NeoCLEAN: a multimodal strategy to enhance environmental cleaning in a resource-limited neonatal unit.

BACKGROUND: Contamination of the hospital environment contributes to neonatal bacterial colonization and infection. Cleaning of hospital surfaces and equipment is seldom audited in resource-limited settings. METHODS: A quasi-experimental study was conducted to assess the impact of a multimodal cleaning intervention for surfaces and equipment in a 30-bed neonatal ward. The intervention included cleaning audits with feedback, cleaning checklists, in-room cleaning wipes and training of staff and mothers in cleaning methods. Cleaning adequacy was evaluated for 100 items (58 surfaces, 42 equipment) using quantitative bacterial surface cultures, adenosine triphosphate bioluminescence assays and fluorescent ultraviolet markers, performed at baseline (P1, October 2019), early intervention (P2, November 2019) and late intervention (P3, February 2020). RESULTS: Environmental swabs (55/300; 18.3%) yielded growth of 78 potential neonatal pathogens with Enterococci, S. marcescens, K. pneumoniae, S. aureus and A. baumannii predominating. Highest aerobic colony counts were noted from moist surfaces such as sinks, milk kitchen surfaces, humidifiers and suction tubing. The proportion of surfaces and equipment exhibiting no bacterial growth increased between phases (P1 = 49%, P2 = 66%, P3 = 69%; p = 0.007). The proportion of surfaces and equipment meeting the ATP "cleanliness" threshold (< 200 relative light units) increased over time (P1 = 40%, P2 = 54%, P3 = 65%; p = 0.002), as did the UV marker removal rate (P1 = 23%, P2 = 71%, P3 = 74%; p < 0.001). CONCLUSION: Routine environmental cleaning of this neonatal ward was sub-optimal at baseline but improved significantly following a multimodal cleaning intervention. Involving mothers and nursing staff was key to achieving improved environmental and equipment cleaning in this resource-limited neonatal unit.

Impact of chlorhexidine baths on suspected sepsis and bloodstream infections in hospitalized neonates in Zambia.

INTRODUCTION: Sepsis is the leading cause of infectious morbidity and mortality among hospitalized neonates. In high-resource pediatric and adult intensive care units, use of aqueous chlorhexidine (CHG) solution has been associated with reduced risk of bloodstream infections (BSI). OBJECTIVES: To assess the impact of bathing of neonates with 2% CHG on BSI, suspected sepsis, and mortality in a low-income country neonatal care unit. METHODS: We conducted a secondary analysis of data from the Sepsis Prevention in Neonates in Zambia (SPINZ) study, a prospective observational cohort study performed at a large public referral hospital in Lusaka, Zambia. The SPINZ study assessed the impact of an infection control bundle (consisting of alcohol hand rub, SMS hygiene reminders, enhanced environmental cleaning, and CHG baths for babies ≥1.5 kg) on sepsis, BSI, and all-cause mortality. Episodic shortages in study staffing resulted in some enrolled babies not receiving a CHG bath. Using Longitudinal Targeted Maximum Likelihood Estimation and Cox proportional hazards regression to adjust for observed confounding, we estimated the causal effect of receiving a CHG bath within the first 3 days of life on suspected sepsis, BSI, and death among inborn babies enrolled during the study implementation and intervention phases. RESULTS: The majority of inborn, enrolled babies ≥1.5 kg received a CHG bath within 3 days of NICU admission (864 of 1233, 70%). We found that CHG bathing reduced the hazard rate of BSI among inborn babies ≥1.5 kg by a factor of 0.58 (p = 0.10, 95% CI: 0.31, 1.11), corresponding to an absolute risk reduction of 9.6 percentage points within a week of admission (p = 0.002, 95% CI: 3.4-15.7 percentage points). We did not find a statistically significant effect of CHG bathing on culture-negative sepsis (p = 0.54) or death (p = 0.85). CONCLUSION: In our single center study, CHG bathing at admission was associated with a reduced risk of BSI due to a pathogenic organism after adjusting for potential confounding. Our results suggest that CHG may be an effective intervention for preventing neonatal sepsis in high-risk, low-income country settings.

Establishing nationally representative central line-associated bloodstream infection surveillance data for paediatric patients in Greece.

