Diagnostic delays in cutaneous coccidioidomycosis: A report from Central California.

Cutaneous Coccidioidomycosis (CC) infection can present with a wide variety of clinical presentations and is well known as a 'great imitator'. We performed a retrospective analysis of patients with CC in a large referral center in Central Valley, California, from 2010 to 2022 using the ICD9 and ICD10 codes for coccidioidomycosis and CC. We identified 40 patients with CC during the study period. The mean age of the study population was 43 years (with standard deviation of 14.08). Among these, 60% were men and 40% women. The appearance of the lesions varied from ulcers, plaques, nodules, blisters, cellulitis, and abscesses. The most common site of CC lesions was in the lower extremities (42.5%), followed by upper extremities (30%), chest and abdomen, head and neck (25% each). Only 22.5% of the 40 cases were diagnosed as CC and 15% were diagnosed as erythema nodosum. Rest were diagnosed initially as bacterial cellulitis in 37.5%, tinea in 7.5%, and others in 12.5%. There was resolution of the cutaneous lesions in all patients with antifungal treatment. The mean time of diagnosis from onset of symptoms on an average was 12 weeks (8-16 weeks) in our study with 75% cases initially misdiagnosed. Comprehensive knowledge about the manifestations and evaluation of CC among primary care providers and emergency room physicians is essential to prevent delays in diagnosis and treatment.

Cutaneous Coccidioidomycosis (CC) is defined as a fungal infection of the skin and/or subcutaneous tissues caused by the Coccidioides fungus. CC has been classified into primary CC which is caused by direct inoculation of the fungal organism into the skin, reactive CC defined as delayed hypersensitivity reaction, and disseminated CC which involves multiple organs infection. CC infection can present with a wide variety of clinical presentations and is well known as a 'great imitator'. Untreated CC can lead to worsening of local infection and the risk of dissemination to other organs. Coccidioidomycosis may be incorrectly diagnosed, and patients are more likely to receive unnecessary antibacterial drugs, laboratory tests, imaging, and invasive procedures, all of which could contribute to unnecessary costs and additional adverse health consequences. We performed a retrospective analysis of patients with CC in a large referral center in Central Valley, California, from 2010 to 2022. The mean time of diagnosis from onset of symptoms on an average was 12 weeks (8­16 weeks) in our study with 75% cases initially misdiagnosed. There is a need for collaboration between doctors and researchers across multiple counties within the Central Valley of California to develop strategies for diagnosing and treating CC and raising awareness in the community about the elevated risk of this infection for prevention and early detection.

Challenges in the Long-term Management of Patients With Coccidioidal Meningitis: A Retrospective Analysis of Treatment and Outcomes.

Background: Coccidioidal meningitis (CM) is the most severe form of disseminated coccidioidomycosis. Despite years of clinical experience, it remains a difficult condition to treat, often requiring surgical procedures, such as placement of a ventriculoperitoneal shunt, in addition to lifelong antifungal therapy. Methods: We performed a retrospective analysis of patients with CM seen in a large referral center in Central Valley, California, from 2010 to 2020. Data pertinent to CM were collected and analyzed. Results: Among 133 patients with CM identified in the 10-year period, nonadherence to antifungal therapy was noted in 43% of patients. Of the 80 patients who underwent ventriculoperitoneal shunt placement for management of intracranial pressure, shunt failure requiring revision surgery occurred in 42 (52.5%). Rehospitalizations due to CM-related reasons occurred in 78 of 133 patients (59%). Twenty-three percent of patients (n = 29) died due to complications from CM, on an average 22 months after the diagnosis of CM. Encephalopathy at presentation was associated with a significantly higher risk of death. Conclusions: Patients with CM in central California are predominantly rural agricultural workers with elevated levels of poverty and low health literacy and many barriers to care, leading to high rates of medication nonadherence and loss to follow-up outpatient care. Management challenges are frequent, such as failure of antifungal therapy, high rates of rehospitalization, and the need for repeated shunt revision surgeries. In addition to the development of curative new antifungal agents, understanding the barriers to patient adherence to care and antifungal therapy and identifying means to overcome such barriers are of paramount importance.

Delayed clearance of monkeypox virus in a patient with co infection with secondary syphilis.

