The epidemiology, mechanisms, diagnosis and treatment of cardiovascular disease in adult patients with HIV.

More than 1.2 million people in the United States have Human Immunodeficiency Virus (HIV) infections but 13% of these people are unaware of their HIV infection. Current combination antiretroviral therapy (ART) does not cure HIV infection but rather suppresses the infection with the virus persisting indefinitely in latent reservoirs in the body. As a consequence of ART, HIV infection has changed from a fatal disease in the past to a chronic disease today. Currently in the United States, more than 45% of HIV+ individuals are greater than 50 years of age and 25% will be greater than 65 years of age by 2030. Atherosclerotic cardiovascular disease (CVD), including myocardial infarction, stroke, and cardiomyopathy, is now the major cause of death in HIV+ individuals. Novel risk factors, including chronic immune activation and inflammation in the body, antiretroviral therapy, and traditional CVD risk factors, such as tobacco and illicit drug use, hyperlipidemia, the metabolic syndrome, diabetes mellitus, hypertension, and chronic renal disease, contribute to cardiovascular atherosclerosis. This article discusses the complex interactions involving HIV infection, the novel and traditional risk factors for CVD, and the antiretroviral HIV therapies which can contribute to CVD in HIV-infected people. In addition, the treatment of HIV+ patients with acute myocardial infarction, stroke, and cardiomyopathy/heart failure are discussed. Current recommended ART and their major side effects are summarized in table format. All medical personnel must be aware of the increasing incidence of CVD on the morbidity and mortality in HIV infected patients and must be watchful for the presence of CVD in their patients with HIV.

Uncommon presentations of common variable immunodeficiency.

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder that causes decreased immunity and increased susceptibility to infections. It affects B lymphocyte differentiation, resulting in predominantly bacterial and less frequently viral, fungal, and protozoal infections. The respiratory and gastrointestinal tracts where antibody defences are essential are usually affected. Individuals with CVID are also predisposed to developing lymphoid and gastrointestinal malignancies. We present two cases with rare infectious and oncological complications of CVID, including a patient with Mycobacterium avium complex-intracellular infection and ovarian cancer, and another patient with group B Streptococcus empyema of the lung with acute myeloid leukaemia. The main objective of this study is to highlight how CVID-induced hypogammaglobulinaemia can lead to rare infections and malignancies. The management of these complications can vary according to severity, but an awareness of their existence is crucial to diagnose them promptly in an already immunocompromised CVID patient.

Multidisciplinary approach in diagnosis and treatment of COVID-19-associated mucormycosis: a description of current reports.

Background: We reviewed the epidemiology, risk factors, pathophysiology, and clinical presentations of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM), then discussed the importance of rapid diagnosis and treatment facilitated by multidisciplinary approach. Main body: India has reported world's highest number of CAM cases where Rhizopus arrhizus was the most predominant etiology. CAM caused by Rhizopus microsporus was the most common from the rest of the world. Multiple risk factors for CAM were identified including diabetes mellitus, inappropriate corticosteroid use, COVID-19-related hypoxia, and lung damage.Rhino-orbito-cerebral mucormycosis (ROCM) accounted for almost 90% of CAM in India while 64% of global cases were ROCM. Less than 10% of CAM from India were pulmonary while the rest of the world reported 21% of pulmonary CAM.CAM is diagnosed by confirmed SARS-CoV2 infection along with clinical, radiological, histopathological, and/or microbiological evidence of mucormycosis. In patients with risks of CAM and associated symptoms, CT or MRI are recommended. If ROCM is suspected, endoscopy and biopsy are recommended. If pulmonary CAM is suspected, tissue biopsies, nasal samples, or bronchoalveolar lavage is recommended with histopathological exams.Early diagnosis, surgical, and pharmaceutical interventions are key to treat mucormycosis. Upon diagnosis, antifungal therapy with liposomal amphotericin B (IV) is considered first-line of therapy. Alternatively, posaconazole (PO/IV) or isavuconazole (PO/IV) can be used. Conclusion: Treating CAM requires a multidisciplinary approach for early diagnosis and prompt initiation of interventions to maximize patient's chance of survival.

