The Combination of Venetoclax and Ixazomib Selectively and Efficiently Kills HIV-Infected Cell Lines but Has Unacceptable Toxicity in Primary Cell Models.

The antiapoptotic protein BCL2 inhibits death of HIV-infected cells. Previously, we showed that the BCL2 inhibitor venetoclax selectively kills acutely HIV-infected cells and reduces HIV DNA in latently infected CD4 T cells ex vivo after reactivation with anti-CD3/anti-CD28. However, there is a need to identify a combination therapy with venetoclax and a clinically relevant latency reversal agent. Ixazomib is an oral proteasome inhibitor which we have shown reactivates latent HIV and predisposes reactivated cells to cell death. Here, we determined that the combination of venetoclax and ixazomib kills more latently HIV-infected cells and leads to greater reduction in HIV replication than either treatment alone in vitro in a T cell model. However, combination treatment of ex vivo CD4 T cells from antiretroviral therapy (ART)-suppressed, HIV-positive participants resulted in unanticipated and unacceptable nonspecific toxicity in primary cells. Therefore, while we show proof of concept that multiple agents can enhance selective killing of HIV-infected cells, the combination of venetoclax and ixazomib has unacceptable toxicity in primary cells, and so further investigation is needed to identify a clinically relevant latency reversal agent to combine with venetoclax as a novel strategy to reduce the size of the HIV reservoir.IMPORTANCE A cure for HIV would require eliminating cells that contain the virus in a latent form from the body. Current antiretroviral medications are unable to rid the body of latently infected cells. Here, we show that a combination of investigational agents-ixazomib plus venetoclax-which reactivate latent virus and predispose infected cells to apoptosis may reduce latent virus in a T cell model, but at the expense of nonspecific toxicity in primary cells.

Preventing central line-associated bloodstream infections: A position paper of the International Society for Infectious Diseases, 2024 update.

A panel of experts convened by the International Society for Infectious Diseases (ISID) has reviewed and consolidated current recommendations for preventing vascular catheter infections, particularly central line-associated bloodstream infections (CLABSIs). This review provides healthcare professionals with insights into key issues such as the rates of CLABSI in high-income countries and low- and middle-income countries, the attributable extra length of stay, cost and mortality, and risk factors. This position paper highlights evidence-based strategies for preventing infections, applicable to both high-income and low- and middle-income countries.

A Case of Oral-Vancomycin-Induced Rash in a Patient with Acute Kidney Injury.

Clostridioides difficile infection (CDI) is one of the most common hospital-acquired infections. Its incidence has increased during the last decade in the community among individuals with no previous risk factors; however, morbidity and mortality are still considered high in elderly patients. Oral Vancomycin and Fidaxomicin are the first lines of treatment for CDI. The systemic bioavailability of oral Vancomycin is thought to be undetectable due to its poor absorption in the gastrointestinal tract; therefore, routine monitoring is not warranted. Only 12 case reports were found in the literature that described adverse reactions associated with oral Vancomycin and its related risk factors. We present a case of a 66-year-old gentleman with severe CDI and acute renal failure who was started on oral Vancomycin upon admission. On day five of treatment, he developed leukocytosis associated with neutrophilia, eosinophilia, and atypical lymphocytes, with no evidence of active infection. Three days later, he developed a pruritic maculopapular rash in more than 50% of his body surface area. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) was ruled out since the patient only had three inclusion criteria for this diagnosis. No clear inciting agent was found. Oral Vancomycin was stopped and supportive treatment was supplied for a presumed Vancomycin-induced allergic reaction. The patient had an excellent response, with complete resolution of the rash and leukocytosis in less than 48 h. By reporting this case, we want to raise awareness among clinicians to remember that, albeit rare, oral Vancomycin can be the cause of adverse drug reactions in patients with severe illnesses.

Lyme disease presenting as complete heart block in a young man: Case report and review of pathogenesis.

Lyme carditis is a serious complication of Lyme disease, the most common vector-borne infection in both the United States and Northern Europe. It is a rare manifestation of Lyme disease that primarily affects young adults with a marked 3:1 male-to-female predominance. The presentation of Lyme carditis is heterogenous and often non-specific, although the most common clinical manifestation is AV block, which can be acute in onset and can rapidly progress to complete heart block. We discuss the case of a young adult male with complete heart block as a complication of Lyme infection, presenting with two episodes of syncope without prodromal symptoms months after tick bites. There are several pathogen, host and environmental factors that can play an important role in the epidemiology and pathogenesis of this serious condition that is reversible if treated in a timely manner. It is important for clinicians to be familiar with the presentation and treatment of this infection that is now being observed in a wider geographic distribution so as to avoid serious long-term complications and unnecessary permanent pacemaking implantation.

Mania: An atypical presentation of probable Streptococcus agalactiae meningoencephalitis.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a common pathogen in the neonatal period, causing meningitis and sepsis. In non-pregnant adults it is an unusual cause of meningitis. We report about an elderly female with several risk factors for invasive GBS infection who developed GBS meningoencephalitis one month after treatment for COVID-19 upper respiratory tract infection. The patient presented with mania, and the classic triad of headache, neck stiffness, and fever was absent which contributed to the delay in diagnosis. Following initiation of treatment with intravenous ceftriaxone she attained full recovery, and her behavior returned to baseline. This case illustrates an unusual presentation of an emerging infection and should alert clinicians about this presentation. By reporting this case we want to raise awareness about mania as a presenting feature of meningoencephalitis. This should lead to more timely diagnosis and better outcomes for future patients.

