Susan T. Cookson

Prospective Evaluation of Risk Factors for Bloodstream Infection in Patients Receiving Home Infusion Therapy

Expenditures are growing rapidly for health care delivered in the home (1, 2), which often includes intravenous therapy. Although intravenous infusion may cause bloodstream infection, few prospective studies have assessed the risk for this infection in the home setting. Needleless infusion devices have been introduced in the hospital and home settings as a way to prevent needlestick injuries. These devices connect the catheter with the infusion tubing, allowing fluids to be administered without the use of a needle. Several investigations among patients receiving home infusion therapy from 1993 to 1995 showed an association between bloodstream infection and needleless devices under certain circumstances (3-7). The investigations were limited: They were retrospective, and some data were not available. We report results of a prospective study of bloodstream infection among patients receiving home infusion therapy. We sought to determine rates of and risk factors for bloodstream infection and to evaluate the importance of needleless devices and other risk factors identified in the investigations cited above. Methods Patients Patients were enrolled at two study sites, one in Toronto, Ontario, Canada, and one in Cleveland, Ohio. The study protocol was approved by the institutional review boards at the Centers for Disease Control and Prevention and at all institutions involved at the two study sites. At the Toronto site, eligible patients included all patients referred to one of five home infusion agencies (which provide approximately 90% of infusion therapy in this region) from any Toronto-area hospital, patients in the Toronto Hospital total parenteral nutrition program, and patients in the Princess Margaret Hospital oncology program. At the Cleveland site, eligible patients included all patients at four hospitals, including The Cleveland Clinic Foundation Hospital, who received infusion therapy from the home infusion agency affiliated with The Cleveland Clinic Foundation. At each site, patients were first asked for verbal consent to participate. Patients who granted this consent were interviewed by a study nurse and were asked to provide written informed consent (in Toronto) or were mailed forms for written consent (in Cleveland). Design This prospective cohort study was performed from 1 April 1996 to 30 April 1997 in Toronto and from 1 May 1996 to 30 May 1997 in Cleveland. For all eligible patients, an anonymous pre-enrollment form without personal identifiers was completed; for patients who consented and were enrolled, additional forms were completed (Table 1). Data for completion of all forms were obtained from the hospital records and infusion agency records and by interviewing patients. Multiple sources were often used, especially to check information provided by patients. On-site study nurses completed all forms and entered information into computer databases. Patients were seen at frequencies ranging from two to three times per day to once per month, depending on diagnosis and indications for therapy. Table 1. Data Collection Forms and Potential Risk Factors Studied An infection form was completed for episodes of suspected infection [Table 1]. Bloodstream infection was diagnosed if all of the following features were present: 1) one or more positive blood cultures, 2) antimicrobial therapy or catheter removal, and 3) no infection at another site that could have caused the bacteremia. For low-virulence organisms, such as coagulase-negative staphylococci, we required the additional criteria of one or more clinical features (fever, chills, or purulent exudate at the catheter insertion site) and at least two positive blood cultures. Episodes that occurred within 2 days of enrollment or hospital discharge were excluded because they would not represent home health care-related infections. Statistical Analysis Data from the catheter, infusion therapy, and infection-control forms were collected and analyzed as time-dependent variables. For example, in a single patient, catheter type A might have been used for days 1 to 14; that catheter might then have been removed and catheter type B inserted and used for days 15 to 45. For such variables, the unit of analysis is the patient, but the values of the variables are allowed to change at different times of follow-up. Patients were included in the study only during periods in which they had a central or midline catheter at home; therefore, the number of days that a patient was followed in the study equals the number of catheter-days. Patients whose catheters had been placed before the study started were included, but bloodstream infections in these patients were included only if they occurred 30 or more days after enrollment, were associated with a different catheter, or were caused by an organism different from that which had caused bloodstream infection before enrollment. For patients who had a bloodstream