Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques

Letermovir potently inhibits the cytomegalovirus (CMV)-terminase complex. Letermovir primary prophylaxis given for the first 3 months after allogeneic hematopoietic cell transplantation (HCT) has been shown to reduce clinically significant CMV infection and is well tolerated. Until now, only case reports or small retrospective series have been published on the use of letermovir for a secondary prophylaxis (SP) of CMV infection or diseases after HCT. Here we report the outcome of 80 consecutive CMV-seropositive adult patients included in the French compassionate program and who received letermovir as a SP after at least 1 CMV episode (infection or disease) since HCT. Letermovir was initiated at a median of 170 (49 to 1829) days after transplant and given orally for a median of 118 (26 to 396) days at the usual daily dose of 480 mg once daily and adjusted to 240 mg once daily when coadministered with cyclosporine. The donors were seronegative in 53% of the cases. Fifty patients had a current or previous graft-versus-host disease (GVHD) and 14 had experienced CMV disease since transplant. Four (5.5%) patients developed CMV breakthrough infections (n = 1) or diseases (n = 3) after the initiation of letermovir. In 3 of these 4 patients, further investigation of virologic resistance showed a CMV UL56 mutation C325Y or W, conferring the high-level letermovir resistance. One or more adverse reactions were declared by the local investigator in 15 (19%) patients. Only 2 patients stopped letermovir SP because of an adverse reaction (pruritus, 1; cytopenia, 1). In our experience, letermovir given as a SP may prevent a new CMV reactivation in a high-risk patient population and can be administered for several weeks, providing a bridge between the pre-emptive or therapeutic treatment of a CMV episode and CMV-specific immune reconstitution, giving time for tapering immunosuppressants. Prospective studies are required to confirm these results.

Abstract Background Profound lymphopenia is an independent predictor of adverse clinical outcomes in sepsis. Interleukin-7 (IL-7) is essential for lymphocyte proliferation and survival. A previous phase II study showed that CYT107, a glycosylated recombinant human IL-7, administered intramuscularly reversed sepsis-induced lymphopenia and improved lymphocyte function. Thepresent study evaluated intravenous administration of CYT107. This prospective, double-blinded, placebo-controlled trial was designed to enroll 40 sepsis patients, randomized 3:1 to CYT107 (10 µg/kg) or placebo, for up to 90 days. Results Twenty-one patients were enrolled (fifteen CYT107 group, six placebo group) at eight French and two US sites. The study was halted early because three of fifteen patients receiving intravenous CYT107 developed fever and respiratory distress approximately 5–8 h after drug administration. Intravenous administration of CYT107 resulted in a two–threefold increase in absolute lymphocyte counts (including in both CD4 + and CD8 + T cells (all p < 0.05)) compared to placebo. This increase was similar to that seen with intramuscular administration of CYT107, was maintained throughout follow-up, reversed severe lymphopenia and was associated with increase in organ support free days (OSFD). However, intravenous CYT107 produced an approximately 100-fold increase in CYT107 blood concentration compared with intramuscular CYT107. No cytokine storm and no formation of antibodies to CYT107 were observed. Conclusion Intravenous CYT107 reversed sepsis-induced lymphopenia. However, compared to intramuscular CYT107 administration, it was associated with transient respiratory distress without long-term sequelae. Because of equivalent positive laboratory and clinical responses, more favorable pharmacokinetics, and better patient tolerability, intramuscular administration of CYT107 is preferable. Trial registration : Clinicaltrials.gov, NCT03821038. Registered 29 January 2019, https://clinicaltrials.gov/ct2/show/NCT03821038?term=NCT03821038&draw=2&rank=1 . Graphical Abstract

