Assessment of the risk of salmonellosis from internally contaminated shell eggs following initial storage at 18 °C (65 °F), compared with 7 °C (45 °F).

In the U.S., chicken-breeder farms that supply hatcheries typically store and transport eggs intended for broiler production at a temperature of 18.3 °C (65 °F). However, in case of surplus, some of these eggs may be diverted to human consumption. According to the U.S. Food and Drug Administration's 'Egg Safety Final Rule,' shell eggs intended for human consumption are required to be held or transported at or below 7.2 °C (45 °F) ambient temperature beginning 36 h after time of lay. We adapted a risk assessment model developed by the U.S. Department of Agriculture's Food Safety Inspection Service, to quantify human exposure to Salmonella Enteritidis and the risk of human salmonellosis if eggs are held and transported at 18.3 °C for up to 5.5 days after time of lay, as has been observed when hatchery eggs are diverted to human consumption, rather than held and transported at 7.2 °C within 36 h after time of lay. Storage at 18.3 °C leads to considerable bacterial growth in internally contaminated eggs. The model predicted that more than 10% of internally contaminated eggs would remain contaminated after in-shell pasteurization resulting in a 5-log10 reduction, and that some bacteria would survive after home-cooking. The model predicted that, alternatively, eggs stored at 7.2 °C after lay would have limited bacterial growth prior to pasteurization, and Salmonella would be very unlikely to be present after pasteurization. The predicted risk of salmonellosis from the consumption of eggs held and transported at 18.3 °C and subsequently diverted to human consumption is 25 times higher than the risk when eggs are held and transported at 7.2 °C.

New data, strategies, and insights for Listeria monocytogenes dose-response models: summary of an interagency workshop, 2011.

Listeria monocytogenes is a leading cause of hospitalization, fetal loss, and death due to foodborne illnesses in the United States. A quantitative assessment of the relative risk of listeriosis associated with the consumption of 23 selected categories of ready-to-eat foods, published by the U.S. Department of Health and Human Services and the U.S. Department of Agriculture in 2003, has been instrumental in identifying the food products and practices that pose the greatest listeriosis risk and has guided the evaluation of potential intervention strategies. Dose-response models, which quantify the relationship between an exposure dose and the probability of adverse health outcomes, were essential components of the risk assessment. However, because of data gaps and limitations in the available data and modeling approaches, considerable uncertainty existed. Since publication of the risk assessment, new data have become available for modeling L. monocytogenes dose-response. At the same time, recent advances in the understanding of L. monocytogenes pathophysiology and strain diversity have warranted a critical reevaluation of the published dose-response models. To discuss strategies for modeling L. monocytogenes dose-response, the Interagency Risk Assessment Consortium (IRAC) and the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) held a scientific workshop in 2011 (details available at http://foodrisk.org/irac/events/). The main findings of the workshop and the most current and relevant data identified during the workshop are summarized and presented in the context of L. monocytogenes dose-response. This article also discusses new insights on dose-response modeling for L. monocytogenes and research opportunities to meet future needs.

The prevalence of multidrug resistance is higher among bovine than human Salmonella enterica serotype Newport, Typhimurium, and 4,5,12:i:- isolates in the United States but differs by serotype and geographic region.

Salmonella represents an important zoonotic pathogen worldwide, but the transmission dynamics between humans and animals as well as within animal populations are incompletely understood. We characterized Salmonella isolates from cattle and humans in two geographic regions of the United States, the Pacific Northwest and the Northeast, using three common subtyping methods (pulsed-field gel electrophoresis [PFGE], multilocus variable number of tandem repeat analysis [MLVA], and multilocus sequence typing [MLST]). In addition, we analyzed the distribution of antimicrobial resistance among human and cattle Salmonella isolates from the two study areas and characterized Salmonella persistence on individual dairy farms. For both Salmonella enterica subsp. enterica serotypes Newport and Typhimurium, we found multidrug resistance to be significantly associated with bovine origin of isolates, with the odds of multidrug resistance for Newport isolates from cattle approximately 18 times higher than for Newport isolates from humans. Isolates from the Northwest were significantly more likely to be multidrug resistant than those from the Northeast, and susceptible and resistant isolates appeared to represent distinct Salmonella subtypes. We detected evidence for strain diversification during Salmonella persistence on farms, which included changes in antimicrobial resistance as well as genetic changes manifested in PFGE and MLVA pattern shifts. While discriminatory power was serotype dependent, the combination of PFGE data with either MLVA or resistance typing data consistently allowed for improved subtype discrimination. Our results are consistent with the idea that cattle are an important reservoir of multidrug-resistant Salmonella infections in humans. In addition, the study provides evidence for the value of including antimicrobial resistance data in epidemiological investigations and highlights the benefits and potential problems of combining subtyping methods.

Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.

PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.

Outcomes of high-dose chemotherapy and autologous stem-cell transplantation in stage IIIB inflammatory breast cancer.

PURPOSE: To evaluate the disease-free survival (DFS) and overall survival (OS), prognostic factors, and treatment-related mortality of women with stage IIIB inflammatory breast cancer (IBC) treated with combined modality therapy (CMT) and high-dose chemotherapy (HDCT) with autologous stem-cell transplantation. PATIENTS AND METHODS: Between 1989 and 1997, 47 consecutive patients with stage IIIB IBC were treated with CMT and HDCT and were the subject of this retrospective analysis. Chemotherapy was administered to all patients before and/or after definitive surgery. Neoadjuvant and adjuvant chemotherapy was administered to 33 and 34 patients, respectively, and 20 patients received both. All patients received HDCT with autologous stem-cell transplantation, and 41 patients received locoregional radiation therapy. Tamoxifen was prescribed to patients with estrogen receptor (ER)-positive cancer. RESULTS: The mean duration of follow-up from diagnosis was 30 months (range, 6 to 91 months) and from HDCT was 22 months (range, 0.5 to 82 months). At 30 months, the Kaplan-Meier estimates of DFS and OS from diagnosis were 57.7% and 59.1%, respectively. At 4 years, the Kaplan-Meier estimates of DFS and OS from diagnosis were 51.3% and 51.7%, respectively. In a multivariate analysis, the only factors associated with better survival were favorable response to neoadjuvant chemotherapy (P =.04) and receipt of tamoxifen (P =.06); however, the benefit of tamoxifen was only demonstrated in patients with ER-positive breast cancer. At last follow-up, 28 patients (59. 6%) were alive and disease-free. Seventeen patients (36.2%) developed recurrent breast cancer. Seventeen patients died: 15 from disease recurrence and two (4.2%) from treatment-related mortality due to HDCT. CONCLUSION: In this analysis, the early results of treatment with CMT and HDCT compare favorably with other series of patients with stage IIIB IBC treated with CMT alone. These outcomes must be confirmed with longer follow-up and controlled studies.

Virus inactivation on hard surfaces or in suspension by chemical disinfectants: systematic review and meta-analysis of norovirus surrogates.

Norovirus (NoV) infections are the leading cause of foodborne illness in the United States. Effective disinfection is important for controlling outbreaks caused by this highly infectious virus but can be difficult to achieve because NoV is very resistant to many common disinfection protocols. The inability of human NoV to replicate in tissue culture complicates NoV research, generally necessitating genome copy quantification, the use of surrogate viruses, or the use of other substitutes such as virus-like particles. To date, comprehensive comparisons among NoV surrogates and between surrogates and human NoV are missing, and it is not clear how best to extrapolate information from surrogate data. We conducted a systematic review and meta-analysis of comparisons of NoV surrogates with regard to their susceptibility to disinfection on hard surfaces or in suspension. Restricting our analysis to those studies in which two or more virus surrogates were compared allowed us to improve the signal-to-noise ratio in our analysis, similar to the epidemiological concept of matching. Using meta-analysis methods, our results indicate that hepatitis A virus, murine norovirus 1, and phage MS2 are significantly more resistant to disinfection than is feline calicivirus, but average differences in viral titer reduction appeared to be modest, 1.5 log PFU or less in all cases. None of the studies that compared surrogates and human NoV met our inclusion criteria, precluding a direct comparison between human NoV and NoV surrogates in this study. For all surrogates with sufficient data available to permit subgroup analyses, we detected strong evidence that the type of disinfectant impacted the relative susceptibility of the surrogates. Therefore, extrapolation of results between surrogates or from surrogates to human NoV must consider the type of disinfectant studied.

Antimicrobial drug resistance patterns among cattle- and human-associated Salmonella strains.

During the year 2004, 178 human and 158 bovine clinical Salmonella isolates were collected across New York State to better understand the transmission dynamics and genetic determinants of antimicrobial resistance among human and bovine hosts. Serotyping, sequence typing, and pulsed-field gel electrophoresis typing results have been reported previously. Here we tested all isolates for phenotypic susceptibility to 15 antimicrobial drugs that are part of the National Antimicrobial Monitoring System bovine susceptibility panel. PCR was performed on a representative subset of unique isolates (n = 53) to screen for the presence of 21 known antimicrobial resistance genes (i.e., ampC, blaTEM-1, blaCMY-2, blaPSE-1, cat1, cat2, cmlA, flo, aadA1, aadA2, aacC2, strA, strB, aphA1-IAB, dhrfI, dhrfXII, sulI, sulII, tetA, tetB, and tetG); selected fluoroquinolone- and nalidixic acid-resistant (n = 3) and -sensitive (n = 6) isolates were also tested for known resistance-conferring mutations in gyrA and parC. Genes responsible for antimicrobial resistance were shared among isolates of human and bovine origin. However, bovine isolates were significantly more likely than human isolates to be multidrug resistant (P < 0.0001; Fisher's exact test). Our analyses showed perfect categorical agreement between phenotypic and genotypic resistance for beta-lactam and chloramphenicol. Our data confirm that resistance profiles of amoxicillin-clavulanic acid, chloramphenicol, kanamycin, and tetracycline were strongly associated with the presence of blaCMY or ampC, flo, aphA1-IAB, and tetA, respectively. Our findings provide evidence for the clinical value of genotypic resistance typing if incorporating multiple known genes that can confer a phenotypic resistance profile.

