ASP Scan (Weekly) for Aug 25, 2017

Resistance in 'lonely' microbes
Severe C diff and fecal transplant
Gonorrhea resistance trends
MRSA, VRE contact precautions
Candida auris uptick
MCR-1 in Dutch chicken
Residents' prescribing
Trial for new antimalarial
Alternatives to carbapenems

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

Microbes living at lower densities develop resistance faster, study says

UK researchers have discovered that microbes living at low populations densities—dubbed "lonely" microbes—have higher rates of mutations that cause antibiotic resistance, according to their study yesterday in PLoS Biology.

A team of scientists from the universities of Manchester, Keele, and Middlesex previously had found that "lonely" Escherichia coli bacteria were nearly 10 times as likely to mutate to resist antibiotics as those living in dense populations. The new study expands their research to 26 microbial species, including viruses, and involved 70 years of data and nearly 500 mutation measurements.

They found that both in the literature and in their own lab experiments the relationship held across the microbes, with higher population densities leading to lower rates of resistance mutations and lower densities leading to the converse. The authors call their finding "density-associated mutation-rate plasticity" (DAMP).

Lead author Rok Krasovec, PhD, said in a University of Manchester news release, "What's exciting about DAMP is that it requires protein molecules that do the same thing in very different microbes, meaning that we can start to understand why mutation rates vary like this. This means that our results could be the first step towards manipulating microbial DAMP clinically as a way to slow the evolution of antibiotic resistance."
Aug 24 PLoS Biol study
Aug 24 University of Manchester news release


Study shows strong promise for fecal transplants for severe C difficile

Originally published by CIDRAP News Aug 24

A study today involving 111 patients found that early fecal microbiota transplantation (FMT) dramatically improves survival in severe Clostridium difficile infections (CDIs).

Writing in Clinical Infectious Diseases, French researchers noted that they included 66 patients with severe CDI in an FMT group and 45 in an antibiotic-only group. The FMT group received vancomycin for 2 to 4 days before and after transplant, while the non-FMT group received one of several antibiotic therapy options, depending on their clinical status, but the vast majority were prescribed vancomycin. Patients were a median of 82 years old, and follow-up was conducted at 3, 6, and 12 months.

Three-month mortality was 42.2% (19/45) in the antibiotic group and 12.1% (8/66) in the FMT group, a 71% reduction. The investigators estimated that only four patients needed to be treated with FMT to save one life at 3 months. Thirty (45.5%) FMTs were performed using fresh stools and 36 (54.5%) with frozen stools, but the researchers found no significant difference between the two.

The authors concluded, "Risk of bias was low because baseline characteristics were similar and multivariate survival models were used."

In response to a perceived need by some to wait to change C difficile treatment recommendations until randomized, double-blind, controlled trials can be launched, the authors pointed to the expense of such studies, among other factors. They said that, given the promising results of their study, "waiting for double-blind randomized controlled trials to update the recommendations and management of the most vulnerable and severely ill C. difficile-infected patients who are at very high risk of mortality . . . does not seem ethical."

In a related commentary, however, Antoine Andremont, MD, PhD, who was not involved in the study, disagreed. Andremont, from the University Paris-Diderot Medical School, cited several reasons for not changing practice standards just yet, including concerns over stalling other key research of C difficiletreatment and prevention (including antibiotic stewardship approaches) and the complex nature of the fecal microbiota.
Aug 24 Clin Infect Dis study
Aug 24 Clin Infect Dis commentary


European data show declining resistance for some gonorrhea antibiotics

Originally published by CIDRAP News Aug 24

New data reported today by the European Centre for Disease Prevention and Control (ECDC) shows antibiotic resistance levels declining for cefixime and ceftriaxone when used to treat gonorrhea. Resistance to azithromycin, however, is on the rise.

The data were gathered from a 2015 antimicrobial susceptibility survey conducted in 24 European Union member states. A total of 2,134 isolates were collected and tested, covering 3% of the gonorrhea cases reported by routine surveillance.

Compared to data from 2014, there was a slightly lower proportion of cefixime resistance in nine member states (1.7% compared to 2.0%), and only one isolate was found to be resistant to ceftriaxone (five were found in 2014). However, five isolates displayed high-level resistance to azithromycin, compared with one in 2014.

The ECDC said the declining resistance levels were partly due to the dual-therapy regimen (ceftriaxone plus azithromycin) currently recommended to treat gonorrhea in the EU. The rising resistance to azithromycin threatens this treatment strategy.

