Low infectivity among asymptomatic patients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) admission test at a tertiary care center, 2020-2022.

We used a strand-specific RT-qPCR to evaluate viral replication as a surrogate for infectiousness among 242 asymptomatic inpatients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) admission test. Only 21 patients (9%) had detectable SARS-CoV-2 minus-strand RNA. Because most patients were found to be noninfectious, our findings support the suspension of asymptomatic admission testing.

Superior Accuracy of Aspergillus Plasma Cell-Free DNA Polymerase Chain Reaction Over Serum Galactomannan for the Diagnosis of Invasive Aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) in immunocompromised hosts carries high morbidity and mortality. Diagnosis is often delayed because definitive diagnosis requires invasive specimen collection, while noninvasive testing with galactomannan is moderately accurate. Plasma cell-free DNA polymerase chain reaction (cfDNA PCR) represents a novel testing modality for the noninvasive diagnosis of invasive fungal disease (IFD). We directly compared the performance of Aspergillus plasma cfDNA PCR with serum galactomannan for the diagnosis of IA during routine clinical practice. METHODS: We conducted a retrospective study of all patients with suspected IFD who had Aspergillus plasma cfDNA PCR testing at Stanford Health Care from 1 September 2020 to 30 October 2022. Patients were categorized into proven, probable, possible, and no IA based on the EORTC/MSG definitions. Primary outcomes included the clinical sensitivity and specificity for Aspergillus plasma cfDNA PCR and galactomannan. RESULTS: Overall, 238 unique patients with Aspergillus plasma cfDNA PCR test results, including 63 positives and 175 nonconsecutive negatives, were included in this study. The majority were immunosuppressed (89.9%) with 22.3% 30-day all-cause mortality. The overall sensitivity and specificity of Aspergillus plasma cfDNA PCR were 86.0% (37 of 43; 95% confidence interval [CI], 72.7-95.7) and 93.1% (121 of 130; 95% CI, 87.4-96.3), respectively. The sensitivity and specificity of serum galactomannan in hematologic malignancies/stem cell transplants were 67.9% (19 of 28; 95% CI, 49.3-82.1) and 89.8% (53 of 59; 95% CI, 79.5-95.3), respectively. The sensitivity of cfDNA PCR was 93.0% (40 of 43; 95% CI, 80.9-98.5) in patients with a new diagnosis of IA. CONCLUSIONS: Aspergillus plasma cfDNA PCR represents a more sensitive alternative to serum galactomannan for noninvasive diagnosis of IA.

Use of a severe acute respiratory coronavirus virus 2 (SARS-CoV-2) strand-specific assay to evaluate for prolonged viral replication >20 days from illness onset.

Severe acute respiratory coronavirus virus 2 (SARS-CoV-2) real-time reverse-transcription polymerase chain reaction (rRT-PCR) strand-specific assay can be used to identify active SARS-CoV-2 viral replication. We describe the characteristics of 337 hospitalized patients with at least 1 minus-strand SARS-CoV-2 assay performed >20 days after illness onset. This test is a novel tool to identify high-risk hospitalized patients with prolonged SARS-CoV-2 replication.

High-titer post-vaccine COVID-19 convalescent plasma for immunocompromised patients during the first omicron surge.

BACKGROUND: Transplant and hematologic malignancy patients have high Coronavirus disease 2019 (COVID-19) mortality and impaired vaccination responses. Omicron variant evades several monoclonal antibodies previously used in immunocompromised patients. Polyclonal COVID-19 convalescent plasma (CCP) may provide broader neutralizing capacity against new variants at high titers. Vaccination increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer in convalescent donors. METHODS: We conducted a retrospective chart review of hospitalized immunocompromised patients with COVID-19 who received high-titer CCP during the first omicron surge, collected from vaccinated donors within 6 months of pre-omicron COVID-19. Data on safety and outcomes were extracted. RESULTS: A total of 44 immunocompromised patients were included, 59.1% with solid organ transplant, 22.7% with hematopoietic cell transplant, 11.4% with hematologic malignancy, and 6.8% with autoimmune disease. Overall, 95% of CCP units transfused were from recently recovered and vaccinated donors and had SARS-CoV-2 antibody results 8- to 37-fold higher than the Food and Drug Administration's cutoff for high-titer CCP. There were two mild transfusion reactions. A total of 30-day mortality was 4.5%. There were no differences in 100-day mortality by underlying diagnosis, levels of immunosuppression, and timing of CCP administration. Patients with higher immunosuppression had significantly higher mean World Health Organization clinical progression scores at 30-day post-CCP compared to those with lower immunosuppression. CONCLUSIONS: CCP is a safe, globally available treatment for immunocompromised patients with COVID-19. Mortality was lower in our cohort than that of COVID-19 patients with similar immunocompromising conditions. Post-vaccine CCP with very high titers should be prioritized for study in immunocompromised patients. Post-vaccine CCP has the potential to keep pace with new variants by overcoming mutations at sufficiently high titer.

