Quantity and size distribution of cough-generated aerosol particles produced by influenza patients during and after illness.

The question of whether influenza is transmitted to a significant degree by aerosols remains controversial, in part, because little is known about the quantity and size of potentially infectious airborne particles produced by people with influenza. In this study, the size and amount of aerosol particles produced by nine subjects during coughing were measured while they had influenza and after they had recovered, using a laser aerosol particle spectrometer with a size range of 0.35 to 10 µm. Individuals with influenza produce a significantly greater volume of aerosol when ill compared with afterward (p = 0.0143). When the patients had influenza, their average cough aerosol volume was 38.3 picoliters (pL) of particles per cough (SD 43.7); after patients recovered, the average volume was 26.4 pL per cough (SD 45.6). The number of particles produced per cough was also higher when subjects had influenza (average 75,400 particles/cough, SD 97,300) compared with afterward (average 52,200, SD 98,600), although the difference did not reach statistical significance (p = 0.1042). The average number of particles expelled per cough varied widely from patient to patient, ranging from 900 to 302,200 particles/cough while subjects had influenza and 1100 to 308,600 particles/cough after recovery. When the subjects had influenza, an average of 63% of each subject's cough aerosol particle volume in the detection range was in the respirable size fraction (SD 22%), indicating that these particles could reach the alveolar region of the lungs if inhaled by another person. This enhancement in aerosol generation during illness may play an important role in influenza transmission and suggests that a better understanding of this phenomenon is needed to predict the production and dissemination of influenza-laden aerosols by people infected with this virus. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a PDF file of demographic information, influenza test results, and volume and peak flow rate during each cough and a PDF file containing number and size of aerosol particles produced.].

Nontuberculous mycobacterial cutaneous infections: an updated review.

Nontuberculous mycobacteria (NTM) cause cutaneous infections more commonly than Mycobacterium tuberculosis, and the incidence of infection with these organisms is increasing with the use of immunosuppressive agents. Diagnosis of NTM cutaneous infections is not always straightforward. Therefore, a high index of clinical suspicion is needed to make a diagnosis of NTM cutaneous infection.

Distribution of airborne influenza virus and respiratory syncytial virus in an urgent care medical clinic.

BACKGROUND: Considerable controversy exists with regard to whether influenza virus and respiratory syncytial virus (RSV) are spread by the inhalation of infectious airborne particles and about the importance of this route, compared with droplet or contact transmission. METHODS: Airborne particles were collected in an urgent care clinic with use of stationary and personal aerosol samplers. The amounts of airborne influenza A, influenza B, and RSV RNA were determined using real-time quantitative polymerase chain reaction. Health care workers and patients participating in the study were tested for influenza. RESULTS: Seventeen percent of the stationary samplers contained influenza A RNA, 1% contained influenza B RNA, and 32% contained RSV RNA. Nineteen percent of the personal samplers contained influenza A RNA, none contained influenza B RNA, and 38% contained RSV RNA. The number of samplers containing influenza RNA correlated well with the number and location of patients with influenza (r= 0.77). Forty-two percent of the influenza A RNA was in particles < or = 4.1 microm in aerodynamic diameter, and 9% of the RSV RNA was in particles < or = 4.1 microm. CONCLUSIONS: Airborne particles containing influenza and RSV RNA were detected throughout a health care facility. The particles were small enough to remain airborne for an extended time and to be inhaled deeply into the respiratory tract. These results support the possibility that influenza and RSV can be transmitted by the airborne route and suggest that further investigation of the potential of these particles to transmit infection is warranted.

Measurement of airborne influenza virus in a hospital emergency department.

Size-fractionated aerosol particles were collected in a hospital emergency department to test for airborne influenza virus. Using real-time polymerase chain reaction, we confirmed the presence of airborne influenza virus and found that 53% of detectable influenza virus particles were within the respirable aerosol fraction. Our results provide evidence that influenza virus may spread through the airborne route.

Candida endophthalmitis: focus on current and future antifungal treatment options.