Several studies from the current 2022 monkeypox (MPX) outbreak have documented co-infections with sexually transmitted infections (STIs), such as gonorrhea, chlamydia, and syphilis. We present a patient with MPX and secondary syphilis who failed to clear the MPX virus 30 days after illness onset despite a 14-day course of tecovirimat therapy.

Double Trouble: A Primary Epstein-Barr Virus Infection Causing Cholestatic Hepatitis and Hemophagocytic Lymphohistiocytosis.

Primary infection with Epstein-Barr virus (EBV) is very common, often manifesting as mononucleosis syndrome with fatigue, sore throat, fever, and enlarged lymph nodes. Liver involvement occurs in many cases with mildly elevated liver enzymes. However, it is rare to see EBV infection present as cholestatic hepatitis. Another rare complication of primary EBV infection is hemophagocytic lymphohistiocytosis (HLH). We describe a patient with primary EBV infection who presented with fatigue and jaundice, subsequent rash, and reactive lymphocytosis. The patient was noted to have cholestatic hepatitis and was highly suspected to have HLH based on laboratory values, including elevated ferritin, triglyceride, and interleukin-2 levels. He showed clinical improvement with HLH treatment using dexamethasone, etoposide, and rituximab. We further review the clinical manifestations, pathogenesis, and management of EBV-associated cholestatic hepatitis and EBV-HLH. Early diagnosis of primary EBV infection is emphasized in order to properly recognize and treat potentially life-threatening complications.

Spinal Arachnoiditis in Patients with Coccidioidomycosis Meningitis-Analysis of Clinical and Imaging Features.

Background: Coccidioidomycosis meningitis (CM) is the most aggressive form of coccidioidomycosis, requiring lifelong antifungal treatment and often cerebrospinal fluid (CSF) diversion. Long-standing CM can be associated with spinal complications such as arachnoiditis. However, studies describing the frequency, clinical, and imaging characteristics of arachnoiditis in patients with CM are limited. Methods: We identified 133 patients with CM based on CSF culture, PCR, or serology between January 2010 and December 2020. Of these, 37 patients underwent spinal imaging. Data on demographics, risk factors, symptoms, antifungal therapy, surgical management, follow-up visits, adherence, serological trends, and imaging findings were reviewed. Results: Abnormal findings were observed in 30 of the 37 patients with CM who underwent spinal imaging. The imaging abnormalities noted in our study included leptomeningeal enhancement (53%), arachnoiditis (53%), syringomyelia (23%), cord signal abnormalities (10%), and osteomyelitis (7%). Of the 30 patients, 90% had symptoms, such as weakness, numbness, or urinary retention. The incidence of arachnoiditis in the present study was 12%. Higher initial CSF protein levels and intra cranial pressure were associated with a higher risk of developing arachnoiditis/syringomyelia. Management of CM was challenging, as evidenced by shunt failure (46%), medication non-compliance (57%), and lack of adequate follow-up (60%). Persistent disabilities were noted in 62% of the patients. Conclusions: Patients with CM develop spinal complications such as arachnoiditis, or syringomyelia. Many cases may go undetected due to lack of symptoms in early stages. CM management challenges such as shunt failure, lack of follow-up care, and medication noncompliance, were frequent.

Strongyloides Hyperinfection Syndrome among COVID-19 Patients Treated with Corticosteroids.

Widespread use of corticosteroids for COVID-19 treatment has led to Strongyloides reactivation and severe disease in patients from endemic areas. We describe a US patient with COVID-19 and Strongyloides hyperinfection syndrome and review other reported cases. Our findings highlight the need for Strongyloides screening and treatment in high-risk populations.

Disseminated Gonorrhea Presenting as Liver Abscess in a Patient With Sickle Cell Disease.

ABSTRACT: Infection caused by Neisseria gonorrhoeae is a global health concern. Occasionally, gonococcal infections may disseminate and cause clinical syndromes, such as arthritis, tenosynovitis, and skin lesions. Here, we report a very rare presentation of a liver abscess due to N. gonorrhoeae in a 29-year-old woman with sickle cell disease without prior genitourinary complaints. The patient was successfully treated using drainage and antimicrobial therapy. Evaluation did not reveal any inherited defects in complement deficiency. It is possible that the underlying immune defects from sickle cell disease and unknown bacterial virulence factors could have contributed to this dissemination. Further research is needed to understand the immunopathogenesis of disseminated gonococcal infections, and efforts to screen and prevent primary infections are ongoing.

