The Limit of Detection Matters: The Case for Benchmarking Severe Acute Respiratory Syndrome Coronavirus 2 Testing.

BACKGROUND: Resolving the coronavirus disease 2019 (COVID-19) pandemic requires diagnostic testing to determine which individuals are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current gold standard is to perform reverse-transcription polymerase chain reaction (PCR) on nasopharyngeal samples. Best-in-class assays demonstrate a limit of detection (LoD) of approximately 100 copies of viral RNA per milliliter of transport media. However, LoDs of currently approved assays vary over 10,000-fold. Assays with higher LoDs will miss infected patients. However, the relative clinical sensitivity of these assays remains unknown. METHODS: Here we model the clinical sensitivities of assays based on their LoD. Cycle threshold (Ct) values were obtained from 4700 first-time positive patients using the Abbott RealTime SARS-CoV-2 Emergency Use Authorization test. We derived viral loads from Ct based on PCR principles and empiric analysis. A sliding scale relationship for predicting clinical sensitivity was developed from analysis of viral load distribution relative to assay LoD. RESULTS: Ct values were reliably repeatable over short time testing windows, providing support for use as a tool to estimate viral load. Viral load was found to be relatively evenly distributed across log10 bins of incremental viral load. Based on these data, each 10-fold increase in LoD is expected to lower assay sensitivity by approximately 13%. CONCLUSIONS: The assay LoD meaningfully impacts clinical performance of SARS-CoV-2 tests. The highest LoDs on the market will miss a majority of infected patients. Assays should therefore be benchmarked against a universal standard to allow cross-comparison of SARS-CoV-2 detection methods.

Infection prevention measures in acute care settings based on severe acute respiratory syndrome coronavirus 2 transmission patterns and risk: a review.

PURPOSE OF REVIEW: During the coronavirus disease 2019 pandemic, when facing extraordinary infection prevention challenges, acute care settings have balanced routine patient safety needs while minimizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission risk to patients and healthcare personnel (HCP). Mitigation strategies in acute care settings are based on a combination of basic science, environmental, and epidemiologic evidence. Here, we review the literature on SARS-CoV-2 transmission, how it has shaped infection prevention interventions in acute care settings, and the results of such measures to reduce transmission. RECENT FINDINGS: HCP adherence to transmission-based precautions in acute care settings, such as the use of personal protective equipment (PPE), is essential to mitigating SARS-CoV-2 spread. Although the SARS-CoV-2 virus has been isolated in nonrespiratory body sites, such exposure has not been shown to definitively cause transmission in humans. Epidemiologic evidence has demonstrated that implementation and adherence to infection prevention strategies reduces acute setting transmission. SUMMARY: Given SARS-CoV-2 infection occurs primarily through respiratory transmission, preventing HCP acquisition requires fidelity to consistent PPE usage. Infection prevention strategies and implementation of transmission-based precautions have reduced spread and outbreaks. Epidemiologic studies of acute care outbreaks often include reports of PPE nonadherence and community exposure contributing to SARS-CoV-2 transmission within this setting.

Neostigmine Administered With MoviPrep Improves Bowel Preparation for Elective Colonoscopy in Patients With Spinal Cord Injury: A Randomized Study.

BACKGROUND: Poor preparation for elective colonoscopy is exceedingly common in persons with spinal cord injury (SCI). This unsatisfactory outcome is likely due to long-standing difficulty with evacuation and decreased colonic motility, which may result in inadequate responses to conventional bowel preparation regimens. We determined whether the addition of neostigmine to MoviPrep before elective colonoscopy produced a higher percentage of acceptable bowel preparations in patients with SCI. METHODS: Twenty-seven SCI subjects were prospectively randomized to 1 of 2 arms: low-volume polyethylene glycol-electrolyte lavage with ascorbic acid (MoviPrep) or MoviPrep plus neostigmine methylsulfate and glycopyrrolate (MoviPrep+NG); 28 able-bodied subjects received MoviPrep alone. The quality of the cleansing preparation for colonoscopy was determined by gastroenterologists "calibrated" to use the Ottawa Scoring System, with an acceptable Ottawa Score (OS) considered to be ≤3. RESULTS: The administration of MoviPrep alone resulted in suboptimal bowel cleansing in the SCI group compared with the able-bodied group (50% vs. 89% of subjects had an acceptable OS; χ=7.94, P=0.05). However, when NG was added to MoviPrep in the SCI group, it markedly improved the quality of the bowel preparation, with 85% of patients then having an acceptable OS. The use of NG resulted in minimal bloating and distention before bowel evacuation (P=0.0005), and eye and muscle twitching; these were resolved within 1 hour after NG administration. No significant differences were noted among the preparation groups for adenoma detection rate (P=0.41). CONCLUSIONS: The combination of MoviPrep+NG was safe, well tolerated, and an effective approach to prepare the bowel for elective colonoscopy in patients with SCI. The side effects of this preparation were significant compared with the other treatment groups but were considered mild and anticipated.

