Stewardship / Resistance Scan for Dec 05, 2018

Severe MRSA in China, Australia
Antibiotic cycling and MRSA, C diff incidence
Antibiotic time-outs

Severe MRSA ST398 infections reported in China, Australia

Two articles yesterday in Emerging Infectious Diseases describe severe infections caused by highly virulent strains of methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 398, a clonal type that is usually associated with animals.

In one article, Chinese researchers report on two MRSA ST398 strains isolated from two patients with severe surgical site infections. Antimicrobial susceptibility testing showed that both strains were resistant to beta-lactam antibiotics but were susceptible to most other antibiotics. Whole-genome sequencing  (WGS) showed the isolates had similar resistance genes (blaZ and mecA) and virulence factors, but did not harbor the tetM tetracycline-resistance gene, which is typically found in livestock-associated (LA) MRSA.

The patients denied any livestock contact, and further genetic analysis showed characteristics of community-associated (CA) MRSA isolates. When tested in a mouse infection model, the strains caused abscesses that were significantly larger than those caused by other CA-MRSA strains previously isolated from patients in China and South Korea.

In the second article, Australian scientists report on a MRSA ST398 isolated from a patient with MRSA bacteremia. Antimicrobial susceptibility testing showed that the isolate was only resistant to beta-lactams, and WGS revealed the presence of the blaZ and mecA resistance genes and several virulence factors, but not the tetM gene.

Phylogenetic analysis indicated the strain had a much closer relationship to CA-MRSA ST398 isolates previously described in China than to LA-MRSA ST398 isolates that have been frequently identified in pigs in Australia. The scientists were not able to establish whether the patient—who was from Singapore but working in Australia—had contact with livestock or had visited China before his illness.

"Unlike LA-MRSA ST398, CA-MRSA ST398 has been shown to be highly virulent and has become the predominant CA-MRSA circulating in Shanghai, China," the authors of the study write. "Thus, continued monitoring of this strain's epidemiology and preventing its widespread transmission is essential.

LA-MRSA ST398 was first identified in pigs and pig farmers in 2003 and is the predominant lineage of LA-MRSA in Europe and North America. To date, most human infections have been found in people with direct animal contact.
Dec 4 Emerg Infect Dis article #1
Dec 4 Emerg Infect Dis article #2


Study finds antibiotic cycling not tied to lower C diff, MRSA incidence

In another study yesterday in Emerging Infectious Diseases, researchers in Northern Ireland reported that an antibiotic cycling strategy implemented at a teaching hospital did not lead to a reduced incidence of healthcare-associated Clostridioides difficile (HA-CDI) or healthcare-associated (HA) MRSA.

The intervention at Antrim Area Hospital involved cyclical restrictions of amoxicillin-clavulanic acid, piperacillin-tazobactam, and clarithromycin over a 2-year period (October 2013 to September 2015). The intervention was based on an analysis of epidemiologic data from 2007 through 2012 that identified macrolides and piperacillin-tazobactam as significantly associated with HA-MRSA and amoxicillin-clavulanic acid as significantly associated with HA-CDI. The policy restricted use of piperacillin-tazobactam and macrolides on alternate months and amoxicillin-clavulanic acid for 2 consecutive months every 4 months.

To determine whether the strategy had an impact on HA-MRSA and HA-CDI incidence and new extended-spectrum beta-lactamase (ESBL) incidence and resistance, the researchers used segmented regression analysis to compare outcome measures before and after introduction of the policy and between the intervention hospital and a control hospital. They also looked at whether any effect observed during the intervention was reversed upon return to standard policy.

The results showed that during the intervention, HA-CDI incidence did not change and HA-MRSA increased significantly at the intervention hospital, while resistance of new ESBL isolates to amoxicillin-clavulanic acid and piperacillin-tazobactam decreased significantly. But after the hospital returned to its standard antibiotic policy, incidence of HA-MRSA decreased, incidence of new ESBLs increased, and ESBL resistance to piperacillin-tazobactam increased.

The authors conclude, "Our results suggest that antibiotic cycling is not an appropriate strategy to reduce the incidence of HA-MRSA or HA-CDI but might be effective in reducing ESBLs." 
Dec 4 Emerg Infect Dis study


Study: Antibiotic 'time-out' strategy doesn't reduce overall use

A multicenter study yesterday in Clinical Infectious Diseases found that a provider-drive antibiotic "time-out" (ATO) did not have an impact on overall antibiotic use but was associated with a decrease in inappropriate therapy.

The ATO strategy, which involves structured conversations during clinical rounds to determine if modification or discontinuation of antibiotic therapy is warranted, was implemented across 11 units located in six hospitals in Maryland. The ATO took place on antibiotic days 3 to 5, and patients receiving any of 23 selected study antibiotics for at least 3 calendar days were eligible.

In the quasi-experimental study, researchers compared hospital antibiotic days of therapy (DOT) per patient admission and total antibiotic DOT per admission during a 6-month baseline period and a 9-month intervention period. They also evaluated the appropriateness of antibiotic therapy on days 3 to 5.

Among the study population, the average hospital DOT was 12.7 per admission and total DOT was 18.9 per admission in the baseline period and 12.2 and 18.2, respectively, in the intervention period. After controlling for study unit and season, there was no difference between hospital DOT or total DOT per admission in the baseline versus intervention period. However, modification in the antibiotic prescription was more common, and there was a decrease in inappropriate antibiotic therapy on days 3 to 5, in the intervention period (45% in the baseline vs. 31% in the intervention).

"We believe that the results of our study contribute to existing evidence supporting the need for ASPs [antibiotic stewardship programs] to achieve goals of optimizing prescriptions and reducing overall antibiotic use," the authors of the study write. "The ATO may be a useful adjunct, but not a replacement for other stewardship interventions."
Dec 4 Clinical Infect Dis study

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