Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.

Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.

Cross-sectional study of the proportion of antibiotic use during childbirth in full-term deliveries in Finland.

PURPOSE: In developed countries, data on the frequency of antibiotics given to mothers during childbirth are limited beyond the overall effect of all various prophylactic indications. Also, data on the impact of such antibiotics to the well-being of term babies are scarce. We aimed to characterize the frequency of antibiotic use during childbirth of term pregnancy. Secondly, we assessed whether the use of antibiotics was associated with any symptoms in infants. METHODS: This was a cross-sectional study of 1019 term deliveries of women participating in the prospective Health and Early Life Microbiota (HELMi) birth cohort study between March 2016 and March 2018 in the capital region of Finland. The data on antibiotic use were collected from the hospital records. RESULTS: In total, 37% of the mothers received antibiotics during childbirth and 100% in Caesarean Sects. (17% of the deliveries). Less than 5% of antibiotics were non-prophylactic. In vaginal deliveries, the most common indication (18%) was prophylaxis for Group B Streptococcus. The most frequently used antibiotics were cefuroxime (22%) and benzylpenicillin (15%), and 56% received only one dose. In infants exposed to antibiotics during delivery, defecation frequency was higher during the first months (p-value < 0.0001- 0.0145), and weight gain was higher at the age of three months (p-value 0.0371). CONCLUSION: More than every third new-born in a developed country is exposed to antibiotics during birth. Our findings support the hypothesis that maternal antibiotics given during birth have an impact on the well-being of the infants. These findings should inform current policies for prophylactic antibiotics in childbirth.

Early deaths associated with community-acquired and healthcare-associated bloodstream infections: a population-based study, Finland, 2004 to 2018.

BackgroundBloodstream infections (BSI) cause substantial morbidity and mortality.AimWe explored the role of causative pathogens and patient characteristics on the outcome of community-acquired (CA) and healthcare-associated (HA) BSI, with particular interest in early death.MethodsWe used national register data to identify all BSI in Finland during 2004-18. We determined the origin of BSI, patients´ underlying comorbidities and deaths within 2 or 30 days from specimen collection. A time-dependent Cox model was applied to evaluate the impact of patient characteristics and causative pathogens on the hazard for death at different time points.ResultsA total of 173,715 BSI were identified; 22,474 (12.9%) were fatal within 30 days and, of these, 6,392 (28.4%) occurred within 2 days (7.9 deaths/100,000 population). The 2-day case fatality rate of HA-BSI was higher than that of CA-BSI (5.4% vs 3.0%). Patients who died within 2 days were older than those alive on day 3 (76 vs 70 years) and had more severe comorbidities. Compared with other BSI, infections leading to death within 2 days were more often polymicrobial (11.8% vs 6.3%) and caused by Pseudomonas aeruginosa (6.2% vs 2.0%), fungi (2.9% vs 1.4%) and multidrug-resistant (MDR) pathogens (2.2% vs 1.8%), which were also predictors of death within 2 days in the model.ConclusionsOverrepresentation of polymicrobial, fungal, P. aeruginosa and MDR aetiology among BSI leading to early death is challenging concerning the initial antimicrobial treatment. Our findings highlight the need for active prevention and prompt recognition of BSI and appropriate antimicrobial treatment.

The outcome and timing of death of 17,767 nosocomial bloodstream infections in acute care hospitals in Finland during 1999-2014.

Few studies covering all patient groups and specialties are available regarding the outcome of nosocomial bloodstream infections (BSI). We analyzed the role of patient characteristics and causative pathogens of nosocomial BSIs reported by the hospitals participating in national surveillance in Finland during 1999-2014, in terms of outcome, with particular interest in those leading to death within 2 days (i.e. early death). National nosocomial BSI surveillance was laboratory-based and hospital-wide. Data on nosocomial BSIs was collected by infection control nurses, and dates of death were obtained from the national population registry with linkage to national identity codes. A total of 17,767 nosocomial BSIs were identified; 557 BSIs (3%) were fatal within 2 days and 1150 (6%) within 1 week. The 1-month case fatality was 14% (2460 BSIs), and 23% of the deaths occurred within 2 days and 47% within 1 week. The patients who died early were older than those who survived > 28 days, and their BSIs were more often related to intensive care. Gram-positive bacteria caused over half of the BSIs of patients who survived, whereas gram-negative bacteria, especially Pseudomonas aeruginosa, caused more often BSIs of patients who died early, and fungi BSIs of patients who died within 1 week. A significant portion of patients with nosocomial BSIs died early, which underlines the importance of rapid recognition of BSI. Hospital-wide surveillance data of causative pathogens can be utilized when composing recommendations for empiric antimicrobial treatment in collaboration with clinicians, as well as when promoting infection prevention.

