PubMed Health⌕ Search

Biomedical subjects

J T DiPiro

Publications and source records attributed to J T DiPiro.

At least 73 records · Page 4Linked to original sources

Single dose systemic antibiotic prophylaxis of surgical wound infections.

The proper duration of antimicrobial use for the prevention of postoperative surgical infection has been a subject of controversy. Currently, more than 40 published clinical trials are available in which the efficacy of single dose surgical prophylaxis with parenteral antimicrobials has been studied. These studies have compared single doses versus multiple doses of the same agent, single doses of antimicrobial versus placebo, single doses of various antimicrobials, and a single dose of one agent versus multiple doses of another agent. In all trials in which single dose regimens were compared with multidose regimens, the single dose regimens resulted in a similar frequency of postoperative wound infections. Single antimicrobial doses, usually cephalosporins given immediately before operation, are effective in preventing wound infections in gastric, biliary, and transurethral operations, hysterectomies and cesarean sections. For colorectal operations, the value of single parenteral doses of various agents has been established; however, it is not clear if there is an added benefit when oral antimicrobials are also used. For open heart operations or those in which prosthetic materials are implanted, the value of single dose regimens has not been established.

Anti-Bacterial Agents↗

Current concepts in clinical therapeutics: intra-abdominal infections.

The etiology, pathophysiology, clinical presentation, and treatment of the two major types of intra-abdominal infections--peritonitis and abscesses--are described. Peritonitis of infectious origin is the acute response of the peritoneum to microorganisms; it is classified as primary (when the source of bacteria is not apparent) or secondary (usually involving perforation of a hollow structure of the GI tract with subsequent release of microbes). Peritonitis results in mortality because of fluid shifts and endotoxins that may cause hypovolemia and shock. Abscesses, purulent collections of fluid physically separated from the surrounding tissues, are the result of chronic inflammation following failure of the body to eradicate a pathogen completely. Secondary intra-abdominal infections are often polymicrobial because of the diversity of organisms in the GI tract. The size of bacterial inocula and the number and types of species present substantially affect patient outcome. The patient with peritonitis usually presents in acute distress, with generalized abdominal pain and faint bowel sounds. The presentation of the patient with intra-abdominal abscess is more variable and less dramatic; pain and fever may be present. The treatment of these infections requires the coordinated use of prompt surgical intervention, support of vital functions, and appropriate antimicrobial therapy. Surgical procedures are used to stop continuing bacterial contamination of the peritoneum, remove foreign material from the abdomen, and drain purulent collections; it is the foundation of treating most types of intra-abdominal infections. Aggressive fluid therapy is required to assure adequate intravascular volumes in most patients. Generally, antimicrobial coverage for both aerobes and anaerobes must be started before culture results are available. Antimicrobial therapy for specific types of infections is given in the article. Surgical procedures are the foundation of treatment of most intra-abdominal infections; antimicrobial agents active against aerobic gram-negative bacilli and anaerobes are important adjuncts.

Abdomen↗

Growth of four microorganisms in polyethylene glycol-electrolyte lavage solution.

The growth of Staphylococcus epidermidis, Serratia marcescens, Pseudomonas aeruginosa, and Candida albicans in reconstituted polyethylene glycol-electrolyte lavage solution (PEG-ELS) stored under refrigeration and at room temperature was studied. A standard inoculum of each organism was added to one of four 4-L containers (one organism per container). From each container 28 aliquots of 25-mL each were removed and stored under refrigeration or at room temperature. One container was not inoculated and served as a control. Duplicate aliquots of the inoculated and the control solutions were filtered and incubated for quantification of organisms on days 0, 1, 2, 4, 8, 16, and 30. Solutions stored at room temperature supported the growth of S. marcescens and Ps. aeruginosa. The counts of these organisms increased to approximately 10(6) colony-forming units (CFU)/mL over 16 days. The counts of Staph. epidermidis in solutions stored at room temperature increased slightly over the first 24 hours and declined steadily to zero after day 4. C. albicans reached a maximum colony count of 5.84 cfu/mL on day 16 and steadily declined to 0.92 cfu/mL on day 30. Solutions stored under refrigeration did not support the growth of any microorganisms. Microbial growth was not detected in any of the control solutions over the 30-day study period. The polyethylene glycol-electrolyte lavage solution studied here should be refrigerated after reconstitution to minimize microbial growth. This solution may be used for up to 30 days after reconstitution when it is stored under refrigeration.

Bacteria↗

Intraoperative serum and tissue activity of cefazolin and cefoxitin.

