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Journal of Case Reports and Images in Infectious Diseases 1, 2018. J Case Rep Images Infect Dis 2018;1:100003Z16EZ2018. www.ijcriinfectiousdiseases.com Zioga et al. 1 Clinically-significant Corynecterium aurimucosum bacteremia: Is it time for a change of perspective? A first documented case and review of the literature Evangelia Anna Maria Zioga, Clara Sala Jofre, Raquel Clivillè Abad, Iolanda Calvet Tort, Virginia Isern Fernández, Lourdes Ferrer Rouscalleda ABSTRACT Introduction: Most Corynebacteria and other gram positive rods have been classically considered contaminants of microbiological samples, however, advances in microbial identification offer a new insight on their pathological significance. In this report, we present a first case of clinically significant bacteremia of urinary origin caused by Corynebacterium aurimucosum and a brief review of the literature. Case Report: Corynebacterium aurimucosum was isolated in both urinary and blood samples of a 94-year old patient with fever and bacteremia. The isolated pathogenic organism was identified in the samples using mass spectometry (MALDI-TOF), and was treated with amoxicillin/clavulanic with clinical improvement and stability at three weeks follow up. This was the first reported case of clinically significant bacteremia caused by this isolate, although infections at different sites have reported. Conclusions: New techniques of microbial identification show Evangelia Anna Maria Zioga 1 , Clara Sala Jofre 1 , Raquel Clivillè Abad 2 , Iolanda Calvet Tort 2 , Virginia Isern Fernán- dez 1 , Lourdes Ferrer Rouscalleda 3 Affiliations: 1 Consultant, Department of Internal Medicine, Hospital Dos de Mayo, Barcelona, Spain; 2 Consultant, Department of Microbiology, Consorci del Laboratori Inter- comarcal de l’Alt Penedès, l’Anoia i el Garraf, Sant Joan Despí, Barcelona, Spain; 3 Chief Consultant, Department of Internal Medicine, Hospital Dos de Mayo, Barcelona, Spain. Corresponding Author: Evangelia Anna Maria Zioga, Hos- pital Dos de Mayo, Carrer del Dos de Maig 301, 08025, Barcelona, Spain; Email: [email protected] Received: 06 September 2018 Accepted: 26 October 2018 Published: 06 December 2018 gaining importance of Corynebacterium spp. in clinically-relevant infections, thus modifying progressively the established spectrum of disease caused by GPRs. Detailed reporting of new cases could contribute to a better understanding of the burden of the disease. Keywords: Aurimucosum, Bacteremia, Corynebacterium, Gram-positive rods How to cite this article Zioga EAM, Jofre CS, Abad RC, Tort IC, Fernández VI, Rouscalleda LF. Clinically-significant Corynecterium aurimucosum bacteremia: Is it time for a change of perspective? A first documented case and review of the literature. J Case Rep Images Infect Dis 2018;1:100003Z16EZ2018. Article ID: 100003Z16EZ2018 ********* doi: 10.5348/100003Z16EZ2018CR INTRODUCTION Corynebacteria are an important part of the commensal flora of the skin and mucous membranes [1]. Except for Corynebacterium diphtheriae, they were once considered contaminants of mucosa, but recent publications in medical bacteriology have established the clinical importance of other corynebacteria species in different types of infections. Microbial identification and strain typing using molecular techniques provides a new insight on the clinical significance of various species of coryneform gram positive rods(GPRs) [2]. CASE REPORT PEER REVIEWED | OPEN ACCESS

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Journal of Case Reports and Images in Infectious Diseases 1, 2018.