Clinical characteristics and population-based attack rates of respiratory syncytial virus versus influenza hospitalizations among adults-An observational study.

BACKGROUND: The clinical significance of respiratory syncytial virus (RSV) among adults remains underinvestigated. We compared the characteristics and population-based attack rates of RSV and influenza hospitalizations. METHODS: During 2018-2020, we recruited hospitalized adults with respiratory infection to our prospective substudy at a tertiary care hospital in Finland and compared the characteristics of RSV and influenza patients. In our retrospective substudy, we calculated the attack rates of all RSV and influenza hospitalizations among adults in the same geographic area during 2016-2020. RESULTS: Of the 537 prospective substudy patients, 31 (6%) had RSV, and 106 (20%) had influenza. Duration of hospitalization, need for intensive care or outcome did not differ significantly between RSV and influenza patients. RSV was more often missed or its diagnosis omitted from medical record (13% vs 1% p = 0.016 and 48% vs 15%, p > 0.001). In the retrospective substudy, the mean attack rates of RSV, influenza A, and influenza B hospitalizations rose with age from 4.1 (range by season 1.9-5.9), 15.4 (12.3-23.3), and 4.7 (0.5-16.2) per 100,000 persons among 18- to 64-year-olds to 58.3 (19.3-117.6), 204.1 (31.0-345.0), and 60.4 (0.0-231.0) per 100,000 persons among 65+-year-olds and varied considerably between seasons. DISCUSSION: While the attack rates of influenza hospitalizations were higher compared with RSV, RSV and influenza hospitalizations were similar in severity. Missing or underreporting of RSV infections may lead to underestimating its disease burden. Both RSV and influenza caused a substantial amount of hospitalizations among the elderly, stressing the need for more effective interventions.

Quantitative insights into effects of intrapartum antibiotics and birth mode on infant gut microbiota in relation to well-being during the first year of life.

Birth mode and maternal intrapartum (IP) antibiotics affect infants' gut microbiota development, but their relative contribution to absolute bacterial abundances and infant health has not been studied. We compared the effects of Cesarean section (CS) delivery and IP antibiotics on infant gut microbiota development and well-being over the first year. We focused on 92 healthy infants born between gestational weeks 37-42 vaginally without antibiotics (N = 26), with IP penicillin (N = 13) or cephalosporin (N = 7) or by CS with IP cephalosporin (N = 33) or other antibiotics (N = 13). Composition and temporal development analysis of the gut microbiota concentrated on 5 time points during the first year of life using 16S rRNA gene amplicon sequencing, integrated with qPCR to obtain absolute abundance estimates. A mediation analysis was carried out to identify taxa linked to gastrointestinal function and discomfort (crying, defecation frequency, and signs of gastrointestinal symptoms), and birth interventions. Based on absolute abundance estimates, the depletion of Bacteroides spp. was found specifically in CS birth, while decreased bifidobacteria and increased Bacilli were common in CS birth and exposure to IP antibiotics in vaginal delivery. The abundances of numerous taxa differed between the birth modes among cephalosporin-exposed infants. Penicillin had a milder impact on the infant gut microbiota than cephalosporin. CS birth and maternal IP antibiotics had both specific and overlapping effects on infants' gut microbiota development. The resulting deviations in the gut microbiota are associated with increased defecation rate, flatulence, perceived stomach pain, and intensity of crying in infancy.

Comparison of the clinical characteristics and outcomes of hospitalized adult COVID-19 and influenza patients - a prospective observational study.

