Antimicrobial Resistance in Focus
As the COVID-19 pandemic enters a more settled phase, clinicians and hospital managers are prioritizing addressing the backlog of non-emergency work that has accumulated over the last 24 months, and infection specialists are reviewing the impact of the pandemic on antimicrobial resistance and what actions need to be taken to prevent healthcare-associated infections in at-risk patients and interrupt chains of transmission where control may have been problematic in recent years.
Preventing Staphylococcus aureus (Staph aureus) and, in particular, methicillin-resistant Staphylococcus aureus (MRSA) transmission and infection, especially in high-risk patients attending non-emergency surgery, remains a priority. However, the optimal approach to both pre-operative decolonization and peri-operative antibiotic prophylaxis is controversial. While the concept of providing blanket cover in terms of nasal and skin decolonization and broad-spectrum antibiotic prophylaxis appears tempting, the potential benefits to individual patients must be balanced against possible risks to the patient and the wider community.
A publication by Branch-Elliman and colleagues [i] provides some initial insights into the risks and benefits of surgical prophylaxis consisting of beta-lactams alone versus a combination with vancomycin. The authors used a large multi-center cohort of national Veterans Administration patients in the United States undergoing heart, joint, vascular, colorectal, and hysterectomy procedures over a 5-year period and used a sophisticated statistical analysis method to compare outcomes in patients who had received vancomycin and beta-lactam combined surgical prophylaxis versus either of the antibiotics alone. The variables studied included the rate of surgical site infection (SSI), acute kidney injury, and Clostridioides difficile infection (CDI).
Around 70,000 patients were included in the analysis. Overall, SSI rates were similar between all the groups except for those undergoing cardiac surgery, where combination antibiotic prophylaxis was associated with a reduction of SSI rates. Among the cardiac surgery patients, only those colonized with MRSA showed a significant benefit from the addition of vancomycin, and it was estimated that the number of patients to be treated to prevent one SSI in MRSA-colonized patients would be 53, compared to 176 in non-MRSA colonized patients. On the adverse side, however, a significant risk of acute kidney injury was found across the board in all surgical patients receiving combination regimens. CDI was not impacted in any groups.
The authors stress that these findings are only observational and that prospective studies would be needed to confirm the findings; however, they do raise the possibility that in the cardiac surgery sub-group at least, there is a suggestion that an MRSA screening directed approach to prophylaxis may maximize benefits of the addition of vancomycin while minimizing harms.
Turning to the question of pre-surgical nasal decolonization, a detailed meta-analysis by Dadshi and colleagues [ii] reviews the world literature regarding the prevalence and trends of mupirocin resistance in Staph aureus and MRSA. The authors note that mupirocin remains the only antibiotic approved for nasal decolonization of both MRSA and methicillin-susceptible Staph aureus (MSSA) in patients and healthcare workers. However, since comprehensive data regarding mupirocin resistance is lacking, this group undertook a systematic review and meta-analysis of the scientific literature on this topic.
2243 articles were initially identified, and after applying relevant exclusion criteria, 87 publications were included in the meta-analysis, with 27 addressing high-level mupirocin resistance in methicillin-susceptible Staph aureus and 60 in MRSA.
Overall, the systematic review showed the prevalence of mupirocin resistance to MRSA to be around 13.8% compared to 7.6% for MSSA, with variations in prevalence across the world, with the Americas, in general, having a higher prevalence. Rates of high-level mupirocin resistance were higher in Asian countries, and the prevalence of high-level resistance was generally similar across both MRSA and MSSA at around 8%.
The authors highlight several limitations to this study. Of course, only published data could be analyzed, and assessment of mupirocin is by no means standard across the world. The paper notes the importance of developing standardized diagnostic tests for mupirocin resistance and of educating clinicians regarding the unrestricted use of mupirocin in patients where it is not specifically required.
Taken together, these two publications make a start in providing some compelling data to suggest that screening high-risk patients pre-operatively and optimizing both nasal decolonization and surgical antibiotic prophylaxis may both benefit individual patients and prevent further development of antimicrobial resistance.
Click here to learn more.
Author: Dr. Beryl Oppenheim
Dr. Beryl Oppenheim is a Senior Director, Medical Affairs at Cepheid.
Beryl is a medically qualified microbiologist who has worked in the National Health Service in England for many years, leading laboratories and infection control teams. Dr. Oppenheim has published widely with more than 100 peer-reviewed publications, and her main research interests include healthcare-associated infections (HAIs), antimicrobial resistance, and infections in the critically ill and immunocompromised host.
References: