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1.
Diseases ; 12(3)2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38534976

ABSTRACT

Introduction: Beta-lactamases are frequently prescribed for Gram-negative bloodstream infections (BSIs). However, chromosomally encoded AmpC-producing Enterobacterales (AE) could overproduce beta-lactamases when exposed to third-generation cephalosporins (3GCs), with a risk of clinical failure. There are few available in vivo data on the subject. Our goal was to assess the potential role of AE as a predictive factor for clinical failure in patients with BSIs. Materials and Methods: We retrospectively analyzed patients admitted to Cannes hospital between 2021 and 2022 for BSIs due to Enterobacterales. Patient demographics, comorbidities, and main clinical and laboratory parameters during hospitalization were collected. The risk factors for clinical instability after 48 h or death, as well as for ineffective initial empirical therapy, were assessed using univariate and multivariate analyses. Results: From January 2021 to December 2022, 101 subjects were included (mean age 79 years, 60% men, 97% with comorbidities, 17% with healthcare-associated infection, 13% with septic shock, 82% with qPitt severity score < 2, 58% with urinary tract infection, and 18% with AE). Septic shock [adjusted odds ratio (ORadj) = 5.30, 95% confidence interval (CI): 1.47-22.19, p = 0.014] and ineffective initial empirical therapy [ORadj 5.54, 95% CI: 1.95-17.01, p = 0.002] were independent predictive factors for clinical instability or death. Extended-spectrum beta-lactamases [ORadj 9.40, 95% CI: 1.70-62.14, p = 0.012], AE group [ORadj 5.89, 95% CI: 1.70-21.40, p = 0.006], and clinical instability or death [ORadj 4.71, 95% CI: 1.44-17.08, p = 0.012] were independently associated with ineffective empirical therapy. Conclusions: Infection with AE was associated with treatment failure. Empirical therapy may result in failure if restricted to 3GC.

2.
Microorganisms ; 11(12)2023 Dec 02.
Article in English | MEDLINE | ID: mdl-38138052

ABSTRACT

Aerococcus urinae is an aerobic Gram-positive coccus that grows as tiny alpha-hemolytic colonies. Actinotignum schaalii is a slow-growing facultative anaerobic Gram-positive rod. These bacteria are part of the urogenital microbiota of healthy patients, but can also be involved in urinary tract infections (UTIs), particularly in elderly men and young children. Because A. urinae and A. schaalii are fastidious and are difficult to identify with phenotypic methods, they are underestimated causes of UTIs. Their growth is slow and requires a blood-enriched medium incubated under an anaerobic or 5% CO2 atmosphere for 48 h and from 24 to 48 h for A. schaalii and A. urinae, respectively. Furthermore, accurate identification is only possible using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or molecular-based methods. In rare cases, these bacteria can be responsible for invasive infections. We describe, here, an unusual case of bacteremic UTI caused by both A. schaalii and A. urinae in an 89-year-old woman. She presented with dyspnea, and bacteriuria was noted. This challenging clinical and microbiological diagnosis was made in our laboratory by Gram staining urine with a leucocyte count >50/µL and/or a bacterial count >14/µL urinary culture on a blood agar plate. After 10 days of antimicrobial treatment consisting of 2 g amoxicillin PO t.i.d., the patient was discharged with a complete clinical and biological recovery. A. schaalii and A. urinae are probably still underestimated causes of UTIs. Microbiologists could consider the presence of these two bacteria using appropriate culture and identification methods in cases where a positive direct examination of urine reveals small Gram-positive rods or cocci, where undocumented UTIs are present in elderly patients, but also where a urinary dipstick is negative for nitrites and is associated with leukocyturia.

