Hyperammonemia syndrome in immunosuppressed individuals.

PURPOSE OF REVIEW: Hyperammonemia syndrome is an increasingly recognized and often fatal condition that occurs in immunosuppressed individuals, most commonly lung transplant recipients. Growing evidence suggests hyperammonemia syndrome is associated with systemic infections caused by urease-producing organisms, namely Ureaplasma spp., an organism unable to grow with routine culturing techniques. This review will summarize the epidemiology and clinical manifestations of hyperammonemia syndrome, as well as diagnostic and management strategies once hyperammonemia syndrome is suspected. RECENT FINDINGS: Hyperammonemia syndrome is being described in increasing frequency in the solid organ transplant population. Morbidity and mortality, even with treatment, is high once hyperammonemia syndrome occurs. Surveillance studies indicate the prevalence of lung donor colonization with Ureaplasma spp. is high, suggesting screening and treatment may be of benefit. Antibiotic resistance is common, and rapid diagnostics can facilitate appropriate antimicrobial therapy in the peri-transplant period. SUMMARY: Hyperammonemia syndrome is most commonly seen in lung transplant recipients and has a high mortality rate once it occurs. Screening for Ureaplasma spp. should be considered in all lung transplant donors.

An outbreak of SARS-CoV-2 on a transplant unit in the early vaccination era.

BACKGROUND: Solid organ transplant recipients are at increased risk of COVID-19-associated morbidity and mortality. AIMS: We describe a nosocomial outbreak investigation on an immunocompromised inpatient unit. METHODS: Patients positive for SARS-CoV-2 were identified. An epidemiologic investigation was assisted with whole genome sequencing of positive samples. RESULTS: Two patients were identified as potential index cases; one presented with diarrhea and was initially not isolated, and the other developed hypoxemia on hospital day 18 before testing positive. Following identification of a SARS-CoV-2 cluster, the unit was closed and all patients and staff received surveillance testing revealing eight additional positive patients and staff members. Whole genome sequencing confirmed an outbreak. Enhanced infection prevention practices mitigated further spread. Asymptomatic patients with COVID-19 were successfully treated with bamlanivimab. DISCUSSION: Preventing SARS-CoV-2 outbreaks in transplant units poses unique challenges as patients may have atypical presentations of COVID-19. Immunocompromised patients who test positive for SARS-CoV-2 while asymptomatic may benefit from monoclonal antibody therapy to prevent disease progression. All hospital staff members working with immunocompromised patients should be promptly encouraged to follow infection prevention behaviors and receive SARS-CoV-2 vaccination. CONCLUSION: SARS-CoV-2 outbreaks on immunocompromised units can be mitigated through prompt identification of cases and robust infection prevention practices.

Disinfection of Virtual Reality Devices in Health Care Settings: In Vitro Assessment and Survey Study.

BACKGROUND: Virtual reality (VR) devices are increasingly used in health care settings. The use among patients has the potential to unintentionally transmit pathogens between patients and hospital staff. No standard operating procedure for disinfection exists to ensure safe use between patients. OBJECTIVE: This study aims to determine the efficacy of disinfectants on VR devices in order to ensure safe use in health care settings. METHODS: Three types of bacteria were inoculated onto porous and nonporous surfaces of 2 VR devices: the Meta Oculus Quest and Meta Oculus Quest 2. Disinfection was performed using either isopropyl alcohol or alcohol-free quaternary ammonium wipes. A quantitative culture was used to assess the adequacy of disinfection. A survey was separately sent out to VR device technicians at other pediatric health care institutes to compare the methods of disinfection and how they were established. RESULTS: Both products achieved adequate disinfection of the treated surfaces; however, a greater log-kill was achieved on nonporous surfaces than on the porous surfaces. Alcohol performed better than quaternary ammonium on porous surfaces. The survey respondents reported a wide variability in disinfection processes with only 1 person reporting an established standard operating procedure. CONCLUSIONS: Disinfection can be achieved through the use of either isopropyl alcohol or quaternary ammonium products. Porous surfaces showed lesser log-kill rates than the nonporous surfaces, indicating that the use of an added barrier may be of benefit and should be a point of future research. Given the variability in the disinfection process across health care systems, a standard operating procedure is proposed.

Impact of Screening and Treatment of Ureaplasma species on Hyperammonemia Syndrome in Lung Transplant Recipients: A Single Center Experience.

