ASP Scan (Weekly) for Jul 21, 2017

Origins of MRSA
Drug-resistant gonorrhea
Antiretroviral-resistant HIV
AMR in the food chain
Stewardship and skin infections
MDR plasmid transfer
Antibiotics and birth defects
Antibiotic Rx in England
Fecal transplant effect on UTIs
Non-prudent abx use in Europe

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

MRSA emerged long before methicillin was introduced, researchers find

Originally published by CIDRAP News Jul 20

A study today in Genome Biology suggests methicillin-resistant Staphylococcus aureus (MRSA) emerged several years before methicillin was used to treat S aureus infections.

To identify the origins of MRSA, which first started to appear shortly after methicillin was introduced in the United Kingdom in 1959 in response to widespread penicillin resistance in S aureus, researchers conducted whole genome sequencing on a collection of 209 MRSA isolates recovered in Europe between 1960 and 1989. In reconstructing the evolutionary history of the isolates, they hoped to identify when the first MRSA lineage arose, and when it acquired the staphylococcal cassette chromosome mec (SCCmec), a collection of genes containing the mecA gene, which is associated with methicillin resistance.

The earliest MRSA isolates belonged to sequence type (ST) 250, and further investigation of 122 isolates with precise dates and places of origin indicated that a SCCmec element had initially been acquired by S aureus around or before 1946. The researchers theorize that widespread use of penicillin to treat S aureus in the 1940s and 1950s then selected for strains carrying the mecA gene, which also encodes penicillin resistance. That would explain why MRSA began to appear within a year of methicillin being introduced in the clinic.

"Our study provides important lessons for future efforts to combat antibiotic resistance," corresponding author and molecular biologist Matthew Holden, PhD, says in a press release from the University of St. Andrews. "It shows that new drugs which are introduced to circumvent known resistance mechanisms, as methicillin was in 1959, can be rendered ineffective by unrecognized, pre-existing adaptations in the bacterial population."

Holden and his colleagues say the findings highlight the importance of continual surveillance of pathogen populations for evidence of emerging adaptations and resistance patterns.
Jul 20 Genome Biol study
Jul 20 University of St. Andrews press release


Australian surveillance shows increase in drug-resistant gonorrhea

Originally Published by CIDRAP News Jul 20

An Australian surveillance system set up last year to provide early warning of the spread of resistant bacteria has detected more than 1,000 cases across the country resistant to last-line antibiotics and an increase in antibiotic-resistant gonorrhea, according to a report yesterday from the Australian Commission on Safety and Quality in Health Care (ACSQHC).

The first report of the National Alert System for Critical Antimicrobial Resistance (CARAlert) revealed 1,064 instances of highly resistant bacteria from Mar 17, 2016, to Mar 31, 2017. Scientists reported at least one strain of bacteria that cannot be treated by last-line antibiotics in every state and territory. These strains are called critical antimicrobial resistances (CARs), and at least 37% of all CARs were from patients in the community, not from hospitalized patients.

An average of 86 entries were made to CARAlert each month.

Before December 2016, the most commonly reported CARs were carbapenemase-producing Enterobacteriaceae (CPE). One type of CPE, called the IMP type, is now endemic on the eastern seaboard.

Since December, the most frequently reported type of CAR was azithromycin-resistant Neisseria gonorrhoeae, which accounted for 67% of all CARs reported to the CARAlert system in February this year and 62% in March. Azithromycin is a key gonorrhea antibiotic.
Jul 19 ACSQHC report
Jul 19 ACSQHC news release


WHO: HIV strains becoming resistant to common antivirals

Originally published by CIDRAP News Jul 20

The World Health Organization (WHO) warned today of growing drug resistance in more than 10% of people beginning antiretroviral treatment for HIV.

The information was based on data from 11 countries surveyed in Africa, Asia, and Latin America. In six of those countries, 10% of newly diagnosed HIV (human immunodeficiency virus) patients have a strain that’s resistant to antivirals. Once the 10% resistance threshold is crossed, the WHO recommends that a country re-evaluate which antivirals are used as first-line treatment.

