Characteristics and Outcomes of US Veterans With Immunocompromised Conditions at High Risk of SARS-CoV-2 Infection With or Without Receipt of Oral Antiviral Agents.

OBJECTIVES: Molnupiravir and nirmatrelvir-ritonavir were the first oral antiviral agents to demonstrate reduced hospitalization or death in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but patients with immunocompromised conditions were not well-represented. The objective of this study was to characterize and compare the clinical outcomes of US veterans with immunocompromised conditions prescribed oral antivirals with those who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection. METHODS: This was a retrospective, observational, nationwide propensity-matched analysis of US veterans with immunocompromised conditions who developed documented SARS-CoV-2 infection. The primary outcome was the composite of any hospitalization or death within 30 days of diagnosis. Secondary outcomes included 30-day comparative rates of (1) any hospitalization, (2) death, (3) intensive care requirement, and (4) subset analyses of outcomes by oral antiviral used and vaccination status. RESULTS: The composite primary outcome was significantly lower in patients receiving oral antiviral therapy compared with those who did not (23/390 [5.9%] vs 57/390 [14.6%]; odds ratio, 0.37; 95% confidence interval, .22-.61). This difference was driven largely by fewer deaths in the oral antiviral group (1/390 [0.3%] vs 19/390 [4.9%]; odds ratio, 0.05; 95% confidence interval, .007-.38). There was no significant difference in rate of intensive care requirement. The composite outcome was improved in vaccinated patients (completing the first series or first booster dose) who received oral antiviral agents compared with those who did not receive oral antiviral agents. Compared with those prescribed nirmatrelvir-ritonavir, patients given molnupiravir were older, had a higher incidence of cautions/contraindications, greater prevalence of tobacco use, and more cardiovascular complications. CONCLUSIONS: Use of molnupiravir or nirmatrelvir-ritonavir was associated with lower incidences of hospitalization or death within 30 days of diagnosis in US veterans with immunocompromised conditions, regardless of vaccination status. These findings support the use of either oral antiviral in this patient population.

Pharmacological options for Candida albicans Endocarditis at the roadblock with irrecoverable prosthetics and drug interactions: a case report and review of literature.

BACKGROUND: Candidemia is the fourth most common nosocomial bloodstream infection. Endocarditis from candidemia is a rare but possibly fatal complication. The efficacy of amphotericin and echinocandins for induction and azoles for suppression has been well studied. Source control of infection, including removal of foreign bodies, remains the cornerstone for the success of any antifungal therapy. CASE PRESENTATION: We are describing a case of a 63-years old patient with multiple comorbidities who developed candidemia secondary to Candida albicans. The prospect of curing the fungemia was made difficult by prosthetic devices, including prosthetic heart valves, intracardiac defibrillator, and inferior vena filter, which could not be extracted due to poor cardiovascular status and higher postoperative mortality risk. Combination therapy with amphotericin and 5-Flucytosine (5FC) was used with the first recurrence. Suppression with fluconazole was contraindicated due to prolonged corrected QT (QTc) interval. Isavuconazole was employed for chronic lifelong suppression. CONCLUSION: Retaining prosthetics in higher surgical risk patients presents us with unique clinical and pharmacological challenges regarding breakthrough infections, drug interaction, and side effects from prolonged suppressive therapies.

Staphylococcus aureus bacteraemia treatment outcomes in patients receiving ticagrelor vs a propensity-matched cohort receiving clopidogrel.

OBJECTIVES: Ticagrelor may improve the outcomes in Staphylococcus aureus bacteraemia (SAB). However, treatment outcome data for these patients remain limited. The primary objective of this study was to characterize the outcomes of patients with SAB who received ticagrelor compared with a cohort who received clopidogrel. METHODS: This was a retrospective, nationwide propensity-matched analysis of patients with SAB who were prescribed ticagrelor or clopidogrel concomitantly with antistaphylococcal therapy. The primary outcome was the comparative all-cause 30-day mortality rate between propensity-matched groups. RESULTS: In total, 1509 patients were prescribed concomitantly with ticagrelor or clopidogrel during treatment of S. aureus bacteraemia; of these, 194 patients were excluded from this study due to an inadequate number of antiplatelet doses within the first week of therapy (n=171) or non-admission to hospital (n=23). Of the remaining 1315 patients, 74 patients received ticagrelor and 1241 patients received clopidogrel. There was no significant difference in all-cause 30-day mortality between the groups [6/74 (8.1%) in the ticagrelor group vs 10/74 (13.5%) in the clopidogrel group; P=0.29]. Multi-variate logistic regression demonstrated that elevated aspartate aminotransferase, systolic blood pressure <90 mmHg, elevated serum creatinine and neurological comorbidity were independently associated with all-cause 30-day mortality. CONCLUSIONS: This study found no difference in all-cause 30-day mortality between the two groups, although overall mortality appeared to be lower compared with other reports. Randomized controlled trials of P2Y12 inhibitors as adjunctive agents to antibiotic therapy for the treatment of serious S. aureus infections are warranted.