Human cytomegalovirus (HCMV) is one of the main causes of serious complications in immunocompromised patients and after congenital infection. There are currently drugs available to treat HCMV infection, targeting viral polymerase, whose use is complicated by toxicity and the emergence of resistance. Maribavir and letermovir are the latest antivirals to have been developed with other targets. The approval of letermovir represents an important innovation for CMV prevention in hematopoietic stem cell transplant recipients, whereas maribavir allowed improving the management of refractory or resistant infections in transplant recipients. However, in case of multidrug resistance or for the prevention and treatment of congenital CMV infection, finding new antivirals or molecules able to inhibit CMV replication with the lowest toxicity remains a critical need. This review presents a range of molecules known to be effective against HCMV. Molecules with a direct action against HCMV include brincidofovir, cyclopropavir and anti-terminase benzimidazole analogs. Artemisinin derivatives, quercetin and baicalein, and anti-cyclooxygenase-2 are derived from natural molecules and are generally used for different indications. Although they have demonstrated indirect anti-CMV activity, few clinical studies were performed with these compounds. Immunomodulating molecules such as leflunomide and everolimus have also demonstrated indirect antiviral activity against HCMV and could be an interesting complement to antiviral therapy. The efficacy of anti-CMV immunoglobulins are discussed in CMV congenital infection and in association with direct antiviral therapy in heart transplanted patients. All molecules are described, with their mode of action against HCMV, preclinical tests, clinical studies and possible resistance. All these molecules have shown anti-HCMV potential as monotherapy or in combination with others. These new approaches could be interesting to validate in clinical trials.

BACKGROUND: Infection prevention and control (IPC) is one of the most cost-effective interventions against antimicrobial resistance (AMR). Yet, IPC knowledge gaps often receive little prominence in AMR research agendas. In this article, we construct IPC research priorities, in order to draw attention to these critical research needs. METHODS: We developed a 4-step framework to identify IPC knowledge gaps from literature (narrative review). These gaps were then translated into research priorities and sent to two groups of European IPC experts for validation and critique through an online survey. RESULTS: Seventy-nine publications were retrieved from the literature review, identifying fifteen IPC research gaps. Forty-four IPC experts, clustered in two groups, vetted them. The experts classified all research gaps as medium or high priority. Overall agreement between both groups was average (Kendall's τ = 0.43), with strong alignment on the highest priorities: (i) the assessment of organizational, socio-economic, and behavioural barriers/facilitators for the implementation of IPC programmes, (ii) the impact of overcrowding on the spread of infections and (iii) the impact of infrastructural changes, at facility level, on the reduction of infections. Feedback from experts also identified an additional research gap on the interaction between the human and hospital microbiomes. CONCLUSIONS: We formulated a list of sixteen research priorities and identified three urgent needs. Now, we encourage researchers, funding agencies, policymakers and relevant stakeholders to start addressing the identified gaps.

Continuous exposure to low concentrations of antibiotics (sub-minimal inhibitory concentration: sub-MIC) is thought to lead to the development of antimicrobial resistance (AMR) in the environmental microbiota. However, the relationship between antibiotic exposure and resistance selection in environmental bacterial communities is still poorly understood and unproven. Therefore, we measured the concentration of twenty antibiotics, resistome quality, and analyzed the taxonomic composition of microorganisms in river biofilms collected upstream (UPS) and downstream (DWS) (at the point of discharge) from the wastewater treatment plant (WWTP) of Poitiers (France). The results of statistical analysis showed that the antibiotic content, resistome, and microbiome composition in biofilms collected UPS were statistically different from that collected DWS. According to Procrustes analysis, microbial community composition and antibiotics content may be determinants of antibiotic resistance genes (ARGs) composition in samples collected DWS. However, network analysis showed that the occurrence and concentration of antibiotics measured in biofilms did not correlate with the occurrence and abundance of antibiotic resistance genes and mobile genetic elements. In addition, network analysis suggested patterns of co-occurrence between several ARGs and three classes of bacteria/algae: Bacteroidetes incertae sedis , Cyanobacteria / Chloroplast , and Nitrospira , in biofilm collected UPS. The absence of a direct effect of antibiotics on the selection of resistance genes in the collected samples suggests that the emergence of antibiotic resistance is probably not only due to the presence of antibiotics but is a more complex process involving the cumulative effect of the interaction between the bacterial communities (biotic) and the abiotic matrix. Nevertheless, this study confirms that WWTP is an important reservoir of various ARGs, and additional efforts and legislation with clearly defined concentration limits for antibiotics and resistance determinants in WWTP effluents are needed to prevent their spread and persistence in the environment.

