Advertisement

  • Loading metrics

Open Access

Peer-reviewed

Research Article

The species distribution and antimicrobial resistance profiles of Nocardia species in China: A systematic review and meta-analysis

  • Chaohong Wang,

    Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Supervision, Writing – original draft, Writing – review & editing

    Affiliation Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯
  • Qing Sun,

    Roles Data curation, Investigation, Validation, Visualization

    Affiliation Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯
  • Jun Yan,

    Roles Data curation, Investigation, Validation, Visualization

    Affiliation Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯
  • Xinlei Liao,

    Roles Data curation

    Affiliation Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯
  • Sibo Long,

    Roles Data curation

    Affiliation Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯
  • Maike Zheng,

    Roles Data curation, Software

    Affiliation Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯
  • Yun Zhang,

    Roles Data curation

    Affiliation Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China

    ⨯
  • Xinting Yang,

    Roles Data curation

    Affiliation Tuberculosis Department, Beijing Chest Hospital, Capital Medical University, Beijing, China

    ⨯
  • Guangli Shi,

    Roles Data curation

    Affiliation Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯
  • Yan Zhao,

    Roles Data curation

    Affiliation Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯
  • Guirong Wang ,

    Roles Conceptualization, Funding acquisition, Project administration, Resources, Writing – review & editing

    wangguirong1230@ccmu.edu.cn (GW); pxm1960@sohu.com (JP)

    Affiliation Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯
  • Junhua Pan

    Roles Conceptualization, Funding acquisition, Project administration

    wangguirong1230@ccmu.edu.cn (GW); pxm1960@sohu.com (JP)

    Affiliation Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China

    ⨯

Abstract

Background

Nocardia species can cause local or disseminated infection. Prompt diagnosis and appropriate treatment of nocardiosis are required, because it can cause significant morbidity and mortality. Knowledge of local species distribution and susceptibility patterns is important to appropriate empiric therapy. However, knowledge on the epidemiology and antimicrobial susceptibility profiles of clinical Nocardia species remains limited in China.

Methods

The data of isolation of Nocardia species were collected from databases such as Pubmed, Web of Science, Embase as well as Chinese databases (CNKI, Wanfang and VIP). Meta-analysis was performed using RevMan 5.3 software. Random effect models were used and tested with Cochran’s Q and I2 statistics taking into account the possibility of heterogeneity between studies.

Results

In total, 791 Nocardia isolates were identified to 19 species levels among all the recruited studies. The most common species were N. farcinica (29.1%, 230/791), followed by N. cyriacigeorgica (25.3%, 200/791), N. brasiliensis (11.8%, 93/791) and N. otitidiscaviarum (7.8%, 62/791). N. farcinica and N. cyriacigeorgica were widely distributed, N. brasiliensis mainly prevalent in the south, N. otitidiscaviarum mainly distributed in the eastern coastal provinces of China. Totally, 70.4% (223/317) Nocardia were cultured from respiratory tract specimens, 16.4% (52/317) from extra-pulmonary specimens, and 13.3% (42/317) from disseminated infection. The proportion of susceptible isolates as follows: linezolid 99.5% (197/198), amikacin 96.0% (190/198), trimethoprim-sulfamethoxazole 92.9% (184/198), imipenem 64.7% (128/198). Susceptibility varied by species of Nocardia.

Conclusions

N. farcinica and N. cyriacigeorgica are the most frequently isolated species, which are widely distributed in China. Pulmonary nocardiosis is the most common type of infection. Trimethoprim-sulfamethoxazole can still be the preferred agent for initial Nocardia infection therapy due to the low resistance rate, linezolid and amikacin could be an alternative to treat nocardiosis or a choice in a combination regimen.

Author summary

Nocardiosis is a neglected tropical disease caused by Nocardia and potentially lifethreatening infection. Despite increasing attention towards the Nocardia infections, the overall epidemiological information and antimicrobial susceptibility profiles of clinical Nocardia species remains limited for China. A systematic review and meta-analysis was conducted using data of 42 qualified publications. Our pooled analysis of these studies demonstrated that N. farcinica and N. cyriacigeorgica are the most frequently isolated species, which are widely distributed in China. Totally, 70.4% (223/317) Nocardia were cultured from respiratory tract specimens. Susceptibility varied by species of Nocardia. Trimethoprim-sulfamethoxazole can still be the preferred agent for initial Nocardia infection therapy due to the low resistance rate, linezolid and amikacin could be an alternative to treat nocardiosis or a choice in a combination regimen.

