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Context: Because of problems with adherence, toxicity, and increasing resistance associated with 6- to 12-month isoniazid regimens, an alternative short-course tuberculosis preventive regimen is needed.Objective: To compare a 2-month regimen of daily rifampin and pyrazinamide with a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with human immunodeficiency virus (HIV) infection.Design: Randomized, open-label controlled trial conducted from September 1991 to May 1996, with follow-up through October 1997.Setting: Outpatient clinics in the United States, Mexico, Haiti, and Brazil.Participants: A total of 1583 HIV-positive persons aged 13 years or older with a positive tuberculin skin test result.Interventions: Patients were randomized to isoniazid, 300 mg/d, with pyridoxine hydrochloride for 12 months (n = 792) or rifampin, 600 mg/d, and pyrazinamide, 20 mg/kg per day, for 2 months (n = 791).Main Outcome Measures: The primary end point was culture-confirmed tuberculosis; secondary end points were proven or probable tuberculosis, adverse events, and death, compared by treatment group.Results: Of patients assigned to rifampin and pyrazinamide, 80% completed the regimen compared with 69% assigned to isoniazid (P<.001). After a mean follow-up of 37 months, 19 patients (2.4%) assigned to rifampin and pyrazinamide and 26 (3.3%) assigned to isoniazid developed confirmed tuberculosis at rates of 0.8 and 1.1 per 100 person-years, respectively (risk ratio, 0.72 [95% confidence interval, 0.40-1.31]; P = .28). In multivariate analysis, there were no significant differences in rates for confirmed or probable tuberculosis (P = .83), HIV progression and/or death (P = .09), or overall adverse events (P = .27), although drug discontinuation was slightly higher in the rifampin and pyrazinamide group (P = .01). Neither regimen appeared to lead to the development of drug-resistant tuberculosis.Conclusions: Our data suggest that for preventing tuberculosis in HIV-infected patients, a daily 2-month regimen of rifampin and pyrazinamide is similar in safety and efficacy to a daily 12-month regimen of isoniazid. This shorter regimen offers practical advantages to both patients and tuberculosis control programs. [ABSTRACT FROM AUTHOR]

Of 4588 pregnant women in a high-risk Haitian population, 443 (9.7%) were serologically positive for the human immunodeficiency virus type 1 (HIV-1). Infants born to women who were HIV-1 seropositive were more likely to be premature, of low birth weight, and malnourished at 3 and 6 months of age than were infants born to women who were HIV-1 seronegative. Increased mortality was observed in infants born to women who were HIV-1 seropositive by 3 months of age. At 12 months of age, 23.4% of the infants born to women who were HIV-1 seropositive had died compared with 10.8% of the infants born to women who were HIV-1 seronegative; at 24 months of age, the mortality rates were 31.3% and 14.2%, respectively. Maternal HIV-1 infections resulted in an 11.7% increase in the overall infant mortality rate in this population. The estimated mother-to-infant HIV-1 transmission rate in these breast-fed infants was 25%, similar to the rates reported for non-breast-fed populations in the United States and Europe. [ABSTRACT FROM AUTHOR]

Background: There remains a need for animal models with human translatability in lung cancer (LC) research. Findings in pigs have high impact on humans due to similar anatomy and physiology. We present the characterization of a bronchoscopically-induced LC model in Oncopigs carrying inducible KRAS G12D and TP53 R167H mutations., Methods: Twelve Oncopigs underwent 29 injections via flexible bronchoscopy. Eighteen Adenovirus-Cre recombinase gene (AdCre) inductions were performed endobronchially (n=6) and transbronchially with a needle (n=12). Eleven control injections were performed without AdCre. Oncopigs underwent serial contrast-enhanced chest CT with clinical follow-up for 29 weeks. Following autopsy, lung and organ tissues underwent histopathology, immunohistochemistry, and RNA-sequencing with comparative analysis with The Cancer Genome Atlas (TCGA) human LC data., Results: All 18 sites of AdCre injections had lung consolidations on CT imaging. Transbronchial injections led to histopathologic invasive cancer and/or carcinoma in situ (CIS) in 11/12 (91.7%), and invasive cancer (excluding CIS) in 8/12 (66.6%). Endobronchial inductions led to invasive cancer in 3/6 (50%). A soft tissue metastasis was observed in one Oncopig. Immunohistochemistry confirmed expression of Pan-CK+/epithelial cancer cells, with macrophages and T cells infiltration in the tumor microenvironment. Transcriptome comparison showed 54.3% overlap with human LC (TCGA), in contrast to 29.88% overlap of KRAS-mutant mouse LC with human LC., Conclusions: The transgenic and immunocompetent Oncopig model has a high rate of LC following bronchoscopic transbronchial induction. Overlap of the Oncopig LC transcriptome with human LC transcriptome was noted. This pig model is expected to have high clinical translatability to the human LC patient.