Last year the US Centers for Disease Control and Prevention (CDC) warned of rising azithromycin resistance rates among US gonorrhea cases. Both the CDC and ECDC said that approximately 25% of gonorrhea isolates are now resistant to tetracycline and ciprofloxacin, former first-line treatments for the sexually transmitted disease.
Aug 24 ECDC report
Jul 15, 2016, CIDRAP News story 
"Gonorrhea growing more resistant to standard treatment"


Forgoing contact precautions not tied to increased MRSA, VRE

Originally published by CIDRAP News Aug 24

Discontinuing contact precautions did not affect the rates of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), according to the results of a retrospective study at a large Detroit hospital published yesterday in the American Journal of Infection Control.

Researchers assessed healthcare-related MRSA and VRE infection rates in the 12 months before and the 12 months after contact precautions were discontinued at an 800-bed teaching hospital in 2013. The study included 36,907 patients treated with contact precautions and 40,439 treated without. Contact precautions include infection-prevention measures in addition to standard precautions, such as gloves, gowns, and private rooms, for serious, easily transmitted diseases.

MRSA and VRE rates for the following infections did not differ significantly in the two study periods: catheter-associated urinary tract infections, ventilator-associated pneumonia, central line–associated bloodstream infections, surgical-site infections, and hospital-acquired MRSA bacteremia.
Aug 23 Am J Infect Control study


CDC reports that Candida auris cases now top 100

Originally published by CIDRAP News Aug 22

The number of Candida auris cases in the United States has risen to 112, according to a case count update yesterday from the Centers for Disease Control and Prevention (CDC).

The multidrug-resistant fungus has now been identified in healthcare facilities in nine states, with the vast majority of cases in New York (77) and New Jersey (23). The count reflects the number clinical cases of C auris infection, which rose from 98 in July. The pathogen has been isolated from an additional 120 patients from healthcare facilities in four of the affected states, meaning those patients were colonized with the fungus but did not show clinical signs of infection.

The CDC warned healthcare facilities about C auris in June 2016 based on reports from other countries about severe invasive infections caused by the fungus, which has shown increasing resistance to all three major classes of antifungal drugs. This type of resistance has not been seen in other Candidaspecies. C auris can also persist on hospital surfaces and appears capable of spreading between patients.

In patients with compromised immune systems, C auris can cause serious invasive infections that affect the bloodstream, heart, brain, ear,            and bones. The CDC estimates that more than 1 in 3 patients with an invasive C auris infection die, and reports from other countries estimate mortality rates as high as 50%.

The CDC encourages all laboratory staff who identify C auris to notify state or local public health authorities and CDC officials.
Aug 21 CDC case count update


Dutch study find MCR-1 gene in a quarter of retail chicken meat samples

Originally published by CIDRAP News Aug 21

Dutch investigators have identified the colistin resistance gene MCR-1 in nearly 25% of samples of Dutch retail chicken meat, according to a new study in Antimicrobial Resistance and Infection Control.

For the study, the investigators bought 214 chicken meat samples from four supermarket chains throughout the Netherlands in 2015. They collected 53 or 54 samples from each chain.

Using polymerase chain reaction testing, the investigators detected the presence of the MCR-1 gene in 24.8% of the samples (53 of 214), then confirmed the presence of the gene in 34 of these 53 samples (64.2%) using a selective culture method. No MCR-2 genes were detected. Of the 34 MCR-1–positive isolates, 32 were E coli and 2 were Klebsiella pneumoniae. In addition to colistin, the 34 isolates showed high levels of resistance to ampicillin (100%), amoxicillin-clavulanic acid (89%), trimethoprim/sulfamethoxazole (69%), and ciprofloxacin (57%).

Multivariable regression analysis showed that chicken samples that were non-free-range (adjusted odds ratio [aOR], 3.0) and were purchased at supermarket chains C (aOR, 34.6) or D (aOR, 37.5) were more likely contain the MCR-1 gene. The large variation between supermarket chains could not be explained with the available information.

In previous studies of MCR-1 in food, researchers found the gene in 28% of Chinese poultry samples and in 19.5% of E coli isolates from South American chicken meat.

Although colistin and other polymixins are used at very low levels in the Netherlands and the MCR-1 gene has been found only sporadically in Dutch patients, the authors of the study say the findings warrant further studies on the underlying mechanisms of spread. "Moreover, continued monitoring of the potential reservoirs for this plasmid-mediated colistin resistance is of utmost importance," they write.
Aug 18 Antimicrob Resist Infect Control study


Survey finds varied antibiotic prescribing practices in pediatric residents

Originally published by CIDRAP News Aug 21

A survey of 85 pediatric residents at two US hospitals found considerable variation among antibiotic prescribing for pneumonia, sinusitis, and other conditions, with three-fourths having prescribed antibiotics for viral infections, according to a study last week in Hospital Pediatrics.

