The impact of COVID-19 monoclonal antibodies on clinical outcomes: A retrospective cohort study.

PURPOSE: Despite progress in the treatment of coronavirus disease 2019 (COVID-19), including the development of monoclonal antibodies (mAbs), more clinical data to support the use of mAbs in outpatients with COVID-19 is needed. This study is designed to determine the impact of bamlanivimab, bamlanivimab/etesevimab, or casirivimab/imdevimab on clinical outcomes within 30 days of COVID-19 diagnosis. METHODS: A retrospective cohort study was conducted at a single academic medical center with 3 campuses in Manhattan, Brooklyn, and Long Island, NY. Patients 12 years of age or older who tested positive for COVID-19 or were treated with a COVID-19-specific therapy, including COVID-19 mAb therapies, at the study site between November 24, 2020, and May 15, 2021, were included. The primary outcomes included rates of emergency department (ED) visit, inpatient admission, intensive care unit (ICU) admission, or death within 30 days from the date of COVID-19 diagnosis. RESULTS: A total of 1,344 mAb-treated patients were propensity matched to 1,344 patients with COVID-19 patients who were not treated with mAb therapy. Within 30 days of diagnosis, among the patients who received mAb therapy, 101 (7.5%) presented to the ED and 79 (5.9%) were admitted. Among the patients who did not receive mAb therapy, 165 (12.3%) presented to the ED and 156 (11.6%) were admitted (relative risk [RR], 0.61 [95% CI, 0.50-0.75] and 0.51 [95% CI, 0.40-0.64], respectively). Four mAb patients (0.3%) and 2.64 control patients (0.2%) were admitted to the ICU (RR, 01.51; 95% CI, 0.45-5.09). Six mAb-treated patients (0.4%) and 3.37 controls (0.3%) died and/or were admitted to hospice (RR, 1.61; 95% CI, 0.54-4.83). mAb therapy in ambulatory patients with COVID-19 decreases the risk of ED presentation and hospital admission within 30 days of diagnosis.

Absence of COVID-19 Disease Among Chronically Ventilated Nursing Home Patients.

OBJECTIVE: To describe the experience of COVID-19 disease among chronically ventilated and nonventilated nursing home patients living in 3 separate nursing homes. DESIGN: Observational study of death, respiratory illness and COVID-19 polymerase chain reaction (PCR) results among residents and staff during nursing home outbreaks in 2020. SETTING AND PARTICIPANTS: 93 chronically ventilated nursing home patients and 1151 nonventilated patients living among 3 separate nursing homes on Long Island, New York, as of March 15, 2020. Illness, PCR results, and antibody studies among staff are also reported. MEASUREMENTS: Data were collected on death rate among chronically ventilated and nonventilated patients between March 15 and May 15, 2020, compared to the same time in 2019; prevalence of PCR positivity among ventilated and nonventilated patients in 2020; reported illness, PCR positivity, and antibody among staff. RESULTS: Total numbers of deaths among chronically ventilated nursing home patients during this time frame were similar to the analogous period 1 year earlier (9 of 93 in 2020 vs 8 of 100 in 2019, P = .8), whereas deaths among nonventilated patients were greatly increased (214 of 1151 in 2020 vs 55 of 1189 in 2019, P < .001). No ventilated patient deaths were clinically judged to be COVID-19 related. No clusters of COVID-19 illness could be demonstrated among ventilated patients. Surveillance PCR testing of ventilator patients failed to reveal COVID-19 positivity (none of 84 ventilator patients vs 81 of 971 nonventilator patients, P < .002). Illness and evidence of COVID-19 infection was demonstrated among staff working both in nonventilator and in ventilator units. CONCLUSIONS AND IMPLICATIONS: COVID-19 infection resulted in illness and death among nonventilated nursing home residents as well as among staff. This was not observed among chronically ventilated patients. The mechanics of chronic ventilation appears to protect chronically ventilated patients from COVID-19 disease.

EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment.

Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication.

Postmarketing experience with Neutrolin® (taurolidine, heparin, calcium citrate) catheter lock solution in hemodialysis patients.

Catheter-related bloodstream infections (CRBSI) are major complications for patients with life-threatening conditions requiring chronic vascular catheterization. The wide range of etiologic microbes and the ongoing development of resistance to antimicrobials with specific mechanisms of action make this an appropriate target for applying a nonspecific antimicrobial therapeutic. Taurolidine hydrolyzes into two antimicrobial moieties, formaldehyde and methylene glycol, which react with microbial surfaces. Neutrolin® (taurolidine, heparin, calcium citrate) was recently introduced in Germany as an antimicrobial catheter lock solution. This postmarketing experience collected data on 201 patients at 20 centers from January 2014 through September 2016. Likely CRBSI was observed in 13 episodes in 47,118 days (0.2759 per 1000 days [0.1468, 0.4718]). Thrombosed catheter was observed in seven catheters in 47,118 days (0.1486 per 1000 days [0.0595, 0.3061]). No adverse drug reactions that led to the discontinuation of Neutrolin® use were reported. Two patients experienced occasional transient dysgeusia. Neutrolin®, when used in conjunction with guideline-based catheter care, showed reduction in the rate of both CRBSI and catheter thrombosis relative to recent historical controls.

Increasing the efficiency and yield of a tuberculosis contact investigation through electronic data systems matching.

BACKGROUND: Electronic health data may improve the timeliness and accuracy of resource-intense contact investigations (CIs) in healthcare settings. METHODS: In September 2013, we initiated a CI around a healthcare worker (HCW) with infectious tuberculosis (TB) who worked in a maternity ward. Two sources of electronic health data were employed: hospital-based electronic medical records (EMRs), to identify patients exposed to the HCW, and an electronic immunization registry, to obtain contact information for exposed infants and their providers at two points during follow-up. RESULTS: Among 954 patients cared for in the maternity ward during the HCW's infectious period, the review of EMRs identified 285 patients (30%) who interacted with the HCW and were, thus, exposed to TB. Matching infants to the immunization registry offered new provider information for 52% and 30% of the infants in the first and second matches. Providers reported evaluation results for the majority of patients (66%). CONCLUSION: Data matching improved the efficiency and yield of this CI, thereby demonstrating the usefulness of enhancing CIs with electronic health data.

Regulatory T cells and the risk of CMV end-organ disease in patients with AIDS.

OBJECTIVES: Cytomegalovirus (CMV)-specific T-cell effectors (CMV-Teff) protect against CMV end-organ disease (EOD). In HIV-infected individuals, their numbers and function vary with CD4 cell numbers and HIV load. The role of regulatory T cells (Treg) in CMV-EOD has not been extensively studied. We investigated the contribution of Treg and Teff toward CMV-EOD in HIV-infected individuals independently of CD4 cell numbers and HIV load and controlling for CMV reactivations. DESIGN: We matched 43 CMV-EOD cases to 93 controls without CMV-EOD, but with similar CD4 cell numbers and HIV plasma RNA. CMV reactivation was investigated by blood DNA polymerase chain reaction over 32 weeks preceding the CMV-EOD in cases and preceding the matching point in controls. METHODS: CMV-Teff and Treg were characterized by the expression of interferon-γ (IFN-γ), interleukin 2, tumor necrosis factor α (TNFα), MIP1ß, granzyme B (GrB), CD107a, TNFα, FOXP3, and CD25. RESULTS: Sixty-five percent cases and 20% controls had CMV reactivations. In multivariate analyses that controlled for CMV reactivations, none of the CMV-Teff subsets correlated with protection, but high CMV-GrB enzyme-linked immunosorbent spot responses and CMV-specific CD4FOXP3+%, CD4TNFα+%, and CD8CD107a% were significant predictors of CMV-EOD. CONCLUSIONS: Because both FOXP3 and GrB have been previously associated with Treg activity, we conclude that CMV-Treg may play an important role in the development of CMV-EOD in advanced HIV disease. We were not able to identify a CMV-Teff subset that could be used as a surrogate of protection against CMV-EOD in this highly immunocompromised population.

