Reverse-zoonoses of 2009 H1N1 pandemic influenza A viruses and evolution in United States swine results in viruses with zoonotic potential.

The 2009 H1N1 pandemic (pdm09) lineage of influenza A virus (IAV) crosses interspecies barriers with frequent human-to-swine spillovers each year. These spillovers reassort and drift within swine populations, leading to genetically and antigenically novel IAV that represent a zoonotic threat. We quantified interspecies transmission of the pdm09 lineage, persistence in swine, and identified how evolution in swine impacted zoonotic risk. Human and swine pdm09 case counts between 2010 and 2020 were correlated and human pdm09 burden and circulation directly impacted the detection of pdm09 in pigs. However, there was a relative absence of pdm09 circulation in humans during the 2020-21 season that was not reflected in swine. During the 2020-21 season, most swine pdm09 detections originated from human-to-swine spillovers from the 2018-19 and 2019-20 seasons that persisted in swine. We identified contemporary swine pdm09 representatives of each persistent spillover and quantified cross-reactivity between human seasonal H1 vaccine strains and the swine strains using a panel of monovalent ferret antisera in hemagglutination inhibition (HI) assays. The swine pdm09s had variable antigenic reactivity to vaccine antisera, but each swine pdm09 clade exhibited significant reduction in cross-reactivity to one or more of the human seasonal vaccine strains. Further supporting zoonotic risk, we showed phylogenetic evidence for 17 swine-to-human transmission events of pdm09 from 2010 to 2021, 11 of which were not previously classified as variants, with each of the zoonotic cases associated with persistent circulation of pdm09 in pigs. These data demonstrate that reverse-zoonoses and evolution of pdm09 in swine results in viruses that are capable of zoonotic transmission and represent a potential pandemic threat.

Tecovirimat Use in Ambulatory and Hospitalized Patients With Monkeypox Virus Infection.

ABSTRACT: In this case series of 20 ambulatory and hospitalized adult patients treated for monkeypox virus at a large academic medical center in Chicago, Illinois, tecovirimat use was reserved for those with or at high risk of severe disease, delayed because of logistical and clinical factors, but well tolerated.

Detection and disease diagnosis trends (2017-2022) for Streptococcus suis, Glaesserella parasuis, Mycoplasma hyorhinis, Actinobacillus suis and Mycoplasma hyosynoviae at Iowa State University Veterinary Diagnostic Laboratory.

BACKGROUND: Accurate measurement of disease associated with endemic bacterial agents in pig populations is challenging due to their commensal ecology, the lack of disease-specific antemortem diagnostic tests, and the polymicrobial nature of swine diagnostic cases. The main objective of this retrospective study was to estimate temporal patterns of agent detection and disease diagnosis for five endemic bacteria that can cause systemic disease in porcine tissue specimens submitted to the Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) from 2017 to 2022. The study also explored the diagnostic value of specific tissue specimens for disease diagnosis, estimated the frequency of polymicrobial diagnosis, and evaluated the association between phase of pig production and disease diagnosis. RESULTS: S. suis and G. parasuis bronchopneumonia increased on average 6 and 4.3%, while S. suis endocarditis increased by 23% per year, respectively. M. hyorhinis and A. suis associated serositis increased yearly by 4.2 and 12.8%, respectively. A significant upward trend in M. hyorhinis arthritis cases was also observed. In contrast, M. hyosynoviae arthritis cases decreased by 33% average/year. Investigation into the diagnostic value of tissues showed that lungs were the most frequently submitted sample, However, the use of lung for systemic disease diagnosis requires caution due to the commensal nature of these agents in the respiratory system, compared to systemic sites that diagnosticians typically target. This study also explored associations between phase of production and specific diseases caused by each agent, showcasing the role of S. suis arthritis in suckling pigs, meningitis in early nursery and endocarditis in growing pigs, and the role of G. parasuis, A. suis, M. hyorhinis and M. hyosynoviae disease mainly in post-weaning phases. Finally, this study highlighted the high frequency of co-detection and -disease diagnosis with other infectious etiologies, such as PRRSV and IAV, demonstrating that to minimize the health impact of these endemic bacterial agents it is imperative to establish effective viral control programs. CONCLUSIONS: Results from this retrospective study demonstrated significant increases in disease diagnosis for S. suis, G. parasuis, M. hyorhinis, and A. suis, and a significant decrease in detection and disease diagnosis of M. hyosynoviae. High frequencies of interactions between these endemic agents and with viral pathogens was also demonstrated. Consequently, improved control programs are needed to mitigate the adverse effect of these endemic bacterial agents on swine health and wellbeing. This includes improving diagnostic procedures, developing more effective vaccine products, fine-tuning antimicrobial approaches, and managing viral co-infections.