Cognition may be related to arterial pulsatility index in HD patients.

AIMS: Hemodialysis (HD) patients have a heavy burden of subclinical cerebrovascular disease and cognitive changes consistent with a vascular etiology. Pulsatility index is associated with microangiopathy of cerebral blood vessels and an increased risk of cerebral infarction. The proposed study was to determine common carotid artery pulsatility index (CCAPI) and its relation to cognition in well-dialyzed HD patients with no history of stroke or dementia and matched controls. METHODS: Observational, cross-sectional study of CCAPI and cognition in 37 hemodialysis outpatients and 18 matched controls with normal kidney function. Non-parametric analyses were used to compare variables between groups. Multiple regression and ANOVA models were used to adjust for risk factor differences. RESULTS: Controls had a lower CCAPI than the HD group (1.7 ± 0.3 vs. 2.1 ± 0.4 cm/s, p = 0.006). HD patients scored significantly lower on all cognitive domains. Attention correlated with CCAPI in HD patients, independent of hypertension, diabetes, hyperlipidemia, and years on HD (r2 = -0.36, p = 0.01). CCAPI correlated with years on HD, independent of traditional cardiovascular risk factors. (r2 = 0.26, p = 0.04). CONCLUSION: In well-dialyzed hemodialysis patients with no history of stroke or dementia, CCAPI may correlate with cognitive function and represent a marker for underlying cerebral microvascular disease.

Examining Antimicrobial Stewardship Program Implementation in Carceral Settings.

Antimicrobial resistance is a global threat that inequitably affects minoritized populations, including Black, Latinx, and Indigenous people-especially in carceral settings-and is largely driven by inappropriate antimicrobial prescribing practices. People whose identities are minoritized are more likely to be incarcerated, and people who are incarcerated experience higher disease risk than people who are not incarcerated. This article draws on a case of dental infection suffered by a woman who is incarcerated to consider key ethical and clinical complexities of antimicrobial prescribing in carceral settings.

Diagnostic stewardship and the coronavirus disease 2019 (COVID-19) pandemic: Lessons learned for prevention of emerging infectious diseases in acute-care settings.

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated the importance of stewardship of viral diagnostic tests to aid infection prevention efforts in healthcare facilities. We highlight diagnostic stewardship lessons learned during the COVID-19 pandemic and discuss how diagnostic stewardship principles can inform management and mitigation of future emerging pathogens in acute-care settings. Diagnostic stewardship during the COVID-19 pandemic evolved as information regarding transmission (eg, routes, timing, and efficiency of transmission) became available. Diagnostic testing approaches varied depending on the availability of tests and when supplies and resources became available. Diagnostic stewardship lessons learned from the COVID-19 pandemic include the importance of prioritizing robust infection prevention mitigation controls above universal admission testing and considering preprocedure testing, contact tracing, and surveillance in the healthcare facility in certain scenarios. In the future, optimal diagnostic stewardship approaches should be tailored to specific pathogen virulence, transmissibility, and transmission routes, as well as disease severity, availability of effective treatments and vaccines, and timing of infectiousness relative to symptoms. This document is part of a series of papers developed by the Society of Healthcare Epidemiology of America on diagnostic stewardship in infection prevention and antibiotic stewardship.1.

Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa.

