[Lactobacillemia: A Rare Entity in Immunocompromised Patients. Description of a Clinical Case and Literature Review].

Bacteremia caused by Lactobacillus is rare, data on its clinical significance are based only on case reports and a limited number of studies, often difficult to interpret. Lactobacillus species is a commensal colonizer of the mouth, gastrointestinal and genitourinary tract. Its significance as a pathogen is overlooked frequently. The diagnosis of these infections requires a mutual relationship between the physician and the microbiologist to rule out contamination risk. Most patients with Lactobacillus bacteremia are immunosuppressed or patients at increased risk of symptomatic bacteremia with comorbidities, treated with broad-spectrum antibiotics and have indwelling venous catheters. Risk factors related to Lactobacillus bacteremia include impaired host defenses and severe underlying diseases, as well as prior surgery and prolonged antibiotic therapy ineffective for lactobacilli. We describe an unusual case of a woman, on chronic hemodialysis treatment, with a sepsis due to Lactobacillus casei and review the literature.

Invasive Ureteral Aspergillosis Causing an Abscess: A Report of a Rare Case.

Aspergillosis is a vicious fungal infection that can develop in immunosuppressed patients. The presence of aspergillosis in the ureter or elsewhere in the genito-urinary tract is highly uncommon and rarely reported in the literature. Here, we present a 54-year-old gentleman, with uncontrolled diabetes, who presented with urosepsis. Right hydronephrosis and ureteric stricture with urinary extravasation were seen on imaging. Right percutaneous nephrostomy was done, with drainage and analysis of the pus revealing the growth of Aspergillus fumigatus species. On open exploration, a ureteric abscess cavity, which was adherent to the duodenum, was drained and uretero-ureterostomy along with feeding jejunostomy was performed. Histopathological examination and special staining confirmed the growth of aspergillosis. The patient was treated with antifungal agents and responded well with an uneventful post-operative recovery.

Global research landscape of health care-associated infections among immunocompromised people before and after the start of the COVID-19 pandemic.

Health care-associated infections (HCAIs) pose a substantial threat to immunocompromised individuals and represent a frequent adverse event in health care delivery. The aim of this study was to evaluate the global research landscape of HCAIs among immunocompromised populations before and during the COVID-19 pandemic. A systematic search of articles published between 2013 and 2022 in the Web of Science Core Collection database was conducted, and content analytics and integrated science mapping were used for data analysis and interpretation. The review identified 1,473 articles. Only 633 articles authored by 4,151 individuals and published in 366 journals were included. The average citation rate was 14.27 per document, and research production grew annually by 9.07% peaking in 2021 during the COVID-19 pandemic but declining in 2022. The United States emerged as the most productive country, with 743 publication appearances and 2,485 citations. Keywords such as "epidemiology," "infection," "mortality," and "risk factors" were frequently encountered in the analyzed literature. The main research themes, including "mortality," "sepsis," "immunosuppression," "expression," and "pneumonia," underscored the focal points of importance within this domain. This study highlighted the growing interest regarding HCAIs in immunocompromised populations, especially during the COVID-19 pandemic. The study findings underscore the need to advance research efforts to understand different immunocompromised states, develop tailored infection prevention measures, and address health care disparities to mitigate the burden of HCAIs among immunocompromised individuals.

Strategies for Diagnosing and Treating Disseminated Methicillin-Sensitive Staphylococcus aureus Infections: Insights From a Pustular Eruption.