According to the WHO, mathematical modeling shows that, in the next 5 years, 135,000 deaths and 105,000 new infections could occur if resistance patterns continue. This would raise HIV treatment costs by an additional $650 million in the 5-year period.

"Antimicrobial drug resistance is a growing challenge to global health and sustainable development," said Tedros Adhanom Ghebreyesus, PhD, director-general of the WHO. "We need to proactively address the rising levels of resistance to HIV drugs if we are to achieve the global target of ending AIDS by 2030."

Resistance to antiretrovirals occurs when people do not take the drugs as prescribed, which often happens when people do not have consistent access to HIV care. The levels of HIV in their blood increase, and they can transmit the new, resistant virus to others, the WHO said.
Jul 20 WHO news release


Codex Alimentarius to revise guidelines on AMR in the food chain

Originally published by CIDRAP News Jul 19

Members of the World Health Organization's (WHO's) food standards–setting body, the Codex Alimentarius Commission, agreed yesterday to update guidelines aimed at reducing antimicrobial resistance along the food chain.

The group, which is meeting this week in Geneva to discuss adoption of several new standards on food safety, agreed to revise and broaden the scope of the Code of Practice to Minimize and Contain Antimicrobial Resistance, a 2005 document that provides guidance for the responsible and prudent use of antimicrobials in food-producing animals.

The revisions will include developing a risk-based guidance on the management of foodborne antimicrobial resistance, with greater focus on the risk to human health associated with the presence of antimicrobial resistant organisms in the food chain. The updated code will also address strategies to reduce the need for antimicrobials in food-producing animals. 

The commission also agreed to develop guidance on the design and implementation of integrated surveillance of foodborne antimicrobial resistance along the food chain. The hope is that a harmonized approach to surveillance will facilitate the exchange and analysis of data from different countries.  
Jul 18 WHO food safety update


Stewardship linked to better outcomes in patients with skin wounds

Originally published by CIDRAP News Jul 19

Appropriate use of antimicrobial agents under the direction of an antimicrobial stewardship program (ASP) can lead to improved outcomes for patients with skin and soft-tissue infections (SSTIs), researchers reported yesterday in the American Journal of Infection Control.

In the quasi-experimental study conducted at three hospitals from a single health system in Des Moines, Iowa, researchers collected prospective and historic control data for the 7-month ASP intervention period (January through July 2012) and a 7-month period from the prior year. The ASP intervention was centered around a new SSTI evidence-based treatment algorithm, passive provider education about the treatment algorithm, and additional education (including phone calls and notes from the medical record) targeting physicians not adhering to the algorithm.

Of the 412 patient charts that were reviewed across the two 7-month periods, a total of 76 and 86 patients were found eligible from the historic and prospective time periods, respectively. The outcomes revealed the proportion of appropriate antibiotic usage in the intervention period was nearly twice that of the historic period, and that patients in the intervention period had a lower median number of days of antipseudomonal antibiotic use, a reduced median number of days from the initial intravenous antibiotic therapy to oral conversion, and fewer SSTI treatment complications.

The authors note, however, that there were some unexpected results. The median length of hospital stays in both periods remained consistent, and there was no significant decrease in the duration of antibiotic therapy in the intervention period. In addition, quicker transition from intravenous to oral antibiotic therapy was not associated with rapid improvement in patients' clinical appearance.

"Although additional positive outcomes may have been expected, it remains apparent that quality improvements can be obtained when guided by stewardship," the authors write.
Jul 18 Am J Infect Control study


Study shows high rate of transfer of MDR plasmid in chicken gut model

Originally published by CIDRAP News Jul 19

UK scientists have demonstrated that the transfer of a multidrug-resistant (MDR) plasmid from Salmonella to Escherichia coli occurs at a high rate in the simulated gut of a chicken, even in the absence of antibiotics, according to a study yesterday in mBio.

