A multistate outbreak of Serratia marcescens bloodstream infection associated with contaminated intravenous magnesium sulfate from a compounding pharmacy.

BACKGROUND: In contrast to pharmaceutical manufacturers, compounding pharmacies adhere to different quality-control standards, which may increase the likelihood of undetected outbreaks. In 2005, the Centers for Disease Control and Prevention received reports of cases of Serratia marcescens bloodstream infection occurring in patients who underwent cardiac surgical procedures in Los Angeles, California, and in New Jersey. An investigation was initiated to determine whether there was a common underlying cause. METHODS: A matched case-control study was conducted in Los Angeles. Case record review and environmental testing were conducted in New Jersey. The Centers for Disease Control and Prevention performed a multistate case-finding investigation; isolates were compared using pulsed-field gel electrophoresis analysis. RESULTS: Nationally distributed magnesium sulfate solution (MgSO(4)) from compounding pharmacy X was the only significant risk factor for S. marcescens bloodstream infection (odds ratio, 6.4; 95% confidence interval, 1.1-38.3) among 6 Los Angeles case patients and 18 control subjects. Five New Jersey case patients received MgSO(4) from a single lot produced by compounding pharmacy X; culture of samples from open and unopened 50-mL bags in this lot yielded S. marcescens. Seven additional case patients from 3 different states were identified. Isolates from all 18 case patients and from samples of MgSO(4) demonstrated indistinguishable pulsed-field gel electrophoresis patterns. Compounding pharmacy X voluntarily recalled the product. Neither the pharmacy nor the US Food and Drug Administration could identify a source of contamination in their investigations of compounding pharmacy X. CONCLUSIONS: A multistate outbreak of S. marcescens bloodstream infection was linked to contaminated MgSO(4) distributed nationally by a compounding pharmacy. Health care personnel should take into account the different quality standards and regulation of compounded parenteral medications distributed in large quantities during investigations of outbreaks of bloodstream infection.

Survey of state practices during the 2004-2005 influenza vaccine shortage.

To describe state-level actions and policies during the 2004-2005 influenza vaccine shortage and determine whether these or other factors were related to vaccination coverage, we surveyed all state health departments (including the District of Columbia). We included 2004-2005 Behavioral Risk Factor Surveillance System data to examine whether state-level actions, policies, or other factors like vaccine supply were related to changes in vaccination coverage in adults aged > or = 65 years from the previous non-shortage year. We found that 96% (n = 49) of states reported adopting or recommending adherence to the initial national interim influenza vaccination recommendations. Of these, at some point during the season, 22% (n = 11) reported local public health agencies issued prioritization recommendations that differed from the state health department's guidance. Eighty percent (n = 41) initiated at least one emergency response activity and 43% (n = 22) referred to or implemented components of their pandemic influenza plans. In 35% (n = 18), emergency or executive orders were issued or legislative action occurred. In a multivariable linear regression model, the availability and use of practitioner contact lists and having a relatively high vaccine supply in early October 2004 were associated with smaller decreases in coverage for adults aged > or = 65 years from the previous non-shortage season (p = 0.003, r2 = 0.26). States over-whelmingly followed national vaccination prioritization guidelines and used a range of activities to manage the 2004-2005 vaccine shortage. The availability and use of practitioner contact lists and having a relatively high vaccine supply early in the season were associated with smaller decreases in coverage from the previous non-shortage season.

Botulism in 4 adults following cosmetic injections with an unlicensed, highly concentrated botulinum preparation.

CONTEXT: Botulism is a potentially lethal paralytic disease caused primarily by toxins of the anaerobic, spore-forming bacterium Clostridium botulinum. Although botulinum toxin A is available by prescription for cosmetic and therapeutic use, no cases of botulism with detectable serum toxin have previously been attributed to cosmetic or therapeutic botulinum toxin injections. On November 27, 2004, 4 suspected botulism case-patients with a link to cosmetic botulinum toxin injections were reported to the Centers for Disease Control and Prevention. OBJECTIVE: To investigate the clinical, epidemiological, and laboratory aspects of 4 suspected cases of iatrogenic botulism. DESIGN, SETTING, AND PATIENTS: Case series on 4 botulism case-patients. MAIN OUTCOME MEASURES: Clinical characteristics of the 4 case-patients, epidemiological associations, and mouse bioassay neutralization test results from case-patient specimens and a toxin sample. RESULTS: Clinical characteristics of the 4 case-patients were consistent with those of naturally occurring botulism. All case-patients had been injected with a highly concentrated, unlicensed preparation of botulinum toxin A and may have received doses 2857 times the estimated human lethal dose by injection. Pretreatment serum toxin levels in 3 of the 4 case-patients were equivalent to 21 to 43 times the estimated human lethal dose; pretreatment serum from the fourth epidemiologically linked case-patient was not available. A 100-microg vial of toxin taken from the same manufacturer's lot as toxin administered to the case-patients contained a toxin amount sufficient to kill approximately 14,286 adults by injection if disseminated evenly. CONCLUSIONS: These laboratory-confirmed cases of botulism demonstrate that clinical use of unlicensed botulinum toxin A can result in severe, life-threatening illness. Further education and regulation are needed to prevent the inappropriate marketing, sale, and clinical use of unlicensed botulinum toxin products.