BACKGROUND: The phase 3 multinational SCARLET study evaluated the efficacy and safety of a recombinant human soluble thrombomodulin (ART-123) for treatment of sepsis-associated coagulopathy (SAC), which correlates with increased mortality risk in patients with sepsis. Although no significant reduction in mortality was observed with ART-123 compared with placebo in the full analysis set (FAS), an efficacy signal of ART-123 was observed in subgroups of patients who sustained coagulopathy until the first treatment and those not administered concomitant heparin. Post hoc analysis was performed of patients treated in France, the country with the largest enrollment (19% of the FAS) and consistent patient enrollment throughout the study duration. METHODS: /L or platelet decrease > 30% within 24 h) and evidence of bacterial infection were included. The primary efficacy outcome was 28-day all-cause mortality. Safety outcomes included adverse, serious adverse, and major bleeding events. This analysis assessed patient characteristics and efficacy and safety outcomes in France compared with the rest of the world (ROW; excluding France). Mortality rates were assessed in patients in France or the ROW with characteristics previously associated with ART-123 efficacy. RESULTS: Baseline characteristics were similar between France and the ROW, but some measurements of disease severity were higher in patients in France. The 28-day all-cause mortality absolute risk reductions (ARRs) with ART-123 were 8.3% in France and 1.1% in the ROW. The greater ARR in France may be related to a higher rate of sustained coagulopathy and lower rate of heparin use. In France and the ROW, 84.6% and 78.0% of patients sustained coagulopathy from the time of initial SAC diagnosis to first treatment with the study drug, and 65.8% and 43.9% did not receive heparin, respectively. The ARRs for these subgroups of patients in France were 13.4% and 16.6%, respectively. Safety of ART-123 was comparable between France and the ROW. CONCLUSIONS: Results from this exploratory analysis suggest that patients with sustained SAC not receiving concomitant heparin may benefit from ART-123, a fact that should be confirmed in future studies with more restrictive inclusion criteria.

Class 1 integrons are widespread genetic elements playing a major role in the dissemination of antibiotic resistance. They allow bacteria to capture, express and exchange antibiotic resistance genes embedded within gene cassettes. Acquisition of gene cassettes is catalysed by the class 1 integron integrase, a site-specific recombinase playing a key role in the integron system. In in vitro planktonic culture, expression of intI1 is controlled by the SOS response, a regulatory network which mediates the repair of DNA damage caused by a wide range of bacterial stress, including antibiotics. However, in vitro experimental conditions are far from the real lifestyle of bacteria in natural environments such as the intestinal tract which is known to be a reservoir of integrons. In this study, we developed an in vivo model of intestinal colonization in gnotobiotic mice and used a recombination assay and quantitative real-time PCR, to investigate the induction of the SOS response and expression and activity of the class 1 integron integrase, IntI1. We found that the basal activity of IntI1 was higher in vivo than in vitro. In addition, we demonstrated that administration of a subinhibitory concentration of ciprofloxacin rapidly induced both the SOS response and intI1 expression that was correlated with an increase of the activity of IntI1. Our findings show that the gut is an environment in which the class 1 integron integrase is induced and active, and they highlight the potential role of integrons in the acquisition and/or expression of resistance genes in the gut, particularly during antibiotic therapy.

Bacteria of the genus Achromobacter are environmental germs, with an unknown reservoir. It can become opportunistic pathogens in immunocompromised patients, causing bacteremia, meningitis, pneumonia, or peritonitis. In recent years, Achromobacter xylosoxidans has emerged with increasing incidence in patients with cystic fibrosis (CF). Recent studies showed that A. xylosoxidans is involved in the degradation of the respiratory function of patients with CF. The respiratory ecosystem of patients with CF is colonized by bacterial species that constantly fight for space and access to nutrients. The type VI secretion system (T6SS) empowers this constant bacterial antagonism, and it is used as a virulence factor in several pathogenic bacteria. This study aimed to investigate the prevalence of the T6SS genes in A. xylosoxidans isolated in patients with CF. We also evaluated clinical and molecular characteristics of T6SS-positive A. xylosoxidans strains. We showed that A. xylosoxidans possesses a T6SS gene cluster and that some environmental and clinical isolates assemble a functional T6SS nanomachine . A. xylosoxidans T6SS is used to target competing bacteria, including other CF-specific pathogens. Finally, we demonstrated the importance of the T6SS in the internalization of A. xylosoxidans in lung epithelial cells and that the T6SS protein Hcp is detected in the sputum of patients with CF. Altogether, these results suggest for the first time a role of T6SS in CF-lung colonization by A. xylosoxidans and opens promising perspective to target this virulence determinant as innovative theranostic options for CF management.