BACKGROUND: Infection with Ureaplasma species (spp) has been linked to fatal hyperammonemia syndrome (HS) in lung transplant recipients. We sought to characterize the epidemiology of Ureaplasma spp in candidates and donors and describe outcomes of antimicrobial therapy in preventing and treating HS. METHODS: Candidate testing for Ureaplasma spp was performed with urine culture and polymerase chain reaction (PCR) pretransplant. Positive candidates were treated with levofloxacin. Donor testing was performed with bronchoalveolar lavage (BAL) culture and PCR intraoperatively. From 7/2014 to 2/2017 patients were treated according to results; from 2/2017 to 10/2018 recipients received empiric levofloxacin and azithromycin at transplant until testing returned negative. HS was defined as new onset altered mental status after transplant with ammonia > 200 µmol/L. RESULTS: In total, 60 patients who underwent lung transplant were included. And 80% (n = 48) of patients had negative screening tests in donor and candidate pre-lung transplant, 8.3% (n = 5) of recipients had positive Ureaplasma spp testing in urine pre-transplant, and 13.3% (n = 8) had positive donor BAL testing at the time of lung transplant. Three patients developed HS a median of 7 days posttransplant; 2 died of HS. Recipients of organs with Ureaplasma spp who received empiric therapy did not develop HS. Donors with Ureaplasma spp were younger and more sexually active. CONCLUSIONS: Donor-derived Ureaplasma spp in lung transplant was associated with HS. Screening lung donors for Ureaplasma spp might allow for targeted therapy to reduce risk for development of HS, but future confirmatory studies are needed.

Genetic Evaluation of Nosocomial Candida auris Transmission.

Whole-genome sequences of Candida auris isolates from nosocomial and nonnosocomial infections were compared. The average numbers of single nucleotide variations were different between the two groups. The small amount of genetic variability between intra- or interhost isolates suggests recovery of all colonizing or infecting genomes for comparison is required for outbreaks.

Cutaneous manifestations of Campylobacter jejuni infection: A case report and review of the literature.

A 51 year old man with active follicular lymphoma presented with several days of erythematous skin nodules on all extremities two weeks after a self-limited diarrheal illness. All serum immunoglobulin levels were found to be low. Blood cultures grew Campylobacter jejuni. The patient was given one week of azithromycin with complete resolution of his skin nodules. The literature of skin manifestations seen in active Campylobacter jejuni infection are reviewed. The majority of cases occur in immunocompromised hosts, many with low or no serum immunoglobulin levels. Postulated mechanisms include a lack of secretory IgA in intestinal mucosa predisposing susceptible patients to translocated enteric pathogens however the precise pathogenesis underlying cutaneous manifestations are unknown.

Disseminated Streptococcus pneumoniae infection associated with an intrauterine device.

Streptococcus pneumoniae is a common pathogen afflicting a wide variety of disease in both immunocompetent and immunocompromised individuals. Presentation can be variable in initial symptomatology leading to difficulties in diagnosis and management. We present a case of septic shock due to Streptococcus pneumoniae associated with an intrauterine device (IUD) in an immunocompromised patient.

Thrombocytopaenia as a Prognostic Indicator in Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Studies suggest that thrombocytopaenia is associated with a higher mortality in several diseases. Little is known about the effect of low platelet count on mortality in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to determine the prognostic value of thrombocytopaenia in these patients by assessing all-cause mortality. METHODS: A total of 1,907 patients with HFrEF, defined by left ventricular ejection fraction <40% on echocardiography, were analysed in this multi-centre retrospective study. All patients were on medical therapy with a beta-blocker and an angiotensin-converting enzyme inhibitor. Patients were categorised into two groups based on platelet count measured within one month of the diagnosis of HFrEF: normal to mild thrombocytopaenia (platelet count 100,000-450,000 per uL); and moderate to severe thrombocytopaenia (platelet count <100,000 per uL). One-year all-cause mortality was compared between the two groups. RESULTS: Mean age was 65±15 years and 62% of patients were male. Overall one-year mortality was 17.2% with higher mortality among patients with HFrEF and moderate/severe thrombocytopaenia compared to those with normal/mild thrombocytopaenia (33.0% vs. 15.4%, p <0.001). After adjusting for baseline characteristics, patients with HFrEF and moderate/severe thrombocytopaenia had a higher mortality compared to patients with normal/mild thrombocytopaenia (HR 1.84, 95% CI 1.33-2.56, p <0.001). CONCLUSION: In patients with HFrEF, higher degree of thrombocytopaenia is associated with higher all-cause mortality. These findings may support the use of platelet counts as a prognostic marker in the assessment of the patient with HFrEF.

Loss of CDKN2B promotes p53-dependent smooth muscle cell apoptosis and aneurysm formation.

