Opportunistic Pulmonary Infections Research Articles

Newly diagnosed advanced HIV infection in an older female in Poland

This paper presents the diagnostic and therapeutic challenges encountered in an older woman with advanced HIV infection. Upon admission, the patient exhibited severe symptoms of interstitial pneumonia and cachexia. During hospitalization, the patient was diagnosed with SARS-CoV-2 infection and a wide spectrum of opportunistic pulmonary infections, including Pneumocystis jiroveci, Candida krusei, and Staphylococcus haemolyticus. Another major diagnostic challenge posed the patient’s prolonged fever, which persisted despite comprehensive treatment. This report underscores the importance of considering new HIV infections in older patients presenting complex clinical pictures, its significant mortality risk in older individuals, and the need for timely initiation and adjustment of antiretroviral therapy.

British HIV Association guidelines on the management of opportunistic infection in people living with HIV: The clinical management of pulmonary opportunistic infections 2024.

British HIV Association guidelines on the management of opportunistic infection in people living with HIV: The clinical management of pulmonary opportunistic infections 2024.

PATHOMORPHOLOGICAL FEATURES OF CRYPTOCOCCOSIS OF THE LUNGS AND CNS IN CASE OF HIV-INFECTION/AIDS

Background. Cryptococcosis is an important opportunistic infection that most commonly presents with meningitis or meningoencephalitis, especially in HIV-infected patients. Pulmonary disease is less common but is probably underdiagnosed because of the nonspecific nature of symptoms or the increased frequency of other pulmonary opportunistic infections.
 Aim: to investigate the pathomorphological features of cryptococcal lesions of the lungs and central nervous system in case of HIV infection/AIDS.
 Materials and methods. Pathomorphological examination was carried out on the autopsy material. HIV infection was diagnosed in the patients during life with serological verification and the patients were registered at the AIDS Center. Ziehl-Neelsen staining, and PAS reaction were used to detect cryptococci in lung and brain tissue. Standard histological preparations were examined under a microscope to clarify or establish the following data: the presence of cryptococci (both encapsulated and non-encapsulated), their localization and density, the presence of an inflammatory infiltrate and its severity.
 Results. The histopathology of lung lesions in cryptococcosis is characterized by the presence of granulomas with numerous cryptococci and a lympho-macrophagic reaction with multinucleated cells of the Langhans type. The total number of cryptococci in the field of vision (x400) is moderate to significant, their dissemination is uneven, localization is in the interstitium and among the inflammatory infiltrate, cryptococci are round in shape, including encapsulated, some deformed. Cryptococcosis of the brain in case of HIV infection/AIDS was characterized by the accumulation of numerous cryptococci in the expanded perivascular space and among the inflammatory infiltrate in meninges of the brain and cerebellum.
 Conclusion. Dissemination of cryptococcosis in the form of meningitis and meningoencephalitis is a prognostically unfavorable sign of the course of the disease. Cryptococcal lung disease was characterized by a polymorphic histological picture with the presence of an interstitial infiltrate and granuloma with multinucleated cells of the Langhans type and numerous cryptococci.

Discovery of Species-Specific Proteotypic Peptides To Establish a Spectral Library Platform for Identification of Nontuberculosis Mycobacteria from Mass Spectrometry-Based Proteomics.

Nontuberculous mycobacteria are opportunistic bacteria pulmonary and extra-pulmonary infections in humans that closely resemble Mycobacterium tuberculosis. Although genome sequencing strategies helped determine NTMs, a common assay for the detection of coinfection by multiple NTMs with M. tuberculosis in the primary attempt of diagnosis is still elusive. Such a lack of efficiency leads to delayed therapy, an inappropriate choice of drugs, drug resistance, disease complications, morbidity, and mortality. Although a high-resolution LC-MS/MS-based multiprotein panel assay can be developed due to its specificity and sensitivity, it needs a library of species-specific peptides as a platform. Toward this, we performed an analysis of proteomes of 9 NTM species with more than 20 million peptide spectrum matches gathered from 26 proteome data sets. Our metaproteomic analyses determined 48,172 species-specific proteotypic peptides across 9 NTMs. Notably, M. smegmatis (26,008), M. abscessus (12,442), M. vaccae (6487), M. fortuitum (1623), M. avium subsp. paratuberculosis (844), M. avium subsp. hominissuis (580), and M. marinum (112) displayed >100 species-specific proteotypic peptides. Finally, these peptides and corresponding spectra have been compiled into a spectral library, FASTA, and JSON formats for future reference and validation in clinical cohorts by the biomedical community for further translation.

