Current Epidemiology and Clinical Features of Cryptococcus Infection in Patients Without Human Immunodeficiency Virus: A Multicenter Study in 46 Hospitals in Australia and New Zealand.

BACKGROUND: Patients without human immunodeficiency virus (HIV) are increasingly recognized as being at risk for cryptococcosis. Knowledge of characteristics of cryptococcosis in these patients remains incomplete. METHODS: We conducted a retrospective study of cryptococcosis in 46 Australian and New Zealand hospitals to compare its frequency in patients with and without HIV and describe its characteristics in patients without HIV. Patients with cryptococcosis between January 2015 and December 2019 were included. RESULTS: Of 475 patients with cryptococcosis, 90% were without HIV (426 of 475) with marked predominance in both Cryptococcus neoformans (88.7%) and Cryptococcus gattii cases (94.3%). Most patients without HIV (60.8%) had a known immunocompromising condition: cancer (n = 91), organ transplantation (n = 81), or other immunocompromising condition (n = 97). Cryptococcosis presented as incidental imaging findings in 16.4% of patients (70 of 426). The serum cryptococcal antigen test was positive in 85.1% of tested patients (319 of 375); high titers independently predicted risk of central nervous system involvement. Lumbar puncture was performed in 167 patients to screen for asymptomatic meningitis, with a positivity rate of 13.2% where meningitis could have been predicted by a high serum cryptococcal antigen titer and/or fungemia in 95% of evaluable cases. One-year all-cause mortality was 20.9% in patients without HIV and 21.7% in patients with HIV (P = .89). CONCLUSIONS: Ninety percent of cryptococcosis cases occurred in patients without HIV (89% and 94% for C. neoformans and C. gattii, respectively). Emerging patient risk groups were evident. A high level of awareness is warranted to diagnose cryptococcosis in patients without HIV.

Extra-pulmonary applications of procalcitonin: an updated literature review.

INTRODUCTION: Procalcitonin (PCT) is a biomarker with established performance in the differentiation between bacterial and viral infections, predominantly in pulmonary infections, as well as the diagnosis and prognosis of bacterial sepsis. However, the role of PCT in extra-pulmonary infections is not well described. AREAS COVERED: We reviewed the role of PCT in commonly experienced extra-pulmonary infections including meningitis, diabetic foot infection, prosthetic joint infection, osteomyelitis, and skin and soft tissue infection. PubMed and Medline online libraries were searched, from 2013 till 2022, for relevant articles. EXPERT OPINION: For meningitis, PCT could distinguish bacterial from viral meningitis. PCT distinguished septic arthritis from different inflammatory states but had variable performance in discriminating septic arthritis from crystal arthropathy. For periprosthetic joint infections, results were inconclusive. PCT had a potential role in diagnosis of more complex infections such as osteomyelitis and diabetic foot infections, but further studies are needed for a definitive cutoff. In skin and soft tissue infections, PCT performance was variable requiring further investigation to define cutoff for the discrimination of cellulitis from necrotizing fasciitis. We find that PCT performed best for meningitis and helps in the reduction of unnecessary antibiotic treatment, but has variable outcomes with other extra-pulmonary infections.

Suboptimal COVID-19 vaccine uptake among hospitalised patients: an opportunity to improve vulnerable, hard-to-reach population vaccine rates.

BACKGROUND: COVID-19 vaccination represents a key preventative part of the Australian public health approach to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Hospital inpatients are frequently high risk for severe COVID-19 and death. Anecdotes of high-risk inpatients being unvaccinated and a lack of electronic medical record (EMR) visibility of COVID-19 vaccination status prompted the present study as these patients could represent a risk to themselves, staff, other patients and service provision. AIMS: To determine the uptake of COVID-19 vaccine among inpatients at an adult Australian tertiary public hospital and identify reasons for non-vaccination. METHODS: A point-prevalence study of patient-reported COVID-19 vaccine status was conducted on 26 October 2021 through an in-person interview with collection of demographic factors and reasons for non-vaccination. RESULTS: Of 368 (68% of inpatients) participants, 280 (76%) reported receiving at least one COVID-19 vaccine dose. Vaccination status was associated with older age, having received the flu vaccine, being born in Australia and not requiring an English-language interpreter. The majority (88%) of participants had at least one comorbid risk factor for severe COVID-19. Of the unvaccinated (n = 88), 67% were willing to be vaccinated with 54% of those indicating vaccination in hospital would be helpful and 42% requesting approval from their doctor. CONCLUSIONS: Vaccine uptake in our cohort is suboptimal. Existing public health programmes have failed to reach this high-risk, vulnerable population. Changes to the national vaccination strategy to include a parallel inhospital programme for all hospital encounters and target culturally and linguistically diverse individuals might improve uptake among this high-risk, hard-to-reach group of patients.

