, proof-of-concept study, to compare untargeted next-generation sequencing with conventional microbiological methods for first-line diagnosis of infection in 101 immunocompromised adults. Patients were followed for 30 days and their blood samples, and in some cases nasopharyngeal swabs and/or biological fluids, were analysed. At the end of the study, expert clinicians evaluated the results of both methods. The primary outcome measure was the detection rate of clinically relevant viruses and bacteria at inclusion.
Clinically relevant viruses and bacteria identified by untargeted next-generation sequencing and conventional methods were concordant for 72 of 101 patients in samples taken at inclusion (κ test=0.2, 95% CI 0.03-0.48). However, clinically relevant viruses and bacteria were detected in a significantly higher proportion of patients with untargeted next-generation sequencing than conventional methods at inclusion (36/101 (36%) vs. 11/101 (11%), respectively, p <0.001), and even when the latter were continued over 30 days (19/101 (19%), p 0.003). Untargeted next-generation sequencing had a high negative predictive value compared with conventional methods (64/65, 95% CI 0.95–1).
Untargeted next-generation sequencing has a high negative predictive value and detects more clinically relevant viruses and bacteria than conventional microbiological methods. Untargeted next-generation sequencing is therefore a promising method for microbiological diagnosis in immunocompromised adults.
Incidence of invasive fungal infections increases over time with the rise in at-risk populations; in particular, patients with acquired immunodeficiencies due to immunosuppressive therapies such as ...anti-tumour necrosis factor-α (TNF-α) treatment, cirrhosis or burns. Some primary immunodeficiencies (PID) can also predispose selectively to invasive fungal diseases. Conversely, some atypical fungal diseases can reveal new PID. Deep dermatophytosis, Candida central nervous system infections or gastrointestinal disease, or disseminated phaeohyphomycosis-revealed CARD9 deficiency. Most patients with inherited chronic mucocutaneous candidiasis were found to carry STAT1 gain-of-function mutations. The spectrum of fungal susceptibility and clinical presentation varies according to the PID. Among acquired immunodeficiencies, immunosuppressive treatments such as TNF-α blocker therapy, which has revolutionized autoimmune disorder treatment, may be complicated by endemic mycosis, aspergillosis, pneumocystosis or cryptococcosis. Burn patients with damaged skin barrier protection are susceptible to severe Candida infections and filamentous fungal infections (such as Aspergillus spp., Mucorales). Moreover, patients with cirrhosis are at increased risk of fungal infections. Therefore, physicians should think of any potential underlying acquired or inherited immunodeficiency in a patient developing an atypical fungal infection, or of a potential fungal disease in the context of an atypical presentation in specific hosts.
•Use of third-generation cephalosporins (3GCs) as definitive treatment for AmpC-producing Enterobacteriaceae is possible.•Initial severity, bacterial species, inoculum size and infection source are ...key parameters to evaluate antibiotic efficacy.•Prospective randomised studies are needed to allow the use of 3GC in infections caused by ESCPM bacteria.
The burden of antibiotic-resistant infections among Gram-negative bacteria is increasing. Resistance to third-generation cephalosporins (3GCs) in Enterobacteriaceae is mainly conferred by the acquisition of β-lactamases or by deregulation of natural genetically-encoded β-lactamase enzymes. Enterobacteriaceae such as Enterobacter spp., Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (ESCPM group) possess chromosomally-encoded inducible AmpC β-lactamases. AmpC can be overproduced as a response to β-lactam antibiotic exposure or by constitutive dysfunction of the AmpC regulation system. This overproduction can lead to the inactivation of 3GCs. Based on small clinical studies, international guidelines and expert recommendations suggest that 3GCs should be avoided as definitive therapy for infections caused by ESCPM group organisms. In this narrative review, we discuss the published literature and evaluate the risk related to 3GC use in the case of documented ESCPM infection.
Based on experimental studies showing synergism with β-lactams and glycopeptides, aminoglycosides have long been considered essential in the treatment of infective endocarditis (IE). However, their ...use is associated with a high risk of renal failure, especially in elderly patients.
The aim of this narrative review was to summarize the evidence to support reducing or even avoiding the use of aminoglycosides for the treatment of IE. We also analysed data supporting the use of aminoglycosides in specific subgroup of IE patients.
PubMed database was searched up to July 2019 to identify relevant studies.
