Stewardship / Resistance Scan for Jul 26, 2017

News brief

New class of antibiotics shows promise against MDR bacteria, plague

An experimental drug that belongs to a new class of antibiotics showed promise in lab tests against multidrug-resistant (MDR) gram-negative bacteria, and was protective against the bacterium that causes plague in mice, according to a study yesterday in mBio.

Researchers from Lille, France, and Duke University demonstrated that LPC-069, a drug in the class called LpxC inhibitors for their ability to inhibit LpxC, a critical gram-negative bacterial enzyme, was effective in cell-culture tests against a dozen pathogenic bacterial taxa. The bacteria were isolated from hospitalized patients in Lille and included MDR strains such as extended-spectrum beta-lactamase–producing and carbapenemase-producing Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii.

The new drug also protected mice from Yersinia pestis, the bacterium that causes plague. A similar drug (called LPC-058) also was effective against Y pestis, but it led to side effects such as diarrhea, accumulation of white blood cells, and, at the highest doses, liver toxicity. LPC-069, in contrast, caused no serious side effects at any of the doses tested.

"Our study shows that LpxC is a viable target, and we can dose the compound (LPC-069) at very high levels without noticeable toxicity," said Pei Zhou, PhD, of Duke, in a press release from the American Society for Microbiology (ASM), which publishes mBio.

LpxC is one of the six essential enzymes in the lipid A pathway in gram-negative bacteria, and Zhou and his colleagues suspect that other essential lipid A enzymes might also be valuable targets for antibiotic treatment. The team next plans to test the efficacy of LPC-069 in animals against a range of gram-negative pathogens.
Jul 25 mBio study
Jul 25 ASM news release

Triple-drug combo to battle superbugs carrying MCR-1 and NDM-5

A study to pinpoint a drug combination to treat bacteria that carry two of the most worrisome antibiotic resistance genes—MCR-1 and NDM-5—found a triple-combination cocktail of antibiotics helped eradicate Escherichia coli that contained both genes.

An E coli isolate containing both resistance genes was recently isolated in a patient from New Jersey, the first such detection in the United States, who had a history of prostate cancer and had recurrent urinary tract infections, raising fears that hospitals may soon be facing large outbreaks of Enterobacteriaceae that produce MCR-1 and New Delhi metallo-beta-lactamase (NDM). Researchers published their findings on a possible treatment in yesterday in mBio.

They assessed bacterial killing of 15 different antibiotics approved by the Food and Drug Administration (FDA), alone and in combination with polymyxin B. The three-drug combination of polymyxin B, aztreonam, and amikacin completely eradicated and suppressed the E coli that harbored both genes, which the researchers said would help clinicians prepare for future cases involving the same type of organism.
Jul 25 mBio study

Recent hospital MRSA drop largely due to soft-tissue infections

US investigators reported today that the decline for hospitalizations for methicillin-resistant Staphylococcus aureus (MRSA) in recent years was primarily due to declines in skin and other soft-tissue infections, and invasive MRSA-related hospitalizations remained largely unchanged.

The researchers, reporting in Clinical Infectious Diseases, calculated rates of MRSA-related hospitalizations from 2010 to 2014 using the National Inpatient Survey (NIS), which includes millions of patient records. The number of MRSA-related hospitalizations decreased 15.8% during that period, from 423,242 to 356,315, and the rate of MRSA-related hospitalizations decreased from 11.31 to 10.08 per 1,000 hospitalizations.

The decline in MRSA-related hospitalizations was primarily attributable to a decrease in unspecified MRSA-related infections which fell from 8.32 to 7.17 per 1,000 hospitalizations. MRSA-related pneumonia infections decreased as well, though only between 2013 and 2014, and accounted for only 13% of the overall decrease, falling from 1.54 to 1.38 per 1,000 hospitalizations. The rate of MRSA-related septicemia, though, increased slightly, from 1.45 to 1.53 per 1,000 hospitalizations.

