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Nevertheless, some patients fail antibiotic therapy, and this review will discuss the approach to such real or perceived failure, as indicated in the algorithm (Fig. 1).

Noninfectious mimics of infection

The body's tissues have a limited repertoire of response to injury, and a multitude of noninfectious illnesses may mimic infection and fail to respond to antibiotic therapy until the correct diagnosis is made. Systemic inflammatory response syndrome, a response to tissue injury, is defined as a derangement in two of the four parameters of temperature, heart rate, respiratory rate, and white blood cell count. Sepsis, defined as systemic inflammatory response syndrome resulting from infection, is effectively mimicked by many diseases that produce fever with generalized manifestations, including vasculitis, drug hypersensitivity, malignant hyperthermia, neuroleptic malignant syndrome, thyroid storm, and adrenal insufficiency [1].

Localized syndromes also resemble a variety of infectious processes. For example, cellulitis is mimicked by contact dermatitis, drug reactions, eosin-ophilic cellulitis, arthritis, malignant infiltration, familial Mediterranean fever, panniculitis, insect stings, phlebitis, and infected Baker's cysts [2]; pulmonary infiltrate and fever imitating pneumonia are seen with pulmonary embolism, aspiration, hemorrhage, pulmonary hypersensitivity, tumor, vasculitis, and sickle cell pneumopathy; a variety of central nervous system processes can resemble meningitis, including medication reactions, vasculi-tis, malignancy, hemorrhage, sarcoidosis, and seizures; pancreatitis and ischemic bowel masquerade as abdominal infections; gastroenteritis is suggested by toxins, inflammatory bowel disease, and hyperthyroidism; and pyogenic arthritis is part of the differential diagnosis of rheumatoid arthritis, synovial tumors, and gout. The above lists are only partial but illustrate the capacity of many sterile illnesses to resemble infection.

Infectious processes not specifically treatable with antibiotics

Some infections will fail antibiotic therapy because they are not specifically treatable. These infections include most viral infections, especially upper respiratory infections and viral meningitis, and toxin-induced illness such as staphylococcal toxic shock. Some infections may appear to respond to antimicrobial therapy because of the anti-inflammatory activity of agents such as azithromycin.

Treatable infection with incomplete response

Frequently, after being treated for infection, a patient will appear to respond but remain febrile (Box 1). Such patients often feel and look better

Initiate Rx

Surgical component: debride necrotic tissue, relieve obstruction, drain collections, remove foreign material, check for metastatic abscess

Surgical component: debride necrotic tissue, relieve obstruction, drain collections, remove foreign material, check for metastatic abscess

Wrong antibiotic: resistance, need for cidal activity, need additional coverage, superinfection, etc.

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