Herpes Simplex Virus and Varicella Zoster Virus Infections in Cancer Patients.

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are alpha herpesviruses that establish life-long latent infection in neuronal ganglia after primary infection. Periodic reactivation of these viruses results in recurrent infections that can have significant impact on patients' quality of life. HSV commonly causes oral and genital mucocutaneous infections whereas VZV is responsible for varicella/chickenpox and herpes zoster/shingles, but cancer patients are at particularly higher risk of complications including disseminated and visceral infections due to impaired cell-mediated immunity. While diagnosis of more common HSV and/or VZV infections is frequently clinically based, immunocompromised hosts may have atypical skin presentation or visceral involvement. Thus, diagnostic confirmation using virus-specific tests such as polymerase chain reaction or immunohistochemical staining is crucial in some cases. Oral acyclovir, valacyclovir and famciclovir are usually used for mild to moderate infections and intravenous acyclovir is the drug of choice for severe or disseminated infections. Foscarnet can be used when acyclovir-resistance is confirmed or suspected. Pharmaceutical prophylaxis against HSV and/or VZV should be considered in high-risk cancers patients. Currently, there is no commercially available vaccine against HSV, but VZV vaccines are available to prevent varicella and zoster.

Balamuthia mandrillaris brain infection: a rare cause of a ring-enhancing central nervous system lesion. Illustrative case.

BACKGROUND: An 80-year-old man presented with subacute mental status change, dizziness, and left-sided vision loss. Magnetic resonance imaging demonstrated a ring-enhancing right parietooccipital lesion. OBSERVATIONS: Biopsy and laboratory testing demonstrated an amoebic Balamuthia mandrillaris infection. Fewer than 200 cases of this infection have been recognized in the United States, and no standardized treatment regimen currently exists. LESSONS: Rapid antimicrobial therapy with miltefosine, azithromycin, fluconazole, flucytosine, sulfadiazine, and albendazole was initiated. The pathophysiology, diagnosis, and management of this infection and the patient's course were reviewed. The importance of biopsy for pathologic and laboratory diagnosis and rapid treatment initiation with a multidisciplinary team was reinforced.

Case-control study evaluating risk factors for SARS-CoV-2 outbreak amongst healthcare personnel at a tertiary care center.

BACKGROUND: Despite several outbreaks of SARS-CoV-2 amongst healthcare personnel (HCP) exposed to COVID-19 patients globally, risk factors for transmission remain poorly understood. METHODS: We conducted an outbreak investigation and case-control study to evaluate SARS-CoV-2 transmission risk in an outbreak among HCP at an academic medical center in California that was confirmed by whole genome sequencing. RESULTS: A total of 7/9 cases and 93/182 controls completed a voluntary survey about risk factors. Compared to controls, cases reported significantly more patient contact time. Cases were also significantly more likely to have performed airway procedures on the index patient, particularly placing the patient on high flow nasal cannula, continuous positive airway pressure (CPAP), or bilevel positive airway pressure (BiPAP) (OR = 11.6; 95% CI = 1.7 -132.1). DISCUSSION: This study highlights the risk of nosocomial infection of SARS-CoV-2 from patients who become infectious midway into their hospitalization. Our findings also reinforce the importance of patient contact time and aerosol-generating procedures as key risk factors for HCP infection with SARS-CoV-2. CONCLUSIONS: Re-testing patients for SARS-CoV-2 after admission in suspicious cases and using N95 masks for all aerosol-generating procedures regardless of initial patient SARS-CoV-2 test results can help reduce the risk of SARS-COV-2 transmission to HCP.

Immune reconstitution inflammatory syndrome in Mycobacterium chimaera mediastinitis: When clinical judgment trumps imaging.

