'Superbug from India resistant to all available antibiotics'

January 16, 2017

Washington, Jan 16: A woman in the US died after being infected by a superbug during her visit to India, say doctors who found that the "nightmare" bacteria was resistant to all available antibiotics.

bacteriaThe infection was caused by carbapenem-resistant Enterobacteriaceae (CRE), a multidrug-resistant organism associated with high mortality.

While CRE are not new to the US, what was new in this case is that the infection was resistant or non-susceptible to all available antimicrobial drugs, researchers said.

The 70-year-old patient in the US was admitted to an acute care hospital last year after an extended trip to India.

She was given a primary diagnosis of systemic inflammatory response syndrome, likely resulting from an infected right hip seroma. The infection was serious; none of the 14 antibiotics physicians used to treat the woman worked.

After the CRE - identified as Klebsiella pneumoniae - was confirmed by lab testing, an isolate from a wound specimen was sent to the CDC for further susceptibility testing and to determine the mechanism of resistance.

That testing confirmed the presence of New Delhi metallo-beta-lactamase (NDM-1), an enzyme that directly breaks down carbapenems, a powerful class of antibiotics that are often used to treat multidrug-resistant infections.

The US Centres for Disease Control and Prevention's antimicrobial testing showed the isolate was resistant to 26 different antibiotics, including all aminoglycosides and polymixins - another class of last-resort antibiotics.

It was also intermittently resistant to tigecycline, an antibiotic developed specifically to overcome drug-resistant organisms. Essentially, there were no treatment options.

Meanwhile, the patient's condition was deteriorating quickly. She died of septic shock in early September last year, less than two months after admission. The woman had been in India for two years and had been hospitalised at least four times there for a right femur fracture and a subsequent hip fracture.

"We feel comfortable saying that she most likely obtained the bug in India," said Lei Chen, senior epidemiologist with the Washoe County Health District in the US.

CRE have been labelled as a "nightmare" bacteria not only because they are already resistant to most antibiotics, but also because they spread easily in hospital settings.

The enzymes that enable resistance are carried on mobile pieces of DNA known as plasmids that can spread to other types of bacteria. NDM-1 enzyme is particularly mobile, researchers said.

"It's what we call a promiscuous plasmid, that seems to move easily between species," said Alex Kallen, a CDC medical epidemiologist.

When CRE bacteria enter the bloodstream, they can be deadly. CRE bacteria kill up to half of patients who get bloodstream infections from them.

NDM-1 was originally identified in 2009 in a Swedish patient who had been hospitalised in India.

The research was published in CDC's Morbidity and Mortality Weekly Report (MMWR).

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Agencies
July 25,2020

The COVID-19 pandemic and the subsequent lockdown saw many people turning chefs overnight, but those who could not turned to online delivery of food. And not just any food, as per a new report, Indians "craved the most for Biryani" during the lockdown.

The "StatEATistics report: The Quarantine Edition" from food delivery platform Swiggy found that Indians ordered biryani over "5.5 lakh times" from their favourite restaurants.

The new normal might have opened a pandora's box of behavioral changes, but some old habits die hard like the love for Biryani, which took the top spot for overall orders. It was followed by butter naan and masala dosa at 3,35,185 and 3,31,423, respectively.

Biryani has topped the list of most ordered dishes for the fourth year in a row, the food delivery platform noted.

Indians didn't forget to indulge their sweet tooth in the uncertain months of lockdown. Their favourite comfort food during the lockdown period was the moist and decadent Choco Lava cake, ordered around 1,29,000 times.

"The humble Gulab Jamun (84,558) and chic Butterscotch Mousse cake (27,317) followed suit," said the report derived from Swiggy's order analysis in the past few months across cities that it is present in.

Also, as birthday parties moved to video calls, and virtual cake cutting sessions, according to the food delivery platform, it delivered nearly "1,20,000 cakes" to complete these celebrations.

According to the report, on average, "65,000 meal orders" were placed by 8 pm each day to make sure food arrived in time for dinner.

"It was the busiest hour for Swiggy delivery partners and restaurants. On average, they (customers) chose to tip Rs.23.65, with one particularly generous customer tipping Rs. 2500!," it added.

For those who only relied on home-made food during the quarantine, Swiggy delivered a whooping 323 million kgs of onions and 56 million kgs of bananas through its grocery section and hence ensured that its consumers were all stocked up.

That said, it also took care of the 'quick-fix meal' tribe -- consumers who resort to the evergreen college hacks of living on instant noodles.

"Around 3,50,000 packets of this ideal easy to cook meal were ordered during the lockdown," it said.

In all, Swiggy delivered 40 million orders across food, groceries, medicines and other household items during India's lockdowns. It also delivered over 73,000 bottles of sanitizers and hand wash along with 47,000 face masks as the definition of essentials' changed during these uncertain times.

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Agencies
July 4,2020

The Union health ministry on Friday revised the dosage of anti-viral drug remdesivir to be administered to coronavirus patients in the moderate stage of illness from the earlier six days to five days as it issued an updated 'Clinical Management Protocols for COVID-19'.

The drug, administered in the form of injection, should be given at a dose of 200 mg on day one followed by 100 mg daily for four days (total five days), the new treatment protocols stated.

The Health Ministry on June 13 had allowed the use of remdesivir for restricted emergency use in moderate cases under "investigational therapies".

"Under emergency use authorisation, remdesivir may be considered for patients in moderate stage requiring oxygen support," the document stated.

