Seroepidemiology and Carriage of Diphtheria in Epidemic-Prone Area and Implications for Vaccination Policy, Vietnam.

In 2019, a community-based, cross-sectional carriage survey and a seroprevalence survey of 1,216 persons 1-55 years of age were conducted in rural Vietnam to investigate the mechanism of diphtheria outbreaks. Seroprevalence was further compared with that of an urban area that had no cases reported for the past decade. Carriage prevalence was 1.4%. The highest prevalence, 4.5%, was observed for children 1-5 years of age. Twenty-seven asymptomatic Coerynebacterium diphtheriae carriers were identified; 9 carriers had tox gene-bearing strains, and 3 had nontoxigenic tox gene-bearing strains. Child malnutrition was associated with low levels of diphtheria toxoid IgG, which might have subsequently increased child carriage prevalence. Different immunity patterns in the 2 populations suggested that the low immunity among children caused by low vaccination coverage increased transmission, resulting in symptomatic infections at school-going age, when vaccine-induced immunity waned most. A school-entry booster dose and improved infant vaccination coverage are recommended to control transmissions.

Clinical Profile of Monomicrobial Corynebacterium Hip and Knee Periprosthetic Joint Infections.

Background: Corynebacterium periprosthetic joint infection (PJI) is a poorly described infectious syndrome. Prior studies included cases of polymicrobial infections. This series describes the clinical characteristics, management, and outcomes of monomicrobial Corynebacterium PJI. Methods: We queried the Mayo Clinic Total Joint Registry for cases of monomicrobial Corynebacterium knee and hip PJI in adults (age ≥18 years) between 2010 and 2019. Results: A total of 20 (1%) out of 2067 PJI cases met our inclusion criteria. Most were males (55%), and the median age was 64 years. Seventy percent had chronic symptoms (>4 weeks). PJI was delayed to late (>3 months postimplantation) in 90%. Three species were identified: C. striatum (70%), C. jeikeium (20%), and C. amycolatum (10%). All tested isolates were susceptible to vancomycin (100%) and linezolid (100%), and most had a minimum inhibitory concentration ≤0.06 mcg/mL to daptomycin (75%). Other agents were less reliable, with high resistance to oral agents commonly used for suppression. Nineteen patients were treated: 37% debridement and implant retention (DAIR), 47% 2-stage exchange, and 16% resection without reimplantation. Of these, failure occurred in 29%, 11%, and 0%, respectively. Conclusions: Corynebacterium PJIs pose a therapeutic challenge due to limited antimicrobial armamentarium and undefined optimal surgical intervention. Vancomycin and linezolid remain the most reliable agents for treatment. DAIR may be attempted for acute PJI, but verification of durable chronic suppression options will be critical for this approach.

Comparative study of bacterial flora in bronchoalveolar lavage fluid of pneumonia patients based on their pneumonia subtypes and comorbidities using 16S ribosomal RNA gene analysis.

INTRODUCTION: The culture method is the gold standard for identifying pathogenic bacteria in patients with pneumonia but often does not reflect the exact bacterial flora in pulmonary lesions of pneumonia, partly owing to easiness or difficulties in culturing certain bacterial species. We aimed to evaluate bacterial flora in bronchoalveolar lavage fluid (BALF) samples directly obtained from pneumonia lesions using 16S ribosomal RNA (rRNA) gene analysis to compare the results of the BALF culture method in each category of pneumonia. METHODS: Bacterial florae were detected by a combination of the culture method, and the clone library method using the 16S rRNA gene sequencing in BALF directly obtained from pneumonia lesions in pneumonia patients from April 2010 to March 2020 at the University of Occupational and Environmental Health, Japan, and affiliated hospitals. Clinical information of these patients was also collected, and lung microbiome was evaluated for each pneumonia category. RESULTS: Among 294 pneumonia patients (120 with community-acquired pneumonia (CAP), 101 with healthcare-associated pneumonia (HCAP), and 73 with hospital-acquired pneumonia (HAP)), significantly higher percentages of obligate anaerobes were detected in CAP than in HCAP and HAP patients by the clone library method. Corynebacterium species were significantly highly detected in HAP patients and patients with cerebrovascular diseases than in patients without, and Streptococcus pneumoniae was frequently detected in patients with diabetes mellitus. CONCLUSION: Obligate anaerobes may be underestimated in patients with CAP. Corynebacterium species should be regarded as the causative bacteria for pneumonia in patients with HAP and cerebrovascular diseases.

