Rare Pathogen Research Articles

Shedding light on negative cultures in osteoarticular infections: leveraging mNGS to unravel risk factors and microbial profiles

BackgroundThe objective of this study is to utilize metagenomic next-generation sequencing (mNGS) to analyze the risk factors causing negative microbial cultures, comprehensively delineate the microbial profiles neglected by traditional cultures, and optimize the pathogenetic diagnostic procedure accordingly.Research design and methodsWe enrolled 341 patients diagnosed with OI at our center between 2016 and 2022, and gathered data including age, gender, clinical diagnosis, duration of antibiotic use prior to sampling, microbial culture results, and mNGS results for these patients. According to microbial detection results, risk factors for negative microbial culture and mNGS results were investigated through univariate and multivariate analyses, and the microbial profile in cases with negative microbial cultures was summarized in conjunction with mNGS results. Building upon this, we suggest strategies to enhance the positivity rate of microbial cultures based on clinical experience.ResultsInvasive osteoarticular infection (IOI), multi-infections, rare pathogen infections, and prior antibiotic use are risk factors for negative microbial cultures. When the duration of prior antibiotic use is ≥3 days, mNGS demonstrates significantly higher pathogen detection efficiency than microbial culture. Moreover, the risk of negative microbial culture increases by 4.8 times with the exposure to each additional risk factor (OR=4.043, 95%CI [2.835, 5.765], P<0.001). Additionally, over one-third of culture-negative OI involve polymicrobial infections or rare pathogens.ConclusionsClinicians should tailor microbial culture strategies based on patient conditions. When needed, they can collaborate with mNGS or optimize microbial culture conditions based on mNGS results to enhance the efficiency of pathogen diagnosis.

Ventriculoperitoneal shunt associated meningitis caused by Globicatella sanguinis: Review of an emerging human pathogen

The genus Globicatella has two species sanguinis and sulfidifaciens. Globicatella sanguinis is an unusual and rare pathogen causing bacteraemia, meningitis, and urinary tract infection in humans. The epidemiology and clinical significance of this pathogen remain largely unkown as Globicatella spp. are rarely isolated from clinical samples. We present a case of 36 year old male who had VP shunt associated meningitis caused by this pathogen. After the extensive literature search till date, we believe that this is the first case of VP shunt associated meningitis in a post trauma patient due to this pathogen. The identification of Globicatella sanguinis was made by Vitek 2 systems and was further confirmed by MALDI-TOF MS. Antibiotic Susceptibility Testing was performed by both Vitek 2 and Kirby bauer disc diffusion method according to CLSI standards for streptococcus spp. Its role as a human pathogen still remains only partially known because of the trouble involved in identification and the small number of reports pertaining to Globicatella. Furthermore, it has been demonstrated that Globicatella spp. are commensal organisms in humans which makes it even more difficult to eatablish it as a cause of disease.

Spontaneous brain abscess formation: challenge of a shifting pathogen spectrum over the last 21 years – a single center experience

BackgroundSpontaneous intracerebral abscess formation is a rare condition presenting with a disabling sequela. The origin of infection can either be primary or secondary to an infection at another location. The site of primary infection - due to the proximity, often the oral cavity, the sinuses, and the orbit - determines the causative pathogens. Treatment often combines surgical and antimicrobial therapies. To determine the microbiology and respective changes and treatment outcome, we performed this retrospective monocentric cohort study of patients requiring surgical treatment of brain abscesses.MethodsPatients undergoing surgical treatment of a primary intracranial abscess between January 2000 and January 2021 in the Department of Neurosurgery, Freiburg University Hospital were included. Demographic, clinical and imaging data were extracted from patients’ medical records and databases. Treatment approaches were also analyzed, and surgical therapy and antibiotic therapy were reported. Outcome was assessed by the modified Rankin score (mRS) and was dichotomized into good (mRS 0–3) and poor (mRS 4–6) outcome.ResultsWe included 65 patients with spontaneous intracerebral abscess that were treated with neurosurgical intervention at our institution. Analysis of the causative pathogens showed an increasing dominance of rare pathogens such as fungi, parasites, mycobacteria and anaerobes. Outcome measured by the mRS was similar from 2005 to 2021.ConclusionsThe pathogen spectrum of spontaneous intracerebral abscess at our institution is shifting with rarer pathogens being increasingly detected. This retrospective analysis highlights the need for microbiological diagnosis and of combined surgical and antibiological treatment.

