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At least 19 recordsLinked to original sources

Diagnostic fibreoptic bronchoscopy in the immunocompromised host with pulmonary infiltrates.

Nineteen immunocompromised patients with pulmonary infiltrates underwent diagnostic fibreoptic bronchoscopy with transbronchial forceps and brush biopsy. A specific diagnosis was obtained in 21/25 procedures (10/11 focal lesions and 11/14 diffuse legions). The most common diagnosis was infection, and organisms isolated included bacteria, fungi, Pneumocystis carinii, and herpes simplex. A pneumothroax requiring tube drainage occurred in two cases and mild lung parenchymal bleeding was noted in two others. It is concluded that fibreoptic bronchoscopy with forceps and brush biopsy can be performed safely with an excellent diagnostic yield in immunocompromised hosts with lung lesions. Supplemental oxygen should be administered during fibreoptic procedures in these patients and platelet transfusions should be given when thrombocytopenia is present.

Adult

Successful treatment of invasive pulmonary aspergillosis in the immunocompromised host.

We have reported the successful treatment of a patient with acute leukemia complicated by pulmonary aspergillosis, a commonly fatal situation. Specific diagnosis was obtained easily by transbronchial lung biopsy. Our therapeutic approach included aggressive treatment of both the underlying malignant process and the aspergillosis with a combination of amphotericin B and rifampin.

Amphotericin B

Pulmonary infections in the compromised host.

Immunocompromised hosts are predisposed to pulmonary infection with a wide variety of pathogens. A cooperative team effort is recommended to complete, in stepwise fashion, the procedures necessary to establish the specific cause of pulmonary infiltrates in the compromised host. The diagnostic approach needs to be individualized, and will depend in part on the urgency of the clinical situation and the skills available at the institution providing treatment.

Aged

Recent advances in Strongyloides screening, diagnostics, therapeutics, and management.

PURPOSE OF REVIEW: Strongyloidiasis affects an estimated 30-100 million people globally and can have life-threatening consequences in immunocompromised hosts, yet it remains underdiagnosed due to limited access and performance of available diagnostics. Novel assays and anthelmintics may reshape screening, diagnosis, treatment, and prevention for at-risk populations. RECENT FINDINGS: Advances in molecular diagnostics coupled with robust stool extraction methods have supplanted traditional parasitologic methods in settings where nucleic acid amplification is feasible. Transition from standard immunoglobulin G (IgG)-based immunoassays to the new IgG- and IgG4-based rapid diagnostic tests using recombinant Strongyloides stercoralis nematode immunodominant E antigen (NIE) and/or S. stercoralis immunoreactive antigen (SsIR) has facilitated serologic screening at the point of care. The World Health Organization now conditionally recommends community-wide ivermectin mass drug administration in highly endemic settings. Regarding new treatment options, moxidectin is noninferior to ivermectin with 93-94% cure rates and a longer half-life, while emodepside shows 80-90% predicted cure rates in early trials and offers a mechanistically distinct option. Understanding of immunosuppressed populations at risk for hyperinfection has expanded, prompting updated screening recommendations. SUMMARY: Serologic and molecular tools are improving screening and diagnosis, and moxidectin and emodepside may broaden treatment options, but data in severe disease and special populations remain limited. Priorities include harmonized screening algorithms and prospective studies in high-risk groups.

Humans

Pneumocystis carinii, Toxoplasma gondii, Cytomegalovirus and the compromised host.

Pneumocystis carinii and Toxoplasma gondii are the two major parasitic protozoan pathogens in the immunocompromised host. Both organisms cause latent infection in humans and many animals. Cats are the definitive hosts for toxoplasmosis; the animal vector for pneumocystis (if any) has not been defined. Toxoplasma is an obligate intracellular parasite, whereas the available evidence suggests that Pneumocystis carinii exists primarily extracellularly. In compromised hosts, pneumocystis infection usually involves only lungs, whereas toxoplasma causes a generalized infection with encephalitis being the principal clinical manifestation. Both types of infection are treated with combinations of folate antagonists (trimethoprim or pyrimethamine with sulfonamide). Both parasites are associated with cytomegalovirus infection in immunosuppressed hosts, an association which may be due to symbiosis between parasites, or to an additive immunosuppressive effect of dual infection on the hosts.

Adolescent

Presumed respiratory syncytial virus pneumonia in an adolescent compromised host.

A 15-year-old boy with nephrotic syndrome, renal insufficiency, and cutaneous anergy had severe pneumonia with pleural effusion. There was serologic evidence of respiratory syncytial virus infection, and extensive microbiologic, histologic, and serologic studies failed to identify any other etiologic agent. Respiratory syncytial virus as a possible cause of severe pneumonia in immunocompromised hosts has not been previously reported.

Adolescent

Overwhelming strongyloidiasis: an unappreciated opportunistic infection.

