Potential for Person-to-Person Transmission of Henipaviruses: A Systematic Review of the Literature.

Nipah virus Bangladesh (NiVB) is a bat-borne zoonosis transmitted between people through the respiratory route. The risk posed by related henipaviruses, including Hendra virus (HeV) and Nipah virus Malaysia (NiVM), is less clear. We conducted a broad search of the literature encompassing both human infections and animal models to synthesize evidence about potential for person-to-person spread. More than 600 human infections have been reported in the literature, but information on viral shedding was only available for 40 case-patients. There is substantial evidence demonstrating person-to-person transmission of NiVB, and some evidence for NiVM. Less direct evidence is available about the risk for person-to-person transmission of HeV, but animals infected with HeV shed more virus in the respiratory tract than those infected with NiVM, suggesting potential for transmission. As the group of known henipaviruses continues to grow, shared protocols for conducting and reporting from human investigations and animal experiments are urgently needed.

Using Colonization to Understand the Burden of Antimicrobial Resistance Across Low- and Middle-Income Countries.

Understanding the burden of antibiotic resistance globally is hindered by incomplete surveillance, particularly across low-resource settings. The Antibiotic Resistance in Communities and Hospitals (ARCH) consortium encompasses sites across 6 resource-limited settings and is intended to address these gaps. Supported by the Centers for Disease Control and Prevention, the ARCH studies seek to characterize the burden of antibiotic resistance by examining colonization prevalence at the community and hospital level and to evaluate for risk factors that are associated with colonization. In this supplement, 7 articles present results from these initial studies. Though future studies identifying and evaluating prevention strategies will be critical to mitigate spreading resistance and its impact on populations, the findings from these studies address important questions surrounding the epidemiology of antibiotic resistance.

Risk Factors for Colonization With Extended-Spectrum Cephalosporin-Resistant and Carbapenem-Resistant Enterobacterales Among Hospitalized Patients in Kenya: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: The spread of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) represents a significant global public health threat. We identified putative risk factors for ESCrE and CRE colonization among patients in 1 urban and 3 rural hospitals in Kenya. METHODS: During a January 2019 and March 2020 cross-sectional study, stool samples were collected from randomized inpatients and tested for ESCrE and CRE. The Vitek2 instrument was used for isolate confirmation and antibiotic susceptibility testing, and least absolute shrinkage and selection operator (LASSO) regression models were used to identify colonization risk factors while varying antibiotic use measures. RESULTS: Most (76%) of the 840 enrolled participants received ≥1 antibiotic in the 14 days preceding their enrollment, primarily ceftriaxone (46%), metronidazole (28%), or benzylpenicillin-gentamycin (23%). For LASSO models that included ceftriaxone administration, ESCrE colonization odds were higher among patients hospitalized for ≥3 days (odds ratio, 2.32 [95% confidence interval, 1.6-3.37]; P < .001), intubated patients (1.73 [1.03-2.91]; P = .009), and persons living with human immunodeficiency virus (1.70 [1.03-2.8]; P = .029). CRE colonization odds were higher among patients receiving ceftriaxone (odds ratio, 2.23 [95% confidence interval, 1.14-4.38]; P = .025) and for every additional day of antibiotic use (1.08 [1.03-1.13]; P = .002). CONCLUSIONS: While CRE colonization was strongly associated with ceftriaxone use and duration of antibiotic use, the odds of ESCrE colonization increased with exposure to the hospital setting and invasive medical devices, which may reflect nosocomial transmission. These data suggest several areas where hospitals can intervene to prevent colonization among hospitalized patients, both through robust infection prevention and control practices and antibiotic stewardship programs.

