Enhancing Candida auris Surveillance in High-Risk Settings by Implementing a High-Throughput Molecular Assay on the Hologic Fusion Open Access Platform.

Candida auris, a resilient pathogenic yeast with frequent multidrug resistance, presents a persistent challenge in healthcare settings. The timely identification of C. auris is crucial for infection control and prevention, especially in facilities facing unique hurdles, such as our institution, which serves four major hospitals and approximately 80% of the Texas inmate population. Understaffing, communal living, and financial constraints exacerbate infection control issues. To address common staff shortages, streamline testing services, and enhance testing efficiency, there was a pressing need for rapid and high-throughput detection of C. auris. This study presents the validation and utility of an assay implemented on the Hologic Fusion Open Access platform using samples collected from high-risk patients' axilla and groin areas, as well as environmental swab samples from patient rooms. Our assay complemented efforts to control C. auris outbreaks within our healthcare system, providing valuable insights into its presence within surveillance samples. This assay demonstrated the value of high-throughput molecular detection platforms in challenging healthcare environments by aiding infection preventionists in containing the spread of C. auris and preventing nosocomial infections. Our research contributes essential data on the suitability and performance of the Hologic Fusion Open Access platform for C. auris detection. These findings hold significant implications for enhancing surveillance and control measures in high-risk settings, making a significant impact on the field of infection control and prevention.

Otitis media: Interactions between host and environment, immune and inflammatory responses.

OBJECTIVE: To review and highlight progress in otitis media (OM) research in the areas of immunology, inflammation, environmental influences and host-pathogen responses from 2019 to 2023. Opportunities for innovative future research were also identified. DATA SOURCES: PubMed database of the National Library of Medicine. REVIEW METHODS: Key topics were assigned to each panel member for detailed review. Search of the literature was from June 2019 until February 2023. Draft reviews were collated, circulated, and discussed among panel members at the 22nd International Symposium on Recent Advances in Otitis Media in June 2023. The final manuscript was prepared and approved by all the panel members. CONCLUSIONS: Important advances were identified in: environmental influences that enhance OM susceptibility; polymicrobial middle ear (ME) infections; the role of adaptive immunity defects in otitis-proneness; additional genes linked to OM; leukocyte contributions to OM pathogenesis and recovery; and novel interventions in OM based on host responses to infection. Innovative areas of research included: identification of novel bacterial genes and pathways important for OM persistence, bacterial adaptations and evolution that enhance chronicity; animal and human ME gene expression, including at the single-cell level; and Sars-CoV-2 infection of the ME and Eustachian tube.

A cluster investigation of Candida auris among hospitalized incarcerated patients.

Objective: Investigate and mitigate a cluster of Candida auris cases among incarcerated patients in a maximum-security prison hospital utilizing contact tracing, screening, whole genome sequencing, and environmental sampling and decontamination. Design: Outbreak investigation. Setting: Inpatient prison hospital affiliated with an academic tertiary referral center. Patients: Inmates of the Texas Department of Criminal Justice. Methods: Epidemiologic and environmental investigations were conducted including contact tracing, point prevalence surveys, and environmental sampling. Whole genome sequencing was performed on positive patient isolates. Results: Following a clinical case of C. auris fungemia, 344 patients underwent C. auris surveillance screening. Eight (2.3%) patients were identified with C. auris colonization. All patients were male. Our index patient was the only clinical case and death. Whole genome sequencing was performed on the nine patient isolates. All isolates were clade III (Africa) and clustered together with the largest SNP difference being 21. Environmental cultures from 7 of 61 rooms (11.5%) were positive following terminal disinfection with bleach. Sites nearest to the patient were most often positive including the hospital bed rails and bedside table. The transmission cluster was successfully mitigated within 60 days of identification. Conclusions: Implementation of an aggressive surveillance and decontamination program resulted in mitigation of a C. auris transmission cluster among our incarcerated patients. This investigation provides valuable insight into C. auris transmission in the incarcerated population, which is not considered a classic high-risk population as well as the challenges faced to stop transmission in a facility that requires the use of shared patient environments.

