ABSTRACT
OBJECTIVE: To study (i) the prevalence and risk factors for carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) in pregnant women, (ii) the maternal-neonatal transmission rate of ESBL-E at birth and (iii) the prevalence of ESBL-E in expressed breast milk of colonized mothers. STUDY DESIGN: In this cross-sectional, population-based study with case follow-up on maternal-neonatal transmission of ESBL-E, women were screened for rectal ESBL-E colonization at 36 weeks of pregnancy and delivery. Possible risk factors for colonization were studied by logistic regression. Infants of ESBL-E-positive mothers were screened for ESBL-E during their first weeks of life. ESBL-encoding genes were detected by PCR and clonal relatedness was investigated by pulsed-field gel electrophoreses. RESULTS: In total, 26 out of 901 (2.9%) women were colonized by ESBL-producing Escherichia coli at 36 weeks of pregnancy. One of the women carried an additional ESBL Klebsiella pneumoniae strain. Adjusted for traveling, African or Asian nationality was a risk factor for colonization; OR=5.62 (2.21, 14.27) (LR-p=0.003). Fourteen women remained ESBL-E carriers at delivery. ESBL-E strains indistinguishable from the strains isolated from their respective mothers were detected in 5 (35.7%) infants during their first days of life (median day 3; range=2 to 8). A total of 146 expressed milk samples were cultured from 25 out of 26 colonized mothers, all were ESBL-E negative. CONCLUSIONS: The prevalence of ESBL-E carriage among pregnant women was low in our region, but the high maternal-neonatal transmission rate suggests that colonized mothers represent a substantial risk for infant colonization.
Subject(s)
Enterobacteriaceae Infections/transmission , Infectious Disease Transmission, Vertical/statistics & numerical data , Pregnancy Complications, Infectious/diagnosis , Prenatal Diagnosis , beta-Lactamases/metabolism , Adult , Carrier State/epidemiology , Cross-Sectional Studies , Enterobacteriaceae/isolation & purification , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae Infections/enzymology , Female , Humans , Infant, Newborn , Logistic Models , Norway/epidemiology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Trimester, Third , Prevalence , Risk AssessmentABSTRACT
The human polyomavirus BK (BKV) causes nephropathy and hemorrhagic cystitis in kidney and bone marrow transplant patients, respectively. The anti-viral cidofovir (CDV) has been used in small case series but the effects on BKV replication are unclear, since polyomaviruses do not encode viral DNA polymerases. We investigated the effects of CDV on BKV(Dunlop) replication in primary human renal proximal tubule epithelial cells (RPTECs). CDV inhibited the generation of viral progeny in a dose-dependent manner yielding a 90% reduction at 40 microg/mL. Early steps such as receptor binding and entry seemed unaffected. Initial large T-antigen transcription and expression were also unaffected, but subsequent intra-cellular BKV DNA replication was reduced by >90%. Late viral mRNA and corresponding protein levels were also 90% reduced. In uninfected RPTECs, CDV 40 microg/mL reduced cellular DNA replication and metabolic activity by 7% and 11% in BrdU and WST-1 assays, respectively. BKV infection increased DNA replication to 142% and metabolic activity to 116%, respectively, which were reduced by CDV 40 microg/mL to levels of uninfected untreated RPTECs. Our results show that CDV inhibits BKV DNA replication downstream of large T-antigen expression and involves significant host cell toxicity. This should be considered in current treatment and drug development.
