Outbreak of OXA-48-producing Enterobacteriaceae in a neonatal intensive care unit in Western Sweden.

In 2015, an outbreak caused by OXA-48-producing Enterobacteriaceae affected a neonatal intensive care unit at a Swedish University Hospital. The aim was to explore the transmission of OXA-48-producing strains between infants and the transfer of resistance plasmids between strains during the outbreak. Twenty-four outbreak isolates from ten suspected cases were whole-genome sequenced. A complete assembly was created for the index isolate (Enterobacter cloacae) and used as a mapping reference to detect its plasmids in the remaining isolates (17 Klebsiella pneumoniae, 4 Klebsiella aerogenes, and 2 Escherichia coli). Strain typing was performed using core genome MLST and SNP analysis. As judged from sequencing and clinical epidemiological data, the outbreak involved nine cases (two developed sepsis) and four OXA-48-producing strains: E. cloacae ST1584 (index case), K. pneumoniae ST25 (eight cases), K. aerogenes ST93 (two cases), and E. coli ST453 (2 cases). Two plasmids from the index strain, pEclA2 and pEclA4, carrying blaOXA48 and blaCMY-4, respectively, were traced to all K. pneumoniae ST25 isolates. Klebsiella aerogenes ST93 and E. coli ST453 harboured either only pEclA2, or both pEclA2 and pEclA4. One suspected case harbouring OXA-162-producing K. pneumoniae ST37 could be excluded from the outbreak. Once initiated by an E. cloacae strain, the outbreak was caused by the dissemination of a K. pneumoniae ST25 strain and involved inter-species horizontal transfer of two resistance plasmids, one of which carried blaOXA-48. To our knowledge, this is the first description of an outbreak of OXA-48-producing Enterobacteriaceae in a neonatal setting in northern Europe.

Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates.

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis.

The effects of exposure to HIV in neonates at a referral hospital in South Africa.

BACKGROUND: Fewer infants are infected with HIV through mother-to-child transmission, making HIV-exposed but uninfected (HEU) infants a growing population. HIV-exposure seems to affect immunology, early growth and development, and is associated with higher morbidity and mortality rates. Currently, there is a lack of information regarding the clinical effects of HIV-exposure during the neonatal period. OBJECTIVES: To identify a possible difference in mortality and common neonatal morbidities in HEU neonates compared to HIV-unexposed neonates. METHODS: This was a retrospective, descriptive study of all neonates admitted to the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital between 1 January 2017 and 31 December 2018. HEU neonates were compared to HIV-unexposed neonates. RESULTS: There were 3236 neonates included, where 855 neonates were HEU. The HEU neonates had significantly lower birth weight and gestational age. The HEU neonates had higher rates of neonatal sepsis (19.8% vs 14.2%, OR 1.49, p <  0.001), specifically for late onset sepsis, and required more respiratory support. NCPAP and invasive ventilation was more common in the HEU group (36.3% vs 31.3% required NCPAP, p = 0.008, and 20.1% vs 15,0% required invasive ventilation, p <  0.001). Chronic lung disease was more common among HIV-exposed neonates (12.2% vs 8.7%, OR 1.46, p = 0.003). The difference in mortality rates between the study groups was not significant (10.8% of HEU neonates and 13.3% of HIV-unexposed). CONCLUSIONS: HEU neonates had higher rates of neonatal sepsis, particularly late-onset sepsis, required more respiratory support and had higher rates of chronic lung disease. Mortality of HEU neonates was not different HIV-unexposed neonates.

C-reactive protein- and clinical symptoms-guided strategy in term neonates with early-onset sepsis reduced antibiotic use and hospital stay: a quality improvement initiative.

