| 1. |
- Gyllensvaerd, Johan, et al.
(author)
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Antibiotic Use in Late Preterm and Full-Term Newborns
- 2024
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In: JAMA Network Open. - : AMER MEDICAL ASSOC. - 2574-3805. ; 7:3
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Journal article (peer-reviewed)abstract
- 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.
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| 2. |
- Selse, M., et al.
(author)
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Outcome of infants with necrotising enterocolitis at Charlotte Maxeke Johannesburg Academic Hospital, South Africa
- 2023
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In: South African Journal of Child Health. - 1994-3032. ; 17:1
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Journal article (peer-reviewed)abstract
- Background. Necrotising enterocolitis (NEC) is an inflammatory disease almost exclusively affecting preterm infants. Previous research has presented a higher mortality rate in infants requiring surgical treatment compared with infants receiving medical treatment. However, the knowledge of mortality and morbidity of the disease in low- and middle-income countries is still limited. Objectives. To review infants with NEC admitted to the neonatal unit at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH), determine a potential difference in mortality between medically and surgically treated infants, and to identify characteristics and factors associated with mortality among these infants. Methods. This retrospective study described infants with NEC born between 1 January 2016 and 31 December 2018 who were admitted to the neonatal unit. The characteristics and survival of these infants were compared using univariate and multivariate analyses. Results. During the study period, 5 061 infants were admitted to the neonatal unit, of which 218 infants were diagnosed with NEC. The period prevalence of NEC was 4.3% among all neonatal infants and 11.0% among very-low-birthweight (VLBW) infants. Mortality was significantly higher among surgically treated infants with NEC compared with medically treated infants (p=0.025, odds ratio 1.888 (95% confidence interval 1.082 - 3.296)). Late-onset sepsis was significantly more common among VLBW infants with NEC (71.3%) compared with VLBW infants without NEC (27.1%). Among infants with late-onset sepsis, Gram-negative bacteria, multidrug-resistant bacteria and fungal sepsis was significantly more common in the group of infants with NEC. Conclusions. Infants with NEC treated surgically at CMJAH have an increased risk of dying compared with those receiving medical treatment, likely due to the severity of disease. Furthermore, this study emphasised the burden of sepsis among infants with NEC and may contribute to a better knowledge of NEC in South Africa.
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| 3. |
- Tång Hallbäck, Erika, 1973, et al.
(author)
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Outbreak of OXA-48-producing Enterobacteriaceae in a neonatal intensive care unit in Western Sweden
- 2023
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In: European Journal of Clinical Microbiology and Infectious Diseases. - : Springer Science and Business Media LLC. - 1435-4373 .- 0934-9723. ; 42:5, s. 597-605
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Journal article (peer-reviewed)abstract
- 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.
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| 4. |
- Huebner, Emily M, et al.
(author)
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Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates.
- 2022
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In: Annals of clinical microbiology and antimicrobials. - : Springer Science and Business Media LLC. - 1476-0711. ; 21:1
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Journal article (peer-reviewed)abstract
- 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.
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| 5. |
- Ingemyr, Kristin, et al.
(author)
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Factors influencing survival and short-term outcomes of very low birth weight infants in a tertiary hospital in Johannesburg
- 2022
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In: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 10
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Journal article (peer-reviewed)abstract
- BackgroundThe 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. ObjectiveTo 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). MethodsThis 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. ResultsOverall 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. ConclusionThe 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.
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| 6. |
- Gudjónsdóttir, Margrét Johansson, et al.
(author)
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Late-onset Neonatal Infections 1997 to 2017 Within a Cohort in Western Sweden-The Last 21 Years of a 43-Year Surveillance.
- 2021
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In: The Pediatric infectious disease journal. - 1532-0987. ; 40:4, s. 359-364
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Journal article (peer-reviewed)abstract
- 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.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.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).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.
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| 7. |
- Mellqvist, Helena, et al.
(author)
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The effects of exposure to HIV in neonates at a referral hospital in South Africa
- 2021
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In: Bmc Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 21:1
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Journal article (peer-reviewed)abstract
- 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.
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| 8. |
- Divé, Iris, et al.
(author)
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Tick-borne encephalitis virus (TBEV) infection in pregnancy: Absence of virus transmission to the fetuses despite severe maternal disease - A case study.
- 2020
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In: Ticks and tick-borne diseases. - : Elsevier BV. - 1877-9603 .- 1877-959X. ; 11:5
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Journal article (peer-reviewed)abstract
- 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.
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| 9. |
- Gustavsson, Lars, et al.
(author)
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Reduced antibiotic use in extremely preterm infants with an antimicrobial stewardship intervention
- 2020
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In: BMJ paediatrics open. - : BMJ. - 2399-9772. ; 4:1
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Journal article (peer-reviewed)abstract
- 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.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).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.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.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.
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| 10. |
- Gyllensvärd, Johan, et al.
(author)
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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.
- 2020
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In: BMC pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 20:1
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Journal article (peer-reviewed)abstract
- 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.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.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 52mg/L (37-62) in period 1 and 42mg/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.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 number: ISRCTN29535824 . Date of registration: 28 May 2020. Retrospectively registered.
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