Risk Factors for Colonization With Multidrug-Resistant Bacteria in Urban and Rural Communities in Kenya: An Antimicrobial Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Colonization with antimicrobial-resistant bacteria increases the risk of drug-resistant infections. We identified risk factors potentially associated with human colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low-income urban and rural communities in Kenya. METHODS: Fecal specimens, demographic and socioeconomic data were collected cross-sectionally from clustered random samples of respondents in urban (Kibera, Nairobi County) and rural (Asembo, Siaya County) communities between January 2019 and March 2020. Presumptive ESCrE isolates were confirmed and tested for antibiotic susceptibility using the VITEK2 instrument. We used a path analytic model to identify potential risk factors for colonization with ESCrE. Only 1 participant was included per household to minimize household cluster effects. RESULTS: Stool samples from 1148 adults (aged ≥18 years) and 268 children (aged <5 years) were analyzed. The likelihood of colonization increased by 12% with increasing visits to hospitals and clinics. Furthermore, individuals who kept poultry were 57% more likely to be colonized with ESCrE than those who did not. Respondents' sex, age, use of improved toilet facilities, and residence in a rural or urban community were associated with healthcare contact patterns and/or poultry keeping and may indirectly affect ESCrE colonization. Prior antibiotic use was not significantly associated with ESCrE colonization in our analysis. CONCLUSIONS: The risk factors associated with ESCrE colonization in communities include healthcare- and community-related factors, indicating that efforts to control antimicrobial resistance in community settings must include community- and hospital-level interventions.

Risk Factors for Community Colonization With Extended-Spectrum Cephalosporin-Resistant Enterobacterales (ESCrE) in Botswana: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: The epidemiology of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) in low- and middle-income countries (LMICs) is poorly described. Identifying risk factors for ESCrE colonization is critical to inform antibiotic resistance reduction strategies because colonization is typically a precursor to infection. METHODS: From 15 January 2020 to 4 September 2020, we surveyed a random sample of clinic patients at 6 sites in Botswana. We also invited each enrolled participant to refer up to 3 adults and children. All participants had rectal swabs collected that were inoculated onto chromogenic media followed by confirmatory testing. Data were collected on demographics, comorbidities, antibiotic use, healthcare exposures, travel, and farm and animal contact. Participants with ESCrE colonization (cases) were compared with noncolonized participants (controls) to identify risk factors for ESCrE colonization using bivariable, stratified, and multivariable analyses. RESULTS: A total of 2000 participants were enrolled. There were 959 (48.0%) clinic participants, 477 (23.9%) adult community participants, and 564 (28.2%) child community participants. The median (interquartile range) age was 30 (12-41) and 1463 (73%) were women. There were 555 cases and 1445 controls (ie, 27.8% of participants were ESCrE colonized). Independent risk factors (adjusted odds ratio [95% confidence interval]) for ESCrE included healthcare exposure (1.37 [1.08-1.73]), foreign travel [1.98 (1.04-3.77]), tending livestock (1.34 [1.03-1.73]), and presence of an ESCrE-colonized household member (1.57 [1.08-2.27]). CONCLUSIONS: Our results suggest healthcare exposure may be important in driving ESCrE. The strong links to livestock exposure and household member ESCrE colonization highlight the potential role of common exposure or household transmission. These findings are critical to inform strategies to curb further emergence of ESCrE in LMICs.

Colonization With Antibiotic-Resistant Bacteria in a Hospital and Associated Communities in Guatemala: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: We estimated the prevalence of colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) from a hospital and associated communities in western Guatemala. METHODS: Randomly selected infants, children, and adults (<1, 1-17, and ≥18 years, respectively) were enrolled from the hospital (n = 641) during the coronavirus disease 2019 (COVID-19) pandemic, March to September 2021. Community participants were enrolled using a 3-stage cluster design between November 2019 and March 2020 (phase 1, n = 381) and between July 2020 and May 2021 (phase 2, with COVID-19 pandemic restrictions, n = 538). Stool samples were streaked onto selective chromogenic agar, and a Vitek 2 instrument was used to verify ESCrE or CRE classification. Prevalence estimates were weighted to account for sampling design. RESULTS: The prevalence of colonization with ESCrE and CRE was higher among hospital patients compared to community participants (ESCrE: 67% vs 46%, P < .01; CRE: 37% vs 1%, P < .01). Hospital ESCrE colonization was higher for adults (72%) compared with children (65%) and infants (60%) (P < .05). Colonization was higher for adults (50%) than children (40%) in the community (P < .05). There was no difference in ESCrE colonization between phase 1 and 2 (45% and 47%, respectively, P > .05), although reported use of antibiotics among households declined (23% and 7%, respectively, P < .001). CONCLUSIONS: While hospitals remain foci for ESCrE and CRE colonization, consistent with the need for infection control programs, community prevalence of ESCrE in this study was high, potentially adding to colonization pressure and transmission in healthcare settings. Better understanding of transmission dynamics and age-related factors is needed.

