Biological characteristics and pathogenicity comparison of Nocardia seriolae isolated from Micropterus salmoides and Channa argus.

Nocardia seriolae is the primary pathogen causing nocardiosis in various fish species, leads to significant economic losses in the aquaculture industry. In this study, 10 bacterial strains isolated from Micropterus salmoides and Channa argus infected with nocardiosis, were identified as N. seriolae by physiological and biochemical identification, as well as 16S rDNA sequencing. Moreover, the key virulence-related genes such as ESX-1, T7SS-2, T7SS-3, EspG1, sodC, sod2 and ESAT6 were all positive, and showing high homology among different strains. Pathogenicity testing revealed mortality rates ranging from 70 to 100%, accompanied by the presence of white nodules in the viscera of deceased fish. The drug sensitivity test demonstrated that LY21811, the most lethal strain, exhibited high sensitivity to nine types of antibiotics, including azithromycin, doxycycline, florfenicol and compound sulfamethoxazole, yet showed complete resistance to ß-lactam antibiotics. Additionally, the tannic acid also demonstrated potent inhibitory effects against LY21811, with a minimum inhibitory concentration of 0.0625 mg/mL. These results showed that N. seriolae originated from M. salmoides and C. argus in Zhejiang Province were highly conserved, demonstrating a high homogeneity in genetic characteristics, pathogenicity and antimicrobial susceptibilities. These results provide a foundation for further research on the pathogenic characteristics and disease prevention of N. seriolae infections.

A Rare Case Report of Disseminated Nocardia Farcinica Granulomatous Hepatitis and Clinical Management Experience.

Background: Nocardiosis is primarily an opportunistic infection affecting immunocompromised individuals, with a predilection for the lungs, brain, or skin in those with compromised immune function. Granulomatous hepatitis caused by Nocardia is a rare clinical manifestation. This study aims to provide a systematic overview of the clinical features of Nocardiosis caused by Nocardia farcinica, enhancing our understanding of this disease. Methods: We report a case of a 75-year-old male with no underlying diseases presenting with a history of "recurrent fever for more than 4 months", along with fatigue, poor appetite, and pleural and abdominal effusion. Despite treatment at multiple hospitals, the patient showed little improvement. Chest CT revealed chronic inflammation, small nodules, bilateral pleural effusion, and pleural thickening. Abdominal CT indicated multiple low-density lesions in the liver, multiple small calcifications, and abdominal effusion. Results: Liver biopsy suggested inflammatory changes, with focal granuloma formation. Metagenomic next-generation sequencing (mNGS) of liver tissue indicated Nocardia farcinica, leading to the final diagnosis of disseminated Nocardia farcinica granulomatous hepatitis. Conclusion: Nocardia infection is a rare disease primarily observed in immunocompromised patients but can also occur in those with normal immune function. The clinical and radiological features lack specificity; however, the utilization of mNGS technology enables rapid identification of the pathogenic microorganism. Nocardia farcinica is generally susceptible to sulfonamide drugs and amikacin, offering viable treatment options.

Pathological Variations and Immune Response in Channa argus Infected with Pathogenic Nocardia seriolae Strain.

