Bacterial bloodstream infections in pediatric allogeneic hematopoietic stem cell recipients before and after implementation of a central line-associated bloodstream infection protocol: A single-center experience.

INTRODUCTION: There are only few reports describing the influence of central line-associated bloodstream infection (CLABSI) prevention strategies on the incidence of bacterial bloodstream infections (BBSIs). METHODS: We performed a retrospective cohort study among pediatric recipients of allogeneic hematopoietic stem cell transplantation (allo-HCT) to assess potential changes in BBSI rates during 3 time periods: pre-CLABSI prevention era (era 1, 2004-2005), CLABSI prevention implementation era (era 2, 2006-2009), and maintenance of CLABSI prevention era (era 3, 2010-2012). BBSI from day 0-365 following allo-HCT were studied. The comparison of person-years incidence rates among different periods was carried out by Poisson regression analysis. RESULTS: The mean age of patients was 10.0 years. During the study period, 126 (65%) of 190 patients had at least a single BBSI. From day 0-30, day 31-100, day 101-180, and day 181-365, 20%, 28%, 30%, and 17% of patients, respectively, experienced BBSIs. The rate of Staphylococcus epidermidis and gram-negative pathogens significantly declined from 3.16-0.93 and 6.32-2.21 per 100 person-months during era 1 and era 3, respectively (P = .001). CONCLUSIONS: Patients undergoing allo-HCT during era 3 were associated with decreased risk of BBSI (P = .012). Maintenance of CLABSI protocols by nursing staff and appropriate education of other care providers is essential to lower incidence of BBSI in this high-risk population, and further strategies to decrease infection burden should be studied.

Adenovirus infection in paediatric allogeneic stem cell transplantation recipients is a major independent factor for significantly increasing the risk of treatment related mortality.

Adenovirus infection is a significant complication in paediatric AlloSCT recipients with a mortality rate for disseminated adenovirus that may exceed 80%. We sought to determine the incidence, risk factors, and associated outcomes of adenovirus infection in 123 consecutive paediatric AlloSCT recipients. Adenovirus was diagnosed by antigen detection or viral culture, and was defined by isolation of virus with presence of correlating clinical symptoms. The probability of developing adenovirus infection was 12.3% (CI(95) 6.0-18.6). There were no statistically significant differences in probability of adenovirus infection in univariate analysis of risk factors including donor source, use of ATG/Alemtuzumab, ≥ Grade II GVHD, among others (age, diagnosis, conditioning regimen). Probability of overall survival for patients that experienced adenovirus infection was 15.4% vs. 50% for those without adenovirus (P = 0.0286). In multivariate analysis, the most important risk factor for an increased risk of death was adenovirus infection [HR 3.15 (CI(95) 1.6-6.18) P = 0.0009]. In this series of paediatric AlloSCT recipients, the development of adenovirus infection was the leading multivariate predictor of treatment-related mortality. Enhanced surveillance with adenovirus PCR and identification of the risk factors associated with poor outcomes from adenovirus infection may identify patients that may benefit from pre-emptive therapeutic interventions including adenovirus-specific cellular immunotherapies.

A comparison of immune reconstitution and graft-versus-host disease following myeloablative conditioning versus reduced toxicity conditioning and umbilical cord blood transplantation in paediatric recipients.

Immune reconstitution appears to be delayed following myeloablative conditioning (MAC) and umbilical cord blood transplantation (UCBT) in paediatric recipients. Although reduced toxicity conditioning (RTC) versus MAC prior to allogeneic stem cell transplantation is associated with decreased transplant-related mortality, the effects of RTC versus MAC prior to UCBT on immune reconstitution and risk of graft-versus-host disease (GVHD) are unknown. In 88 consecutive paediatric recipients of UCBT, we assessed immune cell recovery and immunoglobulin reconstitution at days +100, 180 and 365 and analysed risk factors associated with acute and chronic GVHD. Immune cell subset recovery, immunoglobulin reconstitution, and the incidence of opportunistic infections did not differ significantly between MAC versus RTC groups. In a Cox model, MAC versus RTC recipients had significantly higher risk of grade II-IV acute GVHD [Hazard Ratio (HR) 6·1, P = 0·002] as did recipients of 4/6 vs. 5-6/6 HLA-matched UCBT (HR 3·1, P = 0·03), who also had significantly increased risk of chronic GVHD (HR 18·5, P = 0·04). In multivariate analyses, MAC versus RTC was furthermore associated with significantly increased transplant-related (Odds Ratio 26·8, P = 0·008) and overall mortality (HR = 4·1, P = 0·0001). The use of adoptive cellular immunotherapy to accelerate immune reconstitution and prevent and treat opportunistic infections and malignant relapse following UCBT warrants further investigation.