It is not recommended for those with severe renal impairment and high level of liver enzymes, pregnant and lactating women, and those below 12 years, it said.

The ministry also okayed off-label application of tocilizumab, a drug that modifies the immune system or its functioning, and convalescent plasma for treating COVID-19 patients in the moderate stage of illness as "investigational therapies".

It also recommended hydroxychloroquine for patients during the early course of the disease and not for critically-ill patients.

On June 27, the ministry had included an inexpensive, widely used steroid dexamethasone in treatment protocols for COVID-19 patients in the moderate to severe stages of their illness among other therapeutic measures.

The ministry advised use of dexamethasone, which is already used in a wide range of conditions for its anti-inflammatory and immunosuppressant effects, as an alternative choice to methylprednisolone for managing moderate to severe cases of coronavirus infection.

India's COVID-19 cases soared by over 20,000 in a day for the first time taking the country's total tally to 6,25,544 on Friday while the death toll climbed to 18,213 with 379 new fatalities, according to the Union Health Ministry data updated at 8 am.

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Agencies
July 2,2020

The American pharmaceutical giant Pfizer Inc. and the European biotechnology company BioNTech SE have conducted an experimental trial of a COVID-19 vaccine candidate and found it to be safe, well-tolerated, and capable of generating antibodies in the patients.

The study, which is yet to be peer-reviewed, describes the preliminary clinical data for the candidate vaccine -- nucleoside-modified messenger RNA (modRNA), BNT162b1.

It said the amount of antibodies produced in participants after they received two shots of the vaccine candidate was greater than that reported in patients receiving convalescent plasma from recovered COVID-19 patients.

"I was glad to see Pfizer put up their phase 1 trial data today. Virus neutralizing antibody titers achieved after two doses are greater than convalescent antibody titers," tweeted Peter Hotez, a vaccine scientist from Baylor College of Medicine in the US, who was unrelated to the study.

Researchers, including those from New York University in the US, who were involved in the study, said the candidate vaccine enables human cells to produce an optimised version of the receptor binding domain (RBD) antigen -- a part of the spike (S) protein of SARS-CoV-2 which it uses to gain entry into human cells.

"Robust immunogenicity was observed after vaccination with BNT162b1," the scientists noted in the study.

They said the program is evaluating at least four experimental vaccines, each of which represents a unique combination of mRNA format and target component of the novel coronavirus, SARS-CoV-2.

Based on the study's findings, they said BNT162b1 could be administered in a quantity that was well tolerated, potentially generating a dose dependent production of immune system molecules in the patients.

The research noted that patients treated with the vaccine candidate produced nearly 1.8 to 2.8 fold greater levels of RBD-binding antibodies that could neutralise SARS-CoV-2.

"We are encouraged by the clinical data of BNT162b1, one of four mRNA constructs we are evaluating clinically, and for which we have positive, preliminary, topline findings," said Kathrin U. Jansen, study co-author and Senior Vice President and Head of Vaccine Research & Development, Pfizer.

"We look forward to publishing our clinical data in a peer-reviewed journal as quickly as possible," Jansen said.

According to Ugur Sahin, CEO and Co-founder of BioNTech, and another co-author of the study, the preliminary data are encouraging as they provide an initial signal that BNT162b1 is able to produce neutralising antibody responses in humans.

He said the immune response observed in the patients treated with the experimental vaccine are at, or above, the levels observed from convalescent sera, adding that it does so at "relatively low dose levels."

"We look forward to providing further data updates on BNT162b1," Sahin said.

According to a statement from Pfizer, the initial part of the study included 45 healthy adults 18 to 55 years of age.

It said the priliminary data for BNT162b1 was evaluated in 24 subjects who received two injections of 10 microgrammes ( g) and 30 g -- 12 subjects who received a single injection of 100 g, and 9 subjects who received two doses of a dummy vaccine.

The study noted that participants received two doses, 21 days apart, of placebo, 10 g or 30 g of BNT162b1, or received a single dose of 100 g of the vaccine candidate.

According to the scientists, the highest neutralising concentrations of antibodies were observed seven days after the second dose of 10 g, or 30 g on day 28 after vaccination.

They said the neutralising concentrations were 1.8- and 2.8-times that observed in a panel of 38 blood samples from people who had contracted the virus.

In all 24 subjects who received two vaccinations at 10 g and 30 g dose levels, elevation of RBD-binding antibody concentrations was observed after the second injection, the study noted.

It said these concentrations are 8- and 46.3-times the concentration seen in a panel of 38 blood samples from those infected with the novel coronavirus.

At the 10 g or 30 g dose levels, the scientists said adverse reactions, including low grade fever, were more common after the second dose than the first dose.

According to Pfizer, local reactions and systemic events after injection with 10 g and 30 g of BNT162b1 were "dose-dependent, generally mild to moderate, and transient."

It said the most commonly reported local reaction was injection site pain, which was mild to moderate, except in one of 12 subjects who received a 100 g dose, which was severe.

The study noted that there was no serious adverse events reported by the patients.

Citing the limitations of the research, the scientists said the immunity generated in the participants in the form of the T cells and B cells of their immune system, and the level of immunity needed to protect one from COVID-19 are unknown.

With these preliminary data, along with additional data being generated, Pfizer noted in the statement that the two companies will determine a dose level, and select among multiple vaccine candidates to seek to progress to a large, global safety and efficacy trial, which may involve up to 30,000 healthy participants if regulatory approval to proceed is received.

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