3.
Front Immunol ; 14: 1136723, 2023.
Article in English | MEDLINE | ID: mdl-36949938

ABSTRACT

Introduction: Data on immune response to SARS-CoV-2 vaccine in patients living with HIV (PLWH) over a period longer than 3 months are currently limited. We measured the immune response after BNT162b2 vaccination against SARS-CoV-2 in this population. Methods: We prospectively enrolled PLWH on successful antiretroviral therapy, initiating vaccination with two doses of the BNT162b2 SARS-CoV-2 vaccine administered at six-week interval. SARS-CoV-2 humoral and cellular responses and lymphocyte cell subsets were recorded at inclusion and 6 weeks (W6), 3 months (M3) and 6 months (M6) later. Humoral, humoral strong and cellular responders were defined by IgG titers >10, ≥264BAU/mL and IFN-γ T cell release, respectively. Results: Nineteen subjects without SARS-CoV-2 infection were included (74% men, mean age 51 years, CD4 nadir 399/mm3). All subjects were humoral responders, their antibody titer peak reached at M3. Strong responders' rates were 63% and 21% at M3 and M6, respectively. CD19+CD10+ B cells had increased significantly at W6 then decreased at M3, while CD19+CD27+ B cells remained unchanged. Rates of patients with a cellular response increased from 39% at W6 to 69% at M6. Cellular responders had significantly higher CD3+, CD4+ and CD8+ Effector Memory cells at inclusion (p=0.048, p=0.024, p=0.012, respectively) and CD4+ Terminally Differentiated Effector Memory cells at M3 (p=0.044). Discussion: PLWH have a robust immune response after SARS-CoV-2 vaccination, but a rapid decline in humoral response from 3 months onwards, due to a blunted memory B cell response. Analysis of lymphocyte subsets may help identify optimal times for vaccine boosters.


Subject(s)
COVID-19 Vaccines , COVID-19 , Male , Humans , Middle Aged , Female , BNT162 Vaccine , Platelet Aggregation Inhibitors , SARS-CoV-2
4.
J Vasc Access ; : 11297298231152500, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36726226

ABSTRACT

PURPOSE: Few studies describe the efficacy of antibiotic lock therapy (ALT) in long-term catheter-related bloodstream (CRBSI) infections. We applied local protocols combining Daptomycin (DPT) and Taurolidine ALT, associated with systemic antibiotic treatment (SAT), for conservative management of coagulase-negative Staphylococci (CoNS) CRBSI. METHODS: Patients admitted for CoNS-associated CRBSI and treated with DPT and Taurolidine as ALT were retrospectively analyzed. Success was defined as catheter retention 30 days after ending treatment. Catheter removal within 30 days was considered as failure. RESULTS: From April 2018 to September 2021, 22 subjects with CoNS-associated-CRBSI were included (95% with cancer, mean age 64 years, 59% male). Staphylococcus epidermidis was isolated in 82% of cases. Mean duration of DPT was 3.9 and 3 days as ALT and SAT, respectively. SAT also included Rifampin for 3 days. Taurolidine ALT was started on day 4 and was combined with oral SAT, that is, either Linezolid or Tedizolid. Mean duration of Taurolidine was 10.5 days, while total antibiotic treatment lasted 13.5 days. Clinical success and failure rates were 95% and 5%, respectively. DISCUSSION: Short course DPT as ALT, combined with SAT and Taurolidine ALT, allowed high rates of conservative management of catheters in case of CoNS-associated-CRBSI.

5.
Viruses ; 14(5)2022 04 28.
Article in English | MEDLINE | ID: mdl-35632669

ABSTRACT

Objective: Immunadapt is a study evaluating the impact of combination antiretroviral treatment (cART) simplification on immune activation. We previously showed that switching to dual therapies could be associated six months later with macrophage activation. Followup continued up to 24 months after treatment simplification. Materials and Methods: Immunadapt is a prospective single arm study of successfully treated subjects simplifying cART from triple to dual regimens. Before cART change, at 6 months, and between 18 and 24 months following the switch, we measured IP-10, MCP-1, soluble CD14 (sCD14), soluble CD163 (sCD163), and lipopolysaccharide binding protein. Patients were stratified according to lower or greater likelihood of immune activation (CD4 nadir < 200, previous AIDS-defining event or very-low-level viremia during follow-up). Variables were compared using matched Wilcoxon tests. Results: From April 2019 to September 2021, 14 subjects were included (mean age 60 years, 12 men, 26 years since HIV infection, CD4 nadir 302 cells/mm3, 18 years on cART, 53 months on last cART). Twenty-one months following the switch, all but one subject maintained their viral load < 50 cp/mL. One subject had two viral blips. For the entire population, the sCD163 values increased significantly from baseline (+36%, p = 0.003) and from 6 months after the switch. The other markers did not change. After 6 months, the sCD163 increase was more pronounced in subjects with greater likelihood of immune activation (+53% vs. +19%, p = 0.026) Conclusions: cART simplification to dual therapy was associated with macrophage activation despite successful virological control after almost two years' follow-up. This was more pronounced in those at risk of immune activation.


