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BackgroundInfection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2.MethodsWe performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs.ResultsAmong 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001).ConclusionsIP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

BACKGROUND: Pre-exposure prophylaxis for COVID-19 with tixagevimab/cilgavimab (T/C) received Emergency Use Authorization (EUA) based on results of a clinical trial conducted prior to the emergence of the Omicron variant. The clinical effectiveness of T/C has not been well described in the Omicron era. We examined the incidence of symptomatic illness and hospitalizations among T/C recipients when Omicron accounted for virtually all local cases. METHODS: Through retrospective electronic medical record chart review, we identified patients who received T/C between January 1 -July 31, 2022 within our quaternary referral health system. We determined the incidence of symptomatic COVID-19 infections and hospitalizations due to or presumed to be caused by early Omicron variants before and after receiving T/C (pre-T/C and post-T/C). Chi square and Mann-Whitney Wilcoxon two-sample tests were used to examine differences between the characteristics of those who got COVID-19 before or after T/C prophylaxis, and rate ratios (RR) and 95% confidence intervals (CI) were calculated to assess differences in hospitalization rates for the two groups. RESULTS: Of 1295 T/C recipients, 105 (8.1%) developed symptomatic COVID-19 infection before receiving T/C, and 102 (7.9%) developed symptomatic disease after receiving it. Of the 105 patients who developed symptomatic infection pre-T/C, 26 (24.8%) were hospitalized, compared with six of the 102 patients (5.9%) who were diagnosed with COVID-19 post-T/C (RR = 0.24; 95% CI = 0.10-0.55; p = 0.0002). Seven of the 105 (6.7%) patients infected pre-T/C, but none of the 102 infected post-T/C required ICU care. No COVID-related deaths occurred in either group. The majority of COVID-19 cases among those infected pre-T/C treatment occurred during the Omicron BA.1 surge, while the majority of post-T/C cases occurred when Omicron BA.5 was predominant. In both groups, having at least one dose of vaccine strongly protected against hospitalization (pre-T/C group RR = 0.31, 95% CI = 0.17-0.57, p = 0.02; post-T/C group RR = 0.15; 95% CI = 0.03-0.94; p = 0.04). CONCLUSION: We identified COVID-19 infections after T/C prophylaxis. Among patients who received T/C at our institution, COVID-19 Omicron cases occurring after T/C were one-fourth as likely to require hospitalization compared to those with Omicron prior to T/C. However, due to the presence of changing vaccine coverage, multiple therapies, and changing variants, the effectiveness of T/C in the Omicron era remains difficult to assess.

BackgroundThe microbiome of the human gut serves a role in a number of physiological processes, but can be altered through effects of age, diet, and disturbances such as antibiotics. Several studies have demonstrated that commonly used antibiotics can have sustained impacts on the diversity and the composition of the gut microbiome. The impact of the two most overused antibiotics, azithromycin, and amoxicillin, in the human microbiome has not been thoroughly described. In this study, we recruited a group of individuals and unrelated controls to decipher the effects of the commonly used antibiotics amoxicillin and azithromycin on their gut microbiomes.ResultsWe characterized the gut microbiomes by metagenomic sequencing followed by characterization of the resulting microbial communities. We found that there were clear and sustained effects of the antibiotics on the gut microbial community with significant alterations in the representations of Bifidobacterium species in response to azithromycin (macrolide antibiotic). These results were supported by significant increases identified in putative antibiotic resistance genes associated with macrolide resistance. Importantly, we did not identify these trends in the unrelated control individuals. There were no significant changes observed in other members of the microbial community.ConclusionsAs we continue to focus on the role that the gut microbiome plays and how disturbances induced by antibiotics might affect our overall health, elucidating members of the community most affected by their use is of critical importance to understanding the impacts of common antibiotics on those who take them. Clinical Trial Registration Number NCT05169255. This trial was retrospectively registered on 23-12-2021.

We present a case where Hyphopichia burtonii, a yeast, speciated from peritoneal fluid in a cirrhotic patient with secondary peritonitis. The patient, a man in his 60s with decompensated cirrhosis, was admitted for an upper gastrointestinal (GI) bleed. On admission, he was treated empirically for spontaneous bacterial peritonitis (SBP) but failed to improve with antibiotics. Serial paracenteses revealed polymicrobial peritonitis and rising peritoneal polymorphonuclear leukocytes (PMNs). These findings raised concerns for secondary peritonitis, prompting an abdominal computed tomography (CT) scan which revealed ischemic bowel. Among the peritoneal microbiota isolated, Hyphopichia burtonii predominated. Hyphopichia burtonii has only recently been reported as a human pathogen, previously it had only reported as a pathogen in bats[1,2].

ObjectiveTo describe the issues related to the assignment of surgical wound classification as it pertains to Otolaryngology-Head & Neck surgery, and to present a simple framework by which providers can assign wound classification.Data sourcesLiterature review.ConclusionSurgical wound classification in its current state is limited in its utility. It has recently been disregarded by major risk assessment models, likely due to inaccurate and inconsistent reporting by providers and operative staff. However, if data accuracy is improved, this metric may be useful to inform the risk of surgical site infection. In an era of quality-driven care and reimbursement, surgical wound classification may become an equally important indicator of quality.

