MELBOURNE, Australia (AP) — Novak Djokovic won't be setting the Australian Open record for most men's titles this year, after a shocking second-round loss to wild-card entry Denis Istomin. The former world No. 1 lost 7-6, 5-7, 2-6, 7-6, 6-4.

It was the earliest loss at a major since 2008 for six-time Australian Open champion Djokovic.

Third-seeded Milos Raonic shrugged off a cold and a sore throat to extend his streak of reaching the third round at all seven Australian Opens he's contested with a 6-3, 6-4, 7-6 win over Gilles Muller, who won the Sydney International last week.

Rafael Nadal swept aside 2006 Australian Open finalist Marcos Baghdatis 6-3, 6-1, 6-3 to advance to the third round of the tournament the Spaniard won in 2009.

The 14-time major champion, who lost in the first round of the tournament last year, is looking to win his first major since the 2014 French Open.

On the women's side, Serena Williams, who is also ranked No. 2 and is a six-time Australian Open champion, kept her chase for an Open-era record 23rd major title on track with a 6-3, 6-4 win over Lucie Safarova and Agnieszka Radwanska didn't last much longer than Djokovic, losing her second-round match 6-3, 6-2 to Mirjana Lucic-Baroni.