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.

Gemfibrozil inhibits Legionella pneumophila and Mycobacterium tuberculosis enoyl coenzyme A reductases and blocks intracellular growth of these bacteria in macrophages.

We report here that gemfibrozil (GFZ) inhibits axenic and intracellular growth of Legionella pneumophila and of 27 strains of wild-type and multidrug-resistant Mycobacterium tuberculosis in bacteriological medium and in human and mouse macrophages, respectively. At a concentration of 0.4 mM, GFZ completely inhibited L. pneumophila fatty acid synthesis, while at 0.12 mM it promoted cytoplasmic accumulation of polyhydroxybutyrate. To assess the mechanism(s) of these effects, we cloned an L. pneumophila FabI enoyl reductase homolog that complemented for growth an Escherichia coli strain carrying a temperature-sensitive enoyl reductase and rendered the complemented E. coli strain sensitive to GFZ at the nonpermissive temperature. GFZ noncompetitively inhibited this L. pneumophila FabI homolog, as well as M. tuberculosis InhA and E. coli FabI.

Application of pulsed-field gel electrophoresis to identify the source of bacterial contamination of peripheral blood progenitor cell products.

BACKGROUND: Positive microbial cultures of peripheral blood progenitor cell (PBPC) products, although estimated to be low, are serious events in the manufacture of hematopoietic progenitor cell (HPC) products that warrant a thorough investigation to determine the contamination source. STUDY DESIGN AND METHODS: Two patients underwent autologous PBPC collection. The first patient was admitted before the collection and was febrile intermittently throughout hospitalization. The second patient spiked a low-grade fever by the end of the procedure. The HPC products from each patient were cultured during processing and before infusion. Blood cultures were drawn during febrile episodes and before transplant. Bacterial identification and antimicrobial susceptibilities were performed on all positive cultures. All strains were typed using pulsed-field gel electrophoresis (PFGE) to determine their relatedness. RESULTS: The blood cultures from both patients and their corresponding HPC products grew Staphylococcus epidermidis. The PFGE pattern of the S. epidermidis recovered from each patient blood was indistinguishable from the one recovered from the corresponding HPC product. The gel pattern of the strains recovered from the first patient differed by four bands from the one recovered from the second. For each patient, the antibiotic susceptibility patterns of the blood cultures and the HPC products were identical. Infusion of the contaminated HPC had no adverse event, and the patients engrafted successfully. CONCLUSION: By use of PFGE technology, the contamination source of PBPC products was identified. It is concluded that the contamination resulted from intermittent bacteremia in the donors and was not introduced during laboratory manufacturing.

Outbreak of Mycobacterium abscessus wound infections among "lipotourists" from the United States who underwent abdominoplasty in the Dominican Republic.

BACKGROUND: Some US residents travel abroad to undergo cosmetic surgery for fat removal, a practice referred to as "lipotourism." Mycobacterium abscessus can cause postsurgical wound infection. METHODS: US residents who developed M. abscessus wound infection after undergoing cosmetic surgery in the Dominican Republic in 2003 and 2004 were identified using the Emerging Infections Network listserv. RESULTS: Twenty returning US travelers with M. abscessus infection were detected. Eight patients had matching isolates, as determined by pulsed-field gel electrophoresis and repetitive element polymerase chain reaction. All 8 patients, who had previously been healthy Hispanic women, underwent abdominoplasties at the same clinic in the Dominican Republic. Symptoms first developed 2-18 weeks after the procedure (median interval, 7 weeks). Only 2 of the 8 patients received a correct diagnosis at the initial presentation. Most patients presented with painful, erythematous, draining subcutaneous abdominal nodules. Seven patients underwent drainage procedures. Six patients received a combination of antibiotics that included a macrolide plus cefoxitin, imipenem, amikacin, and/or linezolid; 2 received clarithromycin monotherapy. All patients but 1 were cured after a median of 9 months of therapy (range, 2-12 months). Because of a lack of access to the surgical clinic, the cause of the outbreak of infection was not identified. The patients who were infected with nonmatching isolates underwent surgeries in different facilities but otherwise had demographic characteristics and clinical presentations similar to those of the 8 patients infected with matching isolates. CONCLUSIONS: This case series of M. abscessus infection in US "lipotourists" highlights the risks of traveling abroad for surgery and the potential role of the Internet in identifying and investigating outbreaks.

A low incidence of nontuberculous mycobacterial infections in pediatric hematopoietic stem cell transplantation recipients.