infection during the study, data on patient-days and infections were excluded for 1 month after the infection and were included again thereafter; subsequent bloodstream infections were counted if the patient had a different catheter or if a different organism was isolated. Therefore, some patients had more than one bloodstream infection during the study. By using SAS for Personal Computers (SAS Institute, Inc., Cary, North Carolina), the separate databases were merged into a common database for analysis. Some of the time-dependent risk factors may have changed between the day of microbial invasion and the day on which positive blood cultures were obtained; to account for this effect, bloodstream infections were included in the common database as of 2 days before the date on which they were reported. Incidence density rates (bloodstream infection rates per 1000 catheter-days) were calculated by dividing the number of bloodstream infections by the number of catheter-days and multiplying the result by 1000. Univariable and multivariable analyses were performed by using Cox regression models for time-dependent covariates (8). Factors that were found to be statistically significant (P<0.05) in univariable analysis were considered for inclusion in the multivariable model by using a forward stepwise algorithm. Independently statistically significant variables (P<0.05) were included in the final multivariable model. Selected variables that were not independently significant were then individually inserted into the final regression model to determine hazard ratios and CIs after adjustment for the factors in the final model. We calculated 95% CIs for hazard ratios by subtracting from or adding to the variable estimate 1.96 times its SE and exponentiating the result. All reported P values are two-sided. Role of the Funding Source This study was funded by the U.S. federal government. No proprietary interest had a role in the collection, analysis, or interpretation of the data or in the decision to submit the paper for publication. Results Enrollment Of 1528 eligible patients, 827 (54%) were enrolled: 62% (354 of 569) of eligible patients at the Toronto site and 49% (473 of 959) of those at the Cleveland site. At the Toronto site, the primary reason given for nonenrollment was that patients were overwhelmed by their illness and were not able to cope with anything else. At the Cleveland site, the lower enrollment rate was attributed to the fact that patients were asked to provide informed consent by mail rather than at a face-to-face meeting. All diagnoses included on the pre-enrollment form were listed more often for enrolled than nonenrolled patients; the most common diagnoses of enrolled patients were infections other than HIV (67%) and cancer (24%) (Table 2). Compared with nonenrolled patients, enrolled patients were more likely to receive total parenteral nutrition and less likely to receive chemotherapy. Table 2. Comparison of Patients Who Were Not Enrolled with Enrolled Patients The 827 enrolled patients had 988 catheters. Of these, 433 (44%) were centrally inserted venous catheters, including 215 Hickman catheters and 125 Cook catheters; 324 (33%) were peripherally inserted central catheters, including 218 Per-Q-Cath catheters (Bard Access Systems, Murray Hill, New York); 155 (16%) were midline catheters, including 96 Landmark catheters (Menlo Care, Inc., Menlo Park, California); and 76 (8%) were implanted ports, including 70 Port-A-Cath catheters (SIMS Deltec, Inc., St. Paul, Minnesota). The median follow-up time was 67 days for patients with centrally inserted venous catheters, 27 days for those with peripherally inserted central catheters, 17 days for those with midline catheters, and 155 for those with implanted ports. Among the centrally inserted venous catheters, all were tunneled and cuffed, and none were impregnated with antiseptic agents. We recorded dates of insertion and removal of catheters but not whether catheters were removed because of occlusion. For the 988 catheters, needle access was used in 108 (11%), needleless access was used in 877 (89%), and protected needle access was used in 3 (<1%). Of the needleless accesses, 792 (89%) were Interlink systems (Baxter International, Deerfield, Illinois). Bloodstream Infections A total of 69 bloodstream infections occurred among 59 patients; 50 patients had 1 bloodstream infection, 8 had 2 bloodstream infections, and 1 had 3 bloodstream infections. Among patients with 2 or more bloodstream infections, the median duration between infections was 119 days (range, 40 to 187 days). The blood specimen showing bacteremia was taken from a peripheral vein in 34 infections (49%), the catheter in 21 infections (30%), and an unknown site in 14 infections (20%). Symptoms included fever in 58 infections (84%), chills in 43 infections (62%), redness at the catheter insertion site in 10 infections (14%), and purulence at the catheter insertion site in 5 infections (7%). At the time of infection, the leukocyte count was 100 to 1000