J Case Rep Images Infect Dis 2018;1:100003Z16EZ2018. www.ijcriinfectiousdiseases.com

Zioga et al. 1

CASE REPORT OPEN ACCESS

Clinically-significant Corynecterium aurimucosum bacteremia: Is it time for a change of perspective? A first

documented case and review of the literature

Evangelia Anna Maria Zioga, Clara Sala Jofre, Raquel Clivillè Abad, Iolanda Calvet Tort, Virginia Isern Fernández, Lourdes Ferrer Rouscalleda

ABSTRACT

Introduction: Most Corynebacteria and other gram positive rods have been classically considered contaminants of microbiological samples, however, advances in microbial identification offer a new insight on their pathological significance. In this report, we present a first case of clinically significant bacteremia of urinary origin caused by Corynebacterium aurimucosum and a brief review of the literature. Case Report: Corynebacterium aurimucosum was isolated in both urinary and blood samples of a 94-year old patient with fever and bacteremia. The isolated pathogenic organism was identified in the samples using mass spectometry (MALDI-TOF), and was treated with amoxicillin/clavulanic with clinical improvement and stability at three weeks follow up. This was the first reported case of clinically significant bacteremia caused by this isolate, although infections at different sites have reported. Conclusions: New techniques of microbial identification show

Evangelia Anna Maria Zioga1, Clara Sala Jofre1, Raquel Clivillè Abad2, Iolanda Calvet Tort2, Virginia Isern Fernán-dez1, Lourdes Ferrer Rouscalleda3

Affiliations: 1Consultant, Department of Internal Medicine, Hospital Dos de Mayo, Barcelona, Spain; 2Consultant, Department of Microbiology, Consorci del Laboratori Inter-comarcal de l’Alt Penedès, l’Anoia i el Garraf, Sant Joan Despí, Barcelona, Spain; 3Chief Consultant, Department of Internal Medicine, Hospital Dos de Mayo, Barcelona, Spain.Corresponding Author: Evangelia Anna Maria Zioga, Hos-pital Dos de Mayo, Carrer del Dos de Maig 301, 08025, Barcelona, Spain; Email: [email protected]

Received: 06 September 2018Accepted: 26 October 2018Published: 06 December 2018

gaining importance of Corynebacterium spp. in clinically-relevant infections, thus modifying progressively the established spectrum of disease caused by GPRs. Detailed reporting of new cases could contribute to a better understanding of the burden of the disease.

Keywords: Aurimucosum, Bacteremia, Corynebacterium, Gram-positive rods

How to cite this article

Zioga EAM, Jofre CS, Abad RC, Tort IC, Fernández VI, Rouscalleda LF. Clinically-significant Corynecterium aurimucosum bacteremia: Is it time for a change of perspective? A first documented case and review of the literature. J Case Rep Images Infect Dis 2018;1:100003Z16EZ2018.

Article ID: 100003Z16EZ2018

*********

doi: 10.5348/100003Z16EZ2018CR

INTRODUCTION

Corynebacteria are an important part of the commensal flora of the skin and mucous membranes [1]. Except for Corynebacterium diphtheriae, they were once considered contaminants of mucosa, but recent publications in medical bacteriology have established the clinical importance of other corynebacteria species in different types of infections. Microbial identification and strain typing using molecular techniques provides a new insight on the clinical significance of various species of coryneform gram positive rods(GPRs) [2].

CASE REPORT PEER REVIEWED | OPEN ACCESS

Journal of Case Reports and Images in Infectious Diseases 1, 2018.

J Case Rep Images Infect Dis 2018;1:100003Z16EZ2018. www.ijcriinfectiousdiseases.com

Zioga et al. 2

Corynebacterium aurimucosum was taxonomically first described in 2002 as a new species, and isolated cases of urinary tract infections(UTIs) [3], septic abortion [4] and prosthetic joint infections(PJIs) [5, 6] have been published. However, the spectrum of the disease caused by this pathogen has not been established.

Herein, we report a first documented case of clinically relevant bacteremia secondary to a UTI caused by C.aurimucosum.

CASE REPORT

A 94-year-old man was admitted with a four-day history of malaise. He denied headache, seizure, cough, chest or abdominal pain, diarrhea, dysuria or changes in urinary frequency or urgency. The patient could not recall any recent contact with animals. His past medical history included arterial hypertension, dyslipidemia, ischemic heart disease, prostatic benign hyperplasia, occult hepatitis B infection, a proximal femur fracture treated with osteosynthesis with use of a femoral nail two years before and a giant right inguinal hernia. A contralateral inguinal hernia had been previously surgically treated with introduction of a surgical mesh.

