Risk of surgical site infection after hip hemiarthroplasty of femoral neck fractures: a systematic review and meta-analysis.

INTRODUCTION: Surgical site infection (SSI) is a major complication following hemiarthroplasty surgery for displaced neck of femur fractures. Our aim is to systematically analyse relevant peer-reviewed studies for recent clinical information on the quantitative risk of surgical site infection (SSI) after hemiarthroplasty (HA) of hip fracture patients and on the factors which influence the SSI rates. METHODS: A comprehensive search of electronic databases (PubMed, Cochrane) was performed for clinical articles published between 2005 and 2023 and systematically reviewed with a defined list of inclusion and exclusion criteria. The methodology was undertaken and reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement checklist, while the detailed search strings and study protocol were published in PROSPERO (CRD42023458150). The pooled risks of SSIs were calculated in both primary and subgroup analyses. RESULTS: The primary analysis showed a pooled superficial SSI rate after hemiarthroplasty of 1.3% (95% confidence interval (CI) 0.71; 2.04) from 17 studies with 29,288 patients and a deep SSI rate of 2.14% (1.87; 2.42) from 29 studies with 192,392 patients. Higher infection rates were observed with longer follow-up periods for deep SSI: pooled rates increased from 1.24% (0.73; 1.87) at 1 month to 2.64% (2.03; 3.31) at 12 months. Additionally, studies using defined criteria for infection diagnosis reported higher rates compared to undefined criteria: pooled deep SSI rates were 2.91% (1.40; 4.92) vs. 0.62% (0.34; 0.96) for defined vs. undefined criteria respectively, and 3.18% (2.23; 4.29) vs. 1.7% (1.44; 1.99) for superficial SSI. CONCLUSIONS: The results of this study demonstrate a substantial SSI risk and a high variability of the infection rates following hemiarthroplasty for hip fracture patients. A standardization of infection criteria and an extended follow-up period are advisable and should be considered in guidelines aimed at improving the standard of care for these patients.

[Bone cement as a local antibiotic carrier]. / Knochenzement als lokaler Antibiotikaträger.

BACKGROUND: There is widespread consensus that adjuvant local use of antimicrobial agents in combination with their systemic administration can better prevent and treat implant-associated musculoskeletal infections. The advantage of local antibiotics lies in their particular pharmacokinetics with initially high antibiotic concentrations at the implant site with only low systemic uptake. AIM OF TREATMENT: The aim of local application is to protect the foreign bodies directly at the implantation site from bacterial colonization and biofilm formation (prophylaxis) and to support the eradication of an already established infection after surgical debridement (treatment). Since the observations of Prof. Buchholz, bone cement has been the most frequently used local carrier system. APPLICATION: In cases of infection, surgeons should ideally work together with microbiologists, infectiologists or clinical pharmacists to determine which anti-infective agents are indicated systemically for the patient and which ones are indicated locally with PMMA cement, based on the pathogen(s) and antibiograms. However, for the anti-infective agents administered with bone cement, there is still uncertainty about which agents can be added to this carrier material and at what concentrations. Accordingly, the authors of this review article not only summarize the rationale and evidence for local antibiotic use but also elaborate on the points that must be considered for admixing these agents to the cement.

Patients at a high risk of PJI: Can we reduce the incidence of infection using dual antibiotic-loaded bone cement?

Prosthetic joint infection (PJI) is one of the most devastating complications of orthopedic surgery. However, not all patients are equally at the risk of severe infection. The incidences of PJI vary with the host and surgery-related risk factors. It is now generally accepted that some important medical comorbidities may predispose the patients to a high risk of PJI. Time-consuming and invasive surgical procedures, such as revision arthroplasties, are also associated with a high incidence of PJI, presumably due to the increased risk of surgical site contamination. Effective infection-preventing strategies should begin with identifying and optimizing the patients at a high risk of infection prior to surgery. Optimizing the operating room environment and antibiotic prophylaxis are also essential strategies that help minimize the overall incidence of infection in orthopedic surgery. The ideal antibiotic prophylaxis is still under debate, and discussions have emerged about whether variations or adjustments to the standard protocol are justified in patients at a high risk of infection. This also includes evaluating the possible benefits and risks of using high-dose dual antibiotic-loaded bone cement instead of low-dose single antibiotic-loaded bone cement in arthroplasty. This review summarizes the evidence showing that the combination of two local antibiotics in bone cement exerts a strong and longer-lasting antimicrobial effect against PJI-associated pathogens. This conclusion is consistent with the preliminary clinical studies showing a low incidence of PJI in high-risk patients undergoing cemented hemiarthroplasty, cemented revision, and primary arthroplasty if dual ALBC is used. These results may encourage clinicians to consolidate this hypothesis in a wider clinical range.

Periprosthetic joint infections in femoral neck fracture patients treated with hemiarthroplasty - should we use antibiotic-loaded bone cement?