Atypical Systemic Neonatal Herpes Diagnosed Incidentally in Twin Infants.

Neonatal herpes simplex virus (HSV) infections are serious infections that usually occur in the first few weeks of life. Infants generally present with mucocutaneous lesions, central nervous system infection, and/or systemic disease. In this case report, we describe a set of twins that had unexpected presentations of neonatal HSV. Twin A was diagnosed incidentally on routine eye exam, and Twin B was diagnosed only because his twin was found to be infected; both infants were still hospitalized and were beyond 1 month of age. These twins exhibited atypical manifestations that diverge from the 3 main categories of neonatal HSV and expand our understanding of the spectrum of disease.

Outbreak of coronavirus disease 2019 (COVID-19) among operating room staff of a tertiary referral center: An epidemiologic and environmental investigation.

OBJECTIVE: Investigate an outbreak of coronavirus disease 2019 (COVID-19) among operating room staff utilizing contact tracing, mass testing for severe acute respiratory coronavirus virus 2 (SARS-CoV-2), and environmental sampling. DESIGN: Outbreak investigation. SETTING: University-affiliated tertiary-care referral center. PATIENTS: Operating room staff with positive SARS-CoV-2 molecular testing. METHODS: Epidemiologic and environmental investigations were conducted including contact tracing, environmental surveys, and sampling and review of the operating room schedule for staff-to-staff, staff-to-patient, and patient-to-staff SARS-CoV-2 transmission. RESULTS: In total, 24 healthcare personnel (HCP) tested positive for SARS-CoV-2, including nurses (29%), surgical technologists (25%), and surgical residents (16%). Moreover, 19 HCP (79%) reported having used a communal area, most commonly break rooms (75%). Overall, 20 HCP (83%) reported symptomatic disease. In total, 72 environmental samples were collected from communal areas for SARS-CoV-2 genomic testing; none was positive. Furthermore, 236 surgical cases were reviewed for transmission: 213 (90%) had negative preoperative SARS-CoV-2 testing, 21 (9%) had a positive test on or before the date of surgery, and 2 (<1%) did not have a preoperative test performed. In addition, 40 patients underwent postoperative testing (mean, 13 days to postoperative testing), and 2 returned positive results. Neither of these 2 cases was linked to our outbreak. CONCLUSIONS: Complacency in infection control practices among staff during peak community transmission of SARS-CoV-2 is believed to have driven staff-to-staff transmission. Prompt identification of the outbreak led to rapid interventions, ultimately allowing for uninterrupted surgical service.

Respiratory Syncytial Virus-associated Acute Otitis Media in Infants and Children.

Despite recent declines in the incidence of acute otitis media (AOM), more than 5 million cases and 5-6 million primary AOM visits still occur in young children in the United States, resulting in $4.4 billion direct medical costs annually. Our aims in this review are to describe the role of respiratory syncytial virus (RSV) in the etiology of AOM, discuss the prospect of prevention of RSV-associated AOM through immunization, and suggest future research strategies to assess the impact of immunization on RSV-associated AOM.

A2ML1 and otitis media: novel variants, differential expression, and relevant pathways.

A genetic basis for otitis media is established, however, the role of rare variants in disease etiology is largely unknown. Previously a duplication variant within A2ML1 was identified as a significant risk factor for otitis media in an indigenous Filipino population and in US children. In this report exome and Sanger sequencing was performed using DNA samples from the indigenous Filipino population, Filipino cochlear implantees, US probands, Finnish, and Pakistani families with otitis media. Sixteen novel, damaging A2ML1 variants identified in otitis media patients were rare or low-frequency in population-matched controls. In the indigenous population, both gingivitis and A2ML1 variants including the known duplication variant and the novel splice variant c.4061 + 1 G>C were independently associated with otitis media. Sequencing of salivary RNA samples from indigenous Filipinos demonstrated lower A2ML1 expression according to the carriage of A2ML1 variants. Sequencing of additional salivary RNA samples from US patients with otitis media revealed differentially expressed genes that are highly correlated with A2ML1 expression levels. In particular, RND3 is upregulated in both A2ML1 variant carriers and high-A2ML1 expressors. These findings support a role for A2ML1 in keratinocyte differentiation within the middle ear as part of otitis media pathology and the potential application of ROCK inhibition in otitis media.