Subject(s)
HIV Infections , Biomarkers , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Viral Load , Viremia
6.
Front Med (Lausanne) ; 9: 809154, 2022.
Article in English | MEDLINE | ID: mdl-35308544

ABSTRACT

Objectives: The Delta variant of the novel beta coronavirus responsible for the current coronavirus pandemic (COVID-19) spread across Europe during the summer of 2021. Little is known of vaccine efficacy on this variant. Our aim was to study the prevalence and clinical characteristics of fully vaccinated subjects admitted to hospital for Delta variant COVID-19. Methods: We identified patients admitted to Cannes hospital for Delta-variant-related Covid-19 infection from July to September 2021. Their main demographic parameters, inflammatory markers, and clinical characteristics were recorded. Differences between fully vaccinated subjects and unvaccinated or incompletely vaccinated individuals were analyzed. Results: We included 126 patients (57% male, mean age 64 years, mean delay since symptoms onset 7.8 days). Among admitted patients, 94 (75%) were not vaccinated, 11 (8%) incompletely so and 21 (17%) were fully vaccinated. Fully vaccinated patients were older (77 vs. 61 vs. 62 years, p = 0.003), with fewer days since symptoms onset (5.9 vs. 8.0 vs. 9.3 days, p = 0.035) than unvaccinated or incompletely vaccinated patients, respectively. Severe pneumonia was less frequent among completely vaccinated subjects (67 vs. 84 vs. 100%, p = 0.038), while rates of transfer to the ICU, mechanical ventilation or death did not differ. Thirteen fully vaccinated patients underwent a thoracic CT scan, revealing involvement of lung parenchyma in four of them. Discussion: Prevalence of hospitalization for Delta-variant COVID-19 in fully vaccinated subjects was low and, despite their age and comorbid conditions, these patients had a high rate of favorable outcome.

7.
Front Med (Lausanne) ; 8: 712880, 2021.
Article in English | MEDLINE | ID: mdl-34458287

ABSTRACT

Objectives: The aim of this study was to evaluate the effect on immune activation of switching from a triple-drug to a dual-drug regimen in HIV-1 infected patients on successful combination antiretroviral treatment (cART). Immunadapt is a prospective study evaluating the impact of cART simplification on immune activation. Methods: We prospectively collected blood samples in HIV-1 infected patients on stable and successful cART switching from triple to dual regimens as a simplifying strategy. We compared immune activation markers: high sensitivity CRP, IL-1, IL-6, IL-8, IP-10, MCP-1, TNF-alpha, soluble CD14 (sCD14), soluble CD163 (sCD163), lipopolysaccharide binding protein, and D-dimer before cART change and at least 6 months after the switch. Patients were stratified according to low or high risk factors of immune activation (low CD4 nadir, previous AIDS-defining condition or very-low-level viremia during follow-up). Results: From April 2019 to May 2020, 20 subjects were included (mean age 57 years, 25 years since HIV infection, CD4 666 cells/mm3, CD8 766 cells/mm3, CD4/CD8 0.94, CD4 nadir 326 cells/mm3, 15% with AIDS, 18 years on cART, 6 cART regimens received, current cART duration: 56 months). Fourteen patients were prescribed Dolutegravir + Rilpivirine and six received Dolutegravir + Lamivudine. After 6.9 months, a significant sCD163 increase (+ 25.5% vs. + 0.5%, p = 0.02) was observed in subjects with high risk factors, despite maintaining a viral load <50 cp/ml. Conclusion: cART simplification in favor of dual therapy is associated with macrophage activation in patients at risk of immune activation despite sustained virological control. Risk factors should thus be considered before generalizing such strategies.