Citation: Wang C, Sun Q, Yan J, Liao X, Long S, Zheng M, et al. (2023) The species distribution and antimicrobial resistance profiles of Nocardia species in China: A systematic review and meta-analysis. PLoS Negl Trop Dis 17(7): e0011432. https://doi.org/10.1371/journal.pntd.0011432

Editor: Andrew C. Singer, UK Centre for Ecology and Hydrology, UNITED KINGDOM

Received: December 25, 2022; Accepted: June 5, 2023; Published: July 10, 2023

Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the paper and its Supporting information files.

Funding: Funding was provided by Capital’s Funds for Health Improvement and Research (2022-1G-2162) to JP, Beijing Public Health Experts Project (2022-3-040), Beijing Tongzhou Municipal Science & Technology commission (KJ2022CX044) and Tongzhou Yunhe Project under Grant (YH201917) to GW. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

The genus Nocardia are filamentous, Gram-positive, aerobic, weakly acid-fast bacteria, they are closely related to the genera Corynebacterium and Mycobacterium [1]. Nocardiosis resembles tuberculosis (TB) and non-tuberculous mycobacteria (NTM) disease in most clinical symptoms and radiological manifestations [2–3], which may lead to misdiagnosis or underdiagnosis. China remains a high TB burden country in 2021 and the prevalence of NTM increased considerably [4]. Although increased awareness of Nocardia by clinicians, the knowledge on Nocardia infection remains paucity in China.

To date, more than 200 Nocardia species have been described (http://www.bacterio.net/genus/nocardia), with different species showing different antibiotic susceptibility patterns [1]. The distribution of Nocardia species tends to vary as per geographical regions [5]. Different species may exhibit predilection to certain body sites. A few studies have reported the clinical features, epidemiology and antimicrobial resistance patterns of Nocardia species in China [6,7–11], however, these reports harbored high degrees of variability.

The aim of this study was to elucidate the species distribution and antimicrobial resistance profiles of Nocardia species in China using meta-analysis based on systematic review of articles published until 30 September, 2022. This study will provide more detailed information to overview the magnitude of Nocardia infection and provide guidance on empirical therapy in China.

Method

Search strategies

The available literatures were identified by searching in the electronic database such as: Pubmed, Web of Science, Embase as well as Chinese databases (CNKI, Wanfang and VIP), with medical subject headings (MeSH) terms and a proper use of keywords, published until 30 September, 2022. The search criteria were “Nocardia” “nocardiosis” or “Nocardia disease” and “China”, “Chinese”, etc. Both English articles and Chinese articles were considered.

Inclusion and exclusion criteria

The process of article screening and selection following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 statement guidelines [12]. All original articles which referenced to the standard method for Nocardia species identification and/or antimicrobial resistance tests and presented either the cross-sectional or cohort studies from China were included. The standard identification was based on culture, mass spectrometry or molecular methods (e.g. DNA sequencing, multilocus sequence analysis, metagenomic next-generation sequencing). The antimicrobial resistance test was determined using the standard Broth microdilution method, which following the recommendations of the Clinical and Laboratory Standards Institute.

Articles were excluded for any of the following characteristics: (1) reviews, conference presentations, literature reviews, non-full-text and unpublished data; (2) studies with less than 5 cases; (3) isolates were not identified to species level; (4) data from non-Chinese population.

Data extraction and definitions

After the articles were merged into Excel 2019, the results are de-duplicated and filtered. Two researchers independently extracted the data from eligible studies as follows: first author, year of publication, enrollment time, sample size, province of study, and method of species identification. Inconsistency between the reviewers was resolved through discussion to obtain consensus.

Statistical analysis

Meta-analysis was performed using RevMan 5.3 software. Stratified analyses were performed with respect to the geographic areas, infected sites, culture methods. Random effect models were used and tested with Cochran’s Q and I2 statistics taking into account the possibility of heterogeneity between studies. To assess possible publication bias, value of P<0.05 was considered an indication of statistically significant publication bias using the Egger weighted regression methods.

Results

Characteristics of the included studies

As shown in Fig 1, a total of 4493 related articles were obtained through literature retrieval of keyword combination in the database. In secondary screening and after duplication, 61 articles were included for detailed full text evaluation. We also aggregated the sample collected time, province and hospital involved in the included articles, and 19 articles were deleted due to duplication. Finally, 42 studies were included in present study [6,7,10,11,13–50], including 28 published in Chinese and 14 in English, covering 20 provinces in mainland China and involving 1008 clinical Nocardia isolates. Table 1 summarizes the characteristics of the selected articles.

thumbnail
Download:
Fig 1. Flow diagram of study identification.