The activation of the programmed cell death one (PD1)/PD1 ligand (PD-L1) immune checkpoint pathway is a mechanism of immune evasion characterized by the upregulation of PD-L1 expression by tumor cells and by the tumor microenvironment. This activation leads to the inhibition of PD1-positive T cells and to a decrease in the anti-tumor immune response. Plasmablastic lymphoma (PBL) is an aggressive type of large B-cell lymphoma with limited studies on the frequency of PD1 and PD-L1 expressions and their clinical impact. As PBL is associated with immune suppression in immunocompromised individuals, we hypothesize that the PD1/PD-L1 axis may be relevant in this type of lymphoma. Our study demonstrates a subset of PBL cases with a higher PD-L1 expression by tumor cells [nPD-L1 high , in 4 of 21 (19%) cases] and by tumor microenvironment [macrophages/stromal cells, sPD-L1 high , in 9 of 21 (43%) cases]. While nPD-L1 expression showed no significant correlation with PD1 expression on tumor-infiltrating lymphocytes, or other clinicopathological parameters, it positively correlated with sPD-L1 expression. Moreover, patients with nPD-L1 high had a tendency towards a shorter overall survival (median 9.3 vs. 25.5 months in nPD-L1 low patients). In conclusion, our study provides a rationale to identify, by immunohistochemistry, a subset of nPD-L1 high patients who may benefit from clinical trials of PD1/PD-L1 checkpoint blockade. Further studies on large cohorts are needed to investigate prognostic and predictive biomarkers for the PD1/PD-L1 pathway in PBL patients., (© 2021 by the Association of Clinical Scientists, Inc.)

EF Bart's disease is a rare form of nontransfusion-dependant thalassemia (NTDT) due to the coinheritance of homozygous hemoglobin E ( β E / β E ) genotype with hemoglobin H disease. These individuals are routinely found to have thalassemia intermedia with moderate anemia, increased hemoglobin Bart's and hemoglobin F on electrophoresis. The contribution of hemoglobin F-inducing polymorphisms in this disease has not been described previously. Here, we describe the hematological profile in a young child with coinheritance of G γ -XmnI and A γ -globin gene polymorphisms in EF Bart's disease. Interestingly, in this rare form of NTDT, normal HbF and elevated HbA2 were noted., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Kane M. Laks et al.)

