Infections following chimeric antigen receptor T cell therapy: 2018-2022.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is an emerging therapeutic modality for relapsed and refractory hematological malignancies. Infectious complications following CAR T-cell therapy are not well defined. METHODS: This is a retrospective analysis of data on patients who received CAR T-cell therapy between April 2018 and December 2022 at the Karmanos Cancer Center, Detroit. Patients' data were collected up to their last known clinic or inpatient follow-up visit. An infectious episode was defined as any microbiologically proven or clinically documented infection. RESULTS: Seventy-six patients received therapy with FDA-approved CAR T-cell products. Thirty-three patients (43.4%) had at least one infectious episode. There were 61 infectious episodes during a median follow-up of 184 (96-340) days. Median duration for the onset of infection was 59 (22-209) days. Bacterial and viral infections occurred in 42.6% and 41% of the infectious episodes, respectively. COVID-19 was the most common infectious complication (14.8%). Time-to-event analysis showed that most infections occurred within the first 100 days. Empirical antibiotic use during Cytokine Release Syndrome/Immune effector Cell-Associated Neurotoxicity Syndrome (CRS/ICANS) in the absence of documented bacterial infection was reported in 85.7% of patients. Clostridioides difficile accounted for 11.5% of all infectious episodes. Five of six patients with C. difficile infection had CRS/ICANS and received antibiotics. CONCLUSION: COVID-19 and C. difficile infection were the most common infections following CAR T-cell therapy. Most infections occurred within the first 100 days. Empiric antibiotic use and C. difficile infection were common in patients with CRS/ICANS, in the absence of documented bacterial infection, thus providing an excellent opportunity for antimicrobial stewardship in this population.

Advances in pharmacotherapies for cytomegalovirus infection: what is the current state of play?

INTRODUCTION: Cytomegalovirus (CMV) remains a serious opportunistic infection in hematopoietic cell transplant (HCT) and solid-organ transplant (SOT) recipients. Traditional anti-CMV drugs are limited by toxicities and the development of resistance. Letermovir and maribavir are newly approved antivirals for the prevention and treatment of CMV. AREAS COVERED: Prior reviews have discussed use of letermovir for prevention of CMV after HCT and maribavir for resistant or refractory (R/R) CMV post HCT or SOT. Subsequent data have expanded their use including letermovir for primary CMV prophylaxis in high-risk renal transplant recipients and new recommendations for extending prophylaxis through day + 200 in certain HCT patients. Data on the use of maribavir for first asymptomatic CMV infection post-HCT has also been published. This review compares the pharmacology of anti-CMV agents and discusses the updated literature of these new drugs in the prevention and treatment of CMV. EXPERT OPINION: Letermovir and maribavir are much needed tools that spare toxicities of ganciclovir, foscarnet, and cidofovir. High cost is a challenge preventing their integration into clinical practice in resource-limited countries. Transplant centers need to exercise restraint in overuse to avoid resistance, particularly in the setting of high viral loads.

A Multicenter Assessment of the Outcomes and Toxicities of Foscarnet for Treatment of Acyclovir-Resistant Mucocutaneous Herpes Simplex in Immunocompromised Patients.

Background: Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection is an uncommon problem typically seen in immunocompromised hosts. Systemic treatment options are limited. The performance of foscarnet and its toxicities in this population are poorly characterized. Methods: This was a multicenter retrospective study of adults treated with foscarnet for HSV infection between January 2012 and December 2017. Relevant data were collected including demographics, baseline conditions, previous anti-HSV medications, concomitant medications, HSV outcomes, and adverse events. Acyclovir-resistant HSV infection was defined based on genotypic or phenotypic testing results; refractory infection was defined as infection not improving after 5 days of treatment-dosed antiviral therapy in those not tested for resistance. Results: Twenty-nine patients had 31 episodes of HSV (15/18 resistant; among episodes without resistance testing, 7/10 refractory; 3 not evaluable) treated with foscarnet. All patients were immunocompromised including 19 (66%) with hematologic malignancy and 9 (31%) with HIV. Median duration of foscarnet was 16 days (range, 6-85 days). Fifteen episodes (48%) healed by the end of or after foscarnet. Median time to healing among those with resolution was 38 days (range, 9-1088 days). At least 1 adverse event during therapy was reported in 26 (84%) treatment episodes including 23 (74%) that were considered drug related. Common adverse events were electrolyte disturbance (20 [65%]) and kidney dysfunction (13 [42%]). Foscarnet was discontinued in 10 episodes (32%) due to an adverse event, including 6 due to kidney dysfunction. Conclusions: Among 31 episodes of HSV treated with foscarnet, only half resolved with treatment, and adverse events were common.