Association between neutrophil-lymphocyte ratio and viral load with opportunistic pulmonary infections in human immunodeficiency virus/acquired immunodeficiency syndrome patients

Background: Acquired immunodeficiency syndrome (AIDS) is a syndrome of an opportunistic infectious disease due to decreased immune system by human immunodeficiency virus (HIV) infection. Neutrophil-lymphocyte ratio (NLR) and viral load were used to assess inflammatory status and the amount of HIV virus in the blood. This study aims to determine the association between NLR and viral load in HIV/AIDS patients with the opportunistic pulmonary infections. Methods: This study is an analytic observational study with a cross-sectional design. Data was collected through the medical records of HIV/AIDS patients at Wangaya General Hospital from January 2018 - April 2023. The data analysis method used was the Chi square test as bivariate tests. Results: A total of 139 subjects, the majority of HIV/AIDS patients who had opportunistic pulmonary infections were Balinese ethnicity (45.3%), female (37.6%), age ≥36 years old (54.7%), used ART for ≥3 months (41.5%), viral load <40 copies/ml, NLR ≥2.81 (47.9%), had adherence (43.7%), types of ART were used combination of tenofovir lamivudine efavirenz (45.2%), and private employed (42.5%). A statistically significant association was found between age with opportunistic pulmonary infections (p=0.003; PR=3.082; 95% CI=1.516-6.266). NLR showed a significant association with the incidence of opportunistic pulmonary infections (p=0.003; PR=8.274; 95% CI=1.838-37.249). This study also showed pulmonary tuberculosis (42.37%) as the most common opportunistic pulmonary infections. Conclusions: There is a significant association between NLR levels in HIV/AIDS patients with opportunistic pulmonary infections at Wangaya General Hospital, which the higher NLR levels correlates with higher opportunistic pulmonary infections.

Disparate properties of Burkholderia multivorans and Pseudomonas aeruginosa regarding outer membrane chemical permeabilization to the hydrophobic substances novobiocin and triclosan.

Burkholderia multivorans causes opportunistic pulmonary infections and is intrinsically resistant to many antibacterial compounds including the hydrophobic biocide triclosan. Chemical permeabilization of the Pseudomonas aeruginosa outer membrane affects sensitization to hydrophobic substances. The purpose of the present study was to determine if B. multivorans is similarly susceptive suggesting that outer membrane impermeability properties underlie triclosan resistance. Antibiograms and conventional macrobroth dilution bioassays were employed to establish baseline susceptibility levels to hydrophobic antibacterial compounds. Outer membrane permeabilizers compound 48/80, polymyxin B, polymyxin B-nonapeptide, and ethylenediaminetetraacetic acid were used in attempts to sensitize disparate B. multivorans isolates to the hydrophobic agents novobiocin and triclosan, and to potentiate partitioning of the hydrophobic fluorescent probe 1-N-phenylnapthylamine (NPN). The lipophilic agent resistance profiles for all B. multivorans strains were essentially the same as that of P. aeruginosa except that they were resistant to polymyxin B. Moreover, they resisted sensitization to hydrophobic compounds and remained inaccessible to NPN when treated with outer membrane permeabilizers. These data support the notion that while both phylogenetically-related organisms exhibit general intrinsic resistance properties to hydrophobic substances, the outer membrane of B. multivorans either resists permeabilization by chemical modification or sensitization is mitigated by a supplemental mechanism not present in P. aeruginosa.

Genetic Underpinnings of Carotenogenesis and Light-Induced Transcriptome Remodeling in the Opportunistic Pathogen Mycobacterium kansasii.