Background: Understanding medication use patterns for patients with COVID-19 will provide needed insight into the evolution of COVID-19 treatment over the course of the SARS-CoV-2 pandemic and aid clinical management considerations. Objectives: To systematically determine most frequently used medications among COVID-19 patients overall and by hospitalization status. Secondary objective was use measurement of medications considered potential therapeutic options. Methods: Retrospective cohort study was performed using data from the University of California COVID Research Data Set (UC CORDS) patients between March 10, 2020, and December 31, 2020. Main outcomes were percentages of patients prescribed medications, overall, by age group, and by comorbidity based on hospitalization status for COVID-19 patients. Use percentage by month of COVID-19 diagnosis was measured. Cumulative count of potential therapeutic options was measured over time. Results: Dataset included 22 896 unique patients with COVID-19 (mean [SD] age, 42.4 [20.4] years; 12 154 [53%] women). Most frequently used medications in patients overall were acetaminophen (21.2%), albuterol (14.9%), ondansetron (13.9%), and enoxaparin (10.8%). Dexamethasone use increased from fewer than 50 total hospitalized patients through April who had received the medication, to more than 500 patients by mid-August. Cumulative count of enoxaparin users was the largest throughout the study period. Conclusion and Relevance: In this retrospective cohort study, across age and comorbidity groups, predominant utilization was for supportive care therapy. Dexamethasone and remdesivir experienced large increases in use. Conversely, hydroxychloroquine and azithromycin use markedly dropped. Medication utilization rapidly shifted toward more evidence-concordant treatment of patients with COVID-19 as rigorous study findings emerged.

Background: The County of San Diego Health and Human Services (SDHHSA) established a goal to vaccinate 1.9 million residents as quickly as possible to attain vaccine induced herd immunity. This strategy would minimize the emergence of more transmissible variants, to which some vaccines may be less effective. With this strategy in mind, UC San Diego Health (UCSDH) collaborated with the local health authorities and the San Diego Padres to build a superstation in downtown San Diego in the parking lot of a baseball stadium. Methods: Building on the experience of rapidly vaccinating the UCSDH workforce in mid-December 2020, UCSDH and SDHHSA partnered to more efficiently distribute SARS-CoV-2 vaccine in San Diego County by building a vaccine superstation. The San Diego Padres offered their parking lot as the site; it was centrally located, easily accessible, quick to set up, and semipermanent. They also provided infrastructure support, event coordination, and internet capability. Occupying a space of ~6.5 acres, the superstation included 12 lanes serving 12 cars each, with ~3 cycles every hour, as well as a pedestrian walk-up station. Altogether, the site had the capacity for >5,000 vaccinations daily. This effort required coordination among administration, healthcare providers, IT specialists, and support staff—a daily workforce of >300 persons. The workforce needs were met using a multipronged approach, including flexible staffing, coordination of volunteers, and recruitment of previously retired providers. The private–public partnership enabled the superstation to be up and running in 5 days. Results: The operation was quickly ramped up to provide >6,000 vaccines daily. Initially only open to healthcare workers, on January 17 the superstation was expanded to persons aged >75 years, with further expansion to those aged ≥65 years on January 23. From January 11 to February 5, >100,000 individuals received their first dose of vaccine at the superstation, corresponding to ~31% of all San Diego county vaccinations. Conclusions: Vaccination of as many people as quickly as possible is essential to controlling the pandemic. Unchecked replication of SARS-CoV-2 allows increases the chance that the virus may develop mutations that render vaccines and therapeutics less effective. Our model vaccine superstation was replicated at 3 more sites around the county, the limited allocation of vaccine has been the only barrier to further expansion. A force of 10 superstations could administer a first dose to the remaining 1.6 million county residents within 32 days.Funding: NoDisclosures: None

IntroductionA nurse-triggered sepsis alert called "Code Sepsis" was implemented for early recognition and management of sepsis. The researchers analyzed its impact on antimicrobial use and identified factors associated with infection as source of Code Sepsis.MethodsThe medical records of hospitalized patients with Code Sepsis between January 1 and June 30, 2018, were reviewed. Patients were classified as "Infection" when probable or definitive infection was identified or "No Infection" when a probable or definitive noninfectious source was identified. Patients were categorized as "Escalation" with addition or change to broader-spectrum antimicrobials or "No Escalation" with no change or change to narrower-spectrum antimicrobials. Escalation was classified as "Indicated" with appropriate escalation or "Not Indicated" with inappropriate escalation. Logistic regression model was used to identify factors associated with Infection as Code Sepsis trigger.ResultsCode Sepsis was activated in 529 patients, with Escalation in 246 (46.5%) and No Escalation in 283 (53.5%) patients. Escalation was Indicated in 157 (63.8%) and Not Indicated in 89 (36.2%) patients. Infection was identified in 356 (67.3%) and No Infection in 173 (32.7%) patients. History of HIV (odds ratio [OR] = 2.75, p = 0.03), temperature > 38.3°C or < 36°C (OR = 2.63, p < 0.01), and respiratory rate > 20/minute (OR = 1.56, p = 0.02) were associated with Infection, while surgery within 3 days (OR = 0.30, p < 0.01) was associated with No Infection.ConclusionOne hospital system's Code Sepsis inadvertently identified patients without infections and led to antimicrobial overuse. By refocusing Code Sepsis on early recognition of severe sepsis and septic shock only, the organization hopes to optimize resource utilization and improve patient outcomes.