Efficacy and safety of Isavuconazole for the treatment of invasive Aspergillus infection - an update of the literature.

INTRODUCTION: Invasive aspergillosis is associated with high morbidity and mortality in immunocompromised patients. It is now increasingly reported in critically ill patients, including those with respiratory viral infections, such as influenza and COVID-19. Antifungal management is challenging due to diagnostic delay, adverse drug reactions, drug-drug interactions, narrow therapeutic window, and the emergence of resistance. Isavuconazole is the most recent FDA approved azole for the treatment of invasive aspergillosis, with data continuing to accumulate. AREAS COVERED: The authors review the safety and efficacy of isavuconazole in the management of invasive aspergillosis based on the currently available evidence. The authors also report on the structure, mechanism of action, pharmacokinetic properties, in vitro and in vivo studies as well as clinical safety and efficacy reports of isavuconazole since its FDA approval. EXPERT OPINION: Isavuconazole is non-inferior to voriconazole and is a safe, effective, and better tolerated option for the treatment of invasive aspergillosis. It offers several advantages over other antifungal agents, including having a better adverse event profile with respect to hepatotoxicity, neuro-visual toxicity, QTc prolongation, as well as a stable pharmacokinetic profile obviating the need for therapeutic drug monitoring. Further studies are needed to evaluate its performance in prophylaxis against invasive aspergillosis as well as in the treatment of aspergillosis in critically ill patients without underlying cancer or transplant.

COVID-19-Associated Pulmonary Aspergillosis: A Single-Center Experience in Central Valley, California, January 2020-March 2021.

Reports of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) have been widely published across the world since the onset of the pandemic with varying incidence rates. We retrospectively studied all patients with severe COVID-19 infection who were admitted to our tertiary care center's intensive care units between January 2020 and March 2021, who also had respiratory cultures positive for Aspergillus species. Among a large cohort of 970 patients admitted to the ICU with severe COVID-19 infections during our study period, 48 patients had Aspergillus species growing in respiratory cultures. Based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology (ECMM/ISHAM) consensus criteria, 2 patients in the study had proven CAPA, 9 had probable CAPA, and 37 had possible CAPA. The incidence of CAPA was 5%. The mean duration from a positive COVID-19 test to Aspergillus spp. being recovered from the respiratory cultures was 16 days, and more than half of the patients had preceding fever or worsening respiratory failure despite adequate support and management. Antifungals were given for treatment in 44% of the patients for a mean duration of 13 days. The overall mortality rate in our study population was extremely high with death occurring in 40/48 patients (83%).

Coccidioidal meningitis and neurosyphilis co-infection in a non-HIV patient.

Coccidioides sp. and Treponema pallidum can both cause infections of the central nervous system if untreated. We describe a case of an immunocompetent patient living in an endemic region for Coccidioides who presented with headaches and diplopia and was found to have co-infection of coccidioidal meningitis and neurosyphilis. We highlight the importance of evaluation for CNS co-infections as they may be underdiagnosed, especially in endemic areas for coccidioidomycosis.

Bordetella hinzii Pneumonia and Bacteremia in a Patient with SARS-CoV-2 Infection.

Patients with severe acute respiratory syndrome coronavirus 2 infection may have bacterial co-infections, including pneumonia and bacteremia. Bordetella hinzii infections are rare, may be associated with exposure to poultry, and have been reported mostly among immunocompromised patients. We describe B. hinzii pneumonia and bacteremia in a severe acute respiratory syndrome coronavirus 2 patient.

Cryptococcus neoformans Meningoencephalitis in an Immunocompetent Patient after COVID-19 Infection.

Cryptococcus neoformans is a saprophytic fungus that causes fatal disseminated infections in immunocompromised hosts. Since the onset of the COVID-19 pandemic, multiple cases of secondary viral, bacterial, and fungal infections have been reported in patients after SARS-CoV-2 infection. We describe here a case of severe cryptococcal meningitis that developed in a previously healthy patient one week after treatment of SARS-CoV-2 infection with dexamethasone. This case adds to the growing knowledge of emerging secondary infectious complications including opportunistic pathogens after SARS-CoV-2 infection. While few reports allude to depressed T-cell function and lymphopenia due to SARS-CoV-2 infection, further studies are needed to evaluate the effects of this infection and its treatment on the immune system and its contribution to the emergence of secondary opportunistic infections.