Propensity-matched analysis of the protective effect of ticagrelor versus clopidogrel on the risk of developing Staphylococcus aureus bacteremia.

OBJECTIVE: Recent data indicate that ticagrelor, used in acute coronary syndromes (ACS), has antibacterial effects against Staphylococcus sp. and other effects that may help management of infection. The primary objective of this study was to evaluate the protective effect of ticagrelor in patients who have had an ACS event and the risk of developing Staphylococcus aureus bacteremia (SAB) compared to a propensity-matched cohort receiving clopidogrel. METHODS: This study was a retrospective, nationwide analysis of all patients presenting to any percutaneous coronary intervention-performing Veterans Affairs Medical Center with an ACS episode and resultant prescription for clopidogrel or ticagrelor. The primary outcome was the comparative rate of SAB in patients receiving ticagrelor vs. clopidogrel. RESULTS: Analysis involved 24 456 patients on ticagrelor and 277 277 patients on clopidogrel. There was a statistically significant difference in the number of patients developing SAB between the propensity-matched groups (32 [0.13%] of 24 456 for ticagrelor vs. 71 [0.29%] of 24 456 for clopidogrel; odds ratio (OR), 0.43; 95% confidence interval (CI), 0.28-0.65; P<0.0001). Multivariate logistic regression showed that receipt of clopidogrel, comorbid dermatologic condition, comorbid hematologic condition, and baseline anemia were independently associated with the development of SAB. CONCLUSIONS: The study findings align with recent reports that ticagrelor may have a beneficial role in the prevention of SAB.

Characteristics and outcomes of US Veterans at least 65 years of age at high risk of severe SARS-CoV-2 infection with or without receipt of oral antiviral agents.

OBJECTIVES: Molnupiravir and nirmatrelvir/ritonavir each became available in the United States (US) through the Food and Drug Administration (FDA) emergency use authorization (EUA) in December 2021 after their respective initial prospective randomized controlled trials demonstrated efficacy for patients with mild-to-moderate SARS-CoV-2 active infection considered to be at high risk for progression of disease and hospitalization. Although sufficiently powered for this wide group, the mean age for patients in these studies was only 43 and 46 years of age, respectively. We sought to compare outcomes of US Veterans 65 years and older who received either of these oral antivirals to those who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection. METHODS: The current project was a retrospective, observational, nationwide propensity-matched analysis comparing outcomes of US Veterans 65 years and older who received either of these oral antivirals to US Veterans 65 years and older who did not receive oral antivirals for mild-to-moderate SARS-CoV-2 active infection. RESULTS: The composite primary outcome of admission or death within 30 days of diagnosis was reached less often in those receiving either molnupiravir or nirmatrelvir/ritonavir versus those that received no antiviral (65/1370 [4.75%] vs. 139/1370 [10.2%]; odds ratio 0.44, 95% confidence interval 0.32-0.60, p<0.0001). Baseline differences between Veterans selected for molnupiravir vs. nirmatrelvir/ritonavir therapy were noted, particularly in the number of concomitant medications with cautions or contraindications with nirmatrelvir/ritonavir. CONCLUSIONS: Our findings support the use of molnupiravir or nirmatrelvir/ritonavir in patients 65 years of age and older. Patients with higher medication caution and contraindication burdens to nirmatrelvir/ritonavir are selected for molnupiravir therapy, which in the absence of a prospective head-to-head trial, may limit any efforts to compare the effectiveness of the two drugs.

Development of SARS-CoV-2 infection in patients with rheumatic conditions on hydroxychloroquine monotherapy vs. patients without rheumatic conditions: A retrospective, propensity-matched cohort study.

BACKGROUND: The primary purpose of the current study was to examine whether patients with rheumatologic conditions receiving only chronic hydroxychloroquine therapy for their disease are at less risk of developing SARS-CoV-2 infection than a comparative group of patients without rheumatologic conditions. METHODS: A retrospective, observational, nationwide stratified propensity analysis was conducted comparing patients only on chronic treatment with hydroxychloroquine for their rheumatologic condition to a random sample of patients without rheumatologic conditions and not receiving hydroxychloroquine, utilizing a Veterans Health Administration nationwide clinical administrative database. RESULTS: The 1-to-1 stratified propensity analysis was undertaken using a random sample of patients without rheumatoid conditions and not receiving hydroxychloroquine (n  33,081) and patients with rheumatoid conditions receiving hydroxychloroquine as the lone medication for their condition (n  6047). A total of 5,474 patients in each group were successfully matched. The incidence of documented SARS-CoV-2 infections during the study period did not differ between patients receiving hydroxychloroquine and patients not receiving hydroxychloroquine (41/5,474 [0.749%] vs. 36/5,474 [0.658%], respectively, p = 0.57; Odds ratio [OR] 1.14, 95% confidence interval [CI] 0.73-1.79). There were no statistically-significant differences in secondary outcomes between the two groups in patients who developed active SARS-CoV-2 infection. Multivariate logistic regression to determine independent variables associated with the development of active SARS-CoV-2 infection failed to include receipt of hydroxychloroquine (OR 0.99, 95% CI 0.62-1.56). CONCLUSIONS: Hydroxychloroquine failed to demonstrate a preventative effect against SARS-CoV-2 infection in a large group of patients with rheumatologic conditions compared to patients without rheumatologic conditions.

