Margarita E. Villarino

Microbial Growth and Endotoxin Production in the Intravenous Anesthetic Propofol

OBJECTIVE In this study, we measured microbial growth and endotoxin production in the intravenous anesthetic propofol using 10 different microbial strains; 6 isolated from outbreak cases and 4 from laboratory stock cultures. DESIGN In each trial, endotoxin-free glass tubes containing 10 ml propofol were inoculated with 10(0)-10(3) CFU/ml of the test organism and incubated at 30 degrees C for 72 hours. SETTING In May and June 1990, the Centers for Disease Control received reports of 5 outbreaks in 5 states of postsurgical patient infections and/or pyrogenic reactions. Epidemiologic and laboratory investigations implicated extrinsic contamination of an intravenous anesthetic, propofol, as the probable source of these outbreaks. RESULTS After 24 hours, 9 of the 10 cultures increased in viable counts by 3 to 6 logs. At least 1 ng/ml of endotoxin was produced within 24 hours by Escherichia coli, Enterobacter cloacae, and Acinetobacter calcoaceticus subspecies anitratus. CONCLUSIONS Propofol can support rapid microbial growth and endotoxin production. To avoid infectious complications, scrupulous aseptic technique should be used when preparing or administering this anesthetic.

Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States.

SETTING A large randomized controlled trial recently showed that for treating latent tuberculous infection (LTBI) in persons at high risk of progression to tuberculosis (TB) disease, a 12-dose regimen of weekly rifapentine plus isoniazid (3HP) administered as directly observed treatment (DOT) can be as effective as 9 months of daily self-administered isoniazid (9H). OBJECTIVES To assess the cost-effectiveness of 3HP compared to 9H. DESIGN A computational model was designed to simulate individuals with LTBI treated with 9H or 3HP. Costs and health outcomes were estimated to determine the incremental costs per active TB case prevented and per quality-adjusted life year (QALY) gained by 3HP compared to 9H. RESULTS Over a 20-year period, treatment of LTBI with 3HP rather than 9H resulted in 5.2 fewer cases of TB and 25 fewer lost QALYs per 1000 individuals treated. From the health system and societal perspectives, 3HP would cost respectively US

A CLUSTER OF SEVERE POSTOPERATIVE BLEEDING FOLLOWING OPEN HEART SURGERY

21,525 and

APPLICATION OF MULTILOCUS ENZYME ELECTROPHORESIS TO EPIDEMIOLOGIC INVESTIGATIONS OF XANTHOMONAS MALTOPHILIA

4294 more per TB case prevented, and respectively

Flu-like and Other Systemic Drug Reactions Among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study

4565 and

Three months of weekly rifapentine plus isoniazid is less hepatotoxic than nine months of daily isoniazid for LTBI.

911 more per QALY gained. CONCLUSIONS 3HP may be a cost-effective alternative to 9H, particularly if the cost of rifapentine decreases, the effectiveness of 3HP can be maintained without DOT, and 3HP treatment is limited to those with a high risk of progression to TB disease.

Self-administered versus directly observed once-weekly isoniazid and rifapentine treatment of latent tuberculosis infection

OBJECTIVE To investigate a cluster of postoperative bleeding following open heart surgery. DESIGN A cohort and case/control study. SETTING Palo Alto Veterans Administration Medical Center, Palo Alto, California. PARTICIPANTS Six (21.4%) of 28 patients undergoing open heart surgery who developed severe, nonsurgical, postoperative bleeding from July 1 through August 30, 1988 (outbreak period). All case-patients had chest tube drainage of greater than or equal to 1000 ml within 4 hours of surgery but did not have identifiable bleeding vessel(s) on exploration. RESULTS Upon comparison of the pre-outbreak (January 1986 through June 1988) and the outbreak period, a significant increase was found in the incidence of postoperative nonsurgical bleeding (5/440 versus 6/28, p = .0006), but not of postoperative surgical bleeding (8/440 versus 0/28, p = 1.0). Of all patients undergoing open heart surgery during the outbreak period, case patients were found to be older (67.8 versus 60.6, p = .02) and to have received a larger volume of hetastarch (HES), a synthetic colloidal plasma-volume expander (mean = 19.4 ml/kg versus 14.1 ml/kg, p = .02). CONCLUSIONS We conclude that the use of large volumes of HES during surgery in the elderly open heart surgery patient may increase the risk for severe, nonsurgical postoperative bleeding, probably caused by alterations of the coagulation system. As the incidence of open heart surgery increases among the elderly, surgeons and anesthesiologists should be alert to possible adverse reactions from exposures not associated with adverse reactions in younger patients.