Nocardia seriolae pathogen causes chronic granulomatous disease, reportedly affecting over 40 species of marine and freshwater cultured fish. Hence, research is required to address and eliminate this significant threat to the aquaculture industry. In this respect, a reliable and reproducible infection model needs to be established to better understand the biology of this pathogen and its interactions with the host during infection, as well as to develop new vaccines or other effective treatment methods. In this study, we examined the pathogenicity of the pathogen and the immune response of snakehead (Channa argus) juvenile to N. seriolae using a range of methods and analyses, including pathogen isolation and identification, histopathology, Kaplan-Meier survival curve analysis, and determination of the median lethal dose (LD50) and cytokine expression. We have preliminarily established a N. seriolae - C. argus model. According to our morphological and phylogenetic analysis data, the isolated strain was identified as N. seriolae and named NSE01. Eighteen days post-infection of healthy juvenile C. argus with N. seriolae NSE01, the mortality rate in all four experimental groups (intraperitoneally injected with 1 × 105 CFU/mL - 1 × 108 CFU/mL of bacterial suspension) (n = 120) was 100%. The LD50 of N. seriolae NSE01 for juvenile C. argus was determined to be 1.13 × 106 CFU/fish. Infected juvenile C. argus had significant pathological changes, including visceral tissue swelling, hemorrhage, and the presence of numerous nodules of varying sizes in multiple tissues. Further histopathological examination revealed typical systemic granuloma formation. Additionally, following infection with N. seriolae NSE01, the gene expression of important cytokines, such as Toll-like receptor genes TLR2, TLR13, interleukin-1 receptor genes IL1R1, IL1R2, and interferon regulatory factor IRF2 were significantly upregulated in different tissues, indicating their potential involvement in the host immune response and regulation against N. seriolae. In conclusion, juvenile C. argus can serve as a suitable model for N. seriolae infection. The establishment of this animal model will facilitate the study of the pathogenesis of nocardiosis and the development of vaccines.

Epidemiology, Timing, and Secondary Prophylaxis of Recurrent Nocardiosis.

Background: Nocardia tends to cause infection in immunocompromised patients or those with chronic pulmonary disease. Nocardia is known to recur, prompting the practice of secondary prophylaxis in patients perceived at high risk. However, few data exist regarding the epidemiology of recurrent nocardiosis or the effectiveness of secondary prophylaxis. Methods: We performed a multicenter, retrospective cohort study of adults diagnosed with nocardiosis from November 2011 to April 2022, including patients who completed primary treatment and had at least 30 days of posttreatment follow-up. Propensity score matching was used to analyze the effect of secondary prophylaxis on Nocardia recurrence. Results: Fifteen of 303 (5.0%) patients developed recurrent nocardiosis after primary treatment. Most recurrences were diagnosed either within 60 days (N = 6/15, 40.0%) or between 2 to 3 years (N = 4/15, 26.7%). Patients with primary disseminated infection tended to recur within 1 year, whereas later recurrences were often nondisseminated pulmonary infection. Seventy-eight (25.7%) patients were prescribed secondary prophylaxis, mostly trimethoprim-sulfamethoxazole (N = 67/78). After propensity-matching, secondary prophylaxis was not associated with reduced risk of recurrence (hazard ratio, 0.96; 95% confidence interval, .24-3.83), including in multiple subgroups. Eight (53.3%) patients with recurrent nocardiosis required hospitalization and no patients died from recurrent infection. Conclusions: Recurrent nocardiosis tends to occur either within months because of the same Nocardia species or after several years with a new species. Although we did not find evidence for the effectiveness of secondary prophylaxis, the confidence intervals were wide. However, outcomes of recurrent nocardiosis are generally favorable and may not justify long-term antibiotic prophylaxis for this indication alone.

TB or Not TB: Lung Nocardiosis, a Tuberculosis Mimicker.

Nocardia, a gram-positive bacterium found in soil and water, rarely causes infections in immunocompetent patients. Diagnosing and treating nocardiosis can be challenging due to its infrequency and the similarity of its symptoms to other diseases. We describe the case of a middle-aged male with a history of latent tuberculosis who presented with hemoptysis. Imaging revealed a persistent lung mass, and pathology and microbiology studies confirmed Nocardia infection. The patient was treated with antibiotics and discharged home. Pulmonary nocardiosis can mimic tuberculosis, fungal infections, or malignancies. Immunocompetent patients make up one-third of the cases. Diagnosis can be difficult, as the organism takes time to grow in culture, but molecular techniques and histology can aid in diagnosis. Treatment often involves a six- to 12-month course of trimethoprim-sulfamethoxazole (TMP-SMX). Prompt identification of the etiological agent is essential for effective treatment, especially for immunocompetent patients who may not exhibit typical risk factors.

Intractable Nocardial mycetoma with possible colonisation by Candida species.