The Effect of Nomenclature Revision of Streptococcus bovis to Streptococcus gallolyticus on Subsequent Colon Cancer Screening.

BACKGROUND: Lack of awareness of the taxonomic revision from the familiar Streptococcus bovis to the less familiar Streptococcus gallolyticus may be associated with a decrease in recommended colon cancer screening in patients with bacteremia from this organism. This could subsequently lead to a delay in diagnosis or underdiagnosis of colon cancer and other serious underlying gastrointestinal diseases. The aim of this study was to determine whether the nomenclature change of S. bovis to S. gallolyticus resulted in decreased colon cancer screening. METHODS: This study was a retrospective, observational, nationwide analysis of patients who had positive blood cultures for S. bovis/S. gallolyticus from any Veterans Affairs Medical Center (VAMC) between January 1, 2002, and December 31, 2017. RESULTS: There was no difference in the primary end point of intent for colonoscopy between the S. gallolyticus and S. bovis groups (66.5% [117/176] vs 62.1% [624/1005], respectively; P = .26). The overall mortality rate was 33.8% among 1181 patients included in the study, with a significantly lower mortality in patients with evidence of intent for colonoscopy (29.6% vs 42.5%; P ≤ .001), gastroenterology (GI) consultation (29.8% vs 41.4%; P < .001), infectious diseases (ID) consultation (29.4% vs 39.0%; P = .001), or either consultation (31.9% vs 40.7%; P = .013), compared to those that did not. CONCLUSIONS: There was no difference in colon cancer screening rates between patients with episodes of bacteremia reported as S. bovis and those reported as S. gallolyticus. Overall mortality was lower in patients who had ID consultation, GI consultation, or evidence of colonoscopy.

Capnocytophaga canimorsus Bloodstream Infection Associated with an Urticarial Exanthem.

Background. Capnocytophaga canimorsus is a fastidious, slow-growing, Gram-negative rod that is a commensal bacterium in normal gingival flora of canine and feline species. Infection with the organism may cause disease ranging from flu-like symptoms to disseminated intravascular coagulation (DIC), fulminant sepsis, meningitis, and endocarditis with an overall fatality rate of 6-26%. Risk factors for infection from C. canimorsus include immunosuppression, alcoholism, and asplenia. Case Presentation. We describe an unusual case with a relatively indolent clinical course and an urticarial exanthem in an otherwise young immunocompetent patient with a history of type 1 diabetes. The patient presented to the Emergency Department (ED) with a <1-day history of rhinorrhea, fever, and dyspnea. He met sepsis criteria on initial presentation, but left against medical advice and returned to the ED the following day, with new arthralgias and a diffuse rash, multiple erythematous, tender macules scattered across his trunk and extremities, and tonsillar erythema. He had not taken the doses of the prescribed amoxicillin. Blood cultures two days later signaled positive for growth with the Gram stain showing a Gram-negative rod. Three 7-8 cm tender targetoid lesions with central clearing were identified on the patient's back. The patient reported two nonengorged ticks crawling on his body a week prior and sustaining a dog bite to his ear three weeks before presentation. Ultimately, the organism was identified as C. canimorsus through MALDI-TOF mass spectrometry and additional biochemical testing. He was given appropriate antibiotics and improved clinically thereafter. Despite the patient's bacteremia, he never progressed to fulminant sepsis and followed a mild clinical course with several unusual characteristics. C. canimorsus is an uncommon cause of illness in humans, but is an important pathogen to consider when evaluating a patient with a dog bite, known risk factors, and an urticarial exanthem as empiric treatment may prevent severe outcomes.

Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study.