BACKGROUND: We compared the clinical characteristics, findings, and outcomes of hospitalized patients with coronavirus disease 2019 (COVID-19) or influenza to detect relevant differences. METHODS: From December 2019 to April 2020, we recruited all eligible hospitalized adults with respiratory infection to a prospective observational study at a tertiary care hospital in Finland. Influenza and SARS-CoV-2 infections were confirmed by RT-PCR. Follow-up lasted for 3 months from admission. RESULTS: We included 61 patients, of whom 28 were COVID-19 and 33 influenza patients with median ages of 53 and 56 years. Majority of both COVID-19 and influenza patients were men (61% vs. 67%) and had at least one comorbidity (68% vs. 85%). Pulmonary diseases and current smoking were less common among COVID-19 than influenza patients (5 [18%] vs. 15 [45%], p=.03 and 1 [4%] vs. 10 [30%], p=.008). In chest X-ray at admission, ground-glass opacities (GGOs) and consolidations were more frequent among COVID-19 than influenza patients (19 [68%] and 7 [21%], p<.001). Severe disease and intensive care unit (ICU) admission occurred more often among COVID-19 than influenza patients (26 [93%] vs. 19 [58%], p=.003 and 8 [29%] vs. 2 [6%], p=.034). COVID-19 patients were hospitalized longer than influenza patients (six days [IQR 4-21] vs. 3 [2-4], p<.001). CONCLUSIONS: Bilateral GGOs and consolidations in chest X-ray may help to differentiate COVID-19 from influenza. Hospitalized COVID-19 patients had more severe disease, required longer hospitalization and were admitted to ICU more often than influenza patients, which has important implications for public health policies.

Three cases of fulminant cellulitis caused by non-O1, non-O139 Vibrio cholerae in Southern Finland.

Background: Non-O1, non-O139 Vibrio cholerae is endemic in temperate waters. Most often encountered as the pathogen in transient gastroenteritis, it can also cause severe soft tissue infections. While normally a rare pathogen in Finland, we observed seven cases of non-O1, non-O139 V. cholerae infections in Helsinki University Hospital during the hot summer of 2018. Here we present three of these cases with fulminant V. cholerae cellulitis in detail.Methods: Patients with tissue culture positive soft tissue infections between 2017 and 2019 were identified using a local laboratory database. Patients with severe infections requiring surgical revision were included in this series.Results: Three patients with tissue culture positive non-O1, non-O139 V. cholerae cellulitis were identified. All were treated in the summer of 2018 for fulminant lower leg cellulitis. Two patients were febrile and hemodynamically unstable at presentation. One had septicaemia. Surgical revisions were done within the first week of admission, and defects covered with partial-thickness skin grafts several weeks later. Antibiotic treatment varied and continued until the wounds were healed, between one and over two months in total.

Prevalence and risk factors of squamous intraepithelial lesions of the cervix among HIV-infected women - a long-term follow-up study in a low-prevalence population.

HIV-infected women have high risk for precancerous lesions of the uterine cervix. We studied the prevalence and risk factors of squamous intraepithelial lesions (SIL) among systematically followed HIV-infected women enrolled from a population with low HIV prevalence. The study population consisted of 108 HIV-infected women enrolled between 1989 and 2003 with a mean follow-up 4.4 years. Risk factors of SIL were assessed based on samples collected during 2000-02. The overall rates of atypical glandular cells of uncertain significance (AGUS), atypical squamous cells of uncertain significance (ASCUS), low-grade SIL (LSIL) and high-grade SIL (HSIL) were 4, 24, 15 and 5%, respectively. Reduced CD4-lymphocyte count was associated with an increased prevalence of SIL, whereas duration of HIV infection (< or > or =5 years), use of antiretroviral medication, or HIV viral load (<50 or > or =50 copies/mL) was not. The cumulative risk of developing SIL after 1 and 5 years was 17% (95% confidence interval [CI] 7-27%) and 48% (95% CI 33-63%), respectively. The cumulative risk of SIL was increased among women younger than 31 years (P = 0.04) as well as in women displaying high initial HIV viral load (P = 0.01). Our results from a low HIV-incidence population re-emphasize the importance of guidelines for cytologic screening of HIV-seropositive women.

