Small Colony Variants ofStaphylococcus aureusand Pacemaker-related Infection

Abstract

We describe the first known case of a device-related bloodstream infection caused by Staphylococcus aureus small colony variants. Recurrent pacemaker-related bloodstream infection within a 7-month period illustrates the poor clinical and microbiologic response to prolonged antimicrobial therapy in a patient infected with this S. aureus subpopulation. Infections caused by Staphylococcus aureus range from mild skin infections to acute life-threatening diseases such as pneumonia, osteomyelitis, and endocarditis. However, S. aureus may also cause a chronic disease with persistent and recurrent infections. Skin and soft tissue infections, chronic osteomyelitis, and persistent infections in patients with cystic fibrosis have been associated with small colony variants, a naturally occurring subpopulation of the species S. aureus (1-6). S. aureus small colony variants are characterized as electron transport deficient bacteria because of their auxotrophism to hemin or menadione or are recognized as thymidine-dependent. These variants produce very small, mostly nonpigmented and nonhemolytic colonies. In addition, they also demonstrate various other features that are atypical for S. aureus, including reduced coagulase production, failure to use mannitol, and increased resistance to aminoglycosides and cell-wall active antibiotics (3-10). Furthermore, the ability of these variants to persist intracellularly within nonprofessional phagocytes has been described (3,5,11). Because of their fastidious growth characteristics and unusual morphologic appearance, small colony variants present a challenge both to the microbiologist and the clinician, often resulting in misidentification and misinterpretation (1,2,7,8). Prerequisite for recovering and identifying these variants is the application of extended conventional culture and identification techniques (3,5,8). We report the first case of a pacemaker-related bloodstream infection caused by S. aureus small colony variants. This case illustrates the poor clinical and microbiologic response to prolonged antimicrobial therapy in patients infected with these variants. Case ReportA 63-year-old man was transferred to our facility with the presumptive diagnosis of endocarditis related to a pacemaker-lead infection. Past medical history included hypertension, coronary artery disease, and noninsulindependent diabetes mellitus. A VVI (ventricular ventricular inhibited) pacemaker had been implanted for treatment of sick sinus syndrome 9 years earlier. Six weeks before admission, this device had been removed because of a pocket infection after blunt trauma with dislocation of the device and perforation of the skin. Specimens for microbiologic culture were not obtained at this time. The pacemaker leads were left in place, a gentamicin-containing sponge was applied to the infection site, and a new pacemaker was implanted on the other side of the chest. Four weeks later, the patient sought treatment at the local hospital for a high fever (39.7°C) and chills and a subcutaneous abscess with oxaci...

The role of small-colony variants in failure to diagnose and treat biofilm infections in orthopedics

“…The clinical relevance of SCVs has been unclear for a long time. Many recent studies have shown that SCVs are largely responsible for the recalcitrance of infections caused by biofilms (von Eiff et al 1997, Drenkard and Ausubel 2002, Seifert et al 2003. The significance of SCVs as causative organisms in chronic and recurrent infections has been demonstrated in patients with chronic osteomyelitis (von Eiff et al 1997) and cystic fibrosis (Haussler et al 1999, Drenkard and Ausubel 2002, Kiristis et al 2005).…”

“…Also, P. aeruginosa appears to play a role in the CF lung and P. aeruginosa SCVs were isolated from one-third of NN patients with P. aeruginosa infected lungs (Haussler et al 1999). Recently, implant-related infections due to SCVs have been described, involving pacemakers (Seifert et al 2003), ventriculoperitoneal shunts (Spanu et al 2005), and hip replacements (Sendi et al 2006).…”

“…reduced toxin production), SCVs present a challenge to the clinical microbiologist, often resulting in misidentification (Proctor et al 1995. For example, Seifert et al (2003) described case studies in which blood cultures yielded nonpigmented and non-hemolytic staphylococci, which were initially identified as coagulase-negative staphylococci on the basis of a negative tube coagulation test and the API ID 32 Staph system. However, the morphological appearance of colonies was suggestive of SCVs of S. aureus, and this was confirmed by DNA amplification using the polymerase chain reaction (PCR).…”

Use of Shell-Vial Cell Culture Assay for Isolation of Bacteria from Clinical Specimens: 13 Years of Experience

“…However, some studies suggest that the possible intracellular location of S. aureus may be responsible for negative cultures on axenic medium (54). Besides, S. aureus small colony variants are characterized by their fastidious growth and the atypical morphology of theirs colonies on routine media, making recovery as well as correct identification difficult for microbiological laboratories (49). Indeed, their ability to interrupt electron transport and to form variant subpopulations affords S. aureus a number of survival advantages, including the ability of a subpopulation to persist in an intracellular situation within nonprofessional phagocytes (2,50).…”

Shell Vial Cell Culture as a Tool for Streptobacillus moniliformis “Resuscitation”

“…13 The shell vial culture technique was also helpful in our experience for isolation of unusually fastidious microorganisms, such as a Staphylococcus aureus small-colony variant with a suggested intracellular location. 14,15 In all cases, we hypothesized that cells provided damaged bacteria with some growth factors not present in axenic media and/or that the shell vial procedure with a rinsing step helped to remove potential inhibiting substances. Even if the shell vial culture assay has a very low rate of success, this technique gives valuable results.…”