Pulmonary and psychosocial findings at enrollment in the ACCESS study.

AIM: To assess lung involvement and the association of demographic and psychosocial factors with respiratory health in 736 persons with sarcoidosis at enrollment in A Case Control Etiologic Study of Sarcoidosis (ACCESS). METHODS: 736 patients with biopsy diagnosis of sarcoidosis within 6 months of enrollment were studied at 10 US centers. Lung involvement was evaluated by chest radiography, spirometry and dyspnea questionnaire. Demographics, number of involved extrathoracic organ systems, comorbidities, and health-related quality of life (HRQL) were assessed. RESULTS: 95% of patients had lung involvement. 8% were Scadding Stage 0, 40% I, 37% II, 10% III, and 5% IV 51% reported dyspnea. Increasing radiographic lung stage was associated with decreasing Forced Vital Capacity (FVC) (p < 0.01). Patients with higher stages had more airways obstruction and dyspnea. 46% of cases and 27% of controls had Center for Epidemiologic Studies Depression Scale (CES-D) scores of 9 or greater, (p < 0.001). Age > or = 40, African-American race, body mass index > or = 30kg/m2, and CES-D scores > 9 were associated with decreased FVC and greater dyspnea. Impaired spirometry and greater dyspnea were associated with poorer quality of life. CONCLUSION: A "global" approach to the sarcoidosis patient, including careful assessment of dyspnea and health related quality of life, as well as of lung function and radiographic changes, and any extrathoracic involvement, is important, not only in management of the individual patient, but should also prove beneficial in assessing outcomes in clinical trials in the future.

A preventable outbreak of pneumococcal pneumonia among unvaccinated nursing home residents in New Jersey during 2001.

OBJECTIVE: To characterize risk factors for invasive pneumococcal infection in a nursing home outbreak. DESIGN: Outbreak investigation, case-control study. SETTING: A 114-bed nursing home in New Jersey. PARTICIPANTS: Case-patients were nursing home residents hospitalized with febrile respiratory illness and radiographic findings consistent with pneumonia, and either sputum specimens positive for diplococci or blood cultures positive for Streptococcus pneumoniae, with illness onset during April 3-24, 2001. Control-patients were selected randomly from remaining residents without respiratory symptoms. METHODS: Chart reviews were performed for case-patients and control-patients. Serotyping and susceptibility testing were performed on S. pneumoniae isolates. Long-term-care facilities (LTCFs) were surveyed to assess compliance with a state regulation mandating pneumococcal vaccination of residents 65 years and older. RESULTS: Nine case-patients were identified, with a median age of 86 years (range, 78 to 100 years). The median age of control-patients was 86 years (range, 58 to 95 years). No case-patients versus 9 (50%) control-patients received pneumococcal vaccine before the outbreak (OR, 0; CI95, 0-0.7). Recent antibiotic use, pneumonia history, and physical functioning were not associated with illness. Illness attack rate was 16% among all unvaccinated residents versus 0 among vaccinated residents. S. pneumoniae serotype 14, included in pneumococcal vaccine, was isolated from blood cultures of 7 case-patients. Of 361 LTCFs (42%) that replied to the survey, 28 (8%) were not complying with state immunization regulations. CONCLUSIONS: This outbreak occurred in an LTCF with low vaccine coverage. Implementing standing order programs, enforcing regulations, documenting vaccinations, and providing education might increase coverage among nursing home residents.

Two year prognosis of sarcoidosis: the ACCESS experience.

