Practical Guidance for Clinical Microbiology Laboratories: Microbiologic diagnosis of implant-associated infections

Abstract

SUMMARYImplant-associated infections (IAIs) pose serious threats to patients and can be associated with significant morbidity and mortality. These infections may be difficult to diagnose due, in part, to biofilm formation on device surfaces, and because even when microbes are found, their clinical significance may be unclear. Despite recent advances in laboratory testing, IAIs remain a diagnostic challenge. From a therapeutic standpoint, many IAIs currently require device removal and prolonged courses of antimicrobial therapy to effect a cure. Therefore, making an accurate diagnosis, defining both the presence of infection and the involved microorganisms, is paramount. The sensitivity of standard microbial culture for IAI diagnosis varies depending on the type of IAI, the specimen analyzed, and the culture technique(s) used. Although IAI-specific culture-based diagnostics have been described, the challenge of culture-negative IAIs remains. Given this, molecular assays, including both nucleic acid amplification tests and next-generation sequencing-based assays, have been used. In this review, an overview of these challenging infections is presented, as well as an approach to their diagnosis from a microbiologic perspective.

Keywords: biofilms; cardiac implantable electronic device infection; medical implants; microbiologic diagnosis; periprosthetic joint infection; prosthetic valve endocarditis.

Fig 1

Overview of biomedical devices and their anatomic locations.

Fig 2

Scanning electron microscopic image of a 1.5 × 7.0 mm cortex screw harboring Staphylococcus aureus biofilm on its surface.

Fig 3

Diagnostic criteria for hip or knee periprosthetic joint infection [European Bone and Joint Infection Society and 2018 Parvizi criteria (73, 74)]. CFU, colony-forming unit. *Table reproduced from McNally et al. (73). **Table reproduced from Parvizi et al. (74) with permission. ^aInfection is only likely if there is a positive clinical feature or raised serum C-reactive protein, together with another positive test (synovial fluid, microbiology, histology, or nuclear imaging). ^bExcept in adverse local tissue reaction and crystal arthropathy cases. ^cInterpret with caution when other possible causes of inflammation are present: gout or other crystal arthropathy, metallosis, active inflammatory joint disease (e.g., rheumatoid arthritis), periprosthetic fracture, or the early postoperative period. ^dValues are valid for hips and knee PJI. Parameters are only valid when clear fluid is obtained, and no lavage has been performed. Volume for the analysis should be >250 µL, ideally 1 mL, collected in an ethylenediaminetetraacetic acid-containing tube and analyzed in <1 h, preferentially using automated techniques. For viscous samples, pre-treatment with hyaluronidase improves the accuracy of optical or automated techniques. In case of bloody samples, the adjusted synovial WBC = synovial WBCobserved – [WBCblood/RBCblood × RBCsynovial fluid] should be used. ^eNot valid in cases of adverse local tissue reaction, hematomas, or acute inflammatory arthritis or gout. ^fIf antibiotic treatment has been given (not simple prophylaxis), the results of microbiological analysis may be compromised. In these cases, molecular techniques may have a place. Results of culture may be obtained from preoperative synovial aspiration, preoperative synovial biopsies or (preferred) from intraoperative tissue samples. ^gInterpretation of single positive culture (or <50 CFU/mL in sonication fluid) must be cautious and taken together with other evidence. If a preoperative aspiration identified the same microorganism, they should be considered as two positive confirmatory samples. Uncommon contaminants or virulent organisms (e.g., Staphylococcus aureus or Gram-negative rods) are more likely to represent infection than common contaminants (such as coagulase-negative staphylococci, micrococci, or Cutibacterium acnes). ^hIf centrifugation is used, then the suggested cut-off is 200 CFU/mL to confirm infection. If other variations to the protocol are used, the published cut-offs for each protocol must be applied. ⁱHistological analysis may be from preoperative biopsy, intraoperative tissue samples with either formalin-foxed paraffin embedded, or frozen section. ^jWBC scintigraphy is regarded as positive if the uptake is increased at the 20 h scan, compared to the earlier scans (especially when combined with complementary bone marrow scan). ^kFor patients with inconclusive minor criteria, operative criteria can also be used to fulfill definition for PJI. ^lConsider additional molecular diagnostics such as next-generation sequencing.