Mycobacterium chimaera has been described in postoperative cardiovascular procedures in patients after an outbreak of contaminated 3T heater-cooler units. Immune reconstitution inflammatory syndrome (IRIS) has been mostly reported in immunocompromised patients, especially HIV after starting therapy. Our case is a 52-year-old immunocompetent male who was diagnosed with M. chimaera mediastinitis a year after Type A dissection repair and was started on quadruple antimicrobial therapy. He clinically improved but 8 months into therapy he presented with a declining kidney function, pancytopenia, and hypercalcemia which after bone marrow and kidney biopsies were attributed to IRIS. Our patient's diagnosis spared him subsequent surgery. IRIS during the treatment of nontuberculous mycobacteria must be suspected even in immunocompetent patients as reaching the diagnosis is very helpful in preventing additional diagnostic and therapeutic measures.

Pseudomonas MitraClip® endocarditis: A case report and review of literature.

Endocarditis from Pseudomonas aeruginosa is a rare cause of endocarditis with most of those cases in patients with intravenous drug abuse. The MitraClip® is a relatively new device with few incidences of endocarditis in the literature. Here we present the first reported case of pseudomonal endocarditis of a MitraClip® in a non-IV drug user.

Emergence of Mycobacterium simiae: A retrospective study from a tertiary care center in Lebanon.

OBJECTIVE: The objective of this study is to describe the clinical significance of Mycobacterium simiae at a major tertiary care center in Lebanon. METHODS: This is a retrospective study of patients with positive cultures for M. simiae isolated between 2004 and 2016 at the American University of Beirut Medical Center. RESULTS: This study included 103 M. simiae isolates recovered from 51 patients. Their mean age was 62.7 years. The majority were males and smokers. Specimens were mostly from respiratory sources (97%). Common comorbidities included chronic lung disease (such as chronic obstructive pulmonary disease), solid tumor, systemic disease, and diabetes mellitus. Productive cough and dyspnea were the most common symptoms. Frequent radiographic findings were infiltrates and nodules on chest X-ray and nodules, infiltrates, and bronchiectasis on chest computed tomography scan. Among 18 tested isolates, 5.8% were resistant to clarithromycin, 11.7% to amikacin, and 70-100% to other antimicrobials. Out of 13 patients receiving early treatment, 5 noted improvement, one had recurrence of symptoms, two received alternative diagnosis, and five died. Two of those deaths were related to M. simiae. Common treatment regimens included clarithromycin in different combinations with trimethoprim-sulfamethoxazole, moxifloxacin, and amikacin. Moreover, clofazimine was used in only two patients whose isolates were resistant to all but one agent. Duration of treatment ranged from 6-24 months. CONCLUSION: In Lebanon, M. simiae is increasingly encountered with true infection rates of at least 47%. Furthermore, the prevalence of multidrug resistance among the Lebanese M. simiae isolates is very high limiting the treatment options.

Multi-drug resistant Acinetobacter species: a seven-year experience from a tertiary care center in Lebanon.

Background: Acinetobacter species have become increasingly common in the intensive care units (ICU) over the past two decades, causing serious infections. At the American University of Beirut Medical Center, the incidence of multi-drug resistant Acinetobacter baumannii (MDR-Ab) infections in the ICU increased sharply in 2007 by around 120%, and these infections have continued to cause a serious problem to this day. Methods: We conducted a seven-year prospective cohort study between 2007 and 2014 in the ICU. Early in the epidemic, a case-control study was performed that included MDR-Ab cases diagnosed between 2007 and 2008 and uninfected controls admitted to the ICU during the same time. Results: The total number of patients with MDR-Ab infections diagnosed between 2007 and 2014 was 128. There were also 99 patients with MDR-Ab colonization without evidence of active infection between 2011 and 2014. The incidence of MDR-Ab transmission was 315.4 cases/1000 ICU patient-days. The majority of infections were considered hospital-acquired (84%) and most consisted of respiratory infections (53.1%). The mortality rate of patients with MDR-Ab ranged from 52% to 66%. Conclusion: MDR-Ab infections mostly consisted of ventilator-associated pneumonia and were associated with a very high mortality rate. Infection control measures should be reinforced to control the transmission of these organisms in the ICU.

Increase of blaOXA-23-like in Acinetobacter baumannii at a tertiary care center in Lebanon between 2007 and 2013.