JOURNAL/nrgr/04.03/01300535-202419110-00034/figure1/v/2024-03-08T184507Z/r/image-tiff Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors, leading to progressive photoreceptor loss. Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival. This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation (tcES) in mice affected by inherited retinal degeneration. Additionally, the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans. In this study, we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular, sine, and ramp waveforms. To investigate the functional effects of electrical stimulation on photoreceptors, we used human retinal explant cultures and rhodopsin knockout (Rho-/-) mice, demonstrating progressive photoreceptor degeneration with age. Human retinal explants isolated from the donors' eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro. Photoreceptor density was evaluated by rhodopsin immunolabeling. In vivo Rho-/- mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms. Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response (OMR), respectively. Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas. Oscilloscope recordings indicated effective delivery of rectangular, sine, and ramp waveforms to the retina by transcorneal electrical stimulation, of which the ramp waveform required the lowest voltage. Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes. The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro (~0.5-1.5°C). Electrical stimulation increased photoreceptor survival in human retinal explant cultures, particularly at the ramp waveform. Transcorneal electrical stimulation (rectangular + ramp) waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results. Histology and immunolabeling demonstrated increased photoreceptor survival, improved outer nuclear layer thickness, and increased bipolar cell sprouting in Rho-/- mice. These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina, improves photoreceptor survival in both human and mouse retinas, and increases visual function in Rho-/- mice. Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.

Clinical and radiological septic joint analysis of spontaneous sternoclavicular joint infections: achieving the best outcomes-a systems engineering approach.

OBJECTIVES: Spontaneous sternoclavicular joint infection (SSCJI) is a rare and poorly understood disease process. This study aims to identify factors guiding effective management strategies for SSCJI by using data mining. METHODS: An Institutional Review Board-approved retrospective review of patients from 2 large hospitals (2010-2022) was conducted. SSCJI is defined as a joint infection without direct trauma or radiation, direct instrumentation or contiguous spread. An interdisciplinary team consisting of thoracic surgeons, radiologists, infectious disease specialists, orthopaedic surgeons, hospital information experts and systems engineers selected relevant variables. Small set data mining algorithms, utilizing systems engineering, were employed to assess the impact of variables on patient outcomes. RESULTS: A total of 73 variables were chosen and 54 analysed against 11 different outcomes. Forty-seven patients [mean age 51 (22-82); 77% male] met criteria. Among them, 34 underwent early joint surgical resection (<14 days), 5 patients received delayed surgical intervention (>14 days) and 8 had antibiotic-only management. The antibiotic-only group had comparable outcomes. Indicators of poor outcomes were soft tissue fluid >4.5 cm, previous SSCJI, moderate/significant bony fragments, HgbA1c >13.9% and moderate/significant bony sclerosis. CONCLUSIONS: This study suggests that targeted antibiotic-only therapy should be considered initially for SSCJI cases while concurrently managing comorbidities. Patients displaying indicators of poor outcomes or no symptomatic improvement after antibiotic-only therapy should be considered for surgical joint resection.

Hemodynamic effects of L-threo-3,4-dihydroxyphenylserine (Droxidopa) in hypotensive individuals with spinal cord injury.

OBJECTIVES: To determine the effect of an escalating dose of droxidopa (100, 200, and 400 mg) compared with placebo on seated blood pressure (BP) in hypotensive individuals with spinal cord injury (SCI). Secondarily, we aimed to determine the effect of droxidopa on (1) supine BP and heart rate, (2) the change in BP and heart rate when these individuals were transferred from the supine to the seated position, and (3) adverse event (AE) reporting. DESIGN: Open-label dose titration trial. SETTING: A Veterans Administration Medical Center. PARTICIPANTS: Participants with SCI (C3-T12) (N=10) were studied during 4 laboratory visits. Subjects visited the laboratory for about 5 hours on each visit, which incorporated a 30-minute seated baseline, a 30- to 60-minute supine, and a 4-hour seated postdrug observation. INTERVENTIONS: Placebo on visit 1, droxidopa 100 mg on visit 2, droxidopa 200 mg on visit 3, and droxidopa 400 mg on visit 4. MAIN OUTCOME MEASURES: BP and heart rate changes from baseline to the postdrug period, orthostatic heart rate and BP responses, and subjective AE reporting. RESULTS: Seated BP was significantly elevated with 400 mg droxidopa compared with placebo and 100 mg droxidopa for 3 hours and was elevated for 2 hours compared with 200 mg droxidopa. Increase in supine BP was not worsened following droxidopa, and the expected fall in BP when transferred to the seated position was prevented with droxidopa 200 and 400 mg. There were no significant differences in the heart rate response or AE reporting among the study visits. CONCLUSIONS: Our preliminary findings suggest that droxidopa, at the doses tested, does not cause excessive increases in supine BP and the 400-mg dose appears to be effective at increasing seated BP for up to 3 hours in persons with SCI.