BACKGROUND: Healthcare-associated infections (HCAIs) are associated with increased morbidity and mortality and with excess costs. Central line-associated bloodstream infections (CLABSIs) are the most common HCAIs in neonates and children. AIM: To establish national benchmark data for rates of CLABSI in neonatal and paediatric intensive care units (NICUs and PICUs) and paediatric oncology units (ONCs). METHODS: Active surveillance for CLABSI was conducted from June 2016 to February 2017. A collaborative of 14 NICUs, four PICUs, and six ONCs participated in the programme. Surveillance definitions of central line (CL), central line utilization (CLU) ratio, CLABSI event, and CLABSI rate were based on the Centers for Disease Control and Prevention's 2014 National Healthcare Safety Network criteria. Medical records were assessed daily for calculating CL-days, patient-days, and susceptibility of isolated organisms. FINDINGS: A total of 111 CLABSI episodes were recorded. The overall mean CLABSI rate was 4.41 infections per 1000 CL-days, and the CLU ratio was 0.31. CLABSI rates were 6.02 in NICUs, 6.09 in PICUs, and 2.78 per 1000 CL-days in ONCs. A total of 123 pathogens were isolated. The most common pathogens were Enterobacteriaceae (36%), followed by Gram-positive cocci (29%), non-fermenting Gram-negative bacteria (16%), and fungi (16%). Overall, 37% of Gram-negative pathogens were resistant to third-generation cephalosporins and 37% to carbapenems. CONCLUSION: Nationally representative CLABSI rates were determined for paediatric patients. These data could be used to benchmark and serve as baseline data for the design and evaluation of infection control and antimicrobial stewardship interventions.

Factors associated with persistent colonisation with methicillin-resistant Staphylococcus aureus.

We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.

Loss to follow-up among adolescents with tuberculosis in Gaborone, Botswana.

SETTING: Nine high-burden public tuberculosis (TB) clinics in Gaborone, Botswana. OBJECTIVE: To describe clinical characteristics and outcomes among adolescents with TB and compare loss to follow-up (LTFU) rates with that among youth and adult cases. DESIGN: Retrospective cohort study of TB cases registered from 2012 to 2014. Clinical characteristics and treatment outcomes were compared among adolescents (age 10-19 years), youth (20-24 years) and a systematic sample of adults (⩾25 years). RESULTS: We analyzed 120 adolescent, 210 youth, and 548 adult cases. Adolescents had twice the risk of LTFU over adults (RR 2.0, 95%CI 1.1-3.7, P = 0.03), and higher LTFU than youth; this was not significant (RR 1.4, 95%CI 0.7-2.9, P = 0.32). Of those with human immunodeficiency virus (HIV) infection, 8/35 (22.9%) adolescents were LTFU, compared with 3/51 (5.9%) youth, and 25/407 (6.1%) adults (P = 0.001). In a multivariable model, adolescence (OR 3.0, 95%CI 1.3-6.5, P < 0.01), HIV positivity (OR 2.2, 95%CI 1.1-4.5, P = 0.02), and extra-pulmonary TB (OR 2.2, 95%CI 1.2-4.0, P = 0.01) were each associated with LTFU. CONCLUSION: Adolescents treated for TB had greater LTFU than youth and adults, particularly in the setting of TB-HIV coinfection. Further work should clarify the generalizability of these findings and investigate poor outcomes among adolescents with TB.

Surgical site infections in a longitudinal cohort of neonatal intensive care unit patients.

OBJECTIVE: To estimate the incidence and identify risk factors for surgical site infections (SSIs) among infants in the neonatal intensive care unit (NICU). STUDY DESIGN: A prospective cohort study of infants undergoing surgical procedures from May 2009 to April 2012 in three NICUs was performed. SSI was identified if documented by an attending neonatologist and treated with intravenous antibiotics. Independent risk factors were identified using logistic regression, adjusting for NICU. RESULT: A total of 902 infants underwent 1346 procedures and experienced 60 SSIs (incidence: 4.46/100 surgeries). Risk factors for SSIs included younger chronological age (odds ratio (OR) 1.03 per day decrease, 95% confidence interval (CI) 1.01, 1.04), lower gestational age (OR 1.09 per week decrease, CI 1.02, 1.18), male sex (OR 1.17, CI 1.04, 1.34) and use of central venous catheter (OR 4.40, CI 1.19, 9.62). Only 43% had surgical site cultures obtained and Staphylococcus aureus was most commonly isolated. CONCLUSION: SSIs complicated 4.46% of procedures performed in the NICU. Although few modifiable risk factors for SSIs were identified, future efforts should focus on evaluating the impact of current prevention strategies on the incidence of neonatal SSI.

