Implications of ad-hoc molecular typing for infection control measures in a multi-cluster, multi-phenotypic Serratia marcescens outbreak in a neonatal intensive care unit.

BACKGROUND: Serratia marcescens is known to cause outbreaks in neonatal intensive care units (NICUs). Traditionally epidemiological data, antimicrobial resistance patterns and epidemiological typing have been used to guide infection prevention methods. Whole-genome sequencing (WGS) applications such as core-genome multi-locus sequence typing (cgMLST) applied during an outbreak would potentially yield more information. AIM: To use cgMLST to acquire detailed information on the source and spread of bacteria, enabling more efficient control measures during an S. marcescens outbreak at a NICU. METHODS: Neonates admitted to the NICU of the Leiden University Medical Center (LUMC) during an outbreak between September 2023 and January 2024, with S. marcescens being cultured, were included. Environmental samples were taken to search for a common source, antibiotic susceptibility testing was performed, and antimicrobial resistance genes were analysed. FINDINGS: S. marcescens strains from 17 of the 20 positive patients were available for molecular typing. The cgMLST scheme revealed five different complex types consisting of four separate clusters. Multiple clusters made an unidentified persistent environmental source as cause of the outbreak less likely, leading to a quick downscaling of infection prevention measures. Differences were shown in aminoglycoside resistance patterns of isolates within the same complex types and patients. CONCLUSION: The use of ad-hoc cgMLST provided timely data for rational decision-making during an S. marcescens outbreak at the NICU. Antibiotic phenotyping alone was found not to be suitable for studying clonal spread during this outbreak with S. marcescens.

Central-line-associated bloodstream infection burden among Dutch neonatal intensive care units.

BACKGROUND: The establishment of an epidemiological overview provides valuable insights needed for the (future) dissemination of infection-prevention initiatives. AIM: To describe the nationwide epidemiology of central-line-associated bloodstream infections (CLABSI) among Dutch Neonatal Intensive Care Units (NICUs). METHODS: Data from 2935 neonates born at <32 weeks' gestation and/or with a birth weight <1500 g admitted to all nine Dutch NICUs over a two-year surveillance period (2019-2020) were analysed. Variations in baseline characteristics, CLABSI incidence per 1000 central-line days, pathogen distribution and CLABSI care bundles were evaluated. Multi-variable logistic mixed-modelling was used to identify significant predictors for CLABSI. RESULTS: A total of 1699 (58%) neonates received a central line, in which 160 CLABSI episodes were recorded. Coagulase-negative staphylococci were the most common infecting organisms of all CLABSI episodes (N=100, 63%). An almost six-fold difference in the CLABSI incidence between participating units was found (2.91-16.14 per 1000 line-days). Logistic mixed-modelling revealed longer central line dwell-time (adjusted odds ratio (aOR):1.08, P<0.001), umbilical lines (aOR:1.85, P=0.03) and single rooms (aOR:3.63, P=0.02) to be significant predictors of CLABSI. Variations in bundle elements included intravenous tubing care and antibiotic prophylaxis. CONCLUSIONS: CLABSI remains a common problem in preterm infants in The Netherlands, with substantial variation in incidence between centres. Being the largest collection of data on the burden of neonatal CLABSI in The Netherlands, this epidemiological overview provides a solid foundation for the development of a collaborative platform for continuous surveillance, ideally leading to refinement of national evidence-based guidelines. Future efforts should focus on ensuring availability and extraction of routine patient data in aggregated formats.

Influence of transition from open bay units to single room units in a neonatal intensive care unit on hospital transmission of multi-drug-resistant Enterobacterales.

