Malakoplakia is a rare chronic inflammatory disease resulting from defective bactericidal activity of macrophages following bacterial infection. The most common causative pathogen is Escherichia coli. This condition predominantly affects immunocompromised individuals, particularly those who have undergone kidney transplantation. Malakoplakia is commonly diagnosed histopathologically based on the presence of Michaelis-Gutmann bodies with typical targetoid structures. In this study, we report a case of malakoplakia caused by Klebsiella pneumoniae in a kidney transplant recipient who presented with a urinary tract infection accompanied by acute kidney injury. To our knowledge, no prior case of renal malakoplakia solely attributed to K pneumoniae in a kidney transplant recipient has been reported. Kidney biopsy revealed numerous periodic acid-Schiff (PAS)-positive globules in the tubulointerstitial area. CD68 immunostaining with PAS counterstain demonstrated that the PAS-positive globules were localized within the cytoplasm of CD68-positive histiocytes (ie, von Hansemann cells). Michaelis-Gutmann bodies were observed using Berlin blue staining. The patient was treated with trimethoprim-sulfamethoxazole, and kidney function stabilized. In kidney transplant recipients, the presence of PAS-positive globules in kidney biopsy specimens should prompt consideration of renal parenchymal malakoplakia in the differential diagnosis. Special stains, such as von Kossa and Berlin blue, are essential for supporting the diagnosis.

A man in his 40s who takes adalimumab for Crohn's disease presented with a 1-day history of fever, headache and rapid onset of agitation with reduced consciousness. He was intubated, and a subsequent lumbar puncture revealed severe Streptococcus pneumoniae meningitis. He was started on antibiotics and steroids; however, on sedation hold, he demonstrated abnormal posturing. Neurological imaging revealed extensive cerebral venous sinus thromboses (CVSTs). He was started on a heparin infusion and transferred to a tertiary neurological centre, where he was managed with a split treatment dose of enoxaparin and a 2-week course of IV ceftriaxone. He was extubated on day 4 of admission and made rapid improvements in cognition and function. This case highlights the importance of considering rare neurological complications in cases of severe meningitis in patients who are immunocompromised, as well as recognising CVSTs as a rare but potentially fatal complication in those with pneumococcal meningitis.

Invasive aspergillosis (IA) has traditionally been associated with immunocompromised individuals. Post-viral aspergillosis (PVA) has emerged as a significant secondary complication among patients with viral infections, particularly during the COVID-19 pandemic. This systematic review aimed to summarise the patients' clinical characteristics, diagnostic approaches, treatment options, and outcomes of PVA across various respiratory viral infections. This study was registered in PROSPERO (No. CRD420250652078) and followed the PRISMA 2020 guidelines. We systematically searched PubMed, Embase, Scopus, and Web of Science for publications without a time limitation up to the end of May 2025 reporting clinical data on PVA in patients following infections by respiratory viruses, including SARS-CoV-2, influenza, respiratory syncytial virus (RSV), metapneumovirus, parainfluenza, rhinovirus, adenovirus, and cytomegalovirus (CMV). Overall, the reports highlighted PVA occurrence after infections by SARS-CoV-2, influenza, and CMV. Our analyses revealed that PVA is a clinically heterogeneous but frequently deadly infection in patients who are critically ill, immunocompromised patients, or those receiving corticosteroids, following respiratory viral infections. Among critically ill patients, PVA is a clinically important complication of respiratory viral infections, and timely diagnosis and early initiation of appropriate antifungal therapy- considering that Aspergillus is an aerobic fungus requiring specific culture conditions-play a key role in improving patient outcomes.

Laryngeal mucormycosis is an uncommon form of fungal laryngitis that typically affects immunocompromised individuals. We report a rare such case in a male in his 40s who had recently recovered from severe acute respiratory syndrome-coronavirus disease-19 (SARS CoV-2 infection-COVID 19) and presented with a 1-month history of worsening hoarseness, haemoptysis, and noisy breathing. A chewing gum-like subglottic necrotic mass was biopsied. The rarity of the diagnosis was aided by histopathological and microbial study of the mass, which confirmed mucormycosis. Management included surgical debulking, intravenous liposomal amphotericin B and oral posaconazole followed by staged management of subglottic stenosis.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a multidrug-resistant (MDR) pathogen causing severe infections in immunocompromised patients, prompting the exploration of alternative therapies like bacteriophage therapy. In this study, we isolated and characterized a novel halophilic lytic bacteriophage, Halo KS-7, targeting K. pneumoniae, and used an AI-driven annotation pipeline in Python to analyze its genome and therapeutic potential. Bacteriophages were isolated from Hospital wastewater, purified through plaque isolation, and confirmed using the double-layer agar method. Morphological analysis via transmission electron microscopy (TEM) and plaque assays assessed lytic activity. In vitro assays, including one‑step growth curve and MOI determination, were performed to evaluate the replication kinetics and lytic activity of bacteriophage Halo KS‑7 against carbapenem‑resistant Klebsiella pneumoniae. In vivo efficacy was assessed using a BALB/c mouse wound infection model by monitoring wound contraction and performing blinded histopathological analysis following phage treatment. DNA sequencing was done using Illumina HiSeq 2000, followed by genome assembly, AI-guided annotation, gene prediction, protein function classification, and comparative genomics using CLC Genomics Workbench. We also evaluated host range, temperature stability, pH sensitivity, and salt stress tolerance to assess therapeutic potential. Halo KS-7 exhibited strong lytic activity against CRKP and was classified as a Myoviridae bacteriophage by TEM. Phenotypic assays demonstrated optimal activity at 37 °C and neutral pH, effective activity from pH 4-10, and enhanced performance in high-salinity conditions. Bacteriophage Halo KS-7 exhibited a short latent period (~20 min), a modest burst size (5.73 PFU/cell), and optimal antibacterial activity at MOI 0.1, resulting in sustained suppression of K. pneumoniae growth in vitro. In vivo, Halo KS-7 treatment significantly enhanced wound healing in infected BALB/c mice, achieving near-complete wound closure, effective infection control, and improved histopathological regeneration comparable to uninfected controls. Halo KS-7 have 58.716 kb linear dsDNA genome (44.4% G + C), contains 49 predicted ORFs, lacks integrase, lysogeny, or antibiotic-resistance genes, and includes three tRNA genes (tRNATyr, tRNAPro, and tRNAAsn). It also includes a toxin gene and auxiliary factors like MazG, pyrophosphatase, and HNH endonucleases that enhance bacterial killing without promoting horizontal gene transfer or resistance. Functional annotation assigned ~65% of ORFs to structural, replication, and packaging roles. Comparative genomics showed moderate similarity to other Myoviridae but with distinct accessory features, emphasizing its novelty and therapeutic value. Halo KS-7 is a novel, strictly lytic bacteriophage with strong antibacterial activity and stress resilience, supporting its use as a promising biocontrol agent against CRKP and its potential for clinical development in managing MDR infections.