BACKGROUND: Early-onset sepsis (EOS) is a potentially life-threatening complication of birth. Clinical symptoms are often unspecific and biomarkers have low predictive values for EOS. Therefore, clinical suspicion often leads to antibiotic therapy in neonates with a negative blood culture. In the study we evaluated if a quality improvement initiative could reduce unwarranted antibiotic use in a safe way in term neonates with culture-negative sepsis. METHODS: The quality improvement initiative included new treatment guidelines and were introduced on 11 June 2018. The guidelines included C-reactive protein- and clinical symptoms-guided decision-making and shorter intravenous antibiotic therapy. All term neonates treated for EOS at Ryhov Hospital, Jönköping, Sweden were studied before (period 1: 2016-2017) and after the introduction of the new guidelines (period 2: 11 June 2018 to 30 Sept 2019). Laboratory and clinical data were analysed. RESULTS: There were 7618 term neonates in period 1 and 5005 term neonates in period 2. We identified 140 (1.8%) EOS in period 1 and 97 (1.9%) EOS in period 2. During period 1 and 2, there were 61 (61/140, 44%) and 59 (59/97, 61%) EOS neonates, respectively, who met the criteria for shorter antibiotic treatment. The number of positive blood cultures were seven (0.92/1000 live births) and five (1.0/1000 live births) in period 1 and 2. The median C-reactive protein were 52 mg/L (37-62) in period 1 and 42 mg/L (31-56) in period 2 in the group who met the criteria of the guidelines. The duration of antibiotic therapy (Median: seven vs. five days, p < 0.001) and hospital stay (Median: seven vs. five days, p < 0.001) as well as healthcare costs (decreased by €122,000/year) was reduced in the group who met the criteria after the introduction of the guidelines. CONCLUSION: C-reactive protein- and clinical symptoms-guided decision-making for EOS significantly decreased the duration of antibiotic therapy and hospital stay, and hence reduced healthcare costs, with no reinfection in a cohort of term infants. TRIAL REGISTRATION: Trial registration number: ISRCTN29535824 . Date of registration: 28 May 2020. Retrospectively registered.

Changes in incidence and etiology of early-onset neonatal infections 1997-2017 - a retrospective cohort study in western Sweden.

BACKGROUND: The objective of the study was to evaluate data on early-onset neonatal invasive infections in western Sweden for the period 1997-2017. To identify changes in incidence, etiology and mortality and compare to previous studies from the same area starting from 1975. METHODS: Observational epidemiological, retrospective study on infants 0-6 days of age with a positive culture in blood and/or cerebrospinal fluid between 1997 and 2017. A comparison was made of the incidence between 2008 and 2017 compared to 1997-2007. Changes in the incidence of infections due to Group B streptococci, Staphylococcus aureus and aerobic Gram-negative rods were assessed from 1975. RESULTS: The total incidence, including both recognized pathogens and commensals as causative agents, was 1.1/1000 live births. The incidence declined from 1.4/1000 LB in 1997-2007 to 0.9/1000 LB in 2008-2017 but the case-fatality rate remained unchanged, (8/119 vs 7/90), at 7%. Among the 209 patients identified during 1997-2017 with sepsis or meningitis the most common organisms were Group B streptococci (40%, 84/209), S. aureus (16%, 33/209) and E. coli (9%, 18/209). The incidence of Group B streptococci infections went from 0.9/1000 live births 1987-1996 to 0.45/1000 live births 1997-2017 and all cases were within 72 h. The proportion of extremely preterm infants (< 28 weeks gestation) rose steadily during the study period but there was no rise in infections due to Gram-negative organisms. The spectrum of cultured organisms changed after 72 h as commensal organisms started to emerge. CONCLUSION: There has been a decrease in the incidence of neonatal early-onset infections compared to previous studies in western Sweden. The incidence of GBS infections was not as low as in other reports. Further studies are needed to assess if screening-based intra partum antimicrobial prophylaxis instead of a risk factor-based approach for identifying candidates for intrapartum antimicrobial prophylaxis would be a better option for this study area. KEY NOTES: This study is one of the longest running follow-ups in the world, a follow-up of 43 years of early-onset neonatal infections.The incidence of early-onset GBS infections is higher in Western Sweden compared to other local reports.No difference in the incidence of early-onset GBS depending on the definition of early-onset being within 72 h or 7 days of life.

Very low birthweight infants face an increased risk of bloodstream infections following the removal of umbilical catheters.

AIM: This study examined whether there was a temporal association between removing umbilical catheters and bloodstream infections (BSI) in a neonatal intensive care unit, as this is an area of research that has not received sufficient attention. METHODS: We carried out a retrospective study of all neonates receiving umbilical catheters during 2011 and 2012 in the neonatal intensive care unit at Sahlgrenska University Hospital, Gothenburg, Sweden. The time from umbilical catheter removals to the first subsequent BSI was recorded. RESULTS: A total of 372 infants had umbilical catheters inserted and 146 of these had a birthweight of <1500 g. Antibiotics were discontinued when umbilical catheters were removed in 67 of these low birthweight infants and 20 of them needed to be retreated for BSI within 72 hours. We found that very low birthweight infants had a significantly increased risk of developing BSI if antibiotics were discontinued at the same time as umbilical catheters were removed, rather than being continued after removal (p < 0.001). CONCLUSION: This NICU study demonstrated a temporal association between removing umbilical catheters and BSI in very low birthweight infants weighting <1500 g.