BackgroundThere is a pressing need for digital tools that can leverage big data to help clinicians select effective antibiotic treatments in the absence of timely susceptibility data. Clinical presentation and local epidemiology can inform therapy selection to balance the risk of antimicrobial resistance and patient risk. However, data and clinical expertise must be appropriately integrated into clinical workflows.ObjectiveThe aim of this study is to leverage available data in electronic health records, to develop a data-driven, user-centered, clinical decision support system to navigate patient safety and population health.MethodsWe analyzed 5 years of susceptibility testing (1,078,510 isolates) and patient data (30,761 patients) across a large academic medical center. After curating the data according to the Clinical and Laboratory Standards Institute guidelines, we analyzed and visualized the impact of risk factors on clinical outcomes. On the basis of this data-driven understanding, we developed a probabilistic algorithm that maps these data to individual cases and implemented iBiogram, a prototype digital empiric antimicrobial clinical decision support system, which we evaluated against actual prescribing outcomes.ResultsWe determined patient-specific factors across syndromes and contexts and identified relevant local patterns of antimicrobial resistance by clinical syndrome. Mortality and length of stay differed significantly depending on these factors and could be used to generate heuristic targets for an acceptable risk of underprescription. Combined with the developed remaining risk algorithm, these factors can be used to inform clinicians' reasoning. A retrospective comparison of the iBiogram-suggested therapies versus the actual prescription by physicians showed similar performance for low-risk diseases such as urinary tract infections, whereas iBiogram recognized risk and recommended more appropriate coverage in high mortality conditions such as sepsis.ConclusionsThe application of such data-driven, patient-centered tools may guide empirical prescription for clinicians to balance morbidity and mortality with antimicrobial stewardship.

Abstract Background As of June 2, 2020, 67,113 cases and 321 deaths due to Coronavirus Disease 19 (COVID-19) have been reported in healthcare personnel (HCP) in the United States. Given the close contact of HCP with individuals with COVID-19, it is important to quantify the risk of acquiring COVID-19 in the healthcare setting. Methods We conducted a retrospective cohort study of HCP exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at our academic medical center from March 15, 2020 to May 16, 2020. Exposure during the study period was defined as having contact with patients or other HCP with COVID-19 within 6 feet of distance for at least 90 seconds when HCP’s eyes, nose, or mouth were not covered. HCP with exposures were monitored for symptoms consistent with COVID-19 for 14 days from last exposure and those who developed symptoms were tested for SARS-CoV-2 using RT-PCR. Results We identified 33 exposure events; 19 of which were patient-to-HCP exposures and 14 of which were HCP-to-HCP exposures. These 33 events resulted in 959 exposed HCP among whom 238 (25%) developed one or more symptoms of COVID-19 and required SARS-CoV-2 RT-PCR testing. Testing was performed at 7.1 ± 5.0 (mean ± SD) days from exposure. Of the 238 HCP who were tested, 82% were female and 49% were registered nurses (Table 1). Five HCP tested positive for SARS-CoV-2 by RT-PCR, but one was presumed to have acquired the disease from a household member with confirmed COVID-19. Among the four HCP who were infected due to occupational exposure, three were nurses while one was an environmental service worker (Table 1). Conclusion Despite exposures among HCP, the risk of acquiring symptomatic COVID-19 in the healthcare setting was low with less than 1% of HCP with occupational exposure subsequently diagnosed with COVID-19. With the definition of exposure now changed to at least 15 minutes of close contact without personal protective equipment, we anticipate fewer exposures at our healthcare facility and that much of COVID-19 transmission affecting HCP are due to community exposures. Disclosures All Authors: No reported disclosures

Abstract Background The SARS-CoV-2 pandemic remains a major threat worldwide. Healthcare workers (HCWs) are particularly impacted by the COVID-19 pandemic with high infection rates reported from HCWs in hard-hit regions2,3, raising concerns about nosocomial infections and the effectiveness of personal protective equipment in protecting HCWs. Asymptomatic infection is estimated 17.9% to 33.3%4 and is a common source of transmission5. We designed a HCW testing program to address patient and employee concerns about exposures in the healthcare setting at our 808-bed health system. During the time of employee testing, the mean (range) number of inpatients with a diagnosis of COVID was 30 (22–38) of a mean (range) daily census of 560 (492–602) (approximately 5.4%). Methods This opt-in program offered SARS-CoV-2 testing of asymptomatic HCWs with paired nasopharyngeal or mid-turbinate swab for PCR (Roche) and serum IgG antibody testing (Diazyme). While initially designed as a pilot project in the Emergency Departments and COVID-19 units, it was quickly expanded to a health system-wide initiative. Results From April 22 to June 2, PCR testing was performed on 5826 asymptomatic HCWs with four PCR tests resulting positive (0.09%). Of 5589 serologic tests (anti-SARS-CoV-2 IgG) performed, 57 tested positive (1.02 %). All HCW with a positive IgG had a concurrent negative PCR. Conclusion In this cross-sectional evaluation, the point prevalence of SARS-CoV-2 IgG in asymptomatic HCWs at UC San Diego was less than 1%, supporting modeling estimations at the San Diego County level of very low levels of community exposure at the time of this testing. Further analyses of incidence rates and potential risk factors such as employee roles within the healthcare system, community and healthcare exposures, and home zip code are underway. Asymptomatic HCW testing is a strategy that can provide the perception of additional safety to both the workforce and patients as the health system reopens, while potentially reduce transmission from asymptomatic persons through active case finding and isolation. Disclosures Randy Taplitz, MD, Merck (Advisor or Review Panel member)