BACKGROUND: In France, pneumococcal vaccination in adults is recommended for risk groups (chronic conditions/immunosuppression). We conducted a study on invasive pneumococcal disease (IPD) in adults to identify factors associated with disease severity and death. METHODS: We included IPD cases, excluding meningitis, from 25 acute care hospitals in 6 regions. We defined severe cases as those with shock or severe sepsis or intensive care unit admission/mechanical ventilation. We included deaths occurring within 30 days of hospitalization. Infectious disease specialists collected clinical/microbiological data on cases. RESULTS: During 2014-2017, 908 nonmeningitis IPD cases were diagnosed; 48% were severe, 84% had comorbidities, 21% died. Ninety percent of cases with comorbidities who previously sought health care were not vaccinated against pneumococcus. Compared with previously healthy cases, the risk of severe IPD increased from 20% (adjusted risk ratio [aRR], 1.2; 95% confidence interval [CI], 1.0-1.4) in cases with 1-2 chronic diseases to 30% (aRR, 1.3; 95% CI, 1.0-7.0) in those with >2 chronic diseases. Among risk groups, 13-valent pneumococcal conjugate vaccine (PCV13) serotypes and 23-valent pneumococcal polysaccharide vaccine (PPSV23) nonPCV13 serotypes were more likely to induce severe IPD compared with nonvaccine serotypes (aRR, 1.5; 95% CI, 1.3-1.9; aRR, 1.3; 95% CI, 1.0-1.5, respectively). CONCLUSIONS: We observed a cumulative effect of concurrent comorbidities on severe IPD. Vaccine serotypes were more likely to induce severe IPD among risk groups. The missed opportunities for vaccination underscore the need to enhance vaccination in risk groups.

OBJECTIVES: Evaluation of left atrial pressure is frequently required for mechanically ventilated critically ill patients. The objective of the present study was to evaluate the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for assessment of the pulmonary artery occlusion pressure (a frequent surrogate of left atrial pressure) in this population. DESIGN: A pooled analysis of three prospective cohorts of patients simultaneously assessed with a pulmonary artery catheter and echocardiography. SETTINGS: Medical-surgical intensive care department of two university hospitals in France. PATIENTS: Mechanically ventilated critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 98 included patients (males: 67%; mean ± SD age: 59 ± 16; and mean Simplified Acute Physiology Score 2: 54 ± 20), 53 (54%) experienced septic shock. Using the 2016 American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, the predicted pulmonary artery occlusion pressure was indeterminate in 48 of the 98 patients (49%). Of the 24 patients with an elevated predicted left atrial pressure (grade II/III diastolic dysfunction), only 17 (71%) had a pulmonary artery occlusion pressure greater than or equal to 18 mm Hg. Similarly, 20 of the 26 patients (77%) with a normal predicted left atrial pressure (grade I diastolic dysfunction) had a measured pulmonary artery occlusion pressure less than 18 mm Hg. The sensitivity and specificity of American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines for predicting elevated pulmonary artery occlusion pressure were both 74%. The agreement between echocardiography and the pulmonary artery catheter was moderate (Cohen's Kappa, 0.48; 95% CI, 0.39-0.70). In a proposed alternative algorithm, the best echocardiographic predictors of a normal pulmonary artery occlusion pressure were a lateral e'-wave greater than 8 (for a left ventricular ejection fraction ≥ 45%) or an E/A ratio less than or equal to 1.5 (for a left ventricular ejection fraction < 45%). CONCLUSIONS: The American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines do not accurately assess pulmonary artery occlusion pressure in ventilated critically ill patients. Simple Doppler measurements gave a similar level of diagnostic performance with less uncertainly.

Currently, an extensive effort is ongoing in academia and industry to design cost-effective coatings that can protect the surfaces against microorganisms, by limiting their transmission and growth. Thermal spray can be used to improve the functionality of thermoplastic surfaces by combining an innovative design with the antimicrobial properties of metallic materials. This systematic review deals with copper coatings deposited on thermoplastics by thermal spray techniques. Its aim is to understand the role that surface roughness, material microstructure and surface chemistry plays on the inactivation rate of microorganisms, especially viruses. In addition, a general view of the interaction mechanisms between metallic surface and microorganisms is emphasized. The antimicrobial coatings should be engineered to control the release of metal ions which is directly linked with the lifespan of the microorganism. They must also comply with the ISO 21702:2019 that stipulates suitable methods for antiviral activity measurement on plastics and other non-porous surfaces of antiviral-treated products. The designed coatings should provide long-lasting virus protection and prevent the degradation of the surface. Finally, an outline of the effect of the copper deposition method onto thermoplastic surfaces, coating microstructure, and surface specific oxygen species is presented in correlation with antimicrobial properties.

