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

SETTING: A post-hoc exploratory analysis of a randomized, open-label clinical trial that enrolled 8053 participants from the United States, Canada, Brazil, and Spain. OBJECTIVE: To assess factors associated with non-completion of study follow-up (NCF) in a 33-month latent tuberculous infection treatment trial, PREVENT TB. DESIGN: Participants were randomized to receive 3 months of weekly directly observed therapy vs. 9 months of daily self-administered therapy. NCF was defined as failing to be followed for at least 993 days (33 months) from enrollment. Possible factors associated with NCF were analyzed using univariate and multivariate regression via Cox proportional hazard model. RESULTS: Of 7061 adults selected for analysis, 841 (11.9%) did not complete study follow-up. Homelessness, young age, low education, history of incarceration, smoking, missing an early clinic visit, receiving isoniazid only, and male sex were significantly associated with NCF. Similar results were found in the North American region (United States and Canada) only. In Brazil and Spain, the only significant factor was missing an early clinic visit. CONCLUSIONS: Study subjects at higher risk for NCF were identified by characteristics known at enrollment or in early follow-up. Evaluation of follow-up in other trials might help determine whether the identified factors consistently correlate with retention.

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

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.

Purified protein derivative tuberculin and delayed-type hypersensitivity skin testing in migrant farm workers at risk for tuberculosis and HIV coinfection.

OBJECTIVE: To assess the joint use of purified protein derivative (PPD) and delayed-type hypersensitivity (DTH) antigens in screening individuals of unknown HIV serostatus for tuberculosis (TB) preventive therapy eligibility. DESIGN: Population-based survey. METHODS: A group of migrant farm workers were screened for HIV and skin-tested with PPD, tetanus toxoid (TET), Candida albicans (CAN) and mumps (MUM) antigens by the Mantoux method. Anergy was defined as a < or = 2 mm reaction to all four antigens. Eligibility for preventive therapy was defined as a reaction of > or = 5 mm to PPD among HIV-seropositive individuals, > or = 10 mm among HIV-seronegatives, or anergy. RESULTS: A total of 253 out of 271 individuals had sufficient data for analysis. Of these, 15 (5%) were HIV-seropositive; 183 (75%), 175 (72%) and 157 (65%) reacted to TET, CAN, and MUM, respectively, and 113 (47%) were eligible for preventive therapy [108 (44%) PPD-positive, five (2%) anergic]. Use of PPD alone was 95% sensitive for detecting preventive therapy eligibility; PPD plus one DTH antigen was more sensitive (99%) but less specific (range, 69-85%); PPD plus two DTH antigens was most specific (CAN + MUM, 84%; TET + MUM, 93%; and TET + CAN, 100%). CONCLUSIONS: In this population with 5% HIV seroprevalence, testing for anergy did not significantly increase the detection of preventive therapy eligibility. The use of two DTH antigens is very sensitive and specific. These results support the recommendation of joint PPD and anergy testing for the screening of HIV-seropositive individuals. Our data also suggest, however, that for individuals whose HIV serostatus is unknown, anergy testing should be considered as a screening tool only if the prevalence of anergy is expected to exceed the prevalence of PPD positivity.

Bacteriologic and endotoxin analysis of salvaged blood used in autologous transfusions during cardiac operations.

