Corrigendum to "Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI)" [The Lancet Regional Health - Europe 40 (2024) 100892].

[This corrects the article DOI: 10.1016/j.lanepe.2024.100892.].

Mollaret's Meningitis due to Herpes Simplex Virus 2: A Case Report and Review of the Literature.

Mollaret's meningitis is a rare neurological disorder characterized by recurrent episodes of aseptic lymphocytic meningitis, often associated with herpes simplex virus 2 (HSV-2) infection. We report the case of a 39 y.o. Italian woman who experienced four episodes of aseptic lymphocytic meningitis between 2004 and 2023, diagnosed as Mollaret's meningitis. In each episode, the patient presented with fever, severe headache and photophobia. In two episodes cutaneous vesicles in the left gluteal area preceding meningitis symptoms were also reported. A diagnostic evaluation included a physical-chemical analysis and a real-time PCR of the cerebrospinal fluid (CSF). The CSF presented pleocytosis with lymphocytic predominance and a positive HSV-2 load, with a peak of 1234 copies/mL. The patient was treated successfully with acyclovir, and the symptoms resolved without neurological sequelae. This case highlights the importance of comprehensive diagnostic testing and vigilant monitoring to manage Mollaret's syndrome effectively.

Epidemiological impact of human adenovirus as causative agent of respiratory infections: An Italian multicentre retrospective study, 2022-2023.

Human adenoviruses are the causative agents of 5-7% of viral respiratory infections, mainly caused by species B and C. They can infect all age groups, but children are usually at high risk of infections. Adenovirus epidemiology is well documented in East-Asian countries but little is known about adenovirus circulation in Europe in recent years. This multicentre retrospective study aimed to investigate the circulation and molecular epidemiology of hAdVs. This surveillance collected a total of 54463 respiratory specimens between January 1, 2022 and June 20, 2023 were tested for the presence of respiratory viruses. Our results showed that adenovirus was detected in 6.6 % of all cases of acute respiratory infection included in the study and the median age of positive patients was 3 years, with male children in 1-2 years age group being the most affected. 43.5 % of adenovirus cases were co-infected with at least one other respiratory virus, and rhinovirus was co-detected in 54 % of cases. Genotyping of adenovirus allowed the identification of 6 different genotypes circulating in Italy, among which type B3 was the most frequently detected.

Complete genome sequence of a Listeria monocytogenes serotype 1 isolated from a critically ill patient in Italy, 2023.

Listeria monocytogenes, a concerning foodborne pathogen, causes severe infections in vulnerable subjects such as pregnant women and the elderly. In this article, we present the complete genome sequence of P4_LIS, an L. monocytogenes isolated from a patient with invasive bacteria infection.

Antimicrobial resistance determinants in the oropharyngeal microbiome of 'men having sex with men' attending an sexually transmitted infection clinic.

BACKGROUND: 'Men having sex with men' (MSM) represent a key population with a significant prevalence of pharyngeal Neisseria gonorrhoeae (NG) infections and a high rate of antimicrobial resistance genes in the pharyngeal microbiome. As NG can acquire antibiotic resistance genes from other commensal oropharyngeal bacteria, monitoring the prevalence of these resistance determinants is critical to curtail the spread of NG-resistant strains. PURPOSE AND RESEARCH DESIGN: Here, we assessed the distribution of five resistance genes (pen (A), mtr (R), gyr (A), par (C), msr (D)) in the oropharynx of 164 MSM, attending an Outpatient clinic for STI screening. RESULTS: The most frequently detected resistance gene was msr (D) (88.4%), followed by gyr (A) (67.1%). The distribution of resistance genes was not influenced by pharyngeal gonorrhea nor by the HIV status, whereas a younger age was associated with mtr (R) presence (p = .008). Subjects using mouthwash exhibited significantly lower levels of mtr (R) (p = .0005). Smoking habit was associated with a higher prevalence of par (C) (p = .02). A noteworthy association was observed between the presence of msr (D) gene and the use of antibiotics (p = .014). CONCLUSIONS: Our findings reveal an enrichment of antimicrobial resistance genes in the oropharynx of MSM. These insights could aid in the development of screening programs and antimicrobial stewardship initiatives targeting populations at heightened risk of pharyngeal gonorrhea.

