Microbes on orthopaedic implants do not always mean infection, review finds

A positive microbiological test on an orthopaedic implant does not automatically mean the device is infected, according to a structured narrative review published in Archives of Orthopaedic and Trauma Surgery. The review, led by Liao Chang-sheng and colleagues, examines what it calls the interpretive gray zone: microbial or molecular signals detected on joint prostheses, fracture-fixation devices, or spinal instrumentation in patients who do not meet validated criteria for confirmed implant-related infection. The authors argue that detection and diagnosis are fundamentally different propositions, and that conflating them risks both overtreatment with antibiotics and undertreatment of genuine occult infection.

The problem spans the whole field of implant surgery. Unexpected microbial signals arise with conventional deep-tissue culture, blood culture bottle methods, sonication of explanted hardware, broad-range polymerase chain reaction, 16S rRNA sequencing, and metagenomic next-generation sequencing. The review was based on literature identified in PubMed, Embase, and Web of Science, updated through 27 June 2026, and organized by implant type, reason for implant removal, detection method, host-response evidence, and longitudinal outcome. The authors deliberately did not perform a meta-analysis, because the available studies differed too much in populations, sampling protocols, infection definitions, and microbiological methods to pool.

The least confounded clinical evidence comes from fracture-fixation hardware removed routinely after healing rather than because of failure. Knabl and colleagues studied 57 patients undergoing routine removal of osteosynthesis material without clinical or laboratory evidence of infection; culture or polymerase chain reaction was positive in 56 percent of implants, predominantly for coagulase-negative staphylococci, and scanning electron microscopy showed biofilm-like structures on several devices. Fuchs and colleagues examined 203 osteosynthesis implants removed because of soft-tissue irritation or before arthroplasty, with sonication culture positive in 27 percent, though only 11 percent were considered clinically significant by the authors’ criteria. Previ and colleagues reported sonication-culture positivity in 42.8 percent of 49 devices removed for mechanical reasons, including coagulase-negative staphylococci and Pseudomonas species.

Even these cleaner studies have limits, the review stresses. Routine removal does not exclude unrecognized local inflammation; a single positive culture may reflect handling contamination; polymerase chain reaction may detect non-viable DNA; and microscopy cannot determine whether a surface-associated structure is metabolically active or clinically pathogenic. The justified conclusion is therefore narrow: microbial or biofilm-associated signals can be recovered from orthopaedic devices in the absence of recognized implant failure or overt infection, but whether those signals represent viable, stable, and biologically inert persistence remains unresolved.

By contrast, arthroplasty and spinal revision cohorts labeled presumed aseptic are intrinsically confounded. Pain, loosening, osteolysis, stiffness, or pseudarthrosis may themselves be manifestations of indolent, low-grade infection, so the absence of fever, sinus tract, purulence, or elevated systemic inflammatory markers is not equivalent to the absence of clinically relevant disease. Moojen and colleagues examined 176 total hip arthroplasty revisions classified preoperatively as aseptic using extensive tissue sampling, histology, and broad-range 16S PCR, classifying seven patients as infected and 15 as suspected infection. Bereza and colleagues detected bacterial DNA in 90 percent of 16 presumed-aseptic loosening cases using sonication and 16S PCR, with the associated interface membranes described as infection-type membranes under histopathological classification systems.

Unexpected positive cultures are common in this setting, occurring in roughly 10 to 20 percent of presumed-aseptic hip and knee revisions across heterogeneous series. Low-virulence biofilm-associated organisms, particularly coagulase-negative staphylococci and Cutibacterium acnes, predominate. Neufeld and colleagues reported 110 culture-positive cases among 1,196 presumed-aseptic total hip revisions, or 9.2 percent, with five-year infection-free implant survival of 86.8 percent in the culture-positive group. A systematic review by Mirghaderi and colleagues covering 22 studies and 7,449 presumed-aseptic total hip revisions found an overall unexpected positive culture frequency of approximately 15 percent. In spinal revision surgery, a 2024 systematic review and meta-analysis of 15 studies and 1,057 presumed-aseptic adult procedures reported an overall prevalence of 33.2 percent, with Cutibacterium acnes and coagulase-negative staphylococci predominating, and Agarwal and colleagues identified biofilm on 72 percent of retrieved pedicle screws from ten aseptic pseudarthrosis cases despite negative standard cultures.

Favorable outcomes after revision do not prove that infection was never present, the authors warn. Tissue excision, debridement, component exchange, and perioperative antibiotics may eradicate or substantially reduce a previously occult microbial burden, so outcome data reflect both the initial biological state and the treatment exposure introduced by surgery itself. In a mean 7.5-year follow-up by Boot and colleagues, re-revision occurred in 2 of 21 patients in the infection or suspected-infection group and 13 of 152 in the aseptic-loosening group, without a statistically significant difference. That argues against inevitable progression but does not establish that the positive cases were never infected. Other studies point in different directions: Simon and colleagues found no significant reduction in re-revision after postoperative antibiotics in a propensity-matched cohort, whereas Milandt and colleagues and Hipfl and colleagues reported increased risk in selected total hip arthroplasty populations. The overall evidence supports heterogeneity, not universal benignity.

