In vitro activity of clarithromycin, cefprozil, and other common oral antimicrobial agents against gram-positive and gram-negative pathogens.

Macrolide and beta-lactam antimicrobial agents are frequently used for the treatment of upper and lower respiratory tract infections and skin or skin structure infections. To evaluate the relative in vitro activity of these antimicrobial drugs against organisms commonly involved in these infections, we tested clarithromycin, erythromycin, cefprozil, cefuroxime, cefaclor, cephalexin, amoxicillin, amoxicillin/clavulanate, and doxycycline against 174 gram-positive and gram-negative clinical isolates, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, group A beta-hemolytic streptococci, alpha-hemolytic streptococci, Escherichia coli, and Klebsiella pneumoniae. Manual broth microdilution susceptibility testing was used with a standard inoculum of 5 x 10(4) colony-forming units/well at pH of 7.2. Clarithromycin was the most active agent against streptococci. Methicillin-susceptible S aureus exhibited resistance to both clarithromycin and erythromycin, but was susceptible to cefprozil, cefuroxime, amoxicillin/clavulanate, and doxycycline. Cefprozil was at least as active as cefuroxime, cefaclor, and cephalexin against all organisms tested, but was fourfold less active than doxycycline against E coli and 16-fold less active than clarithromycin versus S pneumoniae. The gram-negative isolates tested showed resistance to clarithromycin and erythromycin; however, cefprozil was as active as amoxicillin/clavulanate against K pneumoniae and E coli. These results demonstrate that clarithromycin provides superior in vitro activity against common streptococci, while cefprozil, cefuroxime, amoxicillin/clavulanate, and doxycycline provide greater activity against methicillin-susceptible S aureus, K pneumoniae, and E coli. Prospective clinical trials are needed to determine the clinical significance of these findings.

Costs of pharmaceutical care: can the profession do anything?

OBJECTIVE: To review some of the factors that influence the cost of pharmaceuticals and the delivery of pharmaceutical care as well as some possible measures for decreasing these costs. DATA SYNTHESIS: Clinical studies have been selected to illustrate factors that may add to the overall cost of pharmaceutical care. CONCLUSIONS: Because of the perceived problems resulting from the introduction of new, expensive pharmaceuticals, possible means of controlling the costs of individual products are discussed. In addition, recommendations for achieving cooperation between pharmaceutical manufacturers and pharmacy practitioners in demonstrating the cost-effectiveness of new products are provided.

Overview of synergy with reference to double beta-lactam combinations.

Combination antimicrobial therapy is used to expand the bacterial coverage over a single agent, to prevent the emergence of resistant organisms, to decrease toxicity by allowing lower doses of both agents, or for synergy. Synergy is one of the most common of these reasons, especially in serious infections. The introduction of new broad-spectrum beta-lactam antimicrobials has led to their combination in the treatment of seriously ill patients. Whereas a combination of an aminoglycoside and a beta-lactam antimicrobial is frequently synergistic, much less is known about synergy between combinations of beta-lactams. In vitro testing shows most combinations of two beta-lactams to be indifferent or additive in their effects; rarely does synergy occur. Antagonism can sometimes be seen, particularly with combinations involving cefoxitin or imipenem, especially if the treated organism is Enterobacter or Pseudomonas. Results of clinical trials comparing double beta-lactam (DBL) therapy with aminoglycoside/beta-lactam combinations show no difference in clinical response rates. Highly active DBL combinations may substitute for standard aminoglycoside-containing regimens in certain situations, even though they are not reliably synergistic. However, in the treatment of seriously ill patients such combinations may be less desirable.

Failure of APACHE II alone as a predictor of mortality in patients receiving total parenteral nutrition.

We followed prospectively over 5 months all medical and surgical ICU patients placed on total parenteral nutrition (TPN) and recorded their Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on the day of admission, on the day TPN was started, length of time in ICU before TPN was started, and the number of days TPN was administered. Sixty-one patients (15 to 82 yr) had an inhospital mortality of 47%. The APACHE II score was significantly higher for nonsurvivors vs. survivors both on the day of admission (24.4 +/- 9.6 vs. 18.4 +/- 6.5; p less than .003) and also on the day TPN was started (21 +/- 8.6 vs. 16.4 +/- 5.6; p less than .002). However, at a 60% risk of dying, specificity was 96.9% and sensitivity 27.6%. The mean number of days before TPN was started was 3.2 and mean number of days on TPN was 9.2 (p = NS). We conclude that calculation of APACHE II score either on ICU admission or on the day TPN is considered does not seem useful in identifying patients who will not benefit from TPN.