Plasmids are highly mobile pieces of DNA that can be shared within and between different bacterial species, enhancing their ability to spread drug resistance. The researchers used an in vitrochemostat system to approximate the chicken cecal microbiota, simulate colonization by an MDR Salmonella pathogen, and examine the dynamics of transfer of its MDR plasmid harboring several genes, including the extended-spectrum beta-lactamase blaCTX-M1. They also assessed the impact of cefotaxime administration on plasmid transfer and microbial diversity.

They demonstrated via polymerase chain reaction testing and whole-genome sequencing that MDR plasmid transfer occurred from Salmonella to E coli isolates. And it occurred to seven E coli sequence types at high rates, even in the absence of cefotaxime usage, with resistant strains isolated within 3 days from the start of the experiment.

The authors concluded, "We show that transfer of a multidrug-resistant plasmid from the zoonotic pathogen Salmonella to commensal Escherichia coli occurs at a high rate, even in the absence of antibiotic administration. Our work demonstrates that the in vitro gut model provides a powerful screening tool that can be used to assess and refine interventions that mitigate the spread of antibiotic resistance in the gut before undertaking animal studies."
Jul 18 mBio study


Several antibiotics linked to higher rates of congenital defects

Originally published by CIDRAP News Jul 19

A large study out of Quebec found that in utero exposure to clindamycin, doxycycline, quinolones, and several other antibiotics was linked to organ-specific malformations in babies, while other antibiotics were not associated with major congenital malformations (MCMs).

Writing in the British Journal of Clinical Pharmacology, the investigators analyzed data on 139,938 infants born in Quebec from 1998 through 2008. They assessed antibiotic exposure in the first trimester of pregnancy and identified congenital malformations in the first year of life.

After adjusting for potential confounders, they determined that clindamycin exposure was associated with a 34% increased risk of MCMs, a 67% added risk of musculoskeletal system malformations, and an 81% rise in ventricular or atrial septal defects.

Doxycycline exposure more than doubled the risk of circulatory system malformation, cardiac malformations, and ventricular/atrial septal defect. They also noted one MCM each with quinolone, moxifloxacin, ofloxacin, macrolide, erythromycin, and phenoxymethylpenicillin.

The researchers found no link to MCMs with amoxicillin, cephalosporins, and nitrofurantoin. The same group in May reported higher rates of miscarriage tied to antibiotic use.
Jul 19 Br J Clin Pharmacol study
May 2 CIDRAP News story "Antibiotics in pregnancy tied to higher miscarriage risk"


More antibiotic prescriptions in UK coming from non-medical prescribers

Originally published by CIDRAP News Jul 18

A retrospective analysis of antibiotic prescriptions in England published yesterday in the Journal of Antimicrobial Chemotherapy found that nearly 8% of all antibiotics dispensed in primary care are prescribed by non-medical prescribers (NMPs), mostly nurses.

In the United Kingdom, NMPs—appropriately qualified non-medical healthcare professionals such as nurses, pharmacists, and allied health professionals—have the authority to independently prescribe medicine within their area of competence. They work in a variety of settings and provide a broad range of healthcare services, and their numbers are rising. To date, however, there have been no available data on the pattern of antibiotic prescribing by NPMs in England.

Using data from the National Health Service (NHS), researchers found that from July 2011 through December 2015, the number of NMPs rose by 38.5% (from 21,545 to 29,836). Of these prescribers, 89.8% were nurses, 9.9% were pharmacists, and 3.3% were allied health professionals. While the rate of all antibiotics dispensed per NMP decreased over the study period, the volume increased, with the percentage of all primary care antibiotics dispensed that were prescribed by NMPs rising from 5.6% to 7.6%, a 37.1% increase.

The vast majority of these dispensed NMP prescriptions for antibiotics were written by nurses, but the percent declined over time, from 28.79 per nurse prescriber at the beginning of 2011 to 26.22 per nurse prescriber by the end of 2015. Dispensed pharmacists' prescriptions for antibiotics, in contrast, increased from 0.83 per prescriber in January 2011 to 4.08 per prescriber in October 2015.

