Is there sufficient evidence to support the use of antibiotic holiday just before the second stage of an infected total hip or knee arthroplasty revision surgery?

Abstract

The practice of implementing an antibiotic holiday before the second stage of hip or knee arthroplasty is currently controversial due to limited evidence for this approach, as per the International Consensus Meeting 2018 on Musculoskeletal Infection. A greater understanding of this issue could augment the quality of Alrayes and Sukeik’s mini-review (2023) on diagnosing, managing, and treating periprosthetic knee infections. However, a significant lack of literature exists concerning the optimal duration for the antibiotic holiday, calling for more research before establishing any clinical guidelines.

Key Words: Septic knee prosthesis revision; Two stages; Antibiotic holiday

Core Tip: Optimising the outcomes of the two-stage revision process for infected hip and knee arthroplasty patients is a crucial topic to address. We wish to highlight that there is no evidence against the use of continuous antibiotic treatment in two-stage septic hip and knee joint arthroplasty. Furthermore, the optimal duration of antibiotic holidays has yet to be determined.

TO THE EDITOR

We found the mini-review by Alrayes and Sukeik[1] to be incredibly informative on the diagnosis, management, and treatment of periprosthetic knee infections. However, we wish to highlight that the evidence supporting antibiotic use before the second stage of arthroplasty revision is limited and inconclusive; hence, definitive conclusions cannot be drawn. In this article, we plan to further elucidate this issue and provide a clear understanding of prosthetic joint infection management. It’s important to mention that the International Consensus Meeting (ICM) on Musculoskeletal Infection in 2018 acknowledged the scanty evidence supporting the need or ideal length of an “antibiotic holiday”[2]. Contrarily, AO Reconstruction supports continual treatment before re-implantation as it believes that the absence of an antibiotic washout does not compromise the accuracy of tissue sampling and microbe cultures[3].

Moreover, Tan et al[4] retrospectively examined 409 patients (282 knees and 127 hips) who underwent two-stage revision arthroplasty. After infected prosthesis removal, comprehensive debridement, and spacer implantation, patients received antibiotics for 4 to 8 wk without surgery. To be included in this study, patients should have shown no signs of infection or had negative lab results at the time of the second-stage revision. The failure rate was reported at 15.6% (64/409), with the average antibiotic holiday around 30 d. No statistically significant difference was found between the length of antibiotic holiday and the infection rates.

Given the lack of strong evidence and high heterogeneity of cohorts due to differing pathogens, varied treatment protocols, and limited follow-up exceeding 24 months, we aim to present a concise review of the available options as suggested by Sousa et al[5].

Carrega et al[6] retrospective study of 102 cases (55 hips, 47 knees) involved two-stage revisions for periprosthetic infections. Following a 6-week antibiotic regimen, a minimum 2-wk antibiotic-free period was introduced to identify any recurrence of the infection. Nine participants were lost to follow-up (two deceased). The success rate of infection-free arthroplasties was 85% (79/93), with a median follow-up of 44 months.

Charette and Melnic[7] proposed the same protocol. Conversely, Janssen et al[8] performed two-stage revisions on infected hip and knee arthroplasties (95 and 25 cases, respectively) using systematic and local antibiotic treatments with gentamicin-PMMA beads for short (average 14 d) or long intervals (average 5.5 months). Importantly, long-term success rates for hip and knee re-implantations with a 2-wk antibiotic-free window were 28/38 and 15/19, respectively.

Klemt et al[9] recommended a longer antibiotic-free period (4 to 6 wk) before the second stage for total knee or hip revision arthroplasty. With an average follow-up of 4.4 years, the success rate was 96 out of 117 cases. Elevated serum inflammation markers indicated a high predictive value for reinfection.

Kuzyk et al[10] advocated for the same length of antibiotic-free period. In their review, the first stage of arthroplasty removal, debridement, spacer insertion, and intravenous antibiotics for 6 to 8 wk was followed by a 2-wk drug holiday. During this period, inflammation markers were monitored, and provided they were within normal limits; the next stage was undertaken.

Regarding infected megaprotheses, Gonzalez et al[11] concluded in a systematic review that two-stage procedures with a 2-wk antibiotic-free period are advisable.

Contrary to popular belief, comprehensive reviews on the management of infected joint arthroplasty have demonstrated that there is insufficient evidence to support an antibiotic-free period[12,13]. This is reinforced by two original cohort studies published in 2019 that reported favorable results without an antibiotic-free period before re-implantation[14,15]. Chang et al[16] supported this view, finding no statistically significant differences between groups that had an antibiotic break and those that did not.

Even in cases with difficult-to-treat pathogens (such as fungi, rifampin-resistant staphylococci, and ciprofloxacin-resistant gram-negative bacteria), the favored approach is to undertake a three-stage process-a spacer exchange and re-implantation, or a “second first-stage”, rather than an antibiotic cessation[3]. Extending the antibiotic treatment interval after these two stages could improve outcomes.

Diagnosis, rather than antibiotic treatment, presents the main challenge when dealing with low-virulence microorganisms[17]. Microbes like coagulase-negative staphylococcus, cutibacterium acnes (previously known as propionibacterium acnes), enterococci, and actinomyces often cause late-onset periprosthetic infections with typically normal non-specific inflammatory markers. Therefore, the use of molecular techniques like multiplex polymerase chain reaction, sonication, and advanced inflammatory markers [including alpha-defensin, interleukin (IL)-6, and IL-8] should be combined with extended periods of microbe cultures. Despite this, these germs are usually sensitive to the antibiotics commonly used in two-stage revisions, requiring no adjustments in treatment or dosage[17].

Undoubtedly, given the limited literature on this topic, it is advisable to proceed with caution when making recommendations concerning antibiotic holiday periods for joint arthroplasty. The implementation of antibiotic holiday period prior to the second stage of hip or knee arthroplasty remains a controversial topic, as there is limited evidence to support this approach according to the ICM 2018 on Musculoskeletal Infection. This should be clarified in the astonishing minireview of Alrayes and Sukeik[1] about diagnosis, management and treatment of periprosthetic knee infections. Furthermore, there is a paucity of literature on the optimal duration of antibiotic holiday, and therefore further research is needed before making any clinical recommendations.