To our knowledge, this is the first study attempting to investigate predisposing factors associated Ab-PJI. Interestingly the well-known predictors of PJI, revision surgeries, non-elective arthroplasties and late infections (PJI diagnosed after 3 months of index surgery) were independently associated with A. baumannii infection. This likely reflects the particular epidemiology of a Brazilian orthopaedic referral center, on which, the rates of nosocomial SSI caused by MDR-GNB is high [25, 26]. In addition, high selective pressure imposed by misuse of empirical broad-spectrum antibiotics is likely to have played a major role [27]. Since then, a local antimicrobial stewardship program has been implemented as a tool towards the appropriateness of antibiotics prescription.
In the microbiological sample, a higher frequency (81.8%) of Ab strains causing PJI was XDR, whereas 12.1% were MDR and only 6.1% were MS. Susceptibility to carbapenems was worryingly low, with only 3% of cases sensitive to imipenem and 6% sensitive to meropenem. The higher prevalence of Ab-PJI at our institution was not assumed to represent an outbreak, but this is rather an endemic nosocomial pathogen typically identified in the intensive care unit (ICU) environment, which presents an overwhelming ability to colonise the human skin. Furthermore, before 2018 the immediate postoperative care for patients who undergo arthroplasty in our hospital was usually performed at ICU, which is likely to have increased the rate of skin colonisation by Ab strains.
Orthopaedic implant-associated infections have traditionally been considered a difficult-to-treat disease due to the formation of bacterial biofilms on the implant surface, and the low levels of antibiotic penetration into bone tissue and biofilms.[28, 29] In addition, the higher levels of bacterial resistance commonly expressed by Ab, makes treatment even more challenging due to the scarcity of available drugs and to antibiotic-related toxicity.[30] Although Ab is ubiquitous in nature and colonises the skin of healthy individuals, most human infections are healthcare-associated. A systematic review by Falagas et al.,[31] which included 55 articles describing Ab infections, associated Ab infections with prolonged hospital stays, intensive care unit treatments, and the use of invasive devices.
Despite the poor availability of studies specifically describing Ab-PJI, the number of osteomyelitis and fracture-related infections caused by Ab seems to be on the rise worldwide, especially those associated with high-kinetic energy trauma and open fractures.[32] Many studies have described a strong association between complex traumatic gunshot wounds resulting in fracture-related infections or osteomyelitis with Ab in various conflict-affected regions, such as Iraq, Afghanistan, and Yemen.[32–35] However, whether Ab is acquired during the injury itself from primary contamination, or is hospital-acquired during the trauma care and subsequent surgical procedures remains unclear. In addition to reports from Middle Eastern countries, a study by Vanegas et al [36] from Colombia addressed osteomyelitis, skin and soft tissue infections and reported an increased number of infections caused by Ab, and strong association with recent hospitalisation or surgery, and previous use of antimicrobials in the past six months. Despite the increased risk of PJI following revision surgeries [37–39], the association between revision arthroplasty and Ab-PJI has not yet been reported in the literature. However, we are aware that implant contamination during surgery is a primary source of infection, and patients previously colonised with Ab may be at increased risk for PJI.
In our study, a 2.6-fold increase in the risk of Ab-PJI was identified among patients undergoing emergency arthroplasties, which suggests that similar to fracture-related infections, post-traumatic arthroplasties may be a predisposing factor to Ab-PJI. The reasons underlying the association between trauma and Ab infection were not elucidated in this study and require further investigation. In addition, we were unable to identify any independent associations between Ab-PJI with closed proximal femoral fractures in the elderly population, the recent hospitalisation history, or recent use of antibiotics. However, non-elective arthroplasties may require longer preoperative hospital stays due to the mandatory propaedeutic for assessing preoperative risks and the need to compensate for clinical comorbidities prior to performing the surgical procedure, which might increase the risk of colonisation by Ab [40]. However, the length of preoperative hospital stays, which could validate this hypothesis, was not a variable that was assessed in the present study.
In our study late PJI was independently associated with Ab infection, and a possible explanation may rely upon the lower level of virulence expression when bacteria expresses multiple antibiotic-resistant mechanisms. Several mechanisms associated with antimicrobial resistance, including pump efflux and biofilm organisation abilities, also decrease the bacterial replicative capacity [41]. This stationary phase, associated with biofilm formation and maturation, is likely to cause Ab infections to develop more slowly, increasing the likelihood of being diagnosed as late PJI.[42, 43] Neither Ab infections nor the surgical strategy used after the infectious diagnosis was independently associated with final outcomes or risks of treatment failure. Few studies have assessed the prognostic factors associated with Ab-PJI development, although some reported high rates of therapeutic failure in Ab-PJI, such as Vasso et al., [19] which described a 33.3% failure rate for Ab-PJI. However, that study was underpowered, assessing only nine patients in a group containing a mix of infections associated with both Ab and P. aeruginosa. Another study that assessed the outcomes of PJI caused by BGN-MDR reported that infections caused by MDR/XDR BGN were associated with high-therapeutic failure rates when DAIR (52.2%) was performed compared with non-DAIR strategies (23.4%) [44]. However, only 3 patients had Ab-PJI in this study, which is not a representative sample.
The present study has potential limitations. First, it was performed as a retrospective study, conducted at a single centre, located in a major city in a developing country, which offers specialised orthopaedic care for the regional population. Consequently, the results obtained at our hospital may not apply to other hospitals. In addition, the identification and sensitivity tests were performed using non-automated methods, and no molecular or genotypic analyses were performed to identify clonal variants or similar patterns of resistance mechanisms. Furthermore, no pairing was performed between the Ab-PJI and Non-Ab-PJI groups to control for preoperative hospitalisation times or the preoperative colonisation by Ab, which could support the hypothesis that PJI contamination occurred intraoperatively. However, this study explored the previously unexamined issue of PJI-predisposing factors and relied on the largest number of Ab infection cases described to date, with a high frequency of MDR/ XDR strains.