Modeling Invasive Aspergillosis Risk for the Application of Prophylaxis Strategies.

The epidemiology of invasive aspergillosis (IA) is evolving. To define the patient groups who will most likely benefit from primary or secondary Aspergillus prophylaxis, particularly those whose medical conditions and IA risk change over time, it is helpful to depict patient populations and their risk periods in a temporal visual model. The Sankey approach provides a dynamic figure to understand the risk of IA for various patient populations. While the figure depicted within this article is static, an internet-based version could provide pop-up highlights of any given flow's origin and destination nodes. A future version could highlight links to publications that support the color-coded incidence rates or other actionable items, such as bundles of applicable pharmacologic or non-pharmacologic interventions. The figure, as part of the upcoming Infectious Diseases Society of America's aspergillosis clinical practice guidelines, can guide decision-making in clinical settings.

False-Positive Human Immunodeficiency Virus Nucleic Acid Amplification Test After Chimeric Antigen Receptor T-Cell Therapy With Ciltacabtagene Autoleucel.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a novel therapeutic option for hematologic malignancies. Human immunodeficiency virus (HIV) nucleic acid amplification tests (NAATs) amplifying 5' long terminal repeat and gag genes cross-react with lentiviral vector-based CAR T-cell products. Cross-reactivity between CAR T-cell products and HIV NAATs may lead to false-positive test results.

Impact of Baseline and Week 2 and Week 4 Posttransplant CMV Cell-Mediated Immunity on Risk of CMV Infections and Mortality in Recipients of Allogeneic Hematopoietic Cell Transplant.

Background: Cytomegalovirus (CMV) infection is a common opportunistic infection after allogeneic hematopoietic cell transplant (alloHCT). We explored whether a change in CMV cell-mediated immunity during the first month after transplant predicts the risk of development of CMV infection and all-cause mortality. Methods: This follow-up analysis is based on data from the REACT study, a multicenter prospective observational study of recipients of alloHCT who were CMV-seropositive. Production of interferon γ following ex vivo stimulation with CMV antigens IE1 (immediate early 1) and pp65 (phosphoprotein 65) was assessed by CMV ELISPOT assay at baseline and 2 and 4 weeks after transplant. Clinically significant CMV infection (CS-CMVi) was defined as CMV viremia and/or disease necessitating antiviral therapy. We evaluated the impact of CMV CMI changes on the risk of CS-CMVi and post transplant mortality. Results: The analysis included 226 recipients of alloHCT with CMV cell-mediated immunity data at baseline and 2 and/or 4 weeks after transplant. CS-CMVi occurred in 64 patients (28%). On Cox regression analyses, independent predictors of CS-CMVi included a negative Δ change from baseline to week 2 of pp65 spot counts (hazard ratio, 3.65 [95% CI, 1.65-8.04]; P = .001) to week 4 of IE1 spot counts (hazard ratio, 2.79 [95% CI, 1.46-5.35]; P = .002), anti-thymocyte globulin conditioning regimen, type of transplant, female sex, and corticosteroid use. Kaplan-Meir analysis showed a significant association of a negative IE1 change from baseline to week 4 and increased all-cause mortality after transplant (log rank test = 0.041). Conclusions: A decrease in CMV-specific T-cell responses during the first month after transplant may predict CS-CMVi and is associated with all-cause mortality in recipients of alloHCT.

