The first important finding of this study is the confirmation that patients in CKD group have a health status different from the general population. Indeed, patients affected by CKD have higher CCI score. Many medical conditions may be responsible for both CKD and PJI. Older age and BMI are well demonstrated as risk factors for PJI [16,17,18,19], and in a case–control study comparing PJI with healthy controls, Breznicky et al. found that these comorbidities were present in 24% of patients with PJI compared with 3% in controls [20]. Obesity, DM, and metabolic syndrome are strong risk factors for both PJI and CKD [21]. Chronic renal failure is strongly associated with the full spectrum of cardiovascular diseases, and this situation has been observed not only in end-stage renal disease patients but also in patients with mild or moderate CKD [22, 23]. Even though the aim of the study was not to define the risk of PJI in patients with CKD, on the basis of our results, we presume that the difference in patient characteristics could impact on the microorganism profile.

Regarding the profile of microorganisms, the most common bacteria found in periprosthetic joint infections are Gram-positive bacteria, especially Staphylococcus and Streptococcus species [24], while fungal PJIs account for less than 1% of all cases [24,25,26]. This study confirmed the predominance of Gram-positive bacteria, in particular Staphylococcus and Streptococcus spp., as the main microorganisms responsible for PJIs. However, the relative frequencies demonstrated increased St. epidermidis and St. aureus and decrease of the other coagulase-negative staphylococci and Cutibacterium acnes in CKD group. MRSA was 2.41 times more frequent in CKD that in control group. One reason could be the higher correlation between CKD and previous history of osteomyelitis, as observed in the current study. MSSA is the most frequently identified pathogen across all types of osteomyelitis, followed by Pseudomonas aeruginosa and MRSA.

Even though we could not determine how many patients in our study were undergoing hemodialysis at the time of THA, we discussed it as a potential risk factor for different microorganism profiles. Hemodialysis is an important source of hematogenous spread of microorganisms, and dialysis-dependent patients have a much greater risk of MRSA infection [27] in literature. Actually, hemodialysis requires ongoing intravenous access via a central catheter or a dialysis shunt, and numerous studies have linked this greater prevalence to catheter-related infections [27]. In Denmark, the incidence of bloodstream infection was 13.7 per 100 person-years in hemodialysis patients and 0.53 per 100 person-years in a population control [28]. Among the causative organisms of catheter-related bacteriemia isolated in the blood samples, S. aureus and MRSA are the most common causative organism. The incidence of S. aureus bacteremia in hemodialysis patients was 46.9-fold that of the general population in Denmark [29].

PJI caused by Gram-negative Enterobacteriaceae (including E. coli) represented 20% of all PJI in CKD group versus 7% in the control group. E. coli, Klebsiella, Serratia marcescens, and Morganella morganii are typically associated to hospital-related infections [30]. They occur more frequently in immunocompromised patients and carriers of invasive medical devices such as catheters. They can cause a wide spectrum of infections such as pneumonia, sepsis, surgical-site infections, and urinary tract infections (UTI). In PJI, their prevalence is about 10% [31]. Patients with CKD are exposed to multiple sources of colonization by nosocomial Gram-negative microorganisms: repeated urinary tract infections [32], higher number of hospitalizations [11], and sepsis [2]. In catheter-related infection in hemodialysis, the most common among the Gram-negative bacteria are E. coli, Enterobacter species, and Klebsiella species [33]. Other studies in Canada found that the relative risks of Pseudomonas aeruginosa and anaerobe infections were increased in hemodialysis patients [34, 35].

PJI caused by fungi account for 1% of total PJI, and in 50% of cases Candida albicans is the causative microorganism [24,25,26]. In this study, Candida albicans and Candida spp. were responsible for 2.3% of hip PJIs in the CKD group. Candida spp. are another typical causative microorganism for hospital-related infections, explaining the increased risk in CKD [36].

