An ultrasound machine and a hospital bed are covered in rubble and debris on Tuesday after a reported airstrike by Syrian government forces in a village in northwestern Idlib province. (Omar Haj Kadour/AFP/Getty Images)

Militants linked to al-Qaeda began a large-scale offensive Tuesday against government targets in western Syria, state media and opposition activists said, prompting a fierce response by pro-government forces and potentially impeding international efforts to quell fighting in that part of the country.

The campaign started Tuesday morning when insurgents — led by Hayat Tahrir al-Sham, a former al-Qaeda affiliate — launched attacks on government-held villages in Hama province, just south of extremist-controlled Idlib province.

Their offensive was met with airstrikes and mortar fire, including attacks on medical facilities and personnel in rebel-held areas, activists said. One medic was reported killed in an airstrike on al-Tih hospital in southern Idlib, according to activists. Further strikes were reported on field hospitals in Khan Sheikhoun, the site of a deadly chemical-weapons attack in April that the United Nations has blamed on Syrian government forces.

The fresh fighting threatened to upend a months-long initiative by Iran, Russia and Turkey to establish what they call “de-escalation zones” in four regions of Syria, including parts of Hama and Idlib, which also hosts a growing number of displaced civilians.

People walk through rubble past a damaged ambulance Tuesday following a reported airstrike by Syrian government forces in the village of al-Tahh, in northwestern Idlib province. (Omar Haj Kadour/AFP/Getty Images)

Hayat Tahrir al-Sham, or HTS, rejected talks that took place over months in the Kazakh capital of Astana. The militant group denounced the negotiations as a “betrayal” and a plot to hand opposition areas over to the Syrian government.

Iran and Russia are staunch backers of President Bashar al-Assad and have contributed troops and military assets to crush Syria’s rebellion. The conflict began in 2011 as a popular uprising but quickly morphed into a brutal civil war, sucking in world powers and fueling the rise of the Islamic State militant group.

The Turkish Foreign Ministry announced last week that Iran, Russia and Turkey had agreed to deploy armed observers on the edge of Idlib, where troops would provide a cordon with checkpoints and watchtowers. It was unclear when those forces would be deployed.

The insurgent offensive Tuesday was the largest in the area since March, according to the Syrian Observatory for Human Rights. The Britain-based monitoring group said the campaign kicked off with heavy shelling and machine-gun fire on government-held villages in northern Hama, including along a highway that links the capital, Damascus, with other provinces.

A spokesman for HTS, Imad al-Din Mujahed, told an opposition outlet that the group did not want to broadcast its reasons for launching the offensive. The outlet, Enab Baladi, quoted a media activist linked with HTS as saying that the battle was in response to the agreement on de-escalation zones.

The militants will continue to fight to prevent the establishment of such a zone in Idlib, said the activist, Abu Baraa al-Qahtani.

Zakaria Zakaria in Istanbul and Heba Habib in Stockholm contributed to this report.