Resolution of whipple disease-induced pulmonary hypertension following antibiotic therapy.

Whipple disease is a disorder caused by Tropheryma whipplei, a ubiquitous Gram-positive bacillus. In addition to gastrointestinal manifestations, many other systems may be involved in Whipple disease. Pulmonary hypertension (PH) is a rare manifestation of Whipple disease, and its clinical course is not well established. We report a case of a 45-year-old woman who presented with typical gastrointestinal manifestations of Whipple disease, which was diagnosed by duodenal biopsy. She was also noted to have elevated pulmonary arterial pressures on transthoracic echocardiography. There was no evidence of left-sided valvular disease, hypertrophy, or dyskinesis, and there was no evidence of endocarditis. The patient was started on intravenous ceftriaxone for 6 weeks and then transitioned to oral trimethoprim-sulfamethoxazole for a year. The patient demonstrated clinical improvement, endoscopic and histologic improvement, and also resolution of PH. This is the third reported case of PH that is convincingly secondary to Whipple disease that resolved after appropriate antibiotic therapy.

Community-associated extended-spectrum ß-lactamase-producing Escherichia coli infection in the United States.

Background. The occurrence of community-associated infections due to extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli has been recognized as a major clinical problem in Europe and other regions. Methods. We conducted a prospective observational study to examine the occurrence of community-associated infections due to ESBL-producing E. coli at centers in the United States. Five academic and community hospitals and their affiliated clinics participated in this study in 2009 and 2010. Sites of acquisition of the organisms (community-associated or healthcare-associated), risk factors, and clinical outcome were investigated. Screening for the global epidemic sequence type (ST) 131 and determination of the ESBL types was conducted by polymerase chain reaction and sequencing. Results. Of the 291 patients infected or colonized with ESBL-producing E. coli as outpatients or within 48 hours of hospitalization, 107 (36.8%) had community-associated infection (81.5% of which represented urinary tract infection), while the remainder had healthcare-associated infection. Independent risk factors for healthcare-associated infection over community-associated infection were the presence of cardiovascular disease, chronic renal failure, dementia, solid organ malignancy, and hospitalization within the previous 12 months. Of the community-associated infections, 54.2% were caused by the globally epidemic ST131 strain, and 91.3% of the isolates produced CTX-M-type ESBL. Conclusions. A substantial portion of community-onset, ESBL-producing E. coli infections now occur among patients without discernible healthcare-associated risk factors in the United States. This epidemiologic shift has implications for the empiric management of community-associated infection when involvement of E. coli is suspected.

Antiviral therapy of two patients with chromosomally-integrated human herpesvirus-6A presenting with cognitive dysfunction.

BACKGROUND: Human herpesvirus 6 (HHV-6) is a neurotropic virus implicated in central nervous system (CNS) dysfunction, multiple sclerosis, seizures and encephalitis. Inherited or "chromosomally integrated" HHV-6 (CIHHV-6) is a condition characterized by high DNA loads and germ line transmission of HHV-6 genomes, which are integrated into the telomere. OBJECTIVES: We previously reported that integrated HHV-6 can be reactivated by trichostatin A in vitro. Therefore, we hypothesized that a broad array of neurological symptoms of CIHHV-6 patients may respond to antiviral drug treatment. STUDY DESIGN: The patients have been treated with antiviral drugs and monitored for viral load, late mRNA, and clinical improvement. RESULTS: Antiviral therapy of two CIHHV patients resulted in successful clinical resolution. However, both patients relapsed on multiple occasions within 4-6 months of cessation of antiviral therapy. CONCLUSIONS: Successful antiviral drug treatment suggests that clinical symptoms of these patients were due to symptomatic reactivation of CIHHV-6. Alternatively, some CIHHV-6 patients may have a reduced resistance to community-acquired HHV-6 strains due to tolerance leading to persistent infections.

