The WHO guideline for SSI prevention was launched as if it were the iPhone8. I immediately went looking for what I think is the intervention with the strongest evidence: pre-op nasal mupirocine and CHX bathing, see why here. After an interesting read I’m pleased that the guideline is clear, but I missed an evaluation on feasibility and the evidence for simplification is turned around.

The guideline:

“Patients undergoing cardiothoracic and orthopaedic surgery with known nasal carriage of S. aureus should receive perioperative intranasal applications of mupirocin 2% ointment with or without a combination of CHG body wash. (Strong recommendation, moderate quality of evidence)”..

and

“in patients with known nasal carriage of S. aureus undergoing other types of surgery perioperative intranasal applications of mupirocin 2% ointment with or without a combination of CHG body wash should be considered.” (Conditional recommendation, moderate quality of evidence)

The critical aspect here is the identification of S. aureus. Immediately after the landmark Bode study we tried to implement pre-op screening in our hospital. Despite considerable efforts we could only conclude (after 6 months) that implementing screening, testing, reporting and treating was hardly feasible. Since then I ask colleagues, and I have an almost 100% confirmation rate of this experience. Unfortunately, this has not yet been reported. You might think: how was this done in that study? Well, enrollment was a problem, just because of the logistics (which also included obtaining informed consent during the study), but the paper is on the screened patients only.

The simple solution is: “don’t screen, treat all”. Treatment is cheaper than screening, and all carriers will be treated as there is no misclassification (due to false-negative test results or sampling error). This guarantees maximum benefit of the intervention. There is no scenario more cost-effective, as long as resistance doesn’t reduce effectiveness considerably, see.

The WHO guideline on this: “The commission strongly believes that decolonization with mupirocin ointment with/without CHG body wash should be performed on known S. aureus carriers only in order to avoid unnecessary treatment and the spread of resistance.”

So, this part of the guideline is based on “strong believes”. That sound medieval, and is justified as follows: “…AMR is an important possible harm associated with the use of mupirocin (1, see at end blog). It was emphasized that an approach to treat all patients, regardless of their carriage status, instead of carriers only increases the likelihood of resistance to mupirocin (2,3). The available evidence (4, 5, 6) and additional studies (7,8) showed no trend towards an increasing prevalence of mupirocin resistance following its short-term use in surgical patients. However, there is evidence that the increased short-term use of mupirocin leads to an increase of resistance to mupirocin and other antibiotics (9). “

If you analyze this reasoning: There is a problem (A, ref 1-3), but no evidence from studies (B, ref 4-8), but there is a problem (C, ref 9).

Part A: comes from 2 reviews addressing the potential problem, but without new empirical data, and a retrospective study on decreasing rates of mupi-R in MRSA I  a single hospital

Part B:  comes from 3 double-blind RCTs (>4500 pts), 1 prospective single center 4-yr longitudinal study) and a review

Part C (used here to overrule part B) comes from a retrospective study on CoNS only that actually led to a prospective study (included in part B) and quantification of the risk of emergence of resistance in S. aureus. In 936 surgical patient, the acquisition rate of mupi-R in CoNS during short-term mupi/CHX use was 7.4/100 patientdays at risk, without any transmission to S. aureus, see. Combining empirical data with a mathematical model yielded that mupi-R acquisition in CoNS constitutes a low risk for mupi-R in S. aureus, see.

My take on this: Surgical patients need protection against S. aureus, which is offered by short-term mupi/CHX. Screening all pre-op is complicated and certainly less cost-effective than “treat all”. Available evidence demonstrates that short-term mupi/CHX use selects for mupi-resistance in CoNS, with a very low transmission rate of mupi-R to S. aureus. Monitoring mupi-R in S. aureus SSI allows timely reconsideration of strategies in case of emergence. In the meantime, many €€€€ (and $$$, ££) can be spend more wisely.

Naturally, mupi-R S. aureus can spread clonally. But that is due to poor hygiene, rather than short-term mupi/CHX use, and should not be used as an argument to withhold cost-effective infection prevention in settings that control spread of S. aureus. Looking forward to reading the rest of the guideline, and to hear what others think.

 

References

1. Poovelikunnel T, Gethin G, Humphreys H. Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. J Antimicrob Chemother. 2015;70(10):2681-92.
2. Cookson BD. The emergence of mupirocin resistance: a challenge to infection control and antibiotic prescribing practice. J Antimicrob Chemother. 1998;41(1):11-8.
3. Talon D, Marion C, Thouverez M, Bertrand X. Mupirocin resistance is not an inevitable consequence of mupirocin use. J Hosp Infect. 2011;79(4):366-7.
4. Konvalinka A, Errett L, Fong IW. Impact of treating Staphylococcus aureus nasal carriers on wound infections in cardiac surgery. J Hosp Infect. 2006;64(2):162-8
5. Perl TM, Cullen JJ, Wenzel RP, Zimmerman MB, Pfaller MA, Sheppard D, et al. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. New Engl J Med. 2002;346(24):1871-7.
6. Kalmeijer MD, Coertjens H, van NieuwlandBollen PM, Bogaers-Hofman D, de Baere GA, Stuurman A, et al. Surgical site infections in orthopedic surgery: the effect of mupirocin nasal ointment in a double-blind, randomized, placebo-controlled study. Clin Infect Dis. 2002;35(4):353-8
7. Fawley WN, Parnell P, Hall J, Wilcox MH. Surveillance for mupirocin resistance following introduction of routine peri-operative prophylaxis with nasal mupirocin. J Hosp Infect. 2006;62(3):327-32
8. Hetem DJ, Bonten MJ. Clinical relevance of mupirocin resistance in Staphylococcus aureus. J Hosp Infect. 2013;85(4):249-56
9. Bathoorn E, Hetem DJ, Alphenaar J, Kusters JG, Bonten MJ. Emergence of high-level mupirocin resistance in coagulase-negative staphylococci associated with increased short-term mupirocin use. J Clin Microbiol. 2012;50(9):2947-50.