Antimicrobials administration

A recent trial in bacteremic septic shock showed that each hour of delay in effective antimicrobial administration over the ensuing 6 h was associated with an average decrease in survival by 7.6%c... 

Whichever antimicrobial regimen is chosen, the patient should be reassessed continually to determine the success or failure of therapies. The clinician should recognize that there are many reasons for poor patient outcome with intraabdominal infection improper antimicrobial administration is only one. The patient may be immunocompromised, which decreases the likelihood of successful outcome with any regimen. It is impossible for antimicrobials to compensate for a nonfunctioning immune system. There may be surgical reasons for poor patient outcome. Failure to identify all intraabdominal foci of infection or leaks from a GI anastomosis may cause continued intraabdominal infection. Even when intraabdominal infection is controlled, accompanying organ system failure, most often renal or respiratory, may lead to patient demise. 

Numerous factors, such as underlying disease, immunosuppressive drug therapy, and antimicrobial administration, determine the immunocompromised host s risk of developing infection. Several risk factors are present concomitantly in many patients (see Table 120-1). 

This wide range of pharmacokinetic properties, along with thek ease of administration, broad spectmm antimicrobial activity, and noninterference with host-defense mechanisms is responsible for thek widespread use five decades after thek discovery. 

Widespread clinical acceptance continues to be accorded to the cephalosporins, and the field is extremely active as firms search for the ultimate contender. Among the characteristics desired is retention of the useful features of the older members (relatively broad spectrum, less antigenicity than the penicillins, relative insensitivity toward 3-lactamases, and convenience of administration) while adding better oral activity and broader antimicrobial activity (particularly potency against Pseudomonas, anaerobes, meningococci, cephalosporinase-carrying organisms, and the like). To a considerable extent these objectives have been met, but the price to the patient has been dramatically increased. 

Recognizing the presumed site of infection and most common pathogens associated with the infectious source should guide antimicrobial choice, dose, and route of administration. For example, community-acquired pneumonia is caused most commonly by S. pneumoniae, E. coli is the primary cause of uncomplicated UTIs, and staphylococci and streptococci are implicated most frequently in skin and skin-structure infections (e.g., cellulitis). 

The drug, dose, duration, and route of administration of the patient s antimicrobial regimen... 

Correct timing of antibiotic administration is imperative to preventing SSI. The National Surgical Infection Prevention Project recommends infusing antimicrobials for surgical prophylaxis within 60 minutes of the first incision. Exceptions to this rule are fluoroquinolones and vancomycin, which can be infused 120 minutes prior to avoid infusion-related reactions.1 No consensus has been reached on whether the infusion should be complete prior to the first incision. However, if a proximal tourniquet is used, antibiotic administration should be complete prior to inflation. 

Studies have found that administration of the antimicrobial should begin as close to the first incision as possible. This is important for antibiotics with short half-lives so that therapeutic concentrations are maintained during the operation and reduce the need for redosing. Beginning the infusion after the first incision is of little value in preventing SSL Stone and associates found that administration of the antimicrobial after the first incision had SSI rates similar to patients who did not receive prophylaxis.20... 

O A risk assessment should be performed at presentation of febrile neutropenia to identify low-risk patients for potential outpatient treatment (see Table 96-3). Patients who do not meet low-risk criteria should be hospitalized for parenteral administration of broad-spectrum antibacterials. The IDSA has published evidence-based guidelines for the management of febrile neutropenia5,12 (Fig. 96-1). The choice of initial antimicrobial agent(s) depends on the following factors ... 

Absorption of antimicrobial agents such as fluoroquinolones and tetracyclines that can be bound by divalent and trivalent cations potentially could be compromised by administration with EN formulas containing these cations. The fluoroquinolones (e.g., levofloxacin and ciprofloxacin) have been best studied in this regard, and results of studies are not consistent. Mechanisms for an interaction between fluoroquinolones and EN formulas other than chelation by cations have been postulated.40 Some institutions hold tube feedings for 30 to 60 minutes or more before and after enteral dosages of fluoroquinolones. Because ciprofloxacin absorption has been shown to be decreased with jejunal administration, this drug probably should not be given by jejunal tube.41... 

Animal and human studies support the use of antibiotics for the prevention of infectious morbidity and mortality in severe ANP. The most effective antimicrobial agents are the fluoroquinolones, imipenem-cilastatin, and metronidazole, which achieve adequate penetration into pancreatic juice and necrotic tissue and inhibit the growth of enteric bacteria. Although a recent meta-analysis [185] suggested that prophylactic antibiotic administration reduces sepsis and mortality and this approach has been recommended by recent guidelines and consensus state-... 

The route of antibiotic administration might be crucial. Animal studies [193, 194] have shown that enteral administration (either by oral or rectal route) of antimicrobials reduces the rate of bacterial translocation and early mortality in rats or mice with experimentally induced pancreatitis. Indeed, in patients with ANP, selective bowel decontamination with oral and rectal antibiotics decreased the infection rate [195]. 

Two concerns with all antimicrobial agents intended for oral administration are the risk of depleting normal gut flora and the potential to induce antibacterial resistance. These aspects have been studied in several trials. 

Rifaximin is a synthetic rifamycin derivative, which acts by inhibiting bacterial ribonucleic acid (RNA) synthesis [48]. It is virtually unabsorbed after oral administration and is, therefore, used primarily to treat gastrointestinal infections. Rifaximin possesses a broad spectrum of antimicrobial activity, covering Gram-positive and Gram-negative bacteria, both arerobic and anaerobic [49], Several studies [44, 49-62] have shown that in patients with HE rifaximin displays an efficacy similar to that of lactulose and neomycin (table 1). A recently published study [62] compared the efficacy and safety of... 

Traditionally, treatment of CGD entailed prophylactic administration of antimicrobial agents in an attempt to prevent occurrence of severe infection. However, affected individuals still experience life-threatening infections, requiring hospitalization and intensive medical care, as often as once a year. Attempts to control these infections rely on strong antimicrobial agents and leukocyte transfusions. 

The use of antimicrobials for this purpose requires consideration of the types of patients who are at risk the procedures causing bacteremia the organisms that are likely to cause endocarditis and the pharmacokinetics, spectrum, cost, and ease of administration of available agents. The objective... 

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