BACKGROUND: It was shown previously that changing the design of a hospital neonatal intensive care unit (NICU) from open bay units (OBUs) to single room units (SRUs) was not associated with a reduction in Gram-negative multi-drug-resistant organism (MDRO) colonization rates. It was therefore hypothesized that colonization mainly occurs vertically, or through parents and healthcare workers, and not through environmental factors, and that transition to SRUs would not decrease the number of clusters of MDROs with an epidemiological link. To investigate this, core-genome multi-locus sequence typing (cgMLST) was applied on MDROs cultured from infants at the study hospital. METHODS: This retrospective cohort study included all infants carrying MDROs admitted to the NICU of a tertiary care academic hospital 2 years prior to the transition from OBUs to SRUs in May 2017, and 1.5 years after the transition (2018-2020). RESULTS: In total, 55 infants were diagnosed with MDRO carriership. Isolates were available from 49 infants for cgMLST. In the OBU period, one cluster involving four of 20 (20%) infants was identified, and in the SRU period, four clusters involving nine of 29 (31%) infants were identified. It was possible to make an epidemiological link in all four SRU MDRO clusters, but this was not possible for the OBU cluster. In the latter case, transmission from an environmental source on the ward seemed likely. CONCLUSION: After transition to SRUs, there was no decrease in the number of clusters of MDROs with an epidemiological link, suggesting that nursing infants in an NICU with an SRU design is not, in itself, protective against the acquisition of MDROs.

Impact of transition from open bay to single room design neonatal intensive care unit on multidrug-resistant organism colonization rates.

BACKGROUND: The influence of the neonatal intensive care unit (NICU) design on the acquisition of multidrug-resistant organisms (MDROs) has not been well-documented. AIM: To examine the effect of single room unit (SRU) versus open bay unit (OBU) design on the incidence of colonization with MDROs and third-generation cephalosporin-resistant bacteria (3G-CRB) in infants admitted to the NICU. METHODS: Retrospective cohort study, including all infants admitted to the NICU of a tertiary care academic hospital two years prior to and two years following the transition from OBU to SRU in May 2017. Weekly cultures of throat and rectum were collected to screen for MDRO carriership. Incidence of colonization (percentage of all infants and incidence density per 1000 patient-days) with MDROs and 3G-CRB were compared between OBU and SRU periods. FINDINGS: Incidence analysis of 1293 NICU infants, identified 3.2% MDRO carriers (2.5% OBU, 4.0% SRU, not significant), including 2.3% extended-spectrum ß-lactamase-producing Enterobacterales carriers, and 18.6% 3G-CRB carriers (17% OBU, 20% SRU, not significant). No differences were found in MDRO incidence density per 1000 patient-days between infants admitted to OBU (1.56) compared to SRU infants (2.63). CONCLUSION: Transition in NICU design from open bay to SRUs was not associated with a reduction in colonization rates with MDROs or 3G-CRB in our hospital. Further research on preventing the acquisition and spread of resistant bacteria at high-risk departments such as the NICU, as well as optimal ward design, are needed.

Borderline oxacillin-resistant Staphylococcus aureus carriage among healthcare workers at neonatal intensive care unit and paediatric ward.

BACKGROUND: During a meticillin-resistant Staphylococcus aureus contact tracing and screening investigation, two borderline oxacillin-resistant Staphylococcus aureus (BORSA)-positive screening cultures were encountered among neonatal intensive care unit (NICU) healthcare workers (HCWs). This finding led to further investigations. AIM: To assess the likelihood of an outbreak with direct transmission among HCWs. METHODS: An infection control team was initiated after the discovery. The team initiated additional infection control measures and evaluated new findings. All NICUs and paediatric ward HCWs were screened for BORSA carriage, and a prospective BORSA seven-week monitoring period for patients was observed. To assess the likelihood of an outbreak with direct transmission among HCWs, the BORSA isolates were analysed using augmented fragment length polymorphism and whole-genome sequencing (WGS). FINDINGS: Positive HCWs were prohibited from clinical work while awaiting the results from the screening programme. In all, 127 NICU and 77 general paediatric ward HCWs were screened for BORSA carriage; five HCWs were BORSA positive. Seventy-two patients were screened during the seven-week period yielding a total of 138 cultures, ranging from one to nine cultures per patient. No spread from HCWs to patients occurred, and the BORSA screening programme was discontinued. WGS analysis with core genome multi-locus sequence typing of all five BORSA strains showed relatedness between two NICU strains. CONCLUSION: During a seven-week period, no transmission from BORSA-positive HCWs to neonates was observed in either screening or clinical cultures. More vigilance and experience is needed to design adequate evidence-based interventions in the future for this vulnerable population.

