Choice of empirical therapy

Any empirical antibiotic regimen should provide broad-spectrum cover, have additive or synergistic effect against the more virulent Gram-negative pathogens, and decrease the emergence of resistant organisms. Knowledge of local prevalence and antimicrobial resistance of pathogens is crucial in the selection of the most appropriate empirical antibiotic regimen. Traditional choices ( Table d) have included an aminoglycoside such as gentamicin paired with a broad-spectrum agent of another class that provides additional cover against Ps. aeruginosa (e.g. a b-lactam compound such as piperacillin or a cephalosporin such as ceftazidime). Nephrotoxicity has been the major problem with such combinations, particularly when used simultaneously with other nephrotoxic agents such as vancomycin or amphotericin B. Therefore combinations of two b-lactams have emerged in an effort to overcome aminoglycoside nephrotoxicity. While such combinations are equally efficacious, their major disadvantage has been the selection of unusual bacteria or resistant organisms such as multiresistant Enterobacter species. Some centers have advocated monotherapy with an agent such as ceftazidime or imipenem. These agents may be adequate to sustain a neutropenic patient for the first 48 h until the results of cultures are available, when specific antimicrobial therapy can be instituted.

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Table 2 Some empirical antimicrobial regimens for neutropenic patients

Table 2 Some empirical antimicrobial regimens for neutropenic patients

Because of the increasing incidence of Gram-positive bacteremia, many investigators have advocated the empirical use of an antibiotic with potent Gram-positive activity such as vancomycin or teicoplanin. Vancomycin causes significant toxicity (renal and skin), and there is no evidence that delay in instigating treatment for Gram-positive infection is associated with increased mortality. Therefore empirical Gram-positive therapy should be reserved for severely neutropenic patients with the following:

1. septic shock;

2. infected intravenous catheters (most catheter-associated bacteremias usually settle with appropriate antibiotics without catheter removal but, in the setting of a persistent bacteremia, catheter removal may become necessary);

3. streptococcal sepsis which is a frequent complication of febrile neutropenia.

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