Journal List > Hanyang Med Rev > v.38(2) > 1111609

Hanyang Med Rev. 2018 Jun;38(2):93-98. English.
Published online Jun 30, 2018.  https://doi.org/10.7599/hmr.2018.38.2.93
© 2018 Hanyang University College of Medicine · Institute of Medical Science
Microbiological Characteristics of Corynebacterium striatum, an Emerging Pathogen
Sae Am Song,1 and Jeong Hwan Shin1,2
1Department of Laboratory Medicine, Inje University College of Medicine, Busan, Korea.
2Paik Institute for Clinical Research, Inje University College of Medicine, Busan, Korea.

Corresponding Author: Jeong Hwan Shin. Department of Laboratory Medicine, Inje University Busan Paik Hospital, 75 Bokjiro, Busanjin-gu, Busan 47392, Korea. Tel: +82-51-890-6475, Fax: +82-51-890-8615, Email: jhsmile@inje.ac.kr
Received Apr 03, 2018; Revised May 05, 2018; Accepted Jun 12, 2018.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


Abstract

C. striatum is part of the normal skin and mucous membrane flora in humans and is widely disseminated in the environment. Traditionally, these strains have been considered contaminants. However, C. striatum has been linked to respiratory infection, bacteremia, and endocarditis; and it is strongly related to nosocomial outbreaks. At present, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) is the most accurate routine identification method. Many C. striatum strains are multi-drug resistant, being susceptible only to vancomycin and linezolid. We should survey the antimicrobial susceptibility results regularly to monitor its resistance and consider it a possible pathogen.

Keywords: Corynebacterium striatum; Emerging pathogen; Resistance

INTRODUCTION

Corynebacterium is a gram-positive bacillus that is widely distributed in the environment [1]. It consists of more than 80 species and is common in the normal flora of human skin and mucous membranes [1]. These organisms traditionally have been considered contaminants and are ignored when they are detected in clinical specimens. However, the association of Corynebacterium species with disease is increasing, and we should consider them true pathogens when they are isolated from usually sterile specimens or invasive indwelling devices and in patients who have received long-term antimicrobial therapy.

In recent years, Corynebacterium striatum has been isolated frequently from clinical specimens, and multi-drug-resistant strains are common. We need to know more precisely about the general characteristics of this organism, its clinical features, an accurate identification method, and antimicrobial resistance. We review the characteristics of C. striatum, an emerging pathogen, focusing on these points.

1. Epidemiology and Clinical Features

Corynebacterium striatum is part of the normal flora of the skin and mucous membranes in humans and is widely disseminated in the environment. It has generally been regarded as a contaminant when isolated from clinical specimens. However, it can have pathogenicity in both immunocompromised and immunocompetent hosts [2] and can colonize various medical devices. Since C. striatum was first reported as a causative pathogen of pleuropulmonary infection in 1980 [3], it has been associated with diverse infections and nosocomial outbreaks. Thus, the organisms have been responsible for respiratory infection [4], infectious endocarditis [5, 6], arthritis [7], cellulitis [8, 9], catheter-related bloodstream infection [10, 11], meningitis [12], skin infection [13], osteomyelitis [14], abscess [15], and wound infection [16]. An important aspect of several of these infections, including infectious endocarditis, sepsis, or meningitis, caused by C. striatum is an association with a nosocomial risk factor such as medical devices [11, 17] and underlying immunosuppressive conditions. Also, it can cause clinically significant infections at multiple sites and exhibited behavior consistent with an emerging pathogen in several studies [18, 19]. Belmares et al. reported infections with this organism, which was the most common among Corynebacterium species [17], to have a mortality rate of 78.6%. There have been occasional reports of C. striatum nosocomial outbreaks in patients with chronic obstructive pulmonary disease (COPD) [20] and those in intensive care units [21]. These studies showed that the most common comorbidity in infected patients is COPD, which means that chronic pulmonary disease with long-time use of respiratory equipment can contribute to respiratory infection or colonization by C. striatum. Furthermore, C. striatum has pathogenicity in specific conditions such as repeated exposure to antibiotics or invasive procedures. Also, several studies have reported that C. striatum can be transmitted from patient to patient via the hands of medical personnel [21, 22]. Thus, enforcing hand hygiene and applying short-period therapeutic devices or antibiotics are significant factors recognized as preventative of nosocomial infection. However, these strains commonly were isolated in outpatient settings, so we can presume that they originated in the community [23].

