ASP Scan (Weekly) for Aug 17, 2018

MRSA colonization
Mupirocin-resistant S aureus in Africa
MCR-3 in English pigs
ESBL E coli in Europe
Complicated UTI treatment trial

VA study finds MRSA colonization significantly increases infection risk

Originally published by CIDRAP News Aug 16

A longitudinal study of inpatients at Department of Veterans Affairs (VA) acute care hospitals has found that methicillin-resistant Staphylococcus aureus (MRSA) colonization significantly increases the risk of MRSA infection, with a substantial number of infections occurring after discharge from the hospital, VA researchers report in Clinical Infectious Diseases.

The retrospective study looked at a cohort of 985,626 inpatient admissions to VA acute care hospitals from 2008 through 2015, focusing only on patients who had surveillance testing for colonization status performed on admission. A patient whose admission MRSA screen and all subsequent screens were negative was categorized as not colonized. A patient who had a positive MRSA screen was classified as an importer, and a patient who had a negative MRSA screen on admission, but a subsequent positive screen, was defined as an acquirer.

For each of the three groups, the researchers calculated the proportion of MRSA infections that occurred prior to discharge and at 30, 90, 180, and 365 days after discharge, then determined the relationship between MRSA colonization status and infection.

Overall, 903,190 patients (91.6%) were found not to be colonized with MRSA during their hospitalization, 72,388 (7.3%) were importers, and 10,048 (1.0%) were acquirers. The MRSA infection rate across the predischarge and 180-day postdischarge time period was 5.5% in importers and 7.0% in acquirers, rising to 11.4% in importers and 11.7% in acquirers who were admitted directly to the intensive care unit. In the multivariable regression analysis, the predischarge hazard ratio for MRSA infection was 29.6 for importers and 28.8 for acquirers compared to those not colonized. When measured at 180 days postdischarge, 63.9% of all pre- and postdischarge infections among importers occurred during the postdischarge period. For acquirers, this value was 61.2%.

"In conclusion, acquisition of MRSA during hospitalization markedly increases the risk to a patient of subsequent infection that may not become manifest until after discharge," the authors wrote. "These factors should be taken into account when optimizing infection control strategies for MRSA."
Aug 11 Clin Infect Dis study


Study indicates high prevalence of mupirocin-resistant S aureus in Africa

Originally published by CIDRAP News Aug 16

A systematic review and meta-analysis yesterday in Antimicrobial Resistance & Infection Control suggests there is a high rate mupirocin-resistant S aureus in Africa.

Mupirocin nasal ointment, alone or in combination with chlorhexidine, is considered the main decolonization strategy for S aureus carriage, which is an important risk factor for subsequent infection among patients with surgical site infections and atopic dermatitis. The emergence of mupirocin-resistant (mupR) S aureus threatens this decolonization strategy. While mupR S aureus has been reported in several countries, there is no data summarizing screening, prevalence, characterization, and geographic spread in Africa.

Using five electronic databases, researchers from South Africa and Nigeria identified 43 eligible studies. Only 12 of 54 African countries (22%) reported data on screening for mupR S aureus. The pooled prevalence of mupR S aureus in Africa, based on 11 human studies conducted in South Africa, Ghana, Libya, Egypt, and Nigeria, was 14%. The proportion of S aureus isolates with the mupA gene, which confers high-level mupirocin resistance (HmupR), ranged between 0.5 and 8%. Isolates that expressed HmupR and low-level resistance (LmupR) ranged between 0.5 and 38% and 4 and 47%, respectively. The frequency of mupR-MRSA isolates ranged between 5 and 50%.

The authors of the study say the findings show the paucity of data on the continent and support the need for mupR S aureus surveillance data to provide information on it epidemiology and clinical significance. In addition, they note the need for data on administration and use of mupirocin in the community and hospital setting in Africa.  
Aug 15 Antimicrob Resist Infect Control study


MCR-3 detected in study of English pigs

Originally published by CIDRAP News Aug 15

A study of pigs has detected the presence of the MCR-3 colistin-resistance gene in England for the first time, United Kingdom researchers reported yesterday in the Journal of Antimicrobial Chemotherapy. But the study also found that stopping the use of colistin can mitigate long-term on-farm persistence.