Role of bone biopsy and deep tissue culture for antibiotic stewardship in diabetic foot osteomyelitis.

OBJECTIVES: To describe organisms most frequently identified on bone biopsy or deep tissue culture and determine how culture data impacted antibiotic management in patients with diabetic foot osteomyelitis (DFO). METHODS: We retrospectively reviewed patients admitted with a diabetic foot ulcer (DFU) between 3 March 2018 and 31 December 2019 and selected for patients diagnosed with infectious osteomyelitis (OM) of the lower extremity. We stratified patients by whether a bone biopsy or deep tissue culture was obtained and compared rates of antibiotic utilization with chi-squared and Fisher's exact tests. RESULTS: Of 305 patients with a DFU, 152 (50%) were clinically diagnosed with DFO. Forty-seven patients received 41 deep tissue cultures and 29 bone biopsy cultures for a total of 70 cultures. Of 45 (64%) positive cultures, 36 (80%) had Gram-positive organisms and 19 (42%) had Gram-negative organisms. MDR organisms were isolated in 7 (15%) patients. Culture data resulted in antibiotic changes in 41 (87%) patients. Therapy was narrowed in 29 (62%) patients and broadened due to inadequate empirical coverage in 4 (9%) patients. Culture data from 18 (40%) patients showed susceptibility to an oral treatment regimen with high bioavailability. There was no significant difference in rates of antibiotic utilization at discharge between patients who underwent bone biopsy or deep tissue culture relative to those who did not (77% versus 75%, P = 0.86), although less MRSA coverage was used (34% versus 50%, P = 0.047). CONCLUSIONS: In patients with DFO, deep tissue and bone biopsy cultures were infrequently obtained but resulted in targeted therapy changes in most patients. Culture data usually allowed for narrowing of antibiotics but revealed inadequate empirical coverage in a subset of patients.

Detection of porcine parainfluenza virus type-1 antibody in swine serum using whole-virus ELISA, indirect fluorescence antibody and virus neutralizing assays.

BACKGROUND: Porcine parainfluenza virus 1 (PPIV-1) is a respiratory virus in the family Paramyxoviridae and genus Respirovirus. It is closely related to bovine parainfluenza virus 3, human parainfluenza virus 1, and Sendai virus. Recent reports suggest PPIV-1 is widespread in swine herds in the United States and abroad. However, seroprevalence studies and the ability to evaluate cross neutralization between heterologous strains is not possible without validated antibody assays. This study describes the development of an indirect fluorescence antibody (IFA) assay, a whole virus enzyme-linked immunosorbent assay (wv-ELISA) and a serum virus neutralization (SVN) assay for the detection of PPIV-1 antibodies using 521 serum samples collected from three longitudinal studies and two different challenge strains in swine. RESULTS: The area under the curve (AUC) of the wv-ELISA (95% CI, 0.93-0.98) was significantly higher (p = 0.03) compared to the IFA (95% CI, 0.90-0.96). However, no significant difference was observed between the IFA and wv-ELISA when compared to the SVN (95% CI, 0.92-0.97). All three assays demonstrated relatively uniform results at a 99% true negative rate, with only 11 disagreements observed between the IFA, wv-ELISA and SVN. CONCLUSIONS: All three serology assays detected PPIV-1 antibody in swine serum of known status that was collected from experimental studies. The SVN detected seroconversion earlier compared to the IFA and the wv-ELISA. Both the wv-ELISA and the SVN had similar diagnostic performance, while the IFA was not as sensitive as the wv-ELISA. All three assays are considered valid for routine diagnostic use. These assays will be important for future studies to screen seronegative swine for research, determine PPIV-1 seroprevalence, and to evaluate vaccine efficacy against PPIV-1 under experimental and field conditions.

