Articles on Medical Diseases and Conditions

Tag: Antibiotics

  • Antibiotics

    Gentamicin.Methods of estimating antibiotic therapeutic effectiveness have been discussed elsewhere (chapter 14). Several antibiotics possess therapeutic ranges whose upper limits border on toxicity. Serum assays for several of these have been developed, most commonly using some type of immunoassay. One example will be used to illustrate general principles. Gentamicin (Garamycin) is one of the aminoglycoside antibiotics that is active against gram-negative organisms, including Pseudomonas aeruginosa. Unfortunately, side effects include ototoxicity and nephrotoxicity. Drug excretion is mainly through renal glomerular filtration. Serum peak levels and residual (trough) levels both provide valuable information. Residual levels are measured just before the next dose. Values at this time correlate best with nephrotoxicity, especially when serum levels are greater than 2 µg/ml. Specimens for peak level determination are obtained approximately 30 minutes after the end of IV infusion and 1 hour after intramuscular injection. Peak levels correlate best with therapeutic effectiveness (i.e., whether adequate serum levels are present) and possibly with ototoxicity. Normal peak values are usually considered 4-8 µg/ml. Values less than 4 µg/ml may be ineffective, whereas those greater than 10 µg/ml predispose to toxicity. Gentamicin assay is desirable because serum levels differ considerably among patients receiving the same dose, and serum gentamicin half-life is equally variable. Standard doses or nomograms based on serum creatinine level fail to predict blood concentration accurately for peak or residual levels in a substantial number of patients even with adequate renal function. When renal function is impaired or when nephrotoxic antibiotics have previously been administered, serum assay becomes essential. It should be mentioned that peak or residual levels within accepted reference limits do not guarantee safety, since some studies have shown onset of renal function decrease in the presence of acceptable serum values.

    Vancomycin. Only a small mount of oral vancomycin is absorbed, so that the oral form is used to kill GI tract bacteria such as Clostridium difficile. Intravenous medication is used for other infections. Intravenous vancomycin is about 50%-60% bound to serum albumin, and 80%-90% is excreted unchanged in the urine. The serum half-life is 2-3 hours in children and 4-8 hours in adults with normal renal function. In renal failure, the serum half-life becomes 7-8 days (range, 4-9 days), and instead of the usual adult IV dose of 500 mg every 6 hours, only 500-1,000 mg once per week is sufficient. Peak and residual (trough) levels are usually recommended. Residual levels are usually obtained just before a dose is given; the reference values are 5-10 mg/100 ml. Unfortunately, different investigators do not agree when to draw specimens after the end of IV infusion for peak values, with times suggested including immediately, 15 minutes, 30 minutes, and 2 hours after the infusion. Vancomycin serum levels apparently fall rapidly for a time after the end of IV infusion and then more slowly. At 15 minutes after the end of infusion, serum values of 25-30 mg/100 ml are equivalent to 30-40 mg/100 ml levels (the most commonly accepted peak value range) at the end of infusion.

  • Septicemia and Bacteremia

    The concept of septicemia should probably be separated from that of bacteremia, although in many studies the two are not clearly separated. In bacteremia, a few bacteria from a focal area of infection escape from time to time into the peripheral blood. However, the main focus remains localized, and symptoms are primarily those that are caused by infection in the particular organ or tissues involved. Bacteremia may occur without infection following certain procedures, such as dental extraction (18%-85%), periodontal surgery (32%-88%), tooth brushing (0%-26%), bronchoscopy (15%), tonsillectomy (28%-38%), upper GI endoscopy (8%-12%), sigmoidoscopy (0%-10%), urethral dilatation (18%-33%), cystoscopy (0%-17%), and prostate transurethral resection (12%-46%). In one representative series, E. coli was isolated in about 20% of patients with bacteremia; S. aureus, 10%; and Klebsiella, pneumococcus, Streptococcus viridans, Bacteroides, and Pseudomonas, about 6% each. The percentage of S. epidermidis isolated varies greatly (3%-34%), probably depending on how many were considered contaminants. Polymicrobial bacteremia is reported in about 7% of cases (range, 0.7%-17%). In septicemia there is widespread and relatively continuous peripheral blood involvement. The characteristic symptoms are systemic, such as marked weakness and shock or near shock. Shock has been reported in 16%-44% of patients with gramegative bacteremia. These symptoms are usually accompanied by high fever and leukocytosis. However, septic patients may be afebrile in 10% (range, 4%-18%) of cases. Leukocytosis occurs in 60%-65% of patients (range, 42%-76%), leukopenia in 10% (range, 7%–17%), bands increased in 70%-75% (range, 62%-84%), and total neutrophils are increased in about 75% (range, 66%-92%). Any bacteria may cause septicemia. More than 50% of cases are due to gramegative rod organisms, with E. coli being the most frequent. Staphylococcus aureus probably is next most common. (In one literature review of seven studies of sepsis published in 1990 and 1991, four studies had predominance of gramegative organisms and three had predominance of gram-positive. In four of the seven studies, the percentage of gramegative and gram-positive organisms was within 10% of each other). The portal of entry of the gramegative organisms is usually from previous urinary tract infection. Many cases of septicemia follow surgery or instrumentation. The source of Staphylococcus septicemia is often very difficult to trace, even at autopsy. However, pneumonia and skin infections (sometimes very small) are the most frequent findings.

    Diagnosis. Blood cultures are the mainstay of bacteremia or septicemia diagnosis. Strict aseptic technique must be used when cultures are obtained, since contamination from skin bacteria may give false or confusing results. In cases of bacteremia or in septicemia with spiking fever, the best time to draw blood cultures is just before or at the rise in temperature. Three culture sets, one drawn every 3 hours, are a reasonable compromise among the widely diverging recommendations in the literature.

    Antibiotics and blood cultures. Blood should be drawn for culture before antibiotic therapy is begun, although a substantial number of cultures are positive despite antibiotics. Certain antibiotic removal devices are commercially available that can be of considerable help in these patients. It is essential that the culture request contain the information that antibiotics have been given, unless they have been stopped for more than 1 week. If penicillin has been used, some laboratories add the antipenicillin enzyme penicillinase to the culture medium. However, others believe that penicillinase is of little value and might actually be a potential source of contamination.