BACKGROUND: Hemiarthroplasty is the most common treatment in elderly patients with displaced intra-capsular femoral neck fracture (FNF). Prosthetic joint infection (PJI) is one of the most feared and frequent complications post-surgery because of the frail health status of these patients and the need for fast track surgery. Therefore, priorities should lie in effective preventive strategies to mitigate this burden. AIM: To determine how much the implementation of the routine use of antibiotic-loaded bone cement (ALBC) as a relatively easy-to-apply amendment to the surgical practice reduces the infection rate in our hemiarthroplasty cohort. METHODS: We retrospectively assessed all demographic, health status and treatment-related data of our FNF patients undergoing cemented hemiarthroplasty in the period from 2011 to 2017; 241 patients were further analyzed after exclusion of patients with cancer-related sequelae and those who died before the end of the 1-year observation period. The PJI rate as diagnosed on basis of the Musculoskeletal Infection Society (MSIS) criteria 2011 was determined for each included patient and compared in function of the bone cement used for hip stem fixation. Patients were split into a group receiving a plain bone cement in the period from January 2011 to June 2013 (non-ALBC group) and into a group receiving an ALBC in the period July 2013 to December 2017 (ALBC group). Data analysis was performed with statistical software. We further calculated the cost-efficacy of the implementation of routine use of ALBC in the second group balancing the in-hospital infection related treatment costs with the extra costs of use of ALBC. RESULTS: In total 241 FNF patients who received cemented hemiarthroplasty in the period from January 2011 to January 2017 were eligible for inclusion in this retrospective study. There were 8 PJI cases identified in the ALBC group among n = 94 patients, whereas 28 PJI cases were observed in the non-ALBC group among n = 147 patients. The statistical analysis showed an infection risk reduction of 55.3% (in particular due to the avoidance of chronic delayed infections) in the ALBC group (95%CI: 6.2%-78.7%; P = 0.0025). The cost-evaluation analysis demonstrated a considerable cost saving of 3.500 € per patient, related to the implementation of routine use of ALBC in this group. CONCLUSION: Use of ALBC is a potent infection preventive factor in FNF patients receiving cemented hemiarthroplasties. It was further found to be highly cost-effective.

Dual antibiotic loaded bone cement in patients at high infection risks in arthroplasty: Rationale of use for prophylaxis and scientific evidence.

In view of the demographic changes and projected increase of arthroplasty procedures worldwide, the number of prosthetic joint infection cases will naturally grow. Therefore, in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance. In the absence of a "miracle weapon" priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks, the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen. Instead of a "one size fits all" philosophy, it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient- and procedure-related risk factors. A stronger focus on the local application mode via use of high dose dual antibiotic-loaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre. The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.

Infection Risk-Adjusted Antibiotic Prophylaxis Strategies in Arthroplasty: Short Review of Evidence and Experiences of a Tertiary Center in Spain.

There is growing body of evidence that important patient-, procedure- and pathogen-related factors are linked to higher risks for prosthetic joint infections (PJI) following arthroplasty surgeries. The prior identification and optimization of such risk factors is considered paramount to minimize the incidence of these infections. Without any doubt, antibiotic prophylaxis remains one of the cornerstones among all preventive measures. However, the ideal antibiotic prophylaxis is still in debate and discussions have emerged, whether certain situations deserve adjustments or variations of the standard protocol taking into account antibiotic resistance surveillance data and patient risk factors for infections. This review aims to provide the reader with an overview of possible antibiotic prophylaxis strategies in response to these risks and discusses the clinical experiences so far obtained. We further present preliminary evidence that the use of a reinforced local antibiotic prophylaxis regimen with high-dose dual antibiotic-loaded bone cement may be an effective and easy-to-apply option in patients at high infection risks.

Risk assessment of antibiotic resistance development by antibiotic-loaded bone cements: is it a clinical concern?

Because of the risk of bacterial biofilm infections, prophylactic use of antibiotics in orthopaedic procedures involving the implantation of large prosthesis systems is considered mandatory.A strategy based on the rationale that local antibiotics released from bone cement or other carriers establish a second antibacterial frontline in and around the prosthesis is considered complementary to the administration of systemic antibiotics.Although less common as a consequence of the initially very high drug concentrations of local antibiotics in the tissues, a selection process of previous high resistance bacteria may occur, leading to antibiotic resistance.The use of antibiotic combinations in bone cement is generally accepted to improve antibiotic efficacy and minimizes the treatment failure risk due to antibiotic resistance. This is important in septic revisions and/or in patients at particularly high risk of infection.On an individual basis, the benefit of a lower infection probability with combined systemic and local antibiotic application should outweigh the risk of the selection of more resistant bacteria. Each prevented infection means that a complex and extended antibiotic therapy with risk of resistance development over time has been avoided.On an epidemiological level there is no clinical evidence that the routine use of bone cement impregnated with appropriate bactericidal antibiotics promotes the widespread development of antibiotic resistance and thereby puts the successful treatment of a prosthetic joint infection at higher risk. Cite this article: EFORT Open Rev 2019;4:576-584. DOI: 10.1302/2058-5241.4.180104.

