Infective and noninfective pulmonary complications occur with biologic agents and targeted small molecule inhibitors used to treat immune-mediated inflammatory conditions. The most common lower respiratory tract infection is bacterial pneumonia. Opportunistic infections including tuberculosis can also occur at increased rates depending on the immunosuppressive agent, specific disease, and epidemiologic background of the patient. The most common noninfectious sequela is drug-induced interstitial lung disease.

Although pneumocystis jirovecii pneumonia (PJP) in non-HIV patients is increasingly recognized, comprehensive data on immunosuppressive drivers remain limited. We conducted a population-based cohort study using a German health insurance's claims data (2015-2023). PJP, comorbidities, immunocompromising conditions and therapies were identified by means of ICD-10-GM-, ATC- and OPS-coded records. 922,200 individuals were assessed for PJP occurrence, hospitalization and 30-day all-cause mortality. An Andersen-Gill model adjusted for key covariates. We identified 171 PJP episodes, with hospitalization in 88.3% and mortality in 24.5%. Frequent immunocompromising causes were hematologic cancers (42.6%), immunosuppressants (28.7%) and steroids (28.7%). Immunosuppression rather than typical CAP risk factors strongly predicted all outcomes (HR 49.9 [31.5-78.9]). Robust associations with PJP occurred for HIV (HR 67.5 [19.4-235]), systemic steroids (> 20 mg prednisone daily equivalent (HR 26.2 [13.2-52.1])) and hematologic cancers (HR 8.5 [4.5-16.3]). Mortality was driven by hematologic cancers (HR 13.9 [4.8-40.2]) and high-dose steroids (HR 8.6 [1.6-47.1]). Malignancy-related immunosuppression and steroids critically affect PJP risk and prognosis.

Strongyloides stercoralis is a soil-transmitted helminth that is increasingly reported in dogs across Europe. While most infections are subclinical, hyperinfection syndrome, marked by excessive larval proliferation and systemic spread, can occur in immunocompromised hosts. An 11-year-old male Boston Terrier dog, originating from southern France with a history of chronic diarrhoea and recent splenectomy was presented with severe regenerative anaemia, thrombocytopenia, and a degenerative left shift. Haemotropic Mycoplasma haemocanis infection was diagnosed, and doxycycline therapy was initiated. During hospitalisation, the dog developed dyspnoea, pneumonia, and progressive pleural effusion containing motile nematode larvae. Strongyloides stercoralis infection was diagnosed by morphological identification of larvae in pleural effusion (third-stage larvae) and faeces (first- and third-stage larvae) and confirmed by PCR targeting mitochondrial cox1 and nuclear 18S rDNA hypervariable regions (HVR) I and IV), followed by sequencing, which revealed the haplotypes HP16 (cox1), VI (HVR-I) and A (HVR-IV). The HVR-IV haplotype A is found in both dogs and humans, characterizing the zoonotic population of S. stercoralis. Respiratory signs worsened despite combined fenbendazole and escalating ivermectin treatment, requiring euthanasia. Post-mortem examination revealed chronic granulomatous pneumonia, a pulmonary carcinomatous nodule, lymphoplasmacytic enterocolitis, and glomerulonephritis. This case represents the first report of S. stercoralis hyperinfection in an adult splenectomised dog. It highlights the importance of including strongyloidiasis in differential diagnoses of dogs with respiratory and gastrointestinal signs, particularly in animals with compromised immunity or relevant travel history.

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that predominantly affects immunocompromised individuals. Reports in immunocompetent children are rare. We report the case of a previously healthy 5½‑year‑old Saudi girl who presented with fever, dry cough, and progressive respiratory distress. Her condition rapidly deteriorated, requiring pediatric intensive care admission and mechanical ventilation due to severe acute respiratory distress syndrome. Her course was complicated by pneumothorax, pneumomediastinum, and extensive surgical emphysema. Extensive microbiological investigations were negative except for bronchoalveolar lavage demonstrating Pneumocystis jirovecii using Gomori methenamine silver staining. The patient was treated with intravenous trimethoprim-sulfamethoxazole and supportive intensive care management with gradual clinical recovery. Immunological evaluation, including lymphocyte subsets, immunoglobulin levels, complement levels, vaccine antibody responses, and whole‑exome sequencing, revealed no evidence of primary or secondary immunodeficiency. Long‑term follow‑up for more than 10 years showed no recurrent severe infections. This case highlights that PJP may rarely occur in immunocompetent children and can present with life‑threatening respiratory failure. Awareness of this possibility is important in severe unexplained pneumonia.

Infectious disease diagnostics has been transformed by metagenomic next-generation sequencing (mNGS), an unbiased approach that detects bacteria, viruses, fungi, and parasites in a single assay. By sequencing all nucleic acids in a sample, mNGS overcomes the narrow detection scope and slow turnaround of conventional tests, substantially improving pathogen detection. In conditions such as meningitis/encephalitis, sepsis, and pneumonia, mNGS frequently identifies etiologies missed by routine diagnostic tests, thereby facilitating earlier pathogen-directed therapy and, in selected settings, improving clinical management and outcomes. This approach is particularly valuable for immunocompromised, pediatric, and intensive care unit (ICU) patients with atypical infections. Currently, clinical mNGS workflows primarily rely on short-read sequencing platforms (e.g., Illumina), whereas long-read platforms (e.g., Nanopore, PacBio) offer advantages for rapid or high-resolution applications. Optimized bioinformatics and stringent quality control are essential for reliable results. Beyond clinical diagnostics, mNGS provides valuable genetic data on antimicrobial resistance (AMR) and pathogen phylogeny, supporting public health and outbreak surveillance (e.g., wastewater monitoring and variant tracking). Current challenges include distinguishing colonization from infection, interpreting sequencing data quantitatively, and reducing cost and turnaround time. Looking ahead, emerging strategies such as targeted panels, rapid automated workflows, and host‑response integration are expected to further shorten time‑to‑result and improve diagnostic specificity. Parallel progress in ethical and regulatory frameworks remains essential to ensure responsible implementation. To support clinical adoption, a standardized framework for clinical interpretation of mNGS results, together with associated training, has been developed and implemented. Overall, mNGS is likely to become an increasingly important component of infectious disease diagnostics, with ongoing innovations expected to broaden its clinical and epidemiological impact.