Abstract Background Early reports have indicated widespread empiric antimicrobial usage in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As data regarding bacterial complications in patients with Coronavirus Disease 2019 (COVID-19) are limited and emerging, it is important to delineate the burden of complications with bacterial pneumonia in patients with COVID-19 and its implication on antimicrobial usage. Methods We conducted a retrospective cohort study of all hospitalized patients diagnosed with COVID-19 based on detection of SARS-CoV-2 on RT-PCR from March 1, 2020 to May 10, 2020. Data were collected retrospectively to determine the presence of bacterial pneumonia among patients hospitalized with COVID-19 and to identify demographics, comorbidities, or laboratory values that may help to distinguish patients with bacterial pneumonia. Fisher’s exact test was used to analyze categorical data and Student’s t test was used to analyze differences between means. Results Among 99 patients hospitalized with COVID-19 during the study period, complication with bacterial pneumonia was seen in 17 (17%) based on sputum, tracheal aspirate or lower respiratory tract cultures performed 8.9 ± 7.8 (mean ± SD) days from the detection of SARS-CoV-2 on RT-PCR. Staphylococcus aureus was the causative organism in 8 (47%) cases while Enterobacteriaceae were isolated in 7 (41%) cases, Burkholderia cepacia in one (6%) and Rahnella aqualitis in one (6%) case. There were no significant differences in demographics, comorbidities, or laboratory findings between patients with or without complication with bacterial pneumonia. However, those with complication with bacterial pneumonia were more likely to be intubated (24% vs. 88%, p< 0.01), on vasopressors (23% vs. 82%, p < 0.01), and require intensive care unit admission (37% vs. 94%, p< 0.01). Conclusion Nosocomial and ventilator-associated pneumonia were commonly seen among hospitalized patients with COVID-19 requiring intubation and intensive care use admission. With complications of bacterial pneumonia common among critically-ill patients infected with SARS-CoV-2, widespread antimicrobial usage may increase the selective pressure for antibiotic resistance in this patient population. Disclosures All Authors: No reported disclosures

BackgroundPublic reporting of Clostridioides difficile infection (CDI) using laboratory-identified events has led some institutions to revert from molecular-based tests to less sensitive testing modalities. At one academic medical center, researchers chose to use nucleic acid amplification test alone in CDI diagnosis with institutional protocols aimed at diagnostic stewardship.MethodsA single-center, quasi-experimental study was conducted to introduce and analyze the effects of various diagnostic stewardship interventions. In April 2017 an order report was created to inform providers of patients' recent bowel movements, laxative use, and prior Clostridioides difficile (CD) testing (Intervention 1). In November 2017 nursing staff were empowered to not send nondiarrheal stools for testing (Intervention 2). In February 2019, an interruptive alert was implemented to prevent testing that was not indicated (Intervention 3). CD testing rates and healthcare facility-onset CDI (HO-CDI) rates were compared before and after the interventions using one-way analysis of variance (ANOVA).ResultsAt baseline, testing for CD after 3 days of admission was performed at mean ± standard deviation of 15.9 ± 1.7 tests/1,000 patient-days. After Intervention 1, it decreased to 12.1 ± 1.1 tests. This further decreased to 10.6 ± 0.8 after Intervention 2 and to 8.1 ± 0.1 after Intervention 3 (p < 0.001). HO-CDI cases per 10,000 patient-days declined from 12.7 ± 1.4 cases at baseline to 10.7 ± 1.2 after Intervention 1, to 8.7 ± 2.4 after Intervention 2, and to 5.8 ± 0.2 after Intervention 3 (p = 0.03).ConclusionA multidisciplinary approach optimizing electronic health record support tools and leveraging nursing education can reduce both testing and HO-CDI rates while using the most sensitive testing modality.

During 2016-2018, San Diego County, California, USA, experienced one of the largest hepatitis A outbreaks in the United States in 2 decades. In close partnership with local healthcare systems, San Diego County Public Health led a public health response to the outbreak that focused on a 3-pronged strategy to vaccinate, sanitize, and educate. Healthcare systems administered nearly half of the vaccinations delivered in San Diego County. At University of California San Diego Health, the use of informatics tools assisted with the identification of at-risk populations and with vaccine delivery across outpatient and inpatient settings. In addition, acute care facilities helped prevent further disease transmission by delaying the discharge of patients with hepatitis A who were experiencing homelessness. We assessed the public health roles that acute care hospitals can play during a large community outbreak and the critical nature of ongoing collaboration between hospitals and public health systems in controlling such outbreaks.