https://doi.org/10.1371/journal.pntd.0011432.g001

thumbnail
Download:
Table 1. Characteristics of studies involved in the current systematic review and meta-analysis.

https://doi.org/10.1371/journal.pntd.0011432.t001

Prevalence of different Nocardia species

In total, 791 Nocardia isolates were identified to 19 species levels among all the recruited studies (Table 2). The most common species were N. farcinica (29.1%, 230/791), followed by N. cyriacigeorgica (25.3%, 200/791), N. brasiliensis (11.8%, 93/791) and N. otitidiscaviarum (7.8%, 62/791) (Fig 2). The four most common isolated Nocardia accounted for 74.0% of all Nocardia species.

thumbnail
Download:
Table 2. Species distribution among the Nocardia isolates from China.

https://doi.org/10.1371/journal.pntd.0011432.t002

thumbnail
Download:
Fig 2. The species distribution of 791 Nocardia isolates.

https://doi.org/10.1371/journal.pntd.0011432.g002

Both species composition and the number of Nocardia isolates demonstrated marked geographic variability. Among 19 Nocardia species, 12 isolated from Northeast, 11 from Southeast, 9 from Northwest, 8 from Southwest and 11 from Central China (Table 3). Besides, the eastern region isolated more Nocardia strains than central and western region. The southern region had more isolates than the northern region, while the southeastern region had the most strains in China (Fig 3). The prevalence of different Nocardia species was also dramatically varied by geographic areas (χ2 = 249.690, P<0.001). In Northern China, N.cyriacigeorgica constituted 36.1% of all the isolated Nocardia and 20.3% in case of Southern China. More N. brasiliensis were isolated in Western China than in Eastern China (26.5% vs 8.9%, P < 0.001). In central China, N. farcinica consisted of 40.0% of all the isolated Nocardia. (Table 3).

thumbnail
Download:
Table 3. Species distribution of the Nocardia isolates among five geographic areas in China.

https://doi.org/10.1371/journal.pntd.0011432.t003

thumbnail
Download:
Fig 3. Distribution of Nocardia isolates in five geographic areas of China.

Distribution of Nocardia isolates in five geographic areas of China. (A) Geographical locations of the total Nocardia isolates, (B) Distribution of N. farcinica, N. cyriacigeorgica, N. brasiliensis and N. otitidiscaviarum. The color-highlighted areas represent those where Nocardia isolates were collected, with the proportion of strains provided in parentheses. (Source of data is the latest version of National Basic Geographic Information System, review number GS(2020)4619).

https://doi.org/10.1371/journal.pntd.0011432.g003

The prevalent Nocardia species showed regional characteristics. N. farcinica and N. cyriacigeorgica appears widely distributed and mainly prevalent in the northeast and central areas of China, N. brasiliensis mainly prevalent in the southwest, N. otitidiscaviarum prefers to be distributed in the east coastal provinces (Fig 3). The forest plots prevalence of N. farcinica, N. cyriacigeorgica, N. brasiliensis and N. otitidiscaviarum were shown in S1 Fig.

Stratified analyses of infection type

Totally, 70.4% (223/317) Nocardia were cultured from respiratory tract specimens, 16.4% (52/317) from extra-pulmonary specimens, and 13.3% (42/317) from disseminated infection (Fig 4). N. farcinica (76/223, 34.1%), N. brasiliensis (24/52, 46.2%) and N. farcinica (13/42, 31.0%) were the most frequently species causing pulmonary infection, extra-pulmonary infection and disseminated infection, respectively (Fig 4). The skin and soft tissue wounds (41/52, 78.9%), including feet infection, are the main sources of extra-pulmonary infection. N. brasiliensis (24/41, 58.5%) and N. terpenica (6/41, 14.6%) are the most common species causing cutaneous nocardiosis.

thumbnail
Download:
Fig 4. Nocardia species distribution grouped by infection types.

https://doi.org/10.1371/journal.pntd.0011432.g004

Effects of cultural method on Nocardia isolation

Among the 42 articles included in this study, 16 of them reported the cultural medium used for Nocardia isolation. The isolation rate of N. farcinica was 80.3% (53/66) by MGIT 960 mycobacterium liquid medium and 22.8% (71/311) using routine columbia blood plate. There was a significant difference (χ2 = 81.478, P < 0.001).

