But Guthrie got a big strikeout of Marlon Byrd in the first to help him wiggle out of a bases-loaded jam. And Guthrie struck out Tucker Barnhart to get out of a first-and-third jam in the fourth.
"The thing about Jeremy is, at times, he'll give up base hits, but he always finds a way to limit the damage," Royals manager Ned Yost said. "He always finds a way to make a big pitch. He never gets too worked up, he doesn't panic in those situations, and he just continues to find a way to make big pitches to get out of big jams."
Guthrie said the key Wednesday night was elevating some fastballs to get the Reds to chase.
"Yeah, [Salvador Perez] asked for quite a few fastballs up in the zone," Guthrie said. "These guys hit the ball well down in the zone, so you have to go higher than higher."
With his third straight strong start -- five hits, two walks, three strikeouts -- Guthrie lowered his ERA to 4.75.
"I didn't have the same type of command I did a couple of starts ago," Guthrie said. "But my location has been a bit better. I've been getting ahead of guys and making good pitches."
Jeffrey Flanagan is a reporter for MLB.com. Follow him on Twitter at @jflanagankc. This story was not subject to the approval of Major League Baseball or its clubs.