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Nature Communications Mar 2022The epidemiology of infectious causes of meningitis in sub-Saharan Africa is not well understood, and a common cause of meningitis in this region, Mycobacterium...
The epidemiology of infectious causes of meningitis in sub-Saharan Africa is not well understood, and a common cause of meningitis in this region, Mycobacterium tuberculosis (TB), is notoriously hard to diagnose. Here we show that integrating cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) with a host gene expression-based machine learning classifier (MLC) enhances diagnostic accuracy for TB meningitis (TBM) and its mimics. 368 HIV-infected Ugandan adults with subacute meningitis were prospectively enrolled. Total RNA and DNA CSF mNGS libraries were sequenced to identify meningitis pathogens. In parallel, a CSF host transcriptomic MLC to distinguish between TBM and other infections was trained and then evaluated in a blinded fashion on an independent dataset. mNGS identifies an array of infectious TBM mimics (and co-infections), including emerging, treatable, and vaccine-preventable pathogens including Wesselsbron virus, Toxoplasma gondii, Streptococcus pneumoniae, Nocardia brasiliensis, measles virus and cytomegalovirus. By leveraging the specificity of mNGS and the sensitivity of an MLC created from CSF host transcriptomes, the combined assay has high sensitivity (88.9%) and specificity (86.7%) for the detection of TBM and its many mimics. Furthermore, we achieve comparable combined assay performance at sequencing depths more amenable to performing diagnostic mNGS in low resource settings.
Topics: Central Nervous System; Humans; Meningitis; Metagenomics; Mycobacterium tuberculosis; Tuberculosis, Meningeal
PubMed: 35354815
DOI: 10.1038/s41467-022-29353-x -
IDCases 2022Bacteria of the genus are implicated in several disease processes but are a rare cause of septic arthritis. Typically, the cause of septic arthritis is dissemination...
Bacteria of the genus are implicated in several disease processes but are a rare cause of septic arthritis. Typically, the cause of septic arthritis is dissemination from a pulmonary infection in an immunocompromised host. Herein we present a case of a 64-year-old male who had received a long course of prednisone for membranous nephropathy and developed a septic arthritis due to . He was treated sequentially with trimethoprim-sulfamethoxazole and amoxicillin-clavulanate, linezolid and amoxicillin-clavulanate, tigecycline and amoxicillin-clavulanate, and omadacycline and amoxicillin-clavulanate. To our knowledge, only two prior cases of septic arthritis without antecedent trauma to the joint or local skin breakdown have been reported. A review of the literature identified 19 other cases of septic arthritis. This case reinforces the need to consider infection in the differential diagnosis in the immunocompromised patient with concurrent pulmonary infection and septic arthritis.
PubMed: 35957806
DOI: 10.1016/j.idcr.2022.e01590 -
Medicina (Kaunas, Lithuania) Mar 2022spp. is a Gram-positive, partially acid-fast aerobic bacterium usually associated with infection in immunocompromised people. The most common sites of infection are the... (Review)
Review
spp. is a Gram-positive, partially acid-fast aerobic bacterium usually associated with infection in immunocompromised people. The most common sites of infection are the skin, lungs, and the brain, however disease can disseminate and affect every organ. Clinical manifestations of cutaneous disease are varied and frequently misdiagnosed. We present a case of an immunocompetent 66-year-old man who sustained a left finger injury while gardening. He was misdiagnosed on several occasions and treated with inappropriate antibiotics against spp. and spp. When infection spread cutaneously, sporotrichoid (lymphocutaneous) nocardiosis was suspected and the patient was started on appropriate therapy with Bactrim which resulted in a cure. We also summarize the literature on lymphocutaneous infection by . By reporting this case, we want to raise awareness among clinicians about unusual causes of cellulitis, the differential diagnosis of lymphocutaneous infection and the importance of obtaining a detailed exposure history to assist in the prompt diagnosis of nocardiosis.
Topics: Aged; Anti-Bacterial Agents; Humans; Male; Nocardia; Nocardia Infections; Skin Diseases, Bacterial
PubMed: 35454327
DOI: 10.3390/medicina58040488 -
Journal of the Formosan Medical... Oct 2022The study aimed to assess the clinical characteristics of patients with nocardiosis, to evaluate the in vitro susceptibility of antimicrobial agents against Nocardia...
BACKGROUND
The study aimed to assess the clinical characteristics of patients with nocardiosis, to evaluate the in vitro susceptibility of antimicrobial agents against Nocardia species, and to explore changes in antimicrobial susceptibilities in this era of multidrug resistance.
METHODS
Nocardia isolates were identified to the species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA, hsp65, and secA1 gene sequencing, and minimum inhibitory concentrations (MICs) of 15 antimicrobial agents were assessed with the broth microdilution method.