We determined the intraoperative serum and wound-muscle concentrations of cefazolin and cefoxitin in 40 patients who were undergoing cholecystectomies. The study employed an open-label design in which all of the patients randomly received cefazolin sodium (20 mg/kg) or cefoxitin sodium (30 mg/kg) intravenously while the patient was in the ward ("on call") or with the induction of anesthesia. Multiple blood and wound-muscle samples were collected intraoperatively and assayed for their cephalosporin concentrations. Considerable differences in intraoperative serum and tissue concentrations between antibiotics were apparent; there were usually higher levels of cefazolin. In all of the patients who received cefazolin sodium, the antimicrobial was detectable in wound tissue at wound closure, while it was detectable in 86% and 38% of patients who received cefoxitin sodium with anesthesia and on call, respectively. Because cefoxitin has a much shorter elimination half-life than cefazolin it seems prudent to administer the agent as close to the start of the operation as possible, and readminister the agent every two to three hours until the wound is closed. For cefazolin, on-call administration appears to be acceptable, with readministration not required for at least four hours.

Abdominal Muscles↗

Cephalosporins for surgical prophylaxis: computer projections of intraoperative availability.

Cephalosporin antibiotics are the most frequently used agents for surgical prophylaxis. Within this class are considerable pharmacokinetic variations that could have significant implications. We used a computer simulation of cephalosporin serum levels to describe concentrations achieved and maintained intraoperatively when the agents are given intravenously "on call" to the operating room or with induction of anesthesia. Intraoperative serum concentrations fall below 1 microgram/ml if an operation lasts longer than 2.3, 2.7, 3.8, or 4.0 hours when cephalothin, cephapirin, cefamandole, or cefoxitin, respectively, is given in usual doses upon induction of anesthesia. When the same agents are given intravenously on call to the operating room, intraoperative serum concentrations fall below 1 microgram/ml for operations lasting longer than 1.1, 1.5, 2.6, or 2.8 hours, respectively. If cephalothin, cephapirin, cefamandole, or cefoxitin is used, it should be given at induction of anesthesia to provide maximal intraoperative serum concentrations. The longer half-life of cefazolin, ceforanide, cefonicid, and cefuroxime is a potential advantage because serum concentrations of these agents are well above 1 microgram/ml for as long as eight to 22 hours even after on-call administration.

Anesthesia, General↗

Intraoperative ceforanide pharmacokinetics and protein binding.

The pharmacokinetics and protein binding of ceforanide were studied in 15 patients undergoing cholecystectomies. Each patient received ceforanide (20 mg/kg) intravenously on arrival in the operating room, after which serial blood samples were collected during the elimination phase for determination of total and free ceforanide concentrations in the serum. A high-pressure liquid chromatography assay was used, with a centrifugal filtration system for free-drug determinations. Serum concentration data for each individual were subjected to linear regression to determine the elimination rate constants (total and free drug), volumes of distribution, and systemic clearances. The mean elimination rate constants were 0.41 and 0.50 h-1 for total and free ceforanide, respectively. The mean percentage of ceforanide bound to serum protein was 87.9%. The relationship of the free ceforanide concentration to the total concentration appeared to be linear. The data were fit to double-reciprocal and half-reciprocal relationships with good agreement, showing one binding site and an association constant range of 1.6 X 10(7) to 1.9 X 10(7) at these in vivo concentrations. The mean volume of distribution and mean systemic clearance of total drug were 100 ml/kg and 45.9 ml/min per 1.73 m2, respectively. Ceforanide consistently produced higher intraoperative total drug concentrations compared with those of cefazolin and cefoxitin from similar studies.

Adolescent↗

Cephalosporins for prophylaxis in operative repair of femoral fractures. Levels in serum, muscle, and hematoma.

We conducted a prospective controlled study of thirty patients who had an open reduction with internal fixation of a closed fracture of the femur. Each patient received cefamandole, cefazolin, or cefoxitin intravenously (twenty-five milligrams per kilogram of body weight) on entry into the operating room. Intraoperatively, samples of blood, muscle, and organizing hematoma were collected for determination of levels of the antimicrobial agent. Throughout the operation, cefazolin was shown to result in significantly higher levels in serum. The mean concentrations in muscle were similar for all three drugs, but the levels in the hematoma were twice as high with cefazolin as with cefamandole or cefoxitin. No correlation was evident between the concentration of any of these antibiotics in the hematoma and the interval between injury and operation.

Adolescent↗

Potential drug interactions in surgical patients.

The incidence and frequency of potentially serious drug interactions were evaluated in hospitalized surgical patients. Drug profiles of patients on the general surgical service of a tertiary-care teaching hospital were retrospectively reviewed for two six-month periods to determine how often drugs that are known for major interactions were prescribed concurrently. Interactions were studied that were relatively well documented and potentially harmful to the patients. A total of 1825 patient profiles were reviewed (21,888 patient days). At least one potential drug interaction was found in 17% of the patients. Interactions were found to occur at the rate of 1 for every 59 patient days. Digoxin and cimetidine were the potential interacting drugs in almost 90% of the cases. Hospitalized surgical patients require close monitoring because they frequently receive potentially interacting drugs.

Cimetidine↗

Prophylactic parenteral cephalosporins in surgery. Are the newer agents better?

