Perinatal colonization with extended-spectrum beta-lactamase-producing and carbapenem-resistant Gram-negative bacteria: a hospital-based cohort study.

BACKGROUND: Antimicrobial resistance (AMR) is a growing global health threat that contributes to substantial neonatal mortality. Bangladesh has reported some of the highest rates of AMR among bacteria causing neonatal sepsis. As AMR colonization among newborns can predispose to infection with these bacteria, we aimed to characterize the frequency of and risk factors for colonization of mothers and newborns during hospitalization for delivery. METHODS: We enrolled pregnant women presenting for delivery to a tertiary care hospital in Faridpur, Bangladesh. We collected vaginal and rectal swabs from mothers pre- and post-delivery, rectal swabs from newborns, and swabs from the hospital environment. Swabs were plated on agars selective for extended-spectrum-beta-lactamase producing bacteria (ESBL-PB) and carbapenem-resistant bacteria (CRB). We performed logistic regression to determine factors associated with ESBL-PB/CRB colonization. RESULTS: We enrolled 177 women and their newborns during February-October 2020. Prior to delivery, 77% of mothers were colonized with ESBL-PB and 15% with CRB. 79% of women underwent cesarean deliveries (C-section). 98% of women received antibiotics. Following delivery, 98% of mothers and 89% of newborns were colonized with ESBL-PB and 89% of mothers and 72% of newborns with CRB. Of 290 environmental samples, 77% were positive for ESBL-PB and 69% for CRB. Maternal pre-delivery colonization was associated with hospitalization during pregnancy (RR for ESBL-PB 1.24, 95% CI 1.10-1.40; CRB 2.46, 95% CI 1.39-4.37). Maternal post-delivery and newborn colonization were associated with C-section (RR for maternal CRB 1.31, 95% CI 1.08-1.59; newborn ESBL-PB 1.34, 95% CI 1.09-1.64; newborn CRB 1.73, 95% CI 1.20-2.47). CONCLUSIONS: In this study, we observed high rates of colonization with ESBL-PB/CRB among mothers and newborns, with pre-delivery colonization linked to prior healthcare exposure. Our results demonstrate this trend may be driven by intense use of antibiotics, frequent C-sections, and a contaminated hospital environment. These findings highlight that greater attention should be given to the use of perinatal antibiotics, improved surgical stewardship for C-sections, and infection prevention practices in healthcare settings to reduce the high prevalence of colonization with AMR organisms.

Identifying the Sources of Intestinal Colonization With Extended-Spectrum ß-Lactamase-Producing Escherichia coli in Healthy Infants in the Community.

The prevalence of fecal colonization with extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-Ec) among children in low- and middle-income countries is alarmingly high. This study aimed to identify the sources of ESBL-Ec colonization in children < 1 year old through comparative analysis of E. coli isolates from child stool, child's mother stool, and point-of-use drinking water from 46 rural households in Bangladesh. The pairwise similarity in antibiotic susceptibility of E. coli from all three sources was evaluated, followed by phylogenetic clustering using enterobacterial repetitive intergenic consensus polymerase chain reaction and whole-genome sequence analysis of the isolates. Matching antibiotic susceptibility and enterobacterial repetitive intergenic consensus polymerase chain reaction patterns were found among ESBL-Ec isolates from child-mother dyads of 24 and 11 households, respectively, from child-water dyads of 5 and 4 households, respectively, and from child-mother-water triads of 3 and 4 households, respectively. Whole-genome sequence analysis of 30 isolates from 10 households revealed that ESBL-Ec from children in five households (50%) was clonally related to ESBL-Ec either from their mothers (2 households), drinking water sources (2 households), or both mother and drinking-water sources (1 household) based on serotype, phylogroup, sequence type, antibiotic resistance genes, mobile genetic elements, core single-nucleotide polymorphisms, and whole-genome multilocus sequence typing. Overall, this study provides empirical evidence that ESBL-Ec colonization in children is linked to the colonization status of mothers and exposure to the household environments contaminated with ESBL-Ec. Interventions such as improved hygiene practices and a safe drinking water supply may help reduce the transmission of ESBL-Ec at the household level.

Isolation and characterisation of carbapenem-resistant Pseudomonas aeruginosa from hospital environments in tertiary care hospitals in Dhaka, Bangladesh.