Strongyloides stercoralis is an intestinal nematode which infects a large portion of the world's population. Individuals with infection confined to the intestinal tract are often asymptomatic but may have abdominal pain, weight loss, diarrhea, and other nonspecific complaints. Enhanced proliferation of the parasite in compromised hosts causes an augmentation of the normal life-cycle. Resultant massive invasion of the gastrointestinal tract and lungs is termed the hyperinfection syndrome. If the worm burden is excessive, parasitic invasion of other tissues occurs and is termed disseminated strongyloidiasis. A variety of underlying conditions appear to predispose to severe infections. These are primarily diseases characterized by immunodeficiency due to defective T-lymphocyte function (Table 1). Individuals with less severe disorders become compromised hosts because of therapeutic regimens consisting of corticosteroids or other immunosuppressive medication. The debilitation of chronic illness or malnutrition also predisposes to systemic stronglyloidiasis. The diagnosis of strongyloidiasis can be readily made by microscopic examination of concentrates of upper small bowel fluid, stool, or sputum. Important clues suggesting this infection include unexplained gram-negative bacillary bacteremia in a compromised host who may have vague abdominal complaints, an ileus pattern on X-ray, and pulmonary infiltrates. Eosinophilia is helpful, if present, but should not be relied upon to exclude the diagnosis. The treatment of systemic infection due to Strongyloides stercoralis with either thiabensazole 25 mg/kg orally twice daily is satisfactory if the diagnosis is made early. Because of several unusual features of this illness in compromised hosts, the standard recommendation for 2 days of therapy should be abandoned in such patients. Immunodeficiency, corticosteroids, and bowel ileus reduce drug efficacy. Thus a longer treatment period of at leuch as blind loops or diverticula necessitate longer treatment. Stool specimens and upper small bowel aspirates should be monitored regularly and treatment continued several days beyond the last evidence of the parasite. In particularly difficult situations where either worm eradication is impossible or reinfection is probable, short monthly courses of antihelminthic therapy seem to be effective in averting recurrent systemic illness. Finally, prevention of hyperinfection or dissemination due to Strongyloides stercoralis can be accomplished by screening immunocompromised hosts with stool and upper small bowel aspirate examinations. These would be especially important prior to initiating chemotherapy, or before giving immunosuppressive medications or corticosteroids to patients with nonneoplastic conditions such as systemic lupus erythematosus, nephrotic syndrome, or renal allografts.

Adult

Evaluation of zoster immune plasma. Treatment of cutaneous disseminated zoster in immunocompromised patients.

Zoster immune plasma (ZIP) was evaluated for treatment of cutaneous disseminated zoster in immunocompromised hosts. Twenty patients were studied: 13 were enrolled in a double-blind protocol, five received ZIP under an open protocol, and two were observed without receiving a transfusion. In the double-blind study, eight patients actually received ZIP; five were given plasma lacking varicella-zoster virus antibodies (control plasma). The clinical course of zoster in the group given ZIP was the same as that of patients given control plasma or no transfusions. Because ZIP did not alter the clinical course of zoster and because zoster patients produced high-antibody titers without ZIP, we concluded that ZIP is not useful for treatment of cutaneous disseminated zoster and should be reserved for prevention or modification of varicella in exposed, susceptible immunocompromised patients.

Adolescent

Septicemia due to Streptococcus equisimilis in a child with acute lymphoblastic leukemia.

A 4-year-old boy with acute lymphoblastic leukemia in relapse with documented septicemia due to group C Streptococci (Streptococcus equisimilis) is described. The patient responded well to therapy with appropriate cytotoxic and antimicrobial agents. There is a general lack of recognition of the pathogenicity of group C Streptococci in man. The potential opportunistic nature of these organisms in immunocompromised hosts and the need for early recognition and appropriate treatment of such infection is emphasized.

Antineoplastic Agents

Type 2 herpes simplex virus infections.

The problems related to herpes simplex virus (HSV) type 2 infections include: (1) the clinical diseases produced primarily at urogenital sites, but also in extragenital areas, and the frequent recurrences of such infections; (2) the severity of the diseases produced in immunocompromised hosts and in newborns, including a varity of ocular manifestations; and (3) the possible role of the virus in human cancers. The usually sexually transmitted mode of spread of this virus has increased current medical concern with this virus. Although laboratory diagnosis of HSV-2 infection is currently available, we still lack effective preventive or therapeutic means for most clinical forms of the infection. However, the great progress made over the past decade in the molecular, virological, immunological and clinicoepidemiological aspects of HSV are providing the necessary tools to attain this goal.

Adolescent

Genetic diversity of clinical Mycobacterium bovis BCG isolates from an immunocompromised patient with BCG infection.