Mycobacterium kansasii (Mk) causes opportunistic pulmonary infections with tuberculosis-like features. The bacterium is well known for its photochromogenicity, i.e., the production of carotenoid pigments in response to light. The genetics defining the photochromogenic phenotype of Mk has not been investigated and defined pigmentation mutants to facilitate studies on the role of carotenes in the bacterium's biology are not available thus far. In this study, we set out to identify genetic determinants involved in Mk photochromogenicity. We screened a library of ~150,000 transposon mutants for colonies with pigmentation abnormalities. The screen rendered a collection of ~200 mutants. Each of these mutants could be assigned to one of four distinct phenotypic groups. The insertion sites in the mutant collection clustered in three chromosomal regions. A combination of phenotypic analysis, sequence bioinformatics, and gene expression studies linked these regions to carotene biosynthesis, carotene degradation, and monounsaturated fatty acid biosynthesis. Furthermore, introduction of the identified carotenoid biosynthetic gene cluster into non-pigmented Mycobacterium smegmatis endowed the bacterium with photochromogenicity. The studies also led to identification of MarR-type and TetR/AcrR-type regulators controlling photochromogenicity and carotenoid breakdown, respectively. Lastly, the work presented also provides a first insight into the Mk transcriptome changes in response to light.

Extracorporeal Membrane Oxygenation Support for Interstitial Lung Disease in Idiopathic Inflammatory Myopathies: An ELSO Registry Analysis.

Extracorporeal Membrane Oxygenation Support for Interstitial Lung Disease in Idiopathic Inflammatory Myopathies: An ELSO Registry Analysis.

Pulmonary Nocardiosis as an Opportunistic Infection in COVID-19.

Secondary bacterial pneumonia infection is frequent in COVID-19 patients. Nocardia are responsible for opportunistic pulmonary infections especially after steroid treatment. We describe a case of pulmonary nocardiosis following critical COVID-19 pneumonia in an 83-year-old male. Two weeks after initiation of dexamethasone 6 mg/L, the patient developed a new episode of acute dyspnea. The sputum cultures identified Nocardia cyriacigeorgica. In spite of intravenous imipenem and cotrimoxazole treatment the patient died. Physicians should be aware of the possibility of nocardiosis in case of deterioration of respiratory status of severe COVID-19 inpatients and perform Nocardia evaluation. This evaluation requires prolonged culture.LEARNING POINTSNocardia are responsible for opportunistic pulmonary infections after steroid treatment.We describe a case of pulmonary nocardiosis following critical COVID-19 pneumonia.Physicians should be aware of the possibility of secondary nocardiosis in COVID-19 inpatients.

An Immunogenic and Slow-Growing Cryptococcal Strain Induces a Chronic Granulomatous Infection in Murine Lungs.

ABSTRACTMany successful pathogens cause latent infections, remaining dormant within the host for years but retaining the ability to reactivate to cause symptomatic disease. The human opportunistic fungal pathogen Cryptococcus neoformans establishes latent pulmonary infections in immunocompetent individuals upon inhalation from the environment. These latent infections are frequently characterized by granulomas, or foci of chronic inflammation, that contain dormant and persistent cryptococcal cells. Immunosuppression can cause these granulomas to break down and release fungal cells that proliferate, disseminate, and eventually cause lethal cryptococcosis. This course of fungal latency and reactivation is understudied due to limited models, as chronic pulmonary granulomas do not typically form in mouse cryptococcal infections. A loss-of-function mutation in the Cryptococcus-specific MAR1 gene was previously described to alter cell surface remodeling in response to host signals. Here, we demonstrate that the mar1Δ mutant strain persists long term in a murine inhalation model of cryptococcosis, inducing a chronic pulmonary granulomatous response. We find that murine infections with the mar1Δ mutant strain are characterized by reduced fungal burden, likely due to the low growth rate of the mar1Δ mutant strain at physiological temperature, and an altered host immune response, likely due to inability of the mar1Δ mutant strain to properly employ virulence factors. We propose that this combination of features in the mar1Δ mutant strain collectively promotes the induction of a more chronic inflammatory response and enables long-term fungal persistence within these granulomatous regions.