Prevalence of Colonization With Antibiotic-Resistant Organisms in Hospitalized and Community Individuals in Bangladesh, a Phenotypic Analysis: Findings From the Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance (AMR) but often lack adequate surveillance to inform mitigation efforts. Colonization can be a useful metric to understand AMR burden. We assessed the colonization prevalence of Enterobacterales with resistance to extended-spectrum cephalosporins, carbapenems, colistin, and methicillin-resistant Staphylococcus aureus among hospital and community dwellers. METHODS: Between April and October 2019, we conducted a period prevalence study in Dhaka, Bangladesh. We collected stool and nasal specimens from adults in 3 hospitals and from community dwellers within the hospitals' catchment area. Specimens were plated on selective agar plates. Isolates underwent identification and antibiotic susceptibility testing using Vitek 2. We performed descriptive analysis and determined population prevalence estimates accounting for clustering at the community level. RESULTS: The majority of both community and hospital participants were colonized with Enterobacterales with resistance to extended-spectrum cephalosporins (78%; 95% confidence interval [95% CI], 73-83; and 82%; 95% CI, 79-85, respectively). Thirty-seven percent (95% CI, 34-41) of hospitalized patients were colonized with carbapenems compared with 9% (95% CI, 6-13) of community individuals. Colistin colonization prevalence was 11% (95% CI, 8-14) in the community versus 7% (95% CI, 6-10) in the hospital. Methicillin-resistant Staphylococcus aureus colonization was similar in both community and hospital participants (22%; 95% CI, 19-26 vs 21% (95% CI, 18-24). CONCLUSIONS: The high burden of AMR colonization observed among hospital and community participants may increase the risk for developing AMR infections and facilitating spread of AMR in both the community and hospital.

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

Genomic landscape of prominent XDR Acinetobacter clonal complexes from Dhaka, Bangladesh.

BACKGROUND: Acinetobacter calcoaceticus-A. baumannii (ACB) complex pathogens are known for their prevalence in nosocomial infections and extensive antimicrobial resistance (AMR) capabilities. While genomic studies worldwide have elucidated the genetic context of antibiotic resistance in major international clones (ICs) of clinical Acinetobacter spp., not much information is available from Bangladesh. In this study, we analysed the AMR profiles of 63 ACB complex strains collected from Dhaka, Bangladesh. Following this, we generated draft genomes of 15 of these strains to understand the prevalence and genomic environments of AMR, virulence and mobilization associated genes in different Acinetobacter clones. RESULTS: Around 84% (n = 53) of the strains were extensively drug resistant (XDR) with two showing pan-drug resistance. Draft genomes generated for 15 strains confirmed 14 to be A. baumannii while one was A. nosocomialis. Most A. baumannii genomes fell under three clonal complexes (CCs): the globally dominant CC1 and CC2, and CC10; one strain had a novel sequence type (ST). AMR phenotype-genotype agreement was observed and the genomes contained various beta-lactamase genes including blaOXA-23 (n = 12), blaOXA-66 (n = 6), and blaNDM-1 (n = 3). All genomes displayed roughly similar virulomes, however some virulence genes such as the Acinetobactin bauA and the type IV pilus gene pilA displayed high genetic variability. CC2 strains carried highest levels of plasmidic gene content and possessed conjugative elements carrying AMR genes, virulence factors and insertion sequences. CONCLUSION: This study presents the first comparative genomic analysis of XDR clinical Acinetobacter spp. from Bangladesh. It highlights the prevalence of different classes of beta-lactamases, mobilome-derived heterogeneity in genetic architecture and virulence gene variability in prominent Acinetobacter clonal complexes in the country. The findings of this study would be valuable in understanding the genomic epidemiology of A. baumannii clones and their association with closely related pathogenic species like A. nosocomialis in Bangladesh.

Human Monkeypox without Viral Prodrome or Sexual Exposure, California, USA, 2022.

We report human monkeypox in a man who returned to the United States from the United Kingdom and reported no sexual contact. He had vesicular and pustular skin lesions but no anogenital involvement. The potential modes of transmission may have implications for the risk of spread and for epidemic control.

Rationale and guidance for strengthening infection prevention and control measures and antimicrobial stewardship programs in Bangladesh: a study protocol.