Candida endophthalmitis is a sight-threatening manifestation of disseminated candidiasis. The occurrence of endogenous candida endophthalmitis in patients with candidemia has ranged from 0-45% in the published literature. In critically ill patients, it has even been associated with increased mortality. In recent years, use of newer antifungal therapies for invasive candidiasis has increased given the rise in infections with non-albicans species of Candida. To identify current practices of the management of endogenous candida endophthalmitis and relevant antifungal drug research in this disease state, we conducted a MEDLINE search (1967-2006) and bibliographic search of the English-language literature. Treatments for candida endophthalmitis have not been evaluated through well-designed, well-powered clinical trials. Data have mainly been presented in case reports, case series, animal studies, pharmacokinetic studies, and as small subsets of larger trials. Traditional systemic therapies have been amphotericin B with or without flucytosine or fluconazole. Cure rates with antifungal drugs alone appear to be much higher in patients with chorioretinitis than in endophthalmitis with vitreal involvement. Pars plana vitrectomy with or without intravitreal amphotericin B injections has been advocated particularly for patients with moderate-to-severe vitritis and substantial vision loss. Information on new antifungal agents for endophthalmitis is limited, despite increasing use in patients with candidemia. Voriconazole may be a particularly attractive agent to consider for infections with fluconazole-resistant, voriconazole-susceptible strains. The current patchwork of animal studies and small patient reports provide clinicians with some insight into the role of newer agents in the treatment of candida endophthalmitis. In general, it appears that chorioretinitis infections can be more readily cured with most systemic antifungal agents, whereas more aggressive treatment, often including vitrectomy with or without intra-vitreal antifungal administration, is needed for patients with endophthalmitis with vitritis.

Association of hemochromatosis with infectious diseases: expanding spectrum.

Withholding iron from potential pathogens is a host defense strategy. There is evidence that iron overload per se compromises the ability of phagocytes to kill microorganisms. Several hypotheses exist to explain the association of hemochromatosis with infection. A combination of mechanisms likely contributes to the increase in susceptibility to infection in these patients. A review of the current literature delineating various pathogens to which patients with hemochromatosis are potentially susceptible, and recent advances in the understanding of the association of hemochromatosis with infection, are discussed.

Use of a patient empowerment tool for hand hygiene.

BACKGROUND: Patient empowerment is recognized as an important component of a multimodal strategy to improve hand hygiene adherence. We examined the attitudes of adult patients and parents of pediatric patients toward a new patient empowerment tool (PET) at our hospital. We also surveyed physicians to determine their perceptions about the PET. METHODS: A cross-sectional survey was performed of hospitalized children's parents and adult patients in a 531-bed tertiary care teaching hospital in West Virginia. Surveys were anonymous and self-administered. A separate survey was administered via e-mail to resident and attending physicians from the departments of internal medicine, pediatrics, and family medicine. RESULTS: Most parents and adult patients felt it was their role to speak up if a provider did not perform hand hygiene, but a smaller number actually felt comfortable using the PET. Only 54.9% of physicians felt that patients should be involved in reminding providers to perform hand hygiene. Overall, physicians indicated that they would prefer a patient to use words rather than the PET to remind them to perform hand hygiene. CONCLUSIONS: In our study, parents and adult patients supported use of the PET, but physicians were less supportive. As the patient empowerment movement grows, we should work to improve physician acceptance of patient involvement if it is to be successful.

Multidisciplinary performance improvement team for reducing health care-associated Clostridium difficile infection.

Clostridium difficile is the most frequent cause of health care-associated diarrhea and is a significant cause of morbidity and mortality. It is also associated with a considerable financial burden. A concerted multidisciplinary approach is required for prevention.

Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers.