Nasopharyngeal microbiota in infants and changes during viral upper respiratory tract infection and acute otitis media.

BACKGROUND: Interferences between pathogenic bacteria and specific commensals are known. We determined the interactions between nasopharyngeal microbial pathogens and commensals during viral upper respiratory tract infection (URI) and acute otitis media (AOM) in infants. METHODS: We analyzed 971 specimens collected monthly and during URI and AOM episodes from 139 infants. The 16S rRNA V4 gene regions were sequenced on the Illumina MiSeq platform. RESULTS: Among the high abundant genus-level nasopharyngeal microbiota were Moraxella, Haemophilus, and Streptococcus (3 otopathogen genera), Corynebacterium, Dolosigranulum, Staphylococcus, Acinetobacter, Pseudomonas, and Bifidobacterium. Bacterial diversity was lower in culture-positive samples for Streptococcus pneumoniae, and Haemophilus influenzae, compared to cultured-negative samples. URI frequencies were positively associated with increasing trend in otopathogen colonization. AOM frequencies were associated with decreasing trend in Micrococcus colonization. During URI and AOM, there were increases in abundance of otopathogen genera and decreases in Pseudomonas, Myroides, Yersinia, and Sphingomonas. Otopathogen abundance was increased during symptomatic viral infection, but not during asymptomatic infection. The risk for AOM complicating URI was reduced by increased abundance of Staphylococcus and Sphingobium. CONCLUSION: Otopathogen genera played the key roles in URI and AOM occurrences. Staphylococcus counteracts otopathogens thus Staphylococcal colonization may be beneficial, rather than harmful. While Sphingobium may play a role in preventing AOM complicating URI, the commonly used probiotic Bifidobacterium did not play a significant role during URI or AOM. The role of less common commensals in counteracting the deleterious effects of otopathogens requires further studies.

Panel 4: Report of the Microbiology Panel.

Objective To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources PubMed database of the National Library of Medicine. Review Methods Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.

Panel 6: Vaccines.

Objective To review the literature on progress regarding (1) effectiveness of vaccines for prevention of otitis media (OM) and (2) development of vaccine antigens for OM bacterial and viral pathogens. Data Sources PubMed database of the National Library of Science. Review Methods We performed literature searches in PubMed for OM pathogens and candidate vaccine antigens, and we restricted the searches to articles in English that were published between July 2011 and June 2015. Panel members reviewed literature in their area of expertise. Conclusions Pneumococcal conjugate vaccines (PCVs) are somewhat effective for the prevention of pneumococcal OM, recurrent OM, OM visits, and tympanostomy tube insertions. Widespread use of PCVs has been associated with shifts in pneumococcal serotypes and bacterial pathogens associated with OM, diminishing PCV effectiveness against AOM. The 10-valent pneumococcal vaccine containing Haemophilus influenzae protein D (PHiD-CV) is effective for pneumococcal OM, but results from studies describing the potential impact on OM due to H influenzae have been inconsistent. Progress in vaccine development for H influenzae, Moraxella catarrhalis, and OM-associated respiratory viruses has been limited. Additional research is needed to extend vaccine protection to additional pneumococcal serotypes and other otopathogens. There are likely to be licensure challenges for protein-based vaccines, and data on correlates of protection for OM vaccine antigens are urgently needed. Implications for Practice OM continues to be a significant health care burden globally. Prevention is preferable to treatment, and vaccine development remains an important goal. As a polymicrobial disease, OM poses significant but not insurmountable challenges for vaccine development.

Zika Virus and Pregnancy: A Review of the Literature and Clinical Considerations.