Penicillins were the most commonly prescribed antibiotics, followed by sulphanomides and trimethoprim, macrolides, tetracyclines, and nitrofurantoin. The data did not allow researchers to make any judgment on the appropriateness of these prescriptions

The authors conclude that with the number of NMPs in England set to rise in coming years, this group should be involved in antimicrobial stewardship efforts.
Jul 17 J Antimicrob Chemother abstract


Small study finds FMT reduces frequency of recurrent UTIs

Originally published by CIDRAP News Jul 18

Fecal microbiota transplantation (FMT) for treatment of recurrent Clostridium difficile infection (CDI) significantly decreased recurrent urinary tract infection (UTI) frequency and improved the antibiotic susceptibility profile of UTI-causing organisms in a small study today in Clinical Infectious Diseases.

In the study, Mayo Clinic investigators retrospectively identified eight patients who had undergone FMT for recurrent CDI (three or more episodes) and had three or more UTIs in the year preceding FMT. These patients were with to a control group of eight patients who had recurrent CDI managed with antibiotics and had three or more UTIs in the year prior to the third CDI episode.

Based on a previous study that found FMT for recurrent CDI eradicated vancomycin-resistant Enterococci (VRE) colonization in 73% of VRE-positive patients, the researchers hypothesized that FMT might also reduce the frequency of recurrent UTIs from antibiotic-resistant organisms by decolonizing multidrug-resistant organisms (MDROs) from the gut.

The results showed a significant decrease in the frequency of UTIs among the case-patients, from a median of four episodes in the year before to one episode in the year after FMT (P = 0.01). Positive urine samples cultured in the year before and after FMT showed a reduction in the most common organisms cultured, with E coli–positive samples dropping from 15 before FMT to 4 after, and Klebsiella pneumoniae-positive samples dropping from 9 to 1. In addition, susceptibility testing conducted after FMT showed a reduction in the number of E coli and K pneumoniae isolates that were resistant to ampicillin, ciprofloxacin, trimethoprim-sulfamethoxazole, and nitrofurantoin.

By comparison, the patients managed with antibiotics saw no difference in the frequency of UTIs in the year before and after the third CDI episode (a median of four UTI episodes), and no changes in antimicrobial resistance patterns in E coli and K pneumoniae isolates before and after antibiotic treatment.

"Although our findings are limited by a small sample size and lack of microbiome profiling, we demonstrate that FMT may decrease the frequency of MDRO UTIs possibly by gut decolonization through reestablishment of colonization resistance," the authors write. "This effect may lead to decreased antibiotic use, morbidity, and cost."
Jul 18 Clin Infect Dis abstract


Report details non-prescription use of antibiotics in Europe

Originally published by CIDRAP News Jul 17

A report today from the European Commission estimates that 7% of antibiotics taken in the European Union (EU) are taken without a prescription.

The report, which describes the results of the ARNA (antimicrobial resistance and the causes of non-prudent use of antibiotics) project, found that the highest self-reported use of non-prescription oral antibiotics was in Romania (20% of all antibiotic users in 2013, and 16% in 2016) and Greece (16% of all antibiotic users in 2013, and 20% in 2016). High rates of non-prescription antibiotics use were also found in Latvia, Bulgaria, Croatia, and Hungary. The antibiotics were obtained from either a pharmacy or healthcare provider without a prescription, or were left over from a previous prescription.

Patient surveys in seven of the ARNA countries suggested lack of knowledge about antibiotics was a major determinant of non-prudent use, while surveys of pharmacists found that patient pressure played a role in the decision to sell antibiotics over-the-counter (OTC) without a prescription, with some pharmacists saying they feared customers might go to another pharmacy if they refused. A majority of pharmacists and general practitioners (GPs) reported being asked to prescribe an antibiotic even though there was no medical indication.

Dialogue meetings in six of the ARNA countries—Cyprus, Greece, Italy, Hungary, Romania, and Spain—resulted in several policy recommendations to reduce non-prudent use of antibiotics. The recommendations included public health campaigns to educate patients and healthcare providers on appropriate antibiotic use, efforts to strengthen collaboration between GPs and pharmacists, increased use of rapid diagnostic tests that can be performed at the point-of-care, and better enforcement of laws to prevent OTC sales.
July 17 ARNA report

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