Corynebacterium striatum infection can occur at any age and in various sites, but it is more common in male patients because the greater sebum output on the skin of males can support the survival of lipophilic diphtheroids such as C. striatum [12, 24, 25]. Virulence factors associated with C. striatum are limited. However, skin barrier damage, a medical device, use of broad-spectrum antibiotics, underlying disease, and poor immune status may influence the occurrence of infection. Corynebacterium striatum is known to be resistant to many antimicrobial treatments. To prevent such infections, it is recommended to remove any artificial device if possible and not to use long-term antimicrobial agents [26, 27]. Therefore, repeated isolation of C. striatum is significant and should not be underappreciated, as it may contribute to the death of some patients [28].

2. Laboratory Diagnosis

Corynebacterium species are gram-positive, slightly curved, typically club-shaped bacilli. Generally, Corynebacterium can be isolated on 5% sheep blood agar-based selective medium at 37℃. The biochemical identification of various species can be difficult because of their biochemical variability. For routine identification, micromethods such as API Coryne strip (bioMérieux, Marcy l'Étoile, France) and RapID® CB Plus or several automated identification systems are commonly used in the clinical microbiology laboratory.

API Coryne strip can be used for suspect colonies, which are tiny grayish, mostly translucent, coryneform organisms. The device consists of 20 microtubes that test carbohydrate fermentation or enzymatic activity. Unfortunately, the device cannot distinguish C. striatum from C. amycolatum because these species have similar phenotypic characteristics. Moreover, the final identification is based on the statistical use of multiplicity. Therefore, the accuracy is relatively low.

Various automated identification systems for Corynebacterium are used routinely. VITEK®2 (bioMérieux) with an anaerobe and Corynebacterium (ANC) identification card employs kinetic analysis utilizing fluorescence, turbidity, and colorimetric technology based on the metabolic processes of the microorganisms. Rennie et al. reported that the correct identification rate of the Vitek2 ANC identification card for Corynebacterium species was 80% to 100% [29]. The Microscan system (Beckman Coulter, Brea, CA, USA) and BD Phoenix system (Becton Dickinson, Franklin Lakes, NJ, USA) also are commercially available for Corynebacterium identification.

The reliable identification techniques include matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA sequencing. MALDI-TOF MS, which is based on the protein composition of microorganisms, has been used in clinical laboratories to identify Corynebacterium species. Vila et al. reported that MALDI-TOF MS analysis is a rapid and consistent system for identification of Corynebacterium at the species level within 15 min [30]. Rong Bao et al. reported the MALDI-TOF identification rate for Corynebacterium as 92% compared with rpoB gene sequencing [31]. Other studies showed similar identification rates, ranging from 92.3% to 100% [32, 33, 34, 35]. Therefore, MALDI-TOF may be a more useful diagnostic method than biochemical assay and can be a primary identification tool.

Various molecular methods have been applied for identification of Corynebacterium species, including 16S rRNA sequencing, rpoB gene sequencing, and restriction fragment-length polymorphism (RFLP), DNA-DNA hybridization, and real-time polymerase chain reaction (PCR). Because the 16S rRNA gene of Corynebacterium shows low intra-genus polymorphism, nearly complete 16S rRNA sequencing (approximately 1,500 bp) is required to identify to the species level. The Rpo B gene also can be used to discriminate Corynebacterium species. Khamis reported that the rpoB gene is polymorphic enough to identify Corynebacterium species [36]. Alibi et al. suggested PCR restriction analysis using the rpoB gene to differentiate C. striatum from other Corynebacterium species [32]. We do not need to use these molecular methods as routine tests, but they can be used as a confirmatory tool when we need to check the final results because of an inappropriate phenotypic method.