Molecular methods add sensitivity but also new interpretive hazards. DNA-based testing cannot distinguish viable organisms from relic DNA, and low microbial biomass amplifies the effects of reagent, environmental, and batch contamination. Carr and colleagues used 16S rRNA sequencing in 248 samples from 41 presumed-aseptic hip and knee revisions and observed greater diversity in implant-derived specimens than in air controls, while Li and colleagues described periprosthetic microbiome patterns in synovial fluid with stronger inflammatory associations for Staphylococcus-dominant profiles than for Cutibacterium-dominant profiles. A 2025 systematic review and meta-analysis found high specificity and promising sensitivity for 16S rDNA PCR, multiplex PCR, and metagenomic next-generation sequencing in periprosthetic joint infection, while emphasizing heterogeneity, contamination control, and interpretation challenges. Biofilm biology, including persister cells, metabolic dormancy, intracellular reservoirs, and tolerance to host immunity and antibiotics, offers a plausible mechanism for prolonged survival of low-burden organisms, and in a murine model methicillin-resistant Staphylococcus epidermidis biofilm persisted with limited osteolysis and relatively modest histological change compared with Staphylococcus aureus. The authors caution that such mechanistic work illustrates biological plausibility but cannot by itself establish clinical causality.

To bring order to this ambiguity, the review proposes a three-domain interpretive framework that complements, but does not replace, validated diagnostic definitions such as the 2018 International Consensus Meeting and evidence-based periprosthetic joint infection criteria, the 2021 European Bone and Joint Infection Society definition, and the fracture-related infection consensus. The first domain is analytical credibility: whether the signal is reproducible and unlikely to be explained by sampling or laboratory contamination, judged by the number and independence of specimens, organism concordance, quantitative burden, time to positivity, negative controls, and reproducibility. The second is biological activity or persistence: whether the signal reflects viable or metabolically active organisms, supported by repeated detection, concordant culture, RNA-based assays, viability-PCR approaches, or direct biofilm evidence. The third is clinical causality: corroborating host response or implant-related pathology such as purulence, sinus tract, histological acute inflammation, synovial leukocytosis, elevated inflammatory biomarkers, progressive osteolysis or loosening, pseudarthrosis, or infection-related reoperation. The authors also note that specimen-count thresholds cannot be universalized: the OSIRIS study found that recovery of an indistinguishable organism from three or more independent specimens gave very high specificity against a histological reference standard, whereas later definitions commonly regard two concordant deep specimens as strong or confirmatory evidence, and performance depends on sampling protocol, organism, and pretest probability.

On management, the review separates evidence from proposal. Observational evidence indicates that routine prolonged antibiotics have not shown consistent benefit for every isolated low-virulence unexpected positive culture, and automatic classification of such a result as active infection is not supported by current evidence. Conversely, a high-virulence organism, repeated concordant deep specimens, purulence, positive histology, or a coherent inflammatory and mechanical phenotype should shift management toward an infection pathway, with decisions made multidisciplinarily. The authors propose that stable coexistence be treated as a longitudinal clinical phenotype or testable hypothesis, defined by sustained clinical stability, no infection-related reoperation, no progressive inflammatory or mechanical evidence attributable to infection, and no dependence on long-term suppressive antimicrobial therapy, rather than as an established diagnostic category. They recommend prospective multicenter cohorts enrolled before microbiological results are known, clinical validation of viability-oriented methods such as RNA-based testing and propidium monoazide-assisted PCR, rigorous contamination controls in low-biomass studies, and outcome research that separates the effect of the detected signal from the effect of revision surgery. The framework has face validity but, the authors acknowledge, requires prospective validation before it can serve as a predictive clinical tool.

Subject of Research: Interpreting unexpected microbial detection on orthopaedic implants in the absence of confirmed infection

Article Title: The boundary between microbial detection and implant-related infection: a structured narrative review of analytical credibility, biological persistence, host response, and clinical causality

Article References: Chang-sheng, L., feng-jun, L., huan-sheng, L., qiang, H., & zong-ke, Z. (2026). The boundary between microbial detection and implant-related infection: a structured narrative review of analytical credibility, biological persistence, host response, and clinical causality. Archives of Orthopaedic and Trauma Surgery, 146(1), Article 366. https://doi.org/10.1007/s00402-026-06505-y

Image Credits: AI Generated

DOI: 10.1007/s00402-026-06505-y

Keywords: orthopaedic implants, periprosthetic joint infection, fracture-related infection, biofilm, unexpected positive cultures, sonication, 16S rRNA sequencing, metagenomic next-generation sequencing, presumed aseptic revision, spinal instrumentation, diagnostic criteria, low-biomass contamination