RESULTS
Eighty-nine isolates from 68 patients were identified to species level. The most common species were Nocardia brasiliensis (n = 28, 31.5%), followed by N. farcinica (n = 24, 27%) and N. cyriacigeorgica (n = 16, 18%). Skin and soft tissue were the most common sites of nocardiosis. In multivariate analysis, cutaneous infection (OR, 0.052; p = 0.009), immunosuppressant use (OR, 16.006; p = 0.013) and Charlson combidity index (OR, 1.522; p = 0.029) were significant predictors for death. In total, 98.9% isolates were susceptible to trimethoprim-sulfamethoxazole and linezolid. Further, the MIC range and resistance rate of all Nocardia species to ceftriaxone, imipenem, and amoxicillin-clavulanic acid were found to generally increase over time.
CONCLUSION
Considering that trimethoprim-sulfamethoxazole is effective against most Nocardia species, it is the antibiotic of choice in Taiwan. Besides, amikacin, tigecycline, and linezolid showed high activity against Nocardia species and are thus good alternatives or additional therapies to treat nocardiosis, depending on patient's underlying conditions and site of infection.
Topics: Amikacin; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Anti-Infective Agents; Ceftriaxone; Humans; Imipenem; Immunosuppressive Agents; Linezolid; Microbial Sensitivity Tests; Nocardia; Nocardia Infections; RNA, Ribosomal, 16S; Taiwan; Tertiary Care Centers; Tigecycline; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 35811270
DOI: 10.1016/j.jfma.2022.06.011 -
Microbes and Infection Sep 2000Nocardia brasiliensis is a Gram-positive bacterium that lives as a saprophyte in soil. In this article the physical properties, chemical composition and taxonomic... (Review)
Review
Nocardia brasiliensis is a Gram-positive bacterium that lives as a saprophyte in soil. In this article the physical properties, chemical composition and taxonomic position of this species is reviewed. Human infections and an experimental model of actinomycetoma in BALB/c mice as well as the host-immune response is described.
Topics: Animals; Humans; Mice; Mycetoma; Nocardia; Nocardia Infections
PubMed: 11018454
DOI: 10.1016/s1286-4579(00)01291-0 -
PLoS Neglected Tropical Diseases 2015Mycetoma is a neglected, chronic, and deforming infectious disease caused by fungi and actinomycetes. In Mexico, N. brasiliensis is the predominant etiologic agent....
BACKGROUND
Mycetoma is a neglected, chronic, and deforming infectious disease caused by fungi and actinomycetes. In Mexico, N. brasiliensis is the predominant etiologic agent. Therapeutic alternatives are necessary because the current drug regimens have several disadvantages. Benzothiazinones (BTZ) are a new class of candidate drugs that inhibit decaprenyl-phosphoribose-epimerase (DprE1), an essential enzyme involved in the cell wall biosynthesis of Corynebacterineae.
METHODOLOGY/PRINCIPAL FINDINGS
In this study, the in vitro activity of the next generation BTZ, PBTZ169, was tested against thirty Nocardia brasiliensis isolates. The MIC50 and MIC90 values for PBTZ169 were 0.0075 and 0.03 μg/mL, respectively. Because Nocardia is a potential intracellular bacterium, a THP-1 macrophage monolayer was infected with N. brasiliensis HUJEG-1 and then treated with PBTZ169, resulting in a decrease in the number of colony-forming units (CFUs) at a concentration of 0.25X the in vitro value. The in vivo activity was evaluated after infecting female BALB/c mice in the right hind food-pad. After 6 weeks, treatment was initiated with PBTZ169 and its activity was compared with the first generation compound, BTZ043. Both BTZ compounds were administered at 100 mg/kg twice daily by gavage, and sulfamethoxazole/trimethoprim (SXT), at 100 mg/kg sulfamethoxazole, was used as a positive control. After 22 weeks of therapy, only PBTZ169 and SXT displayed statistically significant activity.
CONCLUSION
These results indicate that DprE1 inhibitors may be useful for treating infections of Nocardia and may therefore be active against other actinomycetoma agents. We must test combinations of these compounds with other antimicrobial agents, such as linezolid, tedizolid or SXT, that have good to excellent in vivo activity, as well as new DprE1 inhibitors that can achieve higher plasma levels.
Topics: Animals; Cells, Cultured; Female; Humans; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Mycetoma; Nocardia; Piperazines; Spiro Compounds; Thiazines
PubMed: 26474057
DOI: 10.1371/journal.pntd.0004022 -
Infection and Immunity May 1976A model for Nocardia asteroides and Nocardia brasiliensis infections in Swiss white mice has been established without the addition to the inocula of any form of... (Comparative Study)
Comparative Study
A model for Nocardia asteroides and Nocardia brasiliensis infections in Swiss white mice has been established without the addition to the inocula of any form of adjuvant. Serial histopathological studies revealed that these two actinomycetes cause lesions that are quite different in their features. An acute suppurative abscess characterizes the lesions of N. asteroides. In the case of N. brasiliensis infections a granuloma is produced in which a striking feature is the presence of large numbers of foam-laden macrophages, although occasional exceptions to this pattern were noted. Electron microscopic studies demonstrated that these macrophages contain within their cytoplasm organisms in varying stages of degeneration. Repeated mortality studies in mice failed to demonstrate differences in mortality rates produced by N. asteroides and N. brasiliensis. Thus, despite relatively trivial biochemical and antigenic differences between these two species of Nocardia, the local pathogenic response is quite different. The presence in the "brasiliensis lesion" of foamy macrophages with intracellular organisms is reminiscent of the histopathological features of lepromatous leprosy and of disseminated Myocobacterium bovis infection when this occurs in the immune suppressed situation. It is possible that N. brasiliensis infection produces a depression of cellular immunity that modifies the local host response to the organism.