3. Antimicrobial Susceptibility Test and Resistance

The Clinical and Laboratory Standards Institute (CLSI) published “Methods for antimicrobial dilution and disk susceptibility testing of infrequently isolated or fastidious bacteria; Approved Guideline M45-A” in 2006. This guideline provides the information and interpretive criteria for broth microdilution susceptibility testing of Corynebacterium species. However, there are no interpretive criteria for disk diffusion testing. The testing conditions require lysed horse blood-supplemented Mueller-Hinton broth for adequate growth. Moreover, the medium should contain calcium 50 µg/mL for testing of daptomycin. The antimicrobial agents used are as follows: penicillin, cefotaxime (cefepime, ceftriaxone), imipenem (meropenem), vancomycin, daptomycin, gentamicin, erythromycin, ciprofloxacin, doxycycline (tetracycline), clindamycin, trimethoprim-sulfamethoxazole, quinupristin-dalfopristin, and linezolid. The interpretive criteria for penicillin and erythromycin are estimated from the minimum inhibitory concentrations (MICs) of Corynebacterium species. However, the interpretive criteria for cephalosporin, linezolid, and others are adapted from those for Streptococcus, Enterococcus, and Staphylococcus species published in CLSI document M100. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) provides a breakpoint table for interpretation of MICs and zone diameters for Corynebacterium species. Unlike CLSI, EUCAST includes the interpretive criteria for the disk diffusion method. The medium should have 5% defibrinated horse blood and beta-NAD 20 mg/L. The antimicrobial agents tested are benzylpenicillin, ciprofloxacin (moxifloxacin), gentamicin, vancomycin, clindamycin, tetracycline, linezolid, and rifampicin. It is not easy to perform routine antimicrobial susceptibility testing of C. striatum in the clinical laboratory because there is no commercial kit, and growth requires a special medium including horse blood.

Previous reports revealed that C. striatum generally is susceptible to several antimicrobial agents, including penicillin, cefazolin, imipenem, and vancomycin [28, 37]. However, many more recent articles found an increase in multidrug resistance [21, 23, 38]. In Korea, Yoo et al. described bacteremia caused by multidrug-resistant C. striatum [39].

In 2006, C. striatum strains in Japan were all susceptible to vancomycin but showed high-level resistance to erythromycin, tetracycline, rifampin, and ciprofloxacin [40]. In one report from Brazil, 87% of C. striatum were resistant to most antimicrobial agents except vancomycin, linezolid, and tetracycline [41]. Vancomycin was consistently effective in most previous reports of C. striatum testing.

Daptomycin can be considered to treat gram-positive pathogens. Several reports show that Corynebacterium infections can be treated with daptomycin, for which the MICs are low [42, 43]. However, daptomycin-resistant C. striatum is discussed in the literature [43, 44]. Van Hal et al. reported that daptomycin resistance is highly correlated with higher MICs for vancomycin in S. aureus because cellwall thickening can alter the charge of the outer membrane, which reduces daptomycin passage through the cell membrane [45]. However, others found no structural difference between daptomycin-susceptible and -resistant Corynebacterium strains [44, 46]. McElvania TeKippe et al. [43] revealed a very interesting finding concerning daptomycin resistance. They demonstrated the acquisition of high-level resistance when the daptomycin-susceptible isolates were incubated with the drug. This implies the possibility of acquisition of daptomycin resistance in patients treated for a long time with the drug.

The other agent employed to treat C. striatum infection is linezolid because there have been no reports of resistance for Corynebacterium species. However, this drug carries a 34% to 80% rate of adverse effects that result in discontinuation of administration during long courses [47].

Ceftaroline has been explored for uncommon gram-positive pathogens, including C. striatum [48, 49]. The efficacy was variable for C. striatum and other Corynebacterium species. On the other hand, McMullen et al. reported that C. striatum is nearly universally resistant to ceftaroline, although the extent of resistance is variable. They presumed that the resistance is attributable to the modification of penicillin-binding protein and concluded that ceftaroline is not adequate to use as a treatment. McMullen et al. [35] tested the activity of telavancin and revealed achievable MICs for C. striatum treatment.

CONCLUSION

Corynebacterium striatum is part of the normal flora of the skin and mucous membranes in humans. However, it can have pathogenicity in both immunocompromised and immunocompetent hosts. C. striatum has been associated with diverse infections and nosocomial outbreaks including skin infection, respiratory infection, and severe invasive infections. In addition, C. striatum is resistant to many antimicrobial treatments. We should identify C. striatum correctly to the species level and survey the antimicrobial susceptibility results regularly to monitor its resistance.

Notes

CONFLICTS OF INTEREST:The authors have no financial conflicts of interest.

ACKNOWLEDGEMENT

This work was supported by the BioNano Health-Guard Research Center funded by the Ministry of Science, ICT, and Future Planning (MSIP) of Korea as a Global Frontier Project (Grant Number HGUARD_2014M3A6B2060509).

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