OBJECTIVE: Genomewide association studies have implicated allelic variation at 9p21.3 in multiple forms of vascular disease, including atherosclerotic coronary heart disease and abdominal aortic aneurysm. As for other genes at 9p21.3, human expression quantitative trait locus studies have associated expression of the tumor suppressor gene CDKN2B with the risk haplotype, but its potential role in vascular pathobiology remains unclear. METHODS AND RESULTS: Here we used vascular injury models and found that Cdkn2b knockout mice displayed the expected increase in proliferation after injury, but developed reduced neointimal lesions and larger aortic aneurysms. In situ and in vitro studies suggested that these effects were attributable to increased smooth muscle cell apoptosis. Adoptive bone marrow transplant studies confirmed that the observed effects of Cdkn2b were mediated through intrinsic vascular cells and were not dependent on bone marrow-derived inflammatory cells. Mechanistic studies suggested that the observed increase in apoptosis was attributable to a reduction in MDM2 and an increase in p53 signaling, possibly due in part to compensation by other genes at the 9p21.3 locus. Dual inhibition of both Cdkn2b and p53 led to a reversal of the vascular phenotype in each model. CONCLUSIONS: These results suggest that reduced CDKN2B expression and increased smooth muscle cell apoptosis may be one mechanism underlying the 9p21.3 association with aneurysmal disease.

Accuracy of conventional transthoracic echocardiography for the diagnosis of intracardiac right-to-left shunt: a meta-analysis of prospective studies.

BACKGROUND: Paradoxical embolization through a right-to-left shunt (RLS), often from a patent foramen ovale (PFO), has been associated with cryptogenic stroke. While transesophageal echo (TEE) bubble study is the current standard reference for diagnosing PFO, transthoracic echo (TTE) remains the most commonly used screening test for RLS due to its noninvasiveness and easy availability. The aim of this meta-analysis was to determine the accuracy of TTE compared to TEE as the reference. METHODS AND RESULTS: A systematic review of Medline, Cochrane, and Embase was done to look for all the prospective studies assessing for intracardiac RLS using conventional TTE compared to TEE as the reference; both TTE and TEE were performed with a contrast agent and a maneuver to provoke RLS in all studies. A total of 13 studies with 1436 patients fulfilled the inclusion criteria. The weighted mean sensitivity and specificity for TTE were 46% and 99%, respectively. Likewise, the positive likelihood ratio and negative likelihood ratio were 20.85 and 0.57, respectively. Using different contrast agents, different microbubble cutoffs for a positive TTE/TEE, and different cardiac cycle cutoffs for a positive TTE/TEE did not affect the accuracy of TTE. In a population of patients with cryptogenic stroke, a TTE that tests positive for RLS has a 95% probability of being a true positive. CONCLUSION: Transthoracic echocardiogram has a low sensitivity and extremely high specificity, making it a poor rule out test but an excellent rule in test for the detection of intracardiac RLS.

Characterizing healthcare personnel attitudes toward receipt of a voluntary bivalent COVID-19 booster vaccine during a COVID-19 outbreak at a behavioral health hospital in Connecticut.

COVID-19 vaccine uptake in healthcare personnel (HCP) is poor. A cross-sectional survey study of behavioral health HCP was performed. Commonly identified reasons for vaccination were protecting others and oneself. Reasons against were a lack of perceived protection, dosing intervals, and side effects. Assessing vaccination attitudes can assist in uptake strategy.

Pseudo-outbreak of Parengyodontium album related to contaminated saline used in specimen processing in the microbiology laboratory.

We report a cluster of 9 isolates of Parengyodontium album recovered from 4 patients who had surgical tissue specimens processed after dilution with a multiuse diluent saline solution. P album was also identified from a nonclinical sample on agar prepared with the same lot number of saline solution. Our epidemiological investigation revealed this to represent a pseudo-outbreak related to contaminated saline used to process specimens in the microbiology laboratory.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) RNA and viable virus contamination of hospital emergency department surfaces and association with patient coronavirus disease 2019 (COVID-19) status and aerosol-generating procedures.

Emergency departments are high-risk settings for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) surface contamination. Environmental surface samples were obtained in rooms with patients suspected of having COVID-19 who did or did not undergo aerosol-generating procedures (AGPs). SARS-CoV-2 RNA surface contamination was most frequent in rooms occupied by coronavirus disease 2019 (COVID-19) patients who received no AGPs.

A mixed-methods evaluation on the efficacy and perceptions of needleless connector disinfectants.

