HOUSTON -- The bullpen phone rang in the ninth inning after Keegan Thompson threw only one pitch on Wednesday night. Yainer Diaz connected with a fastball for a single, and Cubs manager David Ross wanted lefty Brandon Hughes to start getting ready.

Two pitches later, the Minute Maid Park crowd was rocking as Jake Meyers trotted around the bases, with the train horn blaring and the Cubs moments away from a 7-6 walk-off loss. Meyers’ two-run blast off Thompson initiated a swift downward spiral for a Chicago team searching for its footing amid a five-game losing streak.

“It’s a punch to the gut,” Thompson said. “It’s hard. It just sucks to let the team down.”

And it was easily the Cubs’ worst defeat to date this season.

“We’ve got to win that game,” Cubs manager David Ross said. “We’ve got to pitch better on the back end. The offense did enough tonight. We played good defense. I thought overall, really nice plays. We’ve got to cash that one in.”

The Cubs built a 6-1 lead by the fourth inning behind a pair of home runs from Seiya Suzuki, another jaw-dropping blast from Christopher Morel and contributions from Dansby Swanson (RBI triple) and Ian Happ (sacrifice fly). Lefty Drew Smyly used the early cushion to his advantage, striking out eight over six strong innings.

The bullpen just needed to cover the final three frames for the North Siders.

Ross is still working to find the right late-inning combination. Michael Fulmer faltered as the main ninth-inning arm out of the chute, eliminating the ability for the manager to work backward from that frame. Veteran Brad Boxberger also ran into issues and is now on the injured list with a right forearm strain. Hughes’ availability has been sporadic as he has learned to cope with a left knee issue.

And then there has been Thompson, who was undeniably a multi-inning weapon as a reliever last season. In ‘22, the righty had a 1.47 ERA with 42 strikeouts and 14 walks in 36 2/3 innings out of the ‘pen for Chicago. Thompson returned to the bullpen this year, but the results have not been to the same level.

“I think Keegan’s going to be fine,” Smyly said. “He’s very nasty. All it takes is one good game and another good game, and then you’re back rolling. I don’t think anybody should lose any confidence in him. He’s one of our best pitchers.”

Thompson posted a 0.68 ERA in his first eight outings (13 1/3 innings) this season, but he had nearly as many walks (10) as strikeouts (12) in that run. In the seven games that have followed that stretch, he has been charged with nine runs on 12 hits with four strikeouts and four walks.

One issue the Cubs are dealing with is how often Thompson can pitch. He has responded well to pitching with three days of rest (0.67 ERA with 10 strikeouts and three walks in 13 1/3 innings) this year, but has struggled when used in any other scenario (10.13 ERA with six strikeouts and 11 walks in eight innings).

“We’re trying to get him synced up,” Ross said. “When he’s got enough rest. It feels like it’s something we’ve got to look at -- just him bouncing back a little bit better.”

Thompson said he needed to trust in his approach and routine rather than start hunting for any adjustments. Asked if the righty reached that determination based on underlying data or video comparison, Thompson replied: “It’s just how I feel. It’s my rhythm, my timing, how I’m feeling. Everything feels the same.”

In the latest loss, Adbert Alzolay got through the seventh inning unscathed, but then Mark Leiter Jr. -- with one appearance in the previous eight games -- allowed two runs in the eighth. That was against the heart of Houston’s order, but Leiter looked like the right option given his strong splits (entering Wednesday with a .381 OPS vs. righties and .588 OPS vs. lefties) and overall performance (1.06 ERA in 17 games).

With the Cubs holding a three-run advantage in the ninth, Thompson was summoned from the bullpen. He was tasked with facing the Nos. 7-9 pocket of the lineup, and had an off-day coming Thursday to help with his required rest period.

After Diaz and Meyers tagged Thompson for two runs in a span of three pitches, pinch-hitter Mauricio Dubón drew a walk. Ross pulled the plug on Thompson and had Hughes take over.

“I’m not going to wait around at that point,” Ross said.

That put Hughes in a tough position, and the lefty eventually allowed a walk-off, two-run single to Kyle Tucker with the bases loaded.

“The whole thing is frustrating, for sure,” Ross said. “We’ve got to win that game.”