On admission, he presented elevated arterial pressure, normal heart rate and fever of 38.6ºC. Physical examination was normal. Laboratory parameters were as follows: leukocyte count 7.7×109/L (neutrophils: 66.5%); Hb 14.7 g/dL; platelet count 168×109/L; creatinine 1.1 mg/dL with a glomerular filtration rate(GFR) of 55ml/min/1.73m2; ions, hepatic and coagulation profile were within normal limits. A chest X-ray showed no alveolar consolidations or pleural effusion and a head CT-scan showed no acute lesions. A urinary sample showed 5 red blood cells per high power field(HPF) and 10–20 white blood cells/HPF. A transabdominal ultrasound for evaluation of the urinary tract showed bladder diverticula and prostatic hyperplasia. Two sets of blood cultures were obtained, and treatment with empiric amoxicillin/clavulanic acid was initiated.

Blood was inoculated in 4 Bact-Alert FN and FA bottles and incubated in the VIRTUO system (bioMérieux, France). The cultures were alarmed positive in approximately 17-19 hours. The two positive aerobic samples were inoculated in chocolate PolyVitex agar, trypcase soy agar and McConkey culture media plates. The anaerobic positive sample was inoculated in the same culture media plus Schaedler agar and were all incubated at 35+-2ºC for 18-24 hours in a 5% CO2 environment. The isolated pathogenic organism was identified using mass spectometry (MALDI-TOF) by Bruker Daltonics and MSP Library MBT6903. A score of 2.175 was obtained and a presumptive identification of C.aurimucosum was made. All material used was by bioMérieux (France). Antimicrobial susceptibility testing was carried out manually in MHF plates with a 0.5 mF and after interpretation by breakpoints described in the EUCAST 8.0.2018, we disposed of the following

antibiogram: Penicilin Resistant (R), Ciprofloxacin R, Moxifloxacin R, Gentamycin Sensible(S), Clindamycin S, Tetracyclin S, Vancomycin S, Linezolid S.

A quantitative urine culture was realized by simple drop culture in CLED agar, incubated at 35+-2ºC during 18 hours. >100.000 of the isolated pathogen grew and was identificated by the same methods used for the blood samples, obtaining a score of 1.907 and a presumptive identification of Corynebacterium aurimucosum. The urine sample antibiogram was as follows, identical to the one from the blood samples. Penicilin R, Ciprofloxacin R, Moxifloxacin R , Gentamycin S, Clindamycin S, Tetracyclin S, Vancomycin S, Linezolid S.

Our patient remained febrile with the initial empiric antibiotic regimen, with an elevation of blood count up to 18,09×109/L (neutrophils, 93%), C-reactive protein of 168 mg/L and GFR deterioration up to 40ml/min/1.73m2. The microbiology results were interpreted as bacteremia secondary to a urinary infection by C.aurimucosum and linezolid 600mg twice per day was administered during a week. An abdominopelvic CT-scan did not describe abscesses or fistulae. Our patient presented clinical and laboratory improvement, with normalization of inflammatory parameters. Two control sets of blood cultures failed to grow any microorganisms after a 5-day incubation period. After completing antibiotic treatment, our patient presented a deterioration of renal function without other signs of active infection. An emergency abdominal ultrasound was performed showing acute urinary retention and was proceeded to permanent bladder catheterization with normalization of the GFR at discharge. A three-week follow up showed clinical stability.

DISCUSSION

Catalase-positive Gram-positive bacilli, commonly called “diphtheroids” or “coryneform” bacteria were historically nearly always dismissed as contaminants when recovered from patients, but there is growing evidence that many species within this classification are opportunistic pathogens [1].