ObjectiveTo describe the implementation of technological support important for optimizing clinical management of the COVID-19 pandemic.Materials and methodsOur health system has confirmed prior and current cases of COVID-19. An Incident Command Center was established early in the crisis and helped identify electronic health record (EHR)-based tools to support clinical care.ResultsWe outline the design and implementation of EHR-based rapid screening processes, laboratory testing, clinical decision support, reporting tools, and patient-facing technology related to COVID-19.DiscussionThe EHR is a useful tool to enable rapid deployment of standardized processes. UC San Diego Health built multiple COVID-19-specific tools to support outbreak management, including scripted triaging, electronic check-in, standard ordering and documentation, secure messaging, real-time data analytics, and telemedicine capabilities. Challenges included the need to frequently adjust build to meet rapidly evolving requirements, communication, and adoption, and to coordinate the needs of multiple stakeholders while maintaining high-quality, prepandemic medical care.ConclusionThe EHR is an essential tool in supporting the clinical needs of a health system managing the COVID-19 pandemic.

Abstract Background Balancing antimicrobial stewardship with sepsis management is a challenge. At our academic medical center, a “Code Sepsis” was implemented as a nursing driven initiative to improve early recognition and management of sepsis. Per protocol, Code Sepsis is activated in patients who meet two or more systemic inflammatory response syndrome (SIRS) criteria due to a suspected infection to allow for early implementation of the sepsis bundle, which includes laboratory testing, fluid resuscitation, and antibiotic administration (Figure 1). We analyzed the impact that Code Sepsis had on antimicrobial use among hospitalized patients over a six month period. Methods We reviewed the electronic medical records of hospitalized patients with Code Sepsis activation between January 1, 2018 and June 30, 2018 to determine whether antibiotics were “escalated” or “not escalated.” Among patients who had antibiotic escalation, escalation was classified as “indicated” or “not indicated” (Figure 2). A logistic regression model was used to identify characteristics, SIRS or organ dysfunction criteria predictive of indicated antimicrobial escalation. Results Code Sepsis was activated in 529 patients with antibiotics escalated in 247 (47%) and not escalated in 282 (53%) (Table 1). Among patients whose antibiotics were escalated, 64% (152) had an indication. In 36% (89), escalation was not indicated as Code Sepsis was due to a suspected noninfectious source, known infectious source already on appropriate antimicrobials, or a suspected infectious source in which diagnostic results had already shown the absence of the infection (Figure 2). Odds of indicated antibiotic escalation increased with the number of SIRS and organ dysfunction criteria (Table 2). Conclusion In our efforts to improve sepsis outcomes, we focused on early recognition (Code Sepsis) and intervention (sepsis bundle). However, our Code Sepsis inadvertently led to antibiotic overutilization. By refocusing Code Sepsis on early recognition of severe sepsis and septic shock, we hope to optimize resource utilization and improve patient outcomes. Disclosures All authors: No reported disclosures.

We present a case of intussusception with complete small bowel obstruction caused by intestinal anisakidosis requiring surgical resection. A 30-year-old man presented with acute onset of severe abdominal pain 3 days after eating home-cured salmon gravlax. Despite surgery, the patient developed recurrent abdominal pain on two occasions with evidence of continued inflammation proximal to the surgical anastomosis. He was then treated with albendazole and prednisone, and symptoms improved. A decision was made to prophylactically treat two asymptomatic family members who also consumed home-cured gravlax with albendazole, resulting in one individual passing an intact Anisakis worm in her stool. We suggest that albendazole therapy could be considered as a therapy for continued symptoms of anisakidosis and postexposure prophylaxis of Anisakis larvae ingestion from a common source.

BackgroundBacteria inhabiting the human body have important roles in a number of physiological processes and are known to be shared amongst genetically-related individuals. Far less is known about viruses inhabiting the human body, but their ecology suggests they may be shared between close contacts.ResultsHere, we report the ecology of viruses in the guts and mouths of a cohort and demonstrate that substantial numbers of gut and oral viruses were shared amongst genetically unrelated, cohabitating individuals. Most of these viruses were bacteriophages, and each individual had distinct oral and gut viral ecology from their housemates despite the fact that some of their bacteriophages were shared. The distribution of bacteriophages over time within households indicated that they were frequently transmitted between the microbiomes of household contacts.ConclusionsBecause bacteriophages may shape human oral and gut bacterial ecology, their transmission to household contacts suggests they could have substantial roles in shaping the microbiota within a household.

BackgroundAntibiotics are a mainstay of treatment for bacterial infections worldwide, yet the effects of typical antibiotic prescriptions on human indigenous microbiota have not been thoroughly evaluated. We examined the effects of the two most commonly prescribed antibiotics (amoxicillin and azithromycin) in the USA to discern whether short-term antibiotic courses may have prolonged effects on human microbiota.ResultsWe sampled the feces, saliva, and skin specimens from a cohort of unrelated, cohabitating individuals over 6 months. An individual in each household was given an antibiotic, and the other a placebo to discern antibiotic impacts on microbiota, as well as determine whether antibiotic use might reshape the microbiota of each household. We observed household-specific patterns of microbiota on each body surface, which persevered despite antibiotic perturbations. While the gut microbiota within an individual became more dissimilar over time, there was no evidence that the use of antibiotics accelerated this process when compared to household members. There was a significant change in microbiota diversity in the gut and mouth in response to antibiotics, but analogous patterns were not observed on the skin. Those who received 7 days of amoxicillin generally had greater reductions in diversity compared to those who received 3 days, in contrast to those who received azithromycin.ConclusionsAs few as 3 days of treatment with the most commonly prescribed antibiotics can result in sustained reductions in microbiota diversity, which could have implications for the maintenance of human health and resilience to disease.

