Debo Adegbile testifies during his confirmation hearing before the Senate Judiciary Committee Jan. 8, 2014. He was nominated to head the Justice Department’s civil rights division but was rejected. (Alex Wong/Getty Images)

Even with more than two years left in his term, President Obama’s ability to fill many of his administration’s most important jobs is rapidly diminishing.

White House officials are scrambling to reassess their confirmation strategy in the wake of two major setbacks this month: the Senate’s rejection of lawyer Debo P. Adegbile to head the Justice Department’s civil rights division and signs that surgeon general nominee Vivek H. Murthy could go down in defeat as well. On Tuesday, the administration appointed Karl Remón Thompson as acting head of the Justice Department’s Office of Legal Counsel — bypassing the Senate confirmation process.

But as the White House begins recalibrating its approach, it is grappling with an even broader problem: A number of its executive-branch nominees may not ever get their posts, and the appeal of a Senate-confirmed job is plummeting as a result.

“My advice to people is, don’t change your mailing address at this point,” said New York University public policy professor Paul C. Light, who studies presidential appointments. “The door has pretty much closed on the appointments process, except on some high-profile positions.”

A number of factors have contributed to the administration’s predicament. Senate Democrats took the unusual step in November of eliminating filibusters for most presidential nominations, but now some of their own members facing reelection are reluctant to approve nominees who have sparked outrage among influential voting blocs.

Adegbile, for example, was defeated March 5 in a procedural vote of 52 to 47 after Republicans and some Democrats objected to his involvement in an appeal filed on behalf of Mumia Abu-Jamal, who had been convicted in 1981 of killing a Philadelphia police officer. Many of the same senators are now questioning comments that Murthy, an internist at Brigham and Women’s Hospital in Boston, made in favor of gun control and contraception coverage.

Obama’s nominees have been confirmed at a rate similar to those under Presidents George W. Bush and Bill Clinton — 76.6 percent for Obama compared with 77.9 percent under those two presidents. But longer wait times have become a serious deterrent. As of Wednesday, 114 executive-branch nominees have been waiting an average of 210 days.

The invasive nature of the process, coupled with its unpredictable outcome, has begun deterring some candidates. In addition to the usual financial and professional disclosures, some current nominees have been questioned about Twitter posts and articles they wrote for their college newspaper.

Max Stier, president and chief executive of the nonpartisan Partnership for Public Service, described it as “a living purgatory.”

“It’s a horrific obstacle course that’s clearly dissuading a lot of first-tier talent,” he said.

According to Indiana University public management professor William G. Resh, the average vacancy time for Senate-confirmed executive-branch jobs during a first term was longer under Obama than under any of the three previous presidents, at 265 days.

Sen. Lamar Alexander (R-Tenn.) said in an interview last week that Democrats brought the problem on themselves by creating a “manufactured” crisis and lowering the threshold for nominations. Of 78 nominations pending on Nov. 20, the day before the Senate rules change, Republicans had agreed to confirm half of them under unanimous consent, he said, and only eight of them had been pending for more than nine weeks.

“I agree that today there’s a problem. But I do not agree that in November there was a problem,” Alexander said. “The only cure I know for it is for the Democrats to recognize they’ve made an error that’s set a terrible precedent for this president and future presidents and change the precedent.”

But the administration’s biggest problem lately has been Democrats, some of whom say privately that the White House was arrogant to press for a vote on Adegbile when it was unclear whether the nomination would pass. The move put vulnerable Senate Democrats such as Mark Begich (Alaska), Kay Hagan (N.C.) and Jeanne Shaheen (N.H.) in the position of voting for his confirmation before it failed; when a 60-vote threshold was in effect, the focus was more on moderate Republicans who were unwilling to support Obama’s picks.

White House spokesman Eric Schultz blamed Republicans for the current impasse.

“This administration has adopted the highest ethical standards in history, and the caliber of our nominees and their preparedness to serve reflect that high bar,” he said in a statement, adding that the appointments “are thoroughly vetted. But current congressional Republicans have made no secret of the extraordinary lengths they will go to obstruct the confirmation process.”

Administration officials declined to identify which slots have proved most difficult for them to fill. But a number of agencies have vacancies at the top with no nominees named, including the U.S. Patent and Trademark Office, the Consumer Product Safety Commission and the Council on Environmental Quality.

In other cases, the White House has put up candidates who have yet to receive a Senate vote. At the Justice Department, for example, the Senate has yet to approve nominees to head the national security division, the criminal division, the environment and natural resources division and the Office of Legislative Affairs. In addition to Thompson, one other Justice Department division — the Office of Legal Policy — has an acting director where no nomination has been made.

Then there is Environmental Protection Agency nominee Kenneth Kopocis, who holds an Obama administration record by waiting for 1,017 days as of Wednesday. He has been working as an EPA senior adviser while the Senate considers whether to let him head the agency’s water office.

This month, two senior Republicans on the Senate Environment and Public Works Committee, John Barrasso (Wyo.) and David Vitter (La.), sent a letter to their colleagues saying they should keep blocking Kopocis to demonstrate their opposition to a proposed EPA rule that would expand its control over U.S. waterways.

Indiana University law professor Dawn Johnsen, who was Obama’s first pick to head the Justice Department’s Office of Legal Counsel, waited 14 months for a confirmation vote that never came. She rented a home in Bethesda, moved her family and commuted every week from Maryland to Bloomington, Ind., at her own expense before withdrawing her name from consideration in April 2010.

Johnsen said she is concerned that the only people who can afford to serve in the executive branch are those who already live in the Washington area or are wealthy enough to survive the nomination process.

“I believe it’s harming the diversity of types of individuals who are willing to go through the process, because the harm depends very much on where you’re sitting,” she said.

Murthy, 36, has come under attack for his relative youth, his support for an assault weapons ban and a Twitter posting in October 2012 in which he wrote, “Guns are a health care issue.” Chris Lillis, a primary-care physician in Fredericksburg, Va., who became friends with Murthy working with him in the group Doctors for Obama, noted that major medical organizations such as the American Academy of Pediatrics and American College of Physicians held similar positions and had endorsed Murthy.

“Dr. Murthy’s positions are not at all outside the mainstream,” Lillis said, adding that the attacks on Murthy have had “a chilling effect” on others in the medical field who are interested in public service. “My wife and I started talking [recently], and between my Twitter feed and Facebook, I could never hold a public position in America.”

The White House is still conferring with Senate Democrats on how to advance Murthy’s nomination, including possibly postponing a vote until after the November midterms.

Andrew Arulanandam, spokesman for the National Rifle Association, said the group would continue to keep up the pressure on Murthy and a range of other presidential picks.

“This administration has been very aggressive in terms of using all their political appointees to try and diminish gun rights in this country,” he said. “We are forced as an organization to take a very serious view of every nomination.”

Wesley Lowrey contributed to this report.