A 63-year-old immunocompromised male with a history of renal transplant and stage III large B-cell non-Hodgkin lymphoma undergoing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy presented with fever and a disseminated pustular eruption. Initial laboratory values indicated septicemia. Differential diagnoses included Sweet's syndrome, septic emboli, and leukocytoclastic vasculitis. Punch biopsies and bacterial cultures confirmed disseminated methicillin-sensitive Staphylococcus aureus (MSSA) infection. Histopathology revealed intraepidermal vesiculopustules and bacterial cocci colonies in the superficial dermis, suggesting hematogenous spread. The patient's indwelling venous access port was identified as the infection source and removed. Treatment included antibiotics such as cefepime, vancomycin, fluconazole, and acyclovir, as well as filgrastim for neutropenia. Following port removal and a four-week course of ceftriaxone, the patient's condition improved. This case highlights the importance of clinicopathologic correlation in diagnosing and managing disseminated staphylococcal infections in immunocompromised patients. The rare presentation of vesiculopustular eruptions secondary to MSSA emphasizes the need for prompt identification and treatment to prevent severe complications. This report contributes to the limited literature on disseminated staphylococcal infections presenting as vesiculopustular eruptions in immunocompromised individuals.

Recent updates in treating carbapenem-resistant infections in patients with hematological malignancies.

INTRODUCTION: Patients with hematological malignancies (PHMs) are at increased risk for infections caused by carbapenem-resistant organisms (CROs) due to frequent exposure to broad-spectrum antibiotics and prolonged hospital stays. These infections result in high mortality and morbidity rates along with delays in chemotherapy, longer hospitalizations, and increased health care costs. AREAS COVERED: Treatment alternatives for CRO infections in PHMs. EXPERT OPINION: The best available treatment option for KPC and OXA-48 producers is ceftazidime/avibactam. Imipenem/cilastatin/relebactam and meropenem/vaborbactam remain as the alternative options. They can also be used as salvage therapy in KPC-positive Enterobacterales infections resistant to ceftazidime/avibactam, if in vitro susceptibility is shown. Treatment of metallo-ß-lactamase producers is an unmet need. Ceftazidime/avibactam plus aztreonam or aztreonam/avibactam seems to be the most reliable option for metallo-ß-lactamase producers. As a first-line option for carbapenem-resistant Pseudomonas aeruginosa infections, ceftolozane/tazobactam is preferable and ceftazidime/avibactam and imipenem/cilastatin/relebactam constitute alternative regimens. Although sulbactam/durlobactam is the most reliable option against carbapenem-resistant Acinetobacter baumannii infections, its utility as monotherapy and in PHMs is not yet known. Cefiderocol can be selected as a 'last-resort' option for CRO infections. New risk score models supported by artificial intelligence algorithms can be used to predict the exact risk of infections in previously colonized patients.

A second-generation recombinant BCG strain combines protection against murine tuberculosis with an enhanced safety profile in immunocompromised hosts.

Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). While BCG protects against TB in children, its protection against pulmonary TB in adults is suboptimal, and the development of a better TB vaccine is a global health priority. Previously, we reported two recombinant BCG strains effective against murine TB with low virulence and lung pathology in immunocompromised mice and guinea pigs. We have recently combined these two recombinant BCG strains into one novel vaccine candidate (BCGΔBCG1419c::ESAT6-PE25SS) and evaluated its immunogenicity, efficacy and safety profile in mice. This new vaccine candidate is non-inferior to BCG in protection against TB, presents reduced pro-inflammatory immune responses and displays an enhanced safety profile.

Cutaneous Squamous Cell Carcinoma in Patients with Solid-Organ-Transplant-Associated Immunosuppression.

The management of advanced cutaneous squamous cell carcinoma (CSCC) has been revolutionized by the introduction of immunotherapy. Yet, successful treatment with immunotherapy relies on an adequate antitumor immune response. Patients who are solid-organ transplant recipients (SOTRs) have a higher incidence of CSCC compared to the general population. This review discusses the current knowledge of epidemiology, pathophysiology, and management of patients with CSCC who are immunocompromised because of their chronic exposure to immunosuppressive medications to prevent allograft rejection. First, we discuss the prognostic impact of immunosuppression in patients with CSCC. Next, we review the risk of CSCC development in immunosuppressed patients due to SOT. In addition, we provide an overview of the biological immune disruption present in transplanted immunosuppressed CSCC patients. We discuss the available evidence on the use of immunotherapy and provide a framework for the management approach with SOTRs with CSCC. Finally, we discuss potential novel approaches that are being investigated for the management of immunosuppressed patients with CSCC.