Prevalence and Antibiotic Resistance of Streptococcus agalactiae in Women of Childbearing Age Presenting Urinary Tract Infections from Western Romania.

Urinary tract infections (UTIs) are a common bacterial infection in women of childbearing age. Streptococcus agalactiae (Group B Streptococcus-GBS), a rare causative pathogen of UTIs in this population, is particularly important due to the potential risk during pregnancy, when it can lead to life-threatening neonatal infections. The current study analyzed 17,273 urine samples collected from consecutive women aged 18-45 years from Arad County, Western Romania. A total of 2772 samples tested positive for UTIs. In 130 cases, GBS was identified as the causative agent. Univariate logistic regression analysis revealed that women aged 25-34 years were more likely to test positive for GBS than those aged 18-24 years (cOR = 1.91, 95% CI: 1.07-3.43, p = 0.03). Antibiotic sensitivity testing revealed that all GBS strains were fully sensitive to penicillin, ampicillin, and vancomycin. High resistance was observed for clindamycin (77.34%) and tetracycline (88.46%). While GBS was found to be a rare pathogen in UTIs, our results underscore the importance of monitoring GBS in women of childbearing age, especially due to its risks during pregnancy, and emphasize the need for appropriate antibiotic management.

Non-Pneuomophila Legionnaires' Disease in Cancer Patients

Abstract Non-pneumophila Legionella species are rare atypical bacterial pathogens that are responsible for a minority of Legionnaires' disease cases. Compared to Legionella pneumophila, they are more likely to infect immunosuppressed patients, such as those undergoing treatment for hematological cancers. This paper describes 3 cases of cancer patients who were effectively treated for pneumonia caused by non-pneumophila species, definitively identified via culture or microbial cell-free DNA (mcfDNA) analysis. This paper also compiles a list of other reported cases of cancer patients diagnosed with non-pneumophila Legionnaires' disease. Although diagnosis of pneumonia by a non-pneumophila Legionella species is challenging with currently available techniques, recommended antibiotic regimens are well established in the literature. Although they statistically appear to be uncommon pathogens, non-pneumophila Legionella species should be considered as possible causes when treating immunosuppressed patients with unspecified pneumonia.

Multiple skin abscesses due to Nocardia neocaledoniensis: a case report and literature review

N. neocaledoniensis is a very rare infectious pathogen that causes human disease, particularly in immunocompromised individuals. In this case report, we describe the successful diagnosis of N. neocaledoniensis in a patient confirmed by mNGS and the treatment of multiple skin abscesses due to N. neocaledoniensis infection. mNGS is an important diagnostic method complementary to routine bacterial culture and identification methods, especially for rare, novel, co-infected pathogens, and pathogens that are difficult to culture. This report may provide a reference for the clinical treatment and diagnosis of N. neocaledoniensis infection in humans.

Psychrobacter sanguinis infection in a pediatric patient with craniopharyngioma identified in a blood culture by 16S rRNA sequencing

AbstractPsychrobacter species are gram‐negative bacteria in the Moraxellaceae family. These bacteria are considered rare opportunistic human pathogens, and the infection sites include blood, cerebral spinal fluid, wounds, urine, the ears, and the eyes. Few cases of human infection by these species have been described previously. We report a case of a 10‐year‐old boy with postneurosurgical bacteremia due to Psychrobacter sanguinis infection. This infection was difficult to identify using routine biochemical phenotypical tests. Sequencing of 16S rRNA was performed to identify this pathogen. The patient was successfully treated with antibiotics. In conclusion, P. sanguinis infections are rare but should be considered when cultures remain negative for common pathogens.

Non-Neoformans Cryptococcal Infections in the Post-Coronavirus Disease-19 (COVID-19) Era: Are We Ready to Face the Emerging Challenge?

AbstractCoronaviruses are a large group of viruses that infect animals as well as humans, while it is also suggested that, rarely, coronaviruses that infect animals can evolve and infect humans. Current evidence suggests that severe acute respiratory syndrome (SARS) coronavirus-2 leads to coronavirus disease-19 (COVID-19), the respiratory illness responsible for COVID-19 pandemic, while it has a zoonotic origin, closely related to the bat-origin SARS-like coronavirus. Also, as per the current knowledge, the disease may induce significant and persistent lymphopenia which in turn may increase the risk for various opportunistic infections. Cryptococcus laurentii is one such rare, but serious fungal infection which has been reported in post-COVID-19 disease and is a rising cause of concern since it can turn out to be fatal. The infection is caused by a non-neoformans rare human pathogen. The present case report describes the case of a 45-years old male patient who reported to the Outpatient Department (OPD) for a routine dental complaint with a grossly destructed tooth in left lower back tooth region due to extensive carious involvement, while, simultaneously, presenting with fever since 5 days in the post-COVID-19 phase, and was later diagnosed as being positive for C. laurentii infection on urine culture sensitivity test.