Communication skills training enhances nurses' ability to respond with empathy to parents' emotions in a neonatal intensive care unit.

AIM: We quantitatively analysed the effect of a course in communication on the content of nurse-parent encounters and the ability of nurses to respond to the empathic needs of parents in a level III neonatal intensive care unit. METHODS: We evaluated 36 and 45 nurse-parent encounters audio recorded before and after 13 neonatal nurses attended a communication course. The number of empathic opportunities, the nurses' responses to these and the ways they involved parents in their infants' care were studied. RESULTS: Both before and after the course, the nurses talked more than the parents during the conversations. This nurse-centredness decreased after the course. The use of empathic or exploring responses to empathic opportunities increased from 19.9 ± 9.0% to 53.8 ± 8.9% (p = 0.027), whereas ignoring the feelings of the parents or giving inadequate advice decreased from 63.0 ± 10.0% to 27.5 ± 8.4% (p = 0.043) after the course. Use of statements expressing caring for the parents and encouragement for parents to participate in the care of their infant increased after the course (p = 0.0034 and p = 0.043, respectively). The nurses felt the course was very useful for their profession. CONCLUSION: A course in communication techniques improved nurses' ability to respond to parents' feelings with empathy.

Serotypes of group B streptococci in western Sweden and comparison with serotypes in two previous studies starting from 1988.

BACKGROUND: Group B Streptococci (GBS) are the most common neonatal pathogens and infect immunocompromised and elderly individuals. The species has 10 different serotypes. Serotypes have been studied in the south-west area of Sweden in 1988-1997 and 1998-2001. The aim of this study was to study serotypes in the same area from 2004 to 2009. METHODS: Invasive GBS isolates were collected prospectively from 2004 to 2009 in two counties in western Sweden with a population of 1.8 million, and were serotyped by latex agglutination. Clinical data were obtained from hospital records. During the study period 410 invasive GBS isolates from 398 patients were collected (multiple episodes ≥ 1 month apart). Clinical data were not available for two patients who are excluded. Four isolates were from stillborn neonates, 88 were from live born neonates and infants, and 318 from adults. RESULTS: Serotype III was the most common serotype (48%) in neonates and infants followed by serotypes Ia (18%) and V (16%). In adults serotype V (39%) dominated followed by serotypes III (20%) and Ib (14%). There was a significant increase of serotype V in comparison with the first study (1988-1997) but there were no significant changes in the serotype distribution between the present study and the second study (1998-2001). There were a few cases of serotype VI-IX, both in children and adults, not seen in the previous studies. Serotype V was more common among patients with arthritis than with any other manifestation. CONCLUSIONS: Changes in GBS serotypes occur over time in the same region, which must be considered when GBS vaccines are formulated.

Antibiotic Use in Late Preterm and Full-Term Newborns.

Importance: Antibiotic treatment saves lives in newborns with early-onset sepsis (EOS), but unwarranted antibiotic use is associated with resistant bacteria and adverse outcomes later in life. Surveillance is needed to optimize treatment strategies. Objective: To describe antibiotic use in association with the incidence and mortality from EOS among late-preterm and full-term newborns. Design, Setting, and Participants: The Sweden Neonatal Antibiotic Use study was a nationwide observational study that included all late-preterm and full-term neonates born from January 1, 2012, to December 31, 2020, in neonatal units of all levels. All hospital live births from 34 weeks' gestation during the study period were included in the study. Data were collected from the Swedish Neonatal Quality Register and the Swedish Medical Birth Register. Data were analyzed from August 2022 to May 2023. Exposure: Admission for neonatal intensive care during the first week of life. Main Outcomes and Measures: The main outcomes were the usage of intravenous antibiotics during the first week of life, the duration of antibiotic therapy, the rate of culture-proven EOS, and mortality associated with EOS. Results: A total of 1 025 515 newborns were included in the study; 19 286 neonates (1.88%; 7686 girls [39.9%]; median [IQR] gestational age, 40 [38-41] weeks; median [IQR] birth weight, 3610 [3140-4030] g) received antibiotics during the first week of life, of whom 647 (3.4%) had EOS. The median (IQR) duration of antibiotic treatment in newborns without EOS was 5 (3-7) days, and there were 113 antibiotic-days per 1000 live births. During the study period there was no significant change in the exposure to neonatal antibiotics or antibiotic-days per 1000 live births. The incidence of EOS was 0.63 per 1000 live births, with a significant decrease from 0.74 in 2012 to 0.34 in 2020. Mortality associated with EOS was 1.39% (9 of 647 newborns) and did not change significantly over time. For each newborn with EOS, antibiotic treatment was initiated in 29 newborns and 173 antibiotic-days were dispensed. Conclusions and Relevance: This large nationwide study found that a relatively low exposure to antibiotics is not associated with an increased risk of EOS or associated mortality. Still, future efforts to reduce unwarranted neonatal antibiotic use are needed.