Evaluation of an automated rapid phenotypic antimicrobial susceptibility testing (ASTar, Q-linea AB) applied directly on blood cultures bottles positive for Gram-negative pathogens.

We evaluated the performance of a new rapid phenotypic antimicrobial susceptibility test (ASTar; Q-linea AB) on Gram-negative bacilli, directly from positive blood cultures bottles. MIC values obtained by the routine reference method (Microscan, Beckman Coulter) were compared to the ones provided by the tested method (ASTar). ASTar demonstrated an overall essential agreement of 98% and a category agreement of 96.1%. The overall rate of major errors and very major errors was 2.5% and 3.3%, respectively. ASTar can represent a rapid, simple, and reliable method to speed up information about antimicrobial susceptibility of Gram-negative pathogens from positive blood culture bottles.

Efficacy of the Combined Intrastromal Injection of Voriconazole and Amphotericin B in Recalcitrant Fungal Keratitis.

This study aims to report the efficacy of a combined intrastromal injection in optimizing the outcome of severe mycotic keratitis. Herein, we report a case series of 20 consecutive patients with positive fungal cultures not responding to topical antifungal treatment. Patients received cycles of intrastromal injections of voriconazole (50 µg/0.1 mL) and amphotericin B (2.5 µg/0.1 mL); all patients continued their topical antifungal therapy. The organisms isolated were Fusarium (n = 5), Aspergillus (n = 4), Candida (n = 4), Rhodotorula (n = 2), Penicillium (n = 2), Alternaria (n = 1), Bipolaris (n = 1), and Curvularia (n = 1). The size of the infiltrate varied from 6.5 to 1.5 mm. At presentation, the best corrected visual acuity (BCVA, namely, the best visual acuity achieved with glasses, if needed) was less than 20/400 in all patients, improving to better than 20/400 in eleven patients. Seven patients required surgical intervention; four of them underwent penetrating keratoplasty (PK) à chaud one month after the first intrastromal injection. Patients who underwent surgery achieved a BCVA of 20/40 or better. Combined intrastromal injections before therapeutic penetrating keratoplasty (TPK) effectively reduced ulcer size and graft diameter, preventing infection recurrence. Our results highlight the efficacy of combined intrastromal injections in optimizing outcomes for severe mycotic keratitis undergoing TPK.

Complete genome sequence of invasive Streptococcus pneumoniae serotype 11A causing meningitis in an adult patient, Italy 2022.

Streptococcus pneumoniae is a major global health concern, being a common cause of meningitis in both children and adults. Here, we report the complete genome sequence of P10_PNE_LCR, a S. pneumoniae 11A strain isolated in Northern Italy from an adult patient diagnosed with meningitis.

Consensus recommendation for prenatal, neonatal and postnatal management of congenital cytomegalovirus infection from the European congenital infection initiative (ECCI).

Congenital cytomegalovirus (cCMV) infection carries a significant burden with a 0.64% global prevalence and a 17-20% chance of serious long-term effects in children. Since the last guidelines, our understanding, particularly regarding primary maternal infections, has improved. A cCMV guidelines group was convened under the patronage of the European Society of Clinical Virology in April 2023 to refine these insights. The quality and validity of selected studies were assessed for potential biases and the GRADE framework was employed to evaluate quality of evidence across key domains. The resulting recommendations address managing cCMV, spanning prevention to postnatal care. Emphasizing early and accurate maternal diagnosis through serological tests enhances risk management and prevention strategies, including using valaciclovir to prevent vertical transmission. The guidelines also strive to refine personalized postnatal care based on risk assessments, ensuring targeted interventions for affected families.

The Auditory Pathway in Congenitally Cytomegalovirus-Infected Human Fetuses.

Congenital cytomegalovirus (CMV) infection is the main cause of non-hereditary sensorineural hearing loss (SNHL). In order to shed light on SNHL pathophysiology, we examined the auditory pathway in CMV-infected fetuses; the temporal lobe, in particular the auditory cortex, and the inner ear. We investigated both inner ears and temporal lobes of 20 human CMV-infected fetuses at 21 weeks of gestation. As a negative group, five fetuses from spontaneous miscarriages without CMV infection were studied. Inner ears and temporal lobes were histologically examined, immunohistochemistry for CMV and CMV-PCR were performed. On the auditory cortex, we evaluated the local microglial reaction to the infection. CMV-positive cells were found in 14/20 brains and the damage was classified as severe, moderate, or mild, according to histological features. Fetuses with severe brain damage had a statistically higher temporal lobe viral load and a higher number of activated microglial cells in the auditory cortex compared to fetuses with mild brain damage (p: 0.01; p: 0.01). In the inner ears, the marginal cells of the stria vascularis were the most CMV positive. In our study, CMV affected the auditory pathway, suggesting a tropism for this route. In addition, in the auditory cortex, microglial activation may favor further tissue damage contributing to hearing loss.