INTRODUCTION: The multi-drug resistant nature of Acinetobacter baumannii isolates have rendered many broad-spectrum antimicrobial agents ineffective against them. The purpose of this retrospective study is to define and compare the molecular characteristics of A. baumannii isolates from patients at a tertiary care center in Lebanon from two outbreaks, the first in 2007-2008, as part of a case-controlled study involving A. baumannii cases admitted to the ICU, and the second in 2013. METHODOLOGY: A total of 148 A. baumannii clinical isolates were collected from various clinical specimens during 2007-2008 and 2013. All A. baumannii isolates were screened for blaOXA-23-like and blaOXA-51-like genes of carbapenem resistance. Additionally, in an effort to assess the degree of the isolates' genomic relatedness, random amplification of polymorphic DNA (RAPD) was performed. RESULTS: There was an increase in the prevalence of blaOXA-23-like and blaOXA-51-like genes between the two time periods; however, only 22% isolate genomic relatedness was calculated between 2007-2008 and 2013. Taking 80% as a margin of compatibility, 31 distinct clusters containing 2 to 11 strains were observed when both time periods were analyzed. CONCLUSION: The presence of numerous clusters accompanied by a predominant increase in the prevalence of blaOXA-23-like between 2007 and 2013 suggests a horizontal transmission of the gene within various strains of the species, contributing to the persistent increase in carbapenem resistance over the years. Therefore, infection control measures are required with compliance among all healthcare workers.

Increased blaOXA-23-like prevalence in Acinetobacter baumannii at a tertiary care center in Lebanon (2007-2013).

INTRODUCTION: Acinetobacter baumannii has become one of the most feared organisms in hospital-acquired infections during the past decades. Their multi-drug resistant profiles have rendered many broad-spectrum antibiotics ineffective. The purpose of this retrospective study is to describe and compare molecular characteristics of A. baumannii isolated from patients at a tertiary care center in Lebanon from two outbreaks, the first in 2007-2008 as part of a case-controlled study involving Acinetobacter baumannii cases admitted to the ICU and the second in 2013. METHODOLOGY: A total of 148 A. baumannii clinical isolates were collected from various clinical specimens during 2007-2008 and 2013. All A. baumannii isolates were subjected to PCR amplification of blaOXA-23-like and blaOXA-51-like genes of carbapenem resistance. Random amplification of polymorphic DNA (RAPD) was also performed to assess their genomic relatedness. RESULTS: There was an increase in the prevalence of blaOXA-23-like and blaOXA-51-like between the two time periods; however, only with 22% genomic relatedness between 2007-2008 and 2013 isolates. Taking 80% as margin of compatibility, 31 distinct clusters containing 2 to 11 strains were observed in both time periods. CONCLUSION: The presence of numerous clusters accompanied by a predominant increase in the prevalence of blaOXA-23-like gene between 2007 and 2013 suggests a horizontal transmission of the gene within various strains of the species, constituting a primary factor in the continued increase of carbapenem resistance over the years. As such, infection control measures ought to be taken with the highest priority and compliance among all involved healthcare workers is of utmost importance.

HACEK endocarditis: a review.

INTRODUCTION: The HACEK group, referring to Haemophilus spp., Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae, is a rare cause of infective endocarditis (IE). It causes the majority of Gram-negative endocarditis cases and has an excellent prognosis and simple management if properly identified. However, delay in diagnosis and associated complications can render the infection fatal. AREAS COVERED: Over the past few decades, there have been tremendous advancements in understanding the manifestations and progression of HACEK endocarditis (HE). This review tackles the epidemiology of HE, the microbiological characteristics of each organism in the HACEK group, the methods used to diagnose HE, the clinical manifestations, complications, and mortality of patients with HE, as well as the recommended treatment and preventive methods. Expert Commentary: The lack of robust randomized controlled trials in diagnosis and treatment of HE makes it difficult to determine the optimal management of such infections. Nevertheless, advancements in culturing methods have shown progress in isolating and identifying these fastidious organisms. Positive blood cultures for any of the HACEK organisms in the setting of no definite focus of infection is highly suggestive of HE. In such cases, treatment with ceftriaxone or a fluoroquinolone, even without obtaining antibiotic susceptibilities, should be initiated. Moreover, the decision to proceed with surgical intervention should be individualized. As is the case for other IE, HE requires the collaboration of a multidisciplinary team consisting of the infectious disease specialist, cardiologist, cardiothoracic surgeon, and the microbiologist.