Two Thirds of Mupirocin-Resistant MRSA Wrongly Treated

April 6, 2012 (London, United Kingdom) — Two thirds of patients with high-level mupirocin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) are receiving the wrong treatment because of an inefficient process for reporting sensitivity results.

The findings highlight the widespread need for electronic, integrated systems to improve appropriate and timely prescribing and to prevent development of nosocomial MRSA infections, along with the further development of resistance, according to a United Kingdom (UK)–based study presented here at the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

Philip Howard, consultant antimicrobial pharmacist at Leeds Teaching Hospitals, United Kingdom, led the study and presented the results.

"The results of this study are worrying. It shows we were screening patients for MRSA colonization but not acting on the results. This compromises patient care and wastes hospital resources," Howard told Medscape Medical News.

"All hospitals should check that they don't have a similar problem. Hospitals that use rapid MRSA detection methods but don't check mupirocin sensitivity should reconsider that strategy as we have seen a 12% high-level resistance rate [to mupirocin]."

In the UK, the most widely used Department of Health policy is active MRSA surveillance to detect and isolate MRSA carriers among elective and acute hospital admissions.

"Because we are now screening all admissions, we use large amounts of mupirocin, making it more likely that resistance could emerge," said the consultant pharmacist from one of the UK's leading teaching hospitals. Howard and his colleagues found that high-level mupirocin resistance was running at around 12%, raising the question of whether patients with MRSA were actually receiving the most effective therapy.

He explained that carriers of MRSA identified as having high-level mupirocin resistance should instead be given chlorhexidine/neomycin (Naseptin, Alliance Pharmaceuticals) or, where neomycin resistance also exists, polyhexamethylene biguanide (Prontoderm, B. Braun) for nasal decolonization.

Howard and his colleagues wanted to know the proportion of patients colonized with mupirocin-resistant MRSA as detected by routine screening who were then prescribed effective treatment for nasal decolonization. To answer this question, they decided to conduct a prospective study.

"We followed up all MRSA-positive patients identified with high-level mupirocin resistance to investigate whether they were receiving the decolonization treatment to which their MRSA infection was sensitive and if not, correct their treatment, and educate the staff looking after those patients," Mr. Howard told Medscape Medical News.

The audit involved 49,177 MRSA screening samples submitted to Leeds Teaching Hospital Trust between October 2011 and March 2012. MRSA-positive specimens were reported as mupirocin-sensitive or mupirocin-resistant, and neomycin-sensitive, if necessary. The results were released 48 hours after the initial positive MRSA screen.

In line with the audit, a check then determined whether appropriate treatment was commenced or changed according to current or previous results for all patients with high-level mupirocin-resistant MRSA.

Of the screened samples, 1131 (2.3%) were positive for MRSA. Of these, 137 (12.2%) exhibited high-level mupirocin resistance and a further 40 (29.7%) of these were also resistant to neomycin. "This suggested that our second-line therapy was unlikely to work in these patients, so it was recommended that these patients received polyhexamethylene biguanide instead," reported Howard.

The audit results revealed that some patients were receiving inappropriate treatment.

The current system used to alert healthcare staff to cases of high-level mupirocin resistant MRSA isolates from screening swabs was complex and didn't always work. "It showed that few patients had their treatment adjusted according to the susceptibility results and the stated advice on reports. Most remained on treatment with mupirocin," said Howard.

Specifically, only 47% of inpatients were receiving the correct treatment at the time the decolonization prescription was reviewed by a ward pharmacist, with the remaining 53% requiring an interventional phone call from the consultant pharmacist.

"Surprisingly, even if you came into the hospital and you were known to be colonized with mupirocin-resistant MRSA, you would still only have a 1 in 3 chance of receiving the right treatment," Howard pointed out.

He noted that it was a multidimensional problem, but it was partly due to the 2-stage reporting process and a mistaken belief that mupirocin treats all MRSA.

"Many doctors start empiric therapy but fail to check the final result. In addition, many hospitals use faster PCR [polymerase chain reaction] tests, which determine MRSA status within a few hours, but do not test for susceptibility to antimicrobials."

Delays in acting on information also prevented patients from receiving appropriate therapy. The average delay was 2.36 days from date of authorization to administration of the correct treatment. There were also communication issues related to following up patients who had been discharged before the results became known.

"There's a concern here that a delay in administering appropriate treatment for these patients with mupirocin-resistant MRSA could result in an ineffective decolonization regimen. In turn, this could possibly increase the risk of nosocomial infection in individual patients or increase MRSA transmission within the hospital," he pointed out.

"Systems are now in place to minimize the risk of this happening. However, data warehousing systems commonly used in the US [United States] would further decrease the chance of this happening. These systems link microbiology and susceptibility results to prescribed antibiotics, and flag up mismatches."

He added that the extensive use of mupirocin, especially where resistance already exists, is worrying, especially when more patients are presenting with new MRSA colonization or expressing high-level mupirocin resistance. "The increasing number of reports of high-level mupirocin resistance could mean the potential loss of one of the major treatment methods for controlling MRSA, therefore, mupirocin must be used cautiously and correctly."

Robin Howe, MD, consultant clinical microbiologist, based in the Public Health Wales diagnostic microbiology laboratory, Cardiff, Wales, commented on the work in an interview with Medscape Medical News.

"I'm not entirely surprised at these results given the way health service delivery works, but at the same time it is disappointing," he said. "Our levels of mupirocin resistance in Wales are probably comparable to the ones found in Leeds because there's always an issue around communication of results not only in the lab but to the person who makes the therapeutic decision and the time required to reach them."

He said there was a move to improve communication and recording of results so that those who need the results actually have them available. Electronic methods of recording and relaying results would eventually help resolve the situation as paper-based systems are replaced.

"There's a disconnect between those people taking the results and those who act on them. Historically it was the same person requesting the result and acting upon it but now efficiency measures mean we have lost some continuity of care," he told Medscape Medical News.

Fred Tenover, PhD, executive director, Scientific Affairs, at Cepheid, a molecular diagnostics company based in Sunnyvale, California; adjunct professor of epidemiology at Emory University in Atlanta, Georgia; and consulting professor of pathology at Stanford, California, commented on the results of the Leeds study. Until 2008, was based at the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia.

He told Medscape Medical News that there were 3 key issues regarding the poster. "First the mupirocin resistance result is a critical value and should be communicated as such directly to the physician. In the US, several studies have shown that having the pharmacist deliver data on antimicrobial resistance directly to the physician in charge of the patient works best for optimizing therapy for MRSA."

Second, he added that relying on physicians to read letters did not work, and third, quality control of laboratory results should extend beyond the testing phase and include the accurate delivery of information.

"This was a quality control failure because the correct information was not in the letters that went out to doctors," he remarked. In response to the paper-based system versus an electronic one, he said, "while electronic medical records are becoming quite common in the US, the physician still has to access the data to act on it. If the physician is unaware that there is a critical result, she or he will not look for it. It sounds like there is a need for education around the importance of a mupirocin resistance result for physicians."

Dr. Tenover added that it was noted 10 years ago that putting everyone on mupirocin before surgery instead of testing specific isolates from screening was a disaster and led to widespread resistance. "Thus, targeted testing of organisms is now conducted in most labs. Resistance remains low in most areas in the US: 3-5%."

Mr. Howard and Mr. Howe have disclosed no relevant financial relationships. Dr. Tenover is executive director of Cepheid.

22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). Poster 2378. Presented April 3, 2012.