Autologous blood transfusion is a common method of reducing the need for heterologous blood transfusion during cardiac operations. Recently we investigated an outbreak of severe, nonsurgical postoperative bleeding among patients undergoing heart operations and receiving intraoperative transfusion of blood from a cell conservation device (Cell Saver System, Haemonetics Corp., Braintree, Mass.). As a result of this investigation, we conducted a prospective study to determine if bacterial or endotoxin contamination of the blood collected in the Cell Saver System and used for reinfusion during heart operations contributes to postoperative bleeding complications. Patients' blood samples were collected immediately before operation, at the end of cardiopulmonary bypass, 1 hour postoperatively, and from the Cell Saver System. All blood samples were cultured for bacteria, and all plasma samples were assayed for endotoxin. Preoperatively all patients having heart operations were without signs of infection, 33 of 37 blood cultures taken were negative, and none of the plasma samples had detectable endotoxin. After discontinuance of cardiopulmonary bypass but before delivery of blood from the Cell Saver System, bacteria and endotoxin were detected in 11 of 36 (30.6%) and five of 35 (14.3%) of the patients' blood samples, respectively. The blood aspirated from the open chest and collected by the Cell Saver System was culture positive in 30 of 31 (96.8%) samples, and seven of 29 (24.1%) contained endotoxin. One of 28 blood samples collected 1 hour postoperatively was culture positive, and five of 25 samples contained endotoxin. Of 61 total microorganisms isolated, 50 (82%) were coagulase-negative staphylococci, four (6.6%) aerobic diphtheroids, five (8.2%) anaerobic "diphtheroids" (Propionibacterium acnes), and two (3.2%) gram-negative bacilli. Plasma endotoxin concentrations ranged from 10 to 765 pg/ml. No signs of endotoxemia or unusual bleeding were observed intraoperatively or postoperatively in any of the 38 patients. Although blood collected in the Cell Saver System and used for reinfusion during heart operations often was contaminated with gram-positive bacterial commensals of the skin and low concentrations of endotoxin, no adverse effects were noted in the patients.

Application of multilocus enzyme electrophoresis to epidemiologic investigations of Xanthomonas maltophilia.

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.

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.

Risk factors for epidemic Xanthomonas maltophilia infection/colonization in intensive care unit patients.

OBJECTIVE: To determine risk factors for and modes of transmission of Xanthomonas maltophilia infection/colonization. DESIGN: Surveillance and cohort study. SETTING: A 470-bed tertiary trauma-referral community hospital. PATIENTS: From January 1, 1988 to March 17, 1989, 106 intensive care unit patients developed X maltophilia infection/colonization. We defined a case as any intensive care unit patient who, from July 15, 1988, through March 17, 1989 (epidemic period), had X maltophilia infection/colonization greater than or equal to 48 hours after intensive care unit admission. We identified 45 case patients and 103 control patients (persons in the shock-trauma intensive care unit for greater than or equal to 72 hours during the epidemic period who had no X maltophilia-positive culture). RESULTS: Cases were significantly more likely to occur in the shock-trauma intensive care unit than in all other intensive care units combined. Mechanical ventilation, tracheostomy, being transported to the hospital by airplane, and receipt of a higher mean number of antimicrobials were risk factors for X maltophilia infection/colonization. Risk of X maltophilia infection/colonization was significantly greater among cases exposed to a patient with a X maltophilia surgical wound infection than among those without such exposure (relative risk = 1.3, p = .03). Animate and inanimate cultures revealed X maltophilia contamination of the hospital room of a patient with an X maltophilia surgical wound infection, of respiratory therapy equipment in this patient's room, of respirometers shared between patients, and of shock-trauma intensive care unit personnel's hands. Related environmental and clinical isolates were serotype 10. CONCLUSIONS: Mechanically ventilated patients receiving antimicrobials in the shock-trauma intensive care unit were at increased risk of X maltophilia infection/colonization. Patients with draining X maltophilia surgical wound infections served as reservoirs for X maltophilia, and contamination of the respirometers and the hands of shock-trauma intensive care unit personnel resulted in patient-to-patient transmission of X maltophilia.

A cluster of severe postoperative bleeding following open heart surgery.

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.

Diagnosis and therapy for common sexually transmitted diseases.

During the past decade, as the human immunodeficiency virus (HIV) has appeared, sexually transmitted diseases (STDs) have resurged to epidemic proportions, and STDs have been shown to facilitate transmission of HIV, the diagnosis and treatment of STDs have increased in importance for all clinicians. This article's recommendations for treatment of STDs that might more commonly be seen in a dermatology practice are based on the 1989 Sexually Transmitted Disease Treatment Guidelines of the Centers for Disease Control. Clinicians are encouraged to address actively prevention and treatment of sexual partners, a very important part of the management of STDs.

The multidrug-resistant tuberculosis challenge to public health efforts to control tuberculosis.