Zoonotic Bacterial Respiratory Infections Associated With Cats and Dogs: A Case Series and Literature Review.

Cats and dogs make up an essential part of the household for families in the United States. Close contact with pets can carry a risk of potential infectious disease transmission. This case series outlines causes of zoonotic pneumonia associated with cats and dogs, with a particular focus on the three cases presented of respiratory infection with Bordetella (B.) bronchiseptica and Pasteurella (P.) multocida in patients with an underlying malignancy. B. bronchiseptica is a rare bacterial pathogen in humans that can cause disease in immunocompromised individuals. Interpreting the significance of B. bronchiseptica as a pathogenic agent can be challenging given that this microbe often accompanies other organisms in culture. P. multocida is another important pathogen known to cause severe respiratory infection in immunocompromised populations or those with certain underlying comorbidities. A broadened differential for other bacterial etiologies of zoonotic respiratory infection acquired from dogs or cats includes Francisella tularensis, Yersinia pestis, Coxiella burnetii, and Bartonella henselae. These pathogens should be considered in the correct clinical context. Pets also play a role as reservoirs for the transmission of resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus intermedius group (SIG), and extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae. Immunocompromised individuals must be educated on the potential for household transmission of zoonotic disease and how to limit certain types of close contact with pets. This report also highlights the importance of flea and tick control in pets for the prevention of zoonotic disease spread.

COVID-19 in Immunocompromised Cancer Patients: A Case Series and Review of the Literature.

The global pandemic of the novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented newfound challenges to the oncology community regarding management of disease progression in immunocompromised and cancer patients. Further, the large influx of COVID-19 patients has overwhelmed healthcare facilities, limited access to intensive care unit beds and ventilators, and canceled elective surgeries causing disruptions to the cancer care continuum and re-organization of oncological care. While it is known that the potential threat of infection is greatest in elderly patients (>60 years of age) and patients with underlying comorbidities, there is still insufficient data to determine the risk of COVID-19 in cancer patients. Given the immunosuppressive status in cancer patients arising from chemotherapy and other comorbidities, management of COVID-19 in this patient population carries a unique set of challenges. We report three cases of COVID-19 in immunocompromised cancer patients and discuss the challenges in preventing, diagnosing, and treating this vulnerable group.

Preventing the Spread: A Comprehensive Cancer Center's Journey to Prevent the Spread of Coronavirus Disease (Covid-19) During the 2020 Pandemic.

BACKGROUND: On March 11, 2020, the World Health Organization (WHO) declared Coronavirus Disease (COVID-19) a pandemic. Hospitals around the world began to implement infection prevention and control (IPC) measures to stop further spread and prevent infections within their facilities. Healthcare organizations were challenged to develop response plans, procure personal protective equipment (PPE) that was in limited supply while continuing to provide quality, safe care. METHODS: As a comprehensive cancer center with immunocompromised patients, our efforts began immediately. Preventative measures were established and, as of September 2020, over 14,000 patients have been tested within the facility. From March 2020 through September 2020, only one case of hospital acquired (HA) COVID-19 was identified among our patients. Two cases of suspected community acquired (SCA) cases were also identified. Following the Centers for Disease Control (CDC) guidance, IPC measures were implemented within the facility as information science about the virus developed. This article addresses the IPC measures taken, such as enhancing isolation precautions, implementing screening protocols, disinfecting and reusing N95 respirators, by the center throughout the pandemic as well as the challenges that arouse with a new and emerging infectious disease. CONCLUSIONS: The infection control measures implemented at our comprehensive cancer center during the COVID-19 pandemic allowed our center to continue to provide world class cancer care with minimal COVID-19 infection transmission among patients and team members.

Prospective CYP2C19-Guided Voriconazole Prophylaxis in Patients With Neutropenic Acute Myeloid Leukemia Reduces the Incidence of Subtherapeutic Antifungal Plasma Concentrations.

