Characterizing Ertapenem Neurotoxicity: A Systematic Review and Experience at a Tertiary Medical Center.

Ertapenem-induced neurotoxicity has not been well characterized and is potentially underreported. We conducted a systematic review of the literature and included 11 additional cases from the University of Washington Medicine health system. A total of 125 individual patient cases were included in the data analysis. The mean age was 72 years, and 62% and 42% of patients had renal dysfunction and preexisting central nervous system (CNS) conditions, respectively. Only 15% of patients received inappropriately high ertapenem dosing based on kidney function. Patients developed neurological signs and symptoms after a median of 4 days (interquartile range, 3-9 days). The most common clinical features were seizures (70%), altered level of consciousness or delirium (27%), and hallucinations (17%). An estimated incidence in our health system was 1 in 102 courses of ertapenem. Ertapenem neurotoxicity should be suspected when a patient with renal dysfunction or predisposing CNS conditions develops neurological signs and symptoms, especially within several days after initiating the antibiotic. This study underscores the need for a large prospective study to assess the true incidence and outcomes of ertapenem neurotoxicity.

Effect of a mobile app chatbot and an interactive small-group webinar on COVID-19 vaccine intention and confidence in Japan: a randomised controlled trial.

INTRODUCTION: We investigated the effect of social media-based interventions on COVID-19 vaccine intention (VI) and confidence in Japan. METHODS: We conducted a three-arm randomised controlled trial between 5 November 2021 and 9 January 2022 during a low incidence (<1000/day) of COVID-19 in Japan in the midst of the second and the third waves. Japanese citizens aged ≥20 who had not received any COVID-19 vaccine and did not intend to be vaccinated were randomly assigned to one of the following three groups: (1) a control group, (2) a group using a mobile app chatbot providing information on COVID-19 vaccines and (3) a group using interactive webinars with health professionals. VI and predefined Vaccine Confidence Index (VCI) measuring confidence in the importance, safety and effectiveness were compared before and after the interventions under intention-to-treat principle. Logistic regression models were used to investigate the effect of each intervention on postintervention VI and changes of VCI compared with control. RESULTS: Among 386 participants in each group, 359 (93.0%), 231 (59.8%) and 207 (53.6%) completed the postsurvey for the control, chatbot and webinar groups, respectively. The average duration between the intervention and the postsurvey was 32 days in chatbot group and 27 days in webinar group. VI increased from 0% to 18.5% (95% CI 14.5%, 22.5%) in control group, 15.4% (95% CI 10.8%, 20.1%) in chatbot group and 19.7% (95% CI 14.5%, 24.9%) in webinar group without significant difference (OR for improvement=0.8 (95% CI 0.5, 1.3), p=0.33 between chatbot and control, OR=1.1 (95% CI 0.7, 1.6), p=0.73 between webinar and control). VCI change tended to be larger in chatbot group compared with control group without significant difference (3.3% vs -2.5% in importance, OR for improvement=1.3 (95% CI 0.9, 2.0), p=0.18; 2.5% vs 1.9% in safety, OR=1.1 (95% CI 0.7, 1.9), p=0.62; -2.4% vs -7.6% in effectiveness, OR=1.4 (95% CI 0.9, 2.1), p=0.09). Improvement in VCI was larger in webinar group compared with control group for importance (7.8% vs -2.5%, OR=1.8 (95% CI 1.2, 2.8), p<0.01), effectiveness (6.4% vs -7.6%, OR=2.2 (95% CI 1.4, 3.4), p<0.01) and safety (6.0% vs 1.9%, OR=1.6 (95% CI 1.0, 2.6), p=0.08). CONCLUSION: This study demonstrated that neither the chatbot nor the webinar changed VI importantly compared with control. Interactive webinars could be an effective tool to change vaccine confidence. Further study is needed to identify risk factors associated with decreased vaccine confidence and investigate what intervention can increase VI and vaccine confidence for COVID-19 vaccines. TRIAL REGISTRATION NUMBER: UMIN000045747.

Effects of Live Music on the Perception of Noise in the SICU/PICU: A Patient, Caregiver, and Medical Staff Environmental Study.