Polymerase chain reaction in the diagnosis of invasive aspergillosis: approaches for appropriate use.

Detection of aspergillus by PCR is a helpful tool for early diagnosis. The test has excellent sensitivity and specificity with a high negative predictive value. Well-accepted, standardized method for DNA extraction for PCR testing is to be adopted for all commercial assays and conclusive validation data are awaited in varied clinical settings. This perspective offers guidance for utilizing PCR testing while awaiting such data. Quantification by PCR, species-specific identification assays and detection of resistance genetic markers are of future promise. Herein, we summarize the available data on aspergillus PCR and describe its potential utility through a clinical case scenario-based approach.

Infectious complications after second allogeneic hematopoietic cell transplant in adult patients with hematological malignancies.

We conducted a retrospective review of the infectious complications and outcomes over a 2-year follow-up period of adult patients who received a second allogeneic hematopoietic cell transplant (2nd allo-HCT) during a five-year period at two cancer centers in Michigan. Sixty patients, of whom 44 (73%) had acute leukemia or myelodysplastic syndrome, were studied. The majority (n = 37,62%) received a 2nd allo-HCT because of relapsed leukemia. Infection episodes after the 2nd allo-HCT totaled 112. Bacteria were identified in 76 episodes, the majority of which occurred pre-engraftment. The most common infecting organisms were Enterococcus species and Clostridioides difficile. Viral infections, predominantly cytomegalovirus, accounted for 59 infection episodes and occurred mostly in pre-engraftment and early post-engraftment periods. There were 16 proven/probable fungal infections, of which 9 were invasive aspergillosis or candidiasis. Mortality was 45% (n = 27) at one year and 65% (n = 39) at 2 years after transplant, and 16 deaths (41%) were due to infection. Of those 16 infection deaths, 8 were bacterial, 4 fungal, 2 both bacterial and fungal, and 2 viral. Failure to engraft neutrophils or platelets was significantly associated with decreased survival, p < 0.0001 and p < 0.001, respectively. Infections are common after a 2nd allo-HCT and are associated with a high mortality rate.

Bloodstream Infections in Hematologic Malignancy Patients With Fever and Neutropenia: Are Empirical Antibiotic Therapies in the United States Still Effective?

Background: Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant. Methods: In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation. Results: Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall. Conclusions: In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.

Aspergillus Endophthalmitis: Epidemiology, Pathobiology, and Current Treatments.

Fungal endophthalmitis is one of the leading causes of vision loss worldwide. Post-operative and traumatic injuries are major contributing factors resulting in ocular fungal infections in healthy and, more importantly, immunocompromised individuals. Among the fungal pathogens, the Aspergillus species, Aspergillus fumigatus, continues to be more prevalent in fungal endophthalmitis patients. However, due to overlapping clinical symptoms with other endophthalmitis etiology, fungal endophthalmitis pose a challenge in its diagnosis and treatment. Hence, it is critical to understand its pathobiology to develop and deploy proper therapeutic interventions for combating Aspergillus infections. This review highlights the different modes of Aspergillus transmission and the host immune response during endophthalmitis. Additionally, we discuss recent advancements in the diagnosis of fungal endophthalmitis. Finally, we comprehensively summarize various antifungal regimens and surgical options for the treatment of Aspergillus endophthalmitis.

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.

SARS-CoV-2 infection: Initial viral load (iVL) predicts severity of illness/outcome, and declining trend of iVL in hospitalized patients corresponds with slowing of the pandemic.