Antimicrobial susceptibility profiles

There were 198 isolates with available antibiotic susceptibility data, which performed using the standard Broth microdilution method. The proportion of susceptible isolates as follows: linezolid 99.5% (197/198), amikacin 96.0% (190/198), trimethoprim-sulfamethoxazole 92.9% (184/198), imipenem 64.7% (128/198), tobramycin 63.1% (99/157), gentamicin 62.0% (31/50), minocycline 50.7% (75/148), ceftriaxone 45.7% (80/175) (Table 4). Susceptibility varied by species of Nocardia. While susceptibility for minocycline for N. otitidiscaviarum and N. brasiliensis was 86.4% and 88.9%, respectively; susceptibility for N. farcinica and N. cyriacigeorgica were lower at 21.2% and 38.3%, respectively. N. cyriacigeorgica (90.1%) showed relatively high susceptible rates to imipenem, while N. otitidiscaviarum (7.7%), N. brasiliensis (33.3%) and N. farcinica (45.5%) showed relatively low susceptible rates to imipenem. Most species showed low susceptibility rates to moxifloxacin; however, 79.3% (23/29) N. farcinica and 66.7% (4/6) N. brasiliensis isolates were susceptible to moxifloxacin, respectively (Table 4).

thumbnail
Download:
Table 4. Antimicrobial susceptibility results of Nocardia isolates in China.

https://doi.org/10.1371/journal.pntd.0011432.t004

Discussion

Nocardia are ubiquitous in the environment and could lead to life-threatening infection. With gradually increased incidence, nocardiosis has become a noticeable health threat in China. Nocardia infectons are prone to be misdiagnosed as TB or multidrug-resistant TB [3], when only acid-fast staining and mycobacterial culture are used for the diagnosis of TB [51]. Although increasing attention towards Nocardia infection, there is not an organized monitoring system for Nocardia spp. An epidemiological analysis of Nocardia spp. mainly depends on meta-analysis or systematic review. This study will build a nationwide overview of species distribution and antimicrobial resistance profiles of Nocardia species in China.

The species distribution of Nocardia has unique characteristics worldwide. Our meta-analysis showed that the most common species was N. farcinica (29.1%, 230/791), followed by N. cyriacigeorgica (25.3%, 200/791), N. brasiliensis (11.8%, 93/791) and N. otitidiscaviarum (7.8%, 62/791) in China. Internationally, N. farcinica was the most common species in South Africa (20.5%) [52], Belgium (44%) [53], and France (20.2%) [54], whilst N. cyriacigeorgica was the most common species in Spain (25.3%) [55] and Iran (31.0%) [56], and N. nova was the most common species in the United States (21.6–28%) [57–59] and Australia (29–35.5%) [7,59]. Furthermore, the species composition from different provinces and climates of China demonstrated marked variations. N. farcinica and N. cyriacigeorgica are widely distributed. N. brasiliensis mainly prevalent in the south, which belongs to the subtropical monsoon climate. N. otitidiscaviarum mainly distributed in the eastern coastal provinces of China and it is reasonable to assume that it is determined by the sea. Considering the large size of Chinese territories and different climate conditions, it is important to build a knowledgebase of local prevalence of Nocardia species.

Different species may cause different types of infection. As expected, the most common source for positive Nocardia cultures was respiratory tract specimens in China. Although the frequent association of N. farcinica with brain abscesses, bacteremia, skin and subcutaneous infection has been reported [55,60], in our study, in 223 pulmonary infection cases, 76 (34.1%) were N. farcinica. Moreover, N. brasiliensis was related predominately to cutaneous nocardiosis [9]. In our study, of 51 N. brasiliensis isolates, 24 (47.1%) were recovered from the skin and soft tissue infections.

Nocardia strains are frequently isolated during culture for mycobacteria in high TB burden settings, however, procedures used for decontamination of sputum specimens may be deleterious to Nocardia isolates [61]. Another factor that may limit Nocardia recovery is that egg-base L-J media is not an optimal choice for Nocardia isolation [11,62]. Furthermore, there are 5 antibiotics in MGIT 960 mycobacterium liquid media, which maybe unfavorable to some Nocardia species. Although Nocardia seem to grow well on blood agar and fungal media, some strains may be inhibited by the gentamicin present in inhibitory mold agar [62]. The isolated Nocardia species varied according to the culture methods used.