A Japanese male in his 30s with no underlying medical condition presented with painless nodules after being bitten by a dog during a stay in Bali, Indonesia, 7 years earlier. He was referred to our department with multiple ulcers, nodules, and masses on the right leg. The final diagnosis was mycetoma caused by Nocardia vulneris, which may have been exacerbated by colonization of Candida parapsilosis and C. tropicalis as these yeasts were isolated by culture from the tissue. Treatment with minocycline hydrochloride and sulfamethoxazole trimethoprim showed partial efficacy, but the addition of posaconazole achieved significant efficacy. This suggests that the surmised coexistence of pathogenic yeasts of lower virulency may have made mycetoma in this case intractable.

A case of disseminated nocardiosis with orbital apex involvement and endophthalmitis.

Nocardia is a rare cause of ocular infections and most commonly occurs secondary to trauma. Systemic Nocardiosis may have ocular involvement in rare cases. We report a case of disseminated nocardiosis with orbital apex involvement and endophthalmitis in an immunocompromised patient. The patient presented with respiratory sepsis, and later developed complete ptosis and ophthalmoplegia in the left eye. This was on the background of treatment with high-dose prednisolone. Magnetic resonance imaging showed enhancement of the entire clivus, extending into the left orbital apex and cavernous sinus. The patient was initially treated empirically for CNS tuberculosis. Bronchoscopic cultures returned positive for Nocardia farcinica, and the patient was treated with trimethoprim/sulfamethoxazole and weaned off previous corticosteroids.

Longistylin A from Cajanus cajan (L.) Millsp. disturbs glycerophospholipid metabolism and cytokinin biosynthesis of Nocardia seriolae.

ETHNOPHARMACOLOGICAL RELEVANCE: Nocardiosis is an uncommon infectious disease that bears certain similarities to tuberculosis, with a continuous increase in its incidence and a poor prognosis. In traditional Chinese medicine, the leaves of Cajanus cajan (L.) Millsp. are employed to treat wounds, malaria, coughs, and abdominal pain. AIM OF THE STUDY: In this study, we investigated the effects and mechanisms of longistylin A (LGA), a natural stilbene isolated from C. cajan, as a potential antibiotic against nocardiosis MATERIALS AND METHODS: LGA was isolated from the leaves of C. cajan and assessed using a minimum bactericidal concentration (MBC) determination against Nocardia seriolae. Multi-omics analysis encompassing genes, proteins, and metabolites was conducted to investigate the impact of LGA treatment on N. seriolae. Additionally, quantitative analysis of 40 cytokinins in N. seriolae mycelium was performed to assess the specific effects of LGA treatment on cytokinin levels. Cryo-scanning electron microscopy was utilized to examine morphological changes induced by LGA treatment, particularly in the presence of exogenous trans-zeatin-O-glucoside (tZOG). The therapeutic effect of LGA was investigated by feeding N. seriolae-infected largemouth bass. RESULTS: LGA exhibited significant efficacy against N. seriolae, with MBC value of 2.56µg/mL. Multi-omics analysis revealed that LGA disrupted glycerophospholipid metabolism and hormone biosynthesis by notably reducing the expression of glycerol-3-phosphate dehydrogenase and calmodulin-like protein. Treatment with LGA markedly disrupted 12 distinct cytokinins in N. seriolae mycelium. Additionally, the addition of exogenous tZOG counteracted the inhibitory effects of LGA on filamentous growth, resulting in mycelial elongation and branching. Furthermore, LGA treatment improved the survival rate of largemouth bass infected with N. seriolae. CONCLUSIONS: We found for the first time that LGA from C. cajan exhibited significant efficacy against N. seriolae by interfering with glycerophospholipid metabolism and cytokinin biosynthesis.

Nocardia farcinica brain abscess with torque teno virus co-infection: A case report.

Background: Brain abscesses caused by Nocardia are rare and difficult to diagnose. Nocardia farcinica is among the most common species; however, the conventional diagnosis of N. farcinica infection consists of cerebrospinal fluid (CSF) and blood culture and Gram staining. These procedures prolong the time to diagnosis and initiating treatment. Case presentation: A 69-year-old woman with diabetes mellitus presented with headaches and dizziness persisting for 2 weeks, which was initially diagnosed as a brain abscess. Due to the unusual presentation and rapid progression of symptoms, she underwent surgical resection of the brain abscess. No pathogens were detected in blood or CSF cultures. However, metagenomic next-generation sequencing (mNGS) identified N. farcinica and Torque teno virus in pus extracted from the abscesses. The patient received appropriate antibiotic therapy and recovered fully without any residual neurological deficits. Conclusion: mNGS useful for prompt diagnosis and selection of antibiotic therapy for brain abscesses caused by Nocardia. Surgical intervention is necessary in some cases.