A risk mitigation strategy was implemented to determine if a higher prophylactic voriconazole dosage in patients with CYP2C19 rapid metabolizer neutropenic acute myeloid leukemia (AML) reduces the incidence of subtherapeutic trough concentrations. Patients with AML (n = 263) were preemptively genotyped for CYP2C19*2, *3, and *17 alleles as part of a single-center prospective, interventional, quality improvement study. CYP2C19 rapid metabolizers (CYP2C19*1/*17) were recommended to receive interventional voriconazole 300 mg twice daily, ultrarapid metabolizers (CYP2C19*17/*17) were recommended to avoid voriconazole, and all others received the standard prophylactic dosage of 200 mg twice daily. In this real-world setting, 202 patients (76.8%) were prescribed prophylactic voriconazole, and of these patients 176 (87.1%) received CYP2C19-guided prophylactic dosing. Voriconazole trough concentrations were obtained for 41 of the 58 (70.7%) CYP2C19 rapid metabolizers prescribed prophylactic voriconazole. Interventional voriconazole resulted in higher plasma trough concentrations (median 2.7 µg/mL) compared with the standard prophylactic dosage (median 0.6 µg/mL; P = 0.001). Subtherapeutic concentrations were avoided in 83.8% of CYP2C19 rapid metabolizers receiving interventional dosage compared to 46.2% receiving standard dosage (P = 0.02). CYP2C19 genotyping to preemptively guide prophylactic voriconazole dosing is feasible and may be a potential strategy for reducing the risk of subtherapeutic trough concentrations that potentiate breakthrough fungal infections.

A Case Series of Staphylococcus lugdunensis Infection in Cancer Patients at an Academic Cancer Institute in the United States.

BACKGROUND: Staphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) that is a part of the normal human skin flora. Even though it belongs to CoNS family, it can cause severe and destructive infections in a similar fashion to Staphylococcus aureus. Skin and soft tissue infections (SSTI), bacteremia and endocarditis are amongst the most common clinical presentations. Diagnosis and clinical presentation of infections caused by S. lugdunensis in cancer patients is limited. MATERIALS AND METHODS: We performed a retrospective chart review of 24 patients who had cultures positive for S. lugdunensis. Out of 24 patients, 14 patients were diagnosed with a true infection and 10 other patients were considered to be colonized with this pathogen. We analyzed clinical manifestation, treatment and response to therapy. RESULTS: SSTI was the most common presentation in our study patients. All patients diagnosed with SSTI had a prior surgery or an invasive procedure at the affected site. Five urinary tract infections (UTIs), one catheter-associated bloodstream infection, and a deep pelvic abscess were other reported infections in our study. We observed that S. lugdunensis remains susceptible to a variety of antibiotics, with all isolates susceptible to vancomycin and linezolid and most remain susceptible to fluoroquinolone and trimethoprim/ sulfamethoxazole. All 14 patients received antibiotics and improved. CONCLUSION: In our case series, SSTI was common and diagnosed in 50% of the patients with clinically significant isolates for S. lugdunensis. This is consistent with prior studies indicating that S. lugdunensis is a significant pathogen in SSTIs. UTI was the second most common infection type in our patient population.

Malignancy Trends in HIV-Infected Patients Over the Past 10 Years in a Single-Center Retrospective Observational Study in the United States.

