In the era of antibiotic resistance, emerging epidemics caused by multidrug-resistant organisms have become a big concern globally [21]. Outbreaks of hospital-acquired infections (HAIs) badly affect patient hospitalization courses and desired outcomes with increased morbidity, mortality, and healthcare costs [22, 23]. CLABSI is one of the HAIs that becomes a nightmare, especially among patients admitted to ICU and immunocompromised patients. In the literature, CLABSIs have been predominantly investigated as HAIs in ICU patients; however, the number of patients with CL in other hospital wards increases with more observed CLABSIs outside ICUs [24]. The mean days between line insertion and CLABSI diagnosis in adults, children, and neonates were 17.89, 16.76, and 12.15 days, respectively. Subha Rao et al. reported that all CL would be colonized after 11 days of insertion. In addition, Pitiriga et al. showed a steady increase in CLABSI rates with an increase in CL duration of more than ten days, which agreed with our findings [25, 26].

The mean CLABSI rates per 1000 central line days in this study were consistent with previously estimated rates in 12 Ministry of Health (MOH) Hospitals in Saudi Arabia (2.2–10.5 /1000 CL days); however, were higher than GCC Center for Infection Control and NSHN documented rates [3, 4, 27]. Our findings reflect higher CLABSI rates in MICU and PICU than rates reported in GCC countries by Balkhy et al. (3.1 per 1000 CL days) and globally by Rosenthal et al. (4.1 per 1000 CL days) [2, 3]. Moreover, the CLABSI rates in our ICUs were much higher than in the United States (0.68–0.87 per 1000 CL days) [28].

After the introduction of the CLABSI bundle and the application of best practices to prevent CLABSI development, an improvement in CLABSI rates has been documented with periods of zero rate [4]. Figure 2 shows zero rates for one year in the SICU and PICU during the study period. However, for different reasons, the CLABSI rates increased again in our ICUs and elsewhere [6]; other risk factors of CLABSI, including patient subgroups and comorbidities, should be investigated.

In general, CLABSI itself is considered an important mortality risk factor [29]; the overall 30-day mortality rate in our study was 33.64%, which is comparable with the mortality rates reported by Salgado Yepez et al. (30.3%) and Iordanou et al. (33.3%) and less than mortality rate reported in Saudi MOH hospitals (41.9%) [4, 30, 31]. A significantly lower CLABSI mortality rate was observed in patients with PICC compared with patients with non-tunneled catheters (P < 0.05), which was in line with previous studies [26, 32]. Avoiding CL insertion through the femoral site was recommended to reduce CLABSI occurrence [33]. Our data demonstrate a high prevalence of femoral CL use (29%) and increased CLABSI mortality among patients with femoral site CL insertion; however, this increase was statistically insignificant compared with jugular or subclavian sites.

Regarding the causative agents in our population, the Gram-negative bacteria remained the dominant cause of CLABSI throughout the study period (Figs. 3 and 4). The hospital microflora is usually dynamic, trending more towards Gram-negative predominance was observed in previous studies in the last two decades [7, 10, 33]. The most predominant Gram-negative organisms in our hospital were Enterobacteriaceae spp. (42% of all isolates), followed by Acinetobacter spp. (15%) and Pseudomonas spp. (9%), whereas Mathur et al. found Acinetobacter spp. The most isolated bacteria responsible for CLABSI (28.2%) [34].

Recently published data from Saudi Arabia showed, in line with our findings, the predominance of Gram-negative bacteria, with K. pneumoniae at the top of the list of Enterobacteriaceae as a causative agent of CLABSI [35]. Gram-positive bacteria were less frequently isolated in our population; Coagulase-negative staphylococci were found in 11% of all CLABSI-isolated bacteria, followed by S. aureus (9%). In contrast, the Gram-positive bacteria were, according to Al-Tawfiq et al., the leading CLABSI agents before 2010 [36].

