Two Cases of Viral Re-suppression After M184V + R263K Selection on Dolutegravir/Lamivudine Without Treatment Modification.

Dolutegravir/lamivudine (DTG/3TC) has a high genetic barrier against the development of human immunodeficiency virus drug resistance. We report 2 cases of R263K + M184V mutations during DTG/3TC failure followed by viral suppression after adherence intervention without treatment change that we attribute to residual drug activity, reduced viral fitness, and robust immune competence.

Case Report and Literature Review of Prosthetic Cardiovascular Mucormycosis.

We report a rare case of aorto-bi-iliac prosthetic allograft mucormycosis in a 57-year-old immunocompetent patient in France. Outcome was favorable after surgery and dual antifungal therapy with liposomal amphotericin B and isavuconazole. In a literature review, we identified 12 other cases of prosthetic vascular or heart valve mucormycosis; mortality rate was 38%.

Distribution of Achromobacter Species in 12 French Cystic Fibrosis Centers in 2020 by a Retrospective MALDI-TOF MS Spectrum Analysis.

Achromobacter spp. are nonfermenting Gram-negative bacilli mainly studied among cystic fibrosis (CF) patients. The identification of the 19 species within the genus is time-consuming (nrdA-sequencing), thus data concerning the distribution of the species are limited to specific studies. Recently, we built a database using MALDI-TOF mass spectrometry (MS) (Bruker) that allows rapid and accurate species identification and detection of the multiresistant epidemic clones: A. xylosoxidans ST137 spreading among CF patients in various French and Belgium centers, and A. ruhlandii DES in Denmark. Here, we first assessed whether species identification could be achieved with our database solely by analysis of MS spectra without availability of isolates. Then, we conducted a multicentric study describing the distribution of Achromobacter species and of the clone ST137 among French CF centers. We collected and analyzed with our local database the spectra of Achromobacter isolates from 193 patients (528 samples) from 12 centers during 2020. In total, our approach enabled to conclude for 502/528 samples (95.1%), corresponding to 181 patients. Eleven species were detected, only five being involved in chronic colonization, A. xylosoxidans (86.4%), A. insuavis (9.1%), A. mucicolens (2.3%), A. marplatensis (1.1%) and A. genogroup 3 (1.1%). This study confirmed the high prevalence of A. xylosoxidans in chronic colonizations and the circulation of the clone A. xylosoxidans ST137 in France: four patients in two centers. The present study is the first to report the distribution of Achromobacter species from CF patients samples using retrospective MALDI-TOF/MS data. This easy approach could enable future large-scale epidemiological studies.

Unusual presentation of toxoplasmosis with gastro-intestinal involvement in HLA non-identical stem cell transplantation.

Toxoplasmosis is a life-threatening infection in allogenic stem cell recipients usually involving the brain or retina and more rarely lungs or bone marrow. Digestive involvement has only been reported in AIDS patient. We report about a 38-year-old man who received a haploidentical allograft for acute myeloid leukemia and developed an unusual digestive presentation with severe protein-losing enteropathy following grade III acute digestive GvHD treated with steroids and ruxolitinib. Diagnosis was brought up because of concomitant brain involvement. Digestive symptoms fully recovered after treatment with sulfamethoxazole-trimethoprim. Digestive toxoplasmosis could be considered as a differential diagnosis or complication of severe digestive GvHD.

Underdiagnosis of arbovirus infections in returned travelers in an area with growing circulation of Aedes albopictus in North-Eastern France.

BACKGROUND: Vector-borne diseases such as malaria and arboviruses are common etiologies of post-travel fever. METHODS: After excluding malaria, we retrospectively analyzed the diagnosis of dengue virus (DENV), chikungunya virus (CHIKV), and zika virus (ZIKV) infections following recent travel by patients treated at the Strasbourg University Hospital between 2014 and 2023. Available serums (n = 35) sampled in 2023 were retrospectively tested for DENV, CHIKV, and ZIKV infections. RESULTS: Our results showed that 78% of the 915 malaria-negative patients without changes over the course of ten years had not undergone arbovirus infection testing. Retrospective testing revealed missing arbovirus infections: two DENV infections and one CHIKV infection, representing 8.6% (3/35) of patients for whom no mandatory declaration or vector control could be undertaken. CONCLUSION: Our results highlight the need for early case detection, particularly in the context of the upcoming 2024 Olympic Games.