Background: Antiplatelet therapy is a complicating factor in patients with traumatic brain injuries (TBI), as well as those with hemorrhagic cerebrovascular accidents (CVAs). Platelet Function Assay (PFA)-100 is a coagulation device that can detect platelet dysfunction caused by aspirin and adenosine diphosphate inhibition. Our retrospective study reviewed the effectiveness of PFA-100 in detecting platelet dysfunction caused by aspirin and clopidogrel and determined its clinical importance., Methods: All patients with PFA-100 tests from January 2013 to February 2014 were collected. Diagnoses indicative of a TBI or CVA were chosen for analysis. Patients with a normal PFA-100 indicating no platelet dysfunction but with documented aspirin and/or clopidogrel use were selected. An extensive chart review was performed to determine the relevance to their clinical care., Results: A total of 475 patients were evaluated with a PFA-100 from January 2013 to February 2014. PFA-100 detected platelet dysfunction as the result of pre-injury use of antiplatelet agents in TBI and CVA patients with a sensitivity of only 48.6% and a specificity of 74.8%. Had these antiplatelet medications been known during initial workup, these patients would have had a change in management that may have impacted their outcomes., Conclusion: Despite its common usage, the PFA-100 is an unreliable tool to assist in the management of TBI and CVA patients. Additional investigation into alternative methods for detecting platelet dysfunction is warranted., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months. The aim of three trials in Ethiopia, India, and Uganda was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding., Methods: HIV-infected women breastfeeding their infants were eligible for participation. Participants were randomly assigned to receive either single-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth) or 6 week extended-dose nevirapine (nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8-42 for the infant). The randomisation sequences were generated by computer at a central data coordinating centre. The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth. Analyses were by modified intention to treat, excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth. These studies are registered with ClinicalTrials.gov, numbers NCT00074399, NCT00061321, and NCT00639938., Findings: 2024 liveborn infants randomised in the study had at least one specimen tested before 6 months of age (1047 infants in the single-dose group and 977 infants in the extended-dose group). The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group. At 6 months, 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV (relative risk 0.80, 95% CI 0.58-1.10; p=0.16). At 6 weeks of age, 54 children in the single-dose group and 25 in the extended-dose group were HIV positive (0.54, 0.34-0.85; p=0.009). 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study (p=0.54)., Interpretation: Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age, the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high., Funding: US National Institutes of Health; US National Institute of Allergy and Infectious Diseases; Fogarty International Center.

When real-time disease surveillance is practiced in neighboring states within a region, public health users may benefit from easily sharing their concerns and findings regarding potential health threats. To better understand the need for this capability, an event communications component (ECC) was added to the National Capital Region Disease Surveillance System, an operational biosurveillance system employed in the District of Columbia and in surrounding Maryland and Virginia counties. Through usage analysis and user survey methods, we assessed the value of the enhanced system in daily operational use and during two simulated exercises. Results suggest that the system has utility for regular users of the system as well as suggesting several refinements for future implementations.

Introduction: Syndromic surveillance systems are becoming increasingly common in health departments. These systems represent a substantial improvement in the timeliness of ascertainment of community health status. For the value of such systems to be realized, protocols are needed for review and analysis of the findings that these systems produce., Methods: A workgroup of experienced syndromic surveillance users and developers was convened to discuss approaches to data review and analyses. The discussion was structured to include general principles of the use of syndromic surveillance; how and why specific data are reviewed; integration of multiple data sources; daily versus research uses of systems; how data anomalies are identified by users and surveillance systems; the relative merits of anomalies; how a data anomaly is investigated to determine if it warrants a public health response; and how such a public health response should be framed., Results: From this discussion, a generalized and more detailed process was documented that describes the common elements of analysis used by the workgroup participants., Conclusion: Establishment of a framework for evaluation and response to syndromic surveillance data will facilitate the implementation of these systems and standardization of procedures for validation of system findings. Careful development of an evaluation and response framework should be undertaken to assess whether use of syndromic surveillance systems requires excess work to distinguish between statistical anomalies and important public health events.

Introduction: In concert with increased concerns regarding both biologic terrorism and new natural infectious disease threats (e.g., severe acute respiratory syndrome [SARS] and West Nile virus), as a result of advances in medical informatics, various data sources are available to epidemiologists for routine, prospective monitoring of public health. The synthesis of this evidence requires tools to find anomalies within various data stream combinations while maintaining manageable false alarm rates., Objectives: The objectives of this report are to establish statistical hypotheses to define the compound multivariate problem of surveillance systems, present statistical methods for testing these hypotheses, and examine results of applying these methods to simulated and actual data., Methods: Canonical problems of parallel monitoring and consensus monitoring are considered in this report. Modified Bonferroni methods are examined for parallel monitoring. Both multiple univariate and multivariate methods are applied for consensus monitoring. A multivariate adaptation of Monte Carlo trials, using the injection of epidemic-curve-like signals in the multiple data streams of interest, is presented for evaluation of the various tests., Results: The Monte Carlo test results demonstrate that the multiple univariate combination methods of Fisher and Edgington provide the most robust detection performance across the scenarios tested. As the number of data streams increases, methods based on Hotelling's T2 offer added sensitivity for certain signal scenarios. This potential advantage is clearer when strong correlation exists among the data streams., Conclusion: Parallel and consensus monitoring tools must be blended to enable a surveillance system with distributed sensitivity and controlled alert rates. Whether a multiple univariate or multivariate approach should be used for consensus monitoring depends on the number and distribution of useful data sources and also on their covariance structure and stationarity. Strong, consistent correlation among numerous sources warrants the examination of multivariate control charts.