Critically ill, immunocompromised individuals are vulnerable to both common and uncommon etiologies of respiratory infection. Identifying the etiology of infection has therapeutic, prognostic and public health implications. In some circumstances, immunocompromised patients may be empirically treated with excessively broad antibiotics but ultimately be diagnosed with a common cause of pneumonia. In other circumstances, immunocompromised patients may have a non-specific clinical presentation for severe respiratory failure and be diagnosed with a rare etiology of infection. Because this patient population is at risk for a broad array of infections, it is important to understand the advantages and limitations of sampling and diagnostic techniques. Furthermore, the last decades of research have produced novel methods to enhance diagnostic accuracy. Many of these tests are molecular diagnostics that have high sensitivity, but their clinical impact is unknown, particularly in immunocompromised individuals. In this chapter we discuss various approaches to sampling and microbiologic diagnosis in immuncompromised individuals with severe respiratory failure.

Infectious pneumonias affect millions of individuals annually worldwide, accounting for unacceptably high mortalities in many populations. Following pathogen introduction to the lower respiratory tract by inhalation or aspiration, complex interactions between the host and the microbe determine whether the microbe is cleared or establishes an infectious pneumonia. Even modest variations in the host immune response to pathogens may have potentially profound impacts on pathogenesis, severity, and eventual survival of infectious pneumonias. In this article, the authors summarize the most common conditions that alter host defenses in a manner that predisposes to development of pneumonia.

Pneumocystis jirovecii is an opportunistic fungal pathogen responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients. Antifolate drugs targeting the dihydrofolate reductase (DHFR), including trimethoprim (TMP), remain central to treatment, but studying the effects of mutations in DHFR on resistance to treatment is limited by our inability to culture this organism in vitro or in animal models. We expressed P. jirovecii DHFR (PjDHFR) in Saccharomyces cerevisiae and performed deep mutational scanning (DMS) on this protein to measure the effects of all single amino-acid substitutions on enzyme function and resistance to methotrexate (MTX), a model antifolate which shares structural features with TMP. We integrated experimental results with structural and evolutionary features from multiple biophysical modeling approaches, and by using an interpretable machine-learning framework, we trained a random forest model to classify MTX resistance-conferring mutations in PjDHFR. We then leveraged this framework as a prediction tool to model the effects of mutations on resistance to TMP, which cannot be directly assayed experimentally. Functional measurements from DMS were the strongest contributors to resistance prediction and generally outperformed purely computational features. Resistance-conferring mutations were constrained by function, revealing a functional-resistance trade-off within this essential protein. Feature contribution analyses highlighted key predictors such as distance to ligand, flexibility, stability, and functional trade-off as determinants of resistance. When extrapolated to TMP, the model identified candidate resistance mutations consistent with known biochemical constraints of DHFR. We demonstrate how experimentally measured functional landscapes can be combined with biophysical modeling to help understand and predict antifolate resistance in an unculturable fungal pathogen. Our results provide biological insight into the constraints affecting the evolution of resistance in PjDHFR, and support that resistance arises from mutations altering drug interactions while preserving function. We illustrate how DMS data can enable generalizable, mechanistically interpretable models of drug resistance across structurally related antifolates.

Pneumocystis jirovecii is an opportunistic fungal pathogen responsible for Pneumocystis pneumonia (PCP), a severe infection that remains a major cause of morbidity and mortality among immunocompromised patients, particularly in non-HIV immunosuppressed populations. Despite its recognized clinical relevance and inclusion in the World Health Organization's Fungal Priority Pathogens List, important gaps persist in its diagnosis, epidemiology, and therapeutic management. This study provides a comprehensive bibliometric analysis of global scientific production on P. jirovecii using Scopus as the primary data source. Publications were evaluated for temporal trends, document types, authorship patterns, institutional productivity, collaboration networks, funding sources, thematic evolution, and journal distribution, with additional comparison against other major pneumonia-associated pathogens. A total of 27,396 articles published between 1916 and 2025 were identified. Over the last 50 years, scientific output increased from 10,382 publications in 1975-2000 to 16,496 in 2001-2025, representing an overall growth of 58.9%. Early research expansion was strongly shaped by the HIV/AIDS epidemic, whereas the post-2000 period reflected advances in molecular diagnostics, taxonomic clarification, and broader attention to non-HIV immunosuppressed populations. Although the field has become more diversified and clinically integrated, persistent structural inequities and underinvestment continue to limit progress, particularly in low- and middle-income settings.