Strains of Klebsiella pneumoniae that produce one of three possible carbapenemases—KPC—have recently been identified with increasing frequency among isolates recovered from patients residing along the East Coast of the United States, particularly within the New York City metropolitan region. These strains have exhibited resistance to multiple antibiotic classes, including carbapenem agents. We report a case of nosocomial pneumonia and empyema caused by a KPC‐producing isolate of K. pneumoniae at a large midwestern U.S. tertiary care facility in which the patient was treated with tigecycline. Although the pneumonia was treated successfully, the empyema recurred in association with a treatment‐emergent tigecycline minimum inhibitory concentration (MIC) increase from 0.75 to 2 μg/ml. Clinicians should be aware of the potential occurrence of this treatment‐emergent MIC increase, especially in the setting of sustained tigecycline therapy. In addition, the emergence of carbapenem‐resistant Enterobacteriaceae reinforces the importance of antibiotic stewardship and strict infection control practices.