8.
J Clin Med ; 10(16)2021 Aug 12.
Article in English | MEDLINE | ID: mdl-34441844

ABSTRACT

OBJECTIVES: The variant alpha COVID-19 rapidly spread across Europe in early 2021. While this variant's increased infectivity has been proven, little is known of its clinical presentation and outcomes compared to the old strain. METHODS: We identified patients admitted to the Cannes General Hospital for variant alpha-related COVID-19 infection from January to April 2021. Their main demographic parameters, inflammatory markers and clinical characteristics were recorded. Patients admitted from October to December 2020 for 20E (EU1) COVID-19 were selected as controls. Differences between groups were analyzed. RESULTS: We included 157 patients (mean age 73 years; 58% men; mean delay of symptoms 6.9 days). Comorbidities were present in 92% (mainly hypertension, diabetes and obesity or overweight). The prevalence of comorbidities did not differ between groups. In 28% of cases, patients either died or required transfer to the Intensive Care Unit (ICU). The cause of death or of transfer to the ICU was presumably associated with severe pneumonia. Variant alpha COVID-19 had 3.8-fold higher risk of death or transfer to the ICU compared to the old strain. DISCUSSION: Patients infected with variant alpha COVID-19, despite similar background characteristics, had a higher risk of unfavorable outcomes than those infected with the old strain, suggesting increased virulence related to this variant.

9.
J Gynecol Obstet Hum Reprod ; 48(3): 187-191, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30562580

ABSTRACT

AIM: Premature rupture of membranes (PROM) increases the neonatal morbidity and mortality, because of its association with a high risk of prematurity and infection. The group B streptococcus (GBS) prophylaxis using amoxicillin doesn't seem to be adapted to the emergence of new bacteria found in vaginal samples (VS). Our study aim was to assess, for PROM occurring at 23-34 weeks' gestation (WG), if the presence of ampicillin-resistant enterobacteria in the vaginal microbiome is predictive of an increased risk of early-onset neonatal infection. MATERIAL AND METHODS: We conducted a prospective, observational, single-center study at the Nice Academic Hospital (level 3 maternity ward), between March 16, 2014 and May 3, 2015, that evaluated patients with preterm PROM (24-34 WG). Two groups were constituted according to the VS bacteria isolates and the amoxycillin-resistant enterobacteria found. Two groups of newborns were constituted depending on the suspicion of perinatal maternal-fetal bacterial infection (MFI). An intent-to-treat analysis was performed. RESULTS: Among the 67 patients included, 12 newborns presented a strong MFI suspicion, 83% of which were associated to the group of patients with untreated or amoxycillin-resistant enterobacteria VS isolates. CONCLUSION: Our study showed that vaginal colonization of untreated or amoxycillin-resistant enterobacteria constitutes a major risk factor of neonatal infection.


Subject(s)
Ampicillin Resistance , Enterobacteriaceae Infections , Enterobacteriaceae/pathogenicity , Fetal Membranes, Premature Rupture , Infant, Newborn, Diseases , Pregnancy Complications, Infectious , Vagina/microbiology , Adult , Female , Gestational Age , Humans , Infant, Newborn , Pregnancy , Prospective Studies
10.
Emerg Infect Dis ; 23(5): 845-848, 2017 05.
Article in English | MEDLINE | ID: mdl-28418291

ABSTRACT

After the deaths of 2 preterm neonates with Bacillus cereus systemic infection in the same intensive care unit, we investigated the pathogenic potential of this bacterium. Genetic and virulence analysis indicated the neonates were infected with 2 different strains with a virulence potential similar to environmental strains, indicating likely patient immune response failure.