STUDY OBJECTIVE: To determine whether daily high-dose vitamin C alters the steady-state pharmacokinetics of indinavir, a protease inhibitor indicated for treatment of the human immunodeficiency virus type 1. DESIGN: Prospective, open-label, longitudinal, two-period time series. SETTING: University medical center. SUBJECTS: Seven healthy volunteers. INTERVENTION: Indinavir 800 mg every 8 hours was given to subjects for four doses on days 1 and 2. Plasma samples were then collected for indinavir pharmacokinetic determination. After a 7-day washout period, subjects were given vitamin C 1000 mg/day for 7 days. Beginning on day 6 of vitamin C administration, indinavir 800 mg every 8 hours was restarted for four doses. Plasma was then collected from subjects to determine indinavir pharmacokinetics. All subjects were given a vitamin C content-controlled diet for 1 week before the study began and throughout the study period. MEASUREMENTS AND MAIN RESULTS: Steady-state plasma samples were collected before dosing (0 hr) and 0.5, 1, 2, 3, 4, and 5 hours after dosing to determine indinavir pharmacokinetics. Parameters of interest were maximum plasma concentration (C max ), time to C max , area under the plasma concentration-time curve from 0-5 hours after the dose (AUC 0-5 ), an extrapolated 8-hour AUC (AUC 0-8 ), trough (minimum) plasma concentration (C min ), and oral clearance. Mean steady-state indinavir C max was significantly reduced (20%) after 7 days of vitamin C administration (10.3 +/- 1.5 vs 8.2 +/- 2.9 microg/ml, p=0.04). The corresponding mean AUC 0-8 was also significantly decreased (14%; 26.4 +/- 7.2 vs 22.7 +/- 8.1 microg*hr/ml, p=0.05). Although not statistically significant, the mean indinavir C min was 32% lower in the presence of vitamin C (0.27 +/- 0.17 C vs 0.18 +/- 0.08 microg/ml, p=0.09). Indinavir oral clearance and half-life were not significantly different. CONCLUSION: Concomitant administration of high doses of vitamin C can reduce steady-state indinavir plasma concentrations. Subtherapeutic concentrations of antiretroviral agents have been associated with viral resistance and regimen failure, but the clinical significance of our findings remains to be established.

Comparison of immune response to the influenza vaccine in obese and nonobese healthcare workers.

OBJECTIVE: To determine whether there is a difference in antibody titers and functionality after receipt of the influenza vaccine for obese versus nonobese healthcare workers (HCW). DESIGN: Prospective observational study. SETTING: Tertiary medical center. PARTICIPANTS: Healthcare workers. METHODS Baseline influenza antibody titers for obese and nonobese HCW were recorded during the hospital's 2011 annual influenza vaccination day and follow-up antibody titers were measured 4 weeks later. Antibodies were measured using the hemagglutination inhibition assay and functionality was measured using the micro-neutralization method. RESULTS: Of 200 initial HCWs, 190 completed the study (97 obese and 93 nonobese). Seroprotection after immunization was not significantly different for nonobese compared with obese HCW for each strain (influenza A [H1N1], 99% and 99%; influenza A [H3N2], 100% and 99%; and influenza B, 67% and 71%, respectively) All geometric mean titers measured by micro-neutralization showed statistically significant increases in activity. In comparison, there was no difference in the 4-fold increase in H1N1 or B titers. There was a significant difference in the 4-fold increase of H3N2 titers between the nonobese and obese HCWs (82/93 [88%] vs 64/97 [66%], P=.003) In an ad hoc analysis we found that obese HCWs had a statistically greater number of 4-fold decreases in titers with H1N1 and H3N2. CONCLUSIONS: There was no significant difference in protection from influenza between obese and nonobese HCWs after immunization.

Infrequent occurrence of amphotericin B lipid complex-associated nephrotoxicity in various clinical settings at a university hospital: a retrospective study.