Rapidly progressive and fatal distant spontaneous gas gangrene due to Clostridium septicum after biopsy of malignant cecal mass.

Clostridium species are known to cause myonecrosis and gas gangrene which are often fatal infections in the setting of trauma but also spontaneously in certain populations such as colorectal malignancy, immunosuppression, and neutropenia. We report a case of an 83-year-old male who developed fatal and rapidly progressive gas gangrene due to Clostridium septicum within 48 h after biopsy of suspected malignant cecal mass. To our knowledge, such a drastic, rapid and fatal presentation after a diagnostic biopsy of malignant mass has not been previously reported and is something to be watchful for in suspected colon cancer cases.

Generalized tetanus in a landscaper without obvious wounds.

Tetanus is rare and potentially fatal infection in the US. Its incidence has declined dramatically over the years in developed countries due to robust immunization programs. We describe a case of generalized tetanus in a 66-year-old inadequately vaccinated landscaper who presented with classical symptoms but did not have any open wounds leading to delay in initial diagnosis but was successfully managed once the diagnosis was established.

Central nervous system histoplasmosis: Multicenter retrospective study on clinical features, diagnostic approach and outcome of treatment.

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the cerebrospinal fluid (CSF) in 75% of patients. One year survival was 75% among patients treated initially with amphotericin B, and was highest with liposomal, or deoxycholate formulations. Mortality was higher in immunocompromised patients, and patients 54 years of age, or older. Six percent of patients relapsed, all of whom had the acquired immunodeficiency syndrome (AIDS), and were poorly adherent with treatment.While CNS histoplasmosis occurred most often in immunocompromised individuals, a significant proportion of patients were previously, healthy. The diagnosis can be established by antigen, and antibody testing of the CSF, and serum, and antigen testing of the urine in most patients. Treatment with liposomal amphotericin B (AMB-L) for at least 1 month; followed by itraconazole for at least 1 year, results in survival among the majority of individuals. Patients should be followed for relapse for at least 1 year, after stopping therapy.

Roles of host and viral microRNAs in human cytomegalovirus biology.

Human cytomegalovirus (HCMV) has a relatively large and complex genome, a protracted lytic replication cycle, and employs a strategy of replicational latency as part of its lifelong persistence in the infected host. An important form of gene regulation in plants and animals revolves around a type of small RNA known as microRNA (miRNA). miRNAs can serve as major regulators of key developmental pathways, as well as provide subtle forms of regulatory control. The human genome encodes over 900 miRNAs, and miRNAs are also encoded by some viruses, including HCMV, which encodes at least 14 miRNAs. Some of the HCMV miRNAs are known to target both viral and cellular genes, including important immunomodulators. In addition to expressing their own miRNAs, infections with some viruses, including HCMV, can result in changes in the expression of cellular miRNAs that benefit virus replication. In this review, we summarize the connections between miRNAs and HCMV biology. We describe the nature of miRNA genes, miRNA biogenesis and modes of action, methods for studying miRNAs, HCMV-encoded miRNAs, effects of HCMV infection on cellular miRNA expression, roles of miRNAs in HCMV biology, and possible HCMV-related diagnostic and therapeutic applications of miRNAs.

Abacavir/lamivudine combination in the treatment of HIV: a review.

Abacavir has been at the center of research and clinical interest in the last two years. The frequency of the associated abacavir hypersensitivity syndrome has decreased substantially since the introduction of routine testing for the HLA-B*5701 allele; the activity of the drug in HIV-infected persons with HIV RNA values more than 100,000 copies/mL has been questioned; the possible increased risk of myocardial infarction after recent exposure to abacavir has been debated; and the drug has been moved from the "recommended" category to the "alternative" category in several guidelines. Still, the drug remains a useful agent in combination with other drugs, including lamivudine, for the treatment of HIV infection. This review will focus on the pharmacokinetics, activity, side effects, and resistance profile of both abacavir and lamivudine, including a thorough review of all of the recent studies relevant to both drugs.