BACKGROUND: Hospital-acquired infections (HAIs) and antimicrobial resistance (AMR) are major global health challenges. Drug-resistant infectious diseases continue to rise in developing countries, driven by shortfalls in infection control measures, antibiotic misuse, and scarcity of reliable diagnostics. These escalating global challenges have highlighted the importance of strengthening fundamental infection prevention and control (IPC) measures and implementing effective antimicrobial stewardship programs (ASP). This study aims to present a framework for enhancing IPC measures and ASP efforts to reduce the HAI and AMR burden in Bangladesh. METHODS: This implementation approach will employ a mixed-methods strategy, combining both quantitative and qualitative data from 12 tertiary hospitals in Bangladesh. A baseline assessment will be conducted using the Infection Prevention and Control Assessment Framework (IPCAF) developed by the WHO. We will record IPC practices through direct observations of hand hygiene, personal protective equipment (PPE) utilization, and hospital ward IPC infrastructure. Additionally, data on healthcare providers' knowledge, attitudes, and practices regarding IPC and antibiotic prescribing will be collected using both structured questionnaires and qualitative interviews. We will also assist the hospital leadership with establishing and/or strengthening IPC and ASP committees. Based on baseline assessments of each healthcare facility, tailored interventions and quality improvement projects will be designed and implemented. An end-line assessment will also be conducted after 12 months of intervention using the same assessment tools. The findings will be compared with the baseline to determine changes in IPC and antibiotic stewardship practices. DISCUSSION: Comprehensive assessments of healthcare facilities in low-resource settings are crucial for strengthening IPC measures and ASP activities,. This approach to assessing existing IPC and ASP activities will provide policy-relevant data for addressing current shortfalls. Moreover, this framework proposes identifying institutionally-tailored solutions, which will ensure that response activities are appropriately contextualized, aligned with stakeholder priorities, and offer sustainable solutions. CONCLUSION: Findings from this study can guide the design and implementation of feasible and sustainable interventions in resource-constrained healthcare settings to address gaps in existing IPC and ASP activities. Therefore, this protocol will be applicable across a broad range of settings to improve IPC and ASP and reduce the burden of hospital-acquired infections and AMR.

Evaluation of the effects of repeated disinfection on medical exam gloves: Part 1. Changes in physical integrity.

COVID-19 has created shortages of personal protective equipment. In resource-constrained situations, limited cycles of disinfection and extended use of gloves is recommended by the U.S. Centers for Disease Control and Prevention to conserve supplies. However, these guidelines are based on limited evidence. In this study, serial cycles of hand hygiene were performed on gloved hands using an ethanol-based hand rub (six and 10 cycles), 0.1% sodium hypochlorite (bleach) solution (10 cycles), or soap and water (10 cycles) on latex and nitrile medical exam gloves from the United States and India. A modified water-leak test evaluated glove integrity after repeated applications of these disinfecting agents. When aggregated, dilute bleach demonstrated the lowest difference between treatment and control arms: -2.5 percentage points (95% CI: -5.3 to 0.3) for nitrile, 0.6 percentage points (95% CI: -2.6 to 3.8) for non-powdered latex. For U.S.-purchased gloves tested with six and 10 applications of ethanol-based hand rub, the mean difference in failure risk between treatment and control gloves was within the prespecified non-inferiority margin of five percentage points or less, though some findings were inconclusive since outside the margin. The aggregated difference in failure risk between treatment and control was 3.5 percentage points (0.6 to 6.4) for soap and water, and 2.3 percentage points (-0.5 to 5.0) and 5.0 percentage points (1.8 to 8.2) for 10 and 6 applications of ethanol-based hand rub, respectively. Most leaks occurred in the interdigital webs (35%) and on the fingers (34%). This indicates that some combinations of glove types and disinfection methods may allow for extended use. Ten applications of dilute bleach solution had the least impact on glove integrity. However, the majority of glove and exposure combinations were inconclusive. Additional testing of specific glove and disinfectant combinations may inform future strategies to guide extended use during glove shortages. Additional considerations, not evaluated here, include duration of use, disinfectant chemical permeation, and the effects of hand temperature, movement, and manipulation of instruments on glove integrity.

Evaluation of the effects of repeated disinfection on medical exam gloves: Part 2. Changes in mechanical properties.