BACKGROUND: Lipid-based formulations of amphotericin B (AMB) have been shown to significantly lessen the occurrence of nephrotoxicity associated with the conventional form of AMB. A MEDLINE search of literature published from 1983 to 2002, using the search terms amphotericin B and nephrotoxicity, identified only 1 large, randomized, prospective trial that has tried to compare the nephrotoxicity rates among lipid-based AMB formulations. Using the nephrotoxicity surrogate marker of doubling of serum creatinine (SCr) level, the investigators reported a high rate of AMB lipid complex (ABLC)-associated nephrotoxicity (42.3%). However, enrollment in that study was limited to only febrile neutropenic patients. OBJECTIVE: This retrospective study estimated the rate of ABLC-associated nephrotoxicity in various clinical settings at a university hospital and compared that rate with previously reported rates of nephrotoxicity. METHODS: Data from adult neutropenic and nonneutropenic patients receiving ABLC were collected and the degree of nephrotoxicity was determined using 2 definitions: (1) doubling of baseline SCr level using the peak value within the first 7 days, and (2) end-of-therapy doubling of baseline SCr level using the end-of-therapy value. RESULTS: Data from 33 patients (20 men, 13 women; mean age, 48.6 years) were collected. Using these definitions of ABLC-associated nephrotoxicity, only 2 cases (6.1%) were observed. This rate was significantly below the 42.3% rate reported in the only large published study (95% CI, 1.7-19.6; P < 0.001). The median change in SCr level was 0.1 mg/dL (range, -1.1 to 4.3 mg/dL). Rates of change were higher in patients who died during hospitalization, but the difference was not significant. Use of concomitant nephrotoxic agents did not account for significant changes in SCr level. CONCLUSIONS: Data from this study suggest that ABLC infrequently causes clinically significant nephrotoxicity. Therefore, when formulary decisions are made in the selection of a drug for use in various clinical settings, earlier data derived from a single study in febrile neutropenic patients that suggested a significantly higher rate of nephrotoxicity should be interpreted cautiously. Larger trials with more diverse patient populations are needed to better characterize institutional rates of ABLC-associated nephrotoxicity and to aid formulary decision makers.

Computerized antimicrobial decision support: an offline evaluation of a database-driven empiric antimicrobial guidance program in hospitalized patients with a bloodstream infection.

INTRODUCTION: We developed a computerized antimicrobial guidance program based on the last 5 years of our laboratory culture data augmented by expert infectious disease logic. The program is designed to assist physicians with the targeting of empiric antimicrobials for hospitalized patients by tracking pathogenic bacteria and their evolving antimicrobial resistance profiles. Costs, toxicities, and environmental impact of antimicrobial use also influence the final recommendations. We undertook the following analysis to verify its potential safety and efficacy in hospitalized patients with a bloodstream infection. METHODS: We retrospectively enrolled all inpatients with a positive blood culture for a previously undetermined pathogen during the first 6 months of 2002 and determined the empiric therapy initiated within the 12h before and after the time of culture. Antimicrobial recommendations from the microbiologic decision support tool were then determined by matching specimen (blood), hospital unit, community- versus hospital-acquired category, age category, and gender. Generated antimicrobial recommendations were tailored to patient allergies, age category, and presence of pregnancy, lactation, or hepatic impairment. RESULTS: The microbiology laboratory recorded 226 unique patient/pathogen blood cultures during the study period. Physicians initiated effective empiric therapy in 150 of the 226 cases, for an effectiveness rate of 66%. The computer-guided therapy was effective in 195 of the 226 cases for a rate of 86%. A contingency table analysis showed 55 cases where the computer recommendation was effective but the physicians' selection was not, and eight cases where the physicians' antimicrobials were effective but the computer's were not (P < 0.0001). DISCUSSION: For patients with a bloodstream infection, we found that our computer-guided statistically-derived antimicrobial therapy would potentially improve the rate of effectiveness of empirically chosen antimicrobials.

Knowledge and attitudes of visitors to patients in contact isolation.

In this study, conducted at a tertiary care center, we surveyed visitors to patients in contact isolation to assess their knowledge and attitudes about contact isolation. Although response rates were low, we found that visitors had an overall positive perception and understanding of contact isolation. We think this is likely attributable to the communication and education provided by health care providers to the visitors.

Left knee prosthesis-related Mycobacterium goodii infection.