BACKGROUND: The Bacillus Calmette-Guérin (BCG) vaccine is widely administered to prevent severe tuberculosis but can cause serious adverse events, including disseminated BCGosis, in immunocompromised individuals. However, studies investigating the in vivo genetic adaptation and microevolution of this live-attenuated vaccine during prolonged infection remain limited. METHODS: Two clinical Mycobacterium bovis BCG isolates (BCG01 and BCG02) and a lot-matched vaccine strain (VAC) underwent whole-genome sequencing. Phenotypic drug susceptibility testing was performed on the clinical isolates. Genomic relatedness was assessed using SNP-distance clustering and maximum-likelihood phylogeny against global reference strains. Comparative variant analysis was performed to identify mutations specific to BCG01 and BCG02 relative to VAC, and genotypic drug resistance was assessed using TB-Profiler. RESULTS: Phylogenomic analyses and SNP distance confirmed that both clinical isolates were derived from the BCG Tokyo 172 vaccine strain. BCG02 exhibited twice the mutational burden of BCG01, acquiring mutations in genes associated with cell wall biosynthesis (mas, ppsA), regulatory adaptation (pknK, dnaA), and surface antigens (pecA, PE/PPE). Crucially, whereas BCG01 remained susceptible to first-line drugs, BCG02 acquired a canonical rpoB Ser450Leu mutation (100% frequency) and a heteroresistant inhA Ile194Thr mutation (13% frequency), resulting in multidrug-resistant (MDR) BCGosis. CONCLUSION: Although structurally stable, the BCG Tokyo 172 vaccine strain can undergo rapid, clinically significant microevolution and clonal selection within immunocompromised hosts. The in vivo acquisition of multidrug resistance underscores the critical need for pre-vaccination immune screening and comprehensive laboratory monitoring of BCG-associated adverse events.

BCGosis

Real-world clinical impact of plasma cell-free DNA metagenomic next-generation sequencing assay.

OBJECTIVE: To describe the real-world clinical impact of a commercially available plasma cell-free DNA metagenomic next-generation sequencing assay, the Karius test (KT). METHODS: We retrospectively evaluated the clinical impact of KT by clinical panel adjudication. Descriptive statistics were used to study associations of diagnostic indications, host characteristics, and KT-generated microbiologic patterns with the clinical impact of KT. Multivariable logistic regression modeling was used to further characterize predictors of higher positive clinical impact. RESULTS: We evaluated 1000 unique clinical cases of KT from 941 patients between January 1, 2017-August 31, 2023. The cohort included adult (70%) and pediatric (30%) patients. The overall clinical impact of KT was positive in 16%, negative in 2%, and no clinical impact in 82% of the cases. Among adult patients, multivariable logistic regression modeling showed that culture-negative endocarditis (OR 2.3; 95% CI, 1.11-4.53; P .022) and concern for fastidious/zoonotic/vector-borne pathogens (OR 2.1; 95% CI, 1.11-3.76; P .019) were associated with positive clinical impact of KT. Host immunocompromised status was not reliably associated with a positive clinical impact of KT (OR 1.03; 95% CI, 0.83-1.29; P .7806). No significant predictors of KT clinical impact were found in pediatric patients. Microbiologic result pattern was also a significant predictor of impact. CONCLUSIONS: Our study highlights that despite the positive clinical impact of KT in select situations, most testing results had no clinical impact. We also confirm diagnostic indications where KT may have the highest yield, thereby generating tools for diagnostic stewardship.

Humans

Phage therapy for Klebsiella pneumoniae: Understanding bacteria-phage interactions for therapeutic innovations.

Klebsiella pneumoniae (KP) is a Gram-negative bacterium that commonly resides in the human gastrointestinal tract and can also act as an opportunistic pathogen and cause extra-intestinal infections. KP poses a global health threat because it causes both hospital- and community-acquired infections in immune-competent and immunocompromised hosts. These infections can be multidrug-resistant and/or hypervirulent, making KP infections difficult to treat and deadly. In the absence of effective treatments for recalcitrant KP infections, bacteriophage (phage) therapy is gaining attention as a promising alternative. In this review, we evaluate KP epidemiology and epitope diversity, discuss interactions between KP-targeting phages and their bacterial hosts from an eco-evolutionary perspective, and summarize recent efforts in phage therapy for treating KP infections. We also discuss novel approaches, including genetic engineering and machine learning, as initial steps toward developing KP-targeting phage therapy as a precision medicine approach for an emerging and dangerous pathogen.

Phage Therapy

Pneumocystis pneumonia: a plague of the immunosuppressed.

Pneumocystis carinii pneumonitis is a diffuse bilateral alveolopathy encountered in the immunocompromised host with cancer, a congenital immune deficiency disorder, an organ transplant, severe protein-energy malnutrition or recipients of immunosuppressive therapy for other conditions. The onset is abrupt with fever and tachypnea. No rales are heard and the roentgenogram reveals a diffuse alveolar disease. Once the pneumonitis is evident, the infection is usually fatal if no treatment is given. The diagnosis is best established by the demonstration of the causative organism in specimens obtained by open lung biopsy, or other invasive methods, and stained with Gomori's methenamine silver nitrate, toluidine blue O or polychrome stains. Of the two drugs available for treatment, trimethoprim-sulfamethoxazole is preferred over pentamidine isethionate because of relative difference in adverse effects. With either drug the recovery rate is about 75%. The infection can be prevented in high risk patients by the administration of trimethoprim-sulfamethoxazole prophylactically.

Adult