A whole-blood interferon-gamma release assay (IGRA) is being evaluated for its potential to replace the tuberculin skin test (TST) for detecting Mycobacterium tuberculosis infection. To test the assay in a population in which tuberculosis is highly endemic and in another population that is representative of an urban United States population, 253 volunteers from Ethiopia and 175 volunteers from Baltimore were studied for responsiveness on IGRA compared with a simultaneously performed TST. The agreement between the 2 tests, beyond that due to chance, was 68% among subjects from Baltimore and only 35% among those from Ethiopia. IGRA had a sensitivity of 71%, compared with 95% sensitivity for the TST, among 21 subjects who had undergone treatment for culture-confirmed tuberculosis. The specificity was 85% for IGRA and 96% for TST among 52 subjects with no known history of exposure to tuberculosis. In its current form, with purified protein derivative used as the stimulation antigen, the IGRA was found to perform poorly in comparison to the TST in diagnosing M. tuberculosis infection.

Background: Tuberculosis is a common complication of HIV-1 infection, especially in developing countries. Practical and effective chemoprophylaxis regimens for HIV-1-related tuberculosis are needed. Our aim was to test the efficacy of isoniazid versus rifampicin with pyrazinamide for prevention of tuberculosis in HIV-1-positive individuals., Methods: We compared the efficacy of 6 months of isoniazid with 2 months of rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1-seropositive individuals. Eligible participants were aged 16-77 years, HIV-1 seropositive, had a positive purified-protein derivative (PPD) skin test reaction of at least 5 mm, and had a normal chest radiograph. Participants were randomly assigned partially supervised twice weekly isoniazid for 24 weeks or twice weekly rifampicin and pyrazinamide for 8 weeks. Participants were followed up for up to 4 years for the development of tuberculosis and survival., Findings: Tuberculosis developed in 14 (3.8%) of 370 participants assigned isoniazid and 19 (5.0%) of 380 participants assigned rifampicin and pyrazinamide (Cox model rate ratio 1.3 [95% CI 0.7-2.7]). The Kaplan-Meier estimate of the risk of tuberculosis during the first 10 months after entry was 3.7% among participants who received rifampicin and pyrazinamide compared with 1.0% (p=0.03) among participants who received isoniazid, and 5.4% versus 5.1%, respectively (p=0.9) at 36 months after entry. Higher rates of tuberculosis were observed in people with baseline CD4 percentages (of total lymphocytes) of less than 20 (rate ratio 4.0 [95% CI 1.8-9.0]). There were no significant differences in total mortality at any time., Interpretation: Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults. The better protection among recipients of isoniazid during the first 10 months was most likely secondary to the longer duration of chemoprophylaxis. Preventive therapy for HIV-1-seropositive, PPD-positive individuals could be practical in developing countries with a once weekly clinic visit, but optimum duration of chemoprophylaxis has not been determined.

The aim of the work reported here was to evaluate community-wide screening for HIV infection that was linked to a tuberculosis control program in a population at high risk for both infections. Between May 1990 and August 1992, adults in Cité Soleil, Haiti, were recruited by community health workers at their homes and in clinics for individual, clinic-based counseling and testing for HIV and tuberculosis. All of the screened subjects were offered post-test HIV counseling. Those with active tuberculosis received treatment, while those with latent tuberculosis and HIV infection were offered an opportunity to participate in a trial of antituberculosis chemoprophylaxis. The 10,611 individuals screened for HIV represented 10.0% of the adult population in Cité Soleil. HIV infection was detected in 1,629 (15.4%) and active tuberculosis in 242 (2.3%). Latent M. tuberculosis infection was found in 4,800 (67.5%) of 7,309 community residents who completed tuberculosis screening, 781 (16.3%) of whom were coinfected with HIV. The high prevalence of HIV infection found in this screened population, as compared to other groups undergoing HIV screening in the same community, suggests that people at high risk for HIV infection selectively sought or accepted tuberculosis clinic screening. Also, many people with active tuberculosis were identified earlier in the course of their disease than they would have been in the absence of a screening program. Overall, the results indicate that community-based screening for HIV infection within a tuberculosis control program can result in effective targeting of screening for both infections.