Bacteremia caused by Nocardia farcinica: a case report and literature review.

BACKGROUND: Nocardia farcinica is one of the most common Nocardia species causing human infections. It is an opportunistic pathogen that often infects people with compromised immune systems. It could invade human body through respiratory tract or skin wounds, cause local infection, and affect other organs via hematogenous dissemination. However, N. farcinica-caused bacteremia is uncommon. In this study, we report a case of bacteremia caused by N. farcinica in China. CASE PRESENTATION: An 80-year-old woman was admitted to Peking Union Medical College Hospital with recurrent fever, right abdominal pain for one and a half month, and right adrenal gland occupation. N. farcinica was identified as the causative pathogen using blood culture and plasma metagenomics next-generation sequencing (mNGS). The clinical considerations included bacteremia and adrenal gland abscess caused by Nocardia infection. As the patient was allergic to sulfanilamide, imipenem/cilastatin and linezolid were empirically administered. Unfortunately, the patient eventually died less than a month after the initiation of anti-infection treatment. CONCLUSION: N. farcinica bacteremia is rare and its clinical manifestations are not specific. Its diagnosis depends on etiological examination, which can be confirmed using techniques such as Sanger sequencing and mNGS. In this report, we have reviewed cases of Nocardia bloodstream infection reported in the past decade, hoping to improve clinicians' understanding of Nocardia bloodstream infection and help in its early diagnosis and timely treatment.

Identification and functional analysis of perforin 1 from largemouth bass (Micropterus salmoides).

In this study, we present the first cloning and identification of perforin (MsPRF1) in largemouth bass (Micropterus salmoides). The full-length cDNA of MsPRF1 spans 1572 base pairs, encoding a 58.88 kDa protein consisting of 523 amino acids. Notably, the protein contains MACPF and C2 structural domains. To evaluate the expression levels of MsPRF1 in various healthy largemouth bass tissues, real-time quantitative PCR was employed, revealing the highest expression in the liver and gut. After the largemouth bass were infected by Nocardia seriolae, the mRNA levels of MsPRF1 generally increased within 48 h. Remarkably, the recombinant protein MsPRF1 exhibits inhibitory effects against both Gram-negative and Gram-positive bacteria. Additionally, the largemouth bass showed a higher survival rate in the N. seriolae challenge following the intraperitoneal injection of rMsPRF1, with observed reductions in the tissue bacterial loads. Moreover, rMsPRF1 demonstrated a significant impact on the phagocytic and bactericidal activities of largemouth bass MO/MΦ cells, concurrently upregulating the expression of pro-inflammatory factors. These results demonstrate that MsPRF1 has a potential role in the immune response of largemouth bass against N. seriolae infection.

Nocardia rubra cell-wall skeleton mitigates whole abdominal irradiation-induced intestinal injury via regulating macrophage function.