Baseline procalcitonin as a predictor of bacterial infection and clinical outcomes in COVID-19: A case-control study.

PURPOSE: Coronavirus disease-2019 (COVID-19) is associated with a wide spectrum of clinical symptoms including acute respiratory failure. Biomarkers that can predict outcomes in patients with COVID-19 can assist with patient management. The aim of this study is to evaluate whether procalcitonin (PCT) can predict clinical outcome and bacterial superinfection in patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). METHODS: Adult patients diagnosed with SARS-CoV-2 by nasopharyngeal PCR who were admitted to a tertiary care center in Boston, MA with SARS-CoV-2 infection between March 17 and April 30, 2020 with a baseline PCT value were studied. Patients who were presumed positive for SARS-CoV-2, who lacked PCT levels, or who had a positive urinalysis with negative cultures were excluded. Demographics, clinical and laboratory data were extracted from the electronic medical records. RESULTS: 324 patient charts were reviewed and grouped by clinical and microbiologic outcomes by day 28. Baseline PCT levels were significantly higher for patients who were treated for true bacteremia (p = 0.0005) and bacterial pneumonia (p = 0.00077) compared with the non-bacterial infection group. Baseline PCT positively correlated with the NIAID ordinal scale and survival over time. When compared to other inflammatory biomarkers, PCT showed superiority in predicting bacteremia. CONCLUSIONS: Baseline PCT levels are associated with outcome and bacterial superinfection in patients hospitalized with SARS-CoV-2.

Therapeutic drug monitoring of flucytosine in a cardiac transplant patient receiving continuous veno-venous hemofiltration and intermittent hemodialysis: A case report.

Invasive candidiasis is one of the common infections in solid organ transplant recipients. Guidelines recommend echinocandins or liposomal amphotericin with consideration of flucytosine (5-fluorocytosine; 5-FC) as synergistic therapy for treatment of select deep-seated Candida infections, including complex endovascular infections. Flucytosine undergoes extensive renal elimination; however, optimal dosing in patients with renal impairment, or those requiring renal replacement therapy (RRT), is not well-established. We describe a case of a 60-year old female who underwent orthotopic heart transplant complicated by Candida parapsilosis complex fungemia with mediastinitis and development of end-stage renal disease requiring RRT. Flucytosine therapeutic drug monitoring was performed on continuous veno-venous hemofiltration (CVVH) and intermittent hemodialysis (iHD) to guide appropriate dosing. Our results support 5-FC doses of 25 mg/kg daily while undergoing CVVH with a low fluid replacement rate and 21 mg/kg post-iHD or 17 mg/kg daily while receiving thrice weekly iHD.

Immunosuppressive Agents and Infectious Risk in Transplantation: Managing the "Net State of Immunosuppression".

Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The "net state of immune suppression" is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative viral loads to assess the individual's ability to control latent viral infections. Few studies address adjustment of immunosuppression during active infections; thus, confronted with infection in solid organ recipients, the management of immunosuppression is based largely on clinical experience. This review examines known measures of immune function and the immunologic effects of common immunosuppressive drugs and available studies reporting modification of drug regimens for specific infections. These data provide a conceptual framework for the management of immunosuppression during infection in organ recipients.

COVID-19 in solid organ transplant recipients: Dynamics of disease progression and inflammatory markers in ICU and non-ICU admitted patients.

BACKGROUND: COVID-19 infection varies in severity from minimal symptoms to critical illness associated with a hyperinflammatory response. Data on disease progression in immunosuppressed solid organ transplant (SOT) recipients are limited. METHODS: We examined the electronic medical records of all SOT recipients with COVID-19 from 12 Massachusetts hospitals between February 1, and May 6, 2020. We analyzed the demographics, clinical parameters, course, and outcomes of illness in these patients. RESULTS: Of 52 COVID-19-positive SOT patients, 77% were hospitalized and 35% required ICU admission. Sixty-nine percent of hospitalized patients had immunosuppression reduced, 6% developed suspected rejection. Co-infections occurred in 45% in ICU vs 5% in non-ICU patients (P = .037). A biphasic pattern of evolution of laboratory tests was observed. In the first 5 days of illness, inflammatory markers were moderately increased. Subsequently, WBC, CRP, ferritin, and D Dimer increased with increasing stay in the ICU, and lymphocyte counts were similar. Five patients (16%) died. CONCLUSIONS: Our data indicate that SOT is associated with high rate of hospitalization, ICU admission, and death from COVID-19 compared to data in the general population of patients with COVID-19. Despite reduction in immunosuppression, suspected rejection was rare. The clinical course and trend of laboratory biomarkers is biphasic with a later, pronounced peak in inflammatory markers seen in those admitted to an ICU. CRP is a useful marker to monitor disease progression in SOT.