Many healthcare professionals have been forced, under acute shortages, to extend medical exam gloves beyond their intended single use. Despite limited available literature, the CDC proposed a set of guidelines for repeated exam gloves use, indicating a maximum number of treatments for three widely available disinfectants. This study examines how these treatments affect the mechanical properties of latex and nitrile gloves. Furthermore, an acceptability threshold is proposed for changes in tensile property, specifically elastic modulus, as an indication of degradation. This proposed criterion was also applied to similar studies available in the literature to determine applicability and aid in recommendation development. Three different latex glove brands and three nitrile brands were exposed to repeated treatments of an alcohol-based hand rub, diluted bleach, or soap and water. Tensile tests of samples cut from untreated and treated gloves were performed to assess the change in elastic modulus induced by each treatment. The findings suggest that latex gloves performed well within the CDC recommended guidelines of six repeated treatments for an ethanol-based hand rub and 10 repeated treatments of either dilute bleach or soap and water. Nitrile exam gloves, on the other hand, showed significant changes in elastic modulus, with more inconclusive results among brands. This was especially true for treatment with dilute bleach and soap and water. Further research is needed to investigate the effects of disinfection products on the mechanical integrity of nitrile exam gloves. The results support the use of five repeated treatments of ethanol-based hand rub for nitrile exam gloves, a lower threshold than currently recommended by the CDC. This research also supports that the CDC recommendation of 10 repeated treatment with soap and water is appropriate for latex exam gloves, but not for nitrile exam gloves. Occupational safety and health professionals involved in the selection of disposable exam gloves for infection control should consider the compatibility of the glove polymer type with available disinfectants, especially if extended use with repeated disinfection becomes necessary.

Progressive Vaccinia Acquired through Zoonotic Transmission in a Patient with HIV/AIDS, Colombia.

In March 2015, a patient in Colombia with HIV/AIDS was hospitalized for disseminated ulcers after milking cows that had vesicular lesions on their udders. Vaccinia virus was detected, and the case met criteria for progressive vaccinia acquired by zoonotic transmission. Adherence to an optimized antiretroviral regimen resulted in recovery.

Seroprevalence and Risk Factors Possibly Associated with Emerging Zoonotic Vaccinia Virus in a Farming Community, Colombia.

In 2014, vaccinia virus (VACV) infections were identified among farmworkers in Caquetá Department, Colombia; additional cases were identified in Cundinamarca Department in 2015. VACV, an orthopoxvirus (OPXV) used in the smallpox vaccine, has caused sporadic bovine and human outbreaks in countries such as Brazil and India. In response to the emergence of this disease in Colombia, we surveyed and collected blood from 134 farmworkers and household members from 56 farms in Cundinamarca Department. We tested serum samples for OPXV antibodies and correlated risk factors with seropositivity by using multivariate analyses. Fifty-two percent of farmworkers had OPXV antibodies; this percentage decreased to 31% when we excluded persons who would have been eligible for smallpox vaccination. The major risk factors for seropositivity were municipality, age, smallpox vaccination scar, duration of time working on a farm, and animals having vaccinia-like lesions. This investigation provides evidence for possible emergence of VACV as a zoonosis in South America.

Human Rabies - Puerto Rico, 2015.

On December 1, 2015, the Puerto Rico Department of Health (PRDH) was notified by a local hospital of a suspected human rabies case. The previous evening, a Puerto Rican man aged 54 years arrived at the emergency department with fever, difficulty swallowing, hand paresthesia, cough, and chest tightness. The next morning the patient left against medical advice but returned to the emergency department in the afternoon with worsening symptoms. The patient's wife reported that he had been bitten by a mongoose during the first week of October, but had not sought care for the bite. While being transferred to the intensive care unit, the patient went into cardiac arrest and died. On December 3, rabies was confirmed from specimens collected during autopsy. PRDH conducted an initial rapid risk assessment, and five family members were started on rabies postexposure prophylaxis (PEP).

Human Rabies - Wyoming and Utah, 2015.

