ASP Scan (Weekly) for Feb 03, 2017

Spread of MCR-1 gene
Resistant asymptomatic malaria
ESBL bacteria in travelers
Resistance genes in estuaries
Antibiotic use in travelers
Azithromycin in pregnancy
Antibiotics boost bacterial reproduction

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

MCR-1 identified in California; Vietnam notes link to ag colistin use

Originally published by CIDRAP News Feb 1

The Los Angeles County Department of Public Health (LAC DPH) reported yesterday that a bacterial isolate harboring the MCR-1 gene, which confers resistance to the last-resort antibiotic colistin, has been identified in a patient with an Escherichia coli infection.   

Department officials said in a press release that the patient had most likely acquired the E coli infectionduring international travel, and that there has been no evidence that the infection is spreading in the local healthcare community. The MCR-1 gene has now been reported in six human cases in the United States. 
Jan 31 LAC DPH press release

Meanwhile, a study yesterday in Emerging Infectious Diseases suggests that the spread of the MCR-1 gene in Vietnam is linked to the use of colistin in agriculture. The drug is one of the most commonly used antimicrobials in animal production in Vietnam.

For the study, investigators conducted a systematic, cross-sectional study examining antimicrobial drug use colonization with antimicrobial-resistant E coli in chickens and human in Tien Giang province. They collected fecal samples from 204 chicken farms and 204 rectal swabs from chicken farmers, and additionally collected rectal swabs from age- and sex-matched individuals from the same districts who were not involved in poultry farming.

In a total of 204 chicken and 510 human fecal specimens, the adjusted prevalence of MCR-1 was 59.4% in the chicken samples and 20.6% in the human samples. Of the 200 E coli isolates collected, the MCR-1 gene was detected in 10 of 78 isolates from chickens (12.8%), 2 of 50 isolates from chicken farmers (4%), and in none of the 78 isolates from non-farmers. MCR-1 was also detected in 9 of 38 and 1 off 44 extended spectrum beta-lactamase (ESBL)-producing E coli isolates from chickens and chicken farmers, respectively.

An investigation of risk factors indicated that colonization with MCR-1–carrying bacteria in chickens is associated with the use of colistin on chicken farms, while colonization in humans is associated with exposure to MCR-1–positive chickens, with zoonotic transmission explaining the high prevalence of the gene (34.7%) in farmers.

"Given the potentially serious consequences of the spread of the mcr-1 gene from food production animals to humans, prudent use of antimicrobial drugs in animal production should be enforced globally, including in small-scale and household farms," the authors write.
Jan 31 Emerg Infect Dis dispatch


Myanmar study finds evidence of drug resistance in asymptomatic malaria

Originally published by CIDRAP News Feb 1

Researchers investigating malaria infections in an artemisinin resistance containment zone in Myanmar identified isolates from asymptomatic malaria infections that contained a resistance gene, according to a study yesterday in Emerging Infectious Diseases.

The investigators, from Myanmar and South Korea, analyzed isolates from 1,182 people in the containment zone, which is known to harbor mosquitoes containing the Plasmodium falciparumparasite resistant to the antimalarial drug artemisinin, as well as P vivax resistant to chloroquine. Of the 1,182 people, 549 (46%) had had malaria in the previous 5 years.

The researchers discovered that 28 isolates were from asymptomatic people. Of those, 22 were caused by P vivax, 4 by P falciparum, and 2 by P malariae. Two of the P falciparum isolates harbored K13 mutations, an established artemisinin-resistance marker. Three of the P vivax isolates contained other drug-resistance markers.

The authors conclude, "Our results indicated that drug-resistant malaria parasites may be spreading, even in the containment areas or (pre-)elimination areas; this issue should, therefore, be addressed at a policy level. Detection and elimination of asymptomatic infections are of vital importance."
Jan 31 Emerg Infect Dis study


Chinese report notes high rate of travel in those with ESBL bacteria

Originally published by CIDRAP News Feb 1

A study in the latest issue of The Lancet Infectious Diseases shows that more than two thirds of Chinese patients with extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) infections had traveled recently.