Produce consumption in the United States: an analysis of consumption frequencies, serving sizes, processing forms, and high-consuming population subgroups for microbial risk assessments.

A great variety of fruits and vegetables are available in the United States. These items are produced in various geographic regions by a diverse industry. Produce has been increasingly identified as a vehicle for disease outbreaks. Changes in consumption may explain this increase, but analyses of produce consumption are limited. Comprehensive assessments of the public health risks associated with produce depend on quantitative consumption data, including the population fractions and subgroups of consumers, the quantities consumed by these individuals, and the processing that occurs before consumption. Here, we provide an analysis of nationally representative consumption estimates by estimating consumption frequencies, serving sizes, and processing forms for a variety of produce commodities based on 1999 through 2006 data from "What We Eat in America," the dietary interview component of the National Health and Nutrition Examination Survey performed by the National Center for Health Statistics. Consumption patterns for fresh and heat-treated produce were assessed, compared with U.S. food availability estimates from the U.S. Department of Agriculture Economic Research Service (ERS), and combined with ERS data on temporal trends in food availability and nondomestic produce origins. To identify high-consuming population subgroups, we explored consumer habits and demographic predictors of fresh produce consumption (data available at www.foodrisk.org). Our analysis of common outbreak vehicles revealed limited temporal changes in food availability but frequent consumption as fresh commodities. In addition to providing quantitative consumption estimates for risk assessments, our data clearly show that produce consumption differs among fruits and vegetables, fresh and heat-treated foods, and demographic subgroups. These results are valuable for risk assessments and outbreak investigations and allow targeting of risk communication or interventions to those individuals at greatest risk.

Salmonella Cerro isolated over the past twenty years from various sources in the US represent a single predominant pulsed-field gel electrophoresis type.

Salmonella Cerro prevalence in US dairy cattle has increased significantly during the past decade. Comparison of 237 Salmonella isolates collected from various human and animal sources between 1986 and 2009 using pulsed-field gel electrophoresis, antimicrobial resistance typing, and spvA screening, showed very limited genetic diversity, indicating clonality of this serotype. Improved subtyping methods are clearly needed to analyze the potential emergence of this serotype. Our results thus emphasize the critical importance of population-based pathogen surveillance for the detection and characterization of potentially emerging pathogens, and caution to critically evaluate the adequacy of diagnostic tests for a given study population and diagnostic application.

Vinblastine-associated pulmonary toxicity in patients receiving combination therapy with mitomycin and cisplatin.

Two of 33 patients entered in a local pilot study of mitomycin, vinblastine, and cisplatin for non-small cell lung cancer developed vinblastine-associated pulmonary toxicity. As with other reports of vinca alkaloid-related pulmonary toxicity, the regimen included mitomycin. Based on these cases and others previously reported, the incidence of abrupt pulmonary toxicity following vinca alkaloid administration as part of mitomycin/vinca alkaloid combination appears to be three to six percent. Suggestions for management are given.

Dose-response relationship to dacarbazine demonstrated in a patient with malignant melanoma.

Dacarbazine has shown the most consistent activity of any single chemotherapeutic agent in patients with metastatic melanoma. While the overall rate is 21%, responses fall to less than 10% when hepatic metastases are present. We report a patient with malignant melanoma metastatic to the liver in whom an apparent dose-response relationship to dacarbazine was demonstrated. His liver metastases responded to hepatic artery infusion, progressed with systemic iv therapy, and responded upon reinstitution of hepatic artery infusion.

Phase II trial of trimetrexate for unresectable or metastatic non-small cell bronchogenic carcinoma.

We treated 34 chemotherapy-naive patients with stage IIIb or IV non-small cell lung cancer with trimetrexate 150-200 mg/m2 intravenously over 30 minutes every two weeks. Six of 31 evaluable patients (19%) achieved a partial response. The major toxic effects from this regimen were myelosuppression, nausea/vomiting, and skin rash. We conclude that this well-tolerated schedule of trimetrexate has significant activity as a single agent against non-small cell lung cancer.