In September 2015, a Wyoming woman was admitted to a local hospital with a 5-day history of progressive weakness, ataxia, dysarthria, and dysphagia. Because of respiratory failure, she was transferred to a referral hospital in Utah, where she developed progressive encephalitis. On day 8 of hospitalization, the patient's family told clinicians they recalled that, 1 month before admission, the woman had found a bat on her neck upon waking, but had not sought medical care. The patient's husband subsequently had contacted county invasive species authorities about the incident, but he was not advised to seek health care for evaluation of his wife's risk for rabies. On October 2, CDC confirmed the patient was infected with a rabies virus variant that was enzootic to the silver-haired bat (Lasionycteris noctivagans). The patient died on October 3. Public understanding of rabies risk from bat contact needs to be improved; cooperation among public health and other agencies can aid in referring persons with possible bat exposure for assessment of rabies risk.

In vitro antiretroviral activity and in vivo toxicity of the potential topical microbicide copper phthalocyanine sulfate.

BACKGROUND: Copper has antimicrobial properties and has been studied for its activity against viruses, including HIV. Copper complexed within a phthalocyanine ring, forming copper (II) phthalocyanine sulfate (CuPcS), may have a role in microbicide development when used intravaginally. METHODS: CuPcS toxicity was tested against cervical epithelial cells, TZM-BL cells, peripheral blood mononuclear cells (PBMC), and cervical explant tissues using cell viability assays. In vivo toxicity was assessed following intravaginal administration of CuPcS in female BALB/C mice and measured using a standardized histology grading system on reproductive tract tissues. Efficacy studies for preventing infection with HIV in the presence of various non-toxic concentrations of CuPcS were carried out in TZM-BL, PBMC, and cervical explant cultures using HIV-1BAL and various pseudovirus subtypes. Non-linear regression was applied to the data to determine the EC50/90 and CC50/90. RESULTS: CuPcS demonstrated inhibition of HIV infection in PBMCs at concentrations that were non-toxic in cervical epithelial cells and PBMCs with EC50 values of approximately 50 µg/mL. Reproductive tract tissue analysis revealed no toxicity at 100 mg/mL. Human cervical explant tissues challenged with HIV in the presence of CuPcS also revealed a dose-response effect at preventing HIV infection at non-toxic concentrations with an EC50 value of 65 µg/mL. CONCLUSION: These results suggest that CuPcS may be useful as a topical microbicide in concentrations that can be achieved in the female genital tract.

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.

Risk factors for colonization with extended-spectrum cephalosporin-resistant and carbapenem-resistant Enterobacterales among hospitalized patients in Guatemala: An Antibiotic Resistance in Communities and Hospitals (ARCH) study.

Objectives: The spread of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) and carbapenem-resistant Enterobacterales (CRE) has resulted in increased morbidity, mortality, and health care costs worldwide. To identify the factors associated with ESCrE and CRE colonization within hospitals, we enrolled hospitalized patients at a regional hospital located in Guatemala. Methods: Stool samples were collected from randomly selected patients using a cross-sectional study design (March-September, 2021), and samples were tested for the presence of ESCrE and CRE. Hospital-based and household variables were examined for associations with ESCrE and CRE colonization using lasso regression models, clustered by ward (n = 21). Results: A total of 641 patients were enrolled, of whom complete data sets were available for 593. Colonization with ESCrE (72.3%, n = 429/593) was negatively associated with carbapenem administration (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.11-0.42) and positively associated with ceftriaxone administration (OR 1.61, 95% CI 1.02-2.53), as was reported hospital admission within 30 days of the current hospitalization (OR 2.84, 95% CI 1.19-6.80). Colonization with CRE (34.6%, n = 205 of 593) was associated with carbapenem administration (OR 2.62, 95% CI 1.39-4.97), reported previous hospital admission within 30 days of current hospitalization (OR 2.58, 95% CI 1.17-5.72), hospitalization in wards with more patients (OR 1.05, 95% CI 1.02-1.08), hospitalization for ≥4 days (OR 3.07, 95% CI 1.72-5.46), and intubation (OR 2.51, 95% CI 1.13-5.59). No household-based variables were associated with ESCrE or CRE colonization in hospitalized patients. Conclusion: The hospital-based risk factors identified in this study are similar to what has been reported for risk of health care-associated infections, consistent with colonization being driven by hospital settings rather than community factors. This also suggests that colonization with ESCrE and CRE could be a useful metric to evaluate the efficacy of infection and prevention control programs in clinics and hospitals.