In the past, only C.diphtheriae was thought to be aninfectious agent, but these are now rare given early routine vaccination, with diphtheria-like disease being principally caused by C.ulcerans and rarely C.pseudotuberculosis. Other established pathogens of the Corynobacteria genus include C.urealyticum causing UTIs, C.jeikeium causing systemic infections, and C.kroppenstedtii which has been associated with chronic mastitis [1, 7]. C.striatum is a pathogen at multiple sites [8, 7]. Beyond these examples, potential association between diphtheroids and infections have historically been hindered by the inability to efficiently and accurately identify isolates to the species level, resulting in routine dismissal of results as being of no clinical significance.

However, during the last years, microbial identification and strain typing using molecular techniques has provided

Journal of Case Reports and Images in Infectious Diseases 1, 2018.

J Case Rep Images Infect Dis 2018;1:100003Z16EZ2018. www.ijcriinfectiousdiseases.com

Zioga et al. 3

a more thorough insight on the diversity and significance of human microbiome. These techniques have been recognized as a valuable tool for rapid and accurate identification of bacteria in different samples, providing a new insight on the clinical significance of various species of coryneform GPRs. Although the latter has not been clearly established [2], plenty of species previously identified as contaminants have been gaining attention in cases of clinically relevant identification. Correct identification of Corynebacterium spp. and other GPR species is a very challenging task because it will help to identify the real source of infection and install the appropriate treatment [9].

In 2002, C.aurimucosum was taxonomically described as new species within the genus Corynebacterium, with C.minutissimum as the nearest phylogenetic neighbour [10]. The spectrum of the disease caused by this pathogen has not been established, and reports of isolates of clinical significance from different samples is necessary so as to define the breadth of possible infection.

This strain has been isolated in several clinical samples; it can cause a skin affection or erythrasma [11] and an association with spontaneous abortions has been postulated, as secondary to colonization of the vaginal tract [1, 4]. Prosthetic joint infections caused by C.aurimucosum have been gaining importance, especially after implementation of molecular methods that permits more accurate characterization [5, 6].

Some cases of isolation from urogenital sites have been described, but none with associated bacteremia. A case report of urinary tract infection by C.aurimucosumsecondary to urethroplasty stricture of the urethra was described in 2012 [3]. A retrospective review of gram positive rods isolated in different sample, showed 3 clinically relevant isolation of C.aurimucosum in urine samples, two of which presented in elderly individuals with a history of recurrent culture-proven UTIs, and none of these individuals had been catheterized. The 3 blood samples where C.aurimucosumwas identified, were considered as contaminants with no clinical significance [7]. Another recent retrospective study evaluated the clinical significance of gram-positive rods isolated in blood samples. In this study, 246 blood samples were analyzed, and C.aurimucosum from 4 of them; however, none of them was treated [2]. In the same study, an association on a multivariate analysis was reported between the assessed significance of the isolate and the number of positive blood culture sets, time to positivity of culture and infectious diseases consultation. In our case, the blood culture sets were positive on the first day on cultivation. Other clinical studies, failed to identify bacteremia by C.aurimucosum when reviewing blood samples with Corynebacterium spp. identification [12].

This clinical case describes a rare urinary tract infection caused by Corynebacterium aurimucosum; only four cases of urinary infection by this pathogen had been previously described. However, this is the first report of a clinically significant bacteremia caused by this species.

While the decision as to whether or not treat individual species is certainly influenced by other patient characteristics, the particular species of Corynebacterium identified in different infections may impact treatment decisions made by the healthcare team. Since the burden of the disease has not been yet clearly established, detailed clinical reporting of bacterial identification in different samples and its interpretation could contribute to clinical uncertainty, in this changing era of microbial identification.

CONCLUSION

This case report and review of cases underlines the gaining importance of Corynebacterium species that were previously thought as purely contaminant non-pathogens in clinical practice, especially after the development of molecular techniques for microbial and strain identification, thus modifying progressively the established spectrum of disease caused by GPRs.

REFERENCES

1. Bernard K. The genus corynebacterium and other medically relevant coryneform-like bacteria. J Clin Microbiol 2012 Oct;50(10):3152–8.