This systemic study explored the association of antimicrobial susceptibility profiles and Nocardia species to reach a guideline for the nocardiosis treatment in China. Trimethoprim-sulfamethoxazole constitutes the keystone of nocardiosis treatment [57], while the resistance rates for Nocardia varied among different regions worldwide [57,63]. Only 7.1% (14/198) of all Nocardia isolates were resistant to trimethoprim-sulfamethoxazole in our study, majority of which were N. farcinica (83.6%, 46/55). Our results indicate that trimethoprim-sulfamethoxazole is frequently activite against Nocardia species isolated in China, and could be used as the primary agent to treat nocardiosis, even without antibiotic susceptibility results. Linezolid and amikacin are also effective drugs for most Nocardia species, with 99.5% (197/198) and 96.0% (190/198) activity against clinical isolates, respectively. Linezolid and amikacin could be potentially used for empiric treatment of nocardiosis in China. Imipenem showed good activity for N. cyriacigeorgica with susceptibility rate as 90.1% (64/71) in the current study, however, N. farcinica (45.5%, 25/55) showed relatively low susceptible rates to imipenem. The remaining antimicrobials showed low activity against Nocardia isolates, and the susceptibility profiles were highly variable between different species. Thus, it is imperative to identify Nocardia isolates to the species level and an antimicrobial susceptibility test should be conducted during clinical practice to properly treat nocardiosis. Owing to the absence or delay of species identification and drug susceptibility outcomes, nocardiosis patients may be treated empirical. It is helpful to refer to the local drug resistance prevalence data for the initial drug choice to treat Nocardia infection. Our results will begin to better understand Nocardia species distributed in China and for the choice of empirical therapy.

The present study is the first meta-analysis of Nocardia species distribution and antimicrobial susceptibility patterns in China, but its limitations should also be noted. Nocardia infection is not required to be reported to public health authorities, hence its precise prevalence in China is not available. There were few studies on the incidence of nocardiosis in China. Most of published data focus on clinical manifestations, species distribution, and antimicrobial susceptibility of Nocardia species. Our study could not show the overall prevalence rate of Nocardia infection in China.

Conclusion

Pulmonary nocardiosis is the most common type of infection. N. farcinica and N. cyriacigeorgica are the most frequently isolated species, which are widely distributed in China. Trimethoprim-sulfamethoxazole can still be the preferred agent for initial Nocardia infection therapy due to the low resistance rate, and linezolid and amikacin could be an alternative to treat nocardiosis or a choice in a combination regimen.

Supporting information

S1 Table. PRISMA 2020 checklist.

https://doi.org/10.1371/journal.pntd.0011432.s001

(DOCX)

S1 Fig. Forest plots of proportion of N. farcinica, N. cyriacigeorgica, N. brasiliensis and N. otitidiscaviarum in China.

https://doi.org/10.1371/journal.pntd.0011432.s002

(TIF)