Topics: Animals; Mice; Nocardia; Nocardia Infections; Nocardia asteroides
PubMed: 773837
DOI: 10.1128/iai.13.5.1490-1496.1976 -
Annals of Palliative Medicine Sep 2020Cutaneous nocardiosis is a skin disease mainly caused by Nocardia brasiliensis and Nocardia asteroides. Here, we report a rare case of lymphocutaneous dermatosis in an...
Cutaneous nocardiosis is a skin disease mainly caused by Nocardia brasiliensis and Nocardia asteroides. Here, we report a rare case of lymphocutaneous dermatosis in an 87-year-old Chinese man infected with Nocardia brasiliensis. An 87-year-old Chinese man presented at our hospital after suffering erythema, nodules, abscesses, ulceration, and pain in the left upper limb for 10 days. The patient was initially misdiagnosed as lymphocutaneous sporotrichosis. The results of gram staining, acid-fast staining, mass spectrograph revealed Nocardia brasiliensis and 16S ribosomal RNA (16S rRNA) sequencing of samples showed that the patient had a Nocardia brasiliensis infection. Anti-infective therapy with sulfamethoxazole combined with amoxicillin clavulanate potassium was administered for 10 days, followed by sulfamethoxazole alone for 20 days. After 30 days of treatment, the abscess was treated with repeated pus extraction, debridement of erosion and ulcer, wet compress of povidone iodine solution and spectrum of multi-source instrument. The redness and swelling had subsided, and purulent secretion and ulceration had decreased. Lymphocutaneous nocardiosis can easily be misdiagnosed as sporotrichosis based on its clinical manifestations. However, mass spectrometry analysis showed Nocardia brasiliensis according to the fingerprint of the bacteria and 16S rRNA sequencing to identify bacterial DNA can assist with making a diagnosis. For patients with Nocardia brasiliensis, sulfamethoxazole combined with amoxicillin clavulanate potassium is an effective anti-infective treatment.
Topics: Aged, 80 and over; Humans; Male; Nocardia; Nocardia Infections; RNA, Ribosomal, 16S; Skin Diseases, Bacterial
PubMed: 32921116
DOI: 10.21037/apm-20-1301 -
Scientific Reports Aug 2021The aims of the present study were to profile the antimicrobial susceptibility patterns of a diverse range of Nocardia species isolated in Japan, and to determine the...
The aims of the present study were to profile the antimicrobial susceptibility patterns of a diverse range of Nocardia species isolated in Japan, and to determine the ability of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for species/complex identification. Identification of 153 clinical isolates was performed by full-length 16S rRNA gene sequencing as a reference method to evaluate the usefulness of MALDI-TOF MS identification. Antimicrobial susceptibility testing (AST) for 14 antibiotics was performed using the broth microdilution method against 146 of the isolates. Among the total 153 clinical isolates, Nocardia farcinica complex (25%) was the most common species, followed by Nocardia cyriacigeorgica (18%), Nocardia brasiliensis (9%), Nocardia nova (8%), and Nocardia otitidiscaviarum (7%). Among 150 isolates identified to the species/complex level by 16S rRNA gene sequencing, MALDI-TOF MS with the use of a supplemental Nocardia library (JMLD library ver.ML01) correctly identified 97.3% (n = 146) to the species/complex level and 1.3% (n = 2) to the genus level. Among the 146 Nocardia isolates that underwent AST, the susceptibilities were 100% to linezolid, 96% to amikacin, 94% to trimethoprim-sulfamethoxazole, and 76% to imipenem. None of the trimethoprim-sulfamethoxazole-resistant isolates carried either plasmid-mediated sulfonamide-resistant genes (sul1, sul2) or trimethoprim-resistant genes (dfrA).
Topics: Drug Resistance, Bacterial; Genes, Bacterial; Humans; Japan; Nocardia; Plasmids; RNA, Bacterial; RNA, Ribosomal, 16S
PubMed: 34408177
DOI: 10.1038/s41598-021-95870-2 -
International Journal of Infectious... Mar 2014We report a case of femorotibial osteomyelitis due to Nocardia brasiliensis. Nocardia spp are a rare cause of bone infections, and the majority of such cases are...
We report a case of femorotibial osteomyelitis due to Nocardia brasiliensis. Nocardia spp are a rare cause of bone infections, and the majority of such cases are associated with the spine. This type of osteomyelitis is uncommon, and in the immunocompetent host, is more often related to a chronic evolution following direct inoculation of the microorganism.
Topics: Administration, Intravenous; Amikacin; Anti-Bacterial Agents; Ceftriaxone; Female; Humans; Imipenem; Nocardia; Nocardia Infections; Osteomyelitis; Phylogeny; Specimen Handling; Sulfamethoxazole; Trimethoprim; Young Adult
PubMed: 24362018
DOI: 10.1016/j.ijid.2013.11.002