[Contribution of electronic data interchange to haemovigilance in a hospital--experience in the University Hospital of Reims]. / Qu'apporte l'échange de données informatisé à l'hémovigilance dans un établissement de soins?--expérience du CHU de Reims.

OBJECTIVE: This study aims to describe concrete results, in a hospital, of changing a traceability process to an electronic data interchange (EDI) based model. STUDY DESIGN: In November 2007, EDI was implemented between the blood bank (French Blood Establishment) and the University Hospital of Reims, concerning distribution data of blood products. We report the effects of this change on electronic traceability, after an 18-month follow-up. RESULTS: Final traceability, after the haemovigilance service interventions, remains satisfying at 99.95 % after change. However, spontaneous traceability by clinical services fell brutally, and remains low at 86.1 % (versus 90.6 % before change). Although EDI concerns the informatic reception stage of traceability, both reception stage and final recording stage (transfusion, return to blood bank or destruction of products) were decreased. The process change itself lead to an increase of bad use dysfunctions, but human causes of omission type also increased at each stage. However, the majority of reception stage dysfunctions are technical causes, supported by EDI itself. CONCLUSION: Although the new process was supposed to be more efficient and easier for the user, the global result on traceability by users is negative after 18 months.

Nosocomial infections and infection control in regional anesthesia.

BACKGROUND: Although rare, infectious complications from regional anesthesia and analgesia can be devastating. The literature on this topic consists primarily of surveys, case reports, case series, and studies in which used supplies were cultured. We derived infection control recommendations from the existing literature and compared these recommendations with existing guidelines. METHODS: Structured literature search of the Cochrane Central Register of Controlled Trials, MEDLINE, including old MEDLINE and EMBASE until 2005. Descriptive statistics were cited when applicable. MAIN RESULTS: Incidence rates for infectious complications vary substantially between studies and range from 3.7 to 7.2/100,000 for spinal anesthesia-associated meningitis and from 0.2 to 83/100,000 for epidural anesthesia-associated epidural abscesses. Few comprehensive prospective trials have been conducted and most case reports do not provide complete information about infection control practices. CONCLUSION: Studies using more robust methods are necessary to define the rates of infection after different regional anesthesia procedures and to identify risk factors for infections. Data on risk factors would allow anesthesiologists to develop evidence-based guidelines for placement and care of catheters used for regional anesthesia. A multicenter surveillance system may help anesthesiologists address some of the unanswered questions and to develop evidence-based infection control recommendations.

Future vaccines: recent advances and future prospects.

The 20th century has witnessed the introduction of over 20 vaccines that prevent or even conquer diseases such as smallpox, polio, and measles. The continued threat of infectious diseases demands the creation of many more vaccines, especially against common respiratory and gastrointestinal pathogens. Thanks to recent advances in molecular biology, immunology, and adjuvant technology, the next decade likely will bring a vaccine for HIV/AIDS also. We enter the 21st century with a tempered optimism, proud of past achievements, but mindful of the challenges that lie ahead.

B2 but not B1 cells can contribute to CD4+ T-cell-mediated clearance of rotavirus in SCID mice.