Intensive Care Units (ICUs) require a multidisciplinary team that consists of, but is not limited to, intensivists (clinicians who specialize in critical illness care), pharmacists and nurses, respiratory care therapists, and other medical consultants from a broad range of specialties. The complex and demanding critical care environment provides few opportunities for patients and personal and professional caregivers to evaluate how sound effects them. A growing body of literature attests to noise's adverse influence on patients' sleep, and high sound levels are a source of staff stress, as noise is an ubiquitous and noxious stimuli. Vulnerable patients have a low threshold tolerance to audio-induced stress. Despite these indications, peak sound levels often register as high, as can ventilators, and the documented noise levels in hospitals continue to rise. This baseline study, carried out in two hospitals' Surgical and Pediatric Intensive Care Units, measured the effects of live music on the perception of noise through surveying patients, personal caregivers and staff in randomized conditions of no music, and music as provided by music therapists through our hospital system's environmental music therapy program.

Association between follow-up blood cultures for gram-negative bacilli bacteremia and length of hospital stay and duration of antibiotic treatment: A propensity score-matched cohort study.

OBJECTIVE: It remains unclear whether a follow-up blood culture (FUBC) for gram-negative bacilli (GNB) bacteremia should be routinely or selectively performed. To evaluate the value of the practice, we analyzed the association between current FUBC practices and length of stay, antibiotic treatment duration, and in-hospital mortality. DESIGN: Retrospective cohort study. SETTING: The study was conducted in 4 acute-care hospitals in New York City. PATIENTS: The study included hospitalized adults with GNB bacteremia between 2017 and 2018. METHODS: An FUBC was defined as a blood culture performed between 24 hours and 7 days after an initial blood culture positive for GNB. Using propensity scores for FUBCs performed, patients were matched 1:1 for outcome comparison. RESULTS: In total, 376 hospitalized adults with GNB bacteremia met eligibility criteria. Among them, FUBCs were performed in 271 patients (72%). After propensity score matching, we analyzed 87 pairs of patients with and without an FUBC to compare outcomes. The median length of stay was longer among patients with FUBCs than patients without FUBCs (9 days vs 7 days; P = .017). The median duration of antibiotic treatment was also longer among patients with FUBCs than patients without FUBCs (8 vs 6 days; P = .007). No statistically significant difference was observed in in-hospital mortality between patients with and without an FUBC (odds ratio, 0.37; 95% confidence interval, 0.08-1.36). CONCLUSIONS: Current FUBC practices for GNB bacteremia were associated with prolonged length of stay and duration of antibiotic treatment. Further data to better inform selectivity criteria for FUBCs in GNB bacteremia are needed.

Clinical Features and Mortality of COVID-19-Associated Mucormycosis: A Systematic Review and Meta-Analysis.

The recent increase of COVID-19-associated mucormycosis (CAM) has been commanding global attention. However, basic epidemiologic characteristics have not firmly been established. In this systematic review and meta-analysis, we sought to determine the clinical manifestations, potential risk factors, and outcomes of CAM. Observational studies reporting CAM were searched with PubMed and EMBASE databases in January 2022. We collected data on comorbidities and treatment for COVID-19, and performed a one-group meta-analysis on the frequency of orbital exenteration procedure and mortality of CAM using a random-effect model. Fifty-one observational studies, including a total of 2,312 patients with proven CAM, were identified. Among the 51 studies, 37 were conducted in India, 8 in Egypt, and 6 in other countries. The most common comorbidity was diabetes mellitus (82%). While 57% required oxygenation, 77% received systemic corticosteroids. Among CAM, 97% were rhino-orbital-cerebral (ROCM), and 2.7% were pulmonary mucormycosis. Usual presentations were headache (54%), periorbital swelling/pain (53%), facial swelling/pain (43%), ophthalmoplegia (42%), proptosis (41%), and nasal discharge/congestion (36%). Regarding the outcomes, orbital exenteration was performed in 17% (95% CI: 12-21%, I2 = 83%) of the COVID-19-associated ROCM patients. The mortality of CAM was 29% (95% CI; 22-36%, I2 = 92%). In conclusion, this systematic review and meta-analysis indicated that the most prevalent type of CAM was ROCM, and most CAM patients had diabetes mellitus and received systemic glucocorticoids. Clinicians in the endemic areas should have a high index of suspicion for this invasive fungal complication of COVID-19 when a diabetic patient who received high-dose systemic glucocorticoids developed rhino-orbital symptoms.

Incidence and mortality of COVID-19-associated pulmonary aspergillosis: A systematic review and meta-analysis.