2. Mushtaq A, Chen DJ, Strand GJ, et al. Clinical significance of coryneform Gram-positive rods from blood identified by MALDI-TOF mass spectrometry and their susceptibility profiles - a retrospective chart review. Diagn Microbiol Infect Dis 2016 Jul;85(3):372–6.

3. Lo S, Thiam I, Fall B, et al. Urinary tract infection with Corynebacterium aurimucosum after urethroplasty stricture of the urethra: A case report. J Med Case Rep 2015 Jul 14;9:156.

4. Trost E, Götker S, Schneider J, et al. Complete genome sequence and lifestyle of black-pigmented Corynebacterium aurimucosum ATCC 700975 (formerly C. nigricans CN-1) isolated from a vaginal swab of a woman with spontaneous abortion. BMC Genomics 2010 Feb 5;11:91.

5. Roux V, Drancourt M, Stein A, Riegel P, Raoult D, La Scola B. Corynebacterium species isolated from bone and joint infections identified by 16S rRNA gene sequence analysis. J Clin Microbiol 2004 May;42(5):2231–3.

6. Drancourt M, Berger P, Raoult D. Systematic 16S rRNA gene sequencing of atypical clinical isolates identified 27 new bacterial species associated with humans. J Clin Microbiol 2004 May;42(5):2197–202.

7. Leal SM Jr, Jones M, Gilligan PH. Clinical significance of commensal gram-positive rods routinely isolated from patient samples. J Clin Microbiol 2016 Dec;54(12):2928–36.

8. Boltin D, Katzir M, Bugoslavsky V, et al. Corynebacterium striatum: A classic pathogen eluding diagnosis. Eur J Intern Med 2009 May;20(3):e49–52.

9. Barberis C, Almuzara M, Join-Lambert O, Ramírez MS, Famiglietti A, Vay C. Comparison of the Bruker MALDI-TOF mass spectrometry system and conventional

Journal of Case Reports and Images in Infectious Diseases 1, 2018.

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phenotypic methods for identification of Gram-positive rods. PLoS One 2014 Sep 3;9(9):e106303.

10. Yassin AF, Steiner U, Ludwig W. Corynebacterium aurimucosum sp. nov. and emended description of Corynebacterium minutissimum Collins and Jones (1983). Int J Syst Evol Microbiol 2002 May;52(Pt 3):1001–5.

11. Yasuma A, Ochiai T, Azuma M, et al. Exogenous coproporphyrin III production by Corynebacterium aurimucosum and Microbacterium oxydans in erythrasma lesions. J Med Microbiol 2011 Jul;60(Pt 7):1038–42.

12. Yanai M, Ogasawasa M, Hayashi Y, Suzuki K, Takahashi H, Satomura A. Retrospective evaluation of the clinical characteristics associated with Corynebacterium species bacteremia. Braz J Infect Dis 2018 Jan–Feb;22(1):24–9.

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Author ContributionsEvangelia Anna Maria Zioga – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be publishedClara Sala Jofre – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be publishedRaquel Clivillè Abad – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be publishedIolanda Calvet Tort – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published

Virginia Isern Fernández – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be publishedLourdes Ferrer Rouscalleda – Substantial contributions to conception and design, Acquisition of data, Analysis and interpretation of data, Drafting the article, Revising it critically for important intellectual content, Final approval of the version to be published

Guarantor of SubmissionThe corresponding author is the guarantor of submission.

Source of SupportNone.

Consent StatementWritten informed consent was obtained from the patient for publication of this case report.

Conflict of InterestAuthors declare no conflict of interest.

Data AvailabilityAll relevant data are within the paper and its Supporting Information files.

Copyright© 2018 Evangelia Anna Maria Zioga et al. This article is distributed under the terms of Creative Commons Attribution License which permits unrestricted use, distribution and reproduction in any medium provided the original author(s) and original publisher are properly credited. Please see the copyright policy on the journal website for more information.

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