References

  1. 1. Conville PS, Brown-Elliott BA, Smith T, Zelazny AM. The Complexities of Nocardia Taxonomy and Identification. J Clin Microbiol. 2017; 56(1):e01419–17. pmid:29118169
  2. 2. Duggal SD, Chugh TD. Nocardiosis: A Neglected Disease. Med Princ Pract. 2020; 29(6):514–523. pmid:32422637
  3. 3. Alizadeh SA, Javadi A, Mardaneh J, et al. Development of a SYBR Green Multiplex Real Time PCR for Simultaneous Detection of Mycobacterium Tuberculosis and Nocardia Asteroides in Respiratory Samples. Ethiop J Health Sci. 2021; 31(2):241–246. pmid:34158775
  4. 4. Sun Q, Yan J, Liao X, Wang C, Wang C, Jiang G, et al. Trends and Species Diversity of Non-tuberculous Mycobacteria Isolated From Respiratory Samples in Northern China, 2014–2021. Front Public Health. 2022; 10:923968. pmid:35923959
  5. 5. Tan YE, Chen SC, Halliday CL. Antimicrobial susceptibility profiles and species distribution of medically relevant Nocardia species: Results from a large tertiary laboratory in Australia. J Glob Antimicrob Resist. 2020; 20:110–117. pmid:31400449
  6. 6. Lu S, Qian Z, Mou P, Xie L. Clinical Nocardia species: Identification, clinical characteristics, and antimicrobial susceptibility in Shandong, China. Bosn J Basic Med Sci. 2020; 20(4):531–538. pmid:32415818
  7. 7. Wei M, Xu X, Yang J, Wang P, Liu Y, Wang S, et al. MLSA phylogeny and antimicrobial susceptibility of clinical Nocardia isolates: a multicenter retrospective study in China. BMC Microbiol. 2021; 21(1):342. pmid:34903163
  8. 8. Wang H, Zhu Y, Cui Q, Wu W, Li G, Chen D, et al. Epidemiology and Antimicrobial Resistance Profiles of the Nocardia Species in China, 2009 to 2021. Microbiol Spectr. 2022; 10(2):e0156021. pmid:35234511
  9. 9. Lao C, Tseng M, Chiu C, Chen N, Chen C, Chung W, et al. Clinical manifestations and antimicrobial susceptibility of Nocardia species at a tertiary hospital in Taiwan, 2011–2020. J Formos Med Assoc. 2022; 121(10):2109–2122. pmid:35811270
  10. 10. Huang L, Chen X, Xu H, Sun L, Li C, Guo W, et al. Clinical features, identification, antimicrobial resistance patterns of Nocardia species in China: 2009–2017. Diagn Microbiol Infect Dis. 2019; 94(2):165–172. pmid:30679058
  11. 11. Dong G, Chu P, Guo J, Xie Y, Lu J. Nontuberculous mycobacterial and Nocardia infections mimicking pulmonary tuberculosis: a retrospective study of a general hospital patient population in China. J Med Microbiol. 2020; 69(9):1145–1150. pmid:31021740
  12. 12. Page MJ, Moher D, Bossuyt PM, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021; 372:n160. pmid:33781993
  13. 13. Ding J, Ma B, Wei X, Li Y. Detection of Nocardia by 16S Ribosomal RNA Gene PCR and Metagenomic Next-Generation Sequencing (mNGS). Front Cell Infect Microbiol. 2022; 11:768613. pmid:35071035
  14. 14. Zhong C, Huang P, Zhan Y, Yao Y, Ye J, Zhou H. Clinical Features of Pulmonary Nocardiosis in Patients with Different Underlying Diseases: A Case Series Study. Infect Drug Resist. 2022; 15:1167–1174. Published 2022 Mar 21. pmid:35340670
  15. 15. Li Y, Tang T, Xiao J, Wang J, Li B, Ma L, et al. Clinical analysis of 11 cases of nocardiosis. Open Med (Wars). 2021; 16(1):610–617. pmid:33869782
  16. 16. Guo J, Li S, Xu S, Jiang L, Gao E, Liu Z. Nocardiosis in patients with nephrotic syndrome: a retrospective analysis of 11 cases and a literature review. Int Urol Nephrol. 2020; 52(4):731–738. pmid:32124233
  17. 17. Weng S, Zhang H, Ai J, Gao Y, Liu Y, Xu B, et al. Rapid Detection of Nocardia by Next-Generation Sequencing. Front Cell Infect Microbiol. 2020; 10:13. pmid:32133300
  18. 18. Yi M, Wang L, Xu W, Sheng L, Jiang L, Yang F, et al. Species Distribution And Antibiotic Susceptibility Of Nocardia Isolates From Yantai, China. Infect Drug Resist. 2019; 12:3653–3661. pmid:31819548
  19. 19. Zhao P, Zhang X, Du P, Li G, Li L, Li Z. Susceptibility profiles of Nocardia spp. to antimicrobial and antituberculotic agents detected by a microplate Alamar Blue assay. Sci Rep. 2017; 7:43660. pmid:28252662
  20. 20. Liu H, Lian L, Jiang Y, Huang M, Tan Y, Zhao X, et al. Identification of Species of Nontuberculous Mycobacteria Clinical Isolates from 8 Provinces of China. Biomed Res Int. 2016; 2016:2153910. pmid:27882322