After years of steady decline, there has been an unprecedented resurgence of tuberculosis (TB) in the United States and outbreaks of multidrug-resistant tuberculosis (MDR-TB). The authors assess the nature, epidemiology, and implications of MDR-TB; provide suggestions for preventing drug resistance among patients with drug-susceptible TB; and offer recommendations for managing patients with MDR-TB. They outline the National Action Plan to Combat MDR-TB. Close collaboration among medical practitioners and staff members of TB control programs is needed to ensure the most effective management of patients with TB and their contacts. This collaboration is one of the most important steps for successful control of MDR-TB.

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$21,525 and $4294 more per TB case prevented, and respectively $4565 and $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.

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

SETTING: Two international, multicenter Phase 2 clinical trials examining fluoroquinolone-containing regimens in adults with smear-positive pulmonary tuberculosis (TB), conducted from July 2003 to March 2007. Both trials enrolled human immunodeficiency virus (HIV) infected participants who were not receiving antiretroviral therapy (ART) at TB treatment initiation. OBJECTIVE: To assess the impact of HIV infection on TB treatment outcomes in Phase 2 clinical trials. DESIGN: Cross-protocol analysis comparing the safety, tolerability and outcomes of anti-tuberculosis treatment by HIV status. RESULTS: Of 750 participants who received at least one dose of study treatment, 123 (16%) were HIV-infected. Treatment completion rates were similar by HIV status (81% infected vs. 85% non-infected), as were rates of week 8 culture conversion (66% infected vs. 63% non-infected), and treatment failure (5% infected vs. 3% non-infected). Among HIV-infected participants, treatment failure detected using liquid media was more frequent in those treated thrice weekly (14% thrice weekly vs. 2% daily, P = 0.03). HIV-infected participants more frequently experienced an adverse event during the intensive phase treatment than non-HIV-infected participants (30% vs. 15%, P < 0.01). CONCLUSION: HIV-infected persons not receiving ART had more adverse events during the intensive phase of anti-tuberculosis treatment, but tolerated treatment well. Failure rates were higher among HIV-infected persons treated with thrice-weekly intensive phase therapy.

Epidemic of Serratia marcescens bacteremia in a cardiac intensive care unit.

From 16 July through 27 September 1988, seven cases of nosocomial Serratia marcescens bacteremia occurred in a cardiac care unit. In all seven case patients, S. marcescens was isolated from blood cultures. Two of the seven had other microorganisms identified in the blood culture in which S. marcescens was recovered; one had Enterobacter cloacae, and one had Klebsiella pneumoniae. A case-control study was conducted to identify risk factors for bloodstream infection. Case patients were more likely than controls to have been exposed to an intra-aortic balloon pump pressure transducer (7 of 7 versus 6 of 21; P = 0.001) and to a pulmonary arterial pressure transducer (7 of 7 versus 8 of 21; P = 0.005). Cultures of in-use and in-storage transducers revealed bacterial contamination of the pressure-sensitive membranes of the transducers. S. marcescens blood culture isolates obtained from five of the seven case patients, as well as six S. marcescens isolates from cultured transducers, belonged to serotypes Oundetermined:H1 and Oundetermined:H18. E. cloacae isolates from one case patient and from two stored and two in-use transducers had identical antimicrobial suceptibility patterns. Review of cardiac care unit disinfection practices revealed that the transducers were not processed with high-level disinfection or sterilization between patient uses. We concluded that the transducers had served as reservoirs for this outbreak of bloodstream infection. Because intra-aortic balloon pumps with pressure transducers are being used more frequently in the management of critically ill cardiac patients, their role as infectious reservoirs should be considered in the investigation of nosocomial bacteremia.

Comparable specificity of 2 commercial tuberculin reagents in persons at low risk for tuberculous infection.