OBJECTIVES: Increasing evidence of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection in healthcare facilities poses an alarming threat to public health. There is little evidence on the occurrence of this organism in Bangladeshi hospitals. METHODS: We collected 117 environmental swab samples from two tertiary care hospitals in Dhaka, Bangladesh and tested for Pseudomonas species by nonselective enrichment of swabs followed by plating on Cetrimide agar. We confirmed the isolates as P. aeruginosa by API 20NE test and polymerase chain reaction Polymerase Chain Reaction (PCR) for 16S rRNA gene. We analysed P. aeruginosa isolates for susceptibility against 15 clinically important antibiotics and tested the carbapenem-resistant isolates for metallo ß-lactamase (MBL). All CRPA isolates were characterised for carbapenem-resistant genes, virulence genes and biofilm formation genes. RESULTS: Of 117 swab samples, 82 (70%) were tested positive for P. aeruginosa. All P. aeruginosa isolates were multidrug-resistant, and 39% (n = 32) of isolates were CRPA. Around 56% (n = 18) of CRPA were MBL-producing; 22% (n = 7) of isolates were positive for carbapenemase gene blaNDM followed by 16% (n = 5) for blaVIM and 13% (n = 4) for blaIMP. Sequencing identified these genes as blaNDM-1, blaIMP-13, blaVIM-2 variants. Based on optical density values, 94% (n = 30) of CRPA isolates were capable of producing biofilms. All CRPA isolates (n = 32) were positive for at least 1 of 6 biofilm-associated genes and 4 of 12 virulence genes tested in the study. CONCLUSION: Hospital environments in Bangladesh are contaminated with highly virulent CRPA, which might be a potential source of hospital-acquired infections, accentuating the need for strengthening hospital infection control programs.

Assessing impact of ventilation on airborne transmission of SARS-CoV-2: a cross-sectional analysis of naturally ventilated healthcare settings in Bangladesh.

OBJECTIVES: To evaluate the risk of exposure to SARS-CoV-2 in naturally ventilated hospital settings by measuring parameters of ventilation and comparing these findings with results of bioaerosol sampling. STUDY DESIGN: Cross-sectional study. STUDY SETTING AND STUDY SAMPLE: The study sample included nine hospitals in Dhaka, Bangladesh. Ventilation characteristics and air samples were collected from 86 healthcare spaces during October 2020 to February 2021. PRIMARY OUTCOME: Risk of cumulative SARS-CoV-2 infection by type of healthcare area. SECONDARY OUTCOMES: Ventilation rates by healthcare space; risk of airborne detection of SARS-CoV-2 across healthcare spaces; impact of room characteristics on absolute ventilation; SARS-CoV-2 detection by naturally ventilated versus mechanically ventilated spaces. RESULTS: The majority (78.7%) of naturally ventilated patient care rooms had ventilation rates that fell short of the recommended ventilation rate of 60 L/s/p. Using a modified Wells-Riley equation and local COVID-19 case numbers, we found that over a 40-hour exposure period, outpatient departments posed the highest median risk for infection (7.7%). SARS-CoV-2 RNA was most frequently detected in air samples from non-COVID wards (50.0%) followed by outpatient departments (42.9%). Naturally ventilated spaces (22.6%) had higher rates of SARS-CoV-2 detection compared with mechanically ventilated spaces (8.3%), though the difference was not statistically significant (p=0.128). In multivariable linear regression with calculated elasticity, open door area and cross-ventilation were found to have a significant impact on ventilation. CONCLUSION: Our findings provide evidence that naturally ventilated healthcare settings may pose a high risk for exposure to SARS-CoV-2, particularly among non-COVID-designated spaces, but improving parameters of ventilation can mitigate this risk.

A computational approach to design potential siRNA molecules as a prospective tool for silencing nucleocapsid phosphoprotein and surface glycoprotein gene of SARS-CoV-2.

An outbreak, caused by an RNA virus, SARS-CoV-2 named COVID-19 has become pandemic with a magnitude which is daunting to all public health institutions in the absence of specific antiviral treatment. Surface glycoprotein and nucleocapsid phosphoprotein are two important proteins of this virus facilitating its entry into host cell and genome replication. Small interfering RNA (siRNA) is a prospective tool of the RNA interference (RNAi) pathway for the control of human viral infections by suppressing viral gene expression through hybridization and neutralization of target complementary mRNA. So, in this study, the power of RNA interference technology was harnessed to develop siRNA molecules against specific target genes namely, nucleocapsid phosphoprotein gene and surface glycoprotein gene. Conserved sequence from 139 SARS-CoV-2 strains from around the globe was collected to construct 78 siRNA that can inactivate nucleocapsid phosphoprotein and surface glycoprotein genes. Finally, based on GC content, free energy of folding, free energy of binding, melting temperature, efficacy prediction and molecular docking analysis, 8 siRNA molecules were selected which are proposed to exert the best action. These predicted siRNAs should effectively silence the genes of SARS-CoV-2 during siRNA mediated treatment assisting in the response against SARS-CoV-2.