Parenteral prophylactic cephalosporins used in surgery were compared in 17 published studies. Examination of these studies reveals little justification for preference of one cephalosporin over another. For gastrointestinal, obstetrical-gynecologic, or cardiac operations, newer cephalosporins did not result in substantial decreases in adverse postoperative clinical events (eg, wound infections, intra-abdominal and pelvic infections, and endocarditis) when compared with older cephalosporins. There is no evidence that second- or third-generation cephalosporins result in postoperative infection rates lower than with first-generation cephalosporins.

Cardiac Surgical Procedures↗

Drug interactions: theory versus practice.

Cimetidine inhibition of P-450 oxidative metabolism results in interactions with many drugs, leading to clinically significant drug toxicity. A one-year survey of inpatient prescribing practices revealed a 32.6 percent incidence of concomitant cimetidine and interacting drug use. Retrospective chart review showed statistically significant increased toxic drug plasma levels in patients receiving theophylline and cimetidine, and a strong trend to increased rates of drug toxicity in phenytoin-cimetidine treated patients. Ranitidine appears to be a superior choice in patients receiving drugs metabolized by P-450 oxidation. When cimetidine and known interacting drugs are prescribed together, more frequent assessment of blood levels of the affected drug will be required, increasing substantially the cost to patients. Drug interactions of clinical significance occurring due to altered absorption because of effects of H2-receptor antagonists on gastric secretion are reviewed.

Cimetidine↗

Lack of influence of commonly used drugs on bioassay indicator organisms.

Many commonly used pharmaceutical agents have been found to inhibit bacterial growth in vitro. Determinations of antimicrobial concentrations in sera of patients taking nonrecognized antibacterial agents could possibly be altered if bioassay systems are utilized for the determinations. We therefore attempted to determine the in vitro effect of commonly used drugs on bioassay indicator organisms. Fifty-one different agents (antihistamines, anticholinergics, central nervous system agents, cardiovascular agents, analgesics, steroids, muscle blockers, and other miscellaneous agents) were tested for inhibition or enhancement of the growth of Bacillus subtilis, Staphylococcus aureus, Micrococcus luteus, and Klebsiella pneumoniae. None of the agents tested exhibited any effect on standard in vitro bioassay organisms. Nortriptyline hydrochloride inhibited the growth of B. subtilis and M. luteus at a concentration of 500 micrograms/ml (zones of inhibition, 14 and 13 mm, respectively), but no inhibition was observed with concentrations of 50 micrograms/ml or lower.

Bacteria↗

Factors potentially influencing aminoglycoside use and expenditure.

Factors that may have influenced aminoglycoside use and expenditure in one hospital were examined. Factors that were evaluated as to their influence on aminoglycoside-use patterns were: (1) formulary status; (2) bacterial susceptibility patterns; (3) identified or perceived differences in toxicity; (4) changes in patient population; (5) price paid by the hospital for aminoglycosides; (6) distribution of newsletters or memoranda; (7) advertising and detailing; and (8) pharmacy policies. For FY 1976-77 to 1979-80, the largest proportion of aminoglycoside expense was for gentamicin. During FY 1980-81, the expenditure for gentamicin decreased and tobramycin accounted for the largest proportion of total expenditure. Monthly gentamicin use decreased 20% during FY 1980-81 from the previous year. Tobramycin use increased from January 1979 to November 1980 and decreased from December 1980 to June 1981. Kanamycin use and amikacin use were fairly constant during the study period. Based on temporal relationships, the following factors appeared to influence aminoglycoside use and expenditure: (1) a study conducted at the institution from June 1977 to June 1979 comparing gentamicin and tobramycin nephrotoxicity; (2) a comparative nephrotoxicity study published in a widely circulated medical journal in May 1980; and (3) an intramural newsletter and memorandum distributed in March 1981 encouraging selective aminoglycoside use. The identification of factors that potentially influenced aminoglycoside use can be used to anticipate the future impact of similar events and to devise strategies to influence antimicrobial use.

Aminoglycosides↗

Antimicrobial prophylaxis in surgery: Part 1.

The use of antimicrobial agents for prophylaxis in gastrointestinal, obstetric-gynecologic, cardiovascular-thoracic, orthopedic, and head-and-neck surgery is reviewed. English-language reports of studies on antimicrobial prophylaxis in surgery are reviewed. The methodology of each study was evaluated using predetermined criteria, and "evaluable" regimens are included in this review. For each type of surgical procedure, the discussion covers normal infection rates, probable bacterial contaminants, evaluable studies, and specific treatment recommendations. Regimens found to be evaluable numbered 76, with 72 of these showing a decreased infection rate with antibiotics versus placebo. Statistically significant decreases were found in 57 regimens. When properly used, antimicrobial agents have experimental justification for use in some surgical procedures. Factors that should be considered in the risk-benefit equation include: potential for and significance of surgical infection; cost, adverse effects, and ease of administration of antimicrobial agents; development of resistant microorganisms and of superinfection; and improper reliance on antimicrobial agents with resulting disregard for aseptic technique.

Anti-Bacterial Agents↗