Oesophageal cellulitis caused by Klebsiella pneumoniae infection is extremely rare and is often missed because of its atypical symptoms and endoscopic presentation. In this article, a case of a 56-year-old male with poorly controlled diabetes mellitus who presented with chest pain, acid reflux, nausea, vomiting, and weight loss is reported. Imaging revealed progressive, diffuse oedema and thickening of the oesophageal wall, followed by submucosal stratification, fistula formation, and extraluminal gas bubbles. Endoscopic examination revealed progression from erosions in the upper oesophagus to multiple ulcers, fistulae, and intramural abscess formation in the middle and lower oesophagus. Both secretions and tissue cultures confirmed K. pneumoniae infection. Following comprehensive treatment, including acid suppression, the administration of effective antibiotics, mucosal repair, nutritional support, and appropriate endoscopic debridement to facilitate drainage, the patient's symptoms and endoscopic findings significantly improved, and the development of severe complications, such as oesophagotracheal or oesophagomediastinal fistulae, was avoided. This case highlights the need to consider bacterial infection in the differential diagnosis of atypical oesophageal lesions in immunocompromised hosts and emphasises the importance of pathogen-directed, precise anti-infective therapy.

Background/Objectives: Immunocompromised children undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic disorders face a high risk of serious, life-threatening infections caused by multidrug-resistant (MDR) bacteria. Cefiderocol is a novel siderophore cephalosporin, indicated for use in adult patients with MDR Gram-negative infections. Clinical data in immunocompromised children are limited. To report a multicenter real-life experience from the Infection Working Group of the Italian Pediatric Hematology and Oncology Association (IWG-AIEOP) on the use of cefiderocol in treating pediatric onco-hematologic patients with severe, high-risk infections. Methods: Multicenter retrospective collection of infectious episodes treated with cefiderocol, from January 2021 to December 2024, in patients 18 years or younger, after treatment for malignancies or undergoing HSCT in the AIEOP network, part of a prospective, observational study on the etiology and outcome of febrile episodes among 24 AIEOP centers (code NCT06419426). Results: Fifteen episodes of MDR, life-threatening Gram-negative infections treated with cefiderocol in 13 pediatric onco-hematologic patients were collected. There were eight males and five females, mainly affected by acute leukemia (six lymphoblastic and four myeloid, three other hematologic malignancies). The median age was 11.1 years (range 1-17.4 years), and the median weight was 37.8 kg (range 8-65). Bloodstream infection occurred in 10 of 15 episodes. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Stenotrophomonas maltophilia were isolated in 11, 3, and 1 episodes, respectively. Notably, 11 of 15 isolated pathogens carried a metallo-beta-lactamase (MBL) gene (Verona integron-encoded, VIM, n = 10; New Delhi, NDM, n = 1). All patients achieved infection resolution and were alive and infection-free 90 days after infection onset. Conclusions: Cefiderocol was well tolerated and showed encouraging, favorable clinical outcomes, without serious adverse effects.

Background: End-stage renal disease (ESRD) is an immunocompromised state that confers a high risk of infection. We aimed to integrate bioinformatics analyses with a clinical cohort to explore the association between ESRD and sepsis. Methods: We retrieved transcriptomic data from the Gene Expression Omnibus and used computational tools, including Gene Set Enrichment Analysis, the eXtreme Gradient Boosting algorithm, and Mendelian randomization, to characterize gene expression changes, biological pathways, and genetic features in ESRD and sepsis. A multicenter retrospective cohort of patients with sepsis due to carbapenem-resistant Acinetobacter baumannii (CRAB) pneumonia in intensive care units (ICUs) was used to compare clinical presentation and outcomes between patients with and without ESRD. Results: Differential gene expression analysis showed widespread transcriptomic dysregulation in ESRD, and functional enrichment analysis revealed perturbations in immune signaling and vesicular transport pathways. Both the innate and adaptive immune systems appeared compromised, with marked depletion of lymphoid lineages in ESRD. An XGBoost machine-learning model derived from immune cell enrichment scores demonstrated a similar immune microenvironment in ESRD and sepsis. Mendelian randomization analysis supported an association between genetic variants predisposing to ESRD and an increased risk of sepsis, using genome-wide association study datasets. In the clinical cohort, patients with ESRD had significantly higher Sequential Organ Failure Assessment (SOFA) scores and in-hospital mortality than patients with normal renal function. Conclusions: ESRD shares similar immune microenvironmental features and genetic signatures with sepsis. These shared characteristics may contribute to the greater sepsis severity and poorer outcomes observed in patients with ESRD.