The Chinese/UK/US team collected 3,476 third-generation cephalosporin-resistance Enterobacteriaceae isolates from fecally colonized outpatients (3,322 Escherichia coli, 124 Klebsiella pneumoniae, 16 Proteus mirabilis, and 14 Enterbacter cloacae). Of the 3,476 isolates, 2,115 (61%) were positive for at least one ESBL gene.

Among outpatients with ESBL-E isolates, 1,457 (69%) of 2,115 people had documented travel in the previous 6 months; 273 (19%) of them had traveled abroad and 1,184 (81%) had not. The most common destinations outside of China were other parts of Asia (45%), Europe (24%), and the United States (20%).

The authors conclude, "Although the temporal relationship of travel and sampling in our retrospective analysis makes it difficult to conclude whether patients were colonised with ESBL-E at the time, during, or after travel, our findings suggest that further studies, and perhaps microbiological surveillance, of ESBL-E in international travellers from areas with high colonisation prevalence are warranted."
February Lancet Infect Dis report 

Study finds resistance genes are abundant in Chinese estuaries
Originally published by CIDRAP News Jan 31

A team of researchers has detected a high abundance and diversity of antibiotic resistance genes in Chinese coastal estuaries, according to a study yesterday in Nature Microbiology.

For the study, researchers tested sediment from 18 estuaries over 4,000 km of coastal China and examined their relationship with bacterial communities, antibiotic residues, and socioeconomic factors. They found a total of 259 resistance genes in the estuary samples, with an average of 118 in each estuary at levels around 1 million resistance genes per gram of sediment. The detected genes conferred resistance to almost all major classes of antibiotics used in humans and animals, the authors said, and represented all major resistance mechanisms, including antibiotic deactivation, efflux pumps, and cellular protection.

The most common resistance genes found at each estuary were multidrug and beta-lactam resistance genes, followed by aminoglycoside and tetracycline resistance genes. Vancomycin resistance genes were found at all estuaries.        

When the researchers analyzed antibiotic residues in estuary samples, they found five major antibiotic classes: diaminopyrimidines, tetracyclines, sulfonamides, fluoroquinolones, and macrolides. The concentrations of tetracyclines and macrolides were positively correlated with the total abundance of resistance genes.

Analysis of the relationship between socioeconomic factors and resistance-gene abundance showed that total population, gross domestic product, sewage, and aquaculture production were correlated with the abundance of aminoglycoside, multidrug, and sulfonamide resistance genes.

The authors conclude that anthropogenic activity "appears to be the major driver of abundance and diversity" of resistance genes found in estuaries, and that wastewater streams from municipal sewage treatment and aquaculture are a likely contributor. 
Jan 30 Nat Microbiol abstract


Antibiotic use in travelers linked to colonization with MDR bacteria

Originally published by CIDRAP News Jan 31

A new study from researchers in Sweden and Finland has found that antibiotics taken during travel to subtropical regions can predispose travelers to colonization by drug-resistant bacteria with a high rate of co-resistance to other antibiotics.

In the study, which appeared yesterday in Travelers Medicine and Infectious Disease, the researchers analyzed the isolates of 90 people who had contracted extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) while traveling abroad. The 90 participants were part of an earlier investigation, in which the researchers found that taking antibiotics for traveler's diarrhea (TD) increased the risk of colonization by ESBL-PE, particularly when traveling to regions with poor hygiene and weak antibiotic policy (such as South and Southeast Asia). One of the main takeaways of that study was that travelers should be advised against taking antibiotics for mild or moderate TD.

For this study, the researchers were trying to determine what percentage of those isolates were also co-resistant to non-beta-lactam antibiotics, as co-resistance can complicate treatment of ESBL-PE infections. They considered four major risk factors of colonization, including destination, age, TD, and antibiotic use.

Of the ESBL-PE isolates, 53%, 52%, 73%, and 2% were co-resistant to ciprofloxacin, tobramycin, co-trimoxazole, and nitrofurantoin, respectively. The rates were similar among those with TD and without TD. But when they compared the isolates of the travelers who had taken fluoroquinolones (FQs) to those who had taken no antibiotics, they found co-resistance rates for ciprofloxacin were 95% versus 37%, for tobramycin were 85% versus 43%, for co-trimoxazole were 85% versus 68%, and for nitrofurantoin were 5% versus 2%.