Hematopoietic stem cell transplantation (HSCT) is being used to treat a wide spectrum of clinical disorders but opportunistic infection remains an important factor determining outcomes for these patients. Nontuberculous mycobacterial (NTM) infections are being reported more frequently in HSCT recipients and the incidence of NTM infections in adult recipients is reported to be 0.4%-4.9%. However, the incidence and severity of NTM infections are less well described in pediatric HSCT recipients. Centers for Disease Control and Prevention guidelines were used to define definite and probable NTM infection among 132 children undergoing 169 HSCT between January 2000 and December 2004 at our institution. NTM infection was diagnosed in 5 of 132 pediatric recipients (3.8%). There were no NTM infections diagnosed in the autologous HSCT recipients and the incidence of NTM in allogeneic HSCT recipients was 6.4% (95% confidence interval, 0.8-11.9). The mean age of the HSCT recipients who developed NTM infections was 8 years (range, 2-19 years); 3 were male and 2 were female. Four conditioning regimens included alemtuzumab and 3 had antithymocyte globulin. Of the 5 patients with NTM infections, 2 met the criteria for definite infection and 3 for probable infection. Of the 2 patients with definite NTM infection, 1 had disseminated disease with Mycobacterium avium complex and the other had Mycobacterium chelonae catheter-related bloodstream infection. The probable NTM infections were 1 skin infection with Mycobacterium kansasii and 2 lower respiratory tract infections with M avium complex. Median time to NTM infection was 115 days (range, 14-269 days) after HSCT. Two patients had graft-versus-host disease at the time of NTM infection. All 5 patients received 3-4 antimycobacterial drugs and all NTM infections resolved. In summary, the incidence of NTM infection in pediatric HSCT recipients appears similar to that described in adult HSCT recipients and the outcome appears to be excellent with the proper antibiotic therapy. The increased use of anti-T cell antibodies appears to be associated with an increased risk of NTM infections in pediatric HSCT recipients. Multicenter studies are needed to identify the risk factors, early diagnostic criteria, and optimal therapy.

Prevalence of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in pregnant women.

OBJECTIVE: To estimate the extent of Staphylococcus aureus vaginal-rectal colonization among pregnant women as severe S aureus infections have emerged in pregnant and postpartum women and infants. METHODS: We conducted a prospective surveillance study for methicillin-sensitive S aureus and methicillin-resistant S aureus on all routine de-identified vaginal-rectal prenatal group B streptococcus (GBS) screening cultures submitted to the microbiology laboratory of a tertiary-care facility from January to July 2005. Standard microbiologic techniques and molecular analyses were used to detect community-associated methicillin-resistant S aureus strains. As opposed to health care-associated methicillin-resistant S aureus isolates, community-associated methicillin-resistant S aureus isolates were defined as those possessing the type IV or type V staphylococcal chromosomal cassette mec element and usually lacking a multidrug-resistant phenotype. RESULTS: A total of 2,963 GBS screening cultures were analyzed, from which 743 (25.1%, 95% confidence interval [CI] 23.5-26.7%) GBS isolates and 507 (17.1%, 95% CI 15.7-18.5%) S aureus isolates were identified. Group B streptococcus colonization was significantly associated with S aureus colonization (prevalence odds ratio 2.1, 95% CI 1.7-2.5, P < .001). Of the S aureus isolates, 14 (2.8%, 95% CI 1.4-4.2%) were methicillin-resistant, and 13 of these were determined to be community-associated methicillin-resistant S aureus. CONCLUSION: The prevalence of S aureus colonization identified in GBS screening cultures from pregnant women was substantial and associated with GBS co-colonization. Although we do not advocate routine screening of pregnant women for methicillin-sensitive S aureus and methicillin-resistant S aureus colonization, we recommend continued monitoring of both methicillin-sensitive S aureus and methicillin-resistant S aureus infections in this population and their infants.

Nontuberculous mycobacterial infections in pediatric hematopoietic stem cell transplant recipients: case report and review of the literature.

Nontuberculous mycobacterial (NTM) infections are rarely diagnosed in hematopoietic stem cell transplant (HSCT) recipients. We describe a case of disseminated Mycobacterium avium complex with gastrointestinal tract involvement in a HSCT recipient. We reviewed NTM infections among pediatric HSCT patients at our institution from 2000-2004 and identified 2 additional cases. Fourteen published case reports of NTM disease in children are reviewed.

Rapid screening of urine specimens for bacteriuria by the cellenium system.

This study evaluated the performance of the Cellenium 160 US urine screening system in comparison to that of the semiquantitative culture method. The performance characteristics of the Cellenium system for all clinically significant uropathogens were 89.5% sensitivity, 94.4% specificity, 97.1% negative predictive value, and 81% positive predictive value.

Effect of antiseptic handwashing vs alcohol sanitizer on health care-associated infections in neonatal intensive care units.