A randomized controlled study about the use of eHealth in the home health care of premature infants.

BACKGROUND: One area where the use of information and communication technology (ICT), or eHealth, could be developed is the home health care of premature infants. The aim of this randomized controlled study was to investigate whether the use of video conferencing or a web application improves parents' satisfaction in taking care of a premature infant at home and decreases the need of home visits. In addition, nurses' attitudes regarding the use of these tools were examined. METHOD: Thirty-four families were randomized to one of three groups before their premature infant was discharged from the hospital to home health care: a control group receiving standard home health care (13 families); a web group receiving home health care supplemented with the use of a web application (12 families); a video group with home health care supplemented with video conferencing using Skype (9 families). Families and nursing staff answered questionnaires about the usefulness of ICT. In addition, semi-structured interviews were conducted with 16 families. RESULTS: All the parents in the web group found the web application easy to use. 83% of the families thought it was good to have access to their child's data through the application. All the families in the video group found Skype easy to use and were satisfied with the video calls. 88% of the families thought that video calls were better than ordinary phone calls. 33% of the families in the web group and 75% of those in the video group thought the need for home visits was decreased by the web application or Skype. 50% of the families in the web group and 100% of those in the video group thought the web application or the video calls had helped them feel more confident in caring for their child. Most of the nurses were motivated to use ICT but some were reluctant and avoided using the web application and video conferencing. CONCLUSION: The families were satisfied with both the web application and video conferencing. The families readily embraced the use of ICT, whereas motivating some of the nurses to accept and use ICT was a major challenge.

Factors influencing survival and short-term outcomes of very low birth weight infants in a tertiary hospital in Johannesburg.

Background: The neonatal mortality rate in South Africa is lower than the global average, but still approximately five times higher than some European and Scandinavian countries. Prematurity, and its complications, is the main cause (35%) of neonatal deaths. Objective: To review the maternal, delivery period and infant characteristics in relation to mortality in very low birth weight (VLBW) infants at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). Methods: This was a retrospective descriptive study of VLBW infants admitted to CMJAH between 1 January 2017 and 31 December 2018. All infants with a birth weight between 500 to ≤ 1,500 grams were included. The characteristics and survival of these infants were described using univariate analysis. Results: Overall survival was 66.5%. Provision of antenatal steroids, antenatal care, Cesarean section, female sex, resuscitation at birth, and 5-min Apgar score more than five was related with better survival to discharge. Among respiratory diagnoses, 82.8% were diagnosed with RDS, 70.8% received surfactant therapy and 90.7% received non-invasive respiratory support after resuscitation. At discharge, 59.5% of the mothers were breastfeeding and 30.8% spent time in kangaroo mother care. Conclusion: The two-thirds survival rate of VLBW infants is similar to those in other developing countries but still remains lower than developed countries. This may be improved with better antenatal care attendance, coverage of antenatal steroids, temperature control after birth, improving infection prevention and control practices, breastfeeding rates and kangaroo mother care. The survival rate was lowest amongst extremely low birth weight (ELBW) infants.

Late-onset Neonatal Infections 1997 to 2017 Within a Cohort in Western Sweden-The Last 21 Years of a 43-Year Surveillance.