CONTEXT: One or both commercial tuberculin skin test reagents (Aplisol and Tubersol) may have a high rate of false-positive reactions. OBJECTIVE: To compare the reaction size and specificity of skin testing with Aplisol, Tubersol, and the standard purified protein derivative (PPD-S1). DESIGN: Double-blind trial, conducted between May 14, 1997, and October28, 1997, in which each individual received 4 tuberculin skin reagents at sites assigned at random. SETTING: Health departments and universities in 6 US cities. PARTICIPANTS: A total of 1555 persons at low risk of latent tuberculosis infection. INTERVENTION: Simultaneous skin tests with Aplisol, Tubersol, PPD-S1, and either a second PPD-S1 or PPD-S2 (a proposed new standard). MAIN OUTCOME MEASURE: Reaction size at each injection site measured by 2 investigators blinded to type of reagent. RESULTS: Aplisol produced slightly larger reactions than Tubersol, but this difference did not significantly change skin test interpretation. The mean +/- SD reaction sizes were 3.4+/-4.2 mm with Aplisol, 2.1+/-3.2 mm with Tubersol, and 2.5+/-3.6 mm with PPD-S1. Assuming that all participants were uninfected and using a 10-mm cutoff, the specificities of the tests were high: Aplisol, 98.2%; Tubersol, 99.2%; and PPD-S1, 98.9%. Significant variability was not detected in interobserver, host, and lot-to-lot reagent comparisons. CONCLUSION: Using a cutoff of at least 10 mm, testing with 3 different PPD reagents resulted in similar numbers of uninfected persons being correctly classified.

Rifampin preventive therapy for tuberculosis infection: experience with 157 adolescents.

For persons infected with Mycobacterium tuberculosis resistant to isoniazid (INH), rifampin is recommended for the prevention of active disease. However, the adverse effects and acceptability of this preventive therapy are largely uncharacterized. We prospectively followed 157 high-school students exposed to, and probably infected with, M. tuberculosis strains resistant to INH. All 157 students were prescribed preventive therapy with rifampin (10 mg/kg up to 600 mg daily) for 24 wk. While receiving therapy, 41 (26%) reported one or more adverse effects; of these, 18 had therapy interrupted temporarily, two permanently. Four (2.5%) had alanine aminotransferase elevations greater than two times the upper limit of normal (range, 91 to 161 U/L); of these, one had therapy permanently stopped. Six (3.8%) self-discontinued therapy. No student was found to have active disease during the 2 yr of the study (exact 95% upper confidence limit, 2.2). We assumed that without preventive therapy, seven cases of tuberculosis would have occurred during these 2 yr. Therefore, we estimated that rifampin had a minimum protective effect of 56%. In conclusion, preventive therapy with rifampin was well tolerated and well accepted, and it appears effective in preventing active tuberculosis.

Nosocomial transmission of tuberculosis in a hospital unit for HIV-infected patients.

OBJECTIVE: To assess nosocomial transmission of tuberculosis (TB). DESIGN: A historical cohort study of hospitalized patients with the human immunodeficiency virus (HIV) and a purified protein derivative (PPD) tuberculin skin test survey of health care workers (HCWs). SETTING: A large public teaching hospital in San Juan, Puerto Rico. PATIENTS: For the cohort study, a case patient was defined as any patient in the HIV unit at the hospital who developed culture-positive TB from 31 days or more after admission through December 31, 1989. For the PPD survey, of 1420 HCWs from the hospital, 908 agreed to participate and had sufficient data for analysis. MAIN OUTCOME MEASURES: For the cohort study, to compare the risk of developing active TB among patients who were exposed to hospital roommates with infectious TB and the risk among nonexposed patients. For the HCW PPD survey, to determine the prevalence of and risk factors for tuberculous infection. RESULTS: Eight of 48 (9.7/10,000 person-days) exposed case patients vs four of 192 (0.8/10,000 person-days) nonexposed case patients developed active TB (relative risk [RR] = 11; 95% confidence interval [CI], 2.3, 50.3). Positive PPDs (greater than or equal to 10 mm of induration) in HCWs were associated with older age (P = .0001) and with history of community TB exposure (P = .0002). In a multivariable logistic model that adjusted for these variables, HIV unit nurses (nine of 19) and nurses in the internal medicine ward (45 of 90) had a higher proportion of positive PPDs than the reference group (clerical personnel on other floors: 35 of 188, P = .0005). CONCLUSIONS: These data suggest that patient-to-patient transmission of TB in HIV units can occur and that HCWs are at risk of acquiring TB infection.

Hepatitis A outbreak in a neonatal intensive care unit: risk factors for transmission and evidence of prolonged viral excretion among preterm infants.

