High contribution and impact of resistant gram negative pathogens causing surgical site infections at a multi-hospital healthcare system in Saudi Arabia, 2007–2016

Surgical site infection (SSI) is a global healthcare problem increasing patient morbidity, mortality, and healthcare cost [1, 2]. Despite the fact that more than 50% are preventable [3], SSI remains the most frequent healthcare-associated infections (HAIs) in low and middle income countries, affecting up to 30% of the patients undergoing surgery [1, 4]. Even in high income countries, it is still the second frequent type of HAI, accounting for more than 20% of all HAIs [5]. Several surgical-related practices have been linked to the development of antimicrobial resistance [6]. The presence of resistant pathogens has been shown to augment the clinical and economic impacts of SSI [7]. Therefore, recent SSI guidelines stressed on the appropriate use of antimicrobial prophylaxis to reduce the risk of antimicrobial resistance [6].

Gram positive pathogens (GPPs) are traditionally the most frequently isolated SSI pathogens, with a considerable number of these pathogens are now resistant [5, 8, 9]. For example, 44% of Staphylococcus aureus and 20% of Enterococcus spp. isolated from surgical wounds in the USA are resistant [8, 9]. Unlike the prevalence of SSI in Saudi Arabia, very few studies focused on the causative pathogens and/or their resistance patterns [10‐12]. Moreover, data on surgery-specific pathogens in these reports were absolutely lacking or retrieved from a small number of patients [10‐12]. Likewise, very limited data on the resistance patterns of pathogens causing SSI were reported in the Gulf Cooperation Council (GCC) [10] and the Middle Eastern countries [13, 14]. For example, a study that combined aggregate SSI data from 30 developing countries (including some regional ones) could not present data on pathogen profile nor bacterial resistance [15]. The objective of the current study was to estimate the prevalence and extent of resistance of SSI pathogens identified during HAI surveillance in four tertiary care hospitals in Saudi Arabia; additionally, to compare such data to the US National Healthcare Safety Network (NHSN) hospitals.

The current study shows the distribution of SSI pathogens and their resistance patterns in 6 adult surgical procedures performed over 10 years in a multi-hospital healthcare system located in a high income Middle Eastern country. A number of points should be highlighted while we are interpreting the current findings; they represent only laboratory-confirmed SSI events, as 33% of all SSI events were diagnosed clinically without laboratory confirmation. The data were collected in the presence of a local guideline for surgical prophylaxis consistent with international standards [19]. Additionally, surgical bundle of the Institute for Healthcare Improvement (IHI) was implemented throughout the study [20]. Compliance with the guideline and the surgical bundle, however, has varied widely between surgeries and from time to time (data not shown).

While it is challenging to compare the distribution of SSI pathogens between different studies covering different surgical procedures, Staphylococcus aureus was the most frequent pathogen in the current study as well as studies done in developed [5, 8, 9] and developing countries [1, 21]. For example, it was approximately 23% in the current study compared with 20 to 30% in these studies [1, 5, 8, 9]. However, GNPs were more prevalent in the current study (64%) than seen in developed countries (36–46%) [5, 8, 9]. The prevalence of Pseudomonas aeruginosa and less extent Klebsiella spp. were several folds higher while Escherichia coli was generally similar to those of the US and European hospitals, even after considering surgery-specific data [5, 8, 9]. The high contribution of GNPs in the current study was consistent with several reports from Saudi Arabia [10‐12] and developing countries [1], that showed contribution rates between 55 and 77%. This may be explained by inadequate hand hygiene practices [22] and high environmental burden of GNPs, that are usually more resistant to disinfectants compared with GPPs [23]. However, the high contribution of GNPs may not be simply explained by the difference in the proportions of included procedures as the surgery-specific prevalence of Pseudomonas aeruginosa and Klebsiella spp. in the current study was much higher than corresponding NHSN figures for abdominal, pelvic, cardiac, and orthopedic procedures [8, 9]. Additionally, it is unlikely to reflect differential antimicrobial selection pressure as the local guidelines for antimicrobial prophylaxis were consistent with international standards [19].