Evaluation of Small Molecule Inhibitors of Pseudomonas Virulence factor LasB as Non‐Traditional Immunotherapeutics

Pseudomonas aeruginosa can cause severe opportunistic pulmonary infections associated with mechanical ventilation and the genetic disease cystic fibrosis. Due to its multidrug resistance, it is a priority pathogen for therapeutic development. Inflammation during such infections, which causes destruction of lung architecture and function, is activated in part through the maturation of IL‐1β by the virulence factor LasB. Previous results in mouse models suggest that matrix metalloprotease inhibitor drugs also inhibit LasB, preventing cell death and inflammation caused by caused by P. aeruginosa. We hypothesized that other inhibitors of matrix metalloproteases, including tetracycline‐family antibiotics, could be used to target LasB. We evaluated small molecule inhibitors against LasB activation during infections of macrophages, neutrophils, and monocytes and the synergy of these inhibitors with conventional antibiotics and anti‐inflammatories. We first optimized the drug concentration by testing the ability of the various drugs to inhibit LasB at various dilutions. Using an effective concentration, we then infected the various cell types with P. aeruginosa and analyzed the impact of the inhibitors on cell death and maturation of IL‐1β in infected cells. The results indicate that several tetracycline‐family compounds inhibit LasB during P. aeruginosa infections and decrease cell death. This was true for compounds that had no antimicrobial activity yet still inhibited LasB. In addition, the results suggest that the drugs target different cell types. Together, we find that tetracyclines may have therapeutic benefits, even against resistant bacteria, due to their ability to decrease inflammation. This may serve as an effective adjunctive therapy during infection to limit tissue damage and give the immune system and antibiotics more time to respond.

PULMONARY NOCARDIOSIS WITH BETA THALASSEMIA TRAIT IN AN HIV INFECTED PERSON: A CASE REPORT

People with human immunodeciency virus (HIV) infection are prone to develop pulmonary opportunistic infections like Tuberculosis, Pneumocystis carnii pneumonia (PCP), Pulmonary Nocardiosis. It is often underdiagnosed opportunistic infection since the manifestations are similar to Pulmonary Tuberculosis. We have seen patients being started on Antituberculosis Therapy (ATT) empirically, but is no clinical improvement even after 4 weeks of treatment, due to wrong diagnosis. We present a 63-year-old female patient newly diagnosed with HIV presented with recurring loose stools, vomiting, fever since 8 months, with no chest symptoms. She was evaluated and treated at various Hospitals for chronic Gastro-Intestinal tract illness like Irritable Bowel Syndrome (IBS), Mal Absorption Syndrome, Chronic Diarrhea, Right upper lobe cavitatory tumor-? Carcinoid with Hypertension, and was even advised resection of effected lung, emerged out as an absolute different diagnosis – Pulmonary Nocardiosis with beta Thalassemia trait and promptly responded to treatment. In this case we saw common disease with uncommon presentation.

Clinical characteristics of patients with acquired immunodeficiency syndrome having respiratory symptoms as the initial manifestations: A retrospective study

The aim of the study was to investigate clinical features of patients with AIDS having respiratory symptoms as initial manifestations and help in the early diagnosis. Eighty-eight patients admitted to the Shanghai Pulmonary Hospital were included in the study. General data, clinical manifestations, laboratory tests, chest computed tomography (CT) imaging features, treatments, and prognosis were analyzed. Peripheral leukopenia, lymphopenia, hypoxemia, and reduced percentage of CD4+ T lymphocytes were found in 25.6%, 43.6%, 27.5%, and 94.9% of the patients, respectively. Pneumocystis jirovecii pneumonia (PCP) was the most frequent cause of opportunistic pulmonary infection. Patients with PCP had more bilateral lung involvement and ground-glass shadow in CT manifestations. A follow-up of the 43 patients transferred to the Public Health Center showed improvement in 27 (62.8%), stabilization in 4 (9.3%), worsening in 1 (2.3%), and death in 11 (25.6%) patients. Detailed medical history recording, screening of human immunodeficiency virus antibody, and flow cytometry would improve the diagnostic efficiency of AIDS in patients with diffuse ground-glass shadow in chest CT. Early and empirical treatment could improve the prognosis.

Use of 18F-FDG PET/CT to Differentiate Ectopic Adrenocorticotropic Hormone-Secreting Lung Tumors From Tumor-Like Pulmonary Infections in Patients With Ectopic Cushing Syndrome.