"Thus, use of FQs predisposes not only to contracting ESBL-PE strains but, indeed, also to selecting ESBL-PE strains co-resistant to certain clinically important non-beta-lactam antibiotics," the authors write.

"The data reveal that the perils of antibiotic use during travel are even greater than hitherto recognized."
Jan 30 Travel Med Infect Dis study  


Study shows possible benefit of azithromycin in pregnancy

Originally published by CIDRAP News Jan 30

Giving pregnant women a dose of azithromycin during labor reduces infections in both mothers and newborns, according to a new study in Pediatrics. But an accompanying commentary suggests the harms of azithromycin exposure could outweigh the benefits.

In a post-hoc analysis of a double-blind, placebo-controlled randomized trial, 829 Gambian women were given either an oral dose of azithromycin or a placebo. Investigators were looking to see whether the intervention had an effect on maternal and neonatal clinical infections such as sepsis, which is a high risk in sub-Saharan Africa because of poor nutrition and unhygienic delivery conditions. In Gambia, the authors note, neonatal deaths represent 40% of all deaths in children under the age of 5, and maternal mortality is among of the highest in the developing world.

Overall, the researchers found that maternal infections were lower in the azithromycin group than in the placebo group (3.6% vs. 9.2%), as was the prevalence of mastitis (1.4% vs. 5.1%) and fever (1.9% vs. 5.8%). The overall prevalence of infections was also lower among the newborns of the azithromycin group (18.1% vs. 23.8%), with a marked difference in skin infections (3.1% vs. 6.4%).

"Our results show that azithromycin administered to women in labor reduces maternal and neonatal infections and maternal episodes of fever," the authors write. "Larger trials designed to assess the effect of the intervention on severe morbidity and mortality are urgently needed."

But as noted in the accompanying commentary from two members of the American Academy of Pediatrics Committee on Infectious Diseases, the decrease in infections among the azithromycin group was driven primarily by mastitis in the mothers and skin infections in neonates, none of which were described as severe. In addition, no significant difference in rates of sepsis, malaria, hospitalizations, or deaths in mothers or infants were observed.

Furthermore, the commentary authors write, azithromycin exposure may facilitate the emergence of antimicrobial resistance, could alter the structure and function of the human microbiome, and has been associated with the development of hypertrophic pyloric stenosis in infants.

"In light of the small potential benefits observed in the Oluwalana study, the potential harms of azithromycin exposure likely outweigh the upside for this specific indication," the authors write. They suggest that future studies should assess azithromycin's effects on serious maternal and neonatal infections and evaluate potential harms.
Jan 27 Pediatrics study 
Jan 27 Pediatrics commentary


Research highlights how antibiotics can stimulate bacterial reproduction

Originally published by CIDRAP News Jan 30

A study today in Ecology and Evolution shows that growth of bacteria can be boosted by antibiotics.

In the study, researchers from the University of Exeter in Great Britain were looking to determine the fitness costs associated with antibiotic resistance in Escherichia coli when exposed to the antibiotic doxycycline. Their working assumption was that the bacteria that acquired resistance mutations might proliferate more slowly.

To investigate, the researchers exposed E coli bacteria to eight rounds of antibiotic therapy over 4 days. As expected, the bacteria grew more resistant with each round of treatment. But what was unexpected was that the mutated E. coli reproduced faster after antibiotic exposure and formed much larger populations than bacteria exposed to no antibiotics. Furthermore, the ability to reproduce faster remained after antibiotic exposure ended.

"Our research suggests there could be added benefits for E. coli bacteria when they evolve resistance to clinical levels of antibiotics," lead author Robert Beardmore, BSc, said in a University of Exeter press release. "Bacteria have a remarkable ability to rearrange their DNA and this can stop drugs working, sometimes in a matter of days."
Jan 30 Ecol Evol study
Jan 30 University of Exeter press release

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