MELBOURNE, Australia – It was certainly possible to see trouble ahead for Novak Djokovic based on all the dents in his armor from 2016. But it would have taken a creative mind to see the latest knockout blow coming from 117th-ranked Denis Istomin of Uzbekistan in the second round of the Australian Open on Thursday.

When Istomin was asked how he would have responded if someone suggested such a thing a couple of weeks ago, he answered, "I would have said, 'Are you crazy, or what?' "

Istomin won 7-6 (8), 5-7, 2-6, 7-6 (5), 6-4, delivering the latest blow to Djokovic's battered aura of invincibility. Last June, after winning the French Open for the first time, Djokovic held all four Grand Slam singles titles. But he has not won a major since and has surrendered the No. 1 ranking to Andy Murray, who lost to Djokovic two weeks ago in the final in Doha, Qatar, but is now a solid favorite to win his first Australian Open. Murray played late Thursday against Sam Querrey.

This was Djokovic's earliest exit at a Grand Slam tournament since he lost to Marat Safin in the second round of Wimbledon in 2008. It was his earliest loss in Melbourne since a first-round defeat in 2006, at age 18.

Djokovic was the only one of the men's seeded players to lose on a long day capped by ninth-seeded Rafael Nadal's 6-3, 6-1, 6-3 win over 2006 finalist Marcos Baghdatis.

Women's matches

Angelique Kerber had a straight-sets win for the first time in her first Australian Open title defense, beating Kristyna Pliskova 6-0, 6-4 in the third round.

Kerber will next play 35th-ranked CoCo Vandeweghe, who reached the fourth round in Australia for the first time with a 6-4, 3-6, 7-5 win over 2014 semifinalist Eugenie Bouchard.

Eighth-seeded Svetlana Kuznetsova was broken in the second and third sets when serving for the match before finally beating former No. 1-ranked Jelena Jankovic 6-4, 5-7, 9-7 in a 3-hour, 36-minute match.

Commentator dropped

Commentator Doug Adler was dropped from ESPN's tournament coverage and has apologized for how he spoke about Venus Williams' play in the second round, saying he was describing her aggressive style as "guerrilla" tactics and not comparing her with a "gorilla."

The former tennis pro said he "simply and inadvertently chose the wrong word to describe her play."