Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: systematic review and meta-analysis.

Abstract

Objective To evaluate studies assessing the effectiveness of a bundle of nasal decolonization and glycopeptide prophylaxis for preventing surgical site infections caused by Gram positive bacteria among patients undergoing cardiac operations or total joint replacement procedures.

Design Systematic review and meta-analysis.

Data sources PubMed (1995 to 2011), the Cochrane database of systematic reviews, CINAHL, Embase, and clinicaltrials.gov were searched to identify relevant studies. Pertinent journals and conference abstracts were hand searched. Study authors were contacted if more data were needed.

Eligibility criteria Randomized controlled trials, quasi-experimental studies, and cohort studies that assessed nasal decolonization or glycopeptide prophylaxis, or both, for preventing Gram positive surgical site infections compared with standard care.

Participants Patients undergoing cardiac operations or total joint replacement procedures.

Data extraction and study appraisal Two authors independently extracted data from each paper and a random effects model was used to obtain summary estimates. Risk of bias was assessed using the Downs and Black or the Cochrane scales. Heterogeneity was assessed using the Cochran Q and I² statistics.

Results 39 studies were included. Pooled effects of 17 studies showed that nasal decolonization had a significantly protective effect against surgical site infections associated with Staphylococcus aureus (pooled relative risk 0.39, 95% confidence interval 0.31 to 0.50) when all patients underwent decolonization (0.40, 0.29 to 0.55) and when only S aureus carriers underwent decolonization (0.36, 0.22 to 0.57). Pooled effects of 15 prophylaxis studies showed that glycopeptide prophylaxis was significantly protective against surgical site infections related to methicillin (meticillin) resistant S aureus (MRSA) compared with prophylaxis using β lactam antibiotics (0.40, 0.20 to 0.80), and a non-significant risk factor for methicillin susceptible S aureus infections (1.47, 0.91 to 2.38). Seven studies assessed a bundle including decolonization and glycopeptide prophylaxis for only patients colonized with MRSA and found a significantly protective effect against surgical site infections with Gram positive bacteria (0.41, 0.30 to 0.56).

Conclusions Surgical programs that implement a bundled intervention including both nasal decolonization and glycopeptide prophylaxis for MRSA carriers may decrease rates of surgical site infections caused by S aureus or other Gram positive bacteria.

Discussion

Although multiple studies have assessed the efficacy of interventions to prevent surgical site infections caused by Gram positive bacteria, these interventions are not uniformly applied to surgical patients. Our results showed that nasal decolonization was associated with decreased rates of Gram positive surgical site infections andStaphylococcus aureus surgical site infections among patients undergoing cardiac or orthopedic surgical procedures. However, these results remained statistically significant for S aureus surgical site infections, though not all Gram positive surgical site infections, when the meta-analysis was limited to randomized controlled trials. Additionally, a bundle that included nasal decolonization and glycopeptide prophylaxis for patients who carried methicillin (meticillin) resistant S aureus (MRSA) was associated with significantly decreased rates of surgical site infections caused by Gram positive bacteria and by S aureus.

We also found that routine use of prophylactic glycopeptides protected against MRSA infections but not against all Gram positive surgical site infections. Additionally, dual prophylaxis with a glycopeptide and another antimicrobial agent seemed to be more protective against Gram positive surgical site infections than prophylaxis with glycopeptides alone. This finding is consistent with studies of methicillin susceptible S aureus (MSSA) bacteremia, which found that vancomycin is less effective than a β lactam antibiotic for treating MSSA infections.^63 64 These results are similar to the conclusions of a recent review article, which stated that vancomycin is not recommended for preoperative prophylaxis but may be considered as a component of an MRSA bundle to prevent surgical site infections.⁶⁵

Our meta-analyses were the first to assess a bundle that included nasal decolonization and targeted glycopeptide prophylaxis for MRSA carriers. Other meta-analyses have assessed nasal decolonization or glycopeptide prophylaxis alone,^66 67 68 and our results confirm the findings of the previous studies and extend these by including the results of recent studies. Future meta-analyses should assess other outcomes associated with these interventions. These outcomes could include duration of hospital stay since one group of researchers found that the mean duration of hospital stay was significantly shorter in those randomized to mupirocin and chorhexidine gluconate rather than to placebo.²⁷ Future meta-analyses should also confirm our preliminary findings that these interventions do not open a niche for pathogens other than S aureusto fill, and should also analyze other patient populations such as those requiring trauma surgery to determine if these findings are generalizable to other surgical specialties.

Nasal decolonization protected against S aureus surgical site infections when all patients were decolonized and when only S aureus carriers were decolonized. Routine nasal decolonization of all surgical patients may be easier to implement and more cost effective than using cultures or polymerase chain reaction testing to screen patients preoperatively.⁶⁹ None the less, it may be prudent to reserve mupirocin decolonization for patients who carry S aureus to prevent widespread mupirocin resistance.⁷⁰Similarly, it may be prudent to do further research on targeted prophylaxis with vancomycin before including this bundle in clinical practice. Of note, the pooled relative risks assessing Gram positive surgical site infections were identical for both the decolonization studies and the bundle studies. Thus high quality studies such as cluster randomized trials are still needed to determine whether adding glycopeptide prophylaxis to nasal decolonization will further decrease the incidence of Gram positive surgical site infections.

In our sensitivity analyses we found that nasal decolonization was associated with a 1% risk difference and the bundle was associated with a 0.5% risk difference in Gram positive surgical site infections. Although these differences seem small, they are clinically significant considering that cardiac and orthopedic operations are common and surgical site infections are associated with considerable morbidity. Each year, approximately 300 000 cardiac operations and approximately 900 000 total joint arthroplasties are done in the United States alone.⁷¹ Thus these interventions could prevent 6000 to 12 000 surgical site infections per year in the United States and even more worldwide.