Background: Ionizing radiation (IR)-induced intestinal injury is a major side effect and dose-limiting toxicity in patients receiving radiotherapy. There is an urgent need to identify an effective and safe radioprotectant to reduce radiation-induced intestinal injury. Immunoregulation is considered an effective strategy against IR-induced injury. The purpose of this article was to investigate the protective effect of Nocardia rubra cell wall skeleton (Nr-CWS), an immunomodulator, on radiation-induced intestinal damage and to explore its potential mechanism. Methods: C57BL/6 J male mice exposed to 12 Gy whole abdominal irradiation (WAI) were examined for survival rate, morphology and function of the intestine and spleen, as well as the gut microbiota, to comprehensively evaluate the therapeutic effects of Nr-CWS on radiation-induced intestinal and splenetic injury. To further elucidate the underlying mechanisms of Nr-CWS-mediated intestinal protection, macrophages were depleted by clodronate liposomes to determine whether Nr-CWS-induced radioprotection is macrophage dependent, and the function of peritoneal macrophages stimulated by Nr-CWS was detected in vitro. Results: Our data showed that Nr-CWS promoted the recovery of intestinal barrier function, enhanced leucine-rich repeat-containing G protein-coupled receptor 5+ intestinal stem cell survival and the regeneration of intestinal epithelial cells, maintained intestinal flora homeostasis, protected spleen morphology and function, and improved the outcome of mice exposed to 12 Gy WAI. Mechanistic studies indicated that Nr-CWS recruited macrophages to reduce WAI-induced intestinal damage. Moreover, macrophage depletion by clodronate liposomes blocked Nr-CWS-induced radioprotection. In vitro, we found that Nr-CWS activated the nuclear factor kappa-B signaling pathway and promoted the phagocytosis and migration ability of peritoneal macrophages. Conclusions: Our study suggests the therapeutic effect of Nr-CWS on radiation-induced intestinal injury, and provides possible therapeutic strategy and potential preventive and therapeutic drugs to alleviate it.

The first reported pulmonary nocardiosis caused by Nocardia gipuzkoensis resisted to TMP-SMZ in an immunocompetent patient.

BACKGROUND: . Nocardia gipuzkoensis was first described as a novel and distinct species in 2020 by Imen Nouioui and pulmonary nocardiosis associated with Nocardia gipuzkoensis was once reported in two bronchiectasis patients. Noteworthy, both reported Nocardia gipuzkoensis cases showed sensitivity to Trimethoprim/Sulfamethoxazol (TMP-SMZ), which are usually recommended for empirical therapy. METHODS: We reported the third case of Nocardia gipuzkoensis infection in a 16-year-old girl with chief complaints of cough, persistent chest and back pain. No underlying immuno-suppressive conditions and glucocorticoid use was revealed. Patchy lesions next to spine and located in the posterior basal segment of lower lobes of left lung were seen in thorax computed tomography (CT), but no pathogenic bacteria was detected according to routine laboratory testings. RESULTS: Metagenomic next-generation sequencing (mNGS) combined with Whole Genome Sequencing (WGS) was used to classified our isolate from bronchoalveolar lavage fluid (BALF) as a Nocardia gipuzkoensis. It is worth mentioning that drug susceptibility testing of our isolate showed resistance to TMP-SMZ, which was never reported before. The patient improved remarkably both clinically and radiographically according to the treatment with Imipenem-cilastatin infusion alone. CONCLUSION: mNGS and WGS showed excellent performance in identifying Nocardia genus to the species level and improving detection rate of Nocardia gipuzkoensis ignored by traditional culture. Different from previously reported cases, Nocardia gipuzkoensis infection case showed resistance to TMP-SMZ, which is an unprecedented finding and a crucial addition to our understanding of the antibacterial spectrum of Nocardia gipuzkoensis. The successful treatment with Imipenem-cilastatin infusion alone in this case is a testament to the importance of precise identification and tailored antibiotic therapy.

A rare case of a hard-to-heal ulcer caused by pulmonary Nocardia infection.

DECLARATION OF INTEREST: The authors have no conflicts of interest.

Genomic insights and anti-phytopathogenic potential of siderophore metabolome of endolithic Nocardia mangyaensis NH1.