Universal screening versus risk-based protocols for antibiotic prophylaxis during childbirth to prevent early-onset group B streptococcal disease: a systematic review and meta-analysis.

BACKGROUND: Early-onset group B streptococcal (EOGBS) disease (including sepsis, meningitis, and pneumonia) causes significant morbidity and mortality in newborn infants worldwide. Antibiotic prophylaxis can prevent vertical streptococcal transmission, yet no uniform criteria exist to identify eligible women for prophylaxis. Some guidelines recommend universal GBS screening to pregnant women in their third trimester (screening-based protocol), whereas others employ risk-based protocols. OBJECTIVES: To compare the effectiveness of screening-based versus risk-based protocols in preventing EOGBS disease. SEARCH STRATEGY: Key words for the database searches included GBS, Streptococcus agalactiae, pregnancy, screening, culture-based, risk-based. SELECTION CRITERIA: Studies were included if they investigated EOGBS disease incidence in newborn infants and compared screening or risk-based protocols with each other or with controls. DATA COLLECTION AND ANALYSIS: Risk ratios (RR) and 95% confidence intervals (CI) were determined using Mantel-Haenszel analyses with random effects. MAIN RESULTS: Seventeen eligible studies were included. In this meta-analysis, screening was associated with a reduced risk for EOGBS disease compared either with risk-based protocols (ten studies, RR 0.43, 95% CI 0.32-0.56) or with no policy (four studies, RR 0.31, 95% CI 0.11-0.84). Meta-analysis could not demonstrate a significant effect of risk-based protocols versus no policy (seven studies, RR 0.86, 95% CI 0.61-1.20). In studies reporting on the use of antibiotics, screening was not associated with higher antibiotic administration rates (31 versus 29%). CONCLUSIONS: Screening-based protocols were associated with lower incidences of EOGBS disease compared with risk-based protocols, while not clearly overexposing women to antibiotics. This information is of relevance for future policymaking. TWEETABLE ABSTRACT: Meta-analysis: general screening is associated with lower rates of early-onset group B strep. neonatal sepsis compared with risk-based protocols.

[Efficiency of iodine and selenium enriched drinking water use to prevent deficiency states in population of the Altai Territory].

Numerous epidemiological studies suggest that there is an association between the quality of drinking water and human health. The Altai Territory is a biogeochemical province characterized by deficiency of many trace elements, including iodine and selenium. The measures implemented in organized children's collectives to prevent iodine- and selenium-enriched deficiency states, by providing the supply of drinking waters enriched with iodine and selenium, have demonstrated a more marked effect in preventing iodine deficiency states than that of the water corrected only for the iodine composition.

Genetic variation in CLDN1 and susceptibility to hepatitis C virus infection.

Claudin-1 is a recently discovered co-receptor for hepatitis C virus (HCV) that is required for late-stage binding of the virus. Because variants in the gene that encodes claudin-1 (CLDN1) could play a role in HCV infection, we conducted a 'whole gene association study' among injection drug users (IDUs) to examine whether CLDN1 genetic variants were associated with the risk of HCV infection or with viral clearance. In a cross sectional study, we examined genotype results for 50 single nucleotide polymorphisms (SNPs) across the CLDN1 gene region, comparing genotypes among participants with chronic HCV (n = 658) to those in IDUs who had cleared HCV (n = 199) or remained HCV-uninfected (n = 68). Analyses were controlled for racial ancestry (African-American or European-American) by stratification and logistic regression modeling. We found that participants who remained uninfected more often carried CLDN1 promoter region SNPs -15312C [odds ratio (OR), 1.72; 95% confidence interval (CI) 1.00-2.94; P = 0.048], -7153A (OR, 2.13; 95% CI, 1.25-3.62; P = 0.006) and -5414C (OR, 1.78; 95% CI, 1.06-3.00; P = 0.03). HCV-uninfected participants less often carried CLDN1 IVS1-2983C (OR, 0.55; 95% CI, 0.31-0.97; P = 0.04), which lies in intron 1. CLDN1 -15312C, -7153A and -5414C formed a haplotype in both the African-American and European-American participants and a haplotype analysis supported the association of CLDN1 -7153A in the HCV-uninfected participants. The analyses of HCV clearance revealed no associations with any SNP. These results indicate that genetic variants in regulatory regions of CLDN1 may alter susceptibility to HCV infection.