Risk Factors Associated With Nephrotoxicity During Outpatient Intravenous Vancomycin Administration.

Background: Many studies have described an association between intravenous vancomycin and nephrotoxicity; however, the majority have evaluated incidence and risk factors among hospitalized patients. Outpatient administration of intravenous antibiotics is a growing practice and presents its own set of unique challenges. Objective: The aim of this study was to identify risk factors for vancomycin-associated nephrotoxicity in the outpatient setting. Methods: A case-control study of patients who received intravenous vancomycin through an Outpatient Parenteral Antimicrobial Therapy (OPAT) program was conducted. Patients were identified who developed an acute kidney injury (AKI) during treatment. The primary outcome was the incidence of AKI during treatment. Results: A total of 37 out of 130 patients (28.5%) met the criteria for AKI. AKI was more likely to occur in patients with a longer duration of therapy, higher maximum trough concentration, co-administration of a fluoroquinolone or metronidazole, and those who received another potentially nephrotoxic medication. Co-administration of a fluoroquinolone (OR = 5.96, P = 0.009, [CI: 1.59, 24.38]), any nephrotoxic medication (OR = 11.17, P < 0.001, [CI 3.14, 51.23]), and a higher maximum vancomycin trough (OR = 1.29, P < 0.001, [CI 1.17, 1.44]) were all indicative of a higher odds of an AKI. Conclusion: In this cohort, vancomycin-associated nephrotoxicity was common during outpatient intravenous antibiotic therapy. Co-administration of a fluoroquinolone, any nephrotoxic medication, and a higher maximum vancomycin trough were associated with AKI development. Further study is needed to determine how this impacts long-term clinical outcomes and what measures can be taken to reduce nephrotoxicity risk.

Alternative strategies of posttransplant influenza vaccination in adult solid organ transplant recipients.

Solid organ transplant (SOT) recipients are at increased risk of influenza disease and associated complications. The mainstay of prevention is the annual standard-dose influenza vaccine, as studies showed decreased influenza-related morbidity and mortality in vaccinated SOT recipients compared to those unvaccinated. Nonetheless, the immune response in this high-risk population is suboptimal compared to healthy individuals. Over the past two decades, several vaccination strategies have been investigated to overcome this inadequate immune response in SOT recipients. Howbeit, the best vaccination strategy and optimal timing of influenza vaccination remain unclear. This review will provide a detailed summary of studies of various influenza vaccination strategies in adult SOT recipients, discussing immunogenicity results, and addressing their limitations and knowledge gaps.

An unusual case of Cardiobacterium valvarum causing aortic endograft infection and osteomyelitis.