Treatment outcome of bacteremia due to KPC-producing Klebsiella pneumoniae: superiority of combination antimicrobial regimens.

Klebsiella pneumoniae producing Klebsiella pneumoniae carbapenemase (KPC) has been associated with serious infections and high mortality. The optimal antimicrobial therapy for infection due to KPC-producing K. pneumoniae is not well established. We conducted a retrospective cohort study to evaluate the clinical outcome of patients with bacteremia caused by KPC-producing K. pneumoniae. A total of 41 unique patients with blood cultures growing KPC-producing K. pneumoniae were identified at two medical centers in the United States. Most of the infections were hospital acquired (32; 78%), while the rest of the cases were health care associated (9; 22%). The overall 28-day crude mortality rate was 39.0% (16/41). In the multivariate analysis, definitive therapy with a combination regimen was independently associated with survival (odds ratio, 0.07 [95% confidence interval, 0.009 to 0.71], P = 0.02). The 28-day mortality was 13.3% in the combination therapy group compared with 57.8% in the monotherapy group (P = 0.01). The most commonly used combinations were colistin-polymyxin B or tigecycline combined with a carbapenem. The mortality in this group was 12.5% (1/8). Despite in vitro susceptibility, patients who received monotherapy with colistin-polymyxin B or tigecycline had a higher mortality of 66.7% (8/12). The use of combination therapy for definitive therapy appears to be associated with improved survival in bacteremia due to KPC-producing K. pneumoniae.

Rhodococcus equi infection after reduction mammaplasty in an immunocompetent patient.

The majority of infections caused by R. equi occur in hosts with some degree of cell-mediated immunodeficiency. Immunocompetent individuals are infrequently affected and usually present with localized disease. Infections of the skin or related structures are uncommon and are usually related to environmental contamination. The microbiology laboratory plays a key role in the identification of the organism since it may be mistaken for common skin flora. We describe a 31 year-old woman without medical problems who presented nine weeks after breast reduction with right breast cellulitis and purulent drainage from the surgical wound. She underwent incision and drainage, and cultures of the wound yielded Rhodococcus equi. The patient completed six weeks of antimicrobial therapy with moxifloxacin and rifampin with complete resolution.

Rhodococcus equi infection after reduction mammaplasty in an immunocompetent patient / Infección por Rhodococcus equi luego de cirugía de reducción mamaria en huésped inmunocompetente

The majority of infections caused by R. equi occur in hosts with some degree of cell-mediated immunodeficiency. Immunocompetent individuals are infrequently affected and usually present with localized disease. Infections of the skin or related structures are uncommon and are usually related to environmental contamination. The microbiology laboratory plays a key role in the identification of the organism since it may be mistaken for common skin flora. We describe a 31 year-old woman without medical problems who presented nine weeks after breast reduction with right breast cellulitis and purulent drainage from the surgical wound. She underwent incision and drainage, and cultures of the wound yielded Rhodococcus equi. The patient completed six weeks of antimicrobial therapy with moxifloxacin and rifampin with complete resolution.

La mayoría de las infecciones causadas por Rhodococcus equi ocurren en huéspedes con algún grado de inmunodeficiencia celular. Los individuos inmunocompetentes son afectados con baja frecuencia y suelen presentarse con enfermedad localizada. Las infecciones de la piel o partes blandas son poco frecuentes y están usualmente relacionadas con contaminación ambiental. El laboratorio de microbiología juega un papel clave en la identificación del organismo, ya que este puede confundirse con flora normal de la piel. Se describe una mujer de 31 años sin problemas médicos que consultó nueve semanas después de haber sido sometida a cirugía de reducción mamaria, con celulitis del seno derecho y drenaje purulento de la herida quirúrgica. Se practicó incisión y drenaje quirúrgico y los cultivos de la herida demostraron R. equi. La paciente recibió seis semanas de tratamiento antimicrobiano con moxifloxacina y rifampicina demostrando resolución completa.