Studies utilizing various immunodeficient mouse models of rotavirus (RV) infection demonstrated significant roles of RV-specific secretory immunoglobulin A (IgA), CD4+ T cells, and CD8+ T cells in the clearance of RV and protection from secondary infection. Secretion of small but detectable amounts of IgA in RV-infected alphabeta T-cell receptor knockout mice (11) and distinctive anatomical localization and physiology of B1 cells suggested that B1 cells might be capable of producing RV-specific intestinal IgA in a T-cell-independent fashion and, therefore, be responsible for ablation of RV shedding. We investigated the role of B1 cells in the resolution of primary RV infection using a SCID mouse model. We found that the adoptive transfer of unseparated peritoneal exudate cells ablates RV shedding and leads to the production of high levels of RV-specific intestinal IgA. In contrast, purified B1 cells do not ablate RV shedding and do not induce a T-cell-independent or T-cell-dependent, RV-specific IgA response but do secrete large amounts of polyclonal (total) intestinal IgA. Cotransfer of mixtures of purified B1 cells and B1-cell-depleted peritoneal exudate cells differing in IgA allotypic markers also demonstrated that B2 cells (B1-cell-depleted peritoneal exudate cells) and not B1 cells produced RV-specific IgA. To our knowledge, this is the first observation that B1 cells are unable to cooperate with CD4+ T cells and produce virus-specific intestinal IgA antibody. We also observed that transferred CD4+ T cells alone are capable of resolving RV shedding, although no IgA is secreted. These data suggest that RV-specific IgA may not be obligatory for RV clearance but may protect from reinfection and that effector CD4+ T cells alone can mediate the resolution of primary RV infection. Reconstitution of RV-infected SCID mice with B1 cells results in the outgrowth of contaminating, donor CD4+ T cells that are unable to clear RV, possibly because their oligoclonal specificities may be ineffective against RV antigens.

Induction of intestinal rotavirus-specific antibodies in respiratory, but not gut, lymphoid tissues following mucosal immunization of mice with inactivated rotavirus.

Intranasal (i.n.), but not oral, immunization of mice with inactivated rotavirus induces protection against challenge. To understand the mechanisms by which i.n. immunization with inactivated rotavirus evokes protective immunity, we examined the site of rotavirus-specific B cell activation and the origins of intestinal IgA-secreting B cells following i.n. inoculation of mice with inactivated rhesus rotavirus. We found that (1) i.n., but not oral, inoculation induced partial protection after challenge; (2) i.n., but not oral, inoculation induced production of rotavirus-specific IgM, IgA, and IgG by intestinal lymphoid tissues; and (3) after i.n. inoculation, nasal-associated lymphoid tissues (NALT) and bronchial lymph nodes (BLN) were the sites of initial production of rotavirus-specific antibodies. These studies indicate that after inoculation with inactivated rotavirus, virus-specific effector B cells may be more easily activated in respiratory, compared to intestinal, lymphoid tissues. Additional studies are needed to determine if these observations are due to fundamental differences in the microenvironment of NALT and BLN compared to Peyer's patches or are a function of the anatomic differences between the respiratory and the gastrointestinal tracts.

Outpatient pediatric blood cultures: time to positivity.

OBJECTIVE: Using a continuously monitoring blood culture system, we determined the time to positivity of blood cultures performed on immunocompetent infants and children who were not receiving antibiotics at the time of culture. STUDY DESIGN: This study was conducted prospectively using blood cultures taken in the emergency department and outpatient clinics of an urban pediatric teaching hospital from February 1, 1993, through December 31, 1996. Cultures were excluded if obtained from patients receiving antibiotics, patients with a central line, patients with prosthetic devices, or those being followed by the oncology division. Our measures included: 1) recording the time to positive culture obtained by using a continuously monitoring blood culture instrument, 2) patient information derived from the hospital computer system concerning antibiotic use and the presence of indwelling central venous catheters and prosthetic devices, and 3) a chart review of 10% of patients from whom positive cultures were obtained. RESULTS: During the 47-month study period, 10 200 single bottle blood cultures were obtained, 711 (6.97%) of which became positive. Patients ranged in age from <1 week to 24 years (mean: 2.00 years). Two hundred fifty-eight cultures (36.3%) contained only pathogens, 370 (52%) contained only skin contaminants, and 83 (11.7%) contained a mixture of contaminant and pathogen. Of the 258 cultures containing only pathogens, 14% were positive by 12 hours, 87% by 24 hours, 92% by 36 hours, 95% by 48 hours, 98% by 60 hours, and 99.7% by 72 hours. Ninety-five percent of critical pediatric pathogens including Streptococcus pneumoniae, Salmonella and other Enterobacteriaceae, Neisseria meningitidis, and groups A and B streptococci were detected in <24 hours. CONCLUSION: Because 87% of all cultures containing pathogens were detected within the first 24 hours of incubation, this study can assist emergency department, clinic, and primary care clinicians when making critical decisions concerning patients on whom blood cultures were obtained. Data on time to positivity of blood cultures can be used in conjunction with clinical status to support clinicians in making patient management decisions. Use of short stay (

Infection due to Moraxella osloensis: case report and review of the literature.

