The challenge of antibiotic selection in prosthetic joint infections caused by Corynebacterium striatum: about a case | BMC Infectious Diseases

C. striate has limited sensitivity compared to other Corynebacterium species. Resistance to penicillins, cephalosporins (including variable MICs reported for ceftaroline), carbapenems, clindamycin, and fluoroquinolones is common. Vancomycin, linezolid and daptomycin are often tested sensitive [7]. Current CLSI guidelines provide interpretive criteria for broth microdilution susceptibility testing. Daptomycin susceptibility is often determined by E-test. Disk diffusion is not recommended since 2005, due to indeterminable differences in the size of the diffusion zone due to slow diffusion due to the high molecular weight of daptomycin [11]. However, as with other organisms such as Staphylococcus aureus and Enterococcus spp.Electronic testing leads to variability in susceptibility results depending on the calcium concentration of the Mueller-Hinton agar used [12]although electronic tests with calcium supplement are available and result in equally accurate sensitivity tests [13]. A recently published report of 12 cases of monomicrobial infection C. striated bone and joint infections reports having treated 8 of these patients with an amoxicillin-rifampicin combination. Amoxicillin MICs for 9 organisms in this series ranged from 0.38 to 3 mg/L (1 organism resistant, per EUCAST non-species related criteria) and rifampicin MICs ranged from C. striated difficult. A recent systematic review of antimicrobial therapy for C. striated infections reported 100% susceptibility for included isolates to vancomycin, linezolid, piperacillin/tazobactam, amoxicillin/clavulanic acid, and cefuroxime. However, the review included a total of 85 individual cases from the literature and reported sensitivities for only 8 organisms for piperacillin/tazobactam, 3 organisms for amoxicillin/clavulanic acid, and 2 organisms for cefuroxime. [15]. Reports on C. striated not included in this review indicate that resistance to these agents may be higher, as in the above study by Noussair and colleagues [14] who reported a resistance rate of 66% for piperacillin/tazobactam. These combinations of β-lactam/β-lactamase inhibitors present a reasonable treatment option if susceptibility to these agents has been confirmed.

The development of daptomycin resistance during therapy is a significant concern, as illustrated in our case. The development of high-level resistance to daptomycin (MIC > 256 µg/mL) has been reported in vitro in isolates exposed to daptomycin for 24 h [12]. This has also been reported in the setting of prolonged treatment, one in a case of native valvular endocarditis and in three cases of an infected left ventricular assist device [16,17,18]. While higher doses (>6 mg/kg) of daptomycin have been studied for the treatment of S. aureus [19]the ideal dose for C. striated PJI was not created. The development of high resistance to daptomycin during treatment has been reported in patients receiving doses ranging from 6 to 8 mg/kg [14,15,16, 20]. Two case reports of successful treatment of C. striated endocarditis with daptomycin are available in the current literature, one using daptomycin 10 mg/kg and the other using daptomycin 6 mg/kg plus oral rifampin 300 mg twice daily [21, 22]. Although these cases resulted in positive results, more data are needed to recommend the use of high-dose daptomycin as monotherapy or with the addition of rifampin. The mechanism of daptomycin resistance in C. striate is unique from other gram-positive organisms. In S. aureus, daptomycin resistance develops via a variety of mechanisms attributed to a number of single nucleotide polymorphisms (SNPs). Acquisition of multiple SNPs results in resistance via membrane depolarization, cell wall thickening, and reduced affinity for daptomycin binding [23]. The mechanism of high-level daptomycin resistance in C. striate differs in that a single mutation results in a loss of function at the level of phosphatidylglycerol synthase (pgsA2). The activity of daptomycin depends on the phosphatidylglycerol (PG) concentration of the bacterial cell membrane. The pgsA2 mutation in C. striated allows removal of PG from the cell membrane, altering the composition of the membrane to maintain bacterial cell viability while conferring resistance to daptomycin [24]. It has been demonstrated that this resistance phenotype persists despite the elimination of daptomycin in the culture media, unlike S. aureuswhich often returns once the selective pressure is removed [17]. In general, routine susceptibility testing of daptomycin against C. striated should not be recommended given the significant risk of development of high-level resistance during therapy.

Given our experience with this complicated case, we reviewed a series of prosthetic joint infections (PJI) with C. striated isolated from the operative cultures of our institution. We identified 11 additional cases between July 1, 2015 and July 19, 2019 with a median follow-up of 1.4 years (range 0.4 to 4.4 years) after C. striate isolation (Table 1).

Supplementary Table 1 C. striated hardware infection case details (n=11)

C. striated susceptibilities were performed in seven (63.6%) patients, with all isolates susceptible to vancomycin. Our facility’s sensitivities are performed in an outside laboratory and include ceftriaxone, clindamycin, doxycycline, erythromycin, gentamicin, levofloxacin, linezolid, meropenem, penicillin, and trimethoprim-sulfamethoxazole. Vancomycin and daptomycin sensitivities are performed via electronic testing, if requested. However, only one patient had additional susceptibilities requested for their C. striate isolate sensitive to daptomycin, linezolid and resistant to fluoroquinolones. Ten patients (90.9%) were treated with vancomycin and one with daptomycin for a median duration of 42 days (range 17 to 105 days). Six (54.5%) required additional surgeries of the involved joint, including two amputations or disarticulations, a median of 44 days (range 5-614 days) after isolation from C. striate. Only one had C. striated isolated from subsequent procedures, however this patient (#3) was initially treated with daptomycin, and switched to vancomycin treatment after repeat C. striated insulation. Daptomycin sensitivities were not performed on any of the isolates from this patient. These cases highlight the appearance of C. striate in patients complicated with PJI, although they likely underrepresent the total number of cases at our institution, as the practice of identifying C. striate species level is relatively new in our clinical microbiology laboratory.

C. striated has always been considered a contaminant, especially when grown in tissue culture as part of PJI, which are often polymicrobial. This case highlights the need to consider C. striated pathogen in certain clinical settings. The most appropriate antimicrobial therapy for C. striated PJI includes vancomycin or linezolid, but β-lactams can be considered if sensitive. Treatment of these infections with daptomycin should be avoided even when the isolate appears susceptible due to the risk of developing high-level resistance leading to clinical failure.

Martin E. Berry