Streptococcus salivarius pneumonia-associated pneumomediastinum: a case report and literature review

BackgroundStreptococcus salivarius is an opportunistic pathogen, and there have been no reported cases of Streptococcus salivarius pneumonia to date. Pneumomediastinum is usually secondary to tracheal or esophageal injury and is very rare as a complication of pneumonia. We report a case of Streptococcus salivarius pneumonia complicated by pneumomediastinum, aiming to enhance clinicians’ awareness of rare pathogens and uncommon complications in pneumonia.Case presentationThe patient, a 36-year-old male, presented with a persistent cough and sputum production for one week, accompanied by a sore throat that had developed just one day prior. Chest computed tomography (CT) disclosed pneumomediastinum alongside obstructive atelectasis in the left lower lobe. Streptococcus salivarius infection was conclusively identified through bronchoalveolar lavage metagenomic next-generation sequencing (mNGS), as well as smear and culture analyses. The patient was administered intravenous amoxicillin-clavulanate potassium for a duration of seven days as part of the anti-infection regimen. Given the stability of the patient’s respiratory and circulatory systems, a tube drainage procedure was deemed unnecessary. Post-treatment, the patient’s clinical symptoms notably improved. A subsequent chest CT scan revealed the re-expansion of the left lower lung and near-complete resolution of pneumomediastinum.ConclusionThere are numerous pathogens that can cause pneumonia. While focusing on common pathogens, it is important not to overlook rare ones. When considering infections from rare pathogens, it is recommended to promptly perform a bronchoscopy and submit bronchoalveolar lavage fluid for mNGS to improve pathogen detection rates. During the diagnosis and treatment of pneumonia, it is crucial to be vigilant for rare complications. When a patient presents with symptoms such as dyspnea or subcutaneous emphysema, it is advisable to immediately perform a chest CT scan to rule out pneumomediastinum.

Streptococcus equi Subspecies zooepidemicus Endocarditis and Meningitis in a 62-Year-Old Horse Rider Patient: A Case Report and Literature Review.

The present article presents a case report and literature review concerning the Streptococcus equi subspecies zooepidemicus (SEZ), a rare zoonotic pathogen in humans. The case involves a 62-year-old man with no prior heart disease, presenting with endocarditis, pneumonia, and meningitis following close contact with a horse. The patient underwent urgent aortic valve replacement due to severe valvular damage caused by the infection. Blood and cerebrospinal fluid cultures confirmed the presence of SEZ, and the patient was treated with a combination of antibiotics, followed by a successful step-down to oral therapy using linezolid. A review of 25 additional Streptococcus equi endocarditis cases highlights the rarity of the condition, its association with animal contact, and its tendency to cause multi-site infections, such as pneumonia and meningitis. Early diagnosis, appropriate antibiotic therapy, and, in severe cases, surgical intervention are critical for a favorable outcome. This report emphasizes the importance of recognizing zoonotic infections in at-risk populations and the potential need for public health surveillance in these scenarios.

NONTYPHOIDAL SALMONELLA OSTEOMYELITIS IN IMMUNOCOMPETENT CHILDREN: REPORT OF TWO CASES AND LITERATURE REVIEW.

Salmonella is a rare causative pathogen of osteomyelitis and is commonly detected in patients with sickle cell disease. We described 2 consecutive cases of nontyphoidal Salmonella osteomyelitis identified in immunocompetent children. It is evident that even children without apparent risk factors for immune dysfunctions can be affected, so maintaining clinical suspicion is crucial for early diagnosis and prompt treatment.