Immunocompromised patients for different reasons and patients on total parenteral nutrition are at high risk for developing invasive fungal infections. Multiple predisposing factors for developing CLABSI by Candida spp. were identified according to the age groups; children with intestinal failure, gastrostomy tube, or blood transfusions are a risk group for candida-associated CLABSIs [37]. Lower birth weight of neonates is considered a risk factor for CLABSI with a high proportion of Candida spp. [38]. The prevalence of Candida spp. in CLABSI varies worldwide; Moriyama et al. reported a 4% prevalence of CLABSIs caused by Candida spp. [10]. The prevalence was higher in other studies; it ranged between 11.11% and 13.9% [31, 39]. Our data demonstrate a steady increase in CLABSI rate caused by Candida spp., from 13% to 2015 to 24% in 2020 (Fig. 5). The interplay of multiple factors might explain this trend, such as the improvement of microbiological diagnosis, overuse of broad-spectrum antibiotics, and observed increase of ICU fungal infections in the first year of COVID-19 pandemic (2020), which was the last year of the study period. According to previous studies, C. albicans was the most isolated type of candida in CLABSIs [34, 40]. Surprisingly, C. parapsilosis, a non-albicans Candida, was the most frequently isolated fungi. These findings, along with emerging multidrug-resistant C. auris in three CLABSI cases during the study period, indicate the continuous changes of the nosocomial pathogens and the selective pressure of antimicrobial agents.

Antibacterial susceptibility tests were alarming; more than 70% of Gram-positive isolates were resistant to beta-lactam antibiotics, including carbapenems. Since rifampicin is not recommended as monotherapy for Gram-positive infections, limited options remain to cover Gram-positive bacteria efficiently. The frequency of Gram-positive bacteria as CLABSI pathogens might be constant or even decreased during the study period; however, the proportion of antibiotic resistance increased, as observed in a previous study [41].

The sensitivity profiles of Gram-negative pathogens demonstrate growing resistance rates (Table 4). The sensitivity patterns of potent broad-spectrum antibiotics were not much better; around 30% were resistant to cefepime and carbapenems, whereas 38.2% were resistant to piperacillin-tazobactam. MDROs are microorganisms resistant to at least one antimicrobial agent in three or more antimicrobial categories [20]. Our findings reflect the dilemma of multidrug-resistant pathogens, classified as “superbugs” and expected to kill more than 10 million patients yearly by 2050 [42]. Sixty CLABSI bacterial isolates (29.41%) were multidrug-resistant. In addition, intrinsically multidrug-resistant organisms were isolated from nine samples. Furthermore, In a study conducted by INICC that included 50 ICUs worldwide, the resistance rates to carbapenems and amikacin were 44.3% and 29.87%, respectively [2] Salgado Yepez et al. reported 75% resistance rate of A. baumannii isolates to carbapenems, and more than 72.7% resistance rate of P. aeruginosa isolates to piperacillin-tazobactam and fluoroquinolones [30]. Our data showed emerging carbapenem-resistant Enterobacteriaceae that are on their way to replacing less resistant superbugs.

In the literature, several risk factors for CLABSI development have been identified; these include longer ICU stays, longer duration of CL, higher APACHE II score, parenteral nutrition, massive blood transfusion, use of corticosteroids, applying intra-aortic balloon counter-pulsation, bowel perforation, liver injury, pelvic injury, renal disease, and myocardial infarction [10, 11, 14, 43]. In turn, CLABSI is considered among the top seven causes of death in Western countries, and it has been identified as a mortality risk factor in several studies [2, 29, 44]. However, identifying the mortality risk factors in CLABSI patients was less investigated. Rosenthal et al. reported in two studies the mortality risk factors in patients diagnosed with device-associated HAI, which include older age, long stay in the ICU, female gender, and admission to oncology ICU [29, 45]. Our study findings indicate a significant negative survival correlation with other chronic illnesses, including diabetes mellitus, hypertension, cardiovascular disease, lung disease, renal insufficiency, and the presence of ≥ 3 comorbidities.

This study had considerable limitations. It was a single-center study that included three different age groups, introducing heterogeneity. In addition, as a retrospective study may suffer from a data collection bias by providing less optimal recorded information of some patients. Moreover, specific groups of patients who need advanced healthcare in spatialized centers were not represented adequately in our CLABSI populations, such as oncology patients, HIV/AIDS patients, or transplant patients. These limitations will prevent the generalization of our study findings. However, investigating the trends of CLABSI pathogens over six years and risk factors associated with mortality will help improve the CLABSI approach towards better patient-centered care and favorable outcomes.