The latest Zika virus (ZIKV) outbreak has reached epidemic proportions as it spreads throughout South and Central America. In November 2015, the Brazilian Ministry of Health reported a 20-fold increase in the number of cases of neonatal microcephaly, which corresponds geographically and temporally to the ZIKV outbreak. Case reports have provided some evidence of a causal link between maternal ZIKV infection, fetal microcephaly, and intracranial calcifications. The sparse data regarding ZIKV in pregnancy come solely from case reports and personal communications, and recommendations for management of ZIKV exposure during pregnancy are rapidly evolving. Our objective is to review and synthesize the current literature regarding ZIKV as it pertains to pregnancy and provide some assistance to clinicians who may have to manage a pregnant patient with potential exposure to ZIKV. We will also explore certain aspects of related viruses in pregnancy in hopes to shed light on this little-known topic.

Acute Otitis Media and Other Complications of Viral Respiratory Infection.

BACKGROUND: Viral upper and lower respiratory tract infections (URI, LRI) are common in infants. We determined the prevalence of viral URI and its complications, including acute otitis media (AOM) and LRI, and assessed the effect of bacterial-viral interactions, and genetic and environmental risks on AOM development. METHODS: Healthy infants were enrolled from near birth and followed to the first episode of AOM up to 12 months of age. Nasopharyngeal specimens were collected at monthly intervals (months 1-6, 9) and during viral URI episodes for bacterial culture and viral polymerase chain reaction studies. Subjects were followed closely for AOM development. RESULTS: A total of 367 infants were followed for 286 child-years; 887 URI (305 infants) and 180 AOM episodes (143 infants) were documented. Prevalence of URI, LRI, and AOM in the first year was 3.2, 0.25, and 0.67 per child-year, respectively. Cumulative AOM incidence by ages 3, 6, and 12 months was 6%, 23%, and 46%. Infants with and without AOM had 4.7 and 2.3 URI episodes per child-year, respectively (P < .002). Pathogenic bacterial colonization rates by month were significantly higher in infants with AOM (P < .005). Breastfeeding reduced both URI and AOM risks (P < .05). Significant bacterial-viral interactions occurred with Moraxella catarrhalis and a variety of respiratory viruses and altered URI and AOM risks. CONCLUSIONS: Almost half of infants experienced AOM by age 1. Important AOM risk factors included frequent viral URI, pathogenic bacterial colonization, and lack of breastfeeding. Bacterial-viral interactions may play a significant role in AOM pathogenesis and deserve further investigation.

Use of symptoms and risk factors to predict acute otitis media in infants.

OBJECTIVES: Infants and children with upper respiratory tract infection (URI) often have concurrent acute otitis media (AOM). Young infants have fewer specific symptoms than older children. The purpose of this study was to evaluate the usefulness of symptoms and other risk factors in predicting the presence of AOM in infants. METHODS: Healthy infants, age less than four weeks, were enrolled and followed prospectively for up to age one year. Infants were scheduled for a research visit when their parents noted the onset of symptoms. At each URI visit, parents first reported the severity of symptoms. An investigator then diagnosed the presence or absence of concurrent AOM. Risk factors and symptom scores for infants with and without AOM were studied. RESULTS: Infants (N=193, mean age at first URI 3.9±2.5 months) experienced 360 URI episodes and 63 AOM events. Symptoms consisting of fever, earache, poor feeding, restless sleep, and irritability together (ETG-5) were statistically associated with the prediction of AOM (P=0.006). A multiple variable statistical model (J-Score) that included day care attendance, age, severity of cough and earache best predicted AOM (P<0.001), with 95% specificity. Both ETG-5 and J-score yielded relatively low sensitivity for AOM prediction. CONCLUSIONS: In infants with URI in the first year of life, severity of symptoms was significantly associated with concurrent AOM. Daycare attendance, presence and severity of earache and cough added to better correlation. These observations may have clinical application in identification of infants at risk for AOM.

A neonate born with Mycobacterium cosmeticum bacteraemia.

Mycobacterium cosmeticum is a rapidly growing mycobacterium that was recently identified. However, its role in human infection has not been well described. We present a case of an extremely premature neonate born with bacteraemia due to M. cosmeticum that resolved without sequelae. The infection likely occurred during a prolonged intrauterine transfusion procedure.

Rare A2ML1 variants confer susceptibility to otitis media.