BACKGROUND: HACEK (Haemophilus spp., Aggregatibacter spp., Cardiobacterium spp., Eikenella corrodens, and Kingella spp.) group organisms are responsible for 0.8% to 6% of all infective endocarditis cases, with Cardiobacterium spp. being the third most commonly implicated HACEK microorganism. Within this genus is Cardiobacterium valvarum (C. valvarum), a novel organism described in 2004. To date, only 15 cases of C. valvarum infection have been reported in the English-language literature, and have primarily been cases of infective endocarditis in patients with valvular disease. C. valvarum has not been reported to cause infections spreading to the surrounding bone. CASE PRESENTATION: We present a case of a 57-year-old man with a history of aortic dissection followed by aortic endograft replacement who presented with back pain. He was found to have radiographic evidence of an infected aortic endograft, along with vertebral osteomyelitis, discitis, and epidural phlegmon. Blood cultures identified C. valvarum as the causative organism. The patient was treated with ceftriaxone and surgical intervention was deferred due to the patient's complex anatomy. His course was complicated by septic cerebral emboli resulting in cerebrovascular accident. CONCLUSIONS: This case report highlights C. valvarum, a rare and emerging HACEK group microorganism that warrants consideration in high-risk patients with evidence of subacute infection and disseminated disease. While C. valvarum classically presents as infective endocarditis, extra-cardiac manifestations have also been described. As demonstrated in this case, endograft involvement and osteomyelitis may occur in rare circumstances.

Practical Guide to Vaccination in All Stages of CKD, Including Patients Treated by Dialysis or Kidney Transplantation.

Infection is a major cause of morbidity and mortality in patients with chronic kidney disease (CKD), including those receiving maintenance dialysis or with a kidney transplant. Although responses to vaccines are impaired in these populations, immunizations remain an important component of preventative care due to their favorable safety profiles and the high rate of infection in these patients. Most guidelines for patients with CKD focus on the importance of the hepatitis B, influenza, and pneumococcal vaccines in addition to age-appropriate immunizations. More data are needed to determine the clinical efficacy of these immunizations and others in this population and define optimal dosing and timing for administration. Studies have suggested that there may be a benefit to immunization before the onset of dialysis or transplantation because patients with early-stage CKD generally have higher rates of seroconversion. Because nephrologists often serve as primary care physicians for patients with CKD, it is important to understand the role of vaccinations in the preventive care of this patient population.

Pathogenesis of an experimental coinfection of porcine parainfluenza virus 1 and influenza A virus in commercial nursery swine.

Porcine parainfluenza virus 1 (PPIV-1) is a recently characterized swine respirovirus. Previous experimental studies reported PPIV-1 replicates in the porcine respiratory tract causing minimal clinical disease or lesions. However, it is unknown if PPIV-1 co-infections with viral respiratory pathogens would cause respiratory disease consistent with natural infections reported in the field. The objective of this study was to evaluate if PPIV-1 increases the severity of influenza A virus respiratory disease in swine. Fifty conventional, five-week-old pigs were assigned to one of three challenge groups (n = 15) or a negative control group (n = 5). Pigs were challenged with a γ-cluster H1N2 influenza A virus in swine (IAV-S; A/Swine/North Carolina/00169/2006), PPIV-1 (USA/MN25890NS/2016), inoculum that contained equivalent titers of IAV-S and PPIV-1 (CO-IN), or negative control. Clinical scores representing respiratory disease and nasal swabs were collected daily and all pigs were necropsied five days post inoculation (DPI). The CO-IN group demonstrated a significantly lower percentage of pigs showing respiratory clinical signs relative to the IAV-S challenge group from 2 to 4 DPI. The IAV-S and CO-IN groups had significantly lower microscopic composite lesion scores in the upper respiratory tract compared to the PPIV-1 group although the IAV-S and CO-IN groups had significantly higher microscopic composite lung lesion scores. Collectively, PPIV-1 did not appear to influence severity of clinical disease, macroscopic lesions, or alter viral loads detected in nasal swabs or necropsy tissues when administered as a coinfection with IAV-S. Studies evaluating PPIV-1 coinfections with different strains of IAV-S, different respiratory pathogens or sequential exposure of PPIV-1 and IAV-S are warranted.

Management patterns and outcomes of patients hospitalized with diabetic foot ulcers at one tertiary care hospital.

