Emergence of multidrug-resistant Corynebacterium striatum as a nosocomial pathogen in long-term hospitalized patients with underlying diseases

Abstract

During a 53-month period (March 1994 to August 1998), 48 Corynebacterium striatum isolates recovered from clinical specimens were characterized. The organisms were identified by both phenotypic characteristics and 16S rRNA gene sequence analysis. Thirty-six (75%) were isolated from sputum/bronchial aspirates, 10 (21%) from wound exudates/pus, 1 (2%) from vaginal discharge, and 1 (2%) from an otorrheic specimen. All 48 patients had been hospitalized for treatment of an underlying disease and had received antibiotics previously. The C. striatum isolates were considered pathogenic based on their abundance within polymorphonuclear neutrophils and their dominant growth in culture. Sensitivities of isolates to 11 antibiotics were determined by broth microdilution. MIC₉₀ values of the isolates were 1 μg/mL for vancomycin, 16 μg/mL for penicillin and ampicillin, 32 μg/mL for minocycline, and ≥32 μg/mL for cephalosporins, imipenem, ofloxacin, and macrolides. Restriction fragment-length polymorphism analysis with pulsed-field gel electrophoresis was used to determine the clonal identity. The pulse-field gel electrophoresis profiles revealed 14 distinct patterns with 20 subtypes. The isolates for the nosocomial outbreaks of C. striatum included 3 types (A, D, and E) with 4 subtypes (A1, A2, D2, and E). All 4 genotypes had broad-spectrum resistance to antimicrobial agents. Furthermore, type E strain isolated from 3 patients in the same ward was sensitive only to vancomycin. We conclude that C. striatum should be considered an emerging multidrug-resistant nosocomial pathogen in patients hospitalized for a prolonged period and/or in immunocompromised patients with such underlying conditions as cerebrovascular disease, pulmonary disease, diabetes, or malignancy.

Introduction

Corynebacterium species are widely disseminated in the environment and constitute part of the normal skin and mucous membrane flora (Funke et al., 1997). Although both Corynebacterium amycolatum and Corynebacterium jeikeium are currently recognized as important pathogens (Funke and Bernard, 2003), the significance and prevalence of Corynebacterium striatum as a causative agent of disease are not well understood. Since the first report of bacteremia and empyema with Corynebacterium striatum in a patient with chronic lymphocytic leukemia in 1980 (Bowstead and Santiago, 1980), this organism has been recognized as being responsible for a variety of different infections, including sepsis (Martin et al., 2003, Martinez-Martinez et al., 1997, Peiris et al., 1994, Tumbarello et al., 1994), osteomyelitis (Fernandez-Ayala et al., 2001), septic synovitis with arthritis (Cone et al., 1998), meningitis (Weiss et al., 1996a), CSF shunt infection (Hoy et al., 1997), endocarditis (Markowitz and Coudron, 1990, Melero-Bascones et al., 1996, Rufael and Cohn, 1994), pneumonia/empyema (Cowling and Hall, 1993, Leonard et al., 1994, Martinez-Martinez et al., 1994, Martinez-Martinez et al., 1997, Tarr et al., 2003), pulmonary abscess (Batson et al., 1996), breast abscess (Stone et al., 1997), peritonitis (Bhandari et al., 1995), wound infection (Peiris et al., 1994, Martinez-Martinez et al., 1997), keratitis (Rubinfeld et al., 1989), and intrauterine infection (Peiris et al., 1994). C. striatum infections continue to be reported mainly in immunocompromised patients who have been hospitalized for prolonged periods and who were treated previously with antibiotics (Peiris et al., 1994, Leonard et al., 1994, Tarr et al., 2003).

Opportunistic corynebacteria infections were previously thought to originate endogenously. However, in recent years, the possibility of patient-to-patient transmission in intensive care units has been described in 2 studies by means of restriction fragment-length polymorphism (RFLP) analysis (Leonard et al., 1994, Brandenburg et al., 1996, Kerry-Williams and Noble, 1986, Pitcher et al., 1990). Strains of C. striatum are generally susceptible to a wide range of antimicrobial agents (Martinez-Martinez et al., 1995, Martinez-Martinez et al., 1996, Weiss et al., 1996b), whereas C. amycolatum, C. jeikeium, Corynebacterium urealyticum, and CDC group G are normally resistant to multiple drugs (Funke et al., 1997, Funke and Bernard, 2003).

The objectives of this study were to evaluate the clinical significance of C. striatum infection and identify risk factors associated with it. In addition, we describe the high incidence of multidrug-resistant C. striatum in nosocomial outbreaks.