BACKGROUND: The Centers for Disease Control and Prevention, Atlanta, Ga, recommend use of waterless alcohol hand products in lieu of traditional handwashing for patient care, but there are few data demonstrating the impact of this recommendation on health care-associated infections. OBJECTIVE: To compare the effect of 2 hand hygiene regimens on infection rates and skin condition and microbial counts of nurses' hands in neonatal intensive care units. DESIGN, SETTING, AND PARTICIPANTS: Clinical trial using a crossover design in 2 neonatal intensive care units in Manhattan, NY, from March 1, 2001, to January 31, 2003, including 2932 neonatal hospital admissions (51 760 patient days) and 119 nurse participants. INTERVENTION: Two hand hygiene products were tested: a traditional antiseptic handwash and an alcohol hand sanitizer. Each product was used for 11 consecutive months in each neonatal intensive care unit in random order. RESULTS: After adjusting for study site, birth weight, surgery, and follow-up time, there were no significant differences in neonatal infections between the 2 products; odds ratios for alcohol compared with handwashing were 0.98 (95% confidence interval [CI], 0.77-1.25) for any infection, 0.99 (95% CI, 0.77-1.33) for bloodstream infections, 1.61 (95% CI, 0.57-5.54) for pneumonia, 1.78 (95% CI, 0.94-3.37) for skin and soft tissue infections, and 1.26 (95% CI, 0.42-3.76) for central nervous system infections. The skin condition of participating nurses was significantly improved during the alcohol phase (P = .02 and P = .049 for observer and self-assessments, respectively), but there were no significant differences in mean microbial counts on nurses' hands (3.21 and 3.11 log(10) colony-forming units for handwashing and alcohol, respectively; P = .38). CONCLUSIONS: Infection rates and microbial counts on nurses' hands were equivalent during handwashing and alcohol phases, and nurses' skin condition was improved using alcohol. However, assessing the impact on infection rates of a single intervention is challenging because of multiple contributory factors such as patient risk, unit design, and staff behavior. Other practices such as frequency and quality of hand hygiene are likely to be as important as product in reducing risk of cross-transmission.

Intracameral antibiotic agents for endophthalmitis prophylaxis: a pharmacokinetic model.

PURPOSE: To assess in vitro whether intracameral antibiotic agents are plausibly effective prophylaxis against Staphylococcus aureus endophthalmitis. SETTING: University research laboratory.Staphylococcus aureus was cultured for 8 hours with vancomycin (50 microg/mL) or piperacillin/tazobactam (512/64 microg/mL). Without reducing the bacterial counts, the antibiotic concentration was halved every 2 hours to simulate the half-life of antibiotic agents in the anterior chamber. The number of colony forming units (CFU)/mL was measured at 0, 2, 4, 6, and 8 hours. RESULTS: Vancomycin inhibited the growth of methicillin-resistant S aureus such that the CFU/mL was 1000 times higher in the control group after 8 hours. Piperacillin/tazobactam nearly eliminated 1 oxacillin-susceptible strain and reduced the CFU/mL of another strain 1000-fold. CONCLUSIONS: Intracameral vancomycin may inhibit the growth of S aureus in the anterior chamber after surgery. Inhibiting the growth could increase the chances that the eye's innate defenses would eliminate the bacterial contamination that could cause endophthalmitis.

Prevalence and antimicrobial patterns of Acinetobacter baumannii on hands and nares of hospital personnel and patients: the iceberg phenomenon again.

OBJECTIVE: To determine the prevalence and antimicrobial susceptibility patterns of Acinetobacter baumannii on the hands and nares of health care workers and patients from intensive care and rehabilitation units at two hospitals in northern Manhattan, New York. DESIGN: Prevalence survey of Acinetobacter on the hands and anterior nares of staff (n = 184) and patients (n = 98) in rehabilitation and intensive care units of two hospitals. RESULTS: Twenty subjects (7.1%) had positive test results for A baumannii (6 staff [3.3%] and 14 patients [14.3%]). Five patients had positive test results at both sites, four in the nares only, and 11 on hands only. Among patients, four significant predictors of A baumannii were days on unit (P = .003), location (hospital A or B) (P = .01), surgery (P = .04), and receiving an antifungal agent (P = .02; OR, 5.6; 95% CI, 1.25-24.52). Among staff, predictors were skin damage (P = .02) and employment in hospital B (P = .03). Nine of the 20 subjects (45%) had positive test results for multiresistant strains, one from a staff member and eight from patients. CONCLUSION: Patients whose conditions are not clinically symptomatic for A baumannii, as well as staff, are often colonized. Staff with damaged skin are more likely to be colonized. Control of this organism will only be possible when the principle of the iceberg phenomenon--all patients (and staff) treated with standard, Universal Precautions--is strictly followed. Further, the endemic prevalence of multiresistant strains may be higher than previously appreciated.