OBJECTIVE: Optimizing needleless connector hub disinfection practice is a key strategy in central-line-associated bloodstream infection (CLABSI) prevention. In this mixed-methods evaluation, 3 products with varying scrub times were tested for experimental disinfection followed by a qualitative nursing assessment of each. METHODS: Needleless connectors were inoculated with varying concentrations of Staphylococcus epidermidis, Pseudomonas aeruginosa, and Staphylococcus aureus followed by disinfection with a 70% isopropyl alcohol (IPA) wipe (a 15-second scrub time and a 15-second dry time), a 70% IPA cap (a 10-second scrub time and a 5-second dry time), or a 3.15% chlorhexidine gluconate with 70% IPA (CHG/IPA) wipe (a 5-second scrub time and a 5-second dry time). Cultures of needleless connectors were obtained after disinfection to quantify bacterial reduction. This was followed by surveying a convenience sample of nursing staff with intensive care unit assignments at an academic tertiary hospital on use of each product. RESULTS: All products reduced overall bacterial burden when compared to sterile water controls, however the IPA and CHG/IPA wipes were superior to the IPA caps when product efficacy was compared. Nursing staff noted improved compliance with CHG/IPA wipes compared with the IPA wipes and the IPA caps, with many preferring the lesser scrub and dry times required for disinfection. CONCLUSION: Achieving adequate bacterial disinfection of needleless connectors while maximizing healthcare staff compliance with scrub and dry times may be best achieved with a combination CHG/IPA wipe.

Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection.

The chronic infection hypothesis for novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant emergence is increasingly gaining credence following the appearance of Omicron. Here, we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral genome copies. During the infection, we find an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately 2-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution results in the emergence and persistence of at least three genetically distinct genotypes, suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, we track the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, providing an opportunity for the emergence of genetically divergent variants.

Myometritis with pelvic septic vein thrombophlebitis secondary to Fusobacterium necrophorum sepsis.

A young woman in her 20s presented with fever, abdominal pain and malodourous vaginal discharge. She was found to be in septic shock, in the setting of a recent medical abortion with subsequent intrauterine device placement. Her blood cultures grew Fusobacterium necrophorum Despite appropriate antibiotic therapy, the fever failed to defervesce. Subsequent evaluation revealed septic thrombophlebitis of the right gonadal vein and branches of the right iliac vein. She improved with a prolonged course of targeted antimicrobial therapy.

Colonization with Multidrug-resistant Organisms in Patients with Ventricular Assist Devices.

Infection is a leading cause of morbidity and mortality in patients with ventricular assist devices (VAD). The impact of colonization with multidrug-resistant organisms (MDRO) on outcomes in this cohort is unknown. Patients on VAD support from July 2008 to September 2018 at a single site were evaluated for MDRO colonization after implantation. MDROs included methicillin-resistant Staphylococcus aureus , vancomycin-resistant Enterococcus species, and extended-spectrum beta-lactamase producing gram-negative bacteria. 378 patients with 433 VADs were included. 42.6% (n = 161) of patients were colonized with an MDRO throughout the duration of VAD support. Eighty-two VAD infections occurred, 74.4% (n = 61) of whom were MDRO colonized before infection. MDRO colonization was associated with an increased risk of a subsequent VAD infection (hazard ratio 3.704, p < 0.001). MDRO colonization is common after VAD implantation and is associated with future VAD infections. Further study is needed to determine best management strategies for VAD recipients with MDRO colonization given this increased risk.

Accelerated SARS-CoV-2 intrahost evolution leading to distinct genotypes during chronic infection.

The chronic infection hypothesis for novel SARS-CoV-2 variant emergence is increasingly gaining credence following the appearance of Omicron. Here we investigate intrahost evolution and genetic diversity of lineage B.1.517 during a SARS-CoV-2 chronic infection lasting for 471 days (and still ongoing) with consistently recovered infectious virus and high viral loads. During the infection, we found an accelerated virus evolutionary rate translating to 35 nucleotide substitutions per year, approximately two-fold higher than the global SARS-CoV-2 evolutionary rate. This intrahost evolution led to the emergence and persistence of at least three genetically distinct genotypes suggesting the establishment of spatially structured viral populations continually reseeding different genotypes into the nasopharynx. Finally, using unique molecular indexes for accurate intrahost viral sequencing, we tracked the temporal dynamics of genetic diversity to identify advantageous mutations and highlight hallmark changes for chronic infection. Our findings demonstrate that untreated chronic infections accelerate SARS-CoV-2 evolution, ultimately providing opportunity for the emergence of genetically divergent and potentially highly transmissible variants as seen with Delta and Omicron.