Actinobacteria are one of the predominant groups that successfully colonize and survive in various aquatic, terrestrial and rhizhospheric ecosystems. Among actinobacteria, Nocardia is one of the most important agricultural and industrial bacteria. Screening and isolation of Nocardia related bacteria from extreme habitats such as endolithic environments are beneficial for practical applications in agricultural and environmental biotechnology. In this work, bioinformatics analysis revealed that a novel strain Nocardia mangyaensis NH1 has the capacity to produce structurally varied bioactive compounds, which encoded by non-ribosomal peptide synthases (NRPS), polyketide synthase (PKS), and post-translationally modified peptides (RiPPs). Among NRPS, five gene clusters have a sequence homology with clusters encoding for siderophore synthesis. We also show that N. mangyaensis NH1 accumulates both catechol- and hydroxamate-type siderophores simultaneously under iron-deficient conditions. Untargeted LC-MS/MS analysis revealed a variety of metabolites, including siderophores, lipopeptides, cyclic peptides, and indole-3-acetic acid (IAA) in the culture medium of N. mangyaensis NH1 grown under iron deficiency. We demonstrate that four CAS (chrome azurol S)-positive fractions display variable affinity to metals, with a high Fe3+ chelating capability. Additionally, three of these fractions exhibit antioxidant activity. A combination of iron scavenging metabolites produced by N. mangyaensis NH1 showed antifungal activity against several plant pathogenic fungi. We have shown that the pure culture of N. mangyaensis NH1 and its metabolites have no adverse impact on Arabidopsis seedlings. The ability of N. mangyaensis NH1 to produce siderophores with antifungal, metal-chelating, and antioxidant properties, when supplemented with phytohormones, has the potential to improve the release of macro- and micronutrients, increase soil fertility, promote plant growth and development, and enable the production of biofertilizers across diverse soil systems.

Aggregation-induced emission of TTCPy-3: A novel approach for eradicating Nocardia seriolae infections in aquatic fishes.

Aquatic fishes are threatened by the strong pathogenic bacterium Nocardia seriolae, which challenges the current prevention and treatment approaches. This study introduces luminogens with aggregation-induced emission (AIE) as an innovative and non-antibiotic therapy for N. seriolae. Specifically, the AIE photosensitizer, TTCPy-3 is employed against N. seriolae. We evaluated the antibacterial activity of TTCPy-3 and investigated the killing mechanism against N. seriolae, emphasizing its ability to aggregate within the bacterium and produce reactive oxygen species (ROS). TTCPy-3 could effectively aggregate in N. seriolae, generate ROS, and perform real-time imaging of the bacteria. A bactericidal efficiency of 100% was observed while concentrations exceeding 4 µM in the presence of white light irradiation for 10 min. In vivo, evaluation on zebrafish (Danio rerio) confirmed the superior therapeutic efficacy induced by TTCPy-3 to fight against N. seriolae infections. TTCPy-3 offers a promising strategy for treating nocardiosis of fish, paving the way for alternative treatments beyond traditional antibiotics and potentially addressing antibiotic resistance.

IFN-γ enhances protective efficacy against Nocardia seriolae infection in largemouth bass (Micropterus salmoides).

Introduction: Nocardia seriolae adversely impacts a diverse range of fish species, exhibiting significant pathogenic characteristics that substantially impede the progress of aquaculture. N. seriolae infects in fish has a long incubation period, and clinical symptoms are not obvious in the early stages. There is presently no viable and eco-friendly approach to combat the spread of the disease. According to reports, N. seriolae primarily targets macrophages in tissues after infecting fish and can proliferate massively, leading to the death of fish. Interferon-gamma (IFN-γ) is a crucial molecule that regulates macrophage activation, but little is known about its role in the N. seriolae prevention. Methods: IFN-γ was first defined as largemouth bass (Micropterus salmoides, MsIFN-γ), which has a highly conserved IFN-γ characteristic sequence through homology analysis. The recombinant proteins (rMsIFN-γ) were obtained in Escherichia coli (E. coli) strain BL21 (DE3). The inflammatory response-inducing ability of rMsIFN-γ was assessed in vitro using monocytes/macrophages. Meanwhile, the protective effect of MsIFN-γ in vivo was evaluated by N. seriolae infection largemouth bass model. Results: In the inflammatory response of the monocytes/macrophages activated by rMsIFN-γ, various cytokines were significantly increased. Interestingly, interleukin 1ß (IL-1ß) and tumor necrosis factor alpha (TNF-a) increased by 183- and 12-fold, respectively, after rMsIFN-γ stimulation. rMsIFN-γ improved survival by 42.1% compared with the control. The bacterial load in the liver, spleen and head kidney significantly decreased. rMsIFN-γ was also shown to better induce increased expression of IL-1ß, TNF-α, hepcidin-1(Hep-1), major histocompatibility complex I (MHCI), and MHC II in head kidney, spleen and liver. The histopathological examination demonstrated the transformation of granuloma status from an early necrotic foci to fibrosis in the infection period. Unexpectedly, the development of granulomas was successfully slowed in the rMsIFN-γ group. Discussion: This work paves the way for further research into IFN-γ of largemouth bass and identifies a potential therapeutic target for the prevention of N. seriolae.

