Donald E. Fry

The Importance of Antibiotic Pharmacokinetics in Critical Illness

Antibiotics are the most commonly used drugs in the surgical patient. Pharmacokinetics is the study of processes that result in the delivery of drugs to effector sites. Drug absorption, distribution, biotransformation, and excretion are the critical elements of drug delivery to effector sites. The biologic elimination half-life (t1/2) and the volume of distribution (Vd) are terms used to describe the active processes of pharmacokinetics; t1/2 and Vd are determined for antibiotics by employing healthy volunteers or minimally ill patients. From these data, dosing schedules for each antibiotic are determined. This article reviews the literature on the impact of critical illness and sepsis on antibiotic pharmacokinetics. The data identify that t1/2 may be reduced in the hyperdynamic states of stress and sepsis and that the Vd is expanded. These changes mean that currently accepted dosing regimens of antibiotics in critically ill patients are inadequate. Subtherapeutic antibiotic concentrations in these patients may account for treatment failures and may be of significance in the emergence of bacterial resistance.

Adverse outcomes in surgery: redefinition of postoperative complications

BACKGROUNDnWe propose that excess risk-adjusted, postoperative length of stay (poLOS) is a valid indicator of an adverse outcome.nnnMETHODSnHospital administrative claims data for elective colon resection, coronary bypass graft surgery, and total hip replacement were used from the 100 largest-volume hospitals in the Health Care Cost and Utilization Project for 2005. Risk-adjusted poLOS linear models were designed and outliers were determined using control charts. Costs of hospital care were examined by the presence of coded complications (CCs) and/or being a poLOS outlier.nnnRESULTSnPatterns of CCs and risk-adjusted poLOS outliers were significantly different (P < .0001, chi-square test). For all procedures, costs of care were similar with or without CCs if the patients were not poLOS outliers. For patients who were poLOS outliers, costs were significantly different (Tukey-Kramer test) independent of whether CCs were present or not.nnnCONCLUSIONSnAdverse surgical outcomes are better defined by risk-adjusted poLOS and cost criteria rather than coded or surveillance observations.

Occupational Risk of Infection with Human Immunodeficiency Virus

The risk of HIV infection in surgical settings is a composite of overlapping risks related to the local prevalence of HIV, the route of exposure to HIV-infected blood, and the susceptibility of the worker. Studies continue to suggest that the risk of blood contact, including percutaneous injuries, remains appreciable. Prevention of such exposures in the operating and delivery room by adoption of safer instruments, work practices, and techniques and by the consistent use of appropriate personnel protective equipment must be viewed as a priority.

A "health commons" approach to oral health for low-income populations in a rural state

Oral health needs are urgent in rural states. Creative, broad-based, and collaborative solutions can alleviate these needs. Health commons sites are enhanced, community-based, primary care safety net practices that include medical, behavioral, social, public, and oral health services. Successful intervention requires a comprehensive approach, including attention to enhancing dental service capacity, broadening the scope of the dental skills of locally available providers, expanding the pool of dental providers, creating new interdisciplinary teams in enhanced community-based sites, and developing more comprehensive oral health policy. By incorporating oral health services into the health commons primary care model, access for uninsured and underserved populations is increased. A coalition of motivated stakeholders includes community leaders, safety net providers, legislators, insurers, and medical, dental, and public health providers.

Abdominal Wall Considerations and Complications in Reoperative Surgery

The abdominal wall is the source of significant problems for patients undergoing multiple abdominal operations. The orientation of sequential incisions must be carefully considered to avoid compromise of the abdominal wall blood supply, which may result in either acute (dehiscence) or delayed (ventral hernia) complications. Infections are the most serious problems of the multiply operated on abdominal wall. These complications may range from simple wound infection to necrotizing fasciitis. Management may require only simple drainage of the infection or may entail extensive debridement for the necrotizing processes. Regardless of the cause, the multiply operated on abdominal wall may require reconstruction because of lost fascia. Polypropylene mesh can be employed safely and effectively for this purpose.

Blood culturing practices in a trauma intensive care unit: does concurrent antibiotic use make a difference?

BACKGROUNDnFebrile trauma patients have repeated blood cultures drawn during a prolonged hospitalization. We examined the diagnostic yield of blood cultures in severely injured patients to determine whether concurrent antimicrobial therapy or prophylactic administration of antibiotics affects blood culture growth. We also determined how rapidly growth changed to determine whether total numbers of blood cultures could be decreased. The hypotheses of the study were that concurrent antimicrobial administration affects blood culture yield, prophylactic administration alters the culture result, and repetitive culturing is unnecessary.nnnMETHODSnA retrospective chart review of trauma patients with minimum Injury Severity Score of 15 and minimum 5-day intensive care unit length of stay was performed. The dates and results of blood cultures and antibiotic type and administration dates were recorded. Prophylactic antibiotics were defined as antibiotics administered on admission to the unit. Computer software was used to match the blood culture date to the period of antimicrobial administration. Categorical data were compared using Fishers exact test.nnnRESULTSnTwo hundred fifty-eight patients met entry criteria, and 208 charts were complete for review. One hundred twenty-nine patients had 347 sets of blood cultures drawn. The positive blood culture rate was 10.8% in patients off antibiotics, and 13.9% in patients on antibiotics (p = 0.68). All prophylactic antibiotics included a beta-lactam. Only 18% of positive blood cultures in patients receiving prophylactic antibiotics were sensitive to beta-lactams as opposed to 59% sensitivity in those who did not receive prophylaxis (p = 0.03). One hundred seventy-six sets of blood cultures were performed after an initial positive culture. Only three patients with an initial positive culture had a second positive culture with a different organism. The mean time to culturing a new organism after initial growth was 19 days.nnnCONCLUSIONnConcurrent antimicrobial administration does not alter blood culture yield. Prophylactic administration alters the type of organism cultured. Little new information is gained from repetitive culturing.