Disco Fever: Epidemic Meningococcal Disease in Northeastern Argentina Associated with Disco Patronage

Neisseria meningitidis is a leading cause of adult meningitis worldwide. From 5 to 14 August 1996, 8 cases of meningococcal disease occurred in Corrientes city (population 306,000) in northeastern Argentina. Those infected ranged in age from 15 to 45 years (median, 18.5). To determine risk factors for infection, a case-control study was done. Infecting isolates were serogrouped and underwent phenotyping by multilocus enzyme electrophoresis (MLEE) and pulsed-field gel electrophoresis (PFGE). Those infected were significantly more likely than those not infected to have had exposure to passive or active cigarette smoke or to have attended a particular disco. Isolates available from 6 case-patients were all serogroup C; all had identical MLEE and PFGE patterns. These data suggest that dance clubs or discos may be a focus of transmission of N. meningitidis among young people.

Prevention of nosocomial bloodstream infections: a national and international priority.

Nosocomial bloodstream infections (BSIs) are a major cause of morbidity and mortality in the United States and throughout the world. Approximately 8% of all nosocomial infections reported in the United States are primary BSIs; these infections prolong patient hospitalization, are associated with increased mortality, and are costly to the patient and the healthcare system (average US cost per survivor,

Anaemia, iron status and vitamin A deficiency among adolescent refugees in Kenya and Nepal.

40,000). 14 Surveillance for nosocomial BSIs is the cornerstone of prevention and control. During 1980 to 1989, 25,269 BSIs were reported from 9,027,541 patients discharged from hospitals participating in the National Nosocomial Infections SurveillanceNosocomial bloodstream infections (BSIs) are a major cause of morbidity and mortality in the United States and throughout the world. Approximately 8% of all nosocomial infections reported in the United States are primary BSIs; these infections prolong patient hospitalization, are associated with increased mortality, and are costly to the patient and the healthcare system (average US cost per survivor,

Hepatitis E outbreak, Dadaab refugee camp, Kenya, 2012.

40,000).1-4 Surveillance for nosocomial BSIs is the cornerstone of prevention and control. During 1980 to 1989, 25,269 BSIs were reported from 9,027,541 patients discharged from hospitals participating in the National Nosocomial Infections Surveillance (NNIS) System.5 During this period, the overall BSI rate increased by 70% at large teaching hospitals and by 279% at small nonteaching hospitals. Four pathogens, coagulase-negative Staphylococcus (CNS), Candida species, Staphylococcus aureus, and Enterococcus, accounted for most of the increase. Thus, the major pathogens responsible for the increase in BSI rates are gram-positive organisms rather than gram-negative, which predominated before the 1980s. Furthermore, three of these four pathogens often are treated with vancomycin, but one recently emerged as resistant to vancomycin (Enterococcus), and the other two are pathogens for which there is concern about emergence of vancomycin resistance (CNS and S aureus).6 During January 1990 to April 1995, catheter-associated BSI rates (per 1,000 central catheter days) at NNIS hospital intensive-care units (ICUs) ranged from 4.9 in medical-surgical ICUs to 15.6 in burn ICUs.7 Patients in neonatal ICUs also are at high risk for BSIs, with umbilical and central catheter-associated BSI rates (per 1,000 catheter days) ranging from 4.9 for infants >2,500 grams to 12.9 for those <1,500 grams. Although few data exist on the risk of nosocomial BSIs in developing countries, a point-prevalence study of ICU patients in 17 western European countries found that 20.6% of ICU patients acquired a nosocomial infection and that 12% of these infections were BSIs.8 This and other studies in the United States show that the risk of BSI is increased significantly (odds ratio, 4.6; 95% confidence interval, 3.1 to 6.8) in patients with central venous catheters (CVCs) and that the increasing use of CVCs has influenced the pathogen prevalence dramatically.5,8 Thus, the prevalence of primary BSIs and the pathogens causing these infections are highly correlated with the frequency of use of intravascular catheters. The pathogenesis of intravascular catheterrelated infections is complex and multifactorial. The microorganism may be introduced into the bloodstream by (1) intrinsic contamination, ie, contamination of the device or infusate at the time of manufacture; (2) extrinsic contamination, ie, contamination of the device or infusate after manufacture but before insertion or infusion into the patient; (3) contamination of the catheter after insertion, ie, via the hands of healthcare workers (HCWs) during manip-