BACKGROUND: The objective of the study was to assess the epidemiology of late-onset (LO) neonatal invasive infections with surveillance covering 43 years, starting from 1975. METHODS: Observational epidemiologic, retrospective study including a cohort of infants born in western Sweden in 1997-2017, who had a positive blood and cerebral spinal fluid culture between 3 and 120 days of age. A comparison was made of the incidence between 1997-2007 and 2008-2017. Data on LO infections during 3-27 days of life were assessed from 1975. RESULTS: A total of 473 cases of LO infections were registered in 437 patients. The incidence increased from 2.0 to 3.1/1000 live births (LB) between 1997-2007 and 2008-2017 (P < 0.001). The increase in incidence was most pronounced among infants born <28 weeks gestation (from 255 to 398/1000 LB, P < 0.001). The most frequent pathogens were Staphylococcus aureus (25%), coagulase-negative staphylococci (17%), and Escherichia coli (13%). Infections due to group B Streptococci rose from 0.16/1000 LB to 0.33 (P = 0.03). During the whole surveillance period from 1975 to 2017, there were 579 cases between 3 and 27 days of life. Although the incidence increased in 2008-2017 to 1.9/1000 LB after first declining in 1997-2007, the case-fatality rate continued to decline from 27/284 (9.5%) between 1975 and 1996 to 6/182 (3.3%) in 2008 and 2017 (P = 0.01). CONCLUSIONS: The incidence of LO neonatal invasive infections increased during the study period (1997-2017), but the case-fatality rate remained lower than in the previous surveillance period (1975-1996). Further surveillance and interventions with focus on prevention is critical to counteract the increasing incidence among high-risk infants.

Reduced antibiotic use in extremely preterm infants with an antimicrobial stewardship intervention.

INTRODUCTION: Excessive administration of antibiotics to preterm infants is associated with increased rates of complications. The purpose of the study was to evaluate the effect of an antimicrobial stewardship intervention on antibiotic use in extremely preterm infants. DESIGN SETTING PATIENTS AND INTERVENTION: A before and after study of infants born at ≤28 weeks' gestational age was performed in the neonatal intensive care unit of Queen Silvia's Children's Hospital, Gothenburg, Sweden. Retrospective analysis of the baseline period (January-December 2014) guided the development of a limited antimicrobial stewardship intervention. The intervention consisted of updated local guidelines with a focus on shortened and standardised treatment duration plus increased access to infectious disease consultant advice. It was fully implemented during the intervention period (October 2017-September 2018). OBJECTIVE: Primary aim was to compare antibiotic use, defined as antibiotic treatment days per 1000 patient-days, between the two periods, and the secondary aim was to evaluate the number of days with meropenem-based regimens before and after the intervention. RESULTS: We included 145 infants with a median birth weight of 870 g and median gestational age of 26 weeks. The baseline period comprised 82 infants and 3478 patient-days, the intervention period comprised 63 infants and 2753 patient-days. Overall antibiotic use (treatment and prophylaxis) was 534 versus 466 days per 1000 patient-days during the baseline and intervention periods, respectively. Antibiotic treatment days decreased from 287 to 197 days per 1000 patient-days. The proportion of meropenem-based regimens was 69% versus 44%, respectively. No increases in mortality or reinitiation of antibiotics were seen. CONCLUSIONS: Implementation of a limited antimicrobial stewardship intervention anchored in analysis of previous prescription patterns can contribute to safe decreases in antibiotic use in extremely preterm infants.

Tick-borne encephalitis virus (TBEV) infection in pregnancy: Absence of virus transmission to the fetuses despite severe maternal disease - A case study.

Tick-borne encephalitis (TBE) is an emerging infectious disease in large parts of Europe and Asia. Whereas other members of the Flaviviridae family can harm fetal development, there are only very few reports on TBE virus (TBEV) infections during pregnancy. Thus, the implications for fetal health remain largely unknown. In this study, we present detailed pre- and postnatal health assessment of three children in the context of severe maternal TBEV infection during pregnancy. Following acute TBEV infection of the mothers, intrauterine growth and development of all children were assessed by repetitive prenatal ultrasound. Postnatal examinations included clinical and virological analyses over a follow-up period of 18 months. Prenatally, no signs of intrauterine growth restrictions were observed. All neonates were delivered at term. Umbilical cord blood of the newborns tested negative for TBEV RNA. Virus-specific IgG antibodies were positive at birth but negative at 9 and 11 months of age. Importantly, IgM antibodies remained negative throughout the period of observation. Taken together, these clinical and virological data strongly suggest that fetal TBEV infection did not occur, despite severe manifestations in the mothers.