Objective: To compare the risk of complications following Bacillus Calmette-Guérin (BCG) vaccination among children by maternal and infant HIV-1 infection status as part of an investigation of an outbreak of BCG complications., Methods: A nonconcurrent cohort study of BCG complications among 125 infants born to HIV-1 seropositive and 166 infants born to HIV-1 seronegative mothers was conducted in Cité Soleil, Haiti. Infants were examined at regular intervals until 15 months of age, and complications from BCG were documented. An investigation of BCG vaccination practices was conducted., Results: Mild or moderate complications occurred among 16 of 166 (9.6%) infants born to HIV-1 seronegative mothers compared with 4 of 13 HIV-1-infected infants (30.8%, P = .04) and 10 of 75 (13.3%, P = .39) uninfected infants born to HIV-1-infected mothers. No serious complications were noted. The outbreak of complications was associated with administration of 2.0 to 2.5 times the recommended dose of BCG vaccine., Conclusions: This and five other cohort studies indicate that there may be a small increased risk of complications following BCG vaccination among HIV-1-infected children, but the reactions are usually mild and the risk does not outweigh the benefits of BCG vaccination in populations at high risk of tuberculosis during infancy and childhood.

Two hundred and twenty-five infants were randomly assigned to receive 2 micrograms of plasma-derived hepatitis B vaccine (Heptavax) intradermally (ID-2), 10 micrograms intramuscularly (IM-10), or 2 micrograms intramuscularly (IM-2) in the deltoid region at birth, 2 and 4 months. At 6 months, ID-2 infants were less likely to have developed > or = 10 mIU ml-1 of antibody to hepatitis B surface antigen (anti-HBs) than IM-10 infants (91 versus 100%; p = 0.02) and had a lower geometric mean concentration of anti-HBs (312 mIU ml-1 versus 2248 mIU ml-1; p < 0.01). At 6 months IM-10 infants had significantly lower mean weights and lengths than infants receiving 2 micrograms doses of vaccine. Intramuscular administration of 2 micrograms and 10 micrograms doses of Heptavax in the deltoid of young infants was well tolerated and effective; however, intradermal administration of Heptavax provided no immunological benefit over intramuscular administration and resulted in significantly higher rates of induration and persistent hyperpigmentation. Intramuscular immunization at birth, 2 and 4 months is an acceptable, effective alternative schedule for immunizing infants.

Maternal-infant transmission of HIV-1 occurs in 13-40% of pregnancies. Studies on transmission of maternal immunity to HIV antigens have used antigens from viruses not representative of clinical isolates and have been conflicting. Using a consensus peptide sequence based on HIV isolates found in Haiti, we found that Haitian mothers who transmitted infection to their offspring had significantly higher mean concentrations of IgG1 antibodies to the V3 loop of the primary neutralising domain of the viral envelope (gp 160) than non-transmitters (p = 0.02). Concentrations of IgA antibody to this domain were similar in transmitters and non-transmitters.

Breast milk specimens from human immunodeficiency virus type 1 (HIV-1)-seropositive and HIV-1-seronegative women were examined for the presence of HIV-1 p24 antigen by the antigen capture method and for viral DNA using the polymerase chain reaction. HIV-1 DNA was present in 70% of milk specimens collected from 47 HIV-seropositive women 0-4 days after delivery and in approximately 50% of specimens collected 6 and 12 months postpartum. p24 antigen, present in 24% of milk specimens collected from 37 seropositive women within the first 4 days postpartum, was not detected in any of the subsequent specimens. The presence of HIV-1 DNA or p24 antigen in milk was not significantly associated with maternal CD4 lymphocyte count, beta 2-microglobulin level, or fulfillment of the AIDS clinical case definition. Although the correlation of either HIV-1 proviral DNA or p24 antigen with the presence of infectious virus is not known, these data indicate the need for additional studies examining the role of breastfeeding in maternal-infant transmission of HIV-1.