Among the residents surveyed at Children's National Medical Center in Washington, DC, and Nicklaus Children's Hospital in Miami, only 12% ranked an infectious disease specialist as one of their top three influential sources for antibiotic choice.

Seventy-five percent of respondents said they had prescribed antibiotics for patients they considered to have a viral infection. When asked to identify reasons for prescribing, 63% said they were following instructions from a more senior physician, 21% had concerns of a bacterial infection developing in the future, and 16% cited pressure from patients' parents.

Greater deviation from clinical guidelines was found for antibiotic treatment of sinusitis and community-acquired pneumonia compared with otitis media and streptococcal pharyngitis.

When asked about antibiograms, 54% said they sometimes used one, 25% had never referred to one, and 17% didn't know what an antibiogram was or didn't respond. Half of respondents didn't know how to access their hospital-specific antibiogram, which is a profile of antimicrobial susceptibility testing results for a single pathogen. Just 3% used the profiles very frequently.

The authors conclude, "Results illustrate the need for better promotion and integration of clinical guidelines with antibiograms when developing antibiotic education programs for residents in training. In addition, pediatric hospitalists should play an active role in the implementation of these programs."
Aug 16 Hosp Pediatr study


Patient trial for new antimalarial compound launches in Mali

Originally published by CIDRAP News Aug 21

Drugmaker Novartis and Medicines for Malaria Venture (MMV) today launched a patient trial in Mali for an antimalarial compound with the potential to treat drug-resistant strains of the parasite, according to a company press release.

The trial will test the efficacy of KAF156, which belongs to a novel class of antimalarial compounds called imidazolopiperazines, in combination with an improved formulation of the existing antimalarial lumefantrine. The phase 2b study will test multiple dosing combinations and dosing schedules of the drugs, including the feasibility of single-dose therapy in adults, adolescents, and children.

With resistance and reduced sensitivity to artemisinin and artemisinin-based combination therapies emerging in parts of Asia and more recently in Africa, next-generation antimalarials are urgently needed.

"To build on the gains made against malaria since the turn of the century, we need new medicines that are effective across all types of resistance patterns and geographies, and that are easy to administer, especially to children," David Reddy, PhD, chief executive officer of MMV, said in the release.

The first trial center is already operational in Mali and will be followed by trials in 16 additional centers in nine countries in Africa and Asia.

Novartis is developing KAF156 with scientific and financial support from MMV and the Bill and Melinda Gates Foundation.
Aug 21 Novartis press release


Non-carbapenems could be good option for bloodstream infections

Originally published by CIDRAP News Aug 21

European researchers report in Clinical Infectious Diseases that empiric treatment of bloodstream infections (BSIs) caused by extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-E) with drugs other than carbapenems is not associated with worse outcomes.

While carbapenems are generally considered to be the drug of choice for treating serious infections caused by ESBL-E, their use has substantially increased in recent years, and there is concern that the increase is contributing to the spread of carbapenem resistance. Some recent data have indicated that beta-lactam/beta-lactamase inhibitor combinations are an alternative, but there are few data on other antimicrobials. Alternative agents with potential efficacy could provide more treatment options.

As part of a larger multinational retrospective cohort study on BSIs caused by ESBL-E, researchers set out to assess the impact of empiric therapy with other active drugs (OADs) compared with carbapenem treatment. The main outcome was 30-day all-cause mortality. Secondary outcomes were clinical failure at day 14 and length of hospital stay after BSI. The hypothesis was that treatment with OADs would be associated with higher mortality and lower cure rates.

Overall, 335 patients with BSI due to ESBL-E were included in the study; 249 were treated empirically with a carbapenem and 86 with OADs. The most frequent OADs used were aminoglycosides (43 patients) and fluoroquinolones (20 patients). The most frequent carbapenems used were meropenem (141 patients), imipenem (61 patients), and ertapenem (46 patients.

After controlling for confounders, the researchers found that empiric therapy with OADs was not associated with greater 30-day mortality (hazard ratio [HR], 0.75) or with clinical failure at day 14 (adjusted odds ratio, 0.62). In patients discharged alive, the median length of stay was 16 days for patients treated with carbapenems and 14 days for patients treated with OADs; linear regression analysis after adjusting for propensity score showed no significant association between empiric OAD therapy and length of stay (P = .26).

The authors conclude that while the results cannot be interpreted as indicating that OADs and carbapenems are equally effective because of the limited statistical power of the study, the findings suggest OADs might be an option for empiric regimens for some BSI patients, depending on local susceptibility patterns. 
Aug 19 Clin Infect Dis study

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