The Problem of Culture-Negative Infections

Abstract

Because modern medicine suffers increasingly from the “silo” phenomenon, in which each specialty ponders its problems in isolation, the gradual emergence of a generalized threat to millions of patients is thus poorly countered by the disconnected efforts of small teams that address the same theme without the recognition of common ground. The recent recognition that bacteria have reverted to their natural biofilm strategy (Costerton)in attacking human hosts, in response to advances in immunization (vaccines) and therapy (antibiotics), has been perceived in a piecemeal fashion that is slowly spreading amongst the silos. We respond to medical threats in relation to the immediacy of the dangers to the patient, so the first reaction was to the phenomenal resistance of biofilm infections to antibiotics and to host defense mechanisms, and the past three decades have seen a series of tactical maneuvers involving surgical resection and high-dose antibiotic therapy. While medicine reacted to this serious threat of overt bacterial infections that were not prevented by vaccination, and that persisted in spite of seemingly suitable antibiotic therapy, another equally serious biofilm problem was emerging at the bottoms of several silos. Experienced clinicians in many specialties saw cases in which they were certain that bacteria were involved, because all of the classical signs of infection were present, but the gold standard of diagnosis (culture) was negative. Some of these cases involved medical devices (Khoury et al.), others involved infections of compromised tissues (Hoiby), but the overall fight, conducted in isolation in many silos, was to decide on the correct antibacterial strategy when the bacterial etiology of many important diseases (otitis media, prostatitis) was called into question by negative cultures. Bacteria do not respect the silos created by clinicians and scientists. They have switched from an acute frontal attack by planktonic cells, to a strategy of biofilm growth and chronic attack on infected tissues, and the most serious long-term effect of this tactical change may be that they evade detection by the classic methods of Medical Microbiology.