Recent European Guidelines reduced the use of aminoglycosides in IE, no longer recommended in Staphylococcus aureus native-valve IE, and shortened to 2 weeks for IE related to Enterococcus faecalis and streptococci with penicillin MIC >0.125 μg/mL. In addition, an alternative regimen without aminoglycosides (ampicillin or amoxicillin plus ceftriaxone) is proposed for E. faecalis. Observational studies suggested that gentamicin would not be necessary in the case of staphylococcal prosthetic valve IE as long as rifampicin is maintained. Recent clinical studies showed that for streptococcal IE, gentamicin could be restricted to isolates with penicillin MIC >0.5 μg/mL. For the empirical and definitive treatment of E. faecalis IE, amoxicillin or ampicillin plus ceftriaxone may be considered, irrespective of high-level of aminoglycoside resistance.
In a scenario of progressive increase in the age and frailty of IE patients, the use of aminoglycosides can be reduced or avoided in ~90% cases. This should result in reduced incidence of renal failure, an important prognostic factor in IE.
Currently, contact precautions are recommended for patients colonized or infected with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Recent studies have challenged this ...strategy. This study aimed to assess the rate of ESBL-PE faecal carriage among hospitalized patients according to type of hospital ward, and to identify risk factors associated with carriage.
A point prevalence study was conducted in five different types of hospital ward medical, surgical, intensive care unit (ICU), after care and rehabilitation, and geriatric in eight French hospitals. All patients included in the study provided a fresh stool sample.
In total, 554 patients were included in the study, with a median age of 73 years (range 60–82 years). The overall faecal carriage rate of ESBL-PE was 17.7%. The most frequently encountered species among ESBL-PE was Escherichia coli (71.4%), followed by Klebsiella pneumoniae (14.3%). Risk factors associated with ESBL-PE faecal carriage on univariate analysis were: living in the Paris region (P<0.01) and hospitalization on a geriatric ward (P<0.01). Interestingly, the cumulative duration of hospital stay before screening was not associated with a significantly higher prevalence of ESBL-PE carriage, regardless of ward type. The ESBL-PE colonization rate was much higher for patients hospitalized on geriatric wards (28.1%) and ICUs (21.7%) compared with those for patients hospitalized on surgical wards (14.8%), medical wards (12.8%) or aftercare and rehabilitation (11.2%).
The overall prevalence of ESBL-PE faecal carriage was 17.7%, with only 21% of patients identified previously as carriers. The delay between admission and screening was not associated with an increase in ESBL-PE faecal carriage.
Purpose
The duration of antibiotic treatment for prosthetic valve endocarditis caused by
Streptococcus
spp. is largely based on clinical observations and expert opinion rather than empirical studies. ...Here we assess the impact of a shorter antibiotic duration.
Objectives
To assess the impact of antibiotic treatment duration for streptococcal prosthetic valve endocarditis on 12-month mortality as well as subsequent morbidity resulting in additional cardiac surgical interventions, and rates of relapse and reinfection.
Methods
This retrospective multisite (
N
= 3) study examines two decades of data on patients with streptococcal prosthetic valve endocarditis receiving either 4 or 6 weeks of antibiotics. Overall mortality, relapse, and reinfection rates were also assessed for the entire available follow-up period.
Results
The sample includes 121 patients (median age 72 years, IQR 53; 81). The majority (74%, 89/121) received a ß-lactam antibiotic combined with aminoglycoside in 74% (89/121, median bi-therapy 5 days 1; 14). Twenty-eight patients underwent surgery guided by ESC-guidelines (23%). The 12-month mortality rate was not significantly affected by antibiotic duration (4/40, 10% in the 4-week group vs 3/81, 3.7% in the 6-week group,
p
=0.34) or aminoglycoside usage (
p
=0.1). Similarly, there were no significant differences between the 2 treatment groups for secondary surgical procedures (7/40 vs 21/81,
p
=0.42), relapse or reinfection (1/40 vs 2/81 and 2/40 vs 5/81 respectively).
Conclusions
Our study found no increased adverse outcomes associated with a 4-week antibiotic duration compared to the recommended 6-week regimen. Further randomized trials are needed to ascertain the optimal duration of treatment for streptococcal endocarditis.