Infectious Mediastinitis: A Retrospective Cohort Study.

Background: This study aimed to characterize the demographics, microbiology, management and treatment outcomes of mediastinitis according to the origin of the infection. Methods: This retrospective observational study enrolled patients who had mediastinitis diagnosed according to the criteria defined by the Centers for Disease Control and Prevention and were treated in Strasbourg University Hospital, France, between 1 January 2010 and 31 December 2020. Results: We investigated 151 cases, including 63 cases of poststernotomy mediastinitis (PSM), 60 cases of mediastinitis due to esophageal perforation (MEP) and 17 cases of descending necrotizing mediastinitis (DNM). The mean patient age (standard deviation) was 63 (14.5) years, and 109 of 151 patients were male. Microbiological documentation varied according to the origin of the infection. When documented, PSM cases were mostly monomicrobial (36 of 53 cases [67.9%]) and involved staphylococci (36 of 53 [67.9%]), whereas MEP and DNM cases were mostly plurimicrobial (38 of 48 [79.2%] and 8 of 12 [66.7%], respectively) and involved digestive or oral flora microorganisms, respectively. The median duration of anti-infective treatment was 41 days (interquartile range, 21-56 days), and 122 of 151 patients (80.8%) benefited from early surgical management. The overall 1-year survival rate was estimated to be 64.8% (95% confidence interval, 56.6%-74.3%), but varied from 80.1% for DNM to 61.5% for MEP. Conclusions: Mediastinitis represents a rare yet deadly infection. The present cohort study exhibited the different patterns observed according to the origin of the infection. Greater insight and knowledge on these differences may help guide the management of these complex infections, especially with respect to empirical anti-infective treatments.

Cefepime vs carbapenems for treating third-generation cephalosporin-resistant AmpC ß-lactamase-hyperproducing Enterobacterales bloodstream infections: a multicenter retrospective study.

OBJECTIVES: AmpC ß-lactamase-hyperproducing Enterobacterales (ABLHE) bloodstream infections (BSI) are emerging and leading to therapeutic challenges worldwide. Prescriptions of carbapenems may lead to the emergence of resistance. This study aimed to compare cefepime with carbapenems for the treatment of third-generation cephalosporin-resistant ABLHE BSI. METHODS: This retrospective multicenter study included patients with ABLHE BSI from two tertiary hospitals in France, between July 2017 and July 2022. Non-AmpC-producing Enterobacterales, extended-spectrum ß-lactamase, and carbapenemase-producing Enterobacterales were excluded. Cefepime was prescribed only in case of minimal inhibitory concentration ≤1 mg/l. The primary outcome was 30-day in-hospital mortality from the date of index blood culture. Secondary outcomes were infection recurrence and treatment toxicity. An inverse probability of treatment weighting approach was used to balance the baseline characteristics between the two groups. RESULTS: We analyzed 164 BSI, which included 77 in the cefepime group and 87 in the carbapenem group. In the weighted cohort, the 30-day mortality rates were similar between the cefepime group (23.3%) and the carbapenem group (19.6%) with a relative risk of 1.19 (95% confidence interval, 0.61-2.33 P = 0.614). No significant difference in recurrence or toxicity was found between the two groups. CONCLUSION: This study adds evidence in favor of the use of cefepime for treating third-generation cephalosporin-resistant ABLHE BSI in case of minimal inhibitory concentration ≤ 1 mg/l, which could spare carbapenems.

Staphylococcus epidermidis bloodstream infections are a cause of septic shock in intensive care unit patients.

OBJECTIVES: Staphylococcus epidermidis (SE) is a supposedly low-virulence agent, which may cause proven bloodstream infections (BSIs), with little-known consequences on intensive care unit (ICU) patients. We aimed at studying ICU patients diagnosed with BSIs caused by SE (SE-BSIs). METHODS: We constituted a retrospective cohort in two medical ICUs. SE-BSIs were defined by two or more independent SE-positive blood cultures of the same strain, within 48 hours, without concurrent infection. RESULTS: We included 59 patients; 58% were men (n = 34), with median age of 67 (interquartile range 60-74) years and a simplified acute physiology score II of 59 (36-74) points, and 56% were immunocompromised (n = 33). Among the 37 (63%) patients requiring norepinephrine initiation or increase at the onset of SE-BSI versus patients not requiring vasopressors (37%; n = 22), concomitant arterial lactate levels reached 2.8 (1.9-5.8) versus 1.5 (1.3-2.2) mmol/l (P <0.01), whereas the mean blood pressure was 49 (42-54) versus 61 (56-65) mm Hg (P = 0.01) and the mortality was 46% (n = 17) vs 14% (n = 3) at day 28 (P = 0.01), respectively. Regarding antibiotics, the susceptibility rates toward linezolid and vancomycin were 71% (n = 41/58) and 100% (n = 54/54), respectively. At the time of SE-BSI, all but one patient had a central venous access device. CONCLUSION: This work highlights SE-BSIs as a cause of septic shock, mostly in immunocompromised ICU patients, with increasing concerns about resistance to antibiotics and central line management.