Clonal Dissemination of Candida auris Clinical Isolates in Northern Italy, 2021.

Candida auris is a concerning pathogen in health care due to its ability to spread in medical settings. In this study, we characterized the genome of three C. auris clinical isolates collected in the Emilia-Romagna region of Northeastern Italy from January 2020 to May 2021. Whole-genome sequencing was performed using Illumina iSeq 100 and Oxford Nanopore MinION systems. Genomes were assembled with Flye. Phylogenetic analysis was carried out with RaxML. The ERG11, TAC1b, and FKS1 genes were examined for known substitutions associated with resistance to azoles and caspofungin using Diamond. All three C. auris isolates belonged to clade I (South Asian lineage) and showed high minimum inhibitory concentrations for fluconazole. Two of the three isolates were closely related to the first Italian index case of C. auris occurred in the 2019 and carried similar mutations associated to azole resistance. The third isolate showed a greater phylogenetic distance from these strains and had a different genetic determinant not previously seen in Italy. Our data suggest that two C. auris clinical isolates may have been epidemiologically related to the first outbreak previously observed in Italy, while the remaining isolate may have originated from a different source. Further research is needed to understand C. auris transmission and resistance and to control its spread.

Antimicrobial Resistance of Genital Mycoplasma and Ureaplasma: A Multicentre Study Over a 5-Year Period in Italy (2017-2021).

Updated data on genital Mollicutes prevalence and antimicrobial susceptibility can help provide guidance for antibiotic stewardship and set up effective strategies for infection control policies. In this multicentre study, we assessed the prevalence and the resistance profile of Mycoplasma hominis (MH) and Ureaplasma species (U. parvum/U. urealyticum), analyzing data from 21,210 subjects who provided urogenital samples for Mollicutes detection by culture over a 5-year period (2017-2021) in two high-density urban areas in the North of Italy (i.e., Bologna and Lecco). Overall prevalence of Mollicutes infection was 22.3%, with women showing a significantly higher detection rate than men (p < 0.00001). The prevalence decreased with age (highest prevalence <30 years) and over the years considered. Ureaplasma strains were much more frequently detected (62.3%) compared to MH (8.3%) and to mixed infections (29.4%). Ureaplasma species showed high levels of ciprofloxacin resistance (39.5%), whereas MH strains were nonsusceptible to azithromycin and roxithromycin in about 60% of cases. Over time, a significant decrease of resistance to azithromycin and doxycycline was detected (p < 0.0001 and 0.0004, respectively), in parallel with an important increase of ciprofloxacin-resistance levels (p < 0.0001). Overall, our results revealed that minocycline and josamycin can be first-line drugs for Mollicutes empirical treatment.

First isolation of Mycobacterium saskatchewanense from medical devices.

Mycobacterium saskatchewanense is a species of pigmented slow-growing Non-Tuberculous Mycobacteria (NTM), positive for Mycobacterium avium complex (MAC) by AccuProbe system. MAC organisms have frequently been isolated from different medical devices. This is the first study reporting isolation of M. saskatchewanense from medical devices and highlights the importance of correctly identifying the NTMs that often colonize sanitary water. GenoType Mycobacterium CM CE-IVD kit (CM) was used as the first step of NTM strain identification, and all positive cultures were found to be components of MAC. Then, GenoType NTM-DR CE-IVD kit (NTM-DR) was used to differentiate the different species. Sub-culture on solid media were used for: (i) phenotypical confirmation by colony morphology and Matrix-Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometry; (ii) molecular confirmation by Next Generation Sequencing. All positive cultures were identified as M. intracellulare by CM and NTM-DR assays, whereas colony morphology showed bright yellow scotochromogenic growth. MALDI-TOF analyses identified the strains as M. saskatchewanense with a high score, and identification was confirmed by NGS analysis based on the hsp-65 region. This paper suggests that it is important to actively monitor NTM contamination in medical devices that use sanitary water, to prevent the possibility of patients becoming infected.