The most frequent primary diagnoses associated with "other" MRSA-related infections were cellulitis and abscess infections. Rates of MRSA-related skin and other soft-tissue infections decreased 29%, from 3.8 to 3.0 per 1,000 hospitalizations. Rates for other common primary diagnoses associated with unspecified MRSA-related infections did not change much during the study period.

The authors conclude, "The decrease in rates of noninvasive MRSA hospitalizations may be attributable to a combination of efforts to combat this public health crisis. However, because the decrease was largely confined to community-associated infections, these changes may instead reflect the natural waning of an epidemic."
Jul 26 Clin Infect Dis report

News Scan for Jul 26, 2017

News brief

New MERS case reported in Riyadh

Saudi Arabia’s Ministry of Health (MOH) reported a new MERS case today, the first case since Jul 11.

The patient is a 57-year-old expatriate man from Riyadh. He presented with symptoms of MERS-CoV (Middle East respiratory syndrome coronavirus) infection and is in stable condition. The probable source of his infection is listed as primary, which means it's unlikely he contracted the virus from someone else. He is not a healthcare worker.

As of today, Saudi Arabia's MERS-CoV total cases since 2012 total 1,680, including 684 deaths. Three people are still being treated for infections.
Jul 26 MOH report

Study: flu vaccine effectiveness in seniors declines as frailty rises

Trivalent flu vaccine afforded good protection against influenza in healthy older adults, but the benefit diminished in those who were frailer, Canadian researchers reported today in the Journal of Infectious Diseases.

The prospective, test-negative case-control study included patients age 65 or older from 38 academic and community hospitals from six provinces, mainly from Ontario, during the 2011-12 flu season. The research team used a validated index to measure frailty. They enrolled 320 cases and 564 controls; 601 had been vaccinated. The mean age was 80.6 and 78.7 years, respectively. Cases had a higher frailty baseline than controls.

In their adjusted model, the investigators found that vaccine effectiveness (VE) against hospitalization was 58.0% (95% confidence interval [CI], 34.2% to 73.2%). Adjusting for just frailty yielded a VE estimate of 58.7% (95% CI, 36.2% to 73.2%). However, among healthy older people, VE was 77.6%, declining as frailty increased.

The researchers concluded that the findings challenge commonly held views that VE is poor in older adults and that it helps prevent hospitalization, but with an effect that declines as seniors become frailer. They suggested that frailty is the most important confounder when estimating VE for older adults, and future studies on the impact of flu vaccine in older age-groups should account for frailty.
Jul 26 J Infect Dis abstract

Federal officials urge avoidance of Caribena Maradol papayas from Mexico

In an update into a papaya-linked Salmonella outbreak investigation, the Food and Drug Administration (FDA) yesterday warned consumers to avoid all Caribena brand Maradol papayas. The FDA said it took the step because Texas-based Grande Produce, which distributes the brand, has initiated a limited recall but has not issued a press release to notify consumers about it.

The FDA said Grande Produce's recall affects papayas it distributed nationwide from Jul 7 to Jul 18. The FDA also said illnesses have been reported in states where Grande Produce did not distribute papayas and that it's continuing its investigation.

In an update yesterday the CDC said epidemiologic and lab evidence points to Maradol papayas imported from Mexico as the source of the outbreak. It said so far Caribena brand papayas from Mexico have been identified in the outbreak, but additional brands will be announced as the information becomes available. It urged consumers not to eat, restaurants not to serve, and retailers not to sell Maradol papayas from Mexico.

On Jul 21 the US Centers for Disease Control and Prevention (CDC) announced that a Salmonella Kiambu outbreak likely linked to Maradol papayas has sickened 47 people in 12 states, one of them fatally. The large, oval fruits weigh 3 or more pounds and have green skin that turns yellow when the fruit is ripe. The papayas have salmon-colored flesh.
Jul 25 FDA update
Jul 25 CDC update
Jul 24 CIDRAP News story "Papaya-linked Salmonella outbreak sickens 47 in 12 states"