A duplication variant within the middle ear-specific gene A2ML1 cosegregates with otitis media in an indigenous Filipino pedigree (LOD score = 7.5 at reduced penetrance) and lies within a founder haplotype that is also shared by 3 otitis-prone European-American and Hispanic-American children but is absent in non-otitis-prone children and >62,000 next-generation sequences. We identified seven additional A2ML1 variants in six otitis-prone children. Collectively, our studies support a role for A2ML1 in the pathophysiology of otitis media.

Factors Affecting Staphylococcus aureus Colonization of the Nasopharynx in the First 6 Months of Life.

BACKGROUND: Staphylococcal aureus (SA) colonization in early infancy is common, but the pattern and factors affecting its acquisition and persistence in the first few months of life are not well studied. The aim is to study the rate of SA nasopharyngeal (NP) colonization at monthly intervals in the first 6 months of life and its association with environmental and host factors and other pathogenic NP bacteria. METHODS: Data from a prospective study were analyzed on bacterial cultures of 1765 NP swabs from 367 infants who were followed from birth to 6 months of age. Demographic, breastfeeding, cigarette smoke exposure and day care attendance data were collected at each monthly visit. RESULTS: The rate of infants colonized with SA was highest at age 1 month (25%) and declined to lowest rate by age 6 months (12%). The proportion of SA strains that was methicillin-resistant SA was also highest at age 1 month and declined rapidly by age 4 months (18% vs. 6%, P = 0.05). Colonization with Streptococcus pneumoniae (SP), nontypeable Haemophilus influenzae (NTHI) and Moraxella catarrhalis (MC) increased at different rates up to age 6 months. Univariate analysis showed that SA colonization rate was significantly lower with increasing age, black race, day care attendance, and colonization with NTHI, MC and SP (P < 0.05). Multivariate analysis showed that this effect was independently associated only with increasing age and MC colonization (P < 0.05). Furthermore, the time to first acquisition of SA from one month of age onwards was significantly associated with day care attendance, and NTHI and MC colonization. None of the infants colonized with SA developed SA infections through age 6 months. CONCLUSIONS: SA colonization of NP begins very early in life and declines quickly. Methicillin-resistant SA has lower ability to maintain prolonged colonization status than methicillin-susceptible strains in the first 6 months of life. As the NP is colonized with other respiratory bacterial pathogens, the colonization with SA declines; however, this effect is stronger with Gram-negative bacteria, such as NTHI and MC.

Symptomatic and asymptomatic respiratory viral infections in the first year of life: association with acute otitis media development.

BACKGROUND: Sensitive diagnostic assays have increased the detection of viruses in asymptomatic individuals. The clinical significance of asymptomatic respiratory viral infection in infants is unknown. METHODS: High-throughput, quantitative polymerase chain reaction assays were used to detect 13 common respiratory viruses from nasopharyngeal specimens collected during 2028 visits from 362 infants followed from near birth up to 12 months of age. Specimens were collected at monthly interval (months 1-6 and month 9) and during upper respiratory tract infection (URTI) episodes. Subjects were followed closely for acute otitis media (AOM) development. RESULTS: Viruses were detected in 76% of 394 URTI specimens and 27% of asymptomatic monthly specimens. Rhinovirus was detected most often; multiple viruses were detected in 29% of the specimens. Generalized mixed-model analyses associated symptoms with increasing age and female sex; detection of respiratory syncytial virus (RSV), influenza, rhinovirus, metapneumovirus, and adenovirus was highly associated with symptoms. Increasing age was also associated with multiple virus detection. Overall, 403 asymptomatic viral infections in 237 infants were identified. Viral load was significantly higher in URTI specimens than asymptomatic specimens but did not differentiate cases of URTI with and without AOM complication. The rate of AOM complicating URTI was 27%; no AOM occurred following asymptomatic viral infections. AOM development was associated with increasing age and infection with RSV, rhinovirus, enterovirus, adenovirus, and bocavirus. CONCLUSIONS: Compared to symptomatic infection, asymptomatic viral infection in infants is associated with young age, male sex, low viral load, specific viruses, and single virus detection. Asymptomatic viral infection did not result in AOM.