Decreased Polyunsaturated Fatty Acids in Sickle Cell Anaemia

The purpose of this study was to determine if the growth retardation often associated with sickle cell anaemia could be related in part to a deficiency of essential fatty acids. We reported recently that children with sickle cell disease in Jos, Nigeria have lower levels of serum amino acids and higher levels of urinary amino acids than their healthy counterparts. In the current study, we determined that the serum phospholipids of children with sickle cell anaemia did not deviate in the proportions of the essential fatty acids, linoleic and alpha-linolenic they contain compared to controls. However, their serum phospholipid profiles were significantly different in the proportions of four other fatty acids. Specifically, the phospholipids of children with sickle cell anaemia contained 19 per cent more palmitic acid (P = 0.006), 22 per cent more oleic acid (P = 0.014), 18 per cent less arachidonic acid (P = 0.008), 51 per cent less eicosapentaenoic acid (P = 0.0008), and 43 per cent less decosahexaenoic acid (P = 0.001). These data show that children with sickle cell anaemia are not deficient in essential fatty acids, but that the fatty acid elongation and desaturation pathway is somehow disturbed in this disease.

Altered Urinary Excretion of Lysosomal Hydrolases in Pregnancy

Creatinine concentrations and the activities of five lysosomal hydrolases were measured in the serum and urine of 14 healthy nonpregnant control women and 19 healthy pregnant women. Fractional enzyme excretion (FEE) values for beta-glucuronidase, beta-hexosaminidase, alpha-galactosidase, beta-galactosidase, and alpha-mannosidase were calculated and compared between the two groups of subjects. Fractional enzyme excretion was calculated as the ratio of enzyme clearance to creatinine clearance. The FEE values for beta-galactosidase and alpha-mannosidase between the nonpregnant and pregnant populations were not statistically different; however, relative to the nonpregnant control group, the median FEE values for beta-glucuronidase (P < 0.03), beta-hexosaminidase (P < 0.06), and alpha-galactosidase (P < 0.02) were decreased approximately 1.5-, 1.8-, and 2.7-fold, respectively, in the pregnant population. The median urinary beta-galactosidase activity for the pregnant population, when expressed on the basis of creatinine, was twofold higher than that of the control group (P < 0.0005). These data indicate that with pregnancy there are marked changes in the urinary excretion of selected lysosomal enzymes, particularly alpha-galactosidase and beta-glucuronidase. When the molecular weights of these five hydrolases were compared between kidney homogenate and control urine, a correlation of 0.96 was observed, while the correlation between control serum and control urine was 0.69. This suggests that the FEE value differences between the pregnant and control groups are most likely due to changes in tubule cell metabolism, either decreased secretion or increased reabsorption. These biochemical changes may provide a means of assessing changes in renal function during pregnancy.

Serum cytosolic β-glucosidase elevation and early ischemic injury to guinea pig small intestine ☆ ☆☆

Abstract Background: The lack of an early, sensitive marker for intestinal ischemia has led to delay in diagnosis and worsened outcome for patients with acute onset of this condition. Our preliminary studies revealed that guinea pig cytosolic β-glucosidase (CBG) is expressed predominantly in the small intestine, with lower levels in the liver and pancreas and undetectable levels in other organs. Cytosolic β-glucosidase was investigated as a serum marker of small intestinal ischemia in a guinea pig model. Methods: Guinea pigs underwent anesthesia, sham laparotomy, 30 minutes of mesenteric ischemia followed by 6 hours of reperfusion, 6 hours of sustained mesenteric ischemia, or closed-loop small bowel obstruction. Serum samples were assayed for CBG activity. At the conclusion of the ischemia/reperfusion experiments, small bowel samples were assayed for residual enzyme activity, and paraffin sections were graded for the severity of histologic injury. Results: Serum CBG activity rose rapidly after intestinal ischemia with and without reperfusion. Peak enzyme activities were elevated 23-fold for reperfused animals (P

Protein and energy tolerance by stressed geriatric patients

Nutritional support of stressed geriatric patients remains empiric and has classically been limited by tolerance. Although the hypermetabolic response is known to increase protein and calorie demands, tolerance to increased loads of delivered nutrients in older patients has been questioned. We compared tolerance to nutrient delivery and nitrogen metabolism in 38 stressed surgical patients over age 65 to 38 Injury Severity Score or disease matched younger controls. Twenty-seven of the 31 geriatric patients (87%) who maintained normal renal function (serum creatinine less than 2.0 mg/dl) became azotemic (BUN greater than 30) while receiving 1.5 to 2.0 g of protein per kilogram of ideal body weight compared to only 21% of controls. This phenomenon led to inaccuracies in 17% of geriatric nitrogen balance studies because of unaccounted for serum accumulation of urea nitrogen (compared to only 6% in the control group). When calculated protein requirements were administered to the geriatric group, the mean nitrogen balance was -1.6. Resting energy expenditure as measured by indirect calorimetry demonstrated a strong correlation between actual calorie expenditures and calculated needs based on the Harris-Benedict basal energy expenditure (BEE) multiplied by an activity factor of 1.2 and a stress factor of 1.75 for trauma (r = 0.86, P less than 0.05) or 1.5 for general surgery patients (r = 0.72, P less than 0.05). In summary, energy requirements by stressed geriatric patients can be closely defined by calculation of the Harris-Benedict BEE in conjunction with appropriate activity and stress factors. However, attempts to deliver traditional levels of protein lead to azotemia and are frequently unsuccessful in achieving positive nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)