HIV Productively Infects Highly Differentiated and Exhausted CD4+ T Cells During AIDS.

Background: Throughout HIV infection, productively infected cells generate billions of viral particles and are thus responsible for body-wide HIV dissemination, but their phenotype during AIDS is unknown. As AIDS is associated with immunological changes, analyzing the phenotype of productively infected cells can help understand HIV production during this terminal stage. Methods: Blood samples from 15 untreated viremic participants (recent infection, n=5; long-term infection, n=5; active opportunistic AIDS-defining disease, n=5) and 5 participants virologically controlled on antiretroviral therapy (ART) enrolled in the Analysis of the Persistence, Reservoir and HIV Latency (APRIL) study (NCT05752318) were analyzed. Cells expressing the capsid protein p24 (p24+ cells) after 18 hours of resting or 24 hours of stimulation (HIV-Flow) revealed productively infected cells from viremic participants or translation-competent reservoir cells from treated participants, respectively. Results: The frequency of productively infected cells tended to be higher during AIDS in comparison with recent and long-term infections (median, 340, 72, and 32/million CD4+ T cells, respectively) and correlated with the plasma viral load at all stages of infection. Altogether, these cells were more frequently CD4low, HLA-ABClow, CD45RA-, Ki67+, PD-1+, with a non-negligible contribution from pTfh (CXCR5+PD-1+) cells, and were not significantly enriched in HIV coreceptors CCR5 nor CXCR4 expression. The comparison markers expression between stages showed that productively infected cells during AIDS were enriched in memory and exhausted cells. In contrast, the frequencies of infected pTfh were lower during AIDS compared to non-AIDS stages. A UMAP analysis revealed that total CD4+ T cells were grouped in 7 clusters and that productive p24+ cells were skewed to given clusters throughout the course of infection. Overall, the preferential targets of HIV during the latest stages seemed to be more frequently highly differentiated (memory, TTD-like) and exhausted cells and less frequently pTfh-like cells. In contrast, translation-competent reservoir cells were less frequent (5/million CD4+ T cells) and expressed more frequently HLA-ABC and less frequently PD-1. Conclusions: In long-term infection and AIDS, productively infected cells were differentiated and exhausted. This could indicate that cells with these given features are responsible for HIV production and dissemination in an immune dysfunction environment occurring during the last stages of infection.

High Incidence of Acute Kidney Injury in Patients Treated with High-Dose Amoxicillin and Cloxacillin Combination Therapy.

High-dose amoxicillin and cloxacillin combination therapy is recommended for the empiric treatment of selected patients with infective endocarditis despite a low level of evidence. The main objective of this study was to evaluate the renal tolerance of high-dose intravenous amoxicillin and cloxacillin combination. We studied 27 patients treated with amoxicillin and cloxacillin (≥100 mg/kg daily) for at least 48 h. The primary endpoint was the occurrence of acute kidney injury (AKI). The median patient age was 68 ± 8 years, and 16 (59%) were male. The indication for this combination therapy was suspected or confirmed endocarditis with no bacterial identification in 22 (81%) patients. The primary endpoint occurred in 16 (59%) patients after initiating this combination therapy within an average of 4.4 ± 3.6 days. Among them, seven (26%) patients developed severe AKI, including four (15%) patients who required hemodialysis. Other risk factors for AKI were identified in all patients, including injection of iodinated contrast media in 21 (78%), acute heart failure in 18 (67%), cardiac surgery in 11 (41%), and aminoglycoside use in 9 (33%) patients. This study reports an incidence of 59% of AKI after initiating amoxicillin and cloxacillin combination therapy in a population at high renal risk.