Risk factors and outcome of extended-spectrum ß-lactamase-producing Enterobacter cloacae bloodstream infections.

Enterobacter cloacae is a major nosocomial pathogen that causes serious infections, including bloodstream infections (BSIs). The clinical significance of extended-spectrum ß-lactamase (ESBL) production in E. cloacae is not well established. A multicentre, retrospective, cohort study was conducted to identify clinical characteristics of patients with E. cloacae BSI. ESBL production was confirmed by genotypic methods. A total of 159 patients with E. cloacae BSI were identified at three medical centres in north-eastern USA. Amongst them, 16 patients (10.1%) harboured ESBL-producing E. cloacae. Independent risk factors for ESBL production included admission from a nursing home, the presence of a gastrostomy tube and history of transplant. For the outcome analysis, 15 consecutive patients who had ESBL-producing E. cloacae BSI prior to the study were included. Amongst the 31 patients with ESBL-producing E. cloacae, 8, 9, 4 and 2 patients received a carbapenem, cefepime, piperacillin/tazobactam and ciprofloxacin, respectively, as initial therapy. All patients who received a carbapenem (n=8) were alive at 28 days, whereas 7 (38.9%) of 18 patients who received a non-carbapenem antibiotic did not survive (P=0.06). Clinical failure at 96 h was observed in 2 (25.0%) of 8 patients who received a carbapenem and in 14 (77.8%) of 18 patients who received a non-carbapenem antibiotic (P=0.03). Pulsed-field gel electrophoresis showed little clonality amongst the study isolates. The majority of isolates produced SHV-type ESBL, whereas two isolates produced CTX-M-type ESBL. Initial therapy with a carbapenem appears to be associated with improved clinical outcome in BSI due to ESBL-producing E. cloacae.

Legionella pneumonia and HIV: case reports and review of the literature.

Although Legionnaires' disease occurs more commonly in patients with some degree of immunosuppression (diabetes, chronic lung disease, end stage renal disease, cancer, etc.), it has been infrequently described in patients infected with human immunodeficiency virus (HIV) and AIDS. Some studies suggest that pneumonia caused by Legionella tends to present with more severe clinical features and complications in the HIV-infected population. The use of antibiotic prophylaxis or the association of severe pneumonia with other pathogens may account for under diagnosis of the disease. We diagnosed five cases of Legionella pneumonia in patients with HIV infection at our institution during a 1-year period. The cases seen ranged in severity, regardless of the CD4(+) counts of the patients. Based on our observations, it seems impossible to discern whether HIV infection is an additional risk factor for Legionnaires' disease. We describe those five cases and review the available literature.

Splenic infarction in human babesiosis: two cases and discussion.

We describe 2 patients with Babesia infection who presented with fever and multiple splenic infarcts. There were no other conditions present that could potentially be causes of splenic infarction. Although retinal infarction has been described rarely in patients with babesiosis, splenic infarction has not been reported previously in association with this infection in humans.

Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127.

Chronic hepatitis B virus (HBV) infection is an important cause of morbidity and mortality in subjects coinfected with HIV. Tenofovir disoproxil fumarate (TDF) and adefovir dipivoxil (ADV) are licensed for the treatment of HIV-1 and HBV infection, respectively, but both have in vivo and in vitro activity against HBV. This study evaluated the anti-HBV activity of TDF compared to ADV in HIV/HBV-coinfected subjects. ACTG A5127 was a prospective randomized, double-blind, placebo-controlled trial of daily 10 mg of ADV versus 300 mg of TDF in subjects with HBV and HIV coinfection on stable ART, with serum HBV DNA >/= 100,000 copies/mL, and plasma HIV-1 RNA