A Survey of Refugee Health Assessments in the United States

OBJECTIVE To investigate the prevalence of anaemia (haemoglobin<11.0 to 13.0 g dl(-1) depending on age and sex group), iron deficiency (transferrin receptor concentration>8.3 microg ml(-1)) and vitamin A deficiency (serum retinol <0.7 micromol l(-1)) in adolescent refugees. DESIGN Cross-sectional surveys. SETTING Kakuma refugee camp in Kenya and seven refugee camps in Nepal. SUBJECTS Adolescent refugee residents in these camps. RESULTS Anaemia was present in 46% (95% confidence interval (CI): 42-51) of adolescents in Kenya and in 24% (95% CI: 20-28) of adolescents in Nepal. The sensitivity of palmar pallor in detecting anaemia was 21%. In addition, 43% (95% CI: 36-50) and 53% (95% CI: 46-61) of adolescents in Kenya and Nepal, respectively, had iron deficiency. In both surveys, anaemia occurred more commonly among adolescents with iron deficiency. Vitamin A deficiency was found in 15% (95% CI: 10-20) of adolescents in Kenya and 30% (95% CI: 24-37) of adolescents in Nepal. Night blindness was not more common in adolescents with vitamin A deficiency than in those without vitamin A deficiency. In Kenya, one of the seven adolescents with Bitots spots had vitamin A deficiency. CONCLUSIONS Anaemia, iron deficiency and vitamin A deficiency are common among adolescents in refugee populations. Such adolescents need to increase intakes of these nutrients; however, the lack of routine access makes programmes targeting adolescents difficult. Adolescent refugees should be considered for assessment along with other at-risk groups in displaced populations.