In addition to the low contribution, GPPs causing SSI in the current study were generally less resistant than reported internationally. For example, MRSA rates was 30% in the current study compared with more than 40% in USA [8, 9], Europe [5], and Asia [24, 25]. In Saudi Arabia, there has been a great variability in the published MRSA rates, probably due to mixing community and hospital isolates as well as clinical and surveillance isolates [26, 27]. Nevertheless, the current finding was consistent with the local MRSA rates obtained from HAI specimens (mainly wound), which ranged between 16 and 57% [26]. For VRE, the current rates (13%) was comparable to recent reports from Saudi Arabia [28]. Additionally, it was comparable to international rates [5, 24], with exception of North and South American ones which traditionally have very high rates of VRE [8, 9, 24]. Despite the relatively low resistance of GPPs observed in the current and local studies, reports has warned from an increasing trend in the resistance of GPPs in Saudi Arabia, specially VRE, probably due to overuse of broad-spectrum antimicrobials and development of new resistance patterns [27, 28].

In addition to higher contribution, GNPs causing SSI in the current study were generally more resistant than reported in US hospitals. For example, all GNPs in the current study (with exception of Enterobacter spp.) were more resistant than NHSN hospitals, with significant difference in cephalosporin-resistant Klebsiella spp., MDR Klebsiella spp., and MDR Escherichia coli [8, 9]. On the other hand, the current rates were even lower than the extremely high rates of cephalosporin and carbapenem resistance among GNPs reported in some developing countries such as Egypt [13], India [29], and Iran [14]. The high rate of resistance in GNPs in the current study is probably reflecting a wide range of resistance mechanisms in GNPs observed in our hospitals, such as NDM, OXA 48 and MGrb and outer membrabe protein (OMP) resistance [30‐34]. The high rate of resistance in GNPs in the current study is quite alarming as it already increased the mortality by 25%. Additionally, this can be used as a justification for initiation and continuation of broad-spectrum antibiotics, leading to a vicious cycle of enhancing resistance. Consistent with current data, a local study showed that 77% of pathogens isolated from SSI after abdominal surgery were resistant to the prophylactic antibiotic given preoperatively [11].

With the limited data available locally and regionally, this report can serve as a unique benchmark for caregivers engaged in SSI prophylaxis and antimicrobial stewardship programs. The data were prospectively collected over 10 years by well-trained infection preventionists in 4 hospitals, using the same standard surveillance methodology and the same SSI preventive practices. The relatively large sample size allowed for presenting surgery-specific pathogen distribution and resistance patterns. The use of NHSN resistance definitions allowed for previously unmatched comparisons of resistance patterns between the two differently-matured healthcare systems. Nevertheless, few limitations are acknowledged. The analyzed data were only a sample of a much bigger number of surgeries done in the 4 hospitals during the period covered by the study and almost one-third of SSI were diagnosed clinically. However, these are typical for all studies following the NHSN definitions and NHSN-recommended targeted surveillance methodology. As in other similar studies, underestimation of SSI diagnosis cannot be excluded. However, this should be unlikely, as our population is entitled to free care in our hospitals, which make the likelihood of our patients seeking medical care elsewhere is very low. Despite being beyond of the scope of this paper, the lack of extensive data analysis on the colonization rates and the risk factors that can possibly affect the resistance patterns limit the interpretation of the current findings.

Staphylococcus aureus remains the most frequent SSI pathogen, with 30% are MRSA. GNPs are responsible for approximately 64% of SSI and were generally more resistant than seen in Western countries. Resistant GNPs were associated with increased mortality. Making this information available to caregivers and healthcare leaders is critical to secure resources and ensure support in implementing interventions, such as antimicrobial stewardship programs and evidence-based SSI preventive practices [6].