Federal and state law enforcement officials are aggressively prosecuting crimes involving fentanyl, utilizing statutes that were once rarely used, treating overdose deaths as homicides, seizing enormous quantities of the drug and charging foreign nationals with wide-ranging conspiracies.

The push comes as fentanyl is driving a spike in opioid overdoses, which killed more than 42,000 people in 2016. The Centers for Disease Control said fentanyl — a synthetic opioid so powerful that just a few grains of it can be fatal — is responsible for about 45 percent of those deaths. Prosecutors said they are using any and all means to mitigate damage from the drug, which is coming from Mexico and China and is often found mixed into heroin and cocaine and sometimes is pressed into counterfeit prescription pills.

“Synthetic opioids like fentanyl killed more Americans than any other kind of drug in 2016,” Attorney General Jeff Sessions said in a statement. “In response, the Department of Justice tripled our fentanyl prosecutions in 2017.”

Federal prosecutors charged 267 people with fentanyl-related crimes in the 2017 fiscal year, compared with 74 in FY 2016.

“We’re seeing just a lot more fentanyl cases,” said Mary Daly, the director of opioid enforcement and prevention efforts at the Justice Department. The increase from 2016 to 2017 is “good because that means we’re catching some of it and we’re enforcing the law. But it also means that there’s more fentanyl supply.”

In Omaha on Thursday, federal authorities charged two New Jersey men with possession with intent to distribute fentanyl after Nebraska State Patrol troopers seized more than 118 pounds of the drug during an April 26 traffic stop along Interstate 80, outside of Kearney. The troopers initially suspected that the foil-wrapped fentanyl was cocaine, authorities said.

Nebraska has one of the nation’s lowest rates of opioid overdose, but it has seen some of the country’s largest fentanyl seizures. Since October, law enforcement agencies in the state have seized about 300 pounds of fentanyl, said Matthew Barden, who will head a new Drug Enforcement Administration field office in the state. It will cover Nebraska, Iowa, Minnesota, North Dakota and South Dakota. Much of the fentanyl seized in Nebraska has been intercepted on Interstate 80 or at other travel points, including the Omaha train station.

The increased number of fentanyl seizures and rising drug use in the state have changed the way that authorities do their jobs, said Lt. Jason Scott of the Nebraska State Patrol. The police, like many others around the country, no longer field-test drugs for fear that fentanyl might sicken an officer. In Nebraska, they now take photographic and video evidence of fentanyl seizures and notify the U.S. attorney that most of the evidence will be destroyed because it is too dangerous to keep.

“It’s a paradigm shift,” Scott said. “It’s a huge health risk . . . but we also want good prosecutions.”

Local prosecutions also have skyrocketed as some states enact tougher laws against fentanyl. Prosecutors also are increasingly charging the people who supplied a drug user with a fatal dose of fentanyl, turning to various types of murder and manslaughter charges.

In Pennsylvania, the York County District Attorney’s Office has charged 45 people with drug delivery resulting in death, a first-degree felony, during the past three years.

“We in York County treat every single drug overdose death like a crime scene, like a homicide,” said David Sunday, the York County District Attorney.

That means investigators or detectives collect evidence such as drug paraphernalia or text messages and ask county coroners to perform autopsies. Sunday and other local law enforcement officials said using the drug death statutes are part of a multipronged approach to fighting drug abuse, which includes having first responders carry Naloxone, a drug that reverses opioid overdoses.

“The drug-induced homicide thing is one component of a broader, manifold strategy that’s going to be necessary to take on what has been like a huge disaster,” said Patrick D. Kenneally, the state’s attorney in McHenry County, Ill., where opioid overdose deaths more than tripled from 2013 to 2017, according to the Illinois Department of Public Health. “This was something this community has never faced before, and we felt this really deserved our full-throated response.”

But critics of the drug-induced homicide statutes say they are too punitive and hark back to the war on drugs of the 1980s and 1990s, which disproportionately affected minorities. Another concern is that prosecutors are going after users who provide overdose victims with heroin instead of pursuing the higher-level dealers who more widely distribute the drugs — a worry prosecutors say is unfounded because they use discretion when bringing the cases.

Some worry that the increase in prosecutions could make people hesitant to call 911 to report drug overdoses out of fear of being charged, which, in turn, could lead to more overdose deaths.

“There’s not a shred of evidence that these laws work. It certainly doesn’t deter drug selling,” said Lindsay LaSalle, a senior staff attorney with the New York-based Drug Policy Alliance. The group, which has been tracking instances of prosecutors bringing homicide charges against drug dealers, said at least 20 states have statutes that allow for prosecuting those who provide drugs to users who later die of an overdose.

Sessions has ordered his federal prosecutors to aggressively target drug traffickers and — parting with his predecessor — has directed them to charge defendants with the most serious, provable crimes. Justice Department spokesman Ian Prior said the two factors driving the uptick in fentanyl prosecutions are the increased availability and potency of fentanyl, along with Sessions’s making one of his priorities the prosecution of opioid-related crimes “fueled in large part by fentanyl.”

In San Diego, federal prosecutors have charged four people this year with distribution of fentanyl resulting in death. In February, U.S. Attorney Adam Braverman appointed civil and criminal coordinators who will make opioid prosecutions their top priority.

“We’re going to go after the people who are shipping the precursors, we’re going after the Mexican cartel leaders who are manufacturing it and shipping it to our district and going after the people who are distributing it,” Braverman said.

Federal prosecutors in April charged 10 people, including four Chinese nationals, with selling large quantities of fentanyl over five years in a case that allegedly involved 30 separate aliases, encrypted communications, cryptocurrency, laundered funds and offshore accounts. According to the indictments, the Chinese-based network was moving fentanyl and a fentanyl analogue into the United States and Canada.

The fentanyl pipeline in the case allegedly stretched from Oregon to Ohio to Florida and resulted in several overdose deaths, including 18-year-old Bailey Henke of Grand Forks, N.D. The case also was the first time the United States froze the assets of an alleged fentanyl trafficker.

Increasingly, state prosecutors are kicking cases up to the federal level to invoke stricter penalties, including mandatory minimums.

Susan L. Opper, the district attorney in Waukesha County, Wis., said she refers high-level cases to the U.S. attorney, not those of low-level users.

“We can get more bang for our buck,” she said. “If there’s a death associated, it can be a life imprisonment potential, and we don’t have that at the state level.”