BACKGROUND: Hydroxychloroquine is one of several agents being evaluated in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to examine whether patients with rheumatological conditions receiving chronic hydroxychloroquine therapy are at less risk of developing SARS-CoV-2 infection than those not receiving hydroxychloroquine. METHODS: This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020. A propensity score was calculated for each patient, and each patient who was receiving hydroxychloroquine was matched to two patients who were not receiving hydroxychloroquine (controls). The primary endpoint was the proportion of patients with PCR-confirmed SARS-CoV-2 infection among those receiving chronic hydroxychloroquine versus the propensity-matched patients not receiving chronic hydroxychloroquine between March 1 and June 30, 2020. Secondary outcomes were hospital admission associated with SARS-CoV-2 infection; intensive care requirement associated with SARS-CoV-2 infection; mortality associated with SARS-CoV-2 infection; and overall rates of any hospital admission and mortality (ie, all cause). Multivariate logistic regression analysis was done to determine independent variables for the development of active SARS-CoV-2 infection. FINDINGS: Between March 1 and June 30, 2020, 10 703 patients receiving hydroxychloroquine and 21 406 patients not receiving hydroxychloroquine were included in the primary analysis. The incidence of active SARS-CoV-2 infections during the study period did not differ between patients receiving hydroxychloroquine and patients not receiving hydroxychloroquine (31 [0·3%] of 10 703 vs 78 [0·4%] of 21 406; odds ratio 0·79, 95% CI 0·52-1·20, p=0·27). There were no significant differences in secondary outcomes between the two groups in patients who developed active SARS-CoV-2 infection. For all patients in the study, overall mortality was lower in the hydroxychloroquine group than in the group of patients who did not receive hydroxychloroquine (odds ratio 0·70, 95% CI 0·55-0·89, p=0·0031). In multivariate logistic regression analysis, receipt of hydroxychloroquine was not associated with the development of active SARS-CoV-2 infection (odds ratio 0·79, 95% CI 0·51-1·42). INTERPRETATION: Hydroxychloroquine was not associated with a preventive effect against SARS-CoV-2 infection in a large group of patients with rheumatological conditions. FUNDING: None.

Mycobacterium neoaurum Bloodstream Infection Associated with a Totally Implanted Subclavian Port in an Adult with Diabetes and History of Colon Cancer.

Background. Mycobacterium neoaurum is a rapidly growing nontuberculosis mycobacterium (NTM) that was first isolated from soil in 1972 and is ubiquitous in soil, water, and dust. The first reported case of human infection by M. neoaurum was published in 1988, presenting as a Hickman catheter-related bacteremia in a patient with ovarian cancer. M. neoaurum has since been recognized as a source of predominantly opportunistic bloodstream infections in immunocompromised hosts. We report the case of an adult diabetic male with M. neoaurum bloodstream infection secondary to an infected venous-access port that had been implanted nearly six years prior for temporary chemotherapy. Case Presentation. A 66-year-old male with schizophrenia, type 2 diabetes mellitus, and a history of excision and chemotherapy to treat adenocarcinoma of the colon 6 years prior, presented with fever and behavioral changes. He was found to have a M. neoaurum bloodstream infection secondary to his implanted subclavian port. Multiple preoperative blood cultures, as well as the removed catheter tip culture, were positive for M. neoaurum. The patient's condition improved to near premorbid levels after port removal and 6 weeks of targeted antimicrobial therapy. Discussion and Conclusions. Bloodstream infections due to rapidly growing NTM, such as M. neoaurum, have been infrequently reported; however, improved isolation and identification techniques based on genomic testing are resulting in a more in-depth recognition of these widely scattered environmental microbes in human infections. Nonetheless, lengthy identification and susceptibility processes remain a diagnostic and treatment barrier. Patients such as ours who have a history of malignancy and an indwelling foreign body have most often been reported as acquiring M. neoaurum bacteremia. Fortunately, device removal and appropriate antimicrobial therapy guided by susceptibility data is often enough to manage these atypical mycobacterial infections.

Dendritic cell interactions with Histoplasma and Paracoccidioides.

Fungi are among the most common microbes encountered by humans. More than 100, 000 fungal species have been described in the environment to date, however only a few species cause disease in humans. Fungal infections are of particular importance to immunocompromised hosts in whom disease is often more severe, especially in those with impaired cell-mediated immunity such as individuals with HIV infection, hematologic malignancies, or those receiving TNF-α inhibitors. Nevertheless, environmental disturbances through natural processes or as a consequence of deforestation or construction can expose immunologically competent people to a large number of fungal spores resulting in asymptomatic acquisition to life-threatening disease. In recent decades, the significance of the innate immune system and more importantly the role of dendritic cells (DC) have been found to play a fundamental role in the resolution of fungal infections, such as in dimorphic fungi like Histoplasma and Paracoccidioides. In this review article the general role of DCs will be illustrated as the bridge between the innate and adaptive immune systems, as well as their specific interactions with these 2 dimorphic fungi.

Clostridium subterminale septicemia in a patient with esophageal cancer.

Clostridium subterminale (C. subterminale) is a pathogenic species of Clostridium that has been infrequently isolated. We report a case of C. subterminale bacteremia causing sepsis in a patient with metastatic gastrointestinal malignancy.