Effect of HIV infection on tolerability and bacteriologic outcomes of tuberculosis treatment

OBJECTIVE To test the utility of a newly developed multilocus enzyme electrophoresis typing method for Xanthomonas maltophilia. DESIGN Isolates were first screened by slide agglutination, which served as the standard to characterize the outbreak strains. All isolates were then subjected to multilocus enzyme electrophoresis and the results analyzed based on epidemiological data. SETTING This outbreak occurred in a shock-trauma intensive care unit of a large general community hospital. PATIENTS Patients admitted to the shock-trauma intensive care unit who had X maltophilia isolated from any site greater than or equal to 24 hours after admission met the case definition. Specimens from patients who fit the case definition were characterized, as were specimens from other patients that were used as controls for nonoutbreak isolates. Environmental samples were also evaluated for X maltophilia. RESULTS Most of the 64 isolates received during this outbreak were serotype 10, and when they were subjected to multilocus enzyme electrophoresis, one electrophoretic type predominated and correlated to most outbreak isolates. Unrelated isolates of serotype 10 from other institutions all exhibited unique electrophoretic types. CONCLUSION Application of multilocus enzyme electrophoresis to X maltophilia outbreaks is a valuable addition to the characterization of suspected outbreak strains.

Factors associated with non-completion of follow-up: 33-month latent tuberculous infection treatment trial.

BACKGROUND Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome. METHODS We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study. RESULTS Among 7552 persons who received ≥ 1 dose of study drug, 153 had a SDR: 138/3893 (3.5%) with 3HP vs 15/3659 (0.4%) with 9H (P < .001). In the 3HP arm, 87 (63%) had flu-like syndrome and 23 (17%) had cutaneous reactions; 13/3893 (0.3%) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95% confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95% CI, 2.3, 4.7), female sex (aOR 2.0; 95% CI, 1.4, 2.9), age ≥ 35 years (aOR 2.0; 95% CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P = .009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95% CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95% CI, 1.3, 27.1). CONCLUSIONS SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear. CLINICAL TRIALS REGISTRATION NCT00023452.

Back to the Future: Where Now for Antituberculosis Drugs?

SETTING Nine months of daily isoniazid (9H) and 3 months of once-weekly rifapentine plus isoniazid (3HP) are recommended treatments for latent tuberculous infection (LTBI). The risk profile for 3HP and the contribution of hepatitis C virus (HCV) infection to hepatotoxicity are unclear. OBJECTIVES To evaluate the hepatotoxicity risk associated with 3HP compared to 9H, and factors associated with hepatotoxicity. DESIGN Hepatotoxicity was defined as aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN) with symptoms (nausea, vomiting, jaundice, or fatigue), or AST >5 x ULN. We analyzed risk factors among adults who took at least 1 dose of their assigned treatment. A nested case-control study assessed the role of HCV. RESULTS Of 6862 participants, 77 (1.1%) developed hepatotoxicity; 52 (0.8%) were symptomatic; 1.8% (61/3317) were on 9H and 0.4% (15/3545) were on 3HP (P < 0.0001). Risk factors for hepatotoxicity were age, female sex, white race, non-Hispanic ethnicity, decreased body mass index, elevated baseline AST, and 9H. In the case-control study, HCV infection was associated with hepatotoxicity when controlling for other factors. CONCLUSION The risk of hepatotoxicity during LTBI treatment with 3HP was lower than the risk with 9H. HCV and elevated baseline AST were risk factors for hepatotoxicity. For persons with these risk factors, 3HP may be preferred.