Lock, stock, and Leuconostoc: an unusual presentation of a rare pathogen

Leuconostoc mesenteroides is a Gram-positive bacterium in the Lactobacillaceae family. This species is rarely encountered clinically and in the past was regarded as a contaminant when cultured. Recently it is being recognized as a pathogen responsible for opportunistic infections in immunocompromised patients. Compared to other Gram-positive cocci, Leuconostoc spp. carry intrinsic resistance to vancomycin. It is not common for clinical microbiology laboratories to isolate this organism and instead incorrectly report enterococcus and streptococcus organisms. Here, we present a case of bacteremia resulting in febrile illness and pneumonia in an 81-year-old woman with a history of rheumatoid arthritis and a notable lapse between immunomodulator therapy exposure. She was successfully treated when this organism was identified, and her antibiotic therapy was switched from vancomycin to ampicillin-sulbactam. This case highlights the importance of considering L. mesenteroides as a source of infection in patients predisposed to an immunocompromised state despite this organism’s being a rare pathogen. Keywords: Leuconostoc mesenteroides, rheumatoid arthritis, immunomodulators; vancomycin resistance

Trichomycosis Axillaris.

We report a case of trichomycosis axillaris caused by Corynebacterium glaucum, a rare clinical pathogen.

Fatal course of afulminant gas gangrene of the right hemithorax

The full clinical picture of agas gangrene infection is an absolute rarity. The mechanism of development can be either traumatic or spontaneous (e.g., hematogenous seeding in occult colon carcinoma). In particular, the rare pathogen Clostridium septicum appears to be associated with spontaneously occurring gas gangrene. Diabetes mellitus is asignificant risk factor. The mortality rate of the disease is around 50%, even with maximum therapeutic efforts, and the course of the disease is fulminant in the majority of cases. Initial symptoms are unspecific and make early diagnosis difficult. Treatment consists of high-dose antibiotics in combination with radical surgical debridement and, if necessary, supplementary hyperbaric oxygen therapy.

Vision Loss, Deafness, and Ataxia Complicating Bacterial Meningitis: A Rare Pathogen.

Vision Loss, Deafness, and Ataxia Complicating Bacterial Meningitis: A Rare Pathogen.

Trichophyton soudanense, Trichophyton violaceum, and Trichophyton tonsurans in Munich: Travel- and Migration-Related Cutaneous Fungal Infections

Introduction: Trichophyton soudanense, Trichophyton violaceum, and Trichophyton tonsurans are considered rare pathogens in Germany. They are presumed to infect people from Germany when they are traveling to tropical and subtropical areas. The incidence and the mode of infection with these three fungal pathogens in Munich were investigated to assess their significance for clinical practice. Methods: This monocentric study was conducted at a large European academic dermatology department in Munich from January 1, 2011, till August 30, 2020. We performed a retrospective analysis of medical data of all out- and inpatients presenting at our hospital with a suspected cutaneous fungal infection. Results: A total of 87,229 swabs were collected from 48,916 patients; 11,513 (13.2%) cultures confirmed a fungal infection. One of the three aforementioned dermatophytes was detected in 247 (2.1%) samples. The average patient age was 15.5 years (0–84 years, SD: 15.6) at the time of infection. T. tonsurans was the confirmed pathogen in 137 (55.5%) samples with increasing frequency over time. T. tonsurans spread in 11 cases through close contact with humans (kindergarten, martial arts, accommodation for asylum seekers). T. violaceum was detected in 88 (35.6%) samples with a peak in 2016 and 2017. T. soudanense was detected in 22 (8.9%) samples. A total of 46.7% of all tinea capitis cases were caused by one of these pathogens. Conclusion: In case of tinea capitis, a travel history should be performed and rare fungal infections should be considered in the differential diagnosis.

Augmented pathogen detection in brain abscess using metagenomic next-generation sequencing: a retrospective cohort study.