The introduction of antiretroviral therapy (ART) in 1995 had a dramatic impact on the morbidity and mortality of the HIV population, and subsequently, the natural history of cancer has changed. The purpose of our study was to review the prevalence of AIDS-defining malignancies and non-AIDS defining cancers (NADC), taking into consideration racial and gender variations. After the institutional review board approval, the study was conducted as a retrospective chart review of 279 HIV-infected patients who were treated at the Moffitt Cancer Center between January 1, 2000 and December 31, 2010. The demographic characteristics included gender, ethnicity, race, presence or absence of ART, and the type of malignancy reviewed. Of 233 men, 78 (33.5%) had AIDS-defining malignancies. AIDS-related non-Hodgkin lymphoma (NHL) was detected in 49 (21%) patients and Kaposi sarcoma (KS) in 29 (12%) patients. Two-thirds of male patients had NADC, with anal cancer being the most prevalent (8.5%), followed by Hodgkin lymphoma (6%). AIDS-related NHL was also the predominant malignancy for women with a prevalence of 19.5% followed by invasive cervical cancer (ICC) and breast cancer, both with a similar prevalence of 11%. Kaposi sarcoma and anal cancer were equally detected in 2% of women. The prevalence rates of AIDS-defining malignancies among those of white race were 34%, ranging from 21% for NHL to 13% for KS and 1.5% for ICC. Twenty-one (7.7%) patients had anal cancer. AIDS-defining malignancies were found in 36% of patients of black race and 60% had NHL. Non-AIDS-related NHL was the second most common malignancy, followed by breast cancer and anal cancer with a similar prevalence of 6.5%. Of 279 patients, 53% were taking ART; 39.4% were not taking ART; and in 7.5% of the patients, it was unknown if they were taking ART. In the ART era, our study found NADC to be more prevalent than AIDS-defining malignancies with 60% versus 40%, respectively. Non-Hodgkin lymphoma remained the most common AIDS-related malignancy in both genders. Among the patients with NADC, anal cancer was the predominant malignancy. The increasing incidence of some of the NADC is expected as this population is living longer with chronic exposure of viral replication of virus with oncogenic potential such as Human papillomavirus (HPV), Hepatitis B virus (HBV), Epstein-Barr virus (EBV), and Human herpesvirus 8 (HHV-8). Early ART initiation, aggressive vaccination, and judicious cancer screening are the cornerstone of cancer prevention of this growing population.

Treatment of Enteropathogenic Escherichia coli Diarrhea in Cancer Patients: A Series of Three Cases.

Enteropathogenic Escherichia coli (EPEC) is a common cause of watery diarrhea in children in the developing world and an infrequent cause of significant diarrhea in adult patients. EPEC diarrhea, while not commonly seen in cancer patients, can cause significant distress to patients, and antimicrobial choice for this condition in this patient population is not clearly delineated in the literature. We report 3 cases of EPEC diarrhea in cancer patients and discuss the use of azithromycin for successful treatment of these patients. Positive outcomes were seen while using azithromycin in our first two patients and ciprofloxacin in our third patient.

Infectious Risks and Complications in Adult Leukemic Patients Receiving Blinatumomab.

BACKGROUND: Blinatumomab is an anti-CD19 immunotherapy approved for relapsed/refractory B-cell acute lymphoblastic leukemia (ALL) with significantly increased survival rate. While blinatumomab showed lower rates of infection, neutropenia and mucosal barrier injury versus chemotherapy, its infection risks are not well described. METHODS: All patients who received blinatumomab for ≥ seven days at an academic cancer center from May 2015 to April 2017 were included. Patient characteristics pertinent to infectious risks and complications were examined. RESULTS: Twenty patients with refractory (25%), relapsed (70%), or remitted (5%) B-ALL who received a total of 35 cycles were included. Ten of the 35 cycles were interrupted, none of which were due to infections. Twenty-six infections (n) were observed with lower respiratory (9), gastrointestinal (6) and bacteremia (5) being most common. Compared to patients without nodular, possible mold pneumonia (n=16), patients with nodular pneumonia (n=4) had significantly lower baseline absolute neutrophil count (ANC) (2319 v. 208/µL, p=0.011). There were no differences in baseline characteristics including ANC between bacteremic and non-bacteremic patients. One patient was discharged with no antibacterial prophylaxis since ANC recovered to >500cells/µL, but developed Pseudomonal bacteremia within a week with ANC ~100cells/µL. CONCLUSION: Despite blinatumomab's relatively modest myelosuppression and the lack of mucotoxicity, host factors (e.g., duration and degree of neutropenia/lymphopenia) play a key role and should be considered when choosing anti-microbial prophylaxis. In relapsed/refractory disease, the ANC should be monitored closely post blinatumomab since neutropenia can unexpectedly develop after treatment which may be compounded by the underlying disease and recent chemotherapy effects.

Bacillus cereus Typhlitis in a Patient with Acute Myelogenous Leukemia: A Case Report and Review of the Literature.