Bacteria Associated with Granulomatous Lobular Mastitis and the Potential for Personalized Therapy.

Granulomatous lobular mastitis (GLM), also known as idiopathic granulomatous mastitis (IGM), is a chronic inflammatory lesion of the breast. The incidence of GLM has been increasing in recent years, especially among young women. The etiologies of GLM have not been fully elucidated but are associated with autoimmunity and bacterial infection. Bacteria, especially Corynebacterium species, play important roles in GLM. In this article, we review research progress regarding the bacteriology of GLM attained with the application of several new high-throughput detection techniques. Accurate detection might be important for deepening our understanding of the pathogenesis of GLM and hold promise for personalized GLM therapy.

Clinical characteristics and drug susceptibility patterns of Corynebacterium species in bacteremic patients with hematological disorders.

The aim of this study was to clarify the clinical and microbiological characteristics of Corynebacterium bacteremia in hematological patients. We retrospectively reviewed the medical records of patients with Corynebacterium bacteremia from April 2013 to June 2018. The causative Corynebacterium species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Drug susceptibility tests were performed using the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. In total, 147 cases of Corynebacterium bacteremia were identified during the study period. Corynebacterium striatum was the most frequent pathogen. Catheter-related bloodstream infection was diagnosed in 19.7% of all patients, and moderate/severe oral or severe gastrointestinal mucosal impairment was detected in 19.7%. Polymicrobial infection was found in about 20% of cases, with Enterococcus faecium being the most frequent isolate. The overall 30-day mortality was 34.7% (51/147). Multivariate analysis showed that E. faecium co-infection (odds ratio (OR) 9.3; 95% confidence interval (CI) 2.1-40), systemic corticosteroids (OR 3.6; 95% CI 1.4-8.9), other immunosuppressive drugs (OR 0.32; 95% CI 0.13-0.76), and a Pitt bacteremia score ≥4 (OR 12; 95% CI 3.9-40) were significant risk factors for overall 30-day mortality. The drug susceptibility rates for beta-lactam antimicrobial agents were quite low. All isolates were susceptible to glycopeptides and linezolid. However, some C. striatum isolates were resistant to daptomycin. Corynebacterium bacteremia can occur in the presence of several types of mucosal impairment. Our drug susceptibility data indicate that Corynebacterium bacteremia in hematological patients could be treated by glycopeptides or linezolid.

Direct detection of Corynebacterium striatum, Corynebacterium propinquum, and Corynebacterium simulans in sputum samples by high-resolution melt curve analysis.

BACKGROUND: Pulmonary infections caused by non-diphtheriae corynebacteria are increasing. However, rapid identification of Corynebacterium species poses a challenge due to the low genetic variation within the genus. METHODS: Three reference strains and 99 clinical isolates were used in this study. A qPCR followed by high-resolution melting (HRM) targeting ssrA was performed to simultaneously identify C. striatum, C. propinquum and C. simulans. To further evaluate this assay's performance, 88 clinical sputum samples were tested by HRM and the detection results were compared with those of the traditional culture method and multiple cross-displacement amplification (MCDA) assay. RESULTS: The melting curve produced by a pair of universal primers generated species-specific HRM curve profiles and could distinguish the three target species from other related bacteria. The limit of detection of HRM assay for DNA from the three purified Corynebacterium species was 100 fg. Compared with the culture method, HRM detected 22 additional positive specimens, representing a 23.9% relative increase in detection rate. The HRM assay had 98.4% (95% confidence interval [CI], 90.5-99.9%) sensitivity and 100% (95% CI, 82.8-100%) specificity. Additionally, 95.5% concordance between HRM and MCDA (κ = 0.89 [95% CI, 0.79-0.99]) was noted. CONCLUSIONS: The HRM assay was a simple, rapid, sensitive, and specific diagnostic tool for detecting C. striatum, C. propinquum, and C. simulans, with the potential to contribute to early diagnosis, epidemiological surveillance, and rapid response to outbreak.

