Factors associated with extent of COVID-19 outbreaks: A prospective study in a large hospital network.

BACKGROUND: The COVID-19 pandemic has generated numerous hospital outbreaks. This study aimed to identify factors related to the extent of nosocomial COVID-19 outbreaks in the largest French public health institution. METHODS: An observational study was conducted from July 2020 to September 2021. Outbreaks were defined as at least 2 cases, patients and/or health care workers (HCWs), linked by time and geographic location. Logistic regression was performed to identify risk factors for large outbreaks among nine variables: variant, medical ward, COVID-19 vaccination rate and incidence among HCWs and Paris population, number of weekly COVID-19 tests among HCWs and the positivity rate, epidemic waves. RESULTS: Within 14 months, 799 outbreaks were identified: 450 small ones (≤6 cases) and 349 large ones (≥7 cases), involving 3,260 patients and 3,850 HCWs. In univariate analysis, large outbreaks were positively correlated to geriatrics wards, COVID-19 incidence, and rate of weekly positive tests among HCWs; and negatively correlated to intensive care units, variant Delta, fourth wave, vaccination rates of the Paris region's population and that of the HCWs. In multivariate analysis, factors that remained significant were the type of medical ward and the vaccination rate among HCWs. CONCLUSIONS: Intensive care unit and high vaccination rates among HCWs were associated with a lower risk of large COVID-19 outbreaks, as opposed to geriatric wards, which are associated with a higher risk.

Decrease of hospital- and community-acquired bloodstream infections due to Streptococcus pneumoniae and Streptococcus pyogenes during the first year of the COVID-19 pandemic: A time-series analysis in Paris region.

The impact of the COVID-19 pandemic on bloodstream infections (BSIs) due to Streptococcus pneumoniae and Streptococcus pyogenes was assessed in 25 university hospitals of Paris. Monthly BSIs incidence rates that appeared stable in 2018 and 2019, decreased for the 2 pathogens during the 2 COVID-19 lockdown periods of 2020. Containment policies, including social distancing, masking and hand hygiene strengthening in both community and hospital settings are likely to reduce BSIs due to these pathogens.

Surging bloodstream infections and antimicrobial resistance during the first wave of COVID-19: a study in a large multihospital institution in the Paris region.

OBJECTIVES: This study measured the impact of the first wave of COVID-19 pandemic (COVID-19) (March-April 2020) on the incidence of bloodstream infections (BSIs) at Assistance Publique - Hôpitaux de Paris (APHP), the largest multisite public healthcare institution in France. METHODS: The number of patient admission blood cultures (BCs) collected, number of positive BCs, and antibiotic resistance and consumption were analysed retrospectively for the first quarter of 2020, and also for the first quarter of 2019 for comparison, in 25 APHP hospitals (ca. 14 000 beds). RESULTS: Up to a fourth of patients admitted in March-April 2020 in these hospitals had COVID-19. The BSI rate per 100 admissions increased overall by 24% in March 2020 and 115% in April 2020, and separately for the major pathogens (Escherichia coli, Klebsiella pneumoniae, enterococci, Staphylococcus aureus, Pseudomonas aeruginosa, yeasts). A sharp increase in the rate of BSIs caused by microorganisms resistant to third-generation cephalosporins (3GC) was also observed in March-April 2020, particularly in K. pneumoniae, enterobacterial species naturally producing inducible AmpC (Enterobacter cloacae...), and P. aeruginosa. A concomitant increase in 3GC consumption occurred. CONCLUSIONS: The COVID-19 pandemic had a strong impact on hospital management and also unfavourable effects on severe infections, antimicrobial resistance, and laboratory work diagnostics.

The effects on ovarian activity of delaying versus immediately restarting combined oral contraception after missing three pills and taking ulipristal acetate 30 mg.