Limitations of this study

Our study has some limitations. Firstly, meta-analyses are only as valid as the studies that contribute to the pooled risk ratio. We included many studies that were simple before and after quasi-experimental studies. Additionally, none of the included studies adjusted statistically for potential confounders, thus confounding may be problem, especially among the observational studies. To mitigate this limitation, we performed subset analyses on the results of only randomized controlled trials. Secondly, we did not include studies that did not report or could not provide specific data on Gram positive infections, thus we may have excluded important decolonization and prophylaxis studies. However, nine of 15 contacted investigators submitted additional data for inclusion in the analyses. Thirdly, studies of the association between interventions and Gram positive surgical site infections were heterogeneous, and thus some of the meta-analysis results should be interpreted with caution. Once these studies were stratified by potential sources of heterogeneity, the stratified subsets were homogeneous. For example, nasal decolonization aims to decrease the incidence of endogenous S aureus surgical site infections. The association between nasal decolonization and Gram positive surgical site infections may have been different for studies in which S aureus caused most Gram positive surgical site infections compared with studies in which surgical site infections due to other Gram positive pathogens were common. Thus we limited heterogeneity by doing subset analyses that separated studies focusing on S aureus surgical site infections from those focusing on all Gram positive surgical site infections.

Conclusion

Surgical site infections caused by Gram positive bacteria may be prevented by decolonizing patients who carry S aureus in their nares and potentially by adding a glycopeptide to the usual prophylaxis using β lactam antibiotics for MRSA carriers. High quality randomized controlled trials or cluster randomized trials should be performed to further assess this bundle.

What is already known on this topic

• Surgical site infections (SSIs) are potentially preventable adverse events of cardiac and orthopedic operations
• SSIs significantly increase hospital length of stay, readmission rates, healthcare costs, and mortality rates
• Clinicians and researchers have debated whether nasal decolonization or glycopeptide antibiotic prophylaxis reduce SSIs caused by Gram positive bacteria
• Among patients undergoing cardiac or orthopedic surgery:
• Nasal decolonization with mupirocin ointment was protective against Gram positive SSIs
• Preoperative prophylaxis with anti-methicillin (meticillin) resistant Staphylococcus aureus (MRSA) antibiotics when given to all patients was not protective against Gram positive SSIs
• A bundle that included nasal decolonization and anti-MRSA prophylaxis for MRSA carriers was significantly protective against Gram positive SSIs

What this study adds

 

• Among patients undergoing cardiac or orthopedic surgery:
• Nasal decolonization with mupirocin ointment was protective against Gram positive SSIs
• Preoperative prophylaxis with anti-methicillin (meticillin) resistant Staphylococcus aureus (MRSA) antibiotics when given to all patients was not protective against Gram positive SSIs
• A bundle that included nasal decolonization and anti-MRSA prophylaxis for MRSA carriers was significantly protective against Gram positive SSIs

Source: BMJ

 

 

Epimerox: New Broad-Spectrum Antibiotic Developed, Kills MRSA, Anthrax.

Researchers at the Rockefeller University and a pharmaceutical company have developed a new antibiotic that kills a wide range of bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and Bacillus anthracis, the bacteria that causes anthrax.

According to their paper published in the journal PLoS ONE, the antibiotic called Epimerox targets weaknesses in bacteria that have long been exploited by viruses that attack them, known as phage.

Target selection is critical for the development of new antimicrobial agents. To date, most approaches for target selection have focused on the importance of bacterial survival. However, in addition to survival, scientists believe that molecular targets should be identified by determining which cellular pathways have a low probability for developing resistance.

“For a billion years, phages repeatedly have infected populations of bacteria, and during this period of time they have identified weaknesses in the bacterial armor,” said senior author Prof Vincent Fischetti from the Rockefeller University’s Laboratory of Bacterial Pathogenesis and Immunology. “We’re taking advantage of what phage have ‘learned’ during this period for us to identify new antibiotic targets that we believe will escape the problem of resistance found for other antibiotics.”

The path to identification of this new target spanned more than seven years of effort. The team used a phage-encoded molecule to identify a bacterial target enzyme called 2-epimerase, which is used by Bacillus anthracis to synthesize an essential cell wall structure.

Based on a 2008 study, the team identified a previously unknown regulatory mechanism in 2-epimerase that involves direct interaction between one substrate molecule in the enzyme’s active site and another in the enzyme’s allosteric site. They chose to target the allosteric site of 2-epimerase to develop inhibitory compounds, because it is found in other bacterial 2-epimerases but not in the human equivalent of the enzyme. Through the collaboration with a pharmaceutical company, an inhibitor of 2-epimerase named Epimerox was developed.

First study author Dr Raymond Schuch tested the inhibitor in mice infected with Bacillus anthracis. He found that not only did Epimerox protect the animals from anthrax, but the bacteria did not develop resistance to the inhibitor.

The team also found that Epimerox was able to kill drug-resistant Staphylococcus aureus with no evidence of resistance even after extensive testing.

“Since nearly all Gram-positive bacteria contain 2-epimerase, we believe that Epimerox should be an effective broad-range antibiotic agent,” Prof Fischetti said.

“The long-term evolutionary interaction between phage and bacteria has allowed us to identify targets that bacteria cannot easily change or circumvent. That finding gives us confidence that the probability for developing resistance to Epimerox is rather low, thereby enabling treatment of infections caused by multi-drug-resistant bacteria such as MRSA. It is a very encouraging result at a time when antibiotic resistance is a major health concern.”

Source: /www.sci-news.com