NEW YORK — So far in his first Grand Slam title defense, Andy Murray needed to beat players who are ranked 47th, 49th, 65th and 81st.

He’s well aware things probably will get a tad tougher the rest of the way at the U.S. Open, starting with No. 9 Stanlisas Wawrinka in the quarterfinals.

“Hopefully I’ll start playing a little bit better from now on. I mean, sometimes the first week of a Slam, I’ve played very well. Sometimes you maybe feel like there’s a little bit something to lose,” said Murray, who is 30-2 over the past five major tournaments.

“I’m in the quarterfinals of a Slam. It’s not an easy thing to do,” he said. “I’ll have to up my game.”

In a 6-7 (5), 6-1, 6-4, 6-4 fourth-round victory over Denis Istomin of Uzbekistan on a windy Tuesday night, Murray found reasons to yell at himself for mistakes.

He faltered late in the first set, dropping four points in a row. He also flubbed what should have been a simple volley after Istomin’s between-the-legs shot late in the second. There was more shakiness from Murray in the third set, in which he went up a break, only to lose serve to make it 3-all..

If Murray can get past Wawrinka, who eliminated No. 5 Tomas Berdych 3-6, 6-1, 7-6 (6), 6-2, Djokovic might very well be waiting in the semifinals. The top-seeded Djokovic, whose six major titles include the 2011 U.S. Open, has yet to drop a set and won 45 of 53 service points while beating 43rd-ranked Marcel Granollers 6-3, 6-0, 6-0 Tuesday.