Brain abscess is a severe infection characterized by the accumulation of pus within the brain parenchyma. Accurate identification of the causative pathogens is crucial for effective treatment and improved patient outcomes. This 10-year retrospective, single-center study aimed to compare the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) in brain abscess. We reviewed 612 patients diagnosed with brain abscess and identified 174 cases with confirmed etiology. The median age was 52 years, with 69.5% males. Culture tests predominately identified gram-positive bacteria, particularly Streptococcus spp. Gram-negative bacteria, including Klebsiella spp., were also detected. However, mNGS revealed a more diverse pathogen spectrum, focusing on anaerobes (e.g., Fusobacterium spp., Parvimonas spp., Porphyromonas spp., Prevotella spp., and Tannerella spp.). mNGS exhibited significantly higher overall pathogen-positive rates in pus samples (85.0% vs 50.0%, P = 0.0181) and CSF samples (84.2% vs 7.9%, P < 0.0001) compared to culture. Furthermore, the detection rates for anaerobes displayed a notable disparity, with mNGS yielding significantly higher positive detections in both pus samples (50.0% vs 10%, P = 0.0058) and CSF samples (18.4% vs 0%, P = 0.0115) when compared to culture methods. The assistance of mNGS in pathogen detection, particularly anaerobes in brain abscess, was evident in our findings. mNGS demonstrated the ability to identify rare and fastidious pathogens, even in culture-negative cases. These results emphasize the clinical value of mNGS as a supplement for brain abscess, enabling more comprehensive and accurate pathogen identification.IMPORTANCEThe accurate identification of pathogens causing brain abscess is crucial for effective treatment and improved patient outcomes. In this 10-year retrospective study, the detection performance of conventional culture methods and metagenomic next-generation sequencing (mNGS) was compared. The study analyzed 612 patients with brain abscess and confirmed etiology in 174 cases. The results showed that culture tests predominantly identified gram-positive bacteria, while mNGS unveiled a broader diverse pathogen spectrum, particularly anaerobes. The mNGS method exhibited significantly higher overall rates of pathogen positivity both in pus and cerebrospinal fluid (CSF) samples, surpassing the culture methods. Notably, mNGS detected a significantly higher number of anaerobes in both pus and CSF samples compared to culture methods. These findings underscore the clinical value of mNGS as a supplement for brain abscess diagnosis, enabling more comprehensive and accurate pathogen identification, particularly for rare and fastidious pathogens that evade detection by conventional culture methods.

Clostridium Limosum Lung Abscess in a Heart Transplant Recipient: A Rare Case Report

We report a case of Clostridium limosum lung abscess in a 71-year-old male heart transplant recipient. The patient presented with a week-long history of productive cough and confusion. His medical history included nonischemic dilated cardiomyopathy, chronic renal disease, and past Klebsiella pneumoniae bacteremia, among others. Imaging revealed a thick-walled cavitary lesion in the right lung, initially suspected to be a pulmonary abscess. Lung biopsy culture confirmed the presence of Clostridium limosum, a rare pathogen in humans, typically associated with farm animals. Following six weeks of Piperacillin/Tazobactam treatment, the patient showed significant clinical improvement. This case emphasizes the importance of considering zoonotic pathogens in immunosuppressed patients, especially those with occupational exposure.

A Fatal Co-infections of Aspergillus latus and Pneumocystis jirovecii in COVID-19 Pneumonia Patient: Case Report

Introduction: For coronavirus disease 2019 (COVID-19) positive patients, co-infection with fungi has previously been reported. Owing to non-specific clinical manifestations and radiographic evidence, it is difficult to distinguish fungal infection from COVID-19 alone, resulting in delayed diagnosis and lack of appropriate treatment. Aspergillus latus infection, a newly rare species with life-threatening characteristics, requires rapid detection with accurate diagnosis to reduce mortality. However, there is little literature that provides a reference for a better understanding of this rare pathogen and guides medical practitioners in choosing the right diagnostics and therapies. Case Presentation: We reported a 67-year-old female complaining of fever, cough, and chest tightness, who had previously been hospitalized for a week due to initial COVID-19 pneumonia. On admission, clinical manifestations and radiological evidence were consistent with COVID-19 pneumonia, and there was no obvious improvement after anti-infective therapy. In terms of etiology for the patient, Galactomannan test was positive for Aspergillus genus, and Metagenomic next-generation sequencing further determined co-infections of A. latus and Pneumocystis jirovecii. Subsequently, isolation of A. latus was obtained through microbial culture. Despite targeted antifungal therapy, no clinical improvement was observed, possibly due to delayed diagnosis and treatment. Finally, the patient died of respiratory failure. Conclusions: This case report demonstrated that metagenomic next-generation sequencing is a fast, unbiased, culture-free approach that can increase the detection of rare pathogens, helping clinicians improve the accuracy of clinical diagnosis and take therapeutic action as quickly as possible. Clinicians should be aware of the risk of COVID-19-associated pulmonary Aspergillosis in COVID-19 patients, and we hope to optimize diagnosis and improve outcomes of COVID-19-associated pulmonary Aspergillosis.

A Case Report of Cellulitis Caused by Leclercia adecarboxylata in a Thai Boy: A Common Infection From a Rare Pathogen

A Case Report of Cellulitis Caused by Leclercia adecarboxylata in a Thai Boy: A Common Infection From a Rare Pathogen