To gain a better understanding of the molecular epidemiology of MCR-positive Enterobacteriaceae, circulating plasmids, and their on-farm persistence, researchers from the UK's Animal and Plant Health Agency used whole-genome sequencing to analyze MCR-1-positive Enterobacteriaceae isolates from pig samples on a single pig farm. They collected fecal samples from three cohorts of pigs: one that was initially treated with colistin following diarrhea, a younger cohort that was untreated but overlapped with the first cohort over a period of 5 months, and a third cohort on the same farm 20 months after the initial diagnostic submission.

The results showed that Escherichia coli harboring MCR-1 and multiple resistance genes were detected in the colistin-treated cohort of pigs as well as the untreated cohort. The researchers theorize that the presence of MCR-1 in the untreated pigs may have been because these pigs had moved into accommodations previously occupied by the treated pigs and had been exposed to environmental contamination with MCR-1 E coli. Additionally, the researchers found MCR-3 in seven of the E coli isolates from the treated cohort, with some isolates also harboring multiple copies of MCR-1 on different plasmids.

Neither MCR-1 nor MCR-3 were detected when the farm was re-sampled after 20 months.

"In conclusion, this study indicated that although mcr E. coli had become widespread on a farm in England, measures taken to mitigate on-farm risk were successful," the authors wrote. 
Aug 14 J Antimicrob Chemother study


Study shows emergence of E coli ST131 clade in Europe

Originally published by CIDRAP News Aug 15

In another study yesterday in the Journal of Antimicrobial Chemotherapy, a team of European researchers report the emergence of an extended-spectrum beta-lactamase (ESBL)-producing E coli ST131 clade in European hospital patients.

In the study, 688 ESBL E coli isolates were obtained from rectal swabs of patients in hospitals in Berlin, Geneva, Madrid, and Utrecht. The researchers were looking to assess the prevalence, geographical distribution, and microbiological characteristics of E coli ST13—a multidrug-resistant pandemic clone causing urinary tract and bloodstream infections—and its dominant sublineage, C/H30.

The analysis found that the ST131 detection rate among ESBL E coli carriers was 20.5% (141/688), with 16% (46/295) prevalence in Madrid, 18% (31/172) prevalence in Utrecht, 23% (31/135) in Berlin, and 38% (33/86) in Geneva. Subclone typing further revealed that C/H30 subset compromised the majority of the ST131 isolates (70.2%, 99/141). But there was significant difference in subclone prevalence, with C1/H30R1 isolates more prevalent in Geneva (49%, 16/33) and C2/H30Rx more prevalent in Madrid (67%, 31/46). While the C2/H30Rx isolates were significantly associated with the CTX-M-15 enzyme, the C1/H30R1 isolates were more associated with the CTX-M-27 enzyme.

Isolates belonging to this new ST131-C1-M27 clade have previously been detected among Japanese, French, and German isolates, but the detection of isolates from this clade in all four hospitals suggest it is circulating throughout Europe. The authors of the study say the findings demonstrate a changing epidemiology of ESBLs in Europe caused by ST131 subclones.
Aug 14 J Antimicrob Chemother abstract


Promising phase 2 trial for complicated UTI treatment

Originally published by CIDRAP News Aug 14

A phase 2 clinical trial for Entasis Therapeutics' β-lactamase inhibitor, ETX2514, in combination with sulbactam (ETX2514SUL), suggested safe and efficacious treatment of complicated urinary tract infections (cUTI) including acute pyelonephritis (kidney infection) in adults, the company said in a press release today.

The results will prepare Entasis for a Phase 3 trail in the early part of next year, which will focus on carbapenem-resistant Acinetobacter baumannii infections.

"Infections caused by Gram-negative bacteria are a major healthcare challenge today, as resistance to older antibiotics is growing," said Manos Perros, chief executive officer of Entasis in the press release. "The results of this Phase 2 trial support progression of ETX2514SUL into Phase 3, an important next step in developing our pipeline of pathogen-targeted products against drug-resistant bacterial infections."

The phase 2 trial included 80 patients randomized to receive either a dose of ETX2514SUL (ETX2514 1 g plus sulbactam 1 g) or a matching placebo every 6 hours for 7 days. Patients in both arms also received background therapy with 500 mg IV of  imipenem/cilastatin (IMI) every 6 hours.

According to the press release, ETX2514SUL was generally well tolerated. The adverse event profile of ETX2514SUL was similar to placebo with no serious adverse events reported in either arm.
Aug 13 Entasis press release

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