Non-tuberculous mycobacteria are increasingly being recognized as important human pathogens. We present the case of a 44-year-old non-diabetic male who underwent left total knee arthroplasty for degenerative arthritis after trauma. He developed left knee swelling and progressively worsening pain over the next 4 weeks. He was referred for treatment using whirlpool baths and developed a blister at the surgical incision site. Repeated aspirations of the left knee failed to show any growth of organism on routine cultures. He finally underwent explantation of the left knee prosthesis with antimicrobial spacer placement 4 months later. Cultures of three different intra-operative specimens turned positive for Mycobacterium goodii. This infection was successfully treated with combination oral antimicrobials for 6 months. The patient underwent revision left knee arthroplasty subsequently and was symptom-free until his last follow-up visit 1 year later. This patient highlights the importance of testing for mycobacteria in prosthesis-related infections with previously negative routine bacterial cultures.

Measurements of airborne influenza virus in aerosol particles from human coughs.

Influenza is thought to be communicated from person to person by multiple pathways. However, the relative importance of different routes of influenza transmission is unclear. To better understand the potential for the airborne spread of influenza, we measured the amount and size of aerosol particles containing influenza virus that were produced by coughing. Subjects were recruited from patients presenting at a student health clinic with influenza-like symptoms. Nasopharyngeal swabs were collected from the volunteers and they were asked to cough three times into a spirometer. After each cough, the cough-generated aerosol was collected using a NIOSH two-stage bioaerosol cyclone sampler or an SKC BioSampler. The amount of influenza viral RNA contained in the samplers was analyzed using quantitative real-time reverse-transcription PCR (qPCR) targeting the matrix gene M1. For half of the subjects, viral plaque assays were performed on the nasopharyngeal swabs and cough aerosol samples to determine if viable virus was present. Fifty-eight subjects were tested, of whom 47 were positive for influenza virus by qPCR. Influenza viral RNA was detected in coughs from 38 of these subjects (81%). Thirty-five percent of the influenza RNA was contained in particles>4 µm in aerodynamic diameter, while 23% was in particles 1 to 4 µm and 42% in particles<1 µm. Viable influenza virus was detected in the cough aerosols from 2 of 21 subjects with influenza. These results show that coughing by influenza patients emits aerosol particles containing influenza virus and that much of the viral RNA is contained within particles in the respirable size range. The results support the idea that the airborne route may be a pathway for influenza transmission, especially in the immediate vicinity of an influenza patient. Further research is needed on the viability of airborne influenza viruses and the risk of transmission.

Prospective comparison of tuberculin skin test and QuantiFERON-TB Gold In-Tube assay for the detection of latent tuberculosis infection among healthcare workers in a low-incidence setting.

We compared the results of the tuberculin skin test with the results of the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay among 182 low-risk healthcare workers. Overall agreement and specificity were high, but the tests did not agree on positive results. Only 2 of 5 positive QFT-GIT assay results could be confirmed with repeat analyses. Indeterminate results were associated with potential immunosuppression.

Hand hygiene practices in adult versus pediatric intensive care units at a university hospital before and after intervention.

Observations of hand hygiene practices of the health care workers (HCWs) were carried out at a tertiary care center by a single observer in all adult and pediatric intensive care units (ICUs) before and after educational programs. Access to alcohol-based hand rub was also increased. A survey of HCWs was carried out to determine knowledge of hand hygiene. Before interventions, mean adherence to hand hygiene in all ICUs was 54% with significant difference between adult and pediatric ICUs (p<.0001) (35% vs 90%, respectively). Traditional handwashing versus alcohol-based hand rub use was 72% versus 28%, respectively. Following the interventions, there was a significant increase (p<.0001) in hand hygiene adherence in adult ICUs (81%). 46% of survey respondents believed that alcohol-based hand rub could not be used for methicillin resistant Staphylococcus aureus infection and 21% believed that alcohol-based hand rub could be used if hands were soiled. Overall, adherence to hand hygiene in adult ICUs improved with institution of an educational program and increase in accessibility of alcohol-based hand rub. There was a statistically significant increase in the frequency of alcohol-based hand rub use; however, traditional handwashing was still preferred. The survey of HCWs revealed gaps in knowledge regarding methods of hand hygiene.

An assessment of influenza vaccination among health profession students.

Health profession students work in close proximity to patients and could be a source of nosocomial influenza. We studied the proportion of health profession students presenting for immunization at an influenza immunization campaign. This assessment is useful to guide future campaigns as we prepare for pandemic influenza.