Antimicrobial Treatment Options for Granulomatous Mastitis Caused by Corynebacterium Species

Abstract

cCorynebacterium species are increasingly recognized as important pathogens in granulomatous mastitis. Currently, there are no published treatment protocols for Corynebacterium breast infections. This study describes antimicrobial treatment options in the context of other management strategies used for granulomatous mastitis. Corynebacterium spp. isolated from breast tissue and aspirate samples stored from 2002 to 2013 were identified and determined to the species level using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), 16S RNA sequencing, and rpoB gene targets. The MICs for 12 antimicrobials were performed using Etest for each isolate. Correlations of these with antimicrobial characteristics, choice of antimicrobial, and disease outcome were evaluated. Corynebacterium spp. from breast tissue and aspirate samples were confirmed in 17 isolates from 16 patients. Based on EUCAST breakpoints, Corynebacterium kroppenstedtii isolates (n ‫؍‬ 11) were susceptible to seven antibiotic classes but resistant to ␤-lactam antibiotics. Corynebacterium tuberculostearicum isolates (n ‫؍‬ 4) were multidrug resistant. Two nonlipophilic species were isolated, Corynebacterium glucuronolyticum and Corynebacterium freneyi, both of which have various susceptibilities to antimicrobial agents. Short-course antimicrobial therapy was common (median, 6 courses per subject; range, 1 to 9 courses). Patients with C. kroppenstedtii presented with a hot painful breast mass and underwent multiple surgical procedures (median, 4 procedures; range, 2 to 6 procedures). The management of Corynebacterium breast infections requires a multidisciplinary approach and includes culture and appropriate sensitivity testing to guide antimicrobial therapy. Established infections have a poor outcome, possibly because adequate concentrations of some drugs will be difficult to achieve in lipophilic granulomata. Lipophilic antimicrobial therapy may offer a therapeutic advantage. The role of immunotherapy has not been defined. Granulomatous mastitis (GM) is a rare inflammatory condition that typically occurs in parous women of reproductive age (1). Clinically, it can present as a breast mass with features similar to those of breast malignancy (2). Multiple infective and inflammatory conditions, including tuberculosis (TB), fungal infections, sarcoidosis, amyloidosis, and Wegener's granulomatosis, have been recognized, but recently, attention has been drawn to corynebacterial species as a specific pathogen in this disease. Typically, corynebacterial breast infections are characterized by abscess formation, granulomatous inflammation, and progression to sinus/fistula formation (3). This and other specific diagnoses should be excluded before a diagnosis of idiopathic granulomatous mastitis (IGM) is made (3-5).Commonly, it is the lipophilic species of the Corynebacterium genus that cause mastitis (3, 6-8). As such, a microbiological diagnosis can be challenging, due to their fastidious growth requirements and prolonged incu...

Clinical Significance of Commensal Gram-Positive Rods Routinely Isolated from Patient Samples

“…However, awareness of this histopathological entity is lacking, and it is imperative that clinical microbiologists work to educate their colleagues and residents about novel disease associations, such as C. kroppenstedtii mastitis, with characteristic histopathological findings (27). Consistent with data from several recent reports, 7 of 9 patients in our study were of Hispanic descent (11,12,(28)(29)(30)(31)(32)(33). This association may be due to multiparity, breastfeeding, low socioeconomic status, or birth outside the United States with geographic variation in skin flora (1).…”

The Brief Case: Recurrent Granulomatous Mastitis Due to Corynebacterium kroppenstedtii

“…C. kroppenstedtii is a lipophilic organism that lacks cell envelope mycolic acids, which may explain its tissue tropism for lipid-rich mammary glands (1-3). The diagnosis of granulomatous mastitis due to C. kroppenstedtii, which typically affects young women of reproductive age, can be challenging due to the presence of few organisms in clinical specimens (often limited to cystic spaces), poor Gram staining of corynebacteria, and fastidious growth in culture on routine media, which was evident from our case presentation (C. kroppenstedtii grew both aerobically and anaerobically on different media) (1,3,4). Figure 1 displays a Gram stain and isolation subculture of a clinical specimen of C. kroppenstedtii growing as small dull gray colonies on sheep blood agar at 72 h; only scant growth was observed on chocolate agar at 72 h (image not shown).…”

“…In addition, antibiotics alone are often not sufficient and surgical intervention is required (1,3,4). The patient in our case presentation, who was unique in that she developed mastitis in both breasts consecutively, was given three different classes of antibiotics and had three surgical procedures performed over a 2-month period for her left breast and then was given six different classes of antibiotics and had five surgical procedures performed over a 4-month period for her right breast, without cure.…”

“…The patient in our case presentation, who was unique in that she developed mastitis in both breasts consecutively, was given three different classes of antibiotics and had three surgical procedures performed over a 2-month period for her left breast and then was given six different classes of antibiotics and had five surgical procedures performed over a 4-month period for her right breast, without cure. She received many short courses of antibiotics with low lipid solubility, such as fluoroquinolones and beta-lactam antibiotics, that may not have been able to penetrate adequately into breast tissue (4). This illustrates the concept of clinical resistance, which describes factors that can result in treatment failure, such as inappropriate drug penetration at the site of infection and suboptimal length of treatment despite favorable antimicrobial susceptibility testing results (4, 7).…”

“…An accurate and timely diagnosis of granulomatous mastitis due to C. kroppenstedtii is important because empirical treatment regimens are often ineffective, as many antibiotics are hydrophilic and distribute poorly in lipid-rich environments, such as the breast (3,4). In addition, antibiotics alone are often not sufficient and surgical intervention is required (1,3,4).…”