Diagnostic guidelines should also depend on the medical history of the patient, the anatomic site of infection, and even the primary organism. For

example, P. aeruginosa may occur deeper in the tissues than staphylococci (Kirketerp-Møller et al., 2008; Fazli et al., 2009), and diagnostic criteria for wound infections are also specific to the type of wound (Cutting & White, 2004). IE also illustrates that determining the anatomic site is important, because in this infection, biofilm bacteria colonizing the endocardium are localized on the heart valves (Parsek & Singh, 2003; Mallmann et al., 2009; Moter et al., PLX-4720 nmr 2010). Characteristically, IE, although frequently associated with bacteria that exhibit antibiotic susceptibility in the microbiology lab, requires prolonged (2–6 weeks) antibiotic treatment. Thus, chronicity or recurrence and documentation of antibiotic recalcitrance are important clues for BAI (Hall-Stoodley & Stoodley, 2009). As specific biofilm markers along with definitive signs and symptom criteria for occult or suspected deep biofilm

infections are currently lacking, detection at the site of infection may include advanced imaging techniques such as whole body 18F fluorodeoxyglucose positron emission tomography (PET/CT) (Makis & Stern, 2010; Bensimhon et al., 2011). If such imaging techniques or other signs of occult or foreign body-associated biofilm infection are convincing, then guided (ultrasound or X-ray or surgery), aseptically obtained diagnostic biopsies are, in most cases, Lumacaftor necessary unless bacteria

Vitamin B12 are released from the biofilm to the blood (endocarditis) or secretions such as sputum. Microscopy (indicating microbial aggregates), culture (aerobic and anaerobic on differential media and for 1–2 weeks), and culture-independent broad spectrum methods (PCR) should then be used to detect any bacteria or fungi. Contaminants such as CoNS from skin may also cause biofilm infections on foreign bodies such as intravenous catheters and other implantable devices. Ultimately, indirect methods such as antibody detection can only be used, if their predictive diagnostic value has been proven in clinical studies (Pressler et al., 2009). Similar problems in diagnosing and classifying patients with IE lead to the Duke criteria (Durack et al., 1994) and later modified Duke criteria (Fournier et al., 1996; Li et al., 2000), which have been developed to facilitate and standardize the diagnostic process. A combination of major and minor criteria including echocardiography, microbiological, clinical, and histological findings results in a score, which indicates the probability of IE. However, although the Duke criteria may be helpful and provide a starting point for a BAI algorithm, it must be noted that they are used for one disease, in one organ, whereas biofilm infections are much more diverse.