Susan Whittier

Transfusion of red blood cells after prolonged storage produces harmful effects that are mediated by iron and inflammation

Although red blood cell (RBC) transfusions can be lifesaving, they are not without risk. In critically ill patients, RBC transfusions are associated with increased morbidity and mortality, which may increase with prolonged RBC storage before transfusion. The mechanisms responsible remain unknown. We hypothesized that acute clearance of a subset of damaged, stored RBCs delivers large amounts of iron to the monocyte/macrophage system, inducing inflammation. To test this in a well-controlled setting, we used a murine RBC storage and transfusion model to show that the transfusion of stored RBCs, or washed stored RBCs, increases plasma nontransferrin bound iron (NTBI), produces acute tissue iron deposition, and initiates inflammation. In contrast, the transfusion of fresh RBCs, or the infusion of stored RBC-derived supernatant, ghosts, or stroma-free lysate, does not produce these effects. Furthermore, the insult induced by transfusion of stored RBC synergizes with subclinical endotoxinemia producing clinically overt signs and symptoms. The increased plasma NTBI also enhances bacterial growth in vitro. Taken together, these results suggest that, in a mouse model, the cellular component of leukoreduced, stored RBC units contributes to the harmful effects of RBC transfusion that occur after prolonged storage. Nonetheless, these findings must be confirmed by prospective human studies.

Endemic Pseudomonas aeruginosa Infection in a Neonatal Intensive Care Unit

BACKGROUND Nosocomial infections due to Pseudomonas aeruginosa have been well described, but the environmental reservoir of the organism varies. We conducted an epidemiologic and molecular investigation of endemic P. aeruginosa infection among infants in a neonatal intensive care unit that was associated with carriage of the organisms on the hands of health care workers. METHODS In August 1998, colonization or infection with P. aeruginosa was identified in six infants. Surveillance cultures for P. aeruginosa were obtained from the other 27 infants in the unit, and possible environmental reservoirs were also assessed. The hands of health care workers were inspected and cultured, and risk factors for P. aeruginosa colonization were evaluated. Isolates were analyzed for clonality by pulsed-field gel electrophoresis. RESULTS Surveillance cultures showed that three additional infants were colonized with P. aeruginosa. Cultures of environmental specimens were negative, but cultures of the hands of 10 of 165 health care workers (6 percent) were positive for P. aeruginosa. Increasing age (P=0.05) and a history of the use of artificial fingernails or nail wraps (P=0.03) were both risk factors for colonization of the hands. From January 1997 to August 1998, 49 infants were infected or colonized with P. aeruginosa. Pulsed-field gel electrophoresis demonstrated that 17 of these infants and 1 health care worker who had onychomycosis had the same clone. Infants who were exposed to this health care worker in August 1998 were at greater risk of having this clone than infants who were not exposed to this health care worker (odds ratio, 41.2; 95 percent confidence interval, 1.8 to 940.0; P=0.006). CONCLUSIONS An increased rate of infection and colonization with P. aeruginosa among infants in neonatal intensive care units should be investigated by assessing potential reservoirs, including environmental sources as well as patients and health care workers.

Identification and Antimicrobial Susceptibility of Alcaligenes xylosoxidans Isolated from Patients with Cystic Fibrosis

ABSTRACT In the past decade, potential pathogens, includingAlcaligenes species, have been increasingly recovered from cystic fibrosis (CF) patients. Accurate identification of multiply antibiotic-resistant gram-negative bacilli is critical to understanding the epidemiology and clinical implications of emerging pathogens in CF. We examined the frequency of correct identification ofAlcaligenes spp. by microbiology laboratories affiliated with American CF patient care centers. Selective media, anexotoxin A probe for Pseudomonas aeruginosa, and a commercial identification assay, API 20 NE, were used for identification. The activity of antimicrobial agents against these clinical isolates was determined. A total of 106 strains from 78 patients from 49 CF centers in 22 states were studied. Most (89%) were correctly identified by the referring laboratories as Alcaligenes xylosoxidans. However, 12 (11%) strains were misidentified; these were found to be P. aeruginosa(n = 10), Stenotrophomonas maltophilia(n = 1), and Burkholderia cepacia(n = 1). Minocycline, imipenem, meropenem, piperacillin, and piperacillin-tazobactam were the most active since 51, 59, 51, 50, and 55% of strains, respectively, were inhibited. High concentrations of colistin (100 and 200 μg/ml) inhibited 92% of strains. Chloramphenicol paired with minocycline and ciprofloxacin paired with either imipenem or meropenem were the most active combinations and inhibited 40 and 32%, respectively, of strains. Selective media and biochemical identification proved to be useful strategies for distinguishing A. xylosoxidans from other CF pathogens. Standards for processing CF specimens should be developed, and the optimal method for antimicrobial susceptibility testing ofA. xylosoxidans should be determined.