A diabetic foot ulcer is present in approximately 2.4% of hospitalized patients. Care for diabetic foot ulcers is highly variable. We sought to describe care practice patterns and risk factors for poor outcomes for patients hospitalized with a diabetic foot ulcer in our institution, an 894-bed tertiary care academic hospital located in downtown Chicago, IL. We conducted a retrospective cohort study of patients hospitalized with a diabetic foot ulcer between March 3rd, 2018 and December 31st, 2019. We categorized patients into having an uncomplicated ulcer or a complicated ulcer with cellulitis, wound infection, osteomyelitis, or gangrene. We evaluated rates of diagnostic resource utilization (imaging, cultures, biopsies, and antibiotics) and outcomes of osteomyelitis, amputation, and death. There were 305 patients of interest in the study cohort. A complicated lower extremity ulcer was found in 79% of patients. Amputation was required in 25% of patients, 21% were readmitted, and 13% died. Imaging was obtained in less than 50% of all patients, and in 60% or less of those with osteomyelitis. Bone biopsies were rarely acquired. Empiric antibiotics were prescribed in 77% of patients with osteomyelitis. Male, Black or African-American patients, and those with high Charlson score had the highest risk of poor outcomes. Care practices for patients hospitalized with diabetic foot ulcers were highly variable. Future interventions should target standardization to improve outcomes, with particular attention to health inequities as vulnerable populations have a higher risk of poor outcomes.

A recombinant porcine reproductive and respiratory syndrome virus type 2 field strain derived from two PRRSV-2-modified live virus vaccines.

A porcine reproductive and respiratory syndrome virus (PRRSV) type 2 (PRRSV-2) isolate was obtained from lung samples collected from a 4.5-month-old pig at a wean-to-finish site in Indiana, USA, although no gross or microscopic lesions suggestive of PRRSV infection were observed in the lung tissue. Phylogenetic and molecular evolutionary analyses based on the obtained virus sequences indicated that PRRSV USA/IN105404/2021 was a natural recombinant isolate from Ingelvac PRRS® MLV and Prevacent® PRRS, which are PRRSV-2-modified live virus vaccines commercially available in the United States. This study is the first to report the detection of a PRRSV-2 recombinant strain consisting entirely of two modified live virus vaccine strains under field conditions. Based on clinical data and the absence of lung lesions, this PRRSV-2 recombinant strain was not virulent in swine, although its pathogenicity needs to be confirmed by clinical trials.

Refining PRRSV-2 genetic classification based on global ORF5 sequences and investigation of their geographic distributions and temporal changes.

IMPORTANCE: In this study, comprehensive analysis of 82,237 global porcine reproductive and respiratory syndrome virus type 2 (PRRSV-2) open reading frame 5 sequences spanning from 1989 to 2021 refined PRRSV-2 genetic classification system, which defines 11 lineages and 21 sublineages and provides flexibility for growth if additional lineages, sublineages, or more granular classifications are needed in the future. Geographic distribution and temporal changes of PRRSV-2 were investigated in detail. This is a thorough study describing the molecular epidemiology of global PRRSV-2. In addition, the reference sequences based on the refined genetic classification system are made available to the public for future epidemiological and diagnostic applications worldwide. The data from this study will facilitate global standardization and application of PRRSV-2 genetic classification.

Development, Evaluation, and Clinical Application of PRRSV-2 Vaccine-like Real-Time RT-PCR Assays.