Bacillus cereus is a Gram-positive rod that is now recognized as a rare cause of frank disease in the neutropenic hematologic malignancy patient. Because this pathogen is rarely isolated in clinical specimens, no large studies exist to guide the management of these acutely ill patients. Individual case reports and case series exist in the literature describing various clinical manifestations of B. cereus in the neutropenic patient including bacteremia/septicemia, pneumonia, meningitis/encephalitis, hepatic abscesses, and gastritis. In this report, we describe a case of typhlitis caused by B. cereus in a 74-year-old female with recently diagnosed acute myelogenous leukemia (AML), and we summarize the available English language literature to draw tentative conclusions regarding the clinical manifestations of this organism.

Two cases of disseminated infection following live organism anti-cancer vaccine administration in cancer patients.

Vaccines containing live attenuated bacterial or viral organisms are currently being investigated as potential therapy for locally advanced or metastatic cancers. However, the use of such live organisms in an immunocompromised population, such as patients who recently or are currently receiving chemotherapy, raises the concern that these organisms can themselves disseminate and cause frank infection. We report a hereunto unreported phenomenon of anti-cancer vaccines (containing live attenuated organisms) leading to frank, disseminated infection. We submit that occurrence of this phenomenon must be watched for by all members of the interdisciplinary cancer treatment team.

Mucositis and oral infections secondary to gram negative rods in patients with prolonged neutropenia.

Patients with prolonged neutropenia are at risk for a variety of complications and infections including the development of mucositis and oral ulcers. The changes in oral flora during chemotherapy and its effects on the development of infections of the oral cavity have been studied with inconsistent results. However, there is evidence that supports the colonization of gram negative rods in patients undergoing chemotherapy. In this report, we present two leukemic patients who developed oral ulcers secondary to multi-drug resistant Pseudomonas aeruginosa. It is important to suspect multi-drug resistant gram negative rods in patients with prolonged neutropenia who develop gum infections despite appropriate antibiotic coverage.

Infectious Causes of Right Middle Lobe Syndrome.

Right middle lobe (RML) syndrome is defined as recurrent or chronic obstruction or infection of the middle lobe of the right lung. Nonobstructive causes of middle lobe syndrome include inflammatory processes and defects in the bronchial anatomy and collateral ventilation. We report on 2 case patients with RML syndrome, one due to infection with Mycobacterium avium complex followed by M asiaticum infection and the other due to allergic bronchopulmonary aspergillosis. A history of atopy, asthma, or chronic obstructive pulmonary disease has been reported in up to one-half of those with RML. The diagnosis can be made by plain radiography, computed tomography, and bronchoscopy. Medical treatment consists of bronchodilators, mucolytics, and antimicrobials. Patients whose disease is unresponsive to treatment and those with obstructive RML syndrome can be offered surgical treatment.

Invasive Haemophilus influenzae Infection in Patients With Cancer.

A major cause of morbidity and mortality in patients with cancer is infection. Since the introduction of the Haemophilus influenzae type b (Hib) vaccine in the United States in the 1990s, invasive H influenzae infection has become less common. We report on 5 patients with cancer and invasive H influenzae infection. A literature review was also performed of the dominant Haemophilus subtype and the clinical features associated with the infection and concomitant cancer. Of the 17 cases found in the literature, had hematological malignancies and 1 case each had thymoma, schwannoma, teratoma, and pancreatic, Merkel cell, pharyngeal, laryngeal, and rectal carcinomas. Two cases occurred with AIDS and Kaposi sarcoma. Pneumonia with bacteremia was seen in 8 cases, whereas pleuritis, neck cellulitis, septic arthritis, meningitis, and mediastinitis were diagnosed in the others. No focus of infection was identified in 2 cases. Nontypable H influenzae (NTHi) occurred in 4 cases, and Hib was isolated in 2 cases; serotyping was not reported in the others. Leukocytosis occurred in 7 cases and lymphopenia in 3; no cases presented with neutropenia. Four isolates were positive for beta-lactamase. Susceptibility data were unavailable in 5 case patients. Among serotyped cases, 67% were of the NTHi strain - a finding consistent with the change in the epidemiology of H influenzae since the introduction of the Hib vaccine.

Human Metapneumovirus Infection in Immunocompromised Patients.