In vitro activity of tedizolid against 43 species of Nocardia species.

The purpose of the present study was to evaluate the in vitro activity of tedizolid against several clinically significant species of Nocardia by comparing with that of linezolid. A total of 286 isolates of Nocardia species, including 236 clinical isolates recovered from patients in Japan and 50 strains (43 species) purchased from NITE Biological Resource Center, were studied. Antimicrobial susceptibility testing was performed using the broth microdilution method. For the 286 Nocardia isolates, the minimal inhibitory concentration (MIC)50 and MIC90 values of tedizolid were 0.25 and 0.5 µg/ml, and those of linezolid were 2 and 2 µg/ml, respectively. The distribution of the linezolid/tedizolid ratios (MICs of linezolid/MICs of tedizolid) showed that tedizolid had four- to eight-fold higher activity than linezolid in 96.1% (275/286) of Nocardia isolates. Both the tedizolid and linezolid MIC90 values for Nocardia brasiliensis were two-fold higher than those for the other Nocardia species. Both tedizolid and linezolid had low MIC values, 0.25-1 µg/ml and 0.5-4 µg/ml, respectively, even against nine isolates (five species) that were resistant to trimethoprim/sulfamethoxazole. One Nocardia sputorum isolate showed reduced susceptibility to tedizolid (4 µg/ml). Bioinformatics analysis suggests different resistance mechanisms than the oxazolidinone resistance seen in enterococci and staphylococci.

Clinical characteristics and drug resistance of Nocardia in Henan, China, 2017-2023.

BACKGROUND: The aim of this study was to investigate the clinical features of Nocardia infections, antibiotic resistance profile, choice of antibiotics and treatment outcome, among others. In addition, the study compared the clinical and microbiological characteristics of nocardiosis in bronchiectasis patients and non-bronchiectasis patients. METHODS: Detailed clinical data were collected from the medical records of 71 non-duplicate nocardiosis patients from 2017 to 2023 at a tertiary hospital in Zhengzhou, China. Nocardia isolates were identified to the species level using MALDI-TOF MS and 16S rRNA PCR sequencing. Clinical data were collected from medical records, and drug susceptibility was determined using the broth microdilution method. RESULTS: Of the 71 cases of nocardiosis, 70 (98.6%) were diagnosed as pulmonary infections with common underlying diseases including bronchiectasis, tuberculosis, diabetes mellitus and chronic obstructive pulmonary disease (COPD). Thirteen different strains were found in 71 isolates, the most common of which were N. farcinica (26.8%) and N. cyriacigeorgica (18.3%). All Nocardia strains were 100% susceptible to both TMP-SMX and linezolid, and different Nocardia species showed different patterns of drug susceptibility in vitro. Pulmonary nocardiosis is prone to comorbidities such as bronchiectasis, diabetes mellitus, COPD, etc., and Nocardia is also frequently accompanied by co-infection of the body with pathogens such as Mycobacterium and Aspergillus spp. Sixty-one patients underwent a detailed treatment regimen, of whom 32 (52.5%) received single or multi-drug therapy based on TMP-SMX. Bronchiectasis was associated with a higher frequency of Nocardia infections, and there were significant differences between the bronchiectasis and non-bronchiectasis groups in terms of age distribution, clinical characteristics, identification of Nocardia species, and antibiotic susceptibility (P < 0.05). CONCLUSIONS: Our study contributes to the understanding of the species diversity of Nocardia isolates in Henan, China, and the clinical characteristics of patients with pulmonary nocardiosis infections. Clinical and microbiologic differences between patients with and without bronchiectasis. These findings will contribute to the early diagnosis and treatment of patients.