Hepatitis a vaccine immunogenicity and boostability in adults receiving immunosuppressive therapy and adults living with HIV: a prospective single-Centre cohort study.

INTRODUCTION: Hepatitis A (hepA) vaccination is highly immunogenic in healthy individuals, however there is uncertainty about the immunogenicity in immunocompromised populations (ICPs). METHODS: In this prospective cohort study, people living with HIV (PLWH), patients on immunosuppressive mono- and combination therapy, and controls received two hepA vaccine doses at months 0 and 6-12, or three combined hepA/B vaccine doses at months 0, 1 and 6-12. Antibody levels were measured before and at different time-points post-vaccination (T2, 6, 8, 12 months). The primary endpoint was the seroconversion rate (SCR) at T8, defined as hepA antibodies ≥20 mIU/ml. To assess boostability, an additional vaccine dose was administered 1-5 years after T12 in those with antibodies < 50 mIU/ml, with antibody measurements before and seven days after the booster dose. RESULTS: We included 150 participants. At T2 SCRs ranged between 35-58% in ICPs versus 94% in controls. Among PLWH, patients on monotherapy, combination therapy and controls SCRs at T8 were 33/34 (97%), 32/34 (94%), 25/30 (83%) and 28/28 (100%) respectively. The booster dose resulted in 71% additional seroconversion (17/24), with only patients using combination therapy not responding. CONCLUSIONS: HepA vaccination is highly immunogenic in virologically suppressed PLWH and patients on immunosuppressive monotherapy, with SCRs after the complete hepA vaccination schedule similar to controls and adequate booster responses in case of waning immunity. However, patients using immunosuppressive combination therapy as well as all ICPs who did not receive the complete hepA vaccination schedule, are at risk of non-response to vaccination and post-vaccination antibody measurements are recommended.

Comparative effectiveness of bivalent BA.4-5 or BA.1 mRNA booster vaccines among immunocompromised individuals across three Nordic countries: A nationwide cohort study.

OBJECTIVES: To estimate the effectiveness and waning of the bivalent BA.4-5 or BA.1 mRNA booster vaccine against Covid-19-related hospitalization and death in immunocompromised individuals. METHODS: Nationwide analyses across Nordic countries from 1 September 2022 to 31 October 2023 using a matched cohort design. Individuals boosted with a BA.4-5 or BA.1 vaccine were matched 1:1 with unboosted individuals. The outcomes of interest were country-combined vaccine effectiveness (VE) estimates against Covid-19-related hospitalization and death at day 270 of follow-up. Waning was assessed in 45-day intervals. RESULTS: A total of 352,762 BA.4-5 and 191,070 BA.1 booster vaccine doses were included. At day 270, the comparative VE against Covid-19-related hospitalization was 34.2% (95% CI, 7.1% to 61.3%) for the bivalent BA.4-5 vaccine and 42.6% (95% CI, 31.3% to 53.9%) for the BA.1 vaccine compared with matched unboosted. The comparative VE against Covid-19-related death was 53.9% (95% CI, 38.6% to 69.3%) for the bivalent BA.4-5 vaccine and 57.9% (95% CI, 48.5% to 67.4%) for the BA.1 vaccine. CONCLUSIONS: In immunocompromised individuals, vaccination with bivalent BA.4-5 or BA.1 booster lowered the risk of Covid-19-related hospitalization and death over a follow-up period of 9 months. The effectiveness was highest during the first months since vaccination with subsequent gradual waning.

Treatment of persistent coronavirus disease 2019 (COVID-19) in a B cell acute lymphoblastic leukemia patient with using nirmatrelvir/ritonavir extended course: A case report.

Patients with hematological malignancies are at increased risk of persistent coronavirus disease 2019 (COVID-19) infection, a unique clinical condition, for which the optimal treatment is unknown. Here we report a case of persistent COVID-19 in acute lymphoblastic leukemia (ALL) patient who successfully responded to extended course nirmatrelvir/ritonavir.

