At the start of the COVID-19 outbreak in Michigan, 56.6% of patients hospitalized with this illness caused by the SARS-CoV-2 virus received early empiric antibiotic therapy, though 96.5% of them turned out to have only COVID-19, not bacterial infections (Clin Infect Dis 2020; doi.org/10.1093/cid/ciaa1239). The authors emphasized that this might be an underestimate of empiric antibiotic use, as they excluded from analysis data from patients who received azithromycin, which had been touted along with hydroxychloroquine, as a treatment for COVID-19.
This study was part of MI-COVID19, a statewide quality initiative to improve care for patients hospitalized with COVID-19. The researchers analyzed data from a randomly sampled cohort of 1,705 inpatients at 38 Michigan hospitals between mid-March and mid-June 2020.
Early antibiotic therapy varied widely across facilities, from 27%–84%, but decreased over time. Nearly two-thirds of patients received antibiotics that target community-acquired pathogens, but about one-quarter received medications that target methicillin-resistant Staphylococcus aureus, and another quarter took antibacterials that target pseudomonas. More than half of patients had their antibacterials stopped within 1 day of positive SARS-CoV-2 tests.
As the turnaround time for SARS-CoV-2 diagnostic testing shortened, so too did early antibiotic therapy. In March 54.2% of polymerase chain reaction test results came back within 1 day, climbing to 89.2% in May and dipping to 75% in June. Early antibiotic therapy tracked with these trends; 66.7% of patients received empiric treatment in March, declining to 46.9% in May, and rising to 60% in June.
Procalcitonin results did not prove particularly useful in guiding stewardship efforts, according to the researchers. Nearly 56% of patients who had COVID-19 and a community onset bacterial infection had procalcitonin levels >0.5 ng/mL, but so did 21.2% of those who didn’t have a community-onset bacterial infection. This translated to a 9.3% positive predictive value for community-onset bacterial infection. Conversely, the negative predictive value of procalcitonin concentrations ≤0.1 ng/mL was 98.3%.
TAILOR-PCI: Genotype-guided Antiplatelet Therapy Misses Mark
Genotype-guided antiplatelet therapy in patients with acute coronary syndrome and stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) did not at 12 months yield statistically significant differences from standard care in a primary endpoint of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia (JAMA 2020;324:761-77). Results of the long-anticipated TAILOR-PCI randomized trial did, however, show that genotype-guided therapy reduced major cardiovascular events by 34%.
Both the investigators and editorialists suggested these results mark a milestone rather than the finish line on genotyping in cardiovascular care. “Although these results fell short of the effect size that we predicted, they nevertheless provide a signal that offers support for the benefit of genetically guided therapy,” said study co-leader Naveen Pereira, MD, in a statement.
“The future is clearly pointing toward a personalized strategy for therapeutic interventions, and genotype-guided approaches should be part of this strategy—the question is how much,” wrote the editorialists (JAMA 2020;324:747-9). They added that “clinical evidence at this critical moment” doesn’t support “routine use” of genotype-guided antiplatelet therapy in patients with CAD.
Most patients receive the P2Y12 inhibitor clopidogrel after PCI, but 24% to 40% continue to have platelet reactivity, especially those with CYP2C19*2 or *3 loss-of-function (LOF) variants that reduce activity of the CYP2C19 liver enzyme responsible for metabolizing clopidogrel. The newer agents, prasugrel and ticagrelor, skip this metabolism step and provide more consistent platelet inhibition but also carry higher bleeding risks than clopidogrel. TAILOR-PCI sought to determine how genotype-guided antiplatelet therapy would affect ischemic outcomes in CYP2C19 LOF carriers.
The trial involved 5,302 patients treated from 2013 to 2018 at 40 centers. Half, randomized to genotype-guided care, had point-of-care genotyping, with CYP2C19 LOF carriers receiving ticagrelor and noncarriers taking clopidogrel. The other half, randomized to standard care, received clopidogrel and underwent genotyping at 12 months.
The primary endpoint occurred in 4% of CYP2C19 LOF carriers in the genotype-guided group and in 5.9% of those in the standard care group (hazard ratio, 0.66; P value, 0.06). There also were not statistical differences in the 11 secondary endpoints like major or minor bleeding defined by TIMI criteria and all-cause mortality.
MELD-Na Score Would Reduce Liver Transplant Waiting List Mortality
Use of the MELD-Na score in prioritizing patients for liver transplant could increase the chance of high-risk patients in qualifying for transplant and lower their risk of dying while waiting for an organ, according to research presented at the Digital International Liver Congress. MELD-Na was adopted in the U.S. in 2016 as a means of qualifying patients for transplants but has not been used in Europe.
By incorporating sodium levels MELD-Na accounts for hyponatremia, an important risk-predictor in patients on liver transplant waiting lists, according to the researchers.
The investigators retrospectively analyzed data from 5,223 patients who had been allocated to the Eurotransplant liver transplant waiting list based on their MELD scores, reclassifying them according to their MELD-Na scores.
After 90 days, 21.3% of patients had received a new liver, 24.2% had been removed from the waiting list, and 2.8% had died. More than a quarter of patients (28.5%) had the mildest hyponatremia <135 mmol/L; 8.8% and 2.6% had more severe hyponatremia <130 mmol/L and <125 mmol/L, respectively. The hazard ratio for death was 1.16 per gained MELD point and 1.08 per 1-unit decrease in sodium levels. The researchers calculated that 26.3% of patients who died within 90 days on the waiting list would have had a significantly higher chance of receiving a transplant had MELD-Na been used. This would have amounted to a 4.9% decrease in 90-day waiting list mortality.
Considering the shortage of available livers and increasing prevalence of cirrhosis, having better predictors of mortality and prioritization of transplants is increasingly important, according to the investigators.