Human metapneumovirus (HMPV) is a pathogen associated with respiratory tract infection and is related to avian pneumovirus. Typically, children, the elderly, and those who are immunocompromised are the most susceptible to HMPV infection; however, the virus can infect persons of all ages. In otherwise healthy individuals, HMPV infection is generally self-limiting, but immunocompromised individuals can develop fatal complications. We present a case series of 3 severely immunocompromised patients who were infected with HMPV and describe their clinical course. All 3 patients had acute myeloid leukemia, histories of neutropenic fever, and prolonged hospitalization stays. This case series highlights the severe sequelae observed in individuals infected with HMPV, particularly among those who are immunocompromised.

Primary Gangrenous Cutaneous Mold Infections in a Patient With Cancer and Neutropenia.

BACKGROUND: Opportunistic fungal infections caused by Aspergillus and Candida followed by infections with Fusarium, Rhizopus, Mucor, and Alternaria species are an important cause of morbidity and mortality in patients with hematological malignancies. Cutaneous mucormycosis infections are rare, and the incidence, outcomes, and factors associated with survival in the setting of hematological malignancies are not clear. METHODS: A literature search was conducted for all cases of primary cutaneous mold infections in patients with hematological malignancy, of which 50 cases were found. Our case of a patient with a hematological malignancy who sustained a cat bite that in turn caused a primary cutaneous mold infection is also included. RESULTS: In the 51 cases identified, 66.7% were neutropenic upon presentation, and 54.9% were male with an average age of 32 years. Aspergillus species (33.3%) was the most cited followed by Rhizopus species (19.6%). Overall mortality rate was 29.4% and was observed more frequently in patients with neutropenia (60.0%) and without surgical intervention (73.3%). Survival rate was higher (35.3%) for cases utilizing both antifungal and surgical intervention. The antifungal agent with the highest survival rate was amphotericin B and its formulations (58.8%). CONCLUSIONS: Neutropenia within hematological malignancies demonstrate a risk for developing severe cutaneous fungal infections, of which primary cutaneous mucormycosis can carry significant mortality. Combination antifungal therapy and surgical debridement appears to be associated with higher survival outcomes and warrants further investigation.

Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia.

Diffuse alveolar hemorrhage is a potentially fatal pulmonary disease syndrome that affects individuals with hematological and nonhematological malignancies. The range of inciting factors is wide for this syndrome and includes thrombocytopenia, underlying infection, coagulopathy, and the frequent use of anticoagulants, given the high incidence of venous thrombosis in this population. Dyspnea, fever, and cough are commonly presenting symptoms. However, clinical manifestations can be variable. Obvious bleeding (hemoptysis) is not always present and can pose a potential diagnostic challenge. Without prompt treatment, hypoxia that rapidly progresses to respiratory failure can occur. Diagnosis is primarily based on radiological and bronchoscopic findings. This syndrome is especially common in patients with hematological malignancies, given an even greater propensity for thrombocytopenia as a result of bone marrow suppression as well as the often prolonged immunosuppression in this patient population. The syndrome also has an increased incidence in individuals with hematological malignancies who have received a bone marrow transplant. We present a case series of 5 patients with acute myeloid leukemia presenting with diffuse alveolar hemorrhage at our institution. A comparison of clinical manifestations, radiographic findings, treatment course, and outcomes are described. A review of the literature and general overview of the diagnostic evaluation, differential diagnoses, pathophysiology, and treatment of this syndrome are discussed.

Marijuana Smoking in Patients With Leukemia.

Worldwide, marijuana (cannabis) is a widely used drug. The incidence of marijuana smoking is increasing and is second only to tobacco as the most widely smoked substance in the general population. It is also the second most commonly used recreational drug after alcohol. Some adverse effects of marijuana smoking have been documented; however, the number of studies on the pulmonary effects of marijuana in individuals with leukemia is limited. In our case series, we report on 2 men with acute myeloid leukemia with miliary nodular lung patterns on computed tomography of the chest due to heavy marijuana use. We also report on 2 patients with acute lymphocytic leukemia who had a history of smoking marijuana and then developed lung opacities consistent with mold infection.