PREVENTION OF NOSOCOMIAL TRANSMISSION OF MYCOBACTERIUM TUBERCULOSIS

To the Editor: Hepatitis E virus (HEV) is transmitted through the fecal-oral route and is a common cause of viral hepatitis in developing countries. HEV outbreaks have been documented among forcibly displaced persons living in camps in East Africa, but for >10 years, no cases were documented among Somali refugees (1,2). On August 15, 2012, the US Centers for Disease Control and Prevention (CDC) in Nairobi, Kenya, was notified of a cluster of acute jaundice syndrome (AJS) cases in refugee camps in Dadaab, Kenya. On September 5, a CDC epidemiologist assisted the United Nations High Commissioner for Refugees (UNHCR) and its partners in assessing AJS case-patients in the camp, enhancing surveillance, and improving medical management of case-patients. We present the epidemiologic and laboratory findings for the AJS cases (defined as acute onset of scleral icterus not due to another underlying condition) identified during this outbreak. Dadaab refugee camp is located in eastern Kenya near the border with Somalia. It has existed since 1991 and is the largest refugee camp in the world. Dadaab is composed of 5 smaller camps: Dagahaley, Hagadera, Ifo, Ifo II, and Kambioos. As of December 2012, a total of 460,000 refugees, mainly Somalians, were living in the camps; >25% were recent arrivals displaced by the mid-2011 famine in the Horn of Africa (3). Overcrowding and poor sanitation have led to outbreaks of enteric diseases, including cholera and shigellosis (4); in September 2012, an outbreak of cholera occurred simultaneously with the AJS outbreak. During July 2–November 30, 2012, a total of 339 AJS cases were reported from the camps and 2 nearby villages: 232 (68.4%) from Ifo II, 57 (16.8%) from Kambioos, 26 (7.7%) from Ifo, 12 (3.5%) from Dagahaley, 10 (3.0%) from Hagadera, and 1 each (0.6%) from the nearby Kenyan villages of Biyamadow and Darkanley. The epidemic curve of the outbreak is shown in the Figure. Figure Cases of acute jaundice syndrome, Dadaab, Kenya, July–November 2012. The arrow indicates the point at which outbreak control measures (e.g., construction of new latrines and hygiene messaging) were initiated by health authorities. Of the 339 AJS case-patients, 184 (54.3%) were female. The overall median age was 23.5 years (range 1 month−91 years). The median age among female and male residents was 24 years and 20 years, respectively. Among the 134 women of reproductive age (15−49 years), 72 (53.7%) reported being pregnant; the median gestational age was 17.4 weeks (range 8.7−35.3 weeks). Death was reported for 10 of the 339 case-patients (case-fatality ratio 2.9%), 9 of whom were postpartum mothers (case-fatality ratio 12.5%) and 1 a 2-year-old child. Serum samples were obtained from 170 (50.1%) AJS case-patients for testing at the Kenya Medical Research Institute/CDC laboratories in Nairobi, Kenya. Of the 170 samples, 148 were tested for hepatitis E virus (HEV) IgM by using an ELISA (Diagnostic Systems, Saronno, Italy), and 93 were tested for HEV RNA by using the GeneAmp Gold RNA PCR Reagent Kit (Applied Biosystems, Foster City, CA, USA). Of the 170 samples tested, 131 (77.1%) were positive for HEV IgM, HEV RNA, or both: 120 (81.1%) of 148 tested for HEV IgM and 48 (51.6%) of 93 tested for HEV RNA were positive. In response to the outbreak, UNHCR and partners initiated control measures, including training of health care workers, increasing community awareness, improving hygiene promotion activities, and hastening latrine construction. The outbreak also affected refugee resettlement to the United States and other countries. At the onset of the outbreak, ≈100 Dadaab refugees per month were scheduled for US resettlement. The incubation period for HEV is 15–60 days (5); thus, there was concern that refugees could become ill in transit or within weeks of US resettlement. Acute HEV infection, including progression to fulminant hepatitis, had been reported among travelers returning from regions where the disease is endemic (6). As a precaution, the International Organization for Migration and CDC conducted heightened AJS surveillance during pre-departure and arrival health screenings. As of February 2013, no cases of AJS were reported among refugees from Dadaab who resettled in the United States. Dadaab has faced grave insecurity: aid workers were abducted from the camp in late 2011, and Dadaab has experienced numerous blasts from explosive devices (7). Thus, UNHCR and CDC have been limited in their capacity to collect data and conduct a thorough outbreak investigation to identify risk factors. An earlier study in the Shebelle region of Somalia suggested an increased incidence of HEV during the rainy season and elevated risk for infection in villages dependent on river water (8). Further evaluation is needed to identify the risk factors for HEV transmission and HEV-associated deaths in this region, including the role of person-to-person transmission. UNHCR and CDC investigations of HEV outbreaks in refugee camps in southern Sudan may provide data to answer these questions. HEV is believed to have infected humans for centuries (9); however, the reemergence of the disease in refugee camps is a major concern because of the difficulty in implementing effective preventive measures under camp conditions. Point-of-care tests will be useful for rapidly detecting outbreaks and could potentially save lives. The progress made in developing effective vaccines is encouraging (10). Once available, HEV vaccination should be prioritized in this population, especially for pregnant women.