Case reports of persistent SARS-CoV-2 infection outline within-host viral evolution in immunocompromised patients.

BACKGROUND: SARS-CoV-2 is responsible for the ongoing global pandemic, and the continuous emergence of novel variants threatens fragile populations, such as immunocompromised patients. This subgroup of patients seems to be seriously affected by intrahost viral changes, as the pathogens, which are keen to cause replication inefficiency, affect the impaired immune system, preventing efficient clearance of the virus. Therefore, these patients may represent an optimal reservoir for the development of new circulating SARS-CoV-2 variants. The following study aimed to investigate genomic changes in SARS-CoV-2-positive immunocompromised patients over time. METHODS: SARS-CoV-2-positive nasopharyngeal swabs were collected at different time points for each patient (patient A and patient B), extracted and then analyzed through next-generation sequencing (NGS). The resulting sequences were examined to determine mutation frequencies, describing viral evolution over time. CASE PRESENTATION: Patient A was a 53-year-old patient with onco-hematological disease with prolonged infection lasting for 51 days from May 28th to July 18th, 2022. Three confirmed SARS-CoV-2-positive samples were collected on May 28th, June 15th and July 4th. Patient B was 75 years old and had onco-hematological disease with prolonged infection lasting for 146 days. Two confirmed positive SARS-CoV-2 samples were collected at the following time points: May 21st and August 18th. CONCLUSION: Heat map construction provided evidence of gain and/or loss of mutations over time for both patients, suggesting within-host genomic evolution of the virus. In addition, mutation polymorphisms and changes in the SARS-CoV-2 lineage were observed in Patient B. Sequence analysis revealed high mutational pattern variability, reflecting the high complexity of viral replication dynamics in fragile patients.

What do we know About the Usefulness of 18F-FDG PET-CT for the Management of Invasive Fungal Infection? An International Survey.

BACKGROUND: Recent data support 18F-FDG PET-CT for the management of infections in immunocompromised patients, including invasive fungal infection (IFI). However, its role is not well established in clinical practice. We performed an international survey to evaluate the knowledge of physicians about the usefulness of 18F-FDG PET-CT in IFI, in order to define areas of uncertainty. METHODS: An online survey was distributed to infectious diseases working groups in December 2023-January 2024. It included questions regarding access to 18F-FDG PET-CT, knowledge on its usefulness for IFI and experience of the respondents. A descriptive analysis was performed. RESULTS: 180 respondents answered; 60.5% were Infectious Diseases specialists mainly from Spain (52.8%) and Italy (23.3%). 84.4% had access to 18F-FDG PET-CT at their own center. 85.6% considered that 18F-FDG PET-CT could be better than conventional tests for IFI. In the context of IFI risk, 81.1% would consider performing 18F-FDG PET-CT to study fever without a source and around 50% to evaluate silent lesions and 50% to assess response, including distinguishing residual from active lesions. Based on the results of the follow-up 18F-FDG PET-CT, 56.7% would adjust antifungal therapy duration. 60% would consider a change in the diagnostic or therapeutic strategy in case of increased uptake or new lesions. Uncovering occult lesions (52%) and diagnosing/excluding endocarditis (52.7%) were the situations in which 18F-FDG PET-CT was considered to have the most added value. There was a great variability in responses about timing, duration of uptake, the threshold for discontinuing treatment or the influence of immune status. CONCLUSION: Although the majority considered that 18F-FDG PET-CT may be useful for IFI, many areas of uncertainty remain. There is a need for protocolized research to improve IFI management.

Immune and microbiome modulatory effects of Limosilactobacillus fermentum NCDC 400 in an immunocompromised mouse model.