Early deaths in bloodstream infections: a population-based case series.

A notable portion of deaths in bloodstream infections (BSI) have previously been shown to occur within 2 days after taking the first positive blood culture specimen. The aim of this study was to analyse patients' characteristics and causative pathogens of BSIs, leading to early deaths in order to explore possibilities for prevention. Patients with BSI in Helsinki and Uusimaa region (population = 1.5 million) in 2007 were identified from the National Infectious Disease Register (n = 2181) and their deaths within 2 days after the first positive blood culture from the Population Information System (n = 76). Of the early fatal BSIs, 42 (55%) were community-acquired (CA-BSI) and 34 (45%) healthcare-associated (HA-BSI). Charlson comorbidity index was moderate-to-high (index ≥ 3) in 71% of HA-BSIs and 60% of CA-BSIs. The most common pathogens in CA-BSIs were Streptococcus pneumoniae (29%) and Escherichia coli (24%) and in HA-BSIs Pseudomonas aeruginosa (24%) and Staphylococcus aureus (18%). The respiratory tract (50%) was the most common focus of infection. Empiric antimicrobial treatment was more often appropriate in CA-BSIs vs HA-BSIs (81% vs 41%, p < 0.001), but treatment delays were longer in CA-BSIs. The majority of the BSI patients who died early had severe comorbidities. S. pneumoniae accounted for one third of CA-BSIs, highlighting the potential role of pneumococcal vaccines in prevention. Early recognition of BSI and its origin (CA-BSI vs HA-BSI) is crucial. Continuous surveillance data on causative microbes and resistance trends in hospitals is needed to propose guidelines for empiric antimicrobial therapy of BSIs.

A newborn with domestically acquired legionnaires disease confirmed by molecular typing.

Legionella pneumophila serogroup 6 was recovered from a bronchoalveolar lavage specimen from a 1-week-old, full-term newborn with pneumonia, as well as from water samples from the maternity hospital and the newborn's home (an apartment). Amplified fragment-length polymorphism typing revealed that the strains isolated from the newborn and her home were indistinguishable from each other but were clearly different from the hospital and control strains. To our knowledge, this is the first report of domestic acquisition of legionnaires disease in a newborn to have been confirmed by molecular typing.

Pregnancy outcome among HIV-infected women in the Helsinki metropolitan area.

BACKGROUND: Antiretroviral medication and good obstetric practice have greatly reduced the rate of vertical transmission of human immunodeficiency virus (HIV) infection. The incidence of HIV infection has remained low in Finland. Universal antenatal screening has been offered to all pregnant women since 1998. METHODS: We analyzed the outcomes of 52 pregnancies among 45 HIV-infected mothers delivering at our department during 1993-2003. A multidisciplinary team planned the management strategy individually and supported the mother's adherence to treatment. RESULTS: The incidence of HIV infection among women delivering in our hospital district increased from 0.6/10,000 (95% CI 0-1.6) to 4.8/10,000 (95% CI 1.4-8.2) between 1993 and 2002. HIV infection was diagnosed during pregnancy in 40% (18/45) of the mothers. Antiretroviral medication was used prior to pregnancy in 17 (33%) cases; in 34 (66%) cases of the pregnancies, medication was started during the pregnancy. A good virological response (i.e. HIV RNA load <1000/ml during the last trimester) to antiretroviral medication was achieved in 90% (36/40) of the patients; in 60% (24/40) of cases, the HIV RNA load was below the assay detection limit. One mother with advanced HIV infection succumbed to pneumonia shortly after delivery. Of the infants, 92% were born at term, and their mean (+/-SD) birth weight was 3350 +/- 395 g. The Caesarean section (CS) rate was 25% (13/52). All newborns were in good condition, and their mean umbilical pH was 7.23. All newborns received antiretroviral medication. One infant was infected with HIV, the mother was found HIV-positive postpartum. None of the infants born to mothers known to be HIV positive were infected. CONCLUSIONS: A combination of universal antenatal screening and multidisciplinary management allows individualized treatment and prevents vertical transmission of HIV infection.