In this study, we developed and validated (1) singleplex real-time RT-PCR assays for specific detection of five PRRSV-2 MLV vaccine viruses (Ingelvac MLV, Ingelvac ATP, Fostera, Prime Pac, and Prevacent) and (2) a four-plex real-time RT-PCR assay (IngelvacMLV/Fostera/Prevacent/XIPC) including the internal positive control XIPC for detecting and distinguishing the three most commonly used vaccines in the USA (Prevacent, Ingelvac MLV, and Fostera). The singleplex and 4-plex vaccine-like PCRs and the reference PCR (VetMAXTM PRRSV NA&EU, Thermo Fisher Scientific, Waltham, MA, USA) did not cross-react with non-PRRSV swine viral and bacterial pathogens. The limits of detection of vaccine-like PCRs ranged from 25 to 50 genomic copies/reactions. The vaccine-like PCRs all had excellent intra-assay and inter-assay repeatability. Based on the testing of 531 clinical samples and in comparison to the reference PCR, the diagnostic sensitivity, specificity, and agreement were in the respective range of 94.67-100%, 100%, and 97.78-100% for singleplex PCRs and 94.94-100%, 100%, and 97.78-100% for the 4-plex PCR, with a CT cutoff of 37. In addition, 45 PRRSV-2 isolates representing different genetic lineages/sublineages were tested with the vaccine-like PCRs and the results were verified with sequencing. In summary, the vaccine-like PCRs specifically detect the respective vaccine-like viruses with comparable performances to the reference PCR, and the 4-plex PCR allows to simultaneously detect and differentiate the three most commonly used vaccine viruses in the same sample. PRRSV-2 vaccine-like PCRs provide an additional tool for detecting and characterizing PRRSV-2.

A cluster of six respiratory cultures positive for Mycobacterium xenopi -Clinical characteristics and genomic characterization.

Mycobacterium xenopi is a slow growing non-tuberculous mycobacterium (NTM) isolated from water systems and has been associated with pseudo-outbreaks and pulmonary infections in humans. We observed a cluster of six respiratory cultures positive for M. xenopi within a six-month period at our institution, approximately double our normal isolation rate of this organism. Only three of the six cases met clinical, radiographic, and microbiologic criteria for NTM infection. An investigation led by our hospital's Healthcare Epidemiology and Infection Program found no epidemiologic link between the six patients. Three isolates underwent whole-genome sequencing (WGS) and phylogenetic analysis confirmed they were non-clonal. In vitro susceptibility data found the isolates were sensitive to macrolides, moxifloxacin, and rifabutin. Our findings suggest that isolation of M. xenopi from pulmonary specimens may be increasing, further defines the genomic population structure of this potentially emerging infection, and establishes WGS as a useful tool for outbreak investigation strain typing.

Efficacy of Messenger RNA-1273 Against Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition in Young Adults From March to December 2021.

Background: The efficacy of messenger RNA (mRNA)-1273 against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well defined, particularly among young adults. Methods: Adults aged 18-29 years with no known history of SARS-CoV-2 infection or prior vaccination for coronavirus disease 2019 (COVID-19) were recruited from 44 US sites from 24 March to 13 September 2021 and randomized 1:1 to immediate vaccination (receipt of 2 doses of mRNA-1273 vaccine at months 0 and 1) or the standard of care (receipt of COVID-19 vaccine). Randomized participants were followed up for SARS-CoV-2 infection measured by nasal swab testing and symptomatic COVID-19 measured by nasal swab testing plus symptom assessment and assessed for the primary efficacy outcome. A vaccine-declined observational group was also recruited from 16 June to 8 November 2021 and followed up for SARS-CoV-2 infection as specified for the randomized participants. Results: The study enrolled 1149 in the randomized arms and 311 in the vaccine-declined group and collected >122 000 nasal swab samples. Based on randomized participants, the efficacy of 2 doses of mRNA-1273 vaccine against SARS-CoV-2 infection was 52.6% (95% confidence interval, -14.1% to 80.3%), with the majority of infections due to the Delta variant. Vaccine efficacy against symptomatic COVID-19 was 71.0% (95% confidence interval, -9.5% to 92.3%). Precision was limited owing to curtailed study enrollment and off-study vaccination censoring. The incidence of SARS-CoV-2 infection in the vaccine-declined group was 1.8 times higher than in the standard-of-care group. Conclusions: mRNA-1273 vaccination reduced the incidence of SARS-CoV-2 infection from March to September 2021, but vaccination was only one factor influencing risk. Clinical Trials Registration: NCT04811664.

Comparison of examination-based and self-reported risk factors for cardiovascular disease, Washington State, 2006-2007.