BACKGROUND: Hospitalization of patients infected with the severe acute respiratory syndrome virus 2 (SARS-CoV-2) have remained considerable worldwide. Patients often develop severe complications and have high mortality rates. The cycle threshold (Ct) value derived from nasopharyngeal swab samples using real time polymerase chain reaction (RT-PCR) may be a useful prognostic marker in hospitalized patients with SARS-CoV-2 infection, however, its role in predicting the course of the pandemic has not been evaluated thus far. METHODS: We conducted a retrospective cohort study which included all patients who had a nasopharyngeal sample positive for SARS-CoV-2 between April 4 -June 5, 2020. The Ct value was used to estimate the number of viral particles in a patient sample. The trend in initial viral load on admission on a population level was evaluated. Moreover, patient characteristics and outcomes stratified by viral load categories were compared and initial viral load was assessed as an independent predictor of intubation and in-hospital mortality. RESULTS: A total of 461 hospitalized patients met the inclusion criteria. This study consisted predominantly of acutely infected patients with a median of 4 days since symptom onset to PCR. As the severity of the pandemic eased, there was an increase in the percentage of samples in the low initial viral load category, coinciding with a decrease in deaths. Compared to an initial low viral load, a high initial viral load was an independent predictor of in-hospital mortality (OR 5.5, CI 3.1-9.7, p < 0.001) and intubation (OR 1.82 CI 1.07-3.11, p = 0.03), while an initial intermediate viral load was associated with increased risk of inpatient mortality (OR 1.9, CI 1.14-3.21, p = 0.015) but not with increased risk for intubation. CONCLUSION: The Ct value obtained from nasopharyngeal samples of hospitalized patients on admission may serve as a prognostic marker at an individual level and may help predict the course of the pandemic when evaluated at a population level.

SARS-CoV-2 Viral Load and Myocardial Injury: Independent and Incremental Predictors of Adverse Outcome.

To evaluate the association of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initial viral load (iVL) and the incidence of myocardial injury (MCI) in hospitalized patients with SARS-CoV-2 infection, we conducted a retrospective longitudinal study of hospitalized patients who had a nasopharyngeal swab sample on admission that returned a positive result for SARS-CoV-2 by polymerase chain reaction between April 4 and June 5, 2020. The cycle threshold (Ct) value was used as a surrogate for the iVL level, with a Ct level of 36 or less for elevated iVL and greater than 36 for low iVL. Myocardial injury was defined as an elevated high-sensitivity cardiac troponin I level that was higher than the 99th percentile upper reference limit. A total of 270 patients were included. Of these, 171 (63.3%) had an elevated iVL and 88 (32.6%) had MCI. There was no significant difference in the incidence of MCI in patients with low iVL compared to those with elevated iVL (28 of 99 [28.3%] vs 60 of 171 [35.1%]; P=.25). In a multivariable model, MCI (odds ratio, 3.86; 95% CI, 1.80 to 8.34; P<.001) and elevated iVL (odds ratio, 4.21; 95% CI, 2.06 to 8.61; P<.001) were independent and incremental predictors of in-hospital mortality. The SARS-CoV-2 iVL level is not associated with increased incidence of MCI, although both parameters are strong independent and incremental predictors of mortality. Understanding the MCI mechanisms allows for early focused interventions to improve survival, especially in patients with SARS-CoV-2 infection and high iVL.

Spontaneous Hemoptysis in a Patient With COVID-19.