[Treatment of mild and moderate hypertension with enalapril (multicenter study of enap and enap N in Ukraine)]. / Lechenie miagkoi i umerennoi arterial'noi gipertonii énalaprilom (mnogotsentrovoe issledovanie énapa i énapa-N na Ukraine).

AIM: Assessment of efficiency and safety of enalapril (enap) and its combination with hydrochlorotiaside (enap-N). MATERIALS AND METHODS: 127 patients with mild and moderate blood hypertension entered an open non-comparative multicenter trial. 60 of them received enap (group 1), 67--enap N (group 2). Group 1 patients were given enap for 2 weeks in a dose 10 mg/day. If this dose was not adequate to normalize blood pressure, it was raised to 20-40 mg/day. Patients of group 2 received enap-N one tablet a day for 3 weeks. If the pressure persisted higher than 140/90 mm Hg, the treatment was continued for 3 weeks more in a dose of 2 tablets a day. RESULTS: Blood pressure lowered under 140/90 mm Hg in 40 patients of group 1 (66.7%). Systolic pressure dropped by 10 mm Hg minimum and diastolic by 5 mm minimum in 18 group 1 patients (30%). Enap-N reduced blood pressure under 140-90 mm Hg in 44 of 67 patients (65.7%). Systolic and diastolic pressure dropped, respectively, in 23(34.3%) patients. CONCLUSION: Enap and enap-N tablets were found highly effective and well tolerated. Side effects were caused by lowering of blood pressure.

[Sex and age differences in the peripheral blood aldosterone levels]. / Vozrastnye i polovye razlichiia v soderzhanii al'dosterona v plazme perifericheskoi krovi.

Age-associated and sexual differences in the adrenocortical glomerular zone function of normal subjects were studied by radioimmunoassay. The blood plasma aldosterone content (13.46 +/- 1.18 ng%) of adult females (27) was 20.7% higher than that of the males (22) of the same age (11.15 +/- 0.56 ng%). An increase in the blood aldosterone content in menopause appears to be due to the hyperestrogenic phase (the first menopausal phase in women) and estrogen-stimulated aldosterone synthesis. Sexual differences in aldosterone secretion disappear with age. Aldosterone content is significantly lower in males and females, age over 80 years, than that in younger subjects, and sexual differences are absent.

[Urinary aldosterone excretion and erythrocyte and plasma sodium and potassium ion concentration in persons of different ages]. / Vydelenie al'dosterona s mochoi i soderzhanie ionov kaliia i natriia v éritrotsitakh i plazme krovi u liudei raznogo vozrasta

Practically healthy persons (79 in all) aged from 20 to 80 years and over were examined. The work was aimed at the study of the character of aldosterone excretion and its correlation with the ionic composition of erythrocytes and the peripheral blood plasma in persons at various age periods. As revealed, the activity of glomerular zone of the adrenal cortex in persons aged from 20 to 40 years displayed sexual differences: 1.33 times more aldosterone was excreted with the urine in women than in men. With the advance of age there occurred a functional decrease in the glomerular zone of the adrenal cortex. In senile persons (aged 80 years and over) this difference was entirely eliminated. Sodium ions in erythrocytes increased, but remained unchanged in the peripheral blood plasma. Potassium ion concentration fell both in the erythrocytes and in the blood plasma. A reduction of aldosterone content failed to alter the sodium-retention effect of its action which corresponded to the concept on increase of tissue sensitivity to hormones with the advance of age.