OBJECTIVE: Among combined oral contraception (COC) users, to determine the effect on ovarian activity and ovulation of waiting five days before restarting COC, versus restarting immediately, having taken ulipristal acetate 30 mg (UPA, the dose used for emergency contraception) after missing three consecutive COC pills. STUDY DESIGN: Women already using COC were enrolled for two cycles of COC use (21/7 regimen). In cycle 2, all women omitted COC pills for three consecutive days (days 5,6,7), and on day 8 took UPA 30 mg. They were randomized either to restart their COC pills that same day (immediate restart) or to wait five days (delayed restart). Transvaginal ultrasound, and blood sampling for estradiol and progesterone were undertaken on days 4,8,11,13,15,18,22 and 26. A modified Hoogland score was used to quantify ovarian activity/ovulation and to assess whether luteal phase progesterone concentrations were sufficiently 'adequate' to have conferred a theoretical risk of pregnancy. RESULTS: No one ovulated with risk of pregnancy during the five days following UPA. Among 26 women with immediate restart, none ovulated with a theoretical risk of pregnancy at any time in the cycle. Four of 23 women (17.4% CI [5.0; 38.8]) with delayed restart ovulated with theoretical risk of pregnancy before the end of the cycle. This difference was statistically significant (p = 0.042). CONCLUSION: Women who delay restarting COC for five days after taking UPA 30 mg are at much greater risk of ovulation, and therefore theoretically of pregnancy, than if they restart their COC on the same day as taking UPA. Current recommendations should be revisited. IMPLICATIONS: Women who take UPA-EC after having missed combined oral contraceptive pills are advised to wait five days before restarting the COC. This delay puts them at risk of ovulation and, if intercourse occurs, theoretically therefore of pregnancy. Women who restart their COC pills immediately are much less likely to ovulate. The label for UPA-EC and clinical guidelines on using EC after missed pills should be revisited.

Efficiency of different control measures for preventing carbapenemase-producing enterobacteria and glycopeptide-resistant Enterococcus faecium outbreaks: a 6-year prospective study in a French multihospital institution, January 2010 to December 2015.

An infection control programme was implemented in a 21,000-bed multihospital institution for controlling the spread of carbapenemase-producing Enterobacteriaceae (CPE) and glycopeptide-resistant Enterococcus faecium (GRE), classified as 'emergent extensively drug-resistant bacteria' (eXDR) in France. We evaluated factors associated with outbreaks occurrence (n = 103), which followed 901 eXDR introductions (index case followed or not by secondary cases) from 2010 to 2015. In univariate analysis, knowing that patients had been hospitalised abroad, bacterial species (GRE vs CPE, as well as the CPE Klebsiella pneumoniae compared with the other Enterobacteriaceae species) and type of measures implemented within the first 2 days of hospitalisation were associated with outbreaks occurrence, but not the type of wards where carriers were hospitalised, nor the eXDR colonisation or infection status. In multivariate analysis, occurrence of outbreaks was significantly lower when contact precautions (odds ratio (OR): 0.34; 95% confidence interval (CI): 0.22-0.54) and even more when dedicated nursing staff (OR: 0.09; 95% CI: 0.02-0.39) were implemented around eXDR index cases within the first 2 days of hospitalisation (p < 10 - 3). GRE introductions were more frequently associated with occurrence of outbreaks than CPE (OR: 3.58; 95% CI: 2.32-5.51, p < 10 - 3). A sustained and coordinated strategy is efficient to limit the spread of eXDR at the scale of a large health institution.

Phenotype and genotype for thiopurine methyltransferase activity in the French Caucasian population: impact of age.

OBJECTIVE: Thiopurine drugs are commonly used in pediatric patients for the treatment of acute leukemia, organ transplantation and inflammatory diseases. They are catabolized by the cytosolic thiopurine methyltransferase (TPMT), which is subject to a genetic polymorphism. In children, enzyme activities are immature at birth and developmental patterns vary widely from one enzyme to another. The present study was undertaken to evaluate erythrocyte TPMT activity and the correlation between genotype and phenotype in different age groups from birth to adolescence and adulthood. METHODS: The study included 304 healthy adult blood donors, 147 children and 18 neonates (cord bloods). TPMT activity was measured by liquid chromatography, and genotype was determined using a polymerase chain reaction reverse dot-blot analysis identifying the predominant TPMT mutant alleles (TPMT*3A, TPMT*3B, TPMT*3C, TPMT*2). RESULTS: There was no significant difference in TPMT activity between cord bloods ( n=18) and children ( n=147) (17.48+/-4.04 versus 18.62+/-4.14 respectively, P=0.424). However, TPMT was significantly lower in children than in adults (19.34+/-4.09) ( P=0.033). In the whole population, there were 91.9% homozygous wild type, 7.9% heterozygous mutants and 0.2% homozygous mutants. The frequency of mutant alleles was 3.0% for TPMT*3A, 0.7% for TPMT*2 and 0.4% for TPMT*3C. CONCLUSION: No impact of child development on TPMT activity could be evidenced, suggesting that TPMT activity is already mature at birth. The difference between children and adults was low with reduced clinical impact expected. When individual TPMT activity was compared with genotype, there was an overlapping region where subjects (4.5%, 12 adults, 9 children) were either homozygous wild type or heterozygous, with a TPMT activity below the antimode value. This result highlighted the importance of measuring TPMT activity to detect all patients at risk of thiopurine toxicity.