Aztreonam--an overview.

Aztreonam is the first synthetic monobactam to undergo clinical studies in the U.S. Aztreonam has excellent activity against P. aeruginosa and Enterobacteriaceae, but poor activity against anaerobic and gram-positive organisms. Aztreonam has poor oral bioavailability, but can be given intramuscularly or intravenously in doses of 1-2 g q6-12h. Clinical trials of aztreonam have shown it to be effective in infections of urine, lung, skin, blood, bones and joints, and abdomen with an adverse reaction profile similar to beta-lactams. Aztreonam may be an alternate to aminoglycoside therapy, with the advantage of not being nephrotoxic.

The clinical use of intravenous acyclovir.

Acyclovir (acycloguanosine) is a new antiviral compound with activity against certain herpes viruses. Acyclovir is phosphorylated preferentially in virus-infected cells into its active form, acyclovir triphosphate, an inhibitor of viral-induced DNA polymerase. Acyclovir, which possesses an acyclic carbohydrate moiety, also causes premature DNA chain termination. Acyclovir has shown clinical activity against herpes simplex virus (HSV) types 1 and 2 and varicella zoster virus (VZV), but its usefulness in cytomegalovirus, Epstein-Barr virus, and chronic hepatitis B infections requires further study. In randomized clinical trials of infections caused by HSV and VZV, intravenous acyclovir has been shown to shorten the duration of viral shedding and lesion pain and hasten the resolution of skin lesions, with minimal toxicity.

Developing a formulary for enteral nutrition products.

A formulary for enteral nutrition products was developed at a university hospital. Advice was solicited from clinical dietetics and the medical staff. Reported important product variables were osmolality, caloric density, protein content and source, fat content and source, freedom from lactose, and, for oral supplements, available flavors. Data were also obtained from manufacturers regarding the composition of their products. Products were categorized as follows: liquid supplemental feedings, high calorie supplemental feedings, isotonic tube feedings, high caloric/high nitrogen tube feedings, high nitrogen tube feedings, and blenderized tube feedings. Bids were solicited in April 1981 (and annually thereafter) from manufacturers of the classified enteral nutrition products, and a contract was signed with the manufacturer in each category submitting the lowest bid. In contrast with previous experience, there was no loss from outdated products during the first year of the formulary. Categorizing enteral nutrition products into therapeutic categories appears to be a workable method to limit the number of products used in a hospital, thereby potentially decreasing inventory, waste, and hospital costs. The descriptive category titles also may encourage rational use of these products without promoting allegiance to a particular company or product.

Empiric therapy of febrile granulocytopenic patients.

Antibiotic therapy in granulocytopenic cancer patients, the risk factors predisposing these patients to infection, and the signs, symptoms and types of infections occurring in these patients are reviewed. The four most commonly isolated organism at most cancer treatment centers are Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa and Staphylococcus aureus. Early antimicrobial therapy with broad-spectrum antibiotics before culture results are known produces cure rates of approximately 70%, regardless of the combination used. The most important predictor of response to any antibacterial regimen is a rise in the absolute granulocyte count. The current recommended fever regimen would be carbenicillin (or ticarcillin) with an aminoglycoside. The choice of an aminoglycoside depends on the prevailing organism sensitivities at a particular institution; in many cases, gentamicin sulfate is suitable. Addition of a cephalosporin to the two-drug regimen offers little increase in cure rates, except whem aminoglycoside-resistant Enterobacteriaceae are prevalent. Because of nephrotoxicity produced with combinations of cephalothin sodium and the aminoglycosides, cefazolin sodium would be the current cephalosporin of choice. An alternate third drug to be considered is co-trimoxazole, a broad-spectrum antimicrobial not yet commercially available in parenteral form. In the absence of a clinical response to appropriate antimicrobial therapy in documented infections, granulocyte transfusions may be indicated.