Non-pathogenic Neisseria species of the oropharynx as a reservoir of antimicrobial resistance: a cross-sectional study.

Commensal Neisseria species of the oropharynx represent a significant reservoir of antimicrobial resistance determinants that can be transferred to Neisseria gonorrhoeae. This aspect is particularly crucial in 'men having sex with men' (MSM), a key population in which pharyngeal co-colonization by N. gonorrhoeae and non-pathogenic Neisseria species is frequent and associated with the emergence of antimicrobial resistance. Here, we explored the antimicrobial susceptibility of a large panel of non-pathogenic Neisseria species isolated from the oropharynx of two populations: a group of MSM attending a 'sexually transmitted infection' clinic in Bologna (Italy) (n=108) and a group of males representing a 'general population' (n=119). We collected 246 strains, mainly belonging to N. subflava (60%) and N. flavescens (28%) species. Their antimicrobial susceptibility was evaluated assessing the minimum inhibitory concentrations (MICs) for azithromycin, ciprofloxacin, cefotaxime, and ceftriaxone using E-test strips. Overall, commensal Neisseria spp. showed high rates of resistance to azithromycin (90%; median MICs: 4.0 mg/L), and ciprofloxacin (58%; median MICs: 0.12 mg/L), whereas resistance to cephalosporins was far less common (<15%). Neisseria strains from MSM were found to have significantly higher MICs for azithromycin (p=0.0001) and ciprofloxacin (p<0.0001) compared to those from the general population. However, there was no significant difference in cephalosporin MICs between the two groups. The surveillance of the antimicrobial resistance of non-pathogenic Neisseria spp. could be instrumental in predicting the risk of the spread of multi-drug resistant gonorrhea. This information could be an early predictor of an excessive use of antimicrobials, paving the way to innovative screening and prevention policies.

A 12-month follow-up of the immune response to SARS-CoV-2 primary vaccination: evidence from a real-world study.

A real-world population-based longitudinal study, aimed at determining the magnitude and duration of immunity induced by different types of vaccines against COVID-19, started in 2021 by enrolling a cohort of 2,497 individuals at time of their first vaccination. The study cohort included both healthy adults aged ≤65 years and elderly subjects aged >65 years with two or more co-morbidities. Here, patterns of anti-SARS-CoV-2 humoral and cell-mediated specific immune response, assessed on 1,182 remaining subjects, at 6 (T6) and 12 months (T12) after the first vaccine dose, are described. At T12 median anti-Spike IgG antibody levels were increased compared to T6. The determinants of increased anti-Spike IgG were the receipt of a third vaccine dose between T6 and T12 and being positive for anti-Nucleocapside IgG at T12, a marker of recent infection, while age had no significant effect. The capacity of T12 sera to neutralize in vitro the ancestral B strain and the Omicron BA.5 variant was assessed in a subgroup of vaccinated subjects. A correlation between anti-S IgG levels and sera neutralizing capacity was identified and higher neutralizing capacity was evident in healthy adults compared to frail elderly subjects and in those who were positive for anti-Nucleocapside IgG at T12. Remarkably, one third of T12 sera from anti-Nucleocapside IgG negative older individuals were unable to neutralize the BA.5 variant strain. Finally, the evaluation of T-cell mediated immunity showed that most analysed subjects, independently from age and comorbidity, displayed Spike-specific responses with a high degree of polyfunctionality, especially in the CD8 compartment. In conclusion, vaccinated subjects had high levels of circulating antibodies against SARS-CoV-2 Spike protein 12 months after the primary vaccination, which increased as compared to T6. The enhancing effect could be attributable to the administration of a third vaccine dose but also to the occurrence of breakthrough infection. Older individuals, especially those who were anti-Nucleocapside IgG negative, displayed an impaired capacity to neutralize the BA.5 variant strain. Spike specific T-cell responses, able to sustain immunity and maintain the ability to fight the infection, were present in most of older and younger subjects assayed at T12.

Determinants of Anti-S Immune Response at 12 Months after SARS-CoV-2 Vaccination in a Multicentric European Cohort of Healthcare Workers-ORCHESTRA Project.