An outbreak of Legionella micdadei pneumonia in transplant patients: evaluation, molecular epidemiology, and control

PURPOSE To describe a nosocomial outbreak of Legionella micdadei pneumonia in transplant patients and to characterize the source of the outbreak and the control measures utilized. SUBJECTS AND METHODS We performed retrospective Legionella micdadei serologic testing to enhance case finding in transplant patients with pneumonia that lacked a documented microbial etiology, as well as prospective environmental surveillance of water sites and testing for Legionella in clinical specimens. RESULTS During a 3-month period, 12 cases of Legionella micdadei pneumonia were identified either by culture or serologic testing among 38 renal and cardiac transplant patients. Legionella micdadei isolates from hot water sources were found by pulsed-field gel electrophoresis to have a DNA banding pattern that was identical to the isolates from the first 3 culture-positive cases and from 2 cases that occurred 16 months later. CONCLUSIONS Hospitals caring for organ transplant recipients and other immunosuppressed patients must be aware of the possibility of environmental sources of outbreaks of Legionella infection. A first-line screen with the Legionella urine antigen test will identify Legionella pneumophila serogroup 1. However, specific cultures in outbreak situations should be considered to identify other Legionella pneumophila serotypes and the nonpneumophila Legionella species.

Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial.

We conducted an open-label crossover trial to test whether proton pump inhibitors (PPIs) affect the gastrointestinal microbiome to facilitate Clostridium difficile infection (CDI). Twelve healthy volunteers each donated 2 baseline fecal samples, 4 weeks apart (at weeks 0 and 4). They then took PPIs for 4 weeks (40 mg omeprazole, twice daily) and fecal samples were collected at week 8. Six individuals took the PPIs for an additional 4 weeks (from week 8 to 12) and fecal samples were collected from all subjects at week 12. Samples were analyzed by 16S ribosomal RNA gene sequencing. We found no significant within-individual difference in microbiome diversity when we compared changes during baseline vs changes on PPIs. There were, however, significant changes during PPI use in taxa associated with CDI (increased Enterococcaceae and Streptococcaceae, decreased Clostridiales) and taxa associated with gastrointestinal bacterial overgrowth (increased Micrococcaceae and Staphylococcaceae). In a functional analysis, there were no changes in bile acids on PPIs, but there was an increase in genes involved in bacterial invasion. These alterations could provide a mechanism by which PPIs predispose to CDI. ClinicalTrials.gov ID NCT01901276.

Epidemiology of candidemia at a Children's hospital, 2002 to 2006.

Background: There are few recent studies evaluating trends in the epidemiology of candidemia including changes in species or utilization of antifungal agents in children. Methods: We performed a retrospective case series of candidemia at our childrens hospital from 2002 to 2006. Our objectives were to study trends in the rates of candidemia, demographic characteristics, Candida species, antifungal susceptibility, and antifungal utilization. These data were obtained from the electronic medical records. Results: There were 203 episodes of candidemia in 154 subjects. During the study period, the average rate of candidemia was 5.52 per 1000 patient-discharges and did not change throughout the study. The mean and median ages of subjects were 3 years versus 9 months, respectively, and 38% were less than 3 months of age. Gastrointestinal disorders were a common comorbid condition (33%), especially for subjects with multiple episodes of candidemia. Overall, Candida parapsilosis and Candida albicans caused 43% and 26% of episodes, respectively, and candidemia caused by Candida glabrata (5.3%–23%) and Candida krusei (0%–8.5%) increased during the study. Ninety-eight percent of C. albicans and C. parapsilosis isolates remained susceptible to all antifungal drugs. From 2003–2006, the use of antifungal agents increased from 79 days to 150 days per 1000 hospital-days. Conclusions: While antifungal use at our hospital increased, candidemia rates remained stable. C. parapsilosis was the most common species but other non–C. albicans species increased during the study period. Local epidemiology should be monitored in pediatric populations for potential impact on management strategies.

Diagnosis of pediatric tuberculosis in the modern era.

BACKGROUND Correctly diagnosing tuberculosis (TB) in children is critical to provide appropriate treatment and to detect undiagnosed source cases. However, diagnosing TB in children may be difficult. OBJECTIVE We sought to determine whether Amplicor, a Food and Drug Administration-approved polymerase chain reaction (PCR) assay used to detect Mycobacterium tuberculosis in sputum and computerized tomography (CT) would facilitate the diagnosis of TB in children. We also examined the applicability of the Centers for Disease Control and Prevention clinical case definition for TB. SETTING A university-affiliated pediatric hospital in New York City. SUBJECTS From March, 1995, to November, 1997, 27 children < 15 years of age (mean age, 3.9 years) were evaluated for suspected TB. RESULTS M. tuberculosis was cultured from 5 of 76 (6.6%) gastric aspirate specimens, and PCR detected M. tuberculosis DNA in 3 (4.1%) of these specimens. There was poor correlation between culture and PCR because 6 specimens were discordant. CT scans were diagnostic of mediastinal or hilar adenopathy in 6 children with equivocal or negative chest radiographs and confirmed adenopathy in 8 others. Six children received alternative diagnoses. CONCLUSIONS We conclude that the commercially available PCR technology had very limited utility in detecting M. tuberculosis from gastric aspirates, but CT scans were useful in assessing pediatric patients with suspected TB.