Reduction in the processing of possible blood culture contaminants by the application of a selection criterion.

Possible blood culture (BC) contaminants are generally considered to be skin flora species including coagulase-negative Staphylococci (CNS), Corynebacterium species, Micrococcus species, Bacillus species and Propionibacterium acnes. Prior to October 1, 2016 all possible BC contaminants were fully processed (identification, susceptibility testing) in our laboratory. In order to reduce the laboratory workload from October 1, 2016 a possible contaminant was only processed if it was present in more than one BC pair drawn from the same patient within the same day. The two-year study period was divided in two periods namely period A from January 1, 2016 to September 30, 2016 (first 9 months) and period B from October 1, 2016 to December 31, 2017 (last 15 months). A series of indices (INs) were calculated including among others the Working Rate IN (WR) defined as the total isolates divided to the total number of BCs submitted per month and the CNS Rate (CNSR) defined as the total number of CNS processed divided to the total number of BCs submitted per month. A 23.08% reduction in the CNSR was noted (from 3.51% in period A to 2.70% in period B) whereas the overall WR was reduced from 7.19% in period A to 6.84% in period B. Furthermore, the total number of contaminants processed per month divided to the total number of isolates processed per month was reduced from 54.50% in period A to 42.41% in period B. The reduction in the INs recorded is of great value since it was achieved by the implementation of a simple criterion easily applicable and without any cost.

Infection and colonization by Corynebacterium pseudodiphtheriticum: a 9-year observational study in a university central hospital.

Despite constituting part of the human commensal flora, Corynebacterium pseudodiphtheriticum has been recognized as a potentially infectious agent, most frequently in immunocompromised patients or individuals with other morbidity factors, but significant association to comorbid states remains unproven. This study's purpose was to assess clinical significance, risk factors for infection and antimicrobial susceptibility of C. pseudodiphtheriticum isolates. A retrospective observational study was conducted. Relevance of isolation was determined by clinical, laboratory, and imaging criteria. Forty-nine isolates occurred in 47 episodes. Colonization was assumed in 12% and infection in 78%, of which 51% were nosocomial. Patients with infection were older, with male predominance; both age and gender were statistically significant (p < 0.05) between infection and colonization groups. Although dyslipidemia (58%), arterial hypertension (58%), invasive procedures (56%), and chronic lung disease (50%) were prevalent in the infection group, no comorbidity was a significant risk factor for infection compared with colonization. Charlson comorbidity index showed no statistically difference between groups. Mortality rate was 14% in infection. Respiratory samples were the main isolation product; all tested strains were susceptible to amoxicillin/clavulanate and vancomycin. Resistant strains were observed for clindamycin (77%) and erythromycin (48%). C. pseudodiphtheriticum isolation was associated with infection in most cases. Despite the high prevalence of comorbidities and invasive procedures, no factors other than age and gender were significantly associated with infection. Although C. pseudodiphtheriticum may constitute a contaminant or colonizer in clinical samples, positive cultures in patients with signs and symptoms consistent with infection should not be neglected.

Retrospective evaluation of the clinical characteristics associated with Corynebacterium species bacteremia.

OBJECTIVES: Corynebacterium spp. are becoming recognized as pathogens that potentially cause various infections. We aimed to evaluate the clinical characteristics associated with Corynebacterium spp. bacteremia. PATIENTS AND METHODS: We retrospectively reviewed the medical records of all adult patients who had positive blood cultures for Corynebacterium spp. in a single university hospital between January 2014 and December 2016. Patients were divided into a bacteremia group and a contamination group based on microbiological test results and clinical characteristics. Patients' characteristics, antimicrobial susceptibility of isolated species, antimicrobials administered, and patient outcomes were evaluated. RESULTS: Corynebacterium spp. were isolated from blood samples of 63 patients; Corynebacterium striatum was the predominant isolate. Twenty-eight patients were determined to have bacteremia. Younger age (p=0.023), shorter time to positivity (p=0.006), longer hospital stay (p=0.009), and presence of an indwelling vascular catheter (p=0.002) were observed more often in the bacteremia group compared to the contamination group. The source of infection in most patients with bacteremia was an intravenous catheter. All tested strains were susceptible to vancomycin. Four of the 27 patients with bacteremia died, despite administration of appropriate antimicrobial therapy. CONCLUSIONS: We found that younger age, shorter time to positivity, and presence of an indwelling catheter were related to bacteremia caused by Corynebacterium spp. Appropriate antimicrobials should be administered once Corynebacterium spp. are isolated from the blood and bacteremia is suspected.