A prospective report on the prevalence of heart rate and blood pressure abnormalities in veterans with spinal cord injuries.

OBJECTIVE: Decentralized autonomic cardiovascular regulation may lead to increased prevalence of heart rate (HR) and blood pressure (BP) abnormalities in veterans with SCI. In addition, comorbid medical conditions and prescription medication use may increase HR and BP abnormalities. These abnormalities include bradycardia, and tachycardia, hypotension, hypertension as well as autonomic dysreflexia and orthostatic hypotension; the prevalence of which is unknown. DESIGN: HR and BP data were measured during a routine annual physical examination in 64 veterans with SCI. Measurements of HR and BP were recorded in the seated and supine positions to document the influence of body position and to document intra-subject variability in these assessments. RESULTS: All subjects were chronically injured (20 ± 14 years), 33 subjects were tetraplegic (T: C3-C8), nine had high paraplegia (HP: T1-T6), and 22 had low paraplegia (LP: T7-L2). Regardless of position, the prevalence of bradycardia was increased in the T group, whereas prevalence of tachycardia was increased in the HP and LP groups. Systolic hypotension was more common in the T and HP groups than the LP group and positional effects were most evident in the T group. Systolic hypertension was comparable in the T and HP groups but was twice as prevalent in the LP group. Increased prevalence of individuals with three or more medical conditions and prescribed three or more medications which might influence HR and BP was observed. CONCLUSION: Decentralized autonomic regulation, comorbid medical conditions, and prescription medication use in veterans with SCI result in HR and BP abnormalities; our data suggest that these abnormalities vary depending on the level of injury and orthostatic positioning.

Multidisciplinary Teams for the Management of Infective Endocarditis: A Systematic Review and Meta-analysis.

Background: The management of infective endocarditis (IE) is complex owing to a high burden of morbidity and mortality. Recent guidelines recommend dedicated multidisciplinary teams (MDTs) for the management of IE. The aim of this systematic review and meta-analysis was to evaluate and summarize the effect of MDT management on patient outcomes. Methods: A systematic review was performed and, where feasible, results were meta-analyzed; otherwise, results were summarized narratively. Data extraction and quality assessment were performed in duplicate. Restricted maximum likelihood random effects models were used to calculate unadjusted risk ratios and 95% CIs. Results: Screening of 2343 studies based on title and abstract yielded 60 full-text reviews; 18 studies were summarized narratively, of which 15 were included in a meta-analysis of short-term mortality. Meta-analysis resulted in a risk ratio of 0.61 (95% CI, .47-.78; I2 = 62%) for mortality in favor of a dedicated MDT as compared with usual care. Length of stay was variable, with 55% (10/18) of studies reporting an increased length of stay. Most studies (16/18, 88.9%) reported a decreased time to surgery and an increased rate of surgery (13/18, 73%). No studies reported on patient-reported outcomes. Conclusions: This is the first systematic review and meta-analysis to assess the impact of MDT management on IE. The sum of evidence demonstrated a significant association between MDTs and improved short-term mortality. Further research is needed to evaluate benefits of virtual MDT care, cost-effectiveness, and the impact on patient-reported outcomes and long-term mortality.

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

Navigating the 2021 update to the IDSA/SHEA Clostridioides difficile guidelines: An ethical approach to equitable patient care.

The 2021 focused update to the Infections Diseases Society of America/Society for Healthcare Epidemiology of America (IDSA/SHEA) guidelines for management of Clostridioides difficile infection (CDI) prioritizes the use of fidaxomicin over vancomycin for the treatment of initial and recurrent CDI. These recommendations have significant clinical and financial ramifications for hospitals and patients with CDI. Antimicrobial stewardship programs must balance the needs, goals, and barriers faced by patients and health systems when determining the best treatment strategy for CDI. In this commentary, we provide antimicrobial stewardship programs with a decision-making framework that acknowledges the fundamental principles of ethics to provide equitable patient care.

Assessing changes to N95 respirator filtration efficiency, qualitative and quantitative fit, and seal check with repeated vaporized hydrogen peroxide (VHP) decontamination.