The present study was aimed to assess and validate the safety and functional efficacy of an indigenous probiotic strain Limosilactobacillus fermentum NCDC 400 (hereafter, LFN400) in an immunocompromised murine model. The study included four groups; a normal control (NC) group without immune suppression; an experimental model control (MC) with immune suppression induced via intraperitoneal cyclophosphamide (Cy) administration; and two MC groups orally administered with either low dose (LD) or high dose (HD) of LFN400 at dose 108 and 1010 CFU/mouse/day, respectively, for 15-days. Both control groups received normal saline as placebo control. LFN400 improved specific experimental characteristics including hematological and serum biochemical markers. Compared to MC group, LFN400-fed groups showed markedly (P < 0.05) decreased arrays of detrimental caecal enzymes. We did not observe instances of bacterial translocation of LFN400 from gut to bloodstream or extra-intestinal organs. LFN400 intake significantly (P < 0.05) enhanced spleen cell differentiation, immune and oxidative stress markers, and restored Cy-induced histopathological changes in multiple tissues, including the spleen. There was no genotoxic effect of LFN400 on bone marrow cells. Although not statistically significant, LFN400 feeding moderately increased gut microbiome diversity, supporting the growth of beneficial saccharolytic microorganisms and reducing the presence of pathobionts. The findings demonstrate that the probiotic strain LFN400 possesses in vivo safety and immunomodulatory potency and thus should be considered a potential candidate for future human clinical studies.

Universal azole prophylaxis for prevention of coccidioidomycosis among lung transplant recipients transferring care to a center within a highly endemic region.

BACKGROUND: Coccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown. METHODS: Lung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post-transplant follow-up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions. RESULTS: Forty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work-up for suspected infection during hospitalization. After a median follow-up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post-transplant and >2 years post-transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications. CONCLUSION: Azole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region.

Pneumocystis jirovecii Pneumonia in Patients Treated for Solid Organ Malignancy.

Background: Pneumocystis jirovecii is a fungal pathogen that can present as an opportunistic cause of pneumonia and can occur in individuals with various causes of immunosuppression, including malignancy and treatments for malignancy that confer increased risk. Although the guidelines for use of Pneumocystis prophylaxis in certain populations are clear, the rapid development of novel cancer therapies elicits the need to accurately assess the degree of immunosuppression conferred by these regimens and to determine if patients receiving these therapies warrant Pneumocystis prophylaxis. Case Series: We present 2 cases of Pneumocystis jirovecii pneumonia in patients with invasive ductal carcinoma of the breast treated with a dose-dense chemotherapy regimen consisting of doxorubicin, cyclophosphamide, and paclitaxel. Conclusion: The use of a dose-dense regimen, in which the interval between doses is shortened compared to a standard regimen, has become a common therapy for patients diagnosed with early breast cancer. Although this approach leads to improved disease-free and overall survival, it has also been associated with an increased risk of developing Pneumocystis jirovecii pneumonia. Further research involving patients receiving dose-dense chemotherapy regimens is needed to determine their risk of developing opportunistic infections and whether that risk warrants changes in clinical management.

Cefiderocol as rescue therapy in a cancer immunosuppressed critically ill child: Case description and literature review.

Severe infections caused by multidrug-resistant bacteria have underscored the urgent need for innovative treatment approaches. Novel antimicrobials like cefiderocol have emerged as effective options, but their use in children remains largely unexplored. In this brief report, we describe a severe case of sepsis in a child with an oncohematological disease, caused by a highly drug-resistant strain of Klebsiella pneumoniae. The addition of cefiderocol to other therapies resulted in a successful outcome. Additionally, we provide a literature review of previously published cases involving children treated with this new antibiotic. In our patient, cefiderocol was both safe and effective in combating the multidrug-resistant pathogen. However, further research is needed to better define the indications and safety profile of this novel antibiotic.

Prognostic Factors for Mortality in Patients With Autoimmune Diseases Complicated by Pneumocystis Pneumonia.