BackgroundEctopic adrenocorticotropic hormone (ACTH)-secreting lung tumors represent the most common cause of ectopic Cushing syndrome (ECS). Pulmonary opportunistic infections are associated with ECS. The present study aimed to evaluate the usefulness of 18F-FDG PET/CT for differentiating ectopic ACTH-secreting lung tumors from tumor-like pulmonary infections in patients with ECS.MethodsWe retrospectively reviewed the imaging data of 24 patients with ECS who were suspected to have ACTH-secreting lung tumors and underwent 18F-FDG PET/CT between 2008 and 2019. Eleven patients with lung tumors and 4 with pulmonary infections also had additional somatostatin receptor imaging (99mTc-HYNIC-TOC SPECT/CT or 68Ga-DOTATATE PET/CT).ResultsIn total, 18 patients had lung tumors and six had pulmonary infections. The primary source of ECS remained occult in the six patients with pulmonary infections. The maximum standardized uptake value (SUVmax) for pulmonary infections was significantly higher than that for tumors (P = 0.008). Receiver operating characteristic analysis revealed that a cut-off SUVmax of 4.95 helped in differentiating ACTH-secreting lung tumors from infections with 75% sensitivity and 94.4% specificity. For the 11 patients with ACTH-lung tumors, somatostatin receptor imaging (SRI) was positive in 6; while for the 4 with pulmonary infections, SRI was positive in 2. The sensitivity and specificity of somatostatin receptor imaging (SRI) for detecting ACTH-secreting lung tumor was 54.5% and 50%.ConclusionsOur findings suggest that pulmonary infections exhibit significantly higher FDG uptake than ACTH-secreting lung tumors in 18F-FDG PET/CT. An SUVmax cut-off value of 4.95 may be useful for differentiating the two conditions. Our results also suggested that SRI may not be an effective tool for differentiating the two conditions given the relatively low specificity.

ATS Core Curriculum 2021. Pediatric Pulmonary Medicine: Pulmonary Infections.

The following is a concise review of the Pediatric Pulmonary Medicine Core reviewing pediatric pulmonary infections, diagnostic assays, and imaging techniques presented at the 2021 American Thoracic Society Core Curriculum. Molecular methods have revolutionized microbiology. We highlight the need to collect appropriate samples for detection of specific pathogens or for panels and understand the limitations of the assays. Considerable progress has been made in imaging modalities for detecting pediatric pulmonary infections. Specifically, lung ultrasound and lung magnetic resonance imaging are promising radiation-free diagnostic tools, with results comparable with their radiation-exposing counterparts, for the evaluation and management of pulmonary infections. Clinicians caring for children with pulmonary disease should ensure that patients at risk for nontuberculous mycobacteria disease are identified and receive appropriate nontuberculous mycobacteria screening, monitoring, and treatment. Children with coronavirus disease (COVID-19) typically present with mild symptoms, but some may develop severe disease. Treatment is mainly supportive care, and most patients make a full recovery. Anticipatory guidance and appropriate counseling from pediatricians on social distancing and diagnostic testing remain vital to curbing the pandemic. The pediatric immunocompromised patient is at risk for invasive and opportunistic pulmonary infections. Prompt recognition of predisposing risk factors, combined with knowledge of clinical characteristics of microbial pathogens, can assist in the diagnosis and treatment of specific bacterial, viral, or fungal diseases.

The 1918 influenza and COVID-19 pandemics: The effect of age on outcomes.

The 1918 influenza and COVID-19 pandemics: The effect of age on outcomes.

New coronoviral infection (COVID-19) combined with tuberculosis in patients at late stages of HIV infection with immunodeficiency

The study materials of 23 patients with COVID-19 with newly diagnosed tuberculosis at the late stages of HIV infection with an average CD4 + cells count not exceeding 30 cells/pl of blood and in the absence of antiretroviral therapy (the main group) and 23 patients with no COVID-19 (the comparison group) and the similar parameters are presented. The presence or absence of COVID-19 is characterized by social maladjustment, drug addiction, concomitant viral hepatitis B or C and COPD, generalized tuberculosis with extrapulmonary damage of various organs and the development of other opportunistic pulmonary infections, similar clinical and radiological manifestations, which can only be differentiated by microbiological and molecular genetic research methods. To prevent exogenous infection of the healthy population with COVID-19, it is imperative to organize an active regular examination of all patients with tuberculosis and HIV infection for COVID-19, especially at the later stages, in the TB care office for HIV-infected people at TB dispensaries.