BACKGROUND: The effectiveness of the immunity provided by SARS-CoV-2 vaccines is an important public health issue. We analyzed the determinants of 12-month serology in a multicenter European cohort of vaccinated healthcare workers (HCW). METHODS: We analyzed the sociodemographic characteristics and levels of anti-SARS-CoV-2 spike antibodies (IgG) in a cohort of 16,101 vaccinated HCW from eleven centers in Germany, Italy, Romania, Slovakia and Spain. Considering the skewness of the distribution, the serological levels were transformed using log or cubic standardization and normalized by dividing them by center-specific standard errors. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of one standard deviation of log or cubic antibody level and the corresponding 95% confidence interval (CI) for different factors and combined them in random-effects meta-analyses. RESULTS: We included 16,101 HCW in the analysis. A high antibody level was positively associated with age (RR = 1.04, 95% CI = 1.00-1.08 per 10-year increase), previous infection (RR = 1.78, 95% CI 1.29-2.45) and use of Spikevax [Moderna] with combinations compared to Comirnaty [BioNTech/Pfizer] (RR = 1.07, 95% CI 0.97-1.19) and was negatively associated with the time since last vaccine (RR = 0.94, 95% CI 0.91-0.98 per 30-day increase). CONCLUSIONS: These results provide insight about vaccine-induced immunity to SARS-CoV-2, an analysis of its determinants and quantification of the antibody decay trend with time since vaccination.

Clonal dissemination of Klebsiella pneumoniae resistant to cefiderocol, ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam co-producing KPC and OXA-181 carbapenemase.

Objectives: Herein, we describe the epidemiology of carbapenemase-producing Enterobacterales (CPE) before and during the COVID-19 pandemic. Also, we report the emergence of an outbreak of Klebsiella pneumoniae strains co-producing KPC and OXA-181 carbapenemase, resistant to novel ß-lactam/ß-lactamase inhibitors (ßL-ßLICs) and cefiderocol. Methods: CPE were collected during a period of 3 years from 2019 to 2021. Antimicrobial susceptibility testing for novel ßL-ßLICs and cefiderocol was performed by MIC test strips and microdilution with iron-depleted broth. WGS was performed on 10 selected isolates using the Illumina platform, and resistome analysis was carried out by a web-based pipeline. Results: Between January 2019 and December 2021, we collected 1430 carbapenemase producers from 957 patients with infections due to CPE. KPC was the most common carbapenemase, followed by VIM, OXA-48 and NDM. During 2021, we identified 78 K. pneumoniae co-producing KPC and OXA-181 carbapenemases in 60 patients, resistant to meropenem/vaborbactam and imipenem/relebactam. Resistance to ceftazidime/avibactam and cefiderocol was observed respectively in 7 and 8 out of the 10 sequenced K. pneumoniae. Genome analysis showed that all isolates were clonally related, shared a common porin and plasmid content, and carried blaOXA-181 and blaKPC carbapenemases. Specifically, 4 out of 10 isolates carried blaKPC-3, while 6 harboured mutated blaKPC. Of note, KPC producers resistant to ceftazidime/avibactam and harbouring mutated blaKPC exhibited higher MICs of cefiderocol (median MIC 16 mg/L, IQR 16-16) than strains harbouring WT blaKPC-3 (cefiderocol 9 mg/L, IQR 1.5-16). Conclusions: Our results highlight the need for continuous monitoring of CPE to limit widespread MDR pathogens carrying multiple mechanisms conferring resistance to novel antimicrobial molecules.

Measles virus and cytomegalovirus co-infection, in a child with recent SARS-CoV-2 infection, during COVID-19 pandemic: a case report.

Measles virus (MV) and cytomegalovirus (CMV) may cause pediatric infection. We report the first described case of MV and CMV co-infection in an unvaccinated 13-mo-old girl, with a recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, occurred during coronavirus disease 2019 (COVID-19) pandemic. The COVID-19 pandemic context, combined with patient's complex clinical scenario, presenting symptoms as persistent fever, diarrhea, vomiting, maculopapular rash and edema, in addition to high level of inflammatory markers, led to a suspicion of multisystemic inflammatory syndrome in children (MIS-C). The final diagnosis and the successfully management of the case, discharged after resolution of symptoms, was achieved by a proper virological diagnosis and a close two-way cooperation between pediatricians and clinical microbiologists. The report mainly highlights that awareness about measles should be raised in unvaccinated patients with consistent symptoms, even in the COVID-19 era.