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At least 68 people died in the capital, many of gunshot wounds. Protesters stormed the government building that Bakiyev left behind, smashing trucks through the perimeter fencing.
The US-led NATO alliance said it had temporarily suspended supply flights through Manas and some aircraft had been moved due to the unrest, but the interruption should not significantly affect operations or logistical support in Afghanistan.
Bakiyev came to power in the 2005 "Tulip Revolution" protests, led jointly by Otunbayeva, which ousted Kyrgyzstan's first post-Soviet president, Askar Akayev. She briefly served as acting foreign minister before falling out with Bakiyev.
Gunshot wounds
The opposition said at least 100 people had been killed on Wednesday. The Health Ministry put the death toll in Bishkek at 68 dead, and said 520 people had been injured.
The violence was the deadliest in ex-Soviet Central Asia since government forces in Uzbekistan fired on protesters in the city of Andizhan in May 2005. The Uzbek government said 187 people died, including its forces, but rights groups say several hundred mostly unarmed protesters were killed.
Political unrest over poverty, rising prices and corruption has gripped Kyrgyzstan since early March. The average monthly wage is about $130 and remittances from workers in Russia have fallen sharply during the global economic crisis.
"It was a never ending rip-off. Every day they would raise prices for gas, for water, and in the end is it good to shoot at your own people?" said Alioglu Samedov, 62, a retired lawyer.
Analysts said the unrest would also increase uncertainty for foreign investors in Kyrgyzstan's mining sector and raised the possibility of outside military intervention.
Canadian mining company Centerra Gold said on Wednesday its flagship Kumtor gold mine in Kyrgyzstan had so far been unaffected by the violence, but its shares fell 22 Canadian cents to C$13.32 on the Toronto Stock Exchange.
"Bakiyev is unlikely to return to power but the prevailing uncertainty poses severe risks to foreign investors, raises the possibility of foreign intervention and will directly affect US interests in Central Asia," said Eurasia Group analyst Ana Jelenkovic.
The foreign ministry in China, which shares a border with Kyrgyzstan, said it was "deeply concerned" about the unrest.
Russian Prime Minister Vladimir Putin earlier called for calm and denied Moscow had played a hand in the clashes.