Objectives Pneumocystis pneumonia (PCP) has a poor prognosis in patients with autoimmune diseases. Additionally, the mortality of PCP in autoimmune diseases is higher than that of human immunodeficiency virus-PCP. Therefore, this study aimed to assess the risk factors associated with mortality in patients with autoimmune diseases complicated with PCP. Methods We conducted a retrospective observational study involving 38 patients treated for PCP at Showa University School of Medicine from January 2010 to August 2014. Diagnoses were established based on clinical symptoms, imaging, and laboratory tests, including hypoxemia (partial pressure of oxygen (PaO2) < 70 mmHg), chest computed tomography findings, elevated (1,3)-ß-D-glucan, and positive Pneumocystis jiroveciipolymerase chain reaction tests from sputum samples. Data regarding patient demographics, underlying diseases, therapeutic interventions, and laboratory findings were collected. Statistical comparisons between survivors and non-survivors were performed using Fisher's exact probability test and Mann-Whitney U test for independence test with Stata/SE version 17.0 (StataCorp LLC, College Station, TX). Results The median age of the study group was 72.4 years old, with the majority having rheumatoid arthritis. Mortality occurred in 18% (seven out of 38) of cases. Factors associated with increased mortality include males, higher serum creatinine and C-reactive protein levels, lower albumin and immunoglobulin A levels, and lower PaO2/fraction of inspired oxygen (FiO2) ratio. No significant difference was observed in the rate of intratracheal intubation, ICU management, and hospitalization period. Prophylactic administration of trimethoprim-sulfamethoxazole (TMP-SMX) was not performed in any of the cases. Conclusions This study examined the risk of mortality for PCP in patients with autoimmune diseases. The male gender, low IgA and albumin levels, low PaO2/FiO2 ratio, as well as high creatinine and CRP levels, were identified as significant factors for poor prognosis. These factors can help identify patients at high risk for PCP and guide the consideration of prophylactic TMP-SMX administration. They may also provide insights into when to discontinue prophylactic treatment. Future studies should investigate the administration of prophylactic TMP-SMX. Additionally, the risk of mortality for PCP under the administration of new biological agents, such as anifrolumab, belimumab, and rituximab, or immunosuppressants, such as mycophenolate mofetil and voclosporin, should be evaluated. These findings can contribute to improving PCP prevention and treatment strategies in patients with autoimmune diseases, ultimately leading to better patient outcomes.

Outcomes of Intravenous Immunoglobulin treatment of immunocompromised patients with viral respiratory infections.

BACKGROUND: Limited guidelines exist for treating immunocompromised patients hospitalized for acute viral respiratory infection. Little is known about clinical and economic benefits of IVIG administration in patients with acute viral respiratory infections. OBJECTIVE: We compared clinical and economic outcomes among immunocompromised patients hospitalized with viral respiratory infections who received IVIG to those who did not. METHODS: We performed a retrospective cohort study on all patients hospitalized for a respiratory viral infection between 2011 and 2016 at two large academic centers including data on age, gender, virus species, immunosuppression type, and receipt of IVIG. Outcomes included death, hospital readmission, length of stay (LOS) in the hospital, and the intensive care unit (ICU). RESULTS: A total of 270 patient admissions were reviewed, and 35.6% received IVIG. The average age was 40.6 years, 50% were female and 74% were transplant patients. The most common virus was rhinovirus (50.7%). Use of IVIG was significantly associated with a shorter ICU LOS (ß=-0.534, P=0.012), and a longer hospital LOS (ß=0.887, P<0.01). IVIG administered within 48 hours of hospitalization (n=229) was associated with a shorter ICU LOS (ß=-2.08, P=0.001) and a shorter hospital LOS for patients hospitalized at least 2 days (ß=-0.461, P=0.007). There were no significant differences in readmission rates or death. CONCLUSION: This double-center, retrospective cohort analysis is one of the first studies to evaluate the effect of IVIG on immunocompromised patients hospitalized with respiratory viral infections. IVIG was associated with a shorter hospital and ICU LOS, especially when administered within 48 hours of admission.