Clinical Effectiveness of Conjugate Pneumococcal Vaccination in Hematopoietic Stem Cell Transplantation Recipients.

Hematopoietic stem cell transplantation (HSCT) recipients are vulnerable to invasive pneumococcal disease (IPD), with reported IPD rates ranging from 3.81 to 22.5/1000 HSCT. This IPD risk could relate to immunodeficiency, low vaccination uptake, and poor immunogenicity of pneumococcal polysaccharide vaccine (PPV). Literature comparing the clinical effectiveness of pneumococcal conjugate vaccination (PCV) and PPV after HSCT is limited. In this retrospective analysis of HSCT recipients at our center from 2004 to 2015, we evaluated vaccination uptake and compared IPD rates in patients receiving PPV (pre-2010 group) and PCV (post-2010 group). IPD was determined from microbiological results for all HSCT recipients from January 2004 to June 30, 2019. Eight hundred patients had a total of 842 HSCT events, including autologous HSCT (auto-HSCT; n = 562) and allogeneic HSCT (allo-HSCT; n = 280). More than 90% of the HSCT recipients were enrolled, and >93% of surviving HSCT recipients completed the vaccination protocol. Fifteen IPD episodes occurred in 13 patients between 2004 and June 30, 2019. Thirteen episodes occurred in the pre-2010 group, even though 9 of 13 (69%) serotyped isolates were covered by PPV. Two episodes occurred in the post-2010 group; neither serotype was covered by PCV. Thus, with PCV introduction, IPD rate was significantly reduced from 38.5/1000 unique HSCTs pre-2010 to 4.0/1000 unique HSCTs post-2010 (P < .001). A significant reduction was seen in both auto-HSCTs (from 29.4 to 3.1 /1000 unique auto-HSCTs; P = .011) and allo-HSCTs (from 58.3 to 5.6/1000 unique allo-HSCTs; P = .011). PCV demonstrated superior clinical effectiveness over PPV, highlighting its importance in preventing infectious complications after HSCT. Robust vaccination programs at transplantation centers are needed to optimize vaccination uptake and completion.

Inflammatory bowel disease-specific pregnancy knowledge of gastroenterologists against general practitioners and obstetricians.

BACKGROUND: Patients with inflammatory bowel disease (IBD) tend to have smaller family sizes. Health care professionals (HCPs) may inadvertently provide inaccurate advice to patients resulting in voluntary childlessness or unfavourable pregnancy outcomes. OBJECTIVE: The study aims to objectively measure IBD-specific pregnancy-related knowledge of general practitioners (GPs) and obstetricians/gynaecologists (OB/GYNs) in comparison with gastroenterologists (GEs) using the validated Crohn's and Colitis Pregnancy Knowledge (CCPKnow) questionnaire. METHODS: GPs, OB/GYNs and GEs in two Australian states completed the CCPKnow (range 0-17) and demographic questionnaires. The CCPKnow addresses issues pertaining to conception, IBD inheritance, risk of congenital abnormalities, medication use in the peri-conceptual period, pregnancy and breastfeeding, and mode of delivery. RESULTS: In total, 337 HCPs responded. GPs (n = 188/2086) and OB/GYNs (n = 94/228) had significantly lower knowledge than GEs (n = 55/165) for the composite CCPKnow (medians 11, 13 and 17, respectively, p < 0.001), and almost all domains. GEs were the only group to attain a median CCPKnow score in the top category (14-17). More than 70% of GPs and OB/GYNs expressed discomfort with initiation of IBD medications around conception/pregnancy. GPs (43.6%) and OB/GYNs (45.7%) perceived thiopurine use to be unsafe during pregnancy and to cause serious harm to the baby. CONCLUSIONS: Our study demonstrates that GPs and OB/GYNs have inadequate and variable IBD-specific pregnancy-related knowledge including use of IBD medications. These results support the need for GEs' prime role in a team-based management for IBD patients who are pregnant or planning pregnancy.