We report the results of the French Temporary Authorization of Use (ATU) compassionate program of letermovir for primary prophylaxis conducted in 21 transplant centers. Patients were CMV seropositive allogeneic hematopoietic cell transplantation recipients and at high risk for CMV infection. Primary prophylaxis was defined as initiation of letermovir between day 0 and day +28 post-transplant. Between November 2017 and January 2019, 96 patients with a median age of 56 years received letermovir and follow-up data were available for 78 patients. The median time from transplant to letermovir initiation was 4 days, and the median duration of exposure to letermovir was 78 days, with 57 patients still on treatment at the cutoff date. Letermovir was temporarily discontinued in 4 patients (5.1%) and stopped in 39 patients (50.0%), in most cases due to planned end of treatment (n = 16, 20.5%). Fifteen patients (19.2%) each presented one positive CMV PCR, in median 13 days after letermovir initiation. Clinically significant CMV infection was reported in 5 patients (6.4%). No CMV disease was reported. At least one adverse drug reaction was reported for 12 patients (15.4%). In this early access program, letermovir was effective with comparable results of the phase 3 study with a low rate of clinically significant CMV infection, including in patients who were at high-risk for CMV infection.

OBJECTIVES: To analyse mechanisms of letermovir breakthrough during compassionate primary and secondary prophylaxis. METHODS: Mechanisms of letermovir breakthrough during compassionate primary and secondary prophylaxis were analysed in four patients from the French Named Patient Programme by the French National Reference Centre for Herpesviruses. RESULTS: Of three absolute resistance cases, two were associated with treatment interruption or low letermovir concentrations in blood. A fourth case of breakthrough was not associated with resistance. Next-generation sequencing (NGS) genotyping confirmed rapid emergence of resistant mutants, within 3 months of treatment initiation. CONCLUSIONS: Measurement of letermovir concentration and genotyping should be recommended for patient follow-up during letermovir therapy.

International audience

The emergence and selection of antibiotic resistance is a major public health problem worldwide. The presence of antibiotic-resistant bacteria (ARBs) in natural and anthropogenic environments threatens the sustainability of efforts to reduce resistance in human and animal populations. Here, we use mathematical modeling of the selective effect of antibiotics and contaminants on the dynamics of bacterial resistance in water to analyze longitudinal spatio-temporal data collected in hospital and urban wastewater between 2012 and 2015. Samples were collected monthly during the study period at four different sites in Haute-Savoie, France: hospital and urban wastewater, before and after water treatment plants. Three different categories of exposure variables were collected simultaneously: 1) heavy metals, 2) antibiotics and 3) surfactants for a total of 13 drugs/molecules; in parallel to the normalized abundance of 88 individual genes and mobile genetic elements, mostly conferring resistance to antibiotics. A simple hypothesis-driven model describing weekly antibiotic resistance gene (ARG) dynamics was proposed to fit the available data, assuming that normalized gene abundance is proportional to antibiotic resistant bacteria (ARB) populations in water. The detected compounds were found to influence the dynamics of 17 genes found at multiple sites. While mercury and vancomycin were associated with increased ARG and affected the dynamics of 10 and 12 identified genes respectively, surfactants antagonistically affected the dynamics of three genes. The models proposed here make it possible to analyze the relationship between the persistence of resistance genes in the aquatic environment and specific compounds associated with human activities from longitudinal data. Our analysis of French data over 2012-2015 identified mercury and vancomycin as co-selectors for some ARGs.