Subject(s)
Bacillus cereus/isolation & purification , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/microbiology , Anti-Bacterial Agents/therapeutic use , Bacillus cereus/genetics , Bacillus cereus/pathogenicity , Cross Infection , Drug Therapy, Combination , Fatal Outcome , Female , Gram-Positive Bacterial Infections/drug therapy , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Pregnancy , Ultrasonography, Prenatal , Virulence/genetics , Virulence Factors/genetics
11.
Anaerobe ; 42: 44-49, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27510569

ABSTRACT

Clostridium indolis is an anaerobic spore-forming Gram-positive bacillus belonging to the Clostridium saccharolyticum group. Its clinical significance in human remains poorly known. We describe the first case of osteitis related to C. indolis, identified by MALDI-TOF mass spectrometry and provide a literature review of human infections related to C. saccharolyticum group species.


Subject(s)
Bacterial Proteins/genetics , Clostridium Infections/diagnosis , Clostridium/isolation & purification , Osteitis/diagnosis , RNA, Ribosomal, 16S/genetics , Adult , Anaerobiosis , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/metabolism , Chronic Disease , Clostridium/classification , Clostridium/drug effects , Clostridium/genetics , Clostridium Infections/drug therapy , Clostridium Infections/etiology , Clostridium Infections/microbiology , Enzyme Assays , Female , Fractures, Bone/complications , Fractures, Bone/diagnosis , Fractures, Bone/microbiology , Gene Expression , Humans , Microbial Sensitivity Tests , Osteitis/drug therapy , Osteitis/etiology , Osteitis/microbiology , Phylogeny , RNA, Ribosomal, 16S/metabolism , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
12.
BMC Infect Dis ; 15: 238, 2015 Jun 23.
Article in English | MEDLINE | ID: mdl-26099275

ABSTRACT

BACKGROUND: Helcococcus kunzii is a facultative anaerobic bacterium that was first described by Collins et al. in 1993, and was initially considered as a commensal of the human skin, in particular of lower extremities. Human infections caused by H. kunzii remain rare with only a few cases published in the pubmed database. Nevertheless recent reports indicate that this microorganism has to be considered as an opportunistic pathogen that can be involved in severe infections in human. To the best of our knowledge, we describe here the first known case of infectious endocarditis caused by H. kunzii. CASE PRESENTATION: A 79 year-old man reporting severe polyvascular medical history attended the emergency ward for rapid deterioration of his general state of health. After physical examination and paraclinical investigations, the diagnosis of infectious endocarditis on native mitral valve caused by Helcococcus kunzii was established based on Dukes criteria. MALDI-TOF mass spectrometry and 16S rDNA sequencing allowed an accurate identification to the species level of Helcococcus kunzii. The patient was successfully treated by a medico-surgical approach. The treatment consisted in intravenous amoxicillin during four weeks and mitral valve replacement with a bioprosthestic valve. After an in depth review of patient's medical file, the origin of infection remained unknown. However, a cutaneous portal of entry cannot be excluded as the patient and his General Practitioner reported chronic ulcerations of both feet. CONCLUSIONS: We describe here the first case of endocarditis caused by H. kunzii in an elderly patient with polyvascular disease. This report along with previous data found in the literature emphasizes the invasive potential of this bacterial species as an opportunistic pathogen, in particular for patient with polyvascular diseases. MALDI-TOF mass spectrometry and 16S rDNA sequencing are reliable tools for H. kunzii identification. We also sequenced in this work H.kunzii type strain 103932T CIP and deposited in the Genbank under accession number KM403387. We noticed a 14 base difference between our sequence and the original sequence deposited by Collins et al. under Genbank accession number X69837. Hopefully, the spread of next generation sequencing tools would lead to a more accurate classification of clinical strains.


Subject(s)
DNA, Ribosomal/genetics , Endocarditis, Bacterial/diagnosis , Gram-Positive Bacterial Infections/diagnosis , Mitral Valve , Peptostreptococcus/genetics , Aged , Aortic Aneurysm, Abdominal/complications , Carotid Artery Diseases/complications , Endocarditis, Bacterial/complications , Endocarditis, Bacterial/microbiology , Foot Ulcer/complications , Gram-Positive Bacterial Infections/complications , Gram-Positive Bacterial Infections/microbiology , High-Throughput Nucleotide Sequencing , Humans , Male , Myocardial Ischemia/complications , Peptostreptococcus/isolation & purification , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
14.
J Clin Microbiol ; 52(10): 3813-5, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25056327
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