We describe the successful treatment of Moraxella osloensis bacteremia in a 2-year-old boy who presented with fever, petechial rash, and exacerbation of reactive airway disease. We also review the 12 cases previously reported in the literature.

Migration of antigen-presenting B cells from peripheral to mucosal lymphoid tissues may induce intestinal antigen-specific IgA following parenteral immunization.

Parenterally administered immunizations have long been used to induce protection from mucosal pathogens such as Bordetella pertussis and influenza virus. We previously found that i.m. inoculation of mice with the intestinal pathogen, rotavirus, induced virus-specific Ab production by intestinal lymphocytes. We have now used adoptive transfer studies to identify the cell types responsible for the generation of virus-specific Ab production by gut-associated lymphoid tissue (GALT) after i.m. immunization. Three days after i.m. immunization with rotavirus, cells obtained from the draining peripheral lymph nodes of donor mice were transferred into naive recipient mice. We found that intestinal lymphocytes produced rotavirus-specific Igs (IgM, IgA, and IgG) 2 wk after transfer of either unfractionated cells, or unfractionated cells rendered incapable of cellular division by mitomycin C treatment. Additional studies demonstrated that rotavirus-specific IgA, but not IgG, was produced by intestinal lymphocytes after transfer of purified B cells. Ig allotype analysis revealed that rotavirus-specific IgA was produced by intestinal B cells of recipient origin, suggesting that migration of Ag-presenting B cells from peripheral lymphoid tissues to GALT may contribute to the generation of mucosal IgA responses after parenteral immunization. Strategies that promote Ag uptake and presentation by B cells may enhance mucosal IgA production following parenteral immunization.

Induction of mucosal B-cell memory by intramuscular inoculation of mice with rotavirus.

We investigated the capacity of intramuscular (i.m.) immunization with heterologous-host rotavirus (simian strain RRV) to induce mucosal virus-specific memory B cells in mice. We found that prior i.m. immunization enhanced the magnitude of mucosal virus-specific immunoglobulin A (IgA) production but did not alter the site and timing of induction of virus-specific IgA responses after challenge.

Relative importance of rotavirus-specific effector and memory B cells in protection against challenge.

Adult BALB/c mice were orally inoculated with murine (strain EDIM), simian (strain RRV), or bovine (strain WC3) rotavirus. Six or 16 weeks after inoculation, mice were challenged with EDIM. At the time of challenge and in the days immediately following challenge, production of rotavirus-specific immunoglobulin A (IgA), IgG, and IgM by small intestinal lamina propria lymphocytes (LPL) was determined by fragment culture, and quantities of virus-specific antibodies at the intestinal mucosal surface were determined by intestinal lavage. Mice immunized with EDIM were completely protected against EDIM challenge both 6 and 16 weeks after immunization. Protection was associated with production of high levels of IgA by LPL and detection of virus-specific IgA at the intestinal mucosal surface. In addition, animals immunized and later challenged with EDIM did not develop a boost in antibody responses, suggesting that they were also not reinfected. We also found that in mice immunized with nonmurine rotaviruses, (i) quantities of virus-specific IgA generated following challenge were greater 16 weeks than 6 weeks after immunization, (ii) immunization enhanced the magnitude but did not hasten the onset of production of high quantities of virus-specific IgA by LPL after challenge, and (iii) immunization induced partial protection against challenge; however, protection was not associated with either production of virus-specific antibodies by LPL or detection of virus-specific antibodies at the intestinal mucosal surface.

Immunologic correlates of protection against rotavirus challenge after intramuscular immunization of mice.

The capacity of intramuscular (i.m.) inoculation of mice with homologous or heterologous host rotaviruses to induce protection from challenge was evaluated. i.m. inoculation with live, wild-type rotavirus (murine strain EDIM) induced complete protection from viral shedding after challenge for at least 6 weeks after inoculation; protection was correlated with production of virus-specific immunoglobulin A (IgA) by lamina propria (LP) lymphocytes. i.m. inoculation with inactivated EDIM, cell culture-adapted EDIM, or simian strain RRV was associated with partial protection, characterized by reduced viral shedding after challenge. Partial protection after challenge was not associated with production of virus-specific IgA by LP lymphocytes. The mechanisms by which i.m. inoculation induces virus-specific humoral immune responses in the small intestinal LP were examined.