Anaplasma phagocytophilum Community-Acquired Pneumonia: Case Report and Literature Review.

Anaplasma phagocytophilum is an emerging, Gram-negative, and obligate intracellular pathogen that is infrequently implicated as a causative agent of community-acquired pneumonia. In this paper, we report about an immunocompetent patient from the community who presented with fever, cough, and shortness of breath. Chest X-ray and CT showed bilateral lung infiltrates. Extensive workup for other common and uncommon causes of pneumonia was positive for anaplasmosis. The patient recovered completely with doxycycline therapy. In our literature review, we find that in 80% of reported cases of anaplasmosis pneumonia, empiric treatment did not contain doxycycline, which in some cases led to acute respiratory distress syndrome. Clinicians in tick-borne disease endemic regions should be aware of this unusual presentation of anaplasmosis in order to be able to select appropriate antimicrobial regimens and initiate timely management.

Enterococcus gallinarum endophthalmitis and meningitis in an allogeneic hematopoietic stem cell transplant patient: A case report and literature review.

Endogenous endophthalmitis caused by Enterococcus gallinarum, an organism with intrinsic resistance to vancomycin, has rarely been reported. We present a case of persistent E. gallinarum bacteremia in a female recipient of hematopoietic stem cell transplant (HSCT) complicated by endophthalmitis and meningoventriculitis, resulting in a fatal outcome despite treatment with intravenous ampicillin and daptomycin. Treatment of endophthalmitis often presents a challenge due to the lack of options for antimicrobials with reliable ocular penetration. Therapeutic decisions can become particularly complex with the involvement of drug-resistant pathogens and host characteristics that limit the choice of antimicrobials due to drug toxicity. This case illustrates a rare manifestation of an opportunistic pathogen.

L'endophtalmite endogène causée par l'Enterococcus gallinarum, un organisme ayant une résistance intrinsèque à la vancomycine, est rarement déclarée. Les auteurs présentent un cas de bactériémie à E. gallinarum persistante chez une femme après une greffe de cellules souches hématopoïétiques compliquée par une endophtalmite et une méningoventriculite dont l'issue a été fatale malgré un traitement à l'ampicilline et à la daptomycine par voie intraveineuse. Il est souvent difficile de traiter l'endophtalmite, à cause du manque d'antimicrobiens ayant une pénétration oculaire fiable. Les décisions thérapeutiques peuvent devenir particulièrement complexes en raison des agents pathogènes pharmacorésistants et des caractéristiques de l'hôte qui limitent le choix d'antimicrobiens, dont la toxicité est élevée. Ce cas illustre une manifestation rare d'agent pathogène opportuniste.

Infected Aneurysm of the Native Aorta due to Coccidioides posadasii.

Coccidioidomycosis is an endemic fungal infection that is typically asymptomatic or associated with pulmonary disease. Extrapulmonary disease may involve the skin, bones, or central nervous system, yet endovascular infections are exceedingly rare. We report the first case, to our knowledge, of coccidioidomycosis of the native aorta in an immunocompromised host.

Augmented curation of clinical notes from a massive EHR system reveals symptoms of impending COVID-19 diagnosis.

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVIDpos; n = 2,317) versus COVID-19-negative (COVIDneg; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVIDpos over COVIDneg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVIDpos patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.

Severe hypercalcemia in a patient with extrapulmonary Mycobacterium abscessus: granuloma or immune reconstitution inflammatory syndrome? First case of Mycobacterium abscessus presenting as retroperitoneal lymphadenopathy with severe hypercalcemia: a case report and literature review.

Background: Nontuberculous mycobacterium is a recognized cause of hypercalcemia, particularly in patients with acquired immunodeficiency syndrome (AIDS). Here we describe a case of severe hypercalcemia secondary to Mycobacterium abscessus (M. abscessus) in a patient with AIDS. To the best of our knowledge this is the first case report describing a case of M. abscessus presenting as retroperitoneal lymphadenopathy and severe hypercalcemia. Case description: A 56-year-old man with AIDS presented with altered mental status and somnolence for four days. Laboratory investigations were significant for calcium 16.49 mg/dL (RI 8.9-10.3 mg/dL), 1,25 dihydroxyvitamin D level 44.1 pg/ml (RI 19.9-79.3 pg/ml) and parathyroid hormone (PTH) 4 pg/mL (RI 15-65 pg/mL). CT scan of Abdomen and Pelvis showed hepatosplenomegaly with large retroperitoneal, retrocrural, and mesenteric lymphadenopathy which had an intense focal uptake on Gallium scan. Bone marrow biopsy revealed mild plasmacytosis (5%) with no evidence of myelodysplasia, acute leukemia or lymphoma. A subsequent lymph node biopsy showed fragments of fibrous tissue with lymphohistiocytic infiltrate and many acid-fast bacilli. Pre-antibiotic blood cultures grew Mycobacterium which was identified later as M. abscessus at four weeks. Conclusion: hypercalcemia in HIV-infected patients may suggest malignancy or infectious etiology, among other causes. Clinicians should be aware of the risk of hypercalcemia with nontuberculous mycobacterium (NTM) infection, whether as first manifestation or a late presenter in the disease course after initiating antiretroviral therapy (ART). We suggest careful monitoring of serum calcium level upon diagnosis of NTM infection and after initiation of ART, NTM therapy or vitamin D supplementation.