Retrospective evaluation of the clinical characteristics associated with Corynebacterium species bacteremia

ABSTRACT Objectives: Corynebacterium spp. are becoming recognized as pathogens that potentially cause various infections. We aimed to evaluate the clinical characteristics associated with Corynebacterium spp. bacteremia. Patients and methods: We retrospectively reviewed the medical records of all adult patients who had positive blood cultures for Corynebacterium spp. in a single university hospital between January 2014 and December 2016. Patients were divided into a bacteremia group and a contamination group based on microbiological test results and clinical characteristics. Patients' characteristics, antimicrobial susceptibility of isolated species, antimicrobials administered, and patient outcomes were evaluated. Results: Corynebacterium spp. were isolated from blood samples of 63 patients; Corynebacterium striatum was the predominant isolate. Twenty-eight patients were determined to have bacteremia. Younger age (p = 0.023), shorter time to positivity (p = 0.006), longer hospital stay (p = 0.009), and presence of an indwelling vascular catheter (p = 0.002) were observed more often in the bacteremia group compared to the contamination group. The source of infection in most patients with bacteremia was an intravenous catheter. All tested strains were susceptible to vancomycin. Four of the 27 patients with bacteremia died, despite administration of appropriate antimicrobial therapy. Conclusions: We found that younger age, shorter time to positivity, and presence of an indwelling catheter were related to bacteremia caused by Corynebacterium spp. Appropriate antimicrobials should be administered once Corynebacterium spp. are isolated from the blood and bacteremia is suspected.

Corynebacterium species nasopharyngeal carriage in asymptomatic individuals aged ≥ 65 years in Germany.

PURPOSE: The prevalence of protective anti-diphtheria toxin antibodies decreases with age. Therefore, the elderly might serve as reservoir for potentially toxigenic Corynebacterium (C.) species (C. diphtheriae, C. ulcerans, and C. pseudotuberculosis). This study aimed to examine the colonization rate of the nasopharynx with corynebacteria of individuals aged 65 years and older. METHODS: In the period from October 2012 to June 2013, nasal and throat swabs were taken from 714 asymptomatic subjects aged 65-106 years (average age 77.2) at three regions in Germany and investigated for Corynebacterium species. RESULTS: A total of 402 strains of Corynebacterium species were isolated from 388 out of 714 asymptomatic subjects (carriage rate 54.3%). The carriage rate was significantly higher in study participants living in retirement homes (68.4%) compared to those living autonomously at home (51.1%). Strains were isolated mostly from the nose (99%). Corynebacterium accolens was the most often isolated species (39.8%), followed by C. propinquum (24.1%), C. pseudodiphtheriticum (19.4%), and C. tuberculostearicum (10.2%). No C. diphtheriae, C. ulcerans, and C. pseudotuberculosis strains were isolated. A subsample of 74 subjects was tested serologically for anti-diphtheria antibodies. Protective anti-diphtheria toxin antibodies were found in 29.7% of the subjects; 70.3% showed no protective immunity. CONCLUSIONS: These results suggest that carriage of potentially toxigenic corynebacteria is very rare among people aged 65 and older in Germany. However, the low prevalence of protective anti-diphtheria toxin antibodies might pose a risk for acquiring diphtheria especially for the elderly.

Corynebacterium species causing breast abscesses among patients attending a tertiary care hospital in Chennai, South India.