CASE PRESENTATION: A 65-year-old man presented with shortness of breath, gradually worsening for the previous 2 weeks, associated with dry cough, sore throat, and diarrhea. He denied fever, chills, chest pain, abdominal pain, nausea, or vomiting. He did not have any sick contacts or travel history outside of Michigan. His medical history included hypertension, diabetes mellitus, chronic kidney disease, morbid obesity, paroxysmal atrial fibrillation, and tobacco use. He was taking amiodarone, carvedilol, furosemide, pregabalin, and insulin. The patient appeared to be in mild respiratory distress. He was afebrile and had saturation at 93% on 3 L of oxygen, heart rate of 105 beats/min, BP of 145/99 mm Hg, and respiratory rate of 18 breaths/min. On auscultation, there were crackles on bilateral lung bases and chronic bilateral leg swelling with hyperpigmented changes. His WBC count was 6.0 K/cumm (3.5 to 10.6 K/cumm) with absolute lymphocyte count 0.7 K/cumm (1.0 to 3.8 K/cumm); serum creatinine was 2.81 mg/dL (0.7 to 1.3 mg/dL). He had elevated inflammatory markers (serum ferritin, C-reactive protein, lactate dehydrogenase, D-dimer, and creatinine phosphokinase). Chest radiography showed bilateral pulmonary opacities that were suggestive of multifocal pneumonia (Fig 1). Nasopharyngeal swab for SARS-CoV-2 was positive. Therapy was started with ceftriaxone, doxycycline, hydroxychloroquine, and methylprednisolone 1 mg/kg IV for 3 days. By day 3 of hospitalization, he required endotracheal intubation, vasopressor support, and continuous renal replacement. Blood cultures were negative; respiratory cultures revealed only normal oral flora, so antibiotic therapy was discontinued. On day 10, WBC count increased to 28 K/cumm, and chest radiography showed persistent bilateral opacities with left lower lobe consolidation. Repeat respiratory cultures grew Pseudomonas aeruginosa (Table 1). Antibiotic therapy with IV meropenem was started. His condition steadily improved; eventually by day 20, he was off vasopressors and was extubated. However, on day 23, he experienced significant hemoptysis that required reintubation and vasopressor support.

Azole resistance in Aspergillus species: promising therapeutic options.

INTRODUCTION: Azoles are the first-line antifungal agents used for the treatment of Aspergillus infection. There is an increasing concern for azole resistance all over the world mainly from agricultural fungicide use. Choosing safe and effective antifungal regimens has become a challenge. AREAS COVERED: Here, the authors review the epidemiology, mechanisms, and detection of azole resistance along with management options for azole-resistant Aspergillus infection, including new antifungal agents under development. EXPERT OPINION: Routine global epidemiological surveillance is required to understand azole resistance prevalence. Azole-resistant Aspergillus infections are associated with high mortality. No good therapeutic options are currently available. High index of suspicion of resistance is required if a patient is not responding to 4-7 days of azole therapy, particularly in the areas of resistance. Susceptibility testing for Aspergillus is not routinely available in many parts of the world, which makes it difficult to diagnose azole resistance in Aspergillus infection. There are several new antifungal classes with novel mechanisms of action; clinical trials are ongoing.

Serratia marcescens Infection-Associated Loss of Vision: A Case Report in a Patient with a History of Intravenous Drug Use.

BACKGROUND Serratia marcescens infections have historic association with injection drug use. The present report is about a 53-year-old man with a history of intravenous (IV) drug use who presented with acute loss of vision due to endophthalmitis associated with disseminated S. marcescens infection. CASE REPORT A 53-year-old man with a history of active illicit IV drug use presented with a chief complaint of loss of vision in his left eye for 5 days. He also reported having a fever, chills, and shortness of breath. While in the Emergency Department, he became hypotensive and hypoxic. He needed to be intubated and was started on vasopressor support. An ophthalmological examination was suspicious for endophthalmitis. The patient underwent a vitreous tap with injection of intravitreal antibiotics on the day of admission. An echocardiogram showed severe tricuspid endocarditis requiring valve replacement. He also was found to have a left lung/pleural abscess, which was surgically drained. Later, a left eye vitrectomy was performed and the intravitreal antibiotics were repeated; the treatment was unsuccessful and enucleation eventually was required. In addition, the patient had gastric bleeding and underwent esophagogastroduodenoscopy, which showed ischemic stomach ulcers suggestive of septic emboli. Cultures of the patient's blood, tricuspid valve, lung abscess, and vitreous fluid revealed S. marcescens. He was treated long term with a 2-drug antibiotic regimen and discharged in stable condition. CONCLUSIONS We have presented a rare case of acute loss of vision due to endophthalmitis in a patient with a history of IV drug use, which was associated with disseminated infection with the Gram-negative saprophyte S. marcescens.

Favorable outcome of COVID-19 among African American (AA) renal transplant recipients in Detroit.

