Antimicrobial agents are an adjunct to the normal host immune response. Infections associated with foreign bodies, such as an intravascular catheter, are difficult to eradicate with antimicrobials alone because of organism-produced biofilms that impair phagocytosis. Similarly it is difficult for phagocytic cells to eradicate bacteria amid vegetations of fibrin and platelets on infected heart valves. Prolonged, bactericidal therapy is required with these infections, and outcomes are not always satisfactory. Foreign body devices may have to be removed if sterilization does not occur promptly. Infections in closed spaces with limited perfusion (such as abscesses or chronic osteomyelitis with poorly perfused bone) are difficult to cure without surgical drainage, debridement of the infected tissue, and reestablishment of a good vascular supply.
Optimal antimicrobial therapy requires an understanding of both the pharmacokinetics (e.g., bioavailability and tissue penetration) of the administered drugs and their pharmacodynamics (e.g., metabolism and excretion by the body) in specific patient populations. The bioavailability of orally administered antibiotics varies, depending on the acid stability of the drug; degree of gastric acidity; and whether it is taken with food, antacids, H2 blockers, or other medications. An ileus or profuse diarrhea may alter intestinal transit time and result in unpredictable absorption.
The site and nature of the infection may affect the choice of antimicrobials. Aminoglycosides, active against aerobic organisms only, have significantly reduced activity in abscesses with low pH and oxygen tension. Infections of the central nervous system or the eye necessitate treatment with antimicrobials that penetrate and achieve therapeutic levels in these sites.
Limited renal function (as in premature infants or those with renal failure) requires increasing dosing intervals to allow time for excretion of certain drugs. The larger volume of distribution of certain hydrophilic antimicrobials and increased renal clearance (e.g., in cystic fibrosis) requires higher doses to achieve therapeutic levels. Weight-based dosage regimens may result in overdoses in obese children due to significantly smaller volumes of distribution for hydrophilic drugs. Determining serum drug levels for antibiotics with narrow safety margins (e.g., aminoglycosides and vancomycin) minimizes adverse effects of treatment.
Drug-drug interactions must be considered when multiple antimicrobial agents are used to treat infection. Use of two or more antimicrobial agents may be justified before organism identification or for the benefit of two drugs with different mechanisms of action. Several antimicrobials are administered routinely in combination (e.g., trimethoprim-sulfamethoxazole, amoxicillin-clavulanate) because of synergism(significantly greater bacterial killing or spectrum of activity than when either is used alone). The use of a bacteriostatic drug, such as a tetracycline, along with a β-lactam agent, effective against growing organisms only, may result in antibiotic antagonism, or less bacterial killing in the presence of both drugs than if either is used alone.
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Fever without a Source Fever of Unknown Origin
Core body temperature is normally maintained within 1° C to 1.5° C in a range of 37° C to 38° C. Normal body temperature is generally considered to be 37° C (98.6° F; range, 97° F to 99.6° F). There is a normal diurnal variation, with maximum temperature in the late afternoon. Rectal temperatures higher than 38° C (>100.4° F) generally are considered abnormal, especially if associated with symptoms.