COVID-19-associated pulmonary aspergillosis (CAPA) has been reported worldwide. However, basic epidemiological characteristics have not been well established. In this systematic review and meta-analysis, we aimed to determine the incidence and mortality of CAPA in critically ill patients with COVID-19 to improve guidance on surveillance and prognostication. Observational studies reporting COVID-19-associated pulmonary aspergillosis were searched with PubMed and Embase databases, followed by an additional manual search in April 2021. We performed a one-group meta-analysis on the incidence and mortality of CAPA using a random-effect model. We identified 28 observational studies with a total of 3148 patients to be included in the meta-analysis. Among the 28 studies, 23 were conducted in Europe, two in Mexico and one each in China, Pakistan and the United States. Routine screening for secondary fungal infection was employed in 13 studies. The modified AspICU algorithm was utilised in 15 studies and was the most commonly used case definition and diagnostic algorithm for pulmonary aspergillosis. The incidence and mortality of CAPA in the ICU were estimated to be 10.2% (95% CI, 8.0-12.5; I2  = 82.0%) and 54.9% (95% CI, 45.6-64.2; I2  = 62.7%), respectively. In conclusion, our estimates may be utilised as a basis for surveillance of CAPA and prognostication in the ICU. Large, prospective cohort studies based on the new case definitions of CAPA are warranted to validate our estimates.

Putative invasive pulmonary aspergillosis in critically ill patients with COVID-19: An observational study from New York City.

BACKGROUND: Critically ill patients with coronavirus disease-2019 (COVID-19) are at the theoretical risk of invasive pulmonary aspergillosis (IPA) due to known risk factors. PATIENTS/METHODS: We aimed to describe the clinical features of COVID-19-associated pulmonary aspergillosis at a single centre in New York City. We performed a retrospective chart review of all patients with COVID-19 with Aspergillus isolated from respiratory cultures. RESULTS: A total of seven patients with COVID-19 who had one or more positive respiratory cultures for Aspergillus fumigatus were identified, all of whom were mechanically ventilated in the ICU. Four patients were classified as putative IPA. The median age was 79 years, and all patients were male. The patients had been mechanically ventilated for a mean of 6.8 days (range: 1-14 days) before Aspergillus isolation. Serum galactomannan level was positive for only one patient. The majority of our cases received much higher doses of glucocorticoids than the dosage with a proven mortality benefit. All four patients died. CONCLUSIONS: Vigilance for secondary fungal infections will be needed to reduce adverse outcomes in critically ill patients with COVID-19.

Giant cellulitis-like Sweet syndrome: An underrecognized clinical variant mimicking skin and soft tissue infection.

A new clinical variant of Sweet syndrome, called giant cellulitis-like Sweet syndrome, can masquerade as cellulitis because the patients present with an acute onset of large erythematous plaques, fever, and leukocytosis with neutrophil predominance. This case describes a 90-year-old female with a history of invasive ductal carcinoma of the breast who presented with 3 days of erythema of the right chest and right leg. Physical examination was notable for well-demarcated, blanching erythematous rashes involving the right chest and right lower extremity. Laboratory data was notable for neutrophilic leukocytosis. A clinical diagnosis of cellulitis was made initially, and intravenous cefazolin was initiated. The rash had only partially improved with antibiotics. Skin biopsy revealed a dense neutrophilic infiltrate, which was consistent with Sweet syndrome. Based on the widespread plaques, this case was considered a "giant cellulitis-like" variant of Sweet syndrome. Clinicians should have a high index of suspicion for Sweet syndrome when assessing a patient with fever, neutrophilia and erythematous skin plaques atypical of cellulitis because this condition does not respond to antimicrobial therapy and requires systemic glucocorticoid therapy.

Risk Factors for Positive Follow-Up Blood Cultures in Gram-Negative Bacilli Bacteremia: Implications for Selecting Who Needs Follow-Up Blood Cultures.

BACKGROUND: The value of follow-up blood cultures (FUBCs) to document clearance of bacteremia due to Gram-negative bacilli (GNB) has not been well established. Although previous studies suggested that the yield of FUBCs for GNB bacteremia is low, it remains to be elucidated for whom FUBC may be beneficial and for whom it is unnecessary. METHODS: A retrospective cohort study was performed at 4 acute care hospitals to identify risk factors for positive FUBCs with GNB bacteremia and to better guide clinicians' decisions as to which patients may or may not benefit from FUBCs. Participants included adult patients with GNB bacteremia who had FUBCs and were admitted between January 2017 and December 2018. The primary outcomes were the factors associated with positive FUBCs and the yield of FUBCs with and without the factors. RESULTS: Of 306 patients with GNB bacteremia who had FUBCs, 9.2% (95% confidence interval, 6.2%-13.0%) had the same GNB in FUBCs. In the multivariate logistic regression analysis, end-stage renal disease on hemodialysis, intravascular device, and bacteremia due to extended-spectrum ß-lactamase or carbapenemase-producing organism were identified as independent predictors of positive FUBCs with GNB bacteremia. Approximately 7 FUBCs and 30 FUBCs were needed for patients with ≥1 or no risk factors, respectively, to yield 1 positive result.SummaryThis multi-site retrospective cohort study found that among patients with gram-negative bacilli (GNB) bacteremia, having ESRD on hemodialysis, intravascular devices, or bacteremia due to multi-drug resistant GNB were each independently associated with having a positive follow-up blood culture. CONCLUSIONS: Follow-up blood culture may not be necessary for all patients with GNB bacteremia and has the highest yield in patients with 1 or more risk factors.