Transplant recipients are vulnerable to infections, including COVID-19, given their comorbidities and chronic immunosuppression. In this study, all hospitalized renal transplant recipients (RTR) with a positive nasal swab for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2) seen consecutively between 03/01/2020 and 05/01/2020 at the Detroit Medical Center were included. Data on demographics, clinical presentation, laboratory findings, management, and outcomes were collected. Twenty-five patients were included, all African American (AA) and deceased-donor transplant recipients. The most common presenting symptom was dyspnea, followed by fever, cough and diarrhea. Multifocal opacities on initial chest x-ray were seen in 52% patients and 44% of patients had a presenting oxygen saturation of less than or equal to 94%. Four patients (16%) required transfer to the intensive care unit, one required intubation and one expired. COVID-19-infected RTR in this cohort had low mortality of 4% (n = 1). Despite multiple comorbidities and chronic immunosuppression, our cohort of African American RTR had favorable outcomes compared to other reports on COVID-19 in RTR.

Evaluation of Susceptibility and Innate Immune Response in C57BL/6 and BALB/c Mice During Candida albicans Endophthalmitis.

Purpose: Candida remains the leading cause of fungal endophthalmitis. However, the pathobiology and innate immune responses in this disease are not well characterized. Here, we developed two murine models of candida endophthalmitis and evaluated their disease susceptibility and differential immune response. Methods: Endophthalmitis was induced in C57BL/6 (B6) and BALB/c mice by intravitreal injection of Candida albicans (CA). Disease progression was monitored by slit-lamp examination and clinical scoring, followed by retinal function assessment using electroretinography (ERG). Enucleated eyes were used to estimate fungal burden and retinal tissue damage by hematoxylin and eosin and TUNEL staining. The level of inflammatory mediators were determined by quantitative Polymerase Chain Reaction (qPCR) and enzyme-linked immunosorbent assay, whereas neutrophil infiltration was assessed by flow cytometry and immunostaining. Results: Intravitreal injection of CA at 6500 colony-forming units resulted in sustained (non-resolving) ocular inflammation in both B6 and BALB/c mice as evidenced by increased levels of inflammatory cytokines (tumor necrosis factor-α, interleukin-1ß, and interleukin-6) and chemokine (CXCL2/MIP-2). In both mouse strains, fungal burden peaked at 24 to 48 hours post-infection (hpi) and decreased by 72 to 96 hpi. CA-infected eyes exhibited increased polymorphonuclear neutrophils (PMN) infiltration and retinal tissue damage. Overall retinal function declined rapidly, with a significant reduction in ERG response at 12 hpi and near-total loss by 24 hpi. Differential analyses revealed increased pathology in BALB/c versus B6 mice. Conclusions: C. albicans was able to cause endophthalmitis in mice. Although BALB/c mice were found to be more susceptible to CA endophthalmitis, both BALB/c and B6 models could be used to study fungal endophthalmitis and test therapeutic modalities.

Preventing Varicella-Zoster: Advances With the Recombinant Zoster Vaccine.

Prevention strategies against varicella zoster infection include chemoprophylaxis with acyclovir and live attenuated zoster vaccine. However, resistance to acyclovir has been problematic, and safety concerns have limited the use of the live attenuated vaccine in immunosuppressed patients. Recombinant zoster vaccine, made available in 2017 for the immunocompetent host, has been evaluated for safety, immunogenicity, and efficacy in several immunocompromised settings as well. The present review compares the live attenuated vaccine and the recombinant zoster vaccine and highlights data on the use of recombinant zoster vaccine in different immunocompromised states. Robust data are available for the safety, immunogenicity, and efficacy of the recombinant vaccine in the autologous stem cell population, particularly among patients with multiple myeloma. The vaccine appears safe and immunogenic in populations including those with cancer (solid tumors and hematologic malignancies), HIV-infected patients, and renal transplant recipients. Efficacy and safety data in other populations are awaited before use of the recombinant vaccine can be more widespread. It is anticipated that an increased use of the recombinant zoster vaccine, particularly in immunosuppressed patients, would lead to a decreased use of acyclovir prophylaxis.