INTRODUCTION: Obesity, hypertension, and high cholesterol are risk factors for cardiovascular disease, which accounts for approximately 20% of deaths in Washington State. For most states, self-reports from the Behavioral Risk Factor Surveillance System (BRFSS) provide the primary source of information on these risk factors. The objective of this study was to compare prevalence estimates of self-reported obesity, hypertension, and high cholesterol with examination-based measures of obesity, hypertension, and high-risk lipid profiles. METHODS: During 2006-2007, the Washington Adult Health Survey (WAHS) included self-reported and examination-based measures of a random sample of 672 Washington State residents aged 25 years or older. We compared WAHS examination-based measures with self-reported measures from WAHS and the 2007 Washington BRFSS (WA-BRFSS). RESULTS: The estimated prevalence of obesity from WA-BRFSS (27.1%; 95% confidence interval [CI], 26.3%-27.8%) was lower than estimates derived from WAHS physical measurements (39.2%; 95% CI, 33.6%-45.1%) (P < .001). Prevalence estimates of hypertension based on self-reports from WA-BRFSS (28.1%; 95% CI, 27.4%-28.8%) and WAHS (33.4%; 95% CI, 29.4%-37.7%) were similar to the examination-based estimate (29.4%; 95% CI, 25.8%-33.4%). Prevalence estimates of high cholesterol based on self-reports from WA-BRFSS (38.3%; 95% CI, 37.5%-39.2%) and WAHS (41.8%; 95% CI, 35.8%-48.1%) were similar; both were lower than the examination-based WAHS estimate of high-risk lipid profiles (59.2%; 95% CI, 54.2%-64.2%) (P < .001). CONCLUSION: Self-reported heights and weights underestimate the prevalence of obesity. The prevalence of self-reported high cholesterol is significantly lower than the prevalence of high-risk lipid profiles. Periodic examination-based measurement provides perspective on routinely collected self-reports.

Characterization of Two Porcine Parainfluenza Virus 1 Isolates and Human Parainfluenza Virus 1 Infection in Weaned Nursery Pigs.

Porcine parainfluenza virus 1 (PPIV1) is a newly characterized porcine respiratory virus. Recent experimental challenge studies in three-week-old nursery pigs failed to cause disease. However, it remains unclear how genetic differences contribute to viral pathogenesis. To characterize the pathogenesis of different PPIV1 isolates, three-week-old nursery pigs were challenged with either PPIV1 isolate USA/MN25890NS/2016 (MN16) or USA/IA84915LG/2017 (IA17). A human parainfluenza virus 1 (HPIV1) strain C35 ATCC® VR-94™ was included to evaluate swine as a model for human parainfluenza. All viruses were successfully re-isolated from bronchoalveolar lavage fluid and detected by RT-qPCR at necropsy. Microscopic lung lesions were more severe in the IA17 group compared to the non-challenged negative control (Ctrl) group whereas differences were not found between the MN16 and Ctrl groups. Immunohistochemistry staining in respiratory samples showed a consistent trend of higher levels of PPIV1 signal in the IA17 group followed by the MN16 group, and no PPIV1 signal observed in the HPIV1 or Ctrl groups. This study suggests potential pathogenesis differences between PPIV1 isolates. Additionally, these results indicate that HPIV1 is capable of replicating in nursery pigs after experimental inoculation. However, clinical disease or gross lung lesions were not observed in any of the challenge groups.

Role of Therapeutic Drug Monitoring in the Treatment of Persistent Mycobacterium abscessus Central Nervous System Infection: A Case Report and Review of the Literature.

A patient presenting with recurrent ventriculoperitoneal shunt infection was found to have Mycobacterium abscessus growing from cerebrospinal fluid (CSF), which remained persistently positive. Therapeutic monitoring of clarithromycin, imipenem, and linezolid in CSF and plasma revealed lower than expected concentrations, prompting alternative therapy and culture clearance on hospital day 42.