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