New coronoviral infection (COVID-19) combined with tuberculosis in patients at late stages of HIV infection with immunodeficiency

The study materials of 23 patients with COVID-19, combined with newly diagnosed tuberculosis at the late stages of HIV infection with an average CD4+ cells count not exceeding 30 cells/μl of blood and in the absence of antiretroviral therapy (the main group) and 23 patients with no COVID-19 (the comparison group) and the similar parameters are presented. The presence or absence of COVID-19 is characterized by social maladjustment, drug addiction, concomitant viral hepatitis B or C and COPD, generalized tuberculosis with extrapulmonary damage of various organs and the development of other opportunistic pulmonary infections, similar clinical and radiological manifestations, which can only be differentiated by microbiological and molecular genetic research methods. To prevent exogenous infection of the healthy population with COVID-19, it is imperative to organize an active regular examination of all patients with tuberculosis and HIV infection for COVID-19, especially at the later stages, in the TB care office for HIV-infected people at TB dispensaries.

Elderly patients with concurrent hip fracture and lower respiratory tract infection: the pathogens and prognosis over different bedridden periods

BackgroundElderly patients who experience hip fractures often become bedridden and are at risk of developing lower respiratory tract infections. The current study was to investigate the etiology and bacterial drug resistance patterns of elderly patients with hip fractures and lower respiratory tract infections on prolonged bedridden time and to determine their prognosis.MethodsPatients diagnosed with hip fractures admitted from May 2015 to April 2017 were included. The basic characteristics including the patients’ gender, age, fracture type, operation mode, bedridden duration, length of hospital stay, prognosis, past medical history, routine bloodwork, C-reactive protein (CRP), procalcitonin (PCT), blood biochemistry, blood gas analysis, glycosylated hemoglobin (HbA1C%), sputum smear, sputum culture, and anti-infection and related therapy were recorded. All patients were classified into three groups based on bed rest duration, including short-term (<1 month), mid-term (1–12 months), and long-term (> 12 months). The correlation between the bedridden time and the patients’ basic characteristics, disease history, laboratory examination results, pathogen, anti-infection, and related therapy were evaluated. The risk factors related to the prognosis of the disease were investigated.ResultsProlonged bed rest in patients led to an increase in hospitalization time, mortality rates, and decreased serum albumin levels (P < 0.05). Sputum bacteriological culture results showed that, with bed rest prolongation, the proportion of Pseudomonas aeruginosa and fungal infections increased. Binomial logistic regression of pulmonary infection prognosis, glucocorticoid use during the anti-infective period, prolonged bedridden time, and serum albumin level showed that intravenous use of glucocorticoid during anti-infective treatment, bed rest > 1 year, and low serum albumin level were related to poor prognosis.ConclusionElderly hip fracture patients with prolonged bedridden time had an increased chance of opportunistic pulmonary infection and decreased nutritional status. Glucocorticoids should be used cautiously.

Management of Morbidity and Mortality in a New Zealand White Rabbit Model of SteroidInduced Osteonecrosis of the Femoral Head.

Steroid-induced osteonecrosis of the femoral head (SONFH) is a condition documented in humans and animals exposed to chronic steroid administration. The rabbit has become a preferred animal model for investigating the pathogenesis and treatment of SONFH due to its shared femoral vascular anatomy with human patients, relative size of the femoral head, and general fecundity. However, morbidity and mortality are frequent during the steroid induction period, prior to surgical manipulation. These problems are poorly reported and inadequately described in the literature. In this study, we report the clinical, gross, and histopathologic findings of New Zealand white (NZW) rabbits undergoing the steroid induction phase of the SONFH model. Severe weight loss (>30%), lipemia, hypercholesterolemia, hyperglycemia, and elevations in ALT and AST were consistent findings across all rabbits, although these changes did not differentiate asymptomatic rabbits from those that became clinically symptomatic or died. Euthanized and spontaneously deceased rabbits exhibited hepatomegaly, hepatic lipidosis/glycogenosis, and hepatocellular necrosis, in addition to a lipid-rich and proteinaceous thoracic effusion. A subset of rabbits developed opportunistic pulmonary infections with Bordetella bronchiseptica and Escherichia coli and small intestine infections with Lawsonia intracellularis superimposed on hepatic and thoracic disease. Together, these findings allowed us to establish a clinical decision-making flowchart that reduced morbidities and mortalities in a subsequent cohort of SONFH rabbits. Recognition of these model-associated morbidities is critical for providing optimal clinical care during the disease induction phase of SONFH.