Another potential factor that may help explain the difference in microorganism profile in patients with CKD could be the difference in symbiotic bacteria present in these patients. Prior research has indicated that CKD is associated with gut dysbiosis, and this relationship is referred to as the “gut–kidney axis” [37, 38]. Recently, gut microbiota dysbiosis has emerged as a significant contributor to the progression of chronic kidney disease (CKD) and its associated complications [39]. Gram-negative Enterobacteriaceae, found to be significantly increased in CKD group, seem to be increased in the gut microbiota of patients with CKD [40]. Stanford et al. demonstrated that individuals with CKD, in contrast to healthy controls, exhibit a decreased number of symbiotic species, coupled with increased numbers of potential pathobionts from the Enterobacteriaceae and Streptococcaceae families [41]. Other findings revealed significant alterations in the diversity of intestinal microbiota in fecal samples between patients with stage 3–4 CKD and healthy subjects. The CKD cohort displayed a higher proportion of Gram-negative bacteria and facultative anaerobes [42]. Chisari, Parivizi et al. found that products from increased gut permeability were significantly increased in hip and knee revision for PJI than in revisions for aseptic loosening [43]. Administration of preoperative oral probiotics needs further investigation, as it may reduce the risk of PJI in patients affected by CKD.

The different profile of microorganisms in patients with CKD might have clinical relevance for treatment outcomes. While the overall success of treatment of hip PJI is 70–90% [44, 45], the increased number of PJI due to MRSA, Gram-negative bacteria, and fungi could increase the risk of treatment failure [31, 46]. Reduced antibiotic susceptibility could decrease the chance of success. A study on urine cultures including M. morganii, S. marcescens, Klebsiella, and others found significant decrease in antibiotic susceptibility [47]. Klebsiella spp. and Enterobacter spp. can become resistant to majority of beta-lactam antibiotics during treatment. Carbapenem-resistant Enterobacteriaceae such as E. coli, Klebsiella pneumoniae, and Enterobacter species are difficult to treat, as carbapenem resistance is often accompanied by resistance to additional drug classes and can lead to “pandrug”-resistant bacteria [48]. If surgery represents the mainstay of PJI treatment, prolonged antibiotic therapies are still fundamental for success [49]. For example, a study on debridement, antibiotics, irrigation and implant retention (DAIR) showed a good success rate in cases of early acute infection by multidrug-sensitive bacteria, while in the presence of infection by multidrug-resistant bacteria the treatment failure rate was higher [50]. In patients with CKD, we found higher prevalence of infections caused by Enterococcus spp., Streptococcus spp., and multiple microorganisms that are frequently associated with hospital-acquired colonization or repeated antibiotic treatments. Moreover, a significant proportion of infections were caused by E. coli, Klebsiella, and other Enterobacter species, which often produce extended-spectrum beta-lactamases (ESBLs). These enzymes enable these microorganisms to resist the effects of broad-spectrum cephalosporins and monobactams [51]. In addition, in the Endo-Klinik and Cardiff experiences, PJI caused by those bacteria represent risk factors for failure after one-stage revision [52, 53]. Our hypothesis is that PJI caused by these microorganisms could be associated to antibiotic-resistant phenotypes.

Moreover, owing to renal insufficiency, the use of antibiotics can be restricted in CKD, so that PJI from extremely resistant bacteria can lead to infections that are very difficult to treat [54]. In patients with CKD, two-stage exchange could be indicated for infection control. In selected cases of patients affected by severe comorbidities, 1.5-stage exchange [55] could be a good solution, with implantation of a spacer for indefinite time, which is easier to change in case of infection recurrence or mechanical failure.

There are some limitations to this research. First, it was not possible to determine the complete antibiotic resistance profile of microorganisms; however, it was possible to identify and classify certain strains, such as methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE), because these were explicitly saved in the database under these names. Second, patients in the CKD group were not stratified according to the severity of renal insufficiency. One could expect different microorganism profiles between patients with mild CKD and those who are dialysis-dependent. The different populations characteristics (CCI) can be a confounding factor. However, the strength of the study lies in the large sample size and the complete collection of data regarding microorganism profile.