Rapid identification of genes controlling virulence and immunity in malaria parasites.

Identifying the genetic determinants of phenotypes that impact disease severity is of fundamental importance for the design of new interventions against malaria. Here we present a rapid genome-wide approach capable of identifying multiple genetic drivers of medically relevant phenotypes within malaria parasites via a single experiment at single gene or allele resolution. In a proof of principle study, we found that a previously undescribed single nucleotide polymorphism in the binding domain of the erythrocyte binding like protein (EBL) conferred a dramatic change in red blood cell invasion in mutant rodent malaria parasites Plasmodium yoelii. In the same experiment, we implicated merozoite surface protein 1 (MSP1) and other polymorphic proteins, as the major targets of strain-specific immunity. Using allelic replacement, we provide functional validation of the substitution in the EBL gene controlling the growth rate in the blood stages of the parasites.

Malignant Hypertension with Thrombotic Microangiopathy.

A 49-year-old man with malignant hypertension, acute kidney injury and mental deterioration was referred to our hospital. We initially observed microangiopathic hemolytic anemia, thrombocytopenia and kidney damage, indicating he had thrombotic microangiopathy (TMA). We considered TMA was caused by malignant hypertension and therefore did not start plasma therapy. The French TMA reference center reported that platelet counts and serum creatine levels have high values for predicting severe ADAMTS13 deficiency. The patient fully recovered from his illness after treatment with antihypertensive drugs and intermittent hemodialysis. This case might thus be useful to understand the proper differential diagnosis and treatment of TMA.

Fitz-Hugh-Curtis syndrome lacking typical characteristics of pelvic inflammatory disease.

A 23-year-old Japanese woman, previously a commercial sex worker, presented with a 2-day history of right upper quadrant (RUQ) abdominal pain, worse on deep inspiration. She had noticed increased vaginal discharge 2 months earlier and had developed dull, lower abdominal pain 3 weeks prior to presentation. Although pelvic examination and transvaginal ultrasonography revealed neither a tubal nor ovarian pathology, abdominal CT scan with contrast demonstrated early enhancement of the hepatic capsule, a finding pathognomonic for Fitz-Hugh-Curtis syndrome (FHCS). Cervical discharge PCR assay confirmed Chlamydia trachomatis infection. This case highlights that normal gynaecological evaluation may be insufficient to rule out FHCS, for which physicians should have a high index of suspicion when seeing any woman of reproductive age with RUQ pain.

Identification of odorant-binding protein genes from antennal expressed sequence tags of the onion fly, Delia antiqua.

Insect odorant-binding proteins (OBPs) are thought to play a crucial role in the chemosensation of hydrophobic molecules such as pheromones and host chemicals. The onion fly, Delia antiqua, is a specialist feeder of Allium plants, and utilizes a host odorant n-dipropyl disulfide as a cue for its oviposition. Because n-dipropyl disulfide is a highly hydrophobic compound, some OBPs might be indispensable for perception of it. However, no OBP gene has been identified in D. antiqua. Here, to obtain the DNA sequences of D. antiqua OBPs, we performed an analysis of antennal expressed sequence tags (ESTs). Among 288 EST clones, eight D. antiqua OBP genes were identified for the first time. Phylogenetic analysis revealed that each D. antiqua OBP gene is more closely related to its Drosophila orthologs than to the other D. antiqua OBP genes, suggesting that these OBP genes had emerged before the divergence of Delia and Drosophila species. All of the eight D. antiqua OBPs are expressed not only in the antennae but also in the legs, suggesting additional roles in the taste perception of non-volatile compounds. These findings serve as an important basis for understanding the molecular mechanisms underlying the host adaptations of D. antiqua.