N95 respirators were reprocessed using vaporized hydrogen peroxide to supplement limited supplies during the COVID-19 pandemic. In this study, we found no statistically significant differences in qualitative and quantitative fit or filtration efficiency with reprocessing. Filtration efficiency remained above 95% even at 25 cycles of reprocessing without statistically significant change from cycle 20-25 compared to cycle 0 (P = .10, P = .05, respectively). Vaporous hydrogen peroxide is an effective option to augment N95 respirator supplies.

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Antimicrobial ethicists: Making ethics explicit in antimicrobial stewardship.

Antimicrobial prescribing and the associated discipline of antimicrobial stewardship have inherent ethical and moral dimensions. We contend that the explicit, formal application of ethical principles and frameworks can strengthen and further justify the value of antimicrobial stewardship programs and their work. To illustrate the value of this process, we highlight 3 ethical scenarios that antimicrobial stewardship programs regularly encounter at the prescriber, institutional, and societal levels, and we analyze these scenarios using the Beauchamp and Childress biomedical ethics framework.

Intravenous cephalosporin versus non-cephalosporin-based prophylaxis to prevent surgical site infections in colorectal surgery patients: A systematic review and meta-analysis.

BACKGROUND: Surgical site infection (SSI) is common in colorectal surgery patients and associated with morbidity and mortality. Guidelines recommend preoperative intravenous antimicrobial prophylaxis with aerobic and anaerobic coverage to reduce SSI risk. Cephalosporin based prophylaxis (CBP) regimens are recommended as first-line prophylaxis, and non-cephalosporin based are recommended as alternative prophylaxis (AP). We evaluate the efficacy of CBP versus AP in preventing surgical site infections in colorectal surgery patients. METHODS: A systematic review and meta-analysis was conducted of studies published between 2005 and 2020 in MEDLINE and Web of Science. Studies were excluded if intravenous antimicrobial prophylaxis was not administered, or if oral and intravenous prophylaxis were routinely co-administered. Heterogeneity was reported using the Q-statistic and I2-statistic. Publication bias was evaluated using a funnel plot and Egger test for small study effects. Statistical significance was defined as a two-sided p < 0.05. RESULTS: 11 studies met inclusion criteria. AP was not associated with increased SSI risk at 30 days compared to CBP (OR 1.01, 95% CI 0.91, 1.13; OR < 1 favors AP). There was no effect size variability in subgroup analysis comparing higher-to lower-quality studies (I2 = 99%, P = 0.17). Subgroup analysis by publication year approached a significant difference in effect size between studies published prior to 2014 and later than 2014 (I2 = 99%, P = 0.06). CONCLUSIONS: Meta-analysis of 11 studies of SSI risk in adult colorectal surgery patients suggest that SSI risk is similar for patients receiving CBP or AP, subgroup analysis of studies published since 2014 suggest increased SSI risk with AP compared to CBP.

Diminishing returns, increasing risks: Impact of antibiotic duration of therapy on respiratory bacterial isolates in hospitalized patients during the coronavirus disease 2019 (COVID-19) pandemic.

In 829 hospital encounters for patients with COVID-19, 73.2% included orders for antibiotics; however, only 1.8% had respiratory cultures during the first 3 hospital days isolating bacteria. Case-control analysis of 30 patients and 96 controls found that each antibiotic day increased the risk of isolating multidrug-resistant gram-negative bacteria (MDR-GNB) in respiratory cultures by 6.5%.

Case Report: Refractory Cryptosporidiosis after CAR T-Cell Therapy for Lymphoma.

Cryptosporidial diarrhea is uncommon in immunocompetent individuals, more often seen in severely immunocompromised patients. Severe refractory cases have been described in patients with HIV/AIDS before the advent of modern antiretroviral therapy due to an inability to mount an adequate cellular immune response. We describe an 85-year-old patient post-chimeric antigen receptor T-cell therapy relapsed lymphoma who developed refractory Cryptosporidium spp. diarrhea in the setting of persistent CD4+ cytopenia. Despite receiving multiple antiparasitic agents, including failure of a prolonged course of nitazoxanide, the patient experienced persistent symptoms for 9 months with repeatedly positivity stool Cryptosporidium spp. direct fluorescent antibody (DFA) test. We highlight this case of refractory Cryptosporidium spp. and the importance of recognizing the pathogen in a non-HIV-infected immunosuppressed host.

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).

IMPORTANCE: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. OBJECTIVE: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. MAIN OUTCOMES AND MEASURES: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. RESULTS: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. CONCLUSIONS AND RELEVANCE: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.