Five (0.74%) of 678 women delivering in 1985 at a tertiary referral hospital for high-risk pregnancies and 16 (1.34%) of 1198 women visiting an urban prenatal obstetrics clinic in 1986-1987 had serologic evidence of human immunodeficiency virus type 1 (HIV-1) infection. Unlinked testing (removal of personal identifiers from the blood specimen and the epidemiologic data sheet) of residual serum from hepatitis B virus serologic testing was used. Neither age, marital status, payor status, nor serologic markers of hepatitis B virus infection was useful in identifying women at risk for HIV-1 infection. As a result of these data, we have initiated a program in which counseling is offered to all women and testing for those who consent. Unlinked testing of women who refuse consent is performed for epidemiologic purposes. This will allow us to continue to plan for health care resource needs and to track the course of the epidemic in various subgroups of pregnant women.

Objective: To determine whether a previously observed association between human immunodeficiency virus type 1 (HIV-1) infection and smoking in Haitian women could be explained by confounding high-risk behaviors., Design and Setting: A nested case-control study at a primary care health clinic in Cité Soleil, Haiti., Participants: Women who reported having smoked (n = 89) and randomly selected nonsmokers (n = 329) who had participated in a survey 1 to 12 months earlier evaluating risk factors for HIV-1 infection., Main Outcome Measures: Lifetime sexual practices, smoking, health beliefs and practices, and other factors potentially confounding the relationship between smoking and HIV-1 infection., Results: Compared with nonsmokers, smokers reported higher rates of high-risk behaviors, including more lifetime sex partners (P less than .001), being less likely to be married (P less than .01), and being more likely to have visited folk healers (P less than .01). No intravenous drug use was reported, and no significant differences were noted between smokers and nonsmokers in numbers of past surgical or dental procedures or injections. Adjustment for all factors associated with HIV-1 infection and smoking in regression analyses revealed an independent association between smoking and HIV-1 infection (odds ratio [OR], 3.4; 95% confidence interval [Cl], 1.6 to 7.5). Other factors associated with HIV-1 infection included having more than two life-time sex partners (OR, 3.4; 95% Cl, 1.7 to 6.8) and lower socioeconomic status as reflected by a dirt floor in the home (OR, 8.6; 95% Cl, 3.3 to 22.0)., Conclusions: Smoking is a marker for high-risk sexual behavior and is associated with an increased risk of HIV-1 infection in this population. The persistent association between smoking and HIV-1 infection after adjustment for all known risk factors suggests the possibility of a biologic effect of smoking that warrants further evaluation in other populations.

The radioassay of very small 125I samples in both conventional and side-hole well crystals has been investigated. Using a multichannel analyzer, the source was counted at various positions within these well crystals. The effect of using a single-channel pulse-height analyzer was simulated by summing the counts over a 24-keV range across the primary peak, over a 30-keV range across the sum-coincidence peak, and over a 56-keV range across both peaks. In all crystals the primary peak was independent of sample position within the well over a range of several centimeters. The contribution of the sum-coincidence peak varied significantly with sample position in the conventional well crystals. With the side-hole crystal the counts contributed by the sum-coincidence peak exhibited a 2-cm plateau.

Due to sporadic infections attributed to contaminated multiple-dose medication vials (MDV), some authorities have suggested discarding all MDV within 24 hours. We inoculated 11 commonly used medications with suspensions of 10 bacterial species previously associated with contaminated parenteral solutions and determined microbial persistence at both room and refrigerator temperature. At 22 degrees C, atropine, curare, folic acid, NPH insulin and triamcinolone did not allow microbial persistence beyond 4 hours. Lidocaine and heparin were sterile by 24 hours. Regular insulin, immune serum globulin, and myochrysine allowed persistence for up to 7 days. At 4 degrees C, bacterial persistence was significantly prolonged for all medications including those MDV requiring refrigeration. No organisms proliferated; however, F. meningosepticum and P. maltophilia were particularly persistent at both temperatures. The risk of persistent MDV contamination appears to be dependent upon specific pharmaceutical, microbe and storage temperature interactions. Recommendations for the refrigeration of MDV medications may require reevaluation on a product-by-product basis.