Infectious Disease Burden and Vaccination Needs Among Asylees Versus Refugees, District of Columbia

We conducted a survey among nine geographically dispersed, large metropolitan refugee health programs to estimate the number of U.S. refugee arrivals during 1997 and 1998, the number receiving health assessments, and the percentage of sites offering health services. The nine sites received an estimated 40% of all U.S. refugee arrivals during the study period. Of these refugees, 76% received a health assessment. The completeness of health assessments, including services offered, varied by site; some services were provided by the private sector. Most sites offered services for infectious diseases and vaccinations. While 78% of the sites offered mental health care, but only 33% actually performed mental status examinations. These statistics show that such health services need to be provided on a broader basis and possibly reflect a need to address cultural and language barriers that might be preventing their delivery to this diverse population.

Pyrogenic reactions in patients undergoing cardiac catheterization associated with contaminated glass medicine cups.

The recent resurgence of TB together with the ongoing HIV epidemic has resulted in a larger number of infectious TB patients being admitted to US health care facilities. These patients have become a source for both nosocomial (patient-to-patient) and occupational (patient-to-health care worker) M. tuberculosis transmission. Infectious MDR-TB patients serve as even greater potential infectious sources because they often remain AFB smear and culture positive for months to years. The keys to the prevention of nosocomial and occupational transmission of M. tuberculosis is conducting a risk assessment for each area of the facility and instituting appropriate control measures, having a high index of suspicion by clinicians for infectious TB in those who present with consistent signs and symptoms, rapid triage of such patients to isolation areas and their appropriate clinical work-up, and the institution of effective antituberculous therapy. Infection control personnel should ensure that infectious TB patients are isolated in appropriate isolation rooms (i.e., negative pressure, greater than or equal to 6 ACH, and direct external exhaust of the room air). Health care workers with infectious TB patient contact should be instructed in the epidemiology of M. tuberculosis transmission, the role of respirators in protecting the health care worker from airborne inoculation, and the importance of periodic health care worker TST. The nosocomial TB outbreaks in the 1980s and 1990s document that M. tuberculosis can be transmitted to both patients and health care workers in US health care facilities when appropriate infection control measures are not fully implemented. Follow-up studies at some of these institutions, however, document that when infection control measures similar to the 1990 or 1994 CDC TB Guidelines are fully implemented, M. tuberculosis transmission to both patients and health care workers can be reduced or eliminated. Protection of both patients and health care workers from M. tuberculosis infection is dependent on an understanding and full implementation of the 1994 CDC TB Guidelines.

Evaluation of the acceptability of a needleless vascular-access system by nurses

BACKGROUND Unlike US-bound refugees, asylum seekers (asylees) apply for asylum while residing in the United States and are not provided a medical screening. Infectious disease burden and vaccination needs have not been described among US asylees. METHODS We conducted a retrospective cohort study of 630 asylees and 151 refugees referred to the District of Columbia (DC) Department of Health screening program for an initial US medical screening during September 2003-August 2007. We assessed the prevalence of latent tuberculosis infection (tuberculin skin test reactivity ≥10 mm), human immunodeficiency virus (HIV) and hepatitis B seropositivity, intestinal parasite test positivity, need for vaccinations, and time from date of US arrival to receipt of screening. RESULTS Asylees in DC had a similar prevalence as refugees of latent tuberculosis infection (39% vs 38%, respectively, P = .83), pathogenic intestinal parasites (4% vs 2%, P = .36), and need for adult vaccinations (80% vs 80%, P = .95). Asylees were screened significantly later after US arrival compared with refugees (55 weeks vs 1 week, P < .001). Asylees had higher prevalence of latent tuberculosis infection, hepatitis B and HIV seropositivity, and child and adult vaccination needs than the US population (P < .001). CONCLUSIONS This study of the infectious disease concerns of a US asylee population suggests that in DC, asylees have similar infectious disease burden and prevention needs as refugees and should be screened with the same urgency. Because applicants for US asylum are not linked to prompt medical screenings, DC asylees are typically screened much later, placing them and US communities at risk.