BackgroundInfluenza acts synergistically with bacterial co-pathogens. Few studies have described co-infection in a large cohort with severe influenza infection.ObjectivesTo describe the spectrum and clinical impact of co-infections.Study designRetrospective cohort study of patients with severe influenza infection from September 2013 through April 2014 in intensive care units at 33 U.S. hospitals comparing characteristics of cases with and without co-infection in bivariable and multivariable analysis.ResultsOf 507 adult and pediatric patients, 114 (22.5%) developed bacterial co-infection and 23 (4.5%) developed viral co-infection. Staphylococcus aureus was the most common cause of co-infection, isolated in 47 (9.3%) patients. Characteristics independently associated with the development of bacterial co-infection of adult patients in a logistic regression model included the absence of cardiovascular disease (OR 0.41 [0.23-0.73], p=0.003), leukocytosis (>11K/μl, OR 3.7 [2.2-6.2], p

BackgroundThe role of viruses as members of the human microbiome has gained broader attention with the discovery that human body surfaces are inhabited by sizeable viral communities. The majority of the viruses identified in these communities have been bacteriophages that predate upon cellular microbiota rather than the human host. Phages have the capacity to lyse their hosts or provide them with selective advantages through lysogenic conversion, which could help determine the structure of co-existing bacterial communities. Because conditions such as periodontitis are associated with altered bacterial biota, phage mediated perturbations of bacterial communities have been hypothesized to play a role in promoting periodontal disease. Oral phage communities also differ significantly between periodontal health and disease, but the gene expression of oral phage communities has not been previously examined.ResultsHere, we provide the first report of gene expression profiles from the oral bacteriophage community using RNA sequencing, and find that oral phages are more highly expressed in subjects with relative periodontal health. While lysins were highly expressed, the high proportion of integrases expressed suggests that prophages may account for a considerable proportion of oral phage gene expression. Many of the transcriptome reads matched phages found in the oral cavities of the subjects studied, indicating that phages may account for a substantial proportion of oral gene expression. Reads homologous to siphoviruses that infect Firmicutes were amongst the most prevalent transcriptome reads identified in both periodontal health and disease. Some genes from the phage lytic module were significantly more highly expressed in subjects with periodontal disease, suggesting that periodontitis may favor the expression of some lytic phages.ConclusionsAs we explore the contributions of viruses to the human microbiome, the data presented here suggest varying expression of bacteriophage communities in oral health and disease.

BackgroundInfluenza A (H1N1) pdm09 became the predominant circulating strain in the United States during the 2013-2014 influenza season. Little is known about the epidemiology of severe influenza during this season.MethodsA retrospective cohort study of severely ill patients with influenza infection in intensive care units in 33 US hospitals from September 1, 2013, through April 1, 2014, was conducted to determine risk factors for mortality present on intensive care unit admission and to describe patient characteristics, spectrum of disease, management, and outcomes.ResultsA total of 444 adults and 63 children were admitted to an intensive care unit in a study hospital; 93 adults (20.9%) and 4 children (6.3%) died. By logistic regression analysis, the following factors were significantly associated with mortality among adult patients: older age (>65 years, odds ratio, 3.1 [95% CI, 1.4-6.9], P=.006 and 50-64 years, 2.5 [1.3-4.9], P=.007; reference age 18-49 years), male sex (1.9 [1.1-3.3], P=.031), history of malignant tumor with chemotherapy administered within the prior 6 months (12.1 [3.9-37.0], P

The article discusses the ongoing crisis of sewage contamination in the oceans near the U.S.-Mexico border, exacerbated by inadequate wastewater management. It also highlights efforts to monitor and mitigate environmental and health impacts, including the spread of antimicrobial-resistant bacteria and pollutants like mercury and microplastics, underscoring the urgent need for comprehensive environmental protections and sustainable waste management practices.

Viruses are integral members of the human microbiome. Many of the viruses comprising the human virome have been identified as bacteriophage, and little is known about how they respond to perturbations within the human ecosystem. The intimate association of phage with their cellular hosts suggests their communities may change in response to shifts in bacterial community membership. Alterations to human bacterial biota can result in human disease including a reduction in the host's resilience to pathogens. Here we report the ecology of oral and fecal viral communities and their responses to long-term antibiotic therapy in a cohort of human subjects. We found significant differences between the viral communities of each body site with a more heterogeneous fecal virus community compared with viruses in saliva. We measured the relative diversity of viruses, and found that the oral viromes were significantly more diverse than fecal viromes. There were characteristic changes in the membership of oral and fecal bacterial communities in response to antibiotics, but changes in fecal viral communities were less distinguishing. In the oral cavity, an abundance of papillomaviruses found in subjects on antibiotics suggests an association between antibiotics and papillomavirus production. Despite the abundance of papillomaviruses identified, in neither the oral nor the fecal viromes did antibiotic therapy have any significant impact upon overall viral diversity. There was, however, an apparent expansion of the reservoir of genes putatively involved in resistance to numerous classes of antibiotics in fecal viromes that was not paralleled in oral viromes. The emergence of antibiotic resistance in fecal viromes in response to long-term antibiotic therapy in humans suggests that viruses play an important role in the resilience of human microbial communities to antibiotic disturbances.

BackgroundClustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) are utilized by bacteria to resist encounters with their viruses. Human body surfaces have numerous bacteria that harbor CRISPRs, and their content can provide clues as to the types and features of viruses they may have encountered.ResultsWe investigated the conservation of CRISPR content from streptococci on skin and saliva of human subjects over 8-weeks to determine whether similarities existed in the CRISPR spacer profiles and whether CRISPR spacers were a stable component of each biogeographic site. Most of the CRISPR sequences identified were unique, but a small proportion of spacers from the skin and saliva of each subject matched spacers derived from previously sequenced loci of S. thermophilus and other streptococci. There were significant proportions of CRISPR spacers conserved over the entire 8-week study period for all subjects, and salivary CRISPR spacers sampled in the mornings showed significantly higher levels of conservation than any other time of day. We also found substantial similarities in the spacer repertoires of the skin and saliva of each subject. Many skin-derived spacers matched salivary viruses, supporting that bacteria of the skin may encounter viruses with similar sequences to those found in the mouth. Despite the similarities between skin and salivary spacer repertoires, the variation present was distinct based on each subject and body site.ConclusionsThe conservation of CRISPR spacers in the saliva and the skin of human subjects over the time period studied suggests a relative conservation of the bacteria harboring them.

Viruses are dependent biological entities that interact with the genetic material of most cells on the planet, including the trillions within the human microbiome. Their tremendous diversity renders analysis of human viral communities ("viromes") to be highly complex. Because many of the viruses in humans are bacteriophage, their dynamic interactions with their cellular hosts add greatly to the complexities observed in examining human microbial ecosystems. We are only beginning to be able to study human viral communities on a large scale, mostly as a result of recent and continued advancements in sequencing and bioinformatic technologies. Bacteriophage community diversity in humans not only is inexorably linked to the diversity of their cellular hosts but also is due to their rapid evolution, horizontal gene transfers, and intimate interactions with host nucleic acids. There are vast numbers of observed viral genotypes on many body surfaces studied, including the oral, gastrointestinal, and respiratory tracts, and even in the human bloodstream, which previously was considered a purely sterile environment. The presence of viruses in blood suggests that virome members can traverse mucosal barriers, as indeed these communities are substantially altered when mucosal defenses are weakened. Perhaps the most interesting aspect of human viral communities is the extent to which they can carry gene functions involved in the pathogenesis of their hosts, particularly antibiotic resistance. Persons in close contact with each other have been shown to share a fraction of oral virobiota, which could potentially have important implications for the spread of antibiotic resistance to healthy individuals. Because viruses can have a large impact on ecosystem dynamics through mechanisms such as the transfers of beneficial gene functions or the lysis of certain populations of cellular hosts, they may have both beneficial and detrimental roles that affect human health, including improvements in microbial resilience to disturbances, immune evasion, maintenance of physiologic processes, and altering the microbial community in ways that promote or prevent pathogen colonization.

Viruses are the most abundant members of the human oral microbiome, yet relatively little is known about their biodiversity in humans. To improve our understanding of the DNA viruses that inhabit the human oral cavity, we examined saliva from a cohort of eight unrelated subjects over a 60-day period. Each subject was examined at 11 time points to characterize longitudinal differences in human oral viruses. Our primary goals were to determine whether oral viruses were specific to individuals and whether viral genotypes persisted over time. We found a subset of homologous viral genotypes across all subjects and time points studied, suggesting that certain genotypes may be ubiquitous among healthy human subjects. We also found significant associations between viral genotypes and individual subjects, indicating that viruses are a highly personalized feature of the healthy human oral microbiome. Many of these oral viruses were not transient members of the oral ecosystem, as demonstrated by the persistence of certain viruses throughout the entire 60-day study period. As has previously been demonstrated for bacteria and fungi, membership in the oral viral community was significantly associated with the sex of each subject. Similar characteristics of personalized, sex-specific microflora could not be identified for oral bacterial communities based on 16S rRNA. Our findings that many viruses are stable and individual-specific members of the oral ecosystem suggest that viruses have an important role in the human oral ecosystem.

UnlabelledThe human oral cavity is home to a large and diverse community of viruses that have yet to be characterized in patients with periodontal disease. We recruited and sampled saliva and oral biofilm from a cohort of humans either periodontally healthy or with mild or significant periodontal disease to discern whether there are differences in viral communities that reflect their oral health status. We found communities of viruses inhabiting saliva and the subgingival and supragingival biofilms of each subject that were composed largely of bacteriophage. While there were homologous viruses common to different subjects and biogeographic sites, for most of the subjects, virome compositions were significantly associated with the oral sites from which they were derived. The largest distinctions between virome compositions were found when comparing the subgingival and supragingival biofilms to those of planktonic saliva. Differences in virome composition were significantly associated with oral health status for both subgingival and supragingival biofilm viruses but not for salivary viruses. Among the differences identified in virome compositions was a significant expansion of myoviruses in subgingival biofilm, suggesting that periodontal disease favors lytic phage. We also characterized the bacterial communities in each subject at each biogeographic site by using the V3 hypervariable segment of the 16S rRNA and did not identify distinctions between oral health and disease similar to those found in viral communities. The significantly altered ecology of viruses of oral biofilm in subjects with periodontal disease compared to that of relatively periodontally healthy ones suggests that viruses may serve as useful indicators of oral health status.ImportanceLittle is known about the role or the constituents of viruses as members of the human microbiome. We investigated the composition of human oral viral communities in a group of relatively periodontally healthy subjects or significant periodontitis to determine whether health status may be associated with differences in viruses. We found that most of the viruses present were predators of bacteria. The viruses inhabiting dental plaque were significantly different on the basis of oral health status, while those present in saliva were not. Dental plaque viruses in periodontitis were predicted to be significantly more likely to kill their bacterial hosts than those found in healthy mouths. Because oral diseases such as periodontitis have been shown to have altered bacterial communities, we believe that viruses and their role as drivers of ecosystem diversity are important contributors to the human oral microbiome in health and disease states.