Despite efforts to develop anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody (Ab) immunoassays, reliable serological methods are still needed. We developed a multiplex addressable laser bead immunoassay (ALBIA) to detect and quantify anti-Spike S1 and nucleocapsid N Abs. Recombinant S1 and N proteins were bound to fluorescent beads (ALBIA-IgG-S1/N). Abs were revealed using class-specific anti-human Ig Abs. The performances of the test were analyzed on 575 serum samples including 192 from SARS-CoV-2 polymerase chain reaction–confirmed patients, 13 from seasonal coronaviruses, 70 from different inflammatory/autoimmune diseases, and 300 from healthy donors. Anti-S1 IgM were detected by monoplex ALBIA-IgM-S1. Comparison with chemiluminescent assays or enzyme-linked immunosorbent assays was performed using commercial tests. Multiplex ALBIA-IgG-S1/N was effective in detecting and quantifying anti–SARS-CoV-2 IgG Abs. Two weeks after first symptoms, sensitivity and specificity were 97.7 and 98.0% (anti-S1), and 100 and 98.7% (anti-N), respectively. Agreement with commercial tests was good to excellent, with a higher sensitivity of ALBIA. ALBIA-IgG-S1/N was positive in 53% of patients up to day 7, and in 75% between days 7 and 13. For ALBIA-IgM-S1, sensitivity and specificity were 74.4 and 98.7%, respectively. Patients in intensive care units had higher IgG Ab levels (Mann–Whitney test, p &amp;lt; 0.05). ALBIA provides a robust method for exploring humoral immunity to SARS-CoV-2. Serology should be performed after 2 weeks following first symptoms, when all COVID-19 (coronavirus disease 2019) patients had at least one anti-S1 or anti-N IgG Ab, illustrating the interest of a multiplex test.

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INTRODUCTION: Keratoconus has a significant impact on patients' quality of life (QoL), from diagnosis to the advanced stages of the disease. The aim of this research was to identify domains of QoL affected by this disease and its treatment. METHODS: Phone interviews were conducted using a semi-structured interview guide, with patients with keratoconus stratified according to their current treatment. A board of keratoconus experts helped identify the guide's main themes. RESULTS: Thirty-five patients (rigid contact lenses, n = 9; cross-linking, n = 9; corneal ring implants, n = 8; and corneal transplantation, n = 9) were interviewed by qualitative researchers. Phone interviews revealed several QoL domains affected by the disease and its treatments: "psychological", "social life", "professional life", "financial costs" and "student life". All domains were impacted, independently of the treatment history. Few differences were found between treatment regimens and keratoconus stages. Qualitative analysis enabled the development of a conceptual framework based on Wilson and Cleary's model for patient outcomes common to all patients. This conceptual model describes the relationship between patients' characteristics, their symptoms, their environment, their functional visual impairment and the impact on their QoL. CONCLUSIONS: These qualitative findings supported the generation of a questionnaire to evaluate the impact of keratoconus and its treatment on patients' QoL. Cognitive debriefings confirmed its content validity. The questionnaire is applicable for all stages of keratoconus and treatments and may help tracking change over time in regular clinical settings. Psychometric validation is yet to be performed before its use in research and clinical practices.

Cytomegalovirus infections. Cytomegalovirus (CMV) infections, which are common in children and adolescents, are often asymptomatic or with little specific signs. When they occur in adults, clinical forms may be more severe even in the immunocompetent. CMV is responsible for significant morbidity and mortality in transplant patients. In pregnant women, congenital CMV infection can lead to neurosensory damages requiring diagnosis and early management. The diagnosis of primary infection is based on serology, whereas the monitoring of infection in immunocompromised patients requires the use of polymerase chain reaction. As screening for congenital infection by serology is not recommended so far, it will be realized in an evocative context. Therapeutic options are still limited and expose to haematological or renal toxicity, but new antivirals (maribavir, letermovir) should be available soon to optimize therapeutic management.

Human cytomegalovirus (HCMV) is one of the most important causes of complications in immunocompromised patients and congenital infections. HCMV could also represent an interesting target for treatment to limit the progression of glioblastoma, a highly aggressive tumor. Ganciclovir, foscarnet and cidofovir, which interfere with the activity of the viral polymerase pUL54, are widely used in the treatment of transplant patients. However, their use in pregnant women remains limited or even contraindicated. On the other hand, hyperimmune immunoglobulins and valaciclovir have been shown to have a protective effect on the fetus. However, the toxicity of these treatments and the emergence of resistance mean that new therapeutic strategies need to be identified. Letermovir and maribavir have been developed to inhibit new targets, respectively the terminase complex and UL97 protein kinase. Their respective indications are the prevention of HCMV infection in haematopoietic stem cell transplant patients and the treatment of refractory HCMV infections. Finally, with the development of mRNA vaccines, the hope of one day seeing a prophylactic HCMV vaccine has never been greater. New therapeutic approaches are also being explored, but they still require extensive preclinical and clinical evaluation.