Graphical abstract
Treatment of infective endocarditis (IE) is based on high doses of antibiotics with a prolonged duration. Therapeutic drug monitoring (TDM) allows antibiotic prescription optimization and leads to a ...personalized medicine, but no study evaluates its interest in the management of IE. We conducted a retrospective, bicentric, descriptive study, from January 2007 to December 2019. We included patients cared for IE, defined according to Duke’s criteria, for whom a TDM was requested. Clinical and microbiological data were collected after patients’ charts review. We considered a trough or steady-state concentration target of 20 to 50 mg/L. We included 322 IE episodes, corresponding to 306 patients, with 78.6% (253/326) were considered definite according to Duke’s criteria. Native valves were involved in 60.5% (185/306) with aortic valve in 46.6% (150/322) and mitral in 36.3% (117/322). Echocardiography was positive in 76.7% (247/322) of cases. After TDM, a dosage modification was performed in 51.5% (166/322) (decrease in 84.3% (140/166)). After initial dosage, 46.3% (82/177) and 92.8% (52/56) were considered overdosed, when amoxicillin and cloxacillin were used, respectively. The length of hospital stay was higher for patient overdosed (25 days versus 20 days (
p
= 0.04)), and altered creatinine clearance was associated with overdosage (
p
= 0.01). Our study suggests that the use of current guidelines probably leads to unnecessarily high concentrations in most patients. TDM benefits predominate in patients with altered renal function, but probably limit adverse effects related to overdosing in most patients.
Parvimonas micra is a rare isolate in clinical specimens. We report a case of spondylodiscitis caused by P. micra, a rarely reported Gram positive cocci. The case was an elderly patient with joint ...surgery and ischaemic heart disease history. Infection resolved after adequate antibiotic therapy.
Substantial scientific evidence shows that contamination of environmental surfaces in hospitals plays an important role in the transmission of multidrug-resistant organisms (MDROs). To date, studies ...have failed to identify the risk factors associated with environmental contamination.
To evaluate, compare, and identify factors associated with environmental contamination around carriers of different MDROs.
This was a prospective cohort study from May 2018 to February 2020. A total of 125 patients were included, having been admitted to Avicenne Hospital and Hotel Dieu de France de Beyrouth Hospital who were faecal carriers of MDROs (extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE), carbapenemase-producing Enterobacterales (CPE), vancomycin-resistant enterococci (VRE)). For each patient, quantification of MDRO in stool was undertaken, plus a qualitative evaluation of the presence of MDRO in six different environmental sites; and clinical data were collected.
MDROs comprised ESBL-PE (34%), CPE (45%), and VRE (21%). The most frequent MDRO species was Escherichia coli. Contamination of at least one environmental site was observed for 22 (18%) patients. Only carriage of VanA was associated with a significantly higher risk of dissemination. Having a urinary catheter, carriage of OXA48 and E. coli were protective factors against environmental contamination. There were no significant differences in environmental contamination between E. coli and other Enterobacterales or between ESBL-PE and CPE.
Hospital environmental contamination rates are substantially higher for patients with VRE, compared to the low environment dissemination rates around ESBL-PE and CPE. Further studies on a larger scale are needed to confirm the validity of our findings.
Asymptomatic faecal carriage of Clostridioides difficile has been widely evaluated, but its prevalence across a wide range of clinical departments and related risk factors are not well described. The ...objectives of the PORTADIFF study were to evaluate the prevalence and identifying risk factors leading to asymptomatic carriage of both toxigenic and non-toxigenic C. difficile.
The PORTADIFF study was a 1-day prevalence study carried out in 10 different French hospitals. Adult patients, who agreed to participate, were included in this study and provided a fresh stool sample. C. difficile strains isolated from carriage were characterized by polymerase chain reaction (PCR) detection of tcdA, tcdB, cdtA and cdtB, and PCR ribotyping.
In total, 721 patients were included in this study. The median age was 73 years (range 18–101 years) and the male/female ratio was 1.06. C. difficile (either toxigenic or non-toxigenic strains) was isolated from 79 (11%) patients; 42 (5.8%) strains were toxigenic. The prevalence rates of asymptomatic carriage ranged from 5% on surgical wards to 19% on long-term care wards. The main risk factors associated with asymptomatic carriage were antibiotic treatment within the preceding 3 months (81.8% vs 53.7%; P<0.01), hospitalization within the preceding 2 months (55.8% vs 33%; P<0.01), cumulative duration of hospital stay before study inclusion (mean 50.1 vs 34.5 days; P<0.047), and hospitalization on a ward with high global incidence of C. difficile infection.
Eleven percent of hospitalized patients were asymptomatic carriers of toxigenic or non-toxigenic C. difficile, and may constitute a potential reservoir of C. difficile strains.
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