BackgroundDental plaque is home to a diverse and complex community of bacteria, but has generally been believed to be inhabited by relatively few viruses. We sampled the saliva and dental plaque from 4 healthy human subjects to determine whether plaque was populated by viral communities, and whether there were differences in viral communities specific to subject or sample type.ResultsWe found that the plaque was inhabited by a community of bacteriophage whose membership was mostly subject-specific. There was a significant proportion of viral homologues shared between plaque and salivary viromes within each subject, suggesting that some oral viruses were present in both sites. We also characterized Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) in oral streptococci, as their profiles provide clues to the viruses that oral bacteria may be able to counteract. While there were some CRISPR spacers specific to each sample type, many more were shared across sites and were highly subject specific. Many CRISPR spacers matched viruses present in plaque, suggesting that the evolution of CRISPR loci may have been specific to plaque-derived viruses.ConclusionsOur findings of subject specificity to both plaque-derived viruses and CRISPR profiles suggest that human viral ecology may be highly personalized.

This article examines breakthrough COVID-19 infections in solid organ transplant recipients who received Tixagevimab/Cilgavimab (T/C) prophylaxis. The study found that there is limited data on the effect of T/C prophylaxis on breakthrough infections in this population during the omicron variant era. The analysis included 481 adult solid organ transplant recipients who received T/C at the University of California San Diego Health. The study found that breakthrough infections were associated with being further out from transplant and from the last vaccine dose, as well as cyclosporine use and lower prednisone doses. The study provides insights into the risk factors for breakthrough infections in solid organ transplant recipients receiving T/C prophylaxis, but further research is needed. [Extracted from the article]

AbstractBackgroundMalaria caused by Plasmodium vivax is an experimentally neglected severe disease with a substantial burden on human health. Because of technical limitations, little is known about the biology of this important human pathogen. Whole genome analysis methods on patient-derived material are thus likely to have a substantial impact on our understanding of P. vivax pathogenesis and epidemiology. For example, it will allow study of the evolution and population biology of the parasite, allow parasite transmission patterns to be characterized, and may facilitate the identification of new drug resistance genes. Because parasitemias are typically low and the parasite cannot be readily cultured, on-site leukocyte depletion of blood samples is typically needed to remove human DNA that may be 1000X more abundant than parasite DNA. These features have precluded the analysis of archived blood samples and require the presence of laboratories in close proximity to the collection of field samples for optimal pre-cryopreservation sample preparation.ResultsHere we show that in-solution hybridization capture can be used to extract P. vivax DNA from human contaminating DNA in the laboratory without the need for on-site leukocyte filtration. Using a whole genome capture method, we were able to enrich P. vivax DNA from bulk genomic DNA from less than 0.5% to a median of 55% (range 20%-80%). This level of enrichment allows for efficient analysis of the samples by whole genome sequencing and does not introduce any gross biases into the data. With this method, we obtained greater than 5X coverage across 93% of the P. vivax genome for four P. vivax strains from Iquitos, Peru, which is similar to our results using leukocyte filtration (greater than 5X coverage across 96% ).ConclusionThe whole genome capture technique will enable more efficient whole genome analysis of P. vivax from a larger geographic region and from valuable archived sample collections.

Abstract Background Persistent neutrophilic meningitis is an unusual form of chronic meningitis that is defined as clinical meningitis with a neutrophilic pleocytosis that persists for greater than 7 days despite empiric antimicrobial therapy. Although numerous disease processes can cause this syndrome, the majority of cases are due to opportunistic pathogens infecting immunocompromised hosts. Case Presentation A 47 year-old female presented after basilar skull fracture with persistent neutrophilic meningitis unresponsive to empiric broad-spectrum antibiotics. After more than weeks of intensive therapy, 4 hospitalizations and 3 relapses, Nocardia cyriacigeorgica was identified from cerebral spinal fluid. Induction therapy was begun with Ceftriaxone and trimethoprim-sulfamethoxazole (TMP-SMX) for 6 weeks followed by therapy with TMP-SMX and doxycycline for one year. The patient made a complete recovery without sequelae. Conclusions Due to the difficulty in obtaining a microbiologic diagnosis, appropriate treatment in cases of persistent neutrophilic meningitis is often delayed leading to morbidity, This case highlights a number of the unique features of Nocardia meningitis and the importance of considering Nocardia infection as a cause of persistent neutrophilic meningitis even in immunocompetent patients.

The article focuses on the limitations of hospital antibiograms in predicting antimicrobial susceptibility for individual Enterobacteriaceae isolates, as discussed by Hasegawa et al. Topics include the technical challenges in compiling and analyzing antibiograms, the need for integrating patient-specific factors into clinical decision-making, and the potential benefits of stratified antibiograms for improving empirical therapy.