A cohort of 215 sarcoidosis patients from the ACCESS study underwent a clinical evaluation at study enrollment and two years later. Approximately 80% of subjects had an improved or stable FVC, FEV1, chest radiograph determined by Scadding stage, and dyspnea scale. African-Americans had less improvement in FVC than Caucasians (p = 0.04). Patients with erythema nodosum at presentation were more likely to have improvement in the chest radiograph at two-year follow-up (p = 0.007). Patients with a lower annual family income were more likely to worsen with respect to dyspnea (p = 0.01) and more likely to have new organ involvement at two-year follow-up (p = 0.045). The development of new organ involvement over the two year follow-up period was more common in African-Americans compared to Caucasians (p = 0.002) and more likely in those with extrapulmonary involvement at study entry (p = 0.003). There was an excellent concordance between changes in FVC and FEV1 over the two-year period. However, changes in FVC alone were inadequate to describe the change in pulmonary status of the patients, as changes in chest radiographic findings or the level of dyspnea did often but not always move in the same direction as FVC. In conclusion, data from this heterogeneous United States sarcoidosis population indicate that sarcoidosis tends to improve or remain stable over two years in the majority of patients. Several factors associated with improved or worse outcome over two years were identified.

One-year health assessment of adult survivors of Bacillus anthracis infection.

CONTEXT: Little is known about potential long-term health effects of bioterrorism-related Bacillus anthracis infection. OBJECTIVE: To describe the relationship between anthrax infection and persistent somatic symptoms among adults surviving bioterrorism-related anthrax disease approximately 1 year after illness onset in 2001. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of 15 of 16 adult survivors from September through December 2002 using a clinical interview, a medical review-of-system questionnaire, 2 standardized self-administered questionnaires, and a review of available medical records. MAIN OUTCOME MEASURES: Health complaints summarized by the body system affected and by symptom categories; psychological distress measured by the Revised 90-Item Symptom Checklist; and health-related quality-of-life indices by the Medical Outcomes Study 36-Item Short-Form Health Survey (version 2). RESULTS: The anthrax survivors reported symptoms affecting multiple body systems, significantly greater overall psychological distress (P<.001), and significantly reduced health-related quality-of-life indices compared with US referent populations. Eight survivors (53%) had not returned to work since their infection. Comparing disease manifestations, inhalational survivors reported significantly lower overall physical health than cutaneous survivors (mean scores, 30 vs 41; P =.02). Available medical records could not explain the persisting health complaints. CONCLUSION: The anthrax survivors continued to report significant health problems and poor life adjustment 1 year after onset of bioterrorism-related anthrax disease.

Communicable-disease surveillance in New Jersey.

The DHSS and federal agencies have expanded their surveillance efforts to improve existing methods of reporting notifiable communicable diseases and to include additional data sources that might provide a more comprehensive view of disease activity in New Jersey. Currently, the DHSS is evaluating these efforts and recognizes several issues that need to be addressed, including: assessment of the timeliness, completeness, and accuracy of surveillance data; validation of surveillance data through comparison with hospital uniform billing data; characterization of the sensitivity of alerts through examination of reasons for identified aberrations in disease activity; evaluation of DHSS staffs and LINCS epidemiologists' follow-up efforts in response to alerts; evaluation of cumulative data trends to determine patterns in baseline disease activity (e.g., variations in disease activity attributed to seasonality); development of methods to integrate data from all surveillance efforts to provide timely, comprehensive, and coordinated summaries of disease activity and to distribute these summaries regularly to all New Jersey public health partners to better inform public health and clinical management; and development of a coordinated multi-agency response plan in conjunction with adjacent states. Though the DHSS hopes that these surveillance efforts will contribute to the early detection of sentinel events that might represent possible bioterrorist or emerging infectious disease threats, the DHSS will also need to engage the medical community more fully in surveillance activities. In previous experiences, astute clinicians were responsible for the identification of the first cases of West Nile virus, anthrax, and SARS. Therefore, to further ensure the success of its surveillance efforts, the DHSS will also need to continue educating clinicians about its surveillance activities and the importance of timely reporting of patients with illness patterns that might suggest an unusual infectious disease outbreak associated with bioterrorism or emerging infectious diseases.

New Jersey's smallpox vaccination clinic experiences, 2003.