BACKGROUND: Corynebacterium species other than Corynebacterium diphtheriae were mostly considered contaminants in the past, but there are reports of their association with wide variety of human infections lately. In this study, we look into Corynebacterium species isolated from breast abscess patients and assess their antimicrobial susceptibility pattern and treatment outcomes. MATERIAL AND METHODS: Pus samples from suspected breast abscess cases were examined from October 2014 to September 2015. Growth of Gram-positive bacilli morphologically resembling Corynebacterium species were identified by matrix-assisted laser desorption/ionization- time of flight mass spectrometry identifications generated by the Vitek MS system (bioMérieux, France) (MALDI-TOF Vitek MS system) and antimicrobial susceptibility was done. RESULTS: Corynebacterium species were isolated from 10 female breast abscess patients with median age of 36 years (range 25-59 years). Out of the 10 isolates four isolates were identified as C. kroppenstedtii; one isolate as C. striatum and five isolates were identified as C. amycolatum/C.xerosis. Out of four isolates of C .kroppenstedtii, two isolates were resistant to cotrimoxazole and one C. striatum isolate was resistant to penicillin, ampicillin, cotrimoxazole and clindamycin. Of the five isolates identified as C amycolatum/C xerosis, all were sensitive to vancomycin and linezolid but resistant to clindamycin. All the patients were treated with incision, drainage and antibiotics based on the sensitivity pattern; eight were cured and two patients did not come for follow-up. CONCLUSIONS: Corynebacterium species should be considered one of the causative agents of breast abscess and a varied susceptibility profile amongst the different species makes susceptibility testing important. Identification by MALDI-TOF Vitek MS system may not differentiate between C. amycolatum and C. xerosis.

Practical Utility and Accuracy of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Identification of Corynebacterium Species and Other Medically Relevant Coryneform-Like Bacteria.

BACKGROUND: Corynebacterium species and gram-positive coryneform-like bacteria (coryneforms) are increasingly reported causes of opportunistic infections in immunocompromised patients. Biochemical identification methods for these bacteria are often inaccurate. We evaluated matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) for routine Corynebacterium and coryneform identification. METHODS: A total of 286 Corynebacterium species and coryneforms recovered from patients were identified by MALDI-TOF MS analysis using the Bruker Microflex instrument, Biotyper software version 3.0, and database version 3.1.66 (Bruker Daltonics, Billerica, MA) following formic acid-based, direct on-plate extraction. The spectral cutoff scores used for interpretation were 2.0 or more for species-level identification and 1.7 or more for genus level. Scores lower than 1.7 were considered as no reliable identification. The results were compared with API Coryne (bioMérieux, Durham, NC) and sequencing of 16S ribosomal RNA genes. RESULTS: Of the 231 Corynebacterium (19 species), 99.6% were correctly identified to the genus level and 88.7% to the species level. Of the 55 coryneforms (14 genera), 90.9% were correctly identified to the genus level and 67.3% to the species level. API Coryne was able to identify 89.2% of Corynebacterium species (species level) and 63.6% of coryneforms (genus level). CONCLUSIONS: Rapid on-plate testing yielded identification of more Corynebacterium species and related bacteria than biochemical methods.

Clinical relevance of Corynebacterium pseudodiphtheriticum in lower respiratory tract specimens.

BACKGROUND: Corynebacterium pseudodiphtheriticum may be present as commensal flora of the respiratory tract and therefore it may be difficult to assess clinical relevance when it is cultured from lower respiratory tract specimens. Our objective was to determine the clinical relevance of C. pseudodiphtheriticum as a lower respiratory tract pathogen and to define patients at risk of developing lower respiratory tract infections caused by C. pseudodiphtheriticum. METHODS: We retrospectively identified all lower respiratory tract cultures positive for C. pseudodiphtheriticum over a 10-year period and assessed clinical relevance by predefined criteria. RESULTS: Clinical relevance was likely or possible in 86% of patients. Pre-existent comorbidity was present in 86% of patients, mostly underlying cardiac or pulmonary disease. All isolates were susceptible to amoxicillin. CONCLUSION: C. pseudodiphtheriticum should be considered a clinically relevant pathogen when cultured from the lower respiratory tract in symptomatic patients.