An outbreak of hepatitis A virus (HAV) infection in a neonatal intensive care unit (NICU) provided the opportunity to examine the duration of HAV excretion in infants and the mechanisms by which HAV epidemics are propagated in NICUs. The outbreak affected 13 NICU infants (20%), 22 NICU nurses (24%), 8 other staff caring for NICU infants, and 4 household contacts; 2 seropositive infants (primary cases) received blood transfusions from a donor with HAV infection. Risk factors for infection among nurses were care for a primary infant-case (relative risk [RR], 3.2), drinking beverages in the unit (odds ratio [OR], infinity), and not wearing gloves when taping an intravenous line (OR, 13.7). Among infants, risk factors were care by a nurse who cared for a primary infant-case during the same shift (RR, 6.1). Serial stool samples from infant-cases were tested for HAV antigen (HAV-Ag) by enzyme immunoassay and HAV RNA by nucleic acid amplification using the polymerase chain reaction. Infant-cases excreted HAV-Ag (n = 2) and HAV RNA (n = 3) 4-5 months after they were identified as being infected. Breaks in infection control procedures and possibly prolonged HAV shedding in infants propagated the epidemic in a critical care setting.

Postoperative infections traced to contamination of an intravenous anesthetic, propofol.

BACKGROUND: Between June 1990 and February 1993, the Centers for Disease Control and Prevention conducted investigations at seven hospitals because of unusual outbreaks of bloodstream infections, surgical-site infections, and acute febrile episodes after surgical procedures. METHODS: We conducted case-control or cohort studies, or both, to identify risk factors. A case patient was defined as any patient who had an organism-specific infection or acute febrile episode after a surgical procedure during the study period in that hospital. The investigations also included reviews of procedures, cultures, and microbiologic studies of infecting, contaminating, and colonizing strains. RESULTS: Sixty-two case patients were identified, 49 (79 percent) of whom underwent surgery during an epidemic period. Postoperative complications were more frequent during the epidemic period than before it. Only exposure to propofol, a lipid-based anesthetic agent, was significantly associated with the postoperative complications at all seven hospitals. In six of the outbreaks, an etiologic agent (Staphylococcus aureus, Candida albicans, Moraxella osloensis, Enterobacter agglomerans, or Serratia marcescens) was identified, and the same strains were isolated from the case patients. Although cultures of unopened containers of propofol were negative, at two hospitals cultures of propofol from syringes currently in use were positive. At one hospital, the recovered organism was identical to the organism isolated from the case patients. Interviews with and observation of anesthesiology personnel documented a wide variety of lapses in aseptic techniques. CONCLUSIONS: With the increasing use of lipid-based medications, which support rapid bacterial growth at room temperature, strict aseptic techniques are essential during the handling of these agents to prevent extrinsic contamination and dangerous infectious complications.

Comparison testing of current (PPD-S1) and proposed (PPD-S2) reference tuberculin standards.

Since 1951, the tuberculin PPD-S1 has been used to standardize commercial PPD reagents and perform special tuberculin surveys. PPD-S1 is now in short supply and a new standard (PPD-S2) has been manufactured. To determine if PPD-S2 is equivalent and can replace PPD-S1, we conducted a double-blind clinical trial. Between May 14 and October 28, 1997, 69 subjects with a history of culture-proven tuberculosis (TB patients) and 1,189 subjects with a very low risk for TB infection were enrolled, received four skin tests (with PPD-S1, PPD-S2, and one each of the commercially available PPDs), and had reactions measured by two trained observers. Among the TB patients, we found statistically indistinguishable immunogenicity (mean reaction size +/- standard deviation): 15.6 +/- 6.6 mm for PPD-S1 and 14.8 +/- 5.6 mm for PPD-S2. Among low-risk subjects, the tests had equally high specificities (PPD-S1, 98.7% and PPD-S2, 98. 5%), using a 10-mm cutoff. The number of discordant (negative versus positive) interpretations for PPD-S2, assuming that low-risk subjects who had a >/= 10 mm reaction to PPD-S1 were truly infected, was low (0.5%) and indistinguishable from the rate of discordant interpretations of the same test when read by two different observers (0.8%). The study results indicate that PPD-S2 is qualified to be used as the new U.S. reference standard for PPD tuberculin.