Dendritic cells (DC) activated by CpG DNA ex vivo are potent inducers of host resistance to an intracellular pathogen that is independent of IL-12 derived from the immunizing DC.

We used the model of murine leishmaniasis to evaluate the signals enabling Ag-pulsed dendritic cells (DC) to prime a protective Th1 response in vivo. Bone marrow-derived DC (BMDC) that had been activated by TNF-alpha or CD40 ligation were not able to induce protection against leishmaniasis in susceptible BALB/c mice. In contrast, all mice vaccinated with a single dose of Leishmania major Ag-pulsed BMDC stimulated by prior in vitro exposure to CpG-containing oligodeoxynucleotides (ODN) were completely protected, had a dramatic reduction in parasite burden, and developed an Ag-specific Th1 response. Importantly, systemic administration of CpG ODN was not required. Protection mediated by ex vivo CpG ODN-activated and Ag-pulsed DC was solid, as documented by resistance to reinfection with a higher parasite dose, and long-lasting, as immunized mice were still protected against L. major challenge 16 wk after vaccination. A significantly increased level of protection could also be elicited in resistant C57BL/6 mice. Surprisingly, IL-12 expression by the immunizing BMDC was not required for induction of host resistance. In contrast, the availability of IL-12 derived from recipient cells was essential for the initial triggering of protective immunity by transferred BMDC. Together, these findings demonstrate that the type of stimulatory signal is critical for activating the potential of DC to induce a Th1 response in vivo that confers complete protection against an intracellular pathogen. Moreover, they show that the impact of activated DC on the initiation of a protective Th cell response in vivo may be independent of their ability to produce IL-12.

Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens.

Upon loading with microbial Ag and adoptive transfer, dendritic cells (DC) are able to induce immunity to infections. This offers encouragement for the development of DC-based vaccination strategies. However, the mechanisms underlying the adjuvant effect of DC are not fully understood, and there is a need to identify Ag with which to arm DC. In the present study, we analyzed the role of DC-derived IL-12 in the induction of resistance to Leishmania major, and we evaluated the protective efficacy of DC loaded with individual Leishmania Ag. Using Ag-pulsed Langerhans cells (LC) from IL-12-deficient or wild-type mice for immunization of susceptible animals, we showed that the inability to release IL-12 completely abrogated the capacity of LC to mediate protection against leishmaniasis. This suggests that the availability of donor LC-derived IL-12 is a requirement for the development of protective immunity. In addition, we tested the protective effect of LC loaded with Leishmania homolog of receptor for activated C kinase, gp63, promastigote surface Ag, kinetoplastid membrane protein-11, or Leishmania homolog of eukaryotic ribosomal elongation and initiation factor 4a. The results show that mice vaccinated with LC that had been pulsed with selected molecularly defined parasite proteins are capable of controlling infection with L. major. Moreover, the protective potential of DC pulsed with a given Leishmania Ag correlated with the level of their IL-12 expression. Analysis of the cytokine profile of mice after DC-based vaccination revealed that protection was associated with a shift toward a Th1-type response. Together, these findings emphasize the critical role of IL-12 produced by the sensitizing DC and suggest that the development of a DC-based subunit vaccine is feasible.

The method used to sample ulcers influences the diagnosis of cutaneous leishmaniasis.

Before beginning treatment for cutaneous leishmaniasis, parasitological confirmation of the disease is required. The most commonly used diagnostic procedures are microscopy and culture of samples taken from the active edge of the lesion. In this study, we compared the sensitivity of previous diagnostic procedures with the polymerase chain reaction (PCR), using smears taken from the edge of the lesion and its centre. The sensitivity was greater with smears taken from the centre of the lesion, both for microscopical examination (85%) and for PCR (81%), compared to those obtained from the edge of the lesion (69% and 58% respectively). When PCR was carried out on biopsy material from the edge of the lesion the sensitivity was 63%.

Molecular and antigenic characterization of the Leishmania (Viannia) panamensis kinetoplastid membrane protein-11

The kinetoplastid membrane protein 11 (KMP-11) has been recently described in Leishmania (Leishmania) donovani as a major component of the promastigote membrane. Two oligonucleotide primers were synthesized to PCR-amplify the entire coding region of New World Leishmania species. The Leishmania (Viannia) panamensis amplification product was cloned, sequenced and the putative amino acid sequence determined. A remarkably high degree of sequence homology was observed with the corresponding molecule of L. (L) donovani and L. (L) infantum (97 per cent and 96 per cent respectively). Southern blot analysis showed that the KMP-11 locus is conformed by three copies of the gene. The L. (L) panamensis ORF was subsequently cloned in a high expression vector and the recombinant protein was included and purified from Escherichia coli cultures. Immunoblot analysis showed that 80 per cent, 77 per cent and 100 per cent sera from cutaneous, mucocutaneous and visceral leishmaniasis patients, respectively, recognized the recombinant KMP-11 protein. In a similar assay, 86 per cent of a asymptomatic Leishmania-infected individuals showed IgG antibodies against the rKMP-11. We propose that KMP-11 could be used as a serologic marker for infection and disease caused by Leishmania in America.