  21. 21. Xiao M, Pang L, Chen S, Fan X, Zhang L, Li H, et al. Accurate Identification of Common Pathogenic Nocardia Species: Evaluation of a Multilocus Sequence Analysis Platform and Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry. PLoS One. 2016; 11(1):e0147487. pmid:26808813
  22. 22. Yu X, Lu L, Chen G, Liu Z, Lei H, Song Y, et al. Identification and characterization of non-tuberculous mycobacteria isolated from tuberculosis suspects in Southern-central China. PLoS One. 2014; 9(12):e114353. pmid:25463697
  23. 23. Wu C, Zhang A, Huang S, Qian S, Ying J, Huang X, et al. Clinical characteristics and prognosis of pulmonary nocardiosis in non-immunosuppressed patients. Journal of Clinical Pulmonary Medicine. 2022; 27(7):982–986. (In Chinese)
  24. 24. Cheng Y, Gao J, Gu J, Yuan H, Gao P, Song Y. Identification,clinical characteristics and antimicrobial susceptibility of 10 clinical Nocardia infection cases. Chinese Journal of Microecology. 2022; 34(6):690–696. (In Chinese)
  25. 25. Gao J, Zhang M, Chang J. Clinical analysis of 34 cases of nocardiosis. Chinese Journal of Infection and Chemotherapy. 2022; 22(3):301–306. (In Chinese)
  26. 26. Pan S, Huang D, Sun X. Clinical and drug sensitivity analysis of 10 cases of Nocardia infection. Fujian Medical Journal. 2022; 44(2):103–106F0004. (In Chinese)
  27. 27. Lin Z, Chen T, Wu N. Nocardiosis:a report of 10 cases. Chinese Journal of Infection and Chemotherapy. 2021; 21(6):675–679. (In Chinese)
  28. 28. Cai Z, Jiang X, Liang M. Clinical features of 13 cases of nocardiosis. Chinese Journal of Infection Control. 2021; 20(10):933–937. (In Chinese)
  29. 29. Liao C, Chen J, Long L, Zou M, Huang Y. Clinical features of 24 cases of nocardiosis. Chinese Journal of Infectious Diseases. 2021; 39(10):616–620. (In Chinese)
  30. 30. Xie X, Yang Q, Zheng J, Zeng W, Liang Z, Shao L, et al. Clinical characteristics and prognosis of 44 patients with Nocardia infection. Chinese Journal of Infectious Diseases. 2021; 39(1):35–39. (In Chinese)
  31. 31. Mao Y, Chen L, Weng H. Clinical features of 25 cases of pulmonary nocardiosis. Chinese Journal of Infection and Chemotherapy. 2020; 20(6):613–617. (In Chinese)
  32. 32. Yang P, Zhou K, Kang B, He W, Bai L, Xu X. Clinical analysis of 15 cases of Nocardiosis. Laboratory Medicine and Clinic. 2020; 17(21):3136–3140. (In Chinese)
  33. 33. Zhao L, Zheng H, Jiang P. Clinical characteristics of 12 cases of nocardiosis. Chinese Journal of Nosocomiology. 2020; 30(1):151–155. (In Chinese)
  34. 34. Ma X, Liu Z, Wang A. Nocardia infection: a report of 10 cases and review of literature. CHINESE JOURNAL OF INTERNAL MEDICINE. 2000; 39(1):55–56. (In Chinese)
  35. 35. Ye F, Li S, Cui J, Xie J, Su D, Zeng Q. Pulmonary nocardiosis: a 7-case report and literature review. Journal of Modern Clinical Medical Bioengineering. 2014; 10(3):244–247. (In Chinese)
  36. 36. Zhang X, Yi S, Chen Z, Tan X, Hu P, Guo J, et al. Clinical analysis of 9 cases of Nocardia mallei in tuberculosis hospital. Journal of Chinese Physician. 2018; 20(2):272–274. (In Chinese)
  37. 37. Chen Y, Jia Y, Shi D, Song W, Shi Y. Distribution of Nocardia strains isolated from multicenter clinical isolates in Hebei. Chinese Journal of Clinical Laboratory Science. 2020; 38(10):790–792. (In Chinese)
  38. 38. Wang Y, Yin H, Sui X, Wang J, Cong F. Clinical distribution and drug resistance of Nocardiacausing infections in patients of orthopedics department. Chinese Journal of Nosocomiology. 2015; 25(22):5119–5121. (In Chinese)
  39. 39. Chen Y. Retrospective study on clinical diagnosis and treatment of 19 cases of Nocardiosis. Southwest Medical University. 2020. (In Chinese)
    • 40. Li F, Qin Z, Yang M, Huang S, Li M, Bai J, et al. Clinical characteristics,diagnosis and treatment of pulmonary nocardiosis:A report of 19 cases. Journal of Guangxi Medical University. 2022; 39(7):1147–1152. (In Chinese)
    • 41. Cheng Z, Li G, Shi Z, Zhou X, Jia W. Clinical Characteristics of Nocardia Infection. Journal of Ningxia Medical University. 2017; 39(5):537–540. (In Chinese)
    • 42. Gao Z, Lin Y, Li S, Hong F, Yu X. Clinical analysis of 11 cases of pulmonary nocariasis. Chinese Journal of Practical Internal Medicine. 2013; 10(7):563–564.
    • 43. Chen X. Analysis of clinical data of Nocardiainfection in 13 patients. Chinese Journal of Nosocomiology. 2012; 22(9):1826–1827. (In Chinese)