PURPOSE: During 2003, the New Jersey Department of Health and Senior Services, in collaboration with other agencies, began planning and implementing voluntary smallpox vaccination clinics. METHODS: Surveys were distributed to all vaccinees, hospital bioterrorism coordinators, and local health departments to assess clinic experiences. RESULTS: During January-July 2003, 23 clinics were conducted with more than 1,000 participants. Of 670 persons vaccinated, 529 (79%) completed surveys. We received 65 surveys from 68 (77%) of 84 hospitals, and 25 responses from 22 regional health agencies. CONCLUSIONS: Vaccination is one component of preparedness; future initiatives must incorporate multiagency collaboration and developing public health infrastructure.

Responding to a bioterrorist attack: environmental investigation of anthrax in New Jersey.

A bioterrorism attack using the United States postal system to deliver a hazardous biological agent to specific targets created multiple environmental and occupational exposure risks along the path of the anthrax-containing letters. On October 18, 2001, a suspected case of cutaneous anthrax was confirmed in a postal worker from the Trenton Processing and Distribution Center where at least four suspect letters were postmarked. Over the next three weeks, a team of investigators collected samples at 57 workplaces in New Jersey as part of a comprehensive environmental investigation to assess anthrax contamination as a result of this bioterrorist attack. A total of 1369 samples were collected with positive sample results found in two mail processing and distribution centers, six municipal post offices, and one private company. This large-scale epidemiological and public health investigation conducted by state and federal agencies included environmental evaluations utilizing general industrial hygiene principles. Issues of sampling strategy, methods, agency cooperation and communication, and site assessment coordination are discussed.

Surveillance for anthrax cases associated with contaminated letters, New Jersey, Delaware, and Pennsylvania, 2001.

In October 2001, two inhalational anthrax and four cutaneous anthrax cases, resulting from the processing of Bacillus anthracis-containing envelopes at a New Jersey mail facility, were identified. Subsequently, we initiated stimulated passive hospital-based and enhanced passive surveillance for anthrax-compatible syndromes. From October 24 to December 17, 2001, hospitals reported 240,160 visits and 7,109 intensive-care unit admissions in the surveillance area (population 6.7 million persons). Following a change of reporting criteria on November 8, the average of possible inhalational anthrax reports decreased 83% from 18 to 3 per day; the proportion of reports requiring follow-up increased from 37% (105/286) to 41% (47/116). Clinical follow-up was conducted on 214 of 464 possible inhalational anthrax patients and 98 possible cutaneous anthrax patients; 49 had additional laboratory testing. No additional cases were identified. To verify the limited scope of the outbreak, surveillance was essential, though labor-intensive. The flexibility of the system allowed interim evaluation, thus improving surveillance efficiency.

Multidrug-resistant Salmonella Typhimurium infection from milk contaminated after pasteurization.

An outbreak of multidrug-resistant Salmonella enterica serotype Typhimurium infections occurred in Pennsylvania and New Jersey. A case-control study implicated pasteurized milk from a dairy, and an inspection indicated the potential for contamination after pasteurization. Dairy cattle are the likely reservoir, and milk may be an important vehicle of Salmonella transmission to humans.

A case control etiologic study of sarcoidosis: environmental and occupational risk factors.

Past research suggests that environmental factors may be associated with sarcoidosis risk. We conducted a case control study to test a priori hypotheses that environmental and occupational exposures are associated with sarcoidosis. Ten centers recruited 706 newly diagnosed patients with sarcoidosis and an equal number of age-, race-, and sex-matched control subjects. Interviewers administered questionnaires containing questions regarding occupational and nonoccupational exposures that we assessed in univariable and multivariable analyses. We observed positive associations between sarcoidosis and specific occupations (e.g., agricultural employment, odds ratio [OR] 1.46, confidence interval [CI] 1.13-1.89), exposures (e.g., insecticides at work, OR 1.52, CI 1.14-2.04, and work environments with mold/mildew exposures [environments with possible exposures to microbial bioaerosols], OR 1.61, CI 1.13-2.31). A history of ever smoking cigarettes was less frequent among cases than control subjects (OR 0.62, CI 0.50-0.77). In multivariable modeling, we observed elevated ORs for work in areas with musty odors (OR 1.62, CI 1.24-2.11) and with occupational exposure to insecticides (OR 1.61, CI 1.13-2.28), and a decreased OR related to ever smoking cigarettes (OR 0.65, CI 0.51-0.82). The study did not identify a single, predominant cause of sarcoidosis. We identified several exposures associated with sarcoidosis risk, including insecticides, agricultural employment, and microbial bioaerosols.