Persistence of immunity to varicella-zoster virus after vaccination of healthcare workers.

OBJECTIVE Varicella-zoster virus (VZV) vaccine is recommended to protect susceptible healthcare workers (HCWs) from serious disease and to prevent nosocomial spread of VZV. We evaluated clinical outcomes and serological responses in HCWs after immunization with live attenuated VZV vaccine. DESIGN Vaccinees were immunized from 1979 to 1998 during VZV vaccine trials, as well as after licensure, and followed prospectively for 1 month to 20.6 (mean 4.6) years after vaccination. Sera were tested by fluorescent antibody to membrane antigen (FAMA), latex agglutination (LA), and enzyme-linked immunoassay (EIA) to detect VZV-specific antibodies. STUDY PARTICIPANTS The median age of the 120 HCWs was 26 years; 51 (42%) were males. INTERVENTIONS Ninety eight (82%) of these study subjects received vaccine prepared by Merck and 22 (18%) by SmithKline Beecham; 25, 81, and 14 vaccinees received one dose, two doses, and three doses, respectively. RESULTS The crude attack rate was 10%; 12 of 120 HCWs developed chickenpox 6 months to 8.4 years after vaccination. The attack rates following household and hospital exposures were 18% (4/22) and 8% (6/72), respectively. All resulting illness was mild to moderate (mean 40 vesicles). Seroconversion after vaccination was documented by FAMA in 96% of HCWs, although 31% lost detectable antibodies. Compared with FAMA, LA and EIA were 82% and 74% sensitive and 94% and 89% specific, respectively. CONCLUSIONS The VZV vaccine effectively protected HCWs from varicella, particularly from serious disease. Currently available serological tests are not optimal, and improved assays are needed.

The Breast: A Clean-Contaminated Surgical Site

BACKGROUND Capsular contracture is one of the most common complications associated with breast implants. While the cause of this process has not yet been elucidated, subclinical infection is a likely culprit. OBJECTIVES The authors assess the hypothesis that a probable source of contamination is endogenous breast bacteria, likely originating in the ducts themselves and most concentrated near the nipple. METHODS Twenty-five healthy patients presenting for routine reduction mammaplasty were recruited as study participants. Tissue samples were taken intraoperatively from the periareolar, inframammary, and axillary regions of each sampled breast. Specimens were then processed in the microbiology laboratory, and quantitative bacterial counts were obtained. RESULTS Of the 50 breasts sampled, 19 yielded positive culture results, for a rate of 38%. There was a significant difference in the positive culture rate among all three sites, with increasing quantitative bacterial counts in the axillary, inframammary, and periareolar regions, respectively. The most commonly-identified organisms in this study included various species of Staphylococcus and Propionibacterium acnes, with S. epidermidis being the most common. CONCLUSIONS The breast harbors significant endogenous bacteria that can become the source of spontaneous or postoperative infection. Positive intraoperative cultures with high quantitative counts suggest that breast tissue harbors more bacteria than normal skin flora. Routine perioperative antibiotic prophylaxis may be suboptimal for the prevention of foreign body seeding in this setting. Furthermore, bacterial concentrations are highest in areas with the most ductal tissue, namely the periareolar region. These findings may be helpful when considering which incision site to select for augmentation mammaplasty.

Detection of fecal shedding of rotavirus vaccine in infants following their first dose of pentavalent rotavirus vaccine

Studies on rotavirus vaccine shedding and its potential transmission within households including immunocompromised individuals are needed to better define the potential risks and benefits of vaccination. We examined fecal shedding of pentavalent rotavirus vaccine (RV5) for 9 days following the first dose of vaccine in infants between 6 and 12 weeks of age. Rotavirus antigen was detected by enzyme immunoassay (EIA), and vaccine-type rotavirus was identified by nucleotide sequencing based on genetic relatedness to the RV5 VP6 gene. Stool from 22 (21.4%) of 103 children contained rotavirus antigen-positive specimens on ≥ 1 post-vaccination days. Rotavirus antigen was detected as early as post-vaccination day 3 and as late as day 9, with peak numbers of shedding on post-vaccination days 6 through 8. Vaccine-type rotavirus was detected in all 50 antigen-positive specimens and 8 of 8 antigen-negative specimens. Nine (75%) of 12 EIA-positive and 1 EIA-negative samples tested culture-positive for vaccine-type rotavirus. Fecal shedding of rotavirus vaccine virus after the first dose of RV5 occurred over a wide range of post-vaccination days not previously studied. These findings will help better define the potential for horizontal transmission of vaccine virus among immunocompromised household contacts of vaccinated infants for future studies.