    • 44. He L, Wang Y. Analysis of nocardia infections 16 cases. Journal of Medical Forum. 2011; 32(16):71–73.
    • 45. Lai Z, Wang X, Lin Q, Chen S. Clinical analysis of 5 cases of pulmonary Nocardiosis. Chinese Journal of Postgraduates of Medicine. 2008; 31(4):50–52. (In Chinese)
    • 46. Nong B, Li B, Liang X, Zhou Y. Clinical diagnosis, treatment and prognosis of Nocardia infection. China Pharmaceuticals. 2020; 29(S02):234–235. (In Chinese)
    • 47. Fang Zheng, Hui Shen, Zhiguo Zhou. Clinical characteristics and prognosis analysis of pulmonary nocardiosis in Hunan region:report of 55 cases. Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care. 2020; 27(6):661–664. (In Chinese)
    • 48. Li X, Wang R, Zeng C, Wang M, Feng Y, He Q, et al. Diagnosis and treatment of patients with Nocardia infection (analysis of 21 cases). Shandong Medical Journal. 2022; 62(12):78–80. (In Chinese)
    • 49. Chao S, A X, Zhang Q, Xu W. Identification and evaluation of Nocardia by MS and gene sequencing in plateau area. Very healthy. 2020; (19):79. (In Chinese)
    • 50. Sun Y. To summarize the laboratory characteristics and drug sensitivity of Nocardia pneumonia in patients with HIV. Women’s Health. 2021; (25): 111. (In Chinese)
    • 51. Khadka P, Basnet RB, Rijal BP, Sherchand JB. Pulmonary nocardiosis masquerading renascence of tuberculosis in an immunocompetent host: a case report from Nepal. BMC Res Notes. 2018; 11(1):488. pmid:30016976
    • 52. Lowman W, Aithma N. Antimicrobial susceptibility testing and profiling of Nocardia species and other aerobic actinomycetes from South Africa: comparative evaluation of broth microdilution versus the Etest. J Clin Microbiol. 2010; 48(12):4534–40. pmid:20980572
    • 53. Wauters G, Avesani V, Charlier J, Janssens M, Vaneechoutte M, Delmée M. Distribution of nocardia species in clinical samples and their routine rapid identification in the laboratory. J Clin Microbiol. 2005; 43(6):2624–8. pmid:15956375
    • 54. Lebeaux D, Bergeron E, Berthet J, Djadi-Prat J, Mouniée D, Boiron P, et al. Antibiotic susceptibility testing and species identification of Nocardia isolates: a retrospective analysis of data from a French expert laboratory, 2010–2015. Clin Microbiol Infect. 2019; 25(4):489–495. pmid:29933049
    • 55. Valdezate S, Garrido N, Carrasco G, Medina-Pascual MJ, Villalón P, Navarro AM, et al. Epidemiology and susceptibility to antimicrobial agents of the main Nocardia species in Spain. J Antimicrob Chemother. 2017; 72(3):754–761. pmid:27999029
    • 56. Hashemi-Shahraki A, Heidarieh P, Bostanabad SZ, Hashemzadeh M, Feizabadi MM, Schraufnagel D, et al. Genetic diversity and antimicrobial susceptibility of Nocardia species among patients with nocardiosis. Sci Rep. 2015; 5:17862. pmid:26638771
    • 57. Hamdi AM, Fida M, Deml SM, Abu Saleh OM, Wengenack NL. Retrospective Analysis of Antimicrobial Susceptibility Profiles of Nocardia Species from a Tertiary Hospital and Reference Laboratory, 2011 to 2017. Antimicrob Agents Chemother. 2020; 64(3):e01868–19. pmid:31818815
    • 58. Schlaberg R, Fisher MA, Hanson KE. Susceptibility profiles of Nocardia isolates based on current taxonomy. Antimicrob Agents Chemother. 2014; 58(2):795–800. pmid:24247124
    • 59. Yeoh K, Globan M, Naimo P, Williamson DA, Lea K, Bond K. Identification and antimicrobial susceptibility of referred Nocardia isolates in Victoria, Australia 2009–2019. J Med Microbiol. 2022; 71(8). pmid:35976092
    • 60. Coussement J, Lebeaux D, van Delden C, Guillot H, Freund R, Marbus S, et al. Nocardia Infection in Solid Organ Transplant Recipients: A Multicenter European Case-control Study. Clin Infect Dis. 2016; 63(3):338–45. pmid:27090987
    • 61. Saubolle MA, Sussland D. Nocardiosis: review of clinical and laboratory experience. J Clin Microbiol. 2003; 41(10):4497–501. pmid:14532173
    • 62. Hoza AS, Mfinanga SGS, Moser I, König B. Isolation, biochemical and molecular identification of Nocardia species among TB suspects in northeastern, Tanzania; a forgotten or neglected threat?. BMC Infect Dis. 2017; 17(1):407. pmid:28595598
    • 63. Uhde KB, Pathak S, McCullum I Jr, Jannat-Khah DP, Shadomy SV, Dykewicz CA, et al. Antimicrobial-resistant nocardia isolates, United States, 1995–2004. Clin Infect Dis. 2010; 51(12):1445–8. pmid:21058914