Package confusion attacks such as typosquatting threaten software supply chains. Attackers make packages with names that syntactically or semantically resemble legitimate ones, tricking engineers into installing malware. While prior work has developed defenses against package confusions in some software package registries, notably NPM, PyPI, and RubyGems, gaps remain: high false-positive rates, generalization to more software package ecosystems, and insights from real-world deployment. In this work, we introduce ConfuGuard, a state-of-art detector for package confusion threats. We begin by presenting the first empirical analysis of benign signals derived from prior package confusion data, uncovering their threat patterns, engineering practices, and measurable attributes. Advancing existing detectors, we leverage package metadata to distinguish benign packages, and extend support from three up to seven software package registries. Our approach significantly reduces false positive rates (from 80% to 28%), at the cost of an